作者机构：
[Wu, Yimou; Shi, Zhisheng; Lei, Aihua; Xiang, Lin; Wu, YM; Ding, Nan] Univ South China, Hunan Prov Cooperat Innovat Ctr Mol Target New Dru, Hunan Prov Key Lab Special Pathogens Prevent & Con, Inst Pathogen Biol,Hengyang Med Coll, Hengyang 421001, Peoples R China.;[Wei, Bo] Univ South China, Hengyang Med Coll, Res Lab Translat Med, Hengyang 421001, Peoples R China.
通讯机构：
[Wu, YM ; Wei, B ] U;Univ South China, Hunan Prov Cooperat Innovat Ctr Mol Target New Dru, Hunan Prov Key Lab Special Pathogens Prevent & Con, Inst Pathogen Biol,Hengyang Med Coll, Hengyang 421001, Peoples R China.;Univ South China, Hengyang Med Coll, Res Lab Translat Med, Hengyang 421001, Peoples R China.
摘要：
Mycoplasma pneumoniae (M. pneumoniae) is an atypical bacterial pathogen responsible for community-acquired pneumonia primarily among school-aged children and young adults. Camellia oleifera (C. oleifera) has been used as a medicinal and edible plant in China for centuries, the constituents from which possessed various bioactivities. Notably, flavonoids existing in residues of C. oleifera defatted seeds exhibited significant anti-inflammatory activities. In the present study, we investigated the impact of total flavonoids from C. oleifera (TFCO) seed extract on M. pneumoniae pneumonia. TFCO was obtained using multiple column chromatography methods and identified as kaempferol glycosides via UPLC-HRESIMS. In a M. pneumoniae pneumonia mouse model, TFCO significantly reduced the lung damage, suppressed IL-1 beta, IL-6, and TNF-alpha production, and curbed TLR2 activation triggered by M. pneumoniae. Similarly, in RAW264.7 macrophage cells stimulated by lipid-associated membrane proteins (LAMPs), TFCO suppressed the generation of proinflammatory cytokines and TLR2 expression. Moreover, TFCO diminished the phosphorylation of I kappa B alpha, JNK, ERK, p38, and p65 nuclear translocation in vitro. In conclusion, TFCO alleviated M. pneumoniae-induced lung damage via inhibition of TLR2-mediated NF-kappa B and MAPK pathways, suggesting its potential therapeutic application in M. pneumoniae-triggered lung inflammation.
作者机构：
[Zhou, Jie; Xie, Bibo; Zhao, Feijun; Zhao, FJ; Duan, Junxia; Zhao, Sisi; Liu, Peng; Liu, P; Zhang, Xiaohong] Univ South China, Inst Pathogen Biol, Affiliated Hosp 1, Dept Clin Lab Med,Hengyang Med Coll, Hengyang, Peoples R China.;[Zhou, Jie; Xie, Bibo; Zhao, Feijun; Zhao, FJ; Duan, Junxia; Zhao, Sisi; Liu, Peng; Liu, P; Zhang, Xiaohong] Univ South China, Key Lab Special Pathogen Prevent & Control Hunan, Affiliated Hosp 1, Dept Clin Lab Med,Hengyang Med Coll, Hengyang, Peoples R China.;[Wang, Yali] Univ South China, Hengyang Med Coll, Dept Clin Med Undergrad, Hengyang, Peoples R China.;[Yin, Weiguo] Qingyuan Peoples Hosp, Dept Lab, Qingyuan, Peoples R China.
通讯机构：
[Zhao, FJ ; Liu, P] U;Univ South China, Inst Pathogen Biol, Affiliated Hosp 1, Dept Clin Lab Med,Hengyang Med Coll, Hengyang, Peoples R China.;Univ South China, Key Lab Special Pathogen Prevent & Control Hunan, Affiliated Hosp 1, Dept Clin Lab Med,Hengyang Med Coll, Hengyang, Peoples R China.
