摘要：
Sepsis-associated acute respiratory distress syndrome (ARDS) is a heterogeneous disease with high morbidity and mortality. Lactylation plays a crucial role in sepsis and sepsis-induced lung injury. This study aimed to identify distinct lactylation-based phenotypes in patients with sepsis-associated ARDS and determine relevant molecular biomarkers. We analyzed blood transcriptome and clinical data from patients with sepsis-associated ARDS and calculated the lactylation activity. KEGG pathway analysis, drug sensitivity prediction, and immune cell infiltration analysis were performed. Candidate molecular biomarkers were identified by intersecting the feature genes extracted from four machine learning models. Lactylation activity showed significant heterogeneity among patients with sepsis-associated ARDS, which enabled the classification into low- and high-lactylation activity phenotypes. Patients with high-lactylation experienced longer hospital stays and higher mortality rates, as well as distinct signaling pathways, drug responses, and circulating immune cell abundances. Six key markers (ALDOB, CCT5, EP300, PFKP, PPIA, and SIRT1) were identified to differentiate the two lactylation activity phenotypes, all significantly correlated with circulating immune cell populations. This study revealed significant heterogeneity in lactylation activity phenotypes among patients with sepsis-associated ARDS and identified potential biomarkers to facilitate the application of these phenotypes in clinical practice.
作者机构：
[Zhong, Jing; Zhao, Hu; Zhong, J; Xiao, Qian] Univ South China, Affiliated Hosp 1, Canc Res Inst, Hengyang Med Sch, Hengyang 421001, Hunan, Peoples R China.;[Xiao, Qian] Univ South China, Affiliated Hosp 1, Hengyang Med Sch, Dept Clin Lab Med, Hengyang 421001, Hunan, Peoples R China.;[An, Yangfang] Yiyang Cent Hosp, Yiyang 413099, Hunan, Peoples R China.;[Wang, Mu] Univ South China, Affiliated Nanhua Hosp, Clin Res Inst, Clin Mass Spectrometry Lab, Hengyang, Peoples R China.;[Zhong, Jing] Univ South China, Affiliated Hosp 1, Inst Clin Med, Hengyang Med Sch, Hengyang 421001, Hunan, Peoples R China.
通讯机构：
[Zhong, J ; Wang, M ] U;Univ South China, Affiliated Hosp 1, Canc Res Inst, Hengyang Med Sch, Hengyang 421001, Hunan, Peoples R China.;Univ South China, Affiliated Nanhua Hosp, Clin Res Inst, Clin Mass Spectrometry Lab, Hengyang, Peoples R China.
摘要：
Phospholipids, complex lipids prevalent in the human body, play crucial roles in various pathophysiological processes. Beyond their synthesis and degradation, phospholipids can influence chemoresistance by participating in ferroptosis. Extensive evidence highlights the significant link between tumor drug resistance and phospholipids. Therefore, drugs targeting phospholipid metabolism itself or the synthesis of corresponding composite materials will effectively overcome the difficulties of clinical tumor treatment.
Phospholipids, complex lipids prevalent in the human body, play crucial roles in various pathophysiological processes. Beyond their synthesis and degradation, phospholipids can influence chemoresistance by participating in ferroptosis. Extensive evidence highlights the significant link between tumor drug resistance and phospholipids. Therefore, drugs targeting phospholipid metabolism itself or the synthesis of corresponding composite materials will effectively overcome the difficulties of clinical tumor treatment.
通讯机构：
[Tang, BS ; Qiu, J ; Qiu, J] C;Cent South Univ, Xiangya Hosp, Dept Neurol, Dept Geriatr, Changsha 410008, Peoples R China.;Cent South Univ, Xiangya Hosp, Hunan Key Lab Mol Precis Med, Changsha 41008, Peoples R China.
摘要：
OBJECTIVE: Despite substantial advancements in uncovering the genetic basis of Parkinson's disease (PD), a significant portion of cases characterized by familial PD remain genetically elusive. Here, we reported that biallelic variants in EPG5, a key autophagy gene responsible for Vici syndrome, are associated with PD. METHODS: Whole-exome sequencing (WES) was performed in the first cohort including 171 pedigrees with autosomal recessive PD (ARPD), 1,746 cases of sporadic early-onset PD (sEOPD, age at onset ≤ 50 years) and 1,652 healthy controls. Whole-genome sequencing (WGS) was performed in the second cohort consisting of 1,947 sporadic late-onset PD (sLOPD, age at onset >50 years) and 2,478 healthy controls. RESULTS: We identified 7 participants harboring compound heterozygous variants within the EPG5 gene across 1 family with ARPD (ARPD-F1), 4 sporadic EOPD cases, and 1 sporadic LOPD individual. A total of 10 novel variants in EPG5 were discovered in the 7 individuals, comprising 3 nonsense variants and 7 missense variants. The compound heterozygous variants in the EPG5 gene led to decreased expression of EPG5 protein, and impaired autophagy-lysosome function in cells derived from EPG5-PD individuals. We also revealed several key pathological features, including abnormal accumulation of autophagic vacuoles, aggregation of α-synuclein in skin tissue from EPG5-PD individuals. In mice, EPG5 deficiency led to progressive dopaminergic neurodegeneration in the substantia nigra of the midbrain. INTERPRETATION: Our results unveil a novel association between biallelic variants in EPG5 gene and PD, providing compelling initial evidence for the involvement of EPG5 and autophagy dysregulation in the development of PD. ANN NEUROL 2025.
