摘要：
Capsaicin is the main active ingredient of chili peppers and the most pungent alkaloid. It is reported that capsaicin has many pharmacological effects such as analgesia, anticancer, anti-inflammatory, antibacterial, and anti-obesity. However, the application of capsaicin is limited by its adverse side effects, such as stomach irritation, stomach cramps, and burning sensation. In recent years, many capsaicin derivatives have been synthesized and their biological activities have been evaluated. Some capsaicin derivatives have shown promising activities in cells and animal models. Herein, we described the synthesis and biological activity of capsaicin and its derivatives. It is hoped that the insights obtained in this perspective will facilitate the synthesis of a second generation of capsaicin analogs with improved biological activities.
作者：
Ablikim, M.;Achasov, M. N.;Adlarson, P.;Ai, X. C.;Aliberti, R.;...
期刊：
Journal of High Energy Physics,2024年(1) ISSN：1029-8479
通讯作者：
Ablikim, M
作者机构：
[Li, Xiaoyu; Hu, T.; Chen, T.; Hou, X. T.; Heng, Y. K.; Ji, Q.; Guan, C. Y.; Liao, Y. P.; Ji, X. B.; Dong, M. Y.; Fang, S. S.; Chang, J. F.; Ding, B.; Fu, C. D.; Lin, T.; Cao, G. F.; Fu, Y. W.; Jiang, X. S.; Kiuchi, R.; Gu, M. H.; Dong, L. Y.; Li, L. J.; Fang, Y.; Ji, X. L.; Li, L. K.; Li, H. B.; Liang, H.; Huang, Y. P.; Batozskaya, V.; Chen, X. T.; He, K. L.; Chen, G.; Ablikim, M.; Chang, W. L.; Jing, M. Q.; Chen, Y. B.; Du, M. C.; Ablikim, M; Dong, J.; Chen, M. L.; Hou, G. Y.; Hou, Z. L.; Liu, B. J.; Li, Ke; Chen, H. S.; Cao, N.; Deng, Z. Y.; Cai, X.; Kui, X.; Li, W. G.; Fang, J.; Hu, H. M.; Gong, W. X.; Hu, Y.; Li, F.; Li, G.; Dai, H. L.; Li, W. D.; Fang, W. X.] Inst High Energy Phys, Beijing 100049, Peoples R China.;[Yuan, L.] Beihang Univ, Beijing 100191, Peoples R China.;[Li, Lei] Beijing Inst Petrochem Technol, Beijing 102617, Peoples R China.;[Jaeger, S.; Fritsch, M.; Kuessner, M.; Pelizaeus, M.; Kopf, B.; Wollenberg, L.; Holtmann, T.; de Boer, R. E.; Feldbauer, F.; Wiedner, U.; Heinsius, F. H. H.; Coen, S. C.; Wenzel, C. W.] Bochum Ruhr Univ, D-44780 Bochum, Germany.;[Achasov, M. N.; Nikolaev, I. B.; Muchnoi, N. Yu.] Budker Inst Nucl Phys SB RAS BINP, Novosibirsk 630090, Russia.
通讯机构：
[Ablikim, M ] I;Inst High Energy Phys, Beijing 100049, Peoples R China.
关键词：
e(+)-e(-) Experiments;Particle and Resonance Production;Spectroscopy
摘要：
Based on e(+)e(-) collision data collected at center-of-mass energies from 2.000 to 3.080 GeV by the BESIII detector at the BEPCII collider, a partial wave analysis is performed for the process e(+)e(-) -> (KSKL0)-K-0 pi(0). The results allow the Born cross sections of the process e(+)e(-) -> (KSKL0)-K-0 pi(0), as well as its subprocesses e(+)e(-) -> K*(892)K-0(0) over bar and K-2*(1430)K-0(0) to be measured. The Born cross sections for e(+)e(-) -> (KSKL0)-K-0 pi(0) are consistent with previous measurements by BaBar, but with substantially improved precision. The Born cross section lineshape of the process e(+)e(- )-> K*(892)K-0(0) is consistent with a vector meson state around 2.2 GeV with a significance of 3.2 sigma. A Breit-Wigner fit determines its mass as M-Y = (2164.7 +/- 9.1 +/- 3.1) MeV/c(2) and its width as Gamma(Y) = (32.4 +/- 21.0 +/- 1.8) MeV.