关键词：
Tp0971;Treponema pallidum;immune-protective effect;invasion process
摘要：
Treponema pallidum (T. pallidum), the pathogen of syphilis, can invade organisms through mucous membranes or broken skin and proliferate in the host. It spreads rapidly and causes chronic systemic multi-organ damage. Currently, the invasion and pathogenesis of T. pallidum remain a mystery. In this study, we established a T. pallidum infection model in New Zealand rabbits, and the T. pallidum burden in various tissues and organs was detected to investigate the dynamic spread of T. pallidum in different organs. Our results indicated that the T. pallidum burden in rabbits was in a cyclic and repeated dynamic process of decreasing and increasing after infection. In addition, the localization of lipoprotein Tp0971 was confirmed by using the gel microdroplet method. We found that Tp0971 might be a membrane lipoprotein that exists in the inner and outer membranes of T. pallidum. The immune-protective effect of the T. pallidum infection-dependent antigen Tp0971 was evaluated. Tp0971/CpG can induce high levels of Tp0971-specific antibodies, delay skin damage, and promote healing at the infected sites of T. pallidum in New Zealand rabbits. This indicated that Tp0971 may serve as a vaccine antigen candidate. Our results provide new ideas for future research on the proliferation, spread mechanism, and vaccine development of T. pallidum. IMPORTANCE The past two decades have seen a worldwide resurgence in infections caused by Treponema pallidum (T. pallidum) subsp. pallidum, the syphilis spirochete. The well-recognized capacity of the syphilis spirochete for early dissemination and immune evasion has earned it the designation '' the stealth pathogen.'' There are many hurdles to studying syphilis pathogenesis, most notably the difficulty of culturing and genetically manipulating T. pallidum, as well as the absence of an effective vaccine for T. pallidum prevention. T. pallidum infection in humans is a complex and lengthy process. In this study, we investigated the invasion process and the function of the infection-dependent antigen Tp0971 as an immunogen to inhibit the dissemination of T. pallidum in an animal infection model. This enables a better understanding of the specific pathogenic mechanism of this pathogen, syphilis pathogenesis, and vaccine research.
摘要：
Annexin A2 is a Ca(2+) regulated protein belonging to the Annexin family and is found in the cytoplasm and cell membrane. It can exist in a monomeric form or in a heterotetrameric form with the S100A10 dimer. The research on Annexin A2 in tumours is currently active, and studies on its role in pathogen infection are increasing. Annexin A2 plays a crucial role in the life cycle of viruses by mediating adhesion, internalization, uncoating, transport, and release. In the case of parasites, bacteria, mycoplasma, fungi, and other pathogens, Annexin A2 binds to the ligand on the pathogen, which mediates the pathogen's adhesion to the host cell, ultimately leading to infection and damage to the host. Furthermore, some studies have developed biological or chemical drugs that target Annexin A2, which have demonstrated promising anti-infective effects. Thus, targeting Annexin A2 may present a promising therapeutic approach for the treatment of diverse infectious diseases. In summary, this paper provides an overview of Annexin A2 and its role in various pathogens. It highlights its regulation of pathogen infection and its potential as a therapeutic target for the treatment of infectious diseases.
作者机构：
[Chen, Guangqun; He, Jie; Jiang, Yiling; Yi, Lan; Tan, Hui; Liu, Ran; Ling, Hui; Qi, Su] Univ South China, Canc Res Inst, Hunan Prov Key Lab Canc Cellular & Mol Pathol, Hengyang, Peoples R China.;[Jiang, Yiling; Qi, Su] Univ South China, Affiliated Hosp 1, Dept Oncol, Hengyang, Peoples R China.;[Chen, Guangqun] Loudi Cent Hosp, Dept Oncol, Loudi, Peoples R China.;[Liu, Ran] First Hosp Changsha, Dept Pathol, Changsha, Peoples R China.;[Qi, Su] Univ South China, Canc Res Inst, Coll Hunan Prov, Key Lab Tumor Cellular & Mol Pathol,Hengyang Med C, 28 Changsheng Xi Rd, Hengyang 421001, Peoples R China.