摘要：
Peptides exhibit various biological activities, including biorecognition, cell targeting, and tumor penetration, and can stimulate immune cells to elicit immune responses for tumor immunotherapy. Peptide self-assemblies and peptide-functionalized nanocarriers can reduce the effect of various biological barriers and the degradation by peptidases, enhancing the efficiency of peptide delivery and improving antitumor immune responses. To date, the design and development of peptides with various functionalities have been extensively reviewed for enhanced chemotherapy; however, peptide-mediated tumor immunotherapy using peptides acting on different immune cells, to the knowledge, has not yet been summarized. Thus, this work provides a review of this emerging subject of research, focusing on immunomodulatory anticancer peptides. This review introduces the role of peptides in the immunomodulation of innate and adaptive immune cells, followed by a link between peptides in the innate and adaptive immune systems. The peptides are discussed in detail, following a classification according to their effects on different innate and adaptive immune cells, as well as immune checkpoints. Subsequently, two delivery strategies for peptides as drugs are presented: peptide self-assemblies and peptide-functionalized nanocarriers. The concluding remarks regarding the challenges and potential solutions of peptides for tumor immunotherapy are presented. This work introduces the role of peptides in immune regulation of innate and adaptive immune cells, as well as immune checkpoints. Then this work introduces two strategies for delivering polypeptides: peptide self-assemblies, and peptide-functionalized nanocarriers. Finally, the challenges and prospects of peptides in tumor immunotherapy are summarized. image
通讯机构：
[Tan, XF; Yang, QL ; Chen, GD; Wu, GL] U;Univ South China, Affiliated Hosp 1, Hengyang Med Sch, Dept Hepatopancreatobiliary Surg, Hengyang 421001, Hunan, Peoples R China.;Univ South China, Inst Pharm & Pharmacol, Hengyang Med Sch, Sch Pharmaceut Sci, Hengyang 421001, Hunan, Peoples R China.;Univ South China, Hengyang Med Sch, NHC Key Lab Birth Defect Res & Prevent, Hengyang 421001, Hunan, Peoples R China.;Univ South China, Hengyang Med Sch, MOE Key Lab Rare Pediat Dis, Hengyang 421001, Hunan, Peoples R China.
摘要：
The advancement of mitochondria-targeted near-infrared-II (NIR-II) excitable phototheranostics constitutes a promising strategy for improving fluorescence-image-guided cancer phototherapy. However, developing phototheranostic agents that simultaneously combine high-contrast NIR-II fluorescence imaging with effective multimodal therapeutic techniques remains a substantial challenge. Herein, we reported a shielding-donor–acceptor–donor-shielding structured NIR-II phototheranostic (FCD-T) by a molecular engineering strategy, followed by self-assembly with glutathione-responsive copolymer to form FCD-T nanoparticles. The introduction of functional bithiophene endows FCD-T with significant electron-donating properties and reduces intermolecular π-π stacking interactions. The robust π-conjugation of fluorene with good rigidity would enhance the intramolecular charge transfer capability. Therefore, FCD-T NPs exhibited an NIR-II absorption peak at 1075 nm and an emission peak at 1280 nm. Upon NIR-II light excitation, such nanoparticles could generate excellent photothermal and photodynamic performances with good biocompatibility. Moreover, the NIR-II mitochondria-targeted phototherapy further facilitated mitochondrial apoptosis-related pathways, activating antitumor immunity and inhibiting tumor growth with single irradiation at low doses.
The advancement of mitochondria-targeted near-infrared-II (NIR-II) excitable phototheranostics constitutes a promising strategy for improving fluorescence-image-guided cancer phototherapy. However, developing phototheranostic agents that simultaneously combine high-contrast NIR-II fluorescence imaging with effective multimodal therapeutic techniques remains a substantial challenge. Herein, we reported a shielding-donor–acceptor–donor-shielding structured NIR-II phototheranostic (FCD-T) by a molecular engineering strategy, followed by self-assembly with glutathione-responsive copolymer to form FCD-T nanoparticles. The introduction of functional bithiophene endows FCD-T with significant electron-donating properties and reduces intermolecular π-π stacking interactions. The robust π-conjugation of fluorene with good rigidity would enhance the intramolecular charge transfer capability. Therefore, FCD-T NPs exhibited an NIR-II absorption peak at 1075 nm and an emission peak at 1280 nm. Upon NIR-II light excitation, such nanoparticles could generate excellent photothermal and photodynamic performances with good biocompatibility. Moreover, the NIR-II mitochondria-targeted phototherapy further facilitated mitochondrial apoptosis-related pathways, activating antitumor immunity and inhibiting tumor growth with single irradiation at low doses.
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摘要：
Early recognition is key to improving the prognosis of ischemic stroke (IS), while available imaging methods tend to target events that have already undergone ischemia. A new method to detect early IS is urgently needed, as well as further study of its mechanisms. Viscosity and cysteine (Cys) levels of mitochondria have been associated with ferroptosis and IS. It is possible to identify IS and ferroptosis accurately and early by monitoring changes in mitochondrial Cys and viscosity simultaneously. In this work, a viscosity/Cys dual-responsive mitochondrial-targeted near-infrared (NIR) fluorescent probe ( NVCP ) was constructed for the precise tracking of IS using a two-dimensional design strategy. NVCP consists of a chromophore dyad containing diethylaminostyrene quinolinium rotor and chloro‑sulfonylbenzoxadiazole (SBD-Cl) derivative with two easily distinguished emission bands (λ em = 592 and 670 nm). NVCP performs the way of killing two birds with one stone, that is, the probe exhibits excellent selectivity and sensitivity for detecting viscosity and Cys in living cells with excellent biocompatibility and accurate mitochondrial targeting capability by dual channel imaging mode. In addition, NVCP recognized that the viscosity increases and Cys level decreases in cells when undergoing ferroptosis and oxygen-glucose deprivation (OGD) stress by confocal imaging, flow cytometry, and Western blot experiments. Treatment of ferroptosis inhibitors (ferrostatin-1 (Fer-1) and deferoxamine (DFO)) could reverse the variation tendency of viscosity and Cys. This is the first time that the relationship between ferroptosis and IS was identified through an analysis of Cys and viscosity. More importantly, the ischemic area was also instantly distinguished from normal tissues through fluorescence imaging of NVCP in vivo . The developed NIR dual-responsive probe NVCP toward viscosity and Cys could serve as a sensitive and reliable tool for tracking ferroptosis-related pathological processes during IS.