作者机构：
[Zeng, Huilan] Univ South China, Affiliated Hosp 1, Hengyang Med Sch, Dept Ophthalmol, Hengyang 421001, Hunan, Peoples R China.;[Wadkins, David; Mayberry, Jordan E.; Kuehn, Markus H.; Chen, Nathan] Univ Iowa, Dept Ophthalmol & Visual Sci, Iowa City, IA 52242 USA.;[Wadkins, David; Mayberry, Jordan E.; Kuehn, Markus H.; Chen, Nathan] Iowa City VA Ctr Prevent & Treatment Visual Loss, Iowa City, IA 52246 USA.;[Summers, Daniel W.] Univ Iowa, Dept Biol, Iowa City, IA 52242 USA.
通讯机构：
[Kuehn, MH ] U;Univ Iowa, Dept Ophthalmol & Visual Sci, Iowa City, IA 52242 USA.;Iowa City VA Ctr Prevent & Treatment Visual Loss, Iowa City, IA 52246 USA.
摘要：
Glaucoma is one of the leading causes of irreversible blindness worldwide and vision loss in the disease results from the deterioration of retinal ganglion cells (RGC) and their axons. Metabolic dysfunction of RGC plays a significant role in the onset and progression of the disease in both human patients and rodent models, highlighting the need to better define the mechanisms regulating cellular energy metabolism in glaucoma. This study sought to determine if Sarm1, a gene involved in axonal degeneration and NAD+ metabolism, contributes to glaucomatous RGC loss in a mouse model with chronic elevated intraocular pressure (IOP). Our data demonstrate that after 16weeks of elevated IOP, Sarm1 knockout (KO) mice retain significantly more RGC than control animals. Sarm1 KO mice also performed significantly better when compared to control mice during optomotor testing, indicating that visual function is preserved in this group. Our findings also indicate that Sarm1 KO mice display mild ocular developmental abnormalities, including reduced optic nerve axon diameter and lower visual acuity than controls. Finally, we present data to indicate that SARM1 expression in the optic nerve is most prominently associated with oligodendrocytes. Taken together, these data suggest that attenuating Sarm1 activity through gene therapy, pharmacologic inhibition, or NAD+ supplementation, may be a novel therapeutic approach for patients with glaucoma.
期刊：
Brain and Behavior,2024年14(2):e3373- ISSN：2162-3279
通讯作者：
Chen, YJ
作者机构：
[Chen, Liang; Chen, Yongjun; Xie, Yangzhi] Univ South China, Affiliated Nanhua Hosp, Hengyang Med Sch, Dept Neurol, Hengyang 421001, Peoples R China.;[Chen, Jiacheng] Univ South China, Affiliated Nanhua Hosp, Hengyang Med Sch, Dept Intens Care Unit, Hengyang, Peoples R China.
通讯机构：
[Chen, YJ ] U;Univ South China, Affiliated Nanhua Hosp, Hengyang Med Sch, Dept Neurol, Hengyang 421001, Peoples R China.