通讯机构：
[Qi Su; Qi Su Qi Su Qi Su] H;Hunan Province Key Laboratory of Cancer Cellular and Molecular Pathology, Cancer Research Institute, University of South China, Hengyang, China<&wdkj&>Department of Oncology, First Affiliated Hospital, University of South China, Hengyang, China
摘要：
Exosomes secreted from cells carry rich information from their parent cells, representing a promising biomarker for investigation of diseases. We develop a dual-nanopore biosensor using DNA aptamers to specifically recognize CD63 protein on the exosome's surface, which enables label-free exosome detection based on ionic current change. The sensor allows for sensitive detection of exosomes with a detection limit of 3.4 × 10(6) particles/mL. The dual-nanopore biosensor was able to form an intrapipette electric circuit for ionic current measurement due to its unique structure, which is crucial to achieve detection of exosome secretion from a single cell. We utilized a microwell array chip to entrap a single cell into a confined microwell with small volume, enabling the accumulation of exosomes with high concentration. The dual-nanopore biosensor was positioned into the microwell with a single cell, and monitoring of exosome secretion from a single cell in different cell lines and under different stimulations has been achieved. Our design may provide a useful platform for developing nanopore biosensors for detecting cell secretions from a single living cell.
作者机构：
[Peng, Jianchun; Dai, Yueli; Cao, Yi] Univ South China, Affiliated Hosp 2, Hengyang Med Sch, Dept Radiol, Hengyang, Hunan, Peoples R China.;[Zhou, Hong; Ouyang, Chenyu; Luo, Guanghua] Univ South China, Affiliated Hosp 1, Hengyang Med Sch, Dept Radiol, Hengyang, Hunan, Peoples R China.;[Gao, AB; Gao, Anbo] Univ South China, Affiliated Hosp 2, Clin Res Inst, Hengyang Med Sch, Hengyang, Hunan, Peoples R China.;[Gao, AB; Gao, Anbo] Univ South China, Affiliated Hosp 2, Hengyang Med Sch, Dept Cardiovasc Med, Hengyang, Hunan, Peoples R China.;[Gao, AB; Gao, Anbo] Clin Med Res Ctr Arteriosclerot Dis Hunan Prov, Key Lab Heart Failure Prevent & Treatment Hengyang, Hengyang, Hunan, Peoples R China.
通讯机构：
[Zhou, H ; Gao, AB ] U;Univ South China, Affiliated Hosp 1, Hengyang Med Sch, Dept Radiol, Hengyang, Hunan, Peoples R China.;Univ South China, Affiliated Hosp 2, Clin Res Inst, Hengyang Med Sch, Hengyang, Hunan, Peoples R China.;Univ South China, Affiliated Hosp 2, Hengyang Med Sch, Dept Cardiovasc Med, Hengyang, Hunan, Peoples R China.;Clin Med Res Ctr Arteriosclerot Dis Hunan Prov, Key Lab Heart Failure Prevent & Treatment Hengyang, Hengyang, Hunan, Peoples R China.
摘要：
OBJECTIVE: This study aimed to investigate a variety of machine learning (ML) methods to predict the association between cardiovascular risk factors and coronary artery disease-reporting and data system (CAD-RADS) scores. METHODS: This is a retrospective cohort study. Demographical, cardiovascular risk factors and coronary CT angiography (CCTA) characteristics of the patients were obtained. Coronary artery disease (CAD) was evaluated using CAD-RADS score. The stenosis severity component of the CAD-RADS was stratified into two groups: CAD-RADS score 0-2 group and CAD-RADS score 3-5 group. CAD-RADS scores were predicted with random forest (RF), k-nearest neighbors (KNN), support vector machines (SVM), neural network (NN), decision tree classification (DTC) and linear discriminant analysis (LDA). Prediction sensitivity, specificity, accuracy and area under the curve (AUC) were calculated. Feature importance analysis was utilized to find the most important predictors. RESULTS: A total of 442 CAD patients with CCTA examinations were included in this study. 234 (52.9%) subjects were CAD-RADS score 0-2 group and 208 (47.1%) were CAD-RADS score 3-5 group. CAD-RADS score 3-5 group had a high prevalence of hypertension (66.8%), hyperlipidemia (50%) and diabetes mellitus (DM) (35.1%). Age, systolic blood pressure (SBP), mean arterial pressure, pulse pressure, pulse pressure index, plasma fibrinogen, uric acid and blood urea nitrogen were significantly higher (p<0.001), and high-density lipoprotein (HDL-C) lower (p<0.001) in CAD-RADS score 3-5 group compared to the CAD-RADS score 0-2 group. Nineteen features were chosen to train the models. RF (AUC = 0.832) and LDA (AUC = 0.81) outperformed SVM (AUC = 0.772), NN (AUC = 0.773), DTC (AUC = 0.682), KNN (AUC = 0.707). Feature importance analysis indicated that plasma fibrinogen, age and DM contributed most to CAD-RADS scores. CONCLUSION: ML algorithms are capable of predicting the correlation between cardiovascular risk factors and CAD-RADS scores with high accuracy.