Early recognition is key to improving the prognosis of ischemic stroke (IS), while available imaging methods tend to target events that have already undergone ischemia. A new method to detect early IS is urgently needed, as well as further study of its mechanisms. Viscosity and cysteine (Cys) levels of mitochondria have been associated with ferroptosis and IS. It is possible to identify IS and ferroptosis accurately and early by monitoring changes in mitochondrial Cys and viscosity simultaneously. In this work, a viscosity/Cys dual-responsive mitochondrial-targeted near-infrared (NIR) fluorescent probe ( NVCP ) was constructed for the precise tracking of IS using a two-dimensional design strategy. NVCP consists of a chromophore dyad containing diethylaminostyrene quinolinium rotor and chloro‑sulfonylbenzoxadiazole (SBD-Cl) derivative with two easily distinguished emission bands (λ em = 592 and 670 nm). NVCP performs the way of killing two birds with one stone, that is, the probe exhibits excellent selectivity and sensitivity for detecting viscosity and Cys in living cells with excellent biocompatibility and accurate mitochondrial targeting capability by dual channel imaging mode. In addition, NVCP recognized that the viscosity increases and Cys level decreases in cells when undergoing ferroptosis and oxygen-glucose deprivation (OGD) stress by confocal imaging, flow cytometry, and Western blot experiments. Treatment of ferroptosis inhibitors (ferrostatin-1 (Fer-1) and deferoxamine (DFO)) could reverse the variation tendency of viscosity and Cys. This is the first time that the relationship between ferroptosis and IS was identified through an analysis of Cys and viscosity. More importantly, the ischemic area was also instantly distinguished from normal tissues through fluorescence imaging of NVCP in vivo . The developed NIR dual-responsive probe NVCP toward viscosity and Cys could serve as a sensitive and reliable tool for tracking ferroptosis-related pathological processes during IS.
通讯机构：
[Tan, XF; Yang, QL ; Wu, GL] U;Univ South China, Affiliated Hosp 1, Dept Hepatopancreatobiliary Surg, Hengyang 421001, Hunan, Peoples R China.;Univ South China, Canc Res Inst, Ctr Mol Imaging Probe, Hengyang Med Sch, Hengyang 421001, Hunan, Peoples R China.;Univ South China, NHC Key Lab Birth Defect Res & Prevent, Hengyang 421001, Hunan, Peoples R China.;Univ South China, MOE Key Lab Rare Pediat Dis, Hengyang 421001, Hunan, Peoples R China.
关键词：
NIR-II;Phototheranostics;Endoplasmic reticulum;Triple-negative breast cancer;Intermolecular π–π stacking interaction
摘要：
Triple-negative breast cancer (TNBC) is a highly aggressive subtype of breast cancer characterized by an extremely poor prognosis. Photoimmunotherapy has emerged as a promising strategy for the treatment of TNBC. This approach works by selectively destroying tumor cells, releasing tumor-associated antigens, activating the immune system, and effectively inhibiting tumor proliferation and metastasis. However, the majority of current phototheranostic approaches are hindered by limited tissue penetration in the first near-infrared (NIR-I) and ultraviolet-visible (UV-Vis) regions. Additionally, due to the lack of specific subcellular targets, it may be difficult to effectively treat deep-seated lesions with ambiguous and extensive boundaries caused by TNBC metastases. Consequently, the development of effective, deep-penetrating, organelle-targeted phototheranostics is essential for enhancing treatment outcomes in TNBC. This work proposes a novel molecular design strategy of NIR-II phototheranostics to realize planar rigid conjugation and alkyl chain functionalization. The di-hexaalkyl chains in a vertical configuration on the donor (4H-cyclopenta[2,1-b:3,4-b'] dithiophene) and shielding units (fluorene) are introduced to construct a S-D-A-D-S type NIR-II phototheranostics (IR-FCD). The planar and rigid structure of IR-FCD exhibits a robust intramolecular charge transfer capability, a lower band gap, enhanced photon absorption properties, and significant steric hindrance from vertically arranged alkyl chains to minimize non-radiative energy loss. By incorporating N-(but-3-yn-1-yl)-4-methylbenzenesulfonamide at the terminus of an elongated alkyl chain, followed by self-assembly into DSPE-S-S-PEG2000, NIR-II excitable phototheranostics (IR-FCD-Ts NPs) with endoplasmic reticulum (ER) targeting capability were successfully synthesized for imaging-guided photoimmunotherapy of TNBC. The IR-FCD-Ts NPs demonstrate exceptional optical characteristics, with maximum absorption at 1068nm (extending to 1300nm) and emission at 1273nm (extending to 1700nm), along with a high molar absorption coefficient of 2.76*10(4)L/mol·c at 1064nm in aqueous solution. Under exposure to 1064nm laser irradiation, IR-FCD-Ts NPs exhibit superior photothermal properties and have the potential for photodynamic therapy. By targeting ER, thereby inducing ER stress and significantly enhancing immunogenic cell death (ICD) in tumor cells, it triggers a strong antitumor immune response and inhibits the proliferation and metastasis of TNBC.
摘要：
Channel catfish ( Ictalurus punctatus ), a significant aquaculture species, occupies a prominent position in the aquaculture industry due to its rapid growth, excellent adaptability, and economic value; however, the hemorrhagic disease caused by Aeromonas hydrophila has had a substantial impact on its cultivation. Researches have indicated that cortisol, the main stress hormone, is essential for regulating immune responses. Therefore, in this study, the immune regulatory effects of cortisol on the spleen tissue under Aeromonas hydrophila stimulation were analyzed. Through transcriptomic (RNA-seq) analysis, we identified 167 differentially expressed genes (DEGs) regulated by cortisol. The KEGG enrichment analysis indicated that the DEGs were predominantly associated with various biological pathways, including antigen processing and presentation, bladder cancer, autophagy in animals, lipid metabolism, and atherosclerosis. Protein-protein interaction network analysis further indicated that these DEGs participate in key signaling pathways, including HIF, JAK-STAT, and NF-KB. Our findings demonstrate that cortisol exerts an immunoregulatory effect by modulating these key signaling pathways in the spleen tissue infected with Aeromonas hydrophila , which is of significant importance for understanding the mechanism of cortisol in fish immune responses.