关键词：
M1/M2 polarization;neuroinflammation;Parkinson's disease;regulatory T cell;vitamin D receptor
摘要：
We explored the therapeutic effects of vitamin receptor activation by calcitriol in a mouse model of PD. We found that calcitriol is potent to protect against neuroinflammation and neuronal degeneration by boosting Treg. Vitamin D receptor may be a therapeutic option for PD. Abstract Objective Vitamin D deficiency is a risk factor for Parkinson's disease (PD) and vitamin D supplementation robustly alleviates neurodegeneration in PD models. However, the mechanisms underlying this effect require further clarification. Current evidence suggests that harnessing regulatory T cells (Treg) may mitigate neuronal degeneration. In this study, we investigated the therapeutic effects of vitamin D receptor activation by calcitriol on PD, specifically focusing on its role in Treg. Methods Hemiparkinsonian mice model was established through the injection of 6‐OHDA into the striatum. Mice were pretreated with calcitriol before 6‐OHDA injection. The motor performance, dopaminergic neuronal survival, contents of dopamine, and dopamine metabolites were evaluated. The pro‐inflammatory cytokines levels, T‐cell infiltration, mRNA expression of indicated microglial M1/M2 phenotypic markers, and microglial marker in the midbrain were detected. Populations of Treg in the splenic tissues were assessed using a flow cytometry assay. PC61 monoclonal antibody was applied to deplete Treg in vivo. Results We show that calcitriol supplementation notably improved motor performance and reduced dopaminergic degeneration in the 6‐OHDA‐induced PD model. Mechanistically, calcitriol promoted anti‐inflammatory/neuroprotective Treg and inhibited pro‐inflammatory/neurodestructive effector T‐cell generation in this model. This process significantly inhibited T‐cell infiltration in the midbrain, restrained microglial activation, microglial M1 polarization, and decreased pro‐inflammatory cytokines release. This more favorable inflammatory microenvironment rescued dopaminergic degeneration. To further verify that the anti‐inflammatory effects of calcitriol are associated with Treg expansion, we applied an antibody‐mediated Treg depletion assay. As predicted, the anti‐inflammatory effects of calcitriol in the PD model were diminished following Treg depletion. Conclusion These findings suggest that calcitriol's anti‐inflammatory and neuroprotective effects in PD are associated with its potential to boost Treg expansion.
作者机构：
[Cheng, Pin-Jing; Tang, Lei-Xun; Zheng, Bo; Feng, Song; Wang, Hao-Qiang; Li, Xin-Xiang; Zhao, Ji-Rong; Zhao, Da-Jun; Xue, Jie-Ming; Xiao, Min; Luo, Wen; Li, Bao-Qian] Univ South China, Sch Nucl Sci & Technol, Hengyang 421001, Peoples R China.;[Yi, Han; Chen, Yong-Hao] Chinese Acad Sci, Inst High Energy Phys, Beijing 100049, Peoples R China.;[Yi, Han; Chen, Yong-Hao] Spallat Neutron Source Sci Ctr, Dongguan 523803, Peoples R China.;[Liu, Rong; Yang, Yi-Wei; Han, Zi-Jie] China Acad Engn Phys, Inst Nucl Phys & Chem, Mianyang 621900, Peoples R China.
通讯机构：
[Feng, S ] U;Univ South China, Sch Nucl Sci & Technol, Hengyang 421001, Peoples R China.
关键词：
Neutron-induced total cross section;Natural lead;Time-of-flight;TALYS-1.96;CSNS Back-n white neutron beamline
摘要：
The neutron-induced total cross sections of natural lead have been measured in a wide energy range (0.3 eV–20 MeV) on the back-streaming white neutron beamline (Back-n) at the China Spallation Neutron Source. Neutron energy was determined by the neutron total cross-section spectrometer using the time-of-flight technique. A fast multi-cell fission chamber was used as the neutron detector, and a 10-mm-thick high-purity natural lead sample was employed for the neutron transmission measurements. The on-beam background was determined using Co, In, Ag, and Cd filters. The excitation function of
$$^\text {nat}$$
Pb(n, tot) reaction below 20 MeV was calculated using the TALYS-1.96 nuclear-reaction modeling program. The present results were compared with previous results, the evaluated data available in the five major evaluated nuclear data libraries (i.e., ENDF/B-VIII.0, JEFF-3.3, JENDL-5, CENDL-3.2, and BROND-3.1), and the theoretical calculation curve. Good agreement was found between the new results and those of previous experiments and with the theoretical curves in the corresponding region. This measurement obtained the neutron total cross section of natural lead with good accuracy over a wide energy range and added experimental data in the resonance energy range. This provides more reliable experimental data for nuclear engineering design and nuclear data evaluation of lead.