作者机构：
[Li, Nan-Ping; Zhang, Jing; Wang, Ai-Ping; Luo, Meng-Yi; Wang, Di] Univ South China, Inst Neurosci Res, Hengyang Med Sch, Dept Physiol, Hengyang 421001, Hunan, Peoples R China.;[Gong, Shao-Xin; Gong, SX] Univ South China, Affiliated Hosp 1, Hengyang Med Sch, Dept Pathol, Hengyang 421001, Hunan, Peoples R China.;[Wang, Ai-Ping; Tian, Ying; Luo, Meng-Yi] Univ South China, Affiliated Nanhua Hosp, Inst Clin Res, Hengyang Med SchDept Clin Lab, Hengyang 421002, Hunan, Peoples R China.;[Li, Nan-Ping; Liang, Na] Univ South China, Affiliated Nanhua Hosp, Hengyang Med Sch, Dept Anesthesiol, Hengyang 421002, Hunan, Peoples R China.
通讯机构：
[Wang, AP ; Gong, SX ] U;Univ South China, Inst Neurosci Res, Hengyang Med Sch, Dept Physiol, Hengyang 421001, Hunan, Peoples R China.;Univ South China, Affiliated Hosp 1, Hengyang Med Sch, Dept Pathol, Hengyang 421001, Hunan, Peoples R China.
关键词：
Class of effect;Pulmonary hypertension;Vascular remodeling;miRNAs
摘要：
Pulmonary hypertension (PH) is complex disease as a result of obstructive pulmonary arterial remodeling, which in turn results in elevated pulmonary arterial pressure (PAP) and subsequent right ventricular heart failure, eventually leading to premature death. However, there is still a lack of a diagnostic blood-based biomarker and therapeutic target for PH. Because of the difficulty of diagnosis, new and more easily accessible prevention and treatment strategy are being explored. New target and diagnosis biomarkers should also allow for early diagnosis. In biology, miRNAs are short endogenous RNA molecules that are not coding. It is known that miRNAs can regulate gene expression and affect a variety of biological processes. Besides, miRNAs have been proven to be a crucial factor in PH pathogenesis. miRNAs have various effects on pulmonary vascular remodeling and are expressed differentially in various pulmonary vascular cells. Nowadays, it has been shown to be critical in the functions of different miRNAs in the pathogenesis of PH. Therefore, clarifying the mechanism of miRNAs regulating pulmonary vascular remodeling is of great importance to explore new therapeutic targets of PH and improve the survival qualify and time of patients. This review is focused on the role, mechanism, and potential therapeutic targets of miRNAs in PH and puts forward possible clinical treatment strategies.
摘要：
Congenital syphilis, a significant cause of fetal mortality worldwide, is a congenital infectious disease instigated by the vertical transmission of Treponema pallidum during pregnancy. Clinical manifestations include preterm delivery, stillbirth, neonatal skin lesions, skeletal abnormalities, and central nervous system aberrations. The ongoing increase in the incidence of congenital syphilis, coupled with complexities in diagnosis, necessitates a detailed understanding of its pathogenesis for the development of improved diagnostic approaches, and to interrupt the route of vertical transmission. Drawing from the broader body of research associated with vertical transmission pathogens, we aim to clarify the potential mechanisms by which Treponema pallidum breaches the placental barrier to infect the fetus.
作者机构：
[Peng, Hong; Liu, Zhifeng; Gong, Yongqian; Jiang, Qingshan; Liu, Lijun; Liao, Qingyun; Wang, Qin] Univ South China, Affiliated Hosp 1, Hengyang Med Sch, Dept Otolaryngol, Hengyang, Hunan, Peoples R China.;[Yang, Jing] Univ South China, Canc Res Inst, Hunan Prov Key Lab Tumor Cellular & Mol Pathol, Hengyang, Hunan, Peoples R China.;[Yang, Jing] Univ South China, Affiliated Hosp 1, Hengyang Med Sch, Dept Gastroenterol, Hengyang, Hunan, Peoples R China.;[Zhang, Xin; Lu, Zhaoyi] Cent South Univ, Key Lab Hunan Prov, Otolaryngol Major Dis Res, Changsha, Hunan, Peoples R China.