Channel catfish ( Ictalurus punctatus ), a significant aquaculture species, occupies a prominent position in the aquaculture industry due to its rapid growth, excellent adaptability, and economic value; however, the hemorrhagic disease caused by Aeromonas hydrophila has had a substantial impact on its cultivation. Researches have indicated that cortisol, the main stress hormone, is essential for regulating immune responses. Therefore, in this study, the immune regulatory effects of cortisol on the spleen tissue under Aeromonas hydrophila stimulation were analyzed. Through transcriptomic (RNA-seq) analysis, we identified 167 differentially expressed genes (DEGs) regulated by cortisol. The KEGG enrichment analysis indicated that the DEGs were predominantly associated with various biological pathways, including antigen processing and presentation, bladder cancer, autophagy in animals, lipid metabolism, and atherosclerosis. Protein-protein interaction network analysis further indicated that these DEGs participate in key signaling pathways, including HIF, JAK-STAT, and NF-KB. Our findings demonstrate that cortisol exerts an immunoregulatory effect by modulating these key signaling pathways in the spleen tissue infected with Aeromonas hydrophila , which is of significant importance for understanding the mechanism of cortisol in fish immune responses.
期刊：
Brain and Behavior,2025年15(1):e70245- ISSN：2162-3279
通讯作者：
Xiao, ZJ
作者机构：
[Deng, Limin; Lin, Shudong; Xie, Juan; Chen, Shuangxi; Liu, Guozhi; Xiao, Zijian; Wen, Xuanwei; Li, Sijing; Zhu, Guanghua; Wang, Feiyan; Xiao, ZJ] Univ South China, Affiliated Hosp 1, Multi Res Ctr Brain Disorders, Hengyang Med Sch,Dept Neurol, Hengyang, Hunan, Peoples R China.;[Deng, Limin; Lin, Shudong; Chen, Shuangxi; Liu, Guozhi; Xiao, Zijian; Wen, Xuanwei; Li, Sijing; Zhu, Guanghua; Wang, Feiyan; Xiao, ZJ] Univ South China, Clin Res Ctr Immune Related Encephalopathy Hunan P, Hengyang Med Sch, Hengyang, Hunan, Peoples R China.;[Xie, Juan] Univ South China, Affiliated Hosp 1, Hengyang Med Sch, Dept Emergency, Hengyang, Hunan, Peoples R China.
通讯机构：
[Xiao, ZJ ] U;Univ South China, Affiliated Hosp 1, Multi Res Ctr Brain Disorders, Hengyang Med Sch,Dept Neurol, Hengyang, Hunan, Peoples R China.;Univ South China, Clin Res Ctr Immune Related Encephalopathy Hunan P, Hengyang Med Sch, Hengyang, Hunan, Peoples R China.
关键词：
cerebral amyloid angiopathy (CAA);curcumin;learning and memory;necroptosis;neuroinflammation
摘要：
BACKGROUND AND PURPOSE: Cerebral amyloid angiopathy (CAA) is recognized as a major contributor to progressive cognitive decline and cerebral hemorrhages in the elderly population. Currently, there is a global shortage of safe and effective treatments for this condition. Bisdemethoxycurcumin (BDMC) has been demonstrated to exhibit pharmacological effects with anti-Aβ toxicity properties. Thus, the present study mainly focused on the potential therapeutic effects of BDMC on CAA. METHOD: The 30 male C57BL/6 mice were subjected to chronic treatment with five vascular risk factors (lipopolysaccharide, social stress, streptozotocin, high-cholesterol diet, and copper-containing drinking water) for 35 weeks to establish a CAA mouse model. Of these, 15 CAA mice received oral administration of BDMC (50mg/kg) for two consecutive weeks as an intervention, while the remaining 15 CAA mice received an equal volume of physiological saline by gavage. The study observed the levels of Aβ40 and proinflammatory factors in brain tissue and plasma, Aβ deposition in cerebral blood vessels, microbleeds in brain tissue, expression of proteins related to the cGAS/STING signaling pathway in brain tissue, as well as the contents of p-RIPK-1, p-RIPK-3, p-MLKL, neuronal morphology, and learning and memory abilities in mice. RESULT: The therapeutic administration of BDMC demonstrates a pronounced efficacy in alleviating Aβ burden and cerebral microbleeding in CAA mice, concurrently enhancing learning and memory capabilities. Interestingly, BDMC may inhibits neuroinflammatory responses by reducing the expression of cGAS/STING signaling pathway proteins and suppresses necroptosis. CONCLUSION: Our research findings demonstrate that BDMC exerts therapeutic effects in a mouse model of CAA established through chronic treatment involving five vascular risk factors.
摘要：
The Omicron BA.2.86 subvariants, JN.1, KP.2, and KP.3, have become predominant globally, raising concerns about their immune evasion from vaccines and monoclonal antibody (mAb) treatments. These variants harbor more receptor-binding domain (RBD) mutations than the XBB and EG.5 sub-lineages, which are already known to compromise vaccine and therapeutic efficacy. We evaluated sera from individuals vaccinated with inactivated vaccines, with or without breakthrough infections, as well as COVID-19 convalescents. Our results showed a substantial decrease in serum neutralizing activity against the JN.1, KP.2, XBB.1.5, and EG.5.1 variants compared to BA.2. Additionally, we developed 19 neutralizing antibodies from memory B cells, with some retaining efficacy against earlier Omicron variants. However, potency was notably diminished against newer subvariants like BF.7, BQ.1, XBB.1.5, and BA.2.86. Of mAbs, those isolated from COVID-19 convalescents, particularly SA-3, exhibited exceptional potency across ten variants from BA.2 to KP.2, with IC50 values ranging from 0.006 to 2.546 μg/mL. However, SA-3 had lost neutralizing activity against the KP.3 due to the Q493E mutation, but the KP.3 became susceptible to neutralization by the other mAb, SA-6. In contrast, SA-6 was unable to neutralize KP.2 because of the presence of R346T mutation. Our findings underscore the importance of continuous surveillance of viral evolution and the need for updated vaccines and therapeutics to combat the ongoing evolution of SARS-CoV-2, particularly in the context of emerging variants that escape both vaccine-induced immunity and monoclonal antibody treatments.