摘要：
This review provides an overview of the recent synthesis methods developed and made available for thiophene products preparation. Thiophene being an important sulfur‐containing heterocyclic motif finds use in pharmaceuticals, functional materials, organic chemistry and natural products, its efficient synthesis is equally important. Abstract Thiophene, as an important sulfur‐containing heterocyclic, is widely used in pharmaceuticals, functional materials, and natural products. Furthermore, thiophene is of great interest to synthetic chemists due to its diverse reactivities. Over the past few decades, many synthetic strategies are developed for functionalized thiophenes. Several reviews have been reported. However, there is no review on thiophene synthesis summarized based on the sulfur sources. The current review envisioned to summary the synthesis methods for thiophene with the respect of sulfur sources and give support for choose the appropriate tools to obtain thiophene substrates.
作者机构：
[Wan, Huijuan] Univ South China, Affiliated Hosp 2, Hengyang Med Sch, Dept Nephrol & Rheumatol, Hengyang 421001, Peoples R China.;[Zhang, Ya] Univ South China, Affiliated Nanhua Hosp, Hengyang Med Sch, Dept Gland Surg, Hengyang 421002, Peoples R China.;[Ning, Zhongxing] Sun Yat Sen Univ, Guangxi Hosp Div, Affiliated Hosp 1, Guangzhou, Peoples R China.;[Liu, Mingjiang] Univ South China, Affiliated Nanhua Hosp, Hengyang Med Sch, Dept Hand & Microsurg, Hengyang 421002, Peoples R China.;[Yang, SD; Yang, Shudong] Univ South China, Affiliated Hosp 2, Hengyang Med Sch, Dept Traumat Orthoped, 35 Jiefang Rd, Hengyang 421001, Hunan, Peoples R China.
通讯机构：
[Yang, SD ] U;Univ South China, Affiliated Hosp 2, Hengyang Med Sch, Dept Traumat Orthoped, 35 Jiefang Rd, Hengyang 421001, Hunan, Peoples R China.
摘要：
Rheumatoid Arthritis (RA) is an increasingly prevalent inflammatory disorder worldwide. Its complex etiology has recently brought dietary factors, particularly fiber intake, into focus as potential influencers. Our study investigates the intricate relationship between various sources of dietary fiber and RA, emphasizing the mediating role of the Dietary Inflammatory Index (DII). Leveraging data from the National Health and Nutrition Examination Survey spanning 2011 to 2020. We meticulously assessed dietary fiber intake through dual 24 h dietary recall interviews, while RA diagnoses were established based on comprehensive medical surveys. The relationships between fiber intake, RA prevalence, and DII mediation were analyzed using sophisticated multivariate logistic regression and mediation analysis. Among our study cohort, 7% were diagnosed with RA. We observed a notable inverse correlation between increased total fiber intake, particularly 5 g/day increments, and the incidence of RA, with cereal fiber intake emerging as the primary mitigating factor. Intriguingly, the DII played a significant role in mediating this association, especially regarding cereal fiber. Our findings reveal a significant association between higher cereal fiber consumption and a reduced prevalence of RA. Additionally, the DII stands out as a pivotal mediator in this relationship, highlighting dietary management's critical role in preventing and managing RA.