通讯机构：
[Liu, ZF ] U;Univ South China, Affiliated Hosp 1, Hengyang Med Sch, Dept Otolaryngol, Hengyang, Hunan, Peoples R China.
关键词：
Biomarker;FTH1 (ferritin heavy chain);HNSCC (head and neck squamous cell carcinoma);Metastasis;Prognosis
摘要：
BACKGROUND: Currently, ferritin heavy chain (FTH1) has been increasingly found to play a crucial role in cancer as a core regulator of ferroptosis, while its role of non-ferroptosis in head and neck squamous cell carcinoma (HNSCC) is still unclear. METHODS: Herein, we analyzed the expression level of FTH1 in HNSCC using TCGA database, and FTH1 protein in HNSCC tissues and cell lines was determined by immunohistochemistry (IHC) and western blotting, respectively. Then, its prognostic value and relationship with clinical parameters were investigated in HNSCC patients. Additionally, the biological function of FTH1 in HNSCC was explored. RESULTS: The current study showed that FTH1 is significantly overexpressed in HNSCC tissues and related to poor prognosis and lymph node metastasis of HNSCC. FTH1 knockdown could suppress the metastasis and epithelial-mesenchymal transition (EMT) process of HNSCC. CONCLUSION: Our findings indicate that FTH1 plays a critical role in the progression and metastasis of HNSCC and can serve as a promising prognostic factor and therapeutic target in HNSCC.
作者机构：
[Zhang, Tianqing] First Peoples Hosp Changde City, Dept Cardiol, Changde 415003, Hunan, Peoples R China.;[Deng, Wenxu] Cent Hosp Hengyang, Hengyang 421001, Hunan, Peoples R China.;[Deng, Ying; He, Qi] Peoples Hosp Ningxiang City, Ningxiang, Hunan, Peoples R China.;[Liu, Yao] Univ South China, Affiliated Hosp 2, Hengyang Medcial Sch, Dept Cardiovasc Med, Hunan 421001, Peoples R China.;[Xiao, Sijie] First Peoples Hosp Changde City, Dept Ultrasound, Changde 415003, Peoples R China.
通讯机构：
[Liu, Y ] U;Univ South China, Affiliated Hosp 2, Hengyang Medcial Sch, Dept Cardiovasc Med, Hunan 421001, Peoples R China.
关键词：
Myocardial ischemia-reperfusion injury;Programmed cell death;Traditional Chinese medicine
摘要：
Acute myocardial infarction remains the leading cause of death in humans. Timely restoration of blood perfusion to ischemic myocardium remains the most effective strategy in the treatment of acute myocardial infarction, which can significantly reduce morbidity and mortality. However, after restoration of blood flow and reperfusion, myocardial injury will aggravate and induce apoptosis of cardiomyocytes, a process called myocardial ischemia-reperfusion injury. Studies have shown that the loss and death of cardiomyocytes caused by oxidative stress, iron load, increased lipid peroxidation, inflammation and mitochondrial dysfunction, etc., are involved in myocardial ischemia-reperfusion injury. In recent years, with the in-depth research on the pathology of myocardial ischemia-reperfusion injury, people have gradually realized that there is a new form of cell death in the pathological process of myocardial ischemia-reperfusion injury, namely ferroptosis. A number of studies have found that in the myocardial tissue of patients with acute myocardial infarction, there are pathological changes closely related to ferroptosis, such as iron metabolism disorder, lipid peroxidation, and increased reactive oxygen species free radicals. Natural plant products such as resveratrol, baicalin, cyanidin-3-O-glucoside, naringenin, and astragaloside IV can also exert therapeutic effects by correcting the imbalance of these ferroptosis-related factors and expression levels. Combining with our previous studies, this review summarizes the regulatory mechanism of natural plant products intervening ferroptosis in myocardial ischemia-reperfusion injury in recent years, in order to provide reference information for the development of targeted ferroptosis inhibitor drugs for the treatment of cardiovascular diseases.