The Omicron BA.2.86 subvariants, JN.1, KP.2, and KP.3, have become predominant globally, raising concerns about their immune evasion from vaccines and monoclonal antibody (mAb) treatments. These variants harbor more receptor-binding domain (RBD) mutations than the XBB and EG.5 sub-lineages, which are already known to compromise vaccine and therapeutic efficacy. We evaluated sera from individuals vaccinated with inactivated vaccines, with or without breakthrough infections, as well as COVID-19 convalescents. Our results showed a substantial decrease in serum neutralizing activity against the JN.1, KP.2, XBB.1.5, and EG.5.1 variants compared to BA.2. Additionally, we developed 19 neutralizing antibodies from memory B cells, with some retaining efficacy against earlier Omicron variants. However, potency was notably diminished against newer subvariants like BF.7, BQ.1, XBB.1.5, and BA.2.86. Of mAbs, those isolated from COVID-19 convalescents, particularly SA-3, exhibited exceptional potency across ten variants from BA.2 to KP.2, with IC50 values ranging from 0.006 to 2.546 μg/mL. However, SA-3 had lost neutralizing activity against the KP.3 due to the Q493E mutation, but the KP.3 became susceptible to neutralization by the other mAb, SA-6. In contrast, SA-6 was unable to neutralize KP.2 because of the presence of R346T mutation. Our findings underscore the importance of continuous surveillance of viral evolution and the need for updated vaccines and therapeutics to combat the ongoing evolution of SARS-CoV-2, particularly in the context of emerging variants that escape both vaccine-induced immunity and monoclonal antibody treatments.
作者机构：
[Li, Shuihong; Zhang, Ru; Zuo, Yingying] Univ South China, Inst Pathogen Biol, Hengyang Med Coll, Hengyang 421001, Hunan, Peoples R China.
通讯机构：
[Li, SH ] U;Univ South China, Inst Pathogen Biol, Hengyang Med Coll, Hengyang 421001, Hunan, Peoples R China.
关键词：
M. pneumoniae;MAPK;NF-κB;RAW264.7;rMPN606
摘要：
Mycoplasma pneumoniae ( M. pneumoniae ) is one of the major pathogens causing community-acquired pneumonia (CAP), and its pathogenic mechanism is not fully understood. Inflammatory response is the most basic and common pathological phenomenon of CAP, but the specific mechanism needs further investigation. In this study, the inflammatory action of M. pneumoniae MPN606 protein was confirmed and its molecular mechanism was tentatively investigated. Compared with the control group treated with PBS, stimulation of RAW264.7 cells with rMPN606 can promote the release of NO, increase the expression level of TNF-α and IL⁃6 cytokines, and up-regulate the mRNA transcription levels of iNOS, IL-6 and TNF-α in RAW264.7 cells. In addition, rMPN606 also significantly induced the expression of iNOS protein in RAW264.7 cells, resulting in increased phosphorylation levels of p65, p38 and ERK proteins. The results of cellular immunofluorescence showed that NF-κB was transferred from cytoplasm to nucleus of RAW264.7 cells after stimulation with rMPN606, and nuclear translocation of NF-κB was significantly enhanced. These results indicate that Mycoplasma pneumoniae MPN606 induces M1-type activation of macrophages and secretes pro-inflammatory factors by activating NF-κB and MAPK pathways.
Mycoplasma pneumoniae ( M. pneumoniae ) is one of the major pathogens causing community-acquired pneumonia (CAP), and its pathogenic mechanism is not fully understood. Inflammatory response is the most basic and common pathological phenomenon of CAP, but the specific mechanism needs further investigation. In this study, the inflammatory action of M. pneumoniae MPN606 protein was confirmed and its molecular mechanism was tentatively investigated. Compared with the control group treated with PBS, stimulation of RAW264.7 cells with rMPN606 can promote the release of NO, increase the expression level of TNF-α and IL⁃6 cytokines, and up-regulate the mRNA transcription levels of iNOS, IL-6 and TNF-α in RAW264.7 cells. In addition, rMPN606 also significantly induced the expression of iNOS protein in RAW264.7 cells, resulting in increased phosphorylation levels of p65, p38 and ERK proteins. The results of cellular immunofluorescence showed that NF-κB was transferred from cytoplasm to nucleus of RAW264.7 cells after stimulation with rMPN606, and nuclear translocation of NF-κB was significantly enhanced. These results indicate that Mycoplasma pneumoniae MPN606 induces M1-type activation of macrophages and secretes pro-inflammatory factors by activating NF-κB and MAPK pathways.
作者机构：
[Zeng, Chenlu; Xie, Hailong; Li, Junru; Song, Ge; Liu, Jiajia; Xie, HL] Univ South China, Canc Res Inst Hengyang Med Coll, Key Lab Canc Cellular & Mol Pathol Hunan Prov, Hengyang 421001, Hunan, Peoples R China.;[Zhao, Juanxia] Univ South China, Affiliated Nanhua Hosp, Hengyang Med Coll, Dept Pathol, Hengyang, Hunan, Peoples R China.;[Liu, Bin] Hunan Univ, Coll Biol, Changsha, Hunan, Peoples R China.;[Fan, Jialong; Fan, JL] Changsha Med Univ, Hunan Prov Key Lab Res & Dev Novel Pharmaceut Prep, Changsha 410219, Peoples R China.
通讯机构：
[Fan, JL ] C;[Xie, HL ] U;Univ South China, Canc Res Inst Hengyang Med Coll, Key Lab Canc Cellular & Mol Pathol Hunan Prov, Hengyang 421001, Hunan, Peoples R China.;Changsha Med Univ, Hunan Prov Key Lab Res & Dev Novel Pharmaceut Prep, Changsha 410219, Peoples R China.