期刊：
JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION,2024年331(10):840-849 ISSN：0098-7484
通讯作者：
Li, Fengli;Zi, WJ
作者机构：
[Xu, Xu; Peng, Zhouzhou; Yu, Nizhen; Jiang, Lin; Ma, Jinfu; Huang, Jiacheng; Zi, Wenjie; Li, Linyu; Tian, Yan; Fan, Shitao; Xie, Dongjing; Guo, Changwei; Liu, Xiang; Song, Jiaxing; Yue, Chengsong; Huang, Jiandi; Zi, WJ; Yang, Qingwu; Qiu, Zhongming; Li, Fengli; Hu, Jinrong; Yang, Jie; Yang, Dahong] Third Mil Med Univ, Mil Med Univ 3, Xinqiao Hosp, Dept Neurol, 183 Xinqiao Main St, Chongqing 400037, Peoples R China.;[Xu, Xu; Peng, Zhouzhou; Yu, Nizhen; Jiang, Lin; Ma, Jinfu; Huang, Jiacheng; Zi, Wenjie; Li, Linyu; Tian, Yan; Fan, Shitao; Xie, Dongjing; Guo, Changwei; Liu, Xiang; Song, Jiaxing; Yue, Chengsong; Huang, Jiandi; Zi, WJ; Yang, Qingwu; Qiu, Zhongming; Li, Fengli; Hu, Jinrong; Yang, Jie; Yang, Dahong] Third Mil Med Univ, Army Med Univ, Affiliated Hosp 2, 183 Xinqiao Main St, Chongqing 400037, Peoples R China.;[Chen, Yifei] Kunming Med Univ, Dept Neurol, Affiliated Hosp 1, Kunming, Peoples R China.;[Zheng, Chong] Fujian Med Univ, Dept Neurol, Longyan Affiliated Hosp 1, Longyan, Peoples R China.;[Jiang, Shunfu] Jingdezhen 1 Peoples Hosp, Dept Neurol, Jingdezhen, Peoples R China.
通讯机构：
[Zi, WJ ; Li, FL] T;Third Mil Med Univ, Mil Med Univ 3, Xinqiao Hosp, Dept Neurol, 183 Xinqiao Main St, Chongqing 400037, Peoples R China.;Third Mil Med Univ, Army Med Univ, Affiliated Hosp 2, 183 Xinqiao Main St, Chongqing 400037, Peoples R China.
摘要：
IMPORTANCE: It is uncertain whether intravenous methylprednisolone improves outcomes for patients with acute ischemic stroke due to large-vessel occlusion (LVO) undergoing endovascular thrombectomy. OBJECTIVE: To assess the efficacy and adverse events of adjunctive intravenous low-dose methylprednisolone to endovascular thrombectomy for acute ischemic stroke secondary to LVO. DESIGN, SETTING, AND PARTICIPANTS: This investigator-initiated, randomized, double-blind, placebo-controlled trial was implemented at 82 hospitals in China, enrolling 1680 patients with stroke and proximal intracranial LVO presenting within 24 hours of time last known to be well. Recruitment took place between February 9, 2022, and June 30, 2023, with a final follow-up on September 30, 2023. INTERVENTIONS: Eligible patients were randomly assigned to intravenous methylprednisolone (n = 839) at 2 mg/kg/d or placebo (n = 841) for 3 days adjunctive to endovascular thrombectomy. MAIN OUTCOMES AND MEASURES: The primary efficacy outcome was disability level at 90 days as measured by the overall distribution of the modified Rankin Scale scores (range, 0 [no symptoms] to 6 [death]). The primary safety outcomes included mortality at 90 days and the incidence of symptomatic intracranial hemorrhage within 48 hours. RESULTS: Among 1680 patients randomized (median age, 69 years; 727 female [43.3%]), 1673 (99.6%) completed the trial. The median 90-day modified Rankin Scale score was 3 (IQR, 1-5) in the methylprednisolone group vs 3 (IQR, 1-6) in the placebo group (adjusted generalized odds ratio for a lower level of disability, 1.10 [95% CI, 0.96-1.25]; P = .17). In the methylprednisolone group, there was a lower mortality rate (23.2% vs 28.5%; adjusted risk ratio, 0.84 [95% CI, 0.71-0.98]; P = .03) and a lower rate of symptomatic intracranial hemorrhage (8.6% vs 11.7%; adjusted risk ratio, 0.74 [95% CI, 0.55-0.99]; P = .04) compared with placebo. CONCLUSIONS AND RELEVANCE: Among patients with acute ischemic stroke due to LVO undergoing endovascular thrombectomy, adjunctive methylprednisolone added to endovascular thrombectomy did not significantly improve the degree of overall disability. TRIAL REGISTRATION: ChiCTR.org.cn Identifier: ChiCTR2100051729.