作者机构：
[Liu, Ying; Yang, Ke; He, Longwei; Wang, Peipei; Li, Songjiao] Univ South China, Hengyang Med Sch, Canc Res Inst, Hunan Prov Cooperat Innovat Ctr Mol Target New Dru, Hengyang 421001, Peoples R China.;[Cheng, Dan] Univ South China, Affiliated Nanhua Hosp, Hengyang Med Sch, Clin Res Inst, Hengyang, Peoples R China.
通讯机构：
[Dan Cheng] C;[Longwei He] H;Clinical Research Institute, The Affiliated Nanhua Hospital, Hengyang Medical School, University of South China, Hengyang, China<&wdkj&>Hunan Provincial Key Laboratory of Tumor Microenvironment Responsive Drug Research, Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, Cancer Research Institute, Department of Pharmacy and Pharmacology, Hengyang Medical School, University of South China, Hengyang, 421001, PR China
期刊：
Cancer Immunology, Immunotherapy,2023年72(7):2299-2308 ISSN：0340-7004
通讯作者：
Cui, H.;Liu, L.;Dong, H.;Zeng, L.
作者机构：
[Liu, Li; Wang, Jiaren; Liao, Yanxia; Li, Qimei; Cui, Hao; Zeng, Lin; Xiao, Lushan] Southern Med Univ, Nanfang Hosp, Big Data Ctr, Guangzhou 510515, Peoples R China.;[Liu, Li; He, Jingzhe; Wang, Jiaren; Liao, Yanxia; Li, Ruining; Li, Qimei; Hong, Chang; Cui, Hao; Zeng, Lin; Xiao, Lushan] Southern Med Univ, Nanfang Hosp, Dept Infect Dis, Guangzhou 510515, Peoples R China.;[Zhu, Hongbo] Univ South China, Affiliated Hosp 1, Hengyang Med Sch, Dept Med Oncol, Hengyang 421001, Hunan, Peoples R China.;[Dong, Hanzhi] Jiangxi Canc Hosp, Affiliated Hosp 2, Jiangxi Clin Res Ctr Canc, Dept Med Oncol,Nanchang Med Coll, Nanchang 330029, Peoples R China.
通讯机构：
[Hao Cui; Lin Zeng; Li Liu] B;[Hanzhi Dong] D;Big Data Center, Nanfang Hospital, Southern Medical University, Guangzhou, China<&wdkj&>Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, China<&wdkj&>Department of Medical Oncology, Jiangxi Cancer Hospital, The Second Affiliated Hospital of Nanchang Medical College, Jiangxi Clinical Research Center for Cancer, Nanchang, China<&wdkj&>Big Data Center, Nanfang Hospital, Southern Medical University, Guangzhou, China<&wdkj&>Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, China<&wdkj&>Big Data Center, Nanfang Hospital, Southern Medical University, Guangzhou, China<&wdkj&>Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, China
摘要：
The oldest known highly conserved modification of RNA, N4-acetylcytidine, is widely distributed from archaea to eukaryotes and acts as a posttranscriptional chemical modification of RNA, contributing to the correct reading of specific nucleotide sequences during translation, stabilising mRNA and improving transcription efficiency. Yeast Kre33 and human NAT10, the only known authors of ac4C, modify tRNA with the help of the Tan1/THUMPD1 adapter to stabilise its structure. Currently, the mRNA for N4-acetylcytidine (ac4C), catalysed by NAT10 (N-acetyltransferase 10), has been implicated in a variety of human diseases, particularly cancer. This article reviews advances in the study of ac4C modification of RNA and the ac4C-related gene NAT10 in normal physiological cell development, cancer, premature disease and viral infection and discusses its therapeutic promise and future research challenges.