关键词：
Exosomes;digestive system tumors;drug delivery;tumor therapy;exosome source
摘要：
Digestive system tumors constitute a major subset of malignancies, consistently ranking among the leading causes of mortality globally. Despite limitations inherent in current therapeutic modalities, recent advancements in targeted therapy and drug delivery systems have led to significant improvements in the efficacy of pharmacotherapy for digestive system tumors. In this context, exosomes - naturally occurring nanoscale vesicles - have emerged as promising drug delivery candidates due to their intrinsic molecular transport capabilities, superior biocompatibility, and targeted recognition of tumor cells. The integration of exosomes into cancer therapeutics represents a novel and potentially transformative approach for treating digestive system tumors, which may drive further progress in this field. This review comprehensively examines the sources, loading mechanisms, and therapeutic efficacy of exosomes in the context of digestive system tumor treatment. Furthermore, it discusses the opportunities and challenges associated with exosomes, offering insights into their future role within the therapeutic armamentarium against digestive tumors.
期刊：
JOURNAL OF GLOBAL HEALTH,2025年15:04001 ISSN：2047-2978
通讯作者：
Zhang, YP
作者机构：
[Zhuang, Xinqi; Lei, Xiaoyu; Zhang, Yin-Ping; Zhang, YP; Zhang, Dandan; Zhang, Jianzhong] Xi An Jiao Tong Univ, Hlth Sci Ctr, Sch Nursing, West Yanta Rd 76, Xian 710061, Shaanxi, Peoples R China.;[Zhang, Dandan] Univ South China, Affiliated Nanhua Hosp, Inst Clin Res, Hengyang Med Sch, Hengyang, Hunan, Peoples R China.;[Liu, Fen] Univ South China, Affiliated Hosp 1, Hengyang Med Sch, Dept Gynecol & Obstet, Hengyang, Hunan, Peoples R China.;[Cui, Tianxin] Univ Edinburgh, Sch Hlth Social Sci, Edinburgh, Scotland.
通讯机构：
[Zhang, YP ] X;Xi An Jiao Tong Univ, Hlth Sci Ctr, Sch Nursing, West Yanta Rd 76, Xian 710061, Shaanxi, Peoples R China.
摘要：
BACKGROUND: As fertility rates decline and population ageing intensifies, the conflict between career and childbearing continues to impact clinicians, especially women. Exploring gender differences in the fertility intentions of male and female clinicians could help with identifying barriers to childbearing, developing effective policies to support work-life balance, and addressing the gap in research on gender disparities in this field. METHODS: We conducted a cross-sectional survey among health care personnel in Chinese public hospitals. Through cluster sampling from highly active WeChat groups, we gathered 698 responses from clinicians to the third fertility intention questionnaire online. We then used descriptive statistics and χ(2) tests for analysis. RESULTS: Men (28.28%) had higher intentions of having a third child than women (20.71%) (P = 0.013). In terms of reasons, female clinicians were more concerned than male clinicians about the impact on their career development (P = 0.002), difficulties in job hunting (P = 0.039), and physical injuries caused by multiple births (P < 0.001), and whether the elderly can help (P = 0.001). Conversely, men's apprehensions centred on economic factors such as real house costs (P < 0.001), policy support (P = 0.036), and wives' disagreement (P < 0.001). In discussing governmental interventions, men showed a higher level of interest in policies related to child care (P < 0.001), employment stability for women (P < 0.001), extended maternity leave (P < 0.001), and financial assistance than women (P < 0.001). CONCLUSIONS: Our findings show substantial gender-specific differences in third-child fertility intentions among clinicians. To address this, the government should consider divisions in family roles, future societal needs, and women's career development. Policies should focus on balancing work and family by offering affordable childcare, flexible parenting leave, financial incentives, and career support, ensuring childbirth does not negatively impact women's professional growth, and fostering gender equality in parenting.
作者机构：
[Tang, Li; Wu, Yingying; Li, Na; Liu, Fen; Tan, Xiaofeng; Wang, Minghui; Yang, Qinglai; Tan, XF; Wu, Gui-long; Gong, Hongyu; Xia, Hong; Tang, L] Univ South China, Affiliated Hosp 1, Canc Res Inst, Dept Hepatopancreatobiliary Surg, Hengyang 421001, Hunan, Peoples R China.;[Tang, Li; Wu, Yingying; Li, Na; Liu, Fen; Tan, Xiaofeng; Wang, Minghui; Yang, Qinglai; Tan, XF; Wu, Gui-long; Gong, Hongyu; Xia, Hong; Tang, L] Univ South China, Canc Res Inst, Ctr Mol Imaging Probe, Hengyang 421001, Hunan, Peoples R China.;[Tang, Li; Wu, Yingying; Li, Na; Liu, Fen; Tan, Xiaofeng; Wang, Minghui; Yang, Qinglai; Tan, XF; Wu, Gui-long; Gong, Hongyu; Xia, Hong; Tang, L] Univ South China, Canc Res Inst, Hunan Engn Res Ctr Early Diag & Treatment Liver Ca, Hengyang Med Sch, Hengyang 421001, Hunan, Peoples R China.;[Li, Na; Liu, Fen; Tan, Xiaofeng; Wang, Minghui; Yang, Qinglai] Univ South China, Hengyang Med Sch, Key Lab Rare Pediat Dis, MOE, Hengyang 421001, Hunan, Peoples R China.;[Li, Na; Liu, Fen; Tan, Xiaofeng; Wang, Minghui; Yang, Qinglai] Univ South China, Hengyang Med Sch, NHC Key Lab Birth Defect Res & Prevent, Hengyang 421001, Hunan, Peoples R China.
通讯机构：
[Tan, XF; Yang, QL ; Tang, L] U;Univ South China, Affiliated Hosp 1, Canc Res Inst, Dept Hepatopancreatobiliary Surg, Hengyang 421001, Hunan, Peoples R China.;Univ South China, Canc Res Inst, Ctr Mol Imaging Probe, Hengyang 421001, Hunan, Peoples R China.;Univ South China, Canc Res Inst, Hunan Engn Res Ctr Early Diag & Treatment Liver Ca, Hengyang Med Sch, Hengyang 421001, Hunan, Peoples R China.