摘要：
Treatment of Klebsiella pneumoniae causing pyogenic infections is challenging. The clinical and molecular characteristics of Klebsiella pneumoniae causing pyogenic infections are poorly understood, and antibacterial treatment strategies are limited. We analyzed the clinical and molecular characteristics of K. pneumoniae from patients with pyogenic infections and used time-kill assays to reveal the bactericidal kinetics of antimicrobial agents against hypervirulent K. pneumoniae (hvKp). A total of 54 K. pneumoniae isolates were included, comprising 33 hvKp and 21 classic K. pneumoniae (cKp) isolates, and the hvKp and cKp isolates were identified using five genes (iroB, iucA, rmpA, rmpA2, and peg-344) that have been applied as hvKp strain markers. The median age of all cases was 54 years (25th and 75th percentiles, 50.5 to 70), 62.96% of individuals had diabetes, and 22.22% of isolates were sourced from individuals without underlying disease. The ratios of white blood cells/procalcitonin and C-reactive protein/procalcitonin were potential clinical markers for the identification of suppurative infection caused by hvKp and cKp. The 54 K. pneumoniae isolates were classified into 8 sequence type 11 (ST11) and 46 non-ST11 strains. ST11 strains carrying multiple drug resistance genes have a multidrug resistance phenotype, while non-ST11 strains carrying only intrinsic resistance genes are generally susceptible to antibiotics. Bactericidal kinetics revealed that hvKp isolates were not easily killed by antimicrobials at susceptible breakpoint concentrations compared with cKp. Given the varied clinical and molecular features and the catastrophic pathogenicity of K. pneumoniae, it is critical to determine the characteristics of such isolates for optimal management and effective treatment of K. pneumoniae causing pyogenic infections.IMPORTANCE Klebsiella pneumoniae may cause pyogenic infections, which are potentially life-threatening and bring great challenges for clinical management. However, the clinical and molecular characteristics of K. pneumoniae are poorly understood, and effective antibacterial treatment strategies are limited. We analyzed the clinical and molecular features of 54 isolates from patients with various pyogenic infections. We found that most patients with pyogenic infections had underlying diseases, such as diabetes. The ratio of white blood cells to procalcitonin and the ratio of C-reactive protein to procalcitonin were potential clinical markers for differentiating hypervirulent K. pneumoniae strains from classical K. pneumoniae strains that cause pyogenic infections. K. pneumoniae isolates of ST11 were generally more resistant to antibiotics than non-ST11 isolates. Most importantly, hypervirulent K. pneumoniae strains were more tolerant to antibiotics than classic K. pneumoniae isolates. Klebsiella pneumoniae may cause pyogenic infections, which are potentially life-threatening and bring great challenges for clinical management. However, the clinical and molecular characteristics of K. pneumoniae are poorly understood, and effective antibacterial treatment strategies are limited.
摘要：
OBJECTIVE: Our research group in the early stage identified CD109 as the target of aptamer S3 in nasopharyngeal carcinoma (NPC). This study was to use S3 to connect DNA tetrahedron (DT) and load doxorubicin (Dox) onto DT to develop a targeted delivery system, and explore whether S3-DT-Dox can achieve targeted therapy for NPC. METHODS: Aptamer S3-conjugated DT was synthesized and loaded with Dox. The effects of S3-DT-Dox on NPC cells were investigated with laser confocal microscopy, flow cytometry, and MTS assays. A nude mouse tumor model was established from NPC 5-8F cells, and the in vivo anti-tumor activity of S3-DT-Dox was examined by using fluorescent probe labeling and hematoxylin-eosin staining. RESULTS: The synthesized S3-DT had high purity and stability. S3-DT specifically recognized 5-8F cells and NPC tissues in vitro. When the ratio of S3-DT to Dox was 1:20, S3-DT had the best Dox loading efficiency. The drug release rate reached the maximum (0.402 ± 0.029) at 48h after S3-DT-Dox was prepared and mixed with PBS. S3-DT did not affect Dox toxicity to 5-8F cells, but reduced Dox toxicity to non-target cells. Meanwhile, S3-DT-Dox was able to specifically target the transplanted tumors and inhibit their growth in nude mice, with minor damage to normal tissues. CONCLUSION: Our study highlights the ability and safety of S3-DT-Dox to target NPC cells and inhibit the development NPC.