关键词：
Colorimetric and photothermal detection;Copper peroxide;Point-of-care testing (POCT);Self-carried signal tag;Uranyl ion
摘要：
Background The development of highly sensitive and selective point-of-care testing (POCT) techniques using optical methods for uranyl ion (UO 2 2+ ) is essential for the effective monitoring of acidic uranium contamination. colorimetric methods have gained significant attention for their rapid response times, ease of use, and cost-effectiveness in the quantitative analysis of uranyl ions.
The development of highly sensitive and selective point-of-care testing (POCT) techniques using optical methods for uranyl ion (UO 2 2+ ) is essential for the effective monitoring of acidic uranium contamination. colorimetric methods have gained significant attention for their rapid response times, ease of use, and cost-effectiveness in the quantitative analysis of uranyl ions.
Results Herein, this study presents a self-assembled nanosheet composed of 3,3,5,5-tetramethylbenzidine (TMB) and CuO 2 , designed for the dual-mode colorimetric and photothermal detection of UO 2 2+ . The CuO 2 nanodots could be incorporated into TMB nanosheets by the nanoprecipitation method. The TMB-CuO 2 nanosheets exhibited spontaneous decomposition in acidic environments, leading to the production of Cu 2+ , H 2 O 2 , and TMB, which facilitated in situ TMB oxidation through a Fenton reaction. The UO 2 2+ can form coordination complexes with imines derived from the oxidation products of TMB, leading to significant accumulation and discoloration, thereby enabling the detection of UO 2 2+ with naked eyes and handheld thermometers conveniently. The constructed UO 2 2+ sensor demonstrates acceptable sensitivity and stability, with a linear range of 2.6–78.12 μM and a low detection limit (1.78 μM).
Herein, this study presents a self-assembled nanosheet composed of 3,3,5,5-tetramethylbenzidine (TMB) and CuO 2 , designed for the dual-mode colorimetric and photothermal detection of UO 2 2+ . The CuO 2 nanodots could be incorporated into TMB nanosheets by the nanoprecipitation method. The TMB-CuO 2 nanosheets exhibited spontaneous decomposition in acidic environments, leading to the production of Cu 2+ , H 2 O 2 , and TMB, which facilitated in situ TMB oxidation through a Fenton reaction. The UO 2 2+ can form coordination complexes with imines derived from the oxidation products of TMB, leading to significant accumulation and discoloration, thereby enabling the detection of UO 2 2+ with naked eyes and handheld thermometers conveniently. The constructed UO 2 2+ sensor demonstrates acceptable sensitivity and stability, with a linear range of 2.6–78.12 μM and a low detection limit (1.78 μM).
Significance and novelty This study provides a method for synthesizing self-carried signal tag nanomaterials with enhanced loading capacity, further expanding the application of straightforward colorimetric and thermometric techniques for the sensitive and selective detection of acidic uranium contamination.
This study provides a method for synthesizing self-carried signal tag nanomaterials with enhanced loading capacity, further expanding the application of straightforward colorimetric and thermometric techniques for the sensitive and selective detection of acidic uranium contamination.
摘要：
Persistent and maladaptive drug-related memories represent a key component in drug addiction. Converging evidence from both preclinical and clinical studies has demonstrated the potential efficacy of the memory reconsolidation updating procedure (MRUP), a non-pharmacological strategy intertwining two distinct memory processes: reconsolidation and extinction-alternatively termed "the memory retrieval-extinction procedure". This procedure presents a promising approach to attenuate, if not erase, entrenched drug memories and prevent relapse. The present review delineates the applications, molecular underpinnings, and operational boundaries of MRUP in the context of various forms of substance dependence. Furthermore, we critically examine the methodological limitations of MRUP, postulating potential refinement to optimize its therapeutic efficacy. In addition, we also look at the potential integration of MRUP and neurostimulation treatments in the domain of substance addiction. Overall, existing studies underscore the significant potential of MRUP, suggesting that interventions predicated on it could herald a promising avenue to enhance clinical outcomes in substance addiction therapy.
关键词：
Drug reposition;Enrichment score;Immunoregulation;LINCS;Lenalidomide;Radioprotection
摘要：
Ionizing radiation induces DNA damage and impairs genomic integrity, leading to cell death and tissue injuries or carcinogenesis. Medical radiation protectors are essential and necessary. However, there are limited radioprotectors in clinics, which can't meet the growing demand for countering radiation emergencies. Traditional drug discovery approach has been proven expensive and risky. Computational drug repositioning provides an attractive strategy for radioprotector discovery. Here we constructed a systematic workflow to identify repositioning radioprotectors by comparison of biosimilarity between γ-ray and known medicines characterized by gene expression signatures from GEO and LINCS. Using enrichment scoring, medicines with negative scores were considered as candidates of revising or mitigating radiation injuries. Seven approved medicines were identified, and their targets enriched in steroid and estrogen metabolic, chemical carcinogenesis associated pathways. Lenalidomide, an approved medicine for multiple myeloma and anemia, was further verified as a promising potential radioprotector. It increases survival of mice after lethal doses of irradiation by alleviating bone marrow and intestinal injury in vivo, and inhibits apoptosis of cultured irradiated AHH- 1 and IEC- 6 cells in vitro. This study introduces rational drug repositioning to radiation medicine and provides viable candidates for radioprotective therapeutic regimens.
作者：
Luo, Sihuan;Zhao, Xiaomei;Wang, Yijin;Jiang, Miao;Cao, Yi
期刊：
Food and Chemical Toxicology,2025年197:115304 ISSN：0278-6915
通讯作者：
Cao, Y
作者机构：
[Zhao, Xiaomei; Cao, Yi; Wang, Yijin; Luo, Sihuan] Univ South China, Sch Publ Hlth, Hengyang Med Sch, Hunan Prov Key Lab Typ Environm Pollut & Hlth Haza, Hengyang 421001, Peoples R China.;[Jiang, Miao] Univ South China, Inst Cardiovasc Dis, Hengyang Med Coll, Key Lab Arteriosclerol Hunan Prov,Hunan Int Sci &, Hengyang 421001, Peoples R China.