摘要：
Angiopoietin4(ANGPT4) which plays a significant role in endothelial cell proliferation, survival, angiogenesis and expansion in tumors and other pathological states is a significant regulator of tumor angiogenesis. ANGPT4 expression is enhanced in many cancer cells. For example, the overexpression of ANGPT4 promotes the formation, development and progress of lung adenocarcinoma, glioblastoma and ovarian cancer. Related studies show that ANGPT4 encourages the proliferation, survival and invasion of tumor cells, while promoting the expansion of the tumor vascular system and affecting the tumor immune microenvironment. ANGPT4 can also promote carcinogenesis by affecting the ERK1/2, PI3K/AKT and other signal pathways downstream of tyrosine kinase with immunoglobulin-like and EGF-like domains 2(TIE2) and TIE2. Therefore, ANGPT4 may be a potential and significant biomarker for predicting malignant tumor progression and adverse outcomes. In addition, inhibition of ANGPT4 may be a meaningful cancer treatment. This paper reviews the latest research results of ANGPT4 in preclinical research, and emphasizes its role in carcinogenesis. Additional research on the carcinogenic function of ANGPT4 could provide new insights into cancer biology and novel methods for cancer diagnosis and treatment.
通讯机构：
[Tan, XF; Yang, QL ; Chen, GD] U;Univ South China, Affiliated Hosp 1, Hengyang Med Sch, 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, Hengyang Med Sch, MOE Key Lab Rare Pediat Dis, Hengyang 421001, Hunan, Peoples R China.;Hunan Prov Maternal & Child Hlth Care Hosp, Key Lab Birth Defect Res & Prevent, Natl Hlth Commiss, Changsha 410008, Hunan, Peoples R China.
摘要：
The activable NIR-based phototheranostic nanoplatform (NP) is considered an efficient and reliable tumor treatment due to its strong targeting ability, flexible controllability, minimal side effects, and ideal therapeutic effect. This work describes the rational design of a second near-infrared (NIR-II) fluorescence imaging-guided organic phototheranostic NP (FTEP-TBFc NP). The molecular-engineered phototheranostic NP has a sensitive response to glutathione (GSH), generating hydrogen sulfide (H(2)S) gas, and delivering ferrocene molecules in the tumor microenvironment (TME). Under 808 nm irradiation, FTEP-TBFc could not only simultaneously generate fluorescence, heat, and singlet oxygen but also greatly enhance the generation of reactive oxygen species to improve chemodynamic therapy (CDT) and photodynamic therapy (PDT) at a biosafe laser power of 0.33 W/cm(2). H(2)S inhibits the activity of catalase and cytochrome c oxidase (COX IV) to cause the enhancement of CDT and hypothermal photothermal therapy (HPTT). Moreover, the decreased intracellular GSH concentration further increases CDT's efficacy and downregulates glutathione peroxidase 4 (GPX4) for the accumulation of lipid hydroperoxides, thus causing the ferroptosis process. Collectively, FTEP-TBFc NPs show great potential as a versatile and efficient NP for specific tumor imaging-guided multimodal cancer therapy. This unique strategy provides new perspectives and methods for designing and applying activable biomedical phototheranostics.
摘要：
With the continuous cognition of the relationship between tumor cells and tumor immune microenvironment, immunotherapy based on the immune checkpoint blockade has achieved great breakthroughs, led to improved clinical outcomes, and prolonged survival for cancer patients in recent years. Nevertheless, the de novo or acquired resistance to immunotherapy has greatly counteracted the efficacy, leading to a 20%-40% overall response rate. Thus, further in-depth understanding of the regulation of the tumor microenvironment and antitumor immunity is urgently warranted. Ubiquitination-mediated protein degradation plays vital roles in protein stabilization, activation, and dynamics as well as in cellular homeostasis modulation. The dysregulated ubiquitination and deubiquitination are closely related to the changes in physiological and pathological processes, which subsequently result in a variety of diseases including cancer. In this review, the authors first summarize the current knowledge about the involvement of the ubiquitin-proteasome system in tumor development with the ubiquitin conjugation-regulated stability of p53, phosphatase and tensin homolog, and Myc protein as examples, then dissect the potential implications of ubiquitination-mediated immune checkpoints degradation in tumor microenvironment and immune responses, and finally discuss the effects of therapeutically targeting the ubiquitin-proteasome pathway on immunotherapy, with the goal of providing deep insights into the exploitation of more precise and effective combinational therapy against cancer.