通讯机构：
[Cao, Y ] U;Univ South China, Sch Publ Hlth, Hengyang Med Sch, Hunan Prov Key Lab Typ Environm Pollut & Hlth Haza, Hengyang 421001, Peoples R China.
关键词：
Autophagy;In vivo toxicity;Lipid profiles;Nanoplastics;Oral exposure
摘要：
The wide uses of plastics lead to nanoplastic exposure in reality. Previous studies reported that micro- and nano-plastics (MNPs) disrupted metabolism, but few studies investigated lipid profile changes. Hereby, we exposed mice to vehicles (control), 0.05 or 0.5 mg/kg 20 or 100 nm nanoplastics via gavage, once a day, for 14 days. Albeit no obvious tissue damage, lipidomics data revealed 76 up-regulated and 29 down-regulated lipid molecules in mouse intestines. Further analysis revealed that a number of up-regulated lipid molecules belong to glycerophospholipid (GP). Among GP, we noticed an up-regulation of 9 phosphatidylserine (PS) molecules, and we further verified the presence of autophagosomes and co-localization of typical autophagic lipolysis proteins in intestinal sections, as well as decreased lysosomal associated protein 2 (LAMP2) and increased adipose triglyceride lipase (ATGL) in intestinal homogenates, indicating perturbed autophagic pathway. The exposure also up-regulated 9 phosphatidylinositol (PI) molecules, and we verified a significant decrease of 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR), indicating altered PI3K-signaling pathway. Besides GP, nanoplastics also significantly up-regulated some sphingolipids (SP), such as ceramide (Cer), and some sterol lipids, such as cholesterol derivatives. Combined, these results suggested that oral exposure to nanoplastics altered lipid profiles and related signaling pathway in mouse intestines.
The wide uses of plastics lead to nanoplastic exposure in reality. Previous studies reported that micro- and nano-plastics (MNPs) disrupted metabolism, but few studies investigated lipid profile changes. Hereby, we exposed mice to vehicles (control), 0.05 or 0.5 mg/kg 20 or 100 nm nanoplastics via gavage, once a day, for 14 days. Albeit no obvious tissue damage, lipidomics data revealed 76 up-regulated and 29 down-regulated lipid molecules in mouse intestines. Further analysis revealed that a number of up-regulated lipid molecules belong to glycerophospholipid (GP). Among GP, we noticed an up-regulation of 9 phosphatidylserine (PS) molecules, and we further verified the presence of autophagosomes and co-localization of typical autophagic lipolysis proteins in intestinal sections, as well as decreased lysosomal associated protein 2 (LAMP2) and increased adipose triglyceride lipase (ATGL) in intestinal homogenates, indicating perturbed autophagic pathway. The exposure also up-regulated 9 phosphatidylinositol (PI) molecules, and we verified a significant decrease of 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR), indicating altered PI3K-signaling pathway. Besides GP, nanoplastics also significantly up-regulated some sphingolipids (SP), such as ceramide (Cer), and some sterol lipids, such as cholesterol derivatives. Combined, these results suggested that oral exposure to nanoplastics altered lipid profiles and related signaling pathway in mouse intestines.
作者机构：
[Liu, Ying; Deng, Min; Zhai, Zibo; He, Longwei; Wang, Peipei; Li, Songjiao; Cheng, Dan; He, LW] Univ South China, Hunan Prov Cooperat Innovat Ctr Mol Target New Dru, Hengyang Med Sch, Dept Pharm & Pharmacol, Hengyang 421002, Peoples R China.;[Cheng, Dan] Univ South China, Affiliated Nanhua Hosp, Clin Res Inst, Hengyang Med Sch,Dept Gastroenterol, Hengyang 421002, Peoples R China.;[He, LW; He, Longwei] Henan Normal Univ, Sch Chem & Chem Engn, Xinxiang 453007, Peoples R China.
通讯机构：
[He, LW ] H;[Li, SJ ; He, LW] U;Univ South China, Hunan Prov Cooperat Innovat Ctr Mol Target New Dru, Hengyang Med Sch, Dept Pharm & Pharmacol, Hengyang 421002, Peoples R China.;Henan Normal Univ, Sch Chem & Chem Engn, Xinxiang 453007, Peoples R China.
摘要：
Revealing changes in the tumor microenvironment is crucial for understanding cancer and developing sensitive methods for precise cancer imaging and diagnosis. Intracellular hydrogen peroxide (H(2)O(2)) and microenvironmental factors (e.g., viscosity and polarity) are closely linked to various physiological and pathological processes, making them potential biomarkers for cancer. However, a triple-response theranostic probe for precise tumor imaging and therapy has not yet been achieved due to the lack of effective tools. Herein, we present a mitochondria-targeting near-infrared (NIR) fluorescent probe, VPH-5DF, capable of simultaneously monitoring H(2)O(2), viscosity, and polarity through dual NIR channels. The probe specifically detects H(2)O(2) via NIR emission (λ(em) = 650 nm) and shows high sensitivity to microenvironmental viscosity/polarity in the deep NIR channel (λ(em) ≈ 750 nm). Furthermore, the probe not only monitors mitochondrial polarity, viscosity, and fluctuations in endogenous/exogenous H(2)O(2) levels but also distinguishes cancer cells from normal cells through multiple parameters. Additionally, VPH-5DF can be employed to monitor alterations in H(2)O(2) levels, as well as changes in viscosity and polarity, during drug-induced pyroptosis in living cells. After treatment with VPH-5DF, chemotherapy-induced oxidative damage to the mitochondria in tumor cells activated the pyroptosis pathway, leading to a robust antitumor response, as evidenced in xenograft tumor models. Thus, this triple-response theranostic prodrug offers a new platform for precise in vivo cancer diagnosis and anticancer chemotherapy.