作者机构：
[Yu, Miao; Guo, Xin; Zhang, Kai] Sichuan Univ, Sch Mech Engn, Chengdu 610065, Peoples R China.;[Yu, Miao; Guo, Xin; Zhang, Kai] Sichuan Univ, Yibin Ind Technol Res Inst, Yibin 644000, Peoples R China.;[Kang, Xiaomin] Univ South China, Sch Mech Engn, Hengyang 421001, Peoples R China.;[Zhang, Song] Moutai Inst, Dept Food Sci & Engn, Renhuai 564502, Guizhou, Peoples R China.;[Qian, Lu; Qian, L] South China Univ Technol, Sch Mat Sci & Engn, Guangzhou 510641, Peoples R China.
通讯机构：
[Zhang, S ] M;[Qian, L ] S;Moutai Inst, Dept Food Sci & Engn, Renhuai 564502, Guizhou, Peoples R China.;South China Univ Technol, Sch Mat Sci & Engn, Guangzhou 510641, Peoples R China.
摘要：
Hyaluronic acid (HA), a vital glycosaminoglycan in living organisms, possesses remarkable mechanical and viscoelastic properties that have garnered significant attention in therapeutic, biomedical, and cosmetic applications. However, a comprehensive picture of the physicochemical and biocharacterization of HA at the single-molecule level remains elusive. In this work, atomic force microscopy (AFM)-based single-molecule force spectroscopy (SMFS) and molecular dynamics (MD) simulation were used to investigate the nanomechanics and water retention properties of HA at the single-molecule level. The present study aims to unravel the intricate details of the influence of molecular structure on HA behavior and shed light on its unique attributes. According to the force measurements, the energy used to stretch a HA chain in water is 8.45 kJ/mol, significantly surpassing that of Curdlan (3.45 kJ/mol) and chitin (2.23 kJ/mol), both of which possess molecular structures partially similar to that of HA. Intriguingly, the strength of the intrachain interaction of HA (5.54 kJ/mol) was considerably weaker compared to Curdlan (11.06 kJ/mol) and chitin (or cellulose, 10.76 kJ/mol). This result indicates that HA exhibits a preference for interacting with water rather than with itself, thereby showing enhanced water affinity. Moreover, the force measurements demonstrated that changing the glycosidic bond from β-(1-3) (Curdlan) or β-(1-4) (chitin or cellulose) to β-(1-3) + β-(1-4) (HA) resulted in polysaccharides displaying improved water affinity and more extended conformation. These conclusions were further verified by molecular dynamics (MD) simulations. Overall, our work sheds new light on the nanomechanics and water retention properties of HA at the single-molecule level, offering valuable insights for future research in this field.
作者机构：
[Wei, Rui; Liu, Qingqing; Luo, Jun-Li; Wei, R; Sun, Yangqing; Luo, JL] Cent South Univ, Xiangya Hosp, Dept Oncol, Changsha 410008, Peoples R China.;[Zhong, Shangwei; Luo, Jun-Li; Luo, JL] Univ South China, Affiliated Hosp 2, Canc Res Inst, Hengyang Med Sch, Hengyang 421001, Peoples R China.;[Luo, Jun-Li; Luo, JL] Hunan Prov Maternal & Child Hlth Care Hosp, Natl Hlth Commiss, Key Lab Birth Defect Res & Prevent, Changsha 410008, Peoples R China.
通讯机构：
[Wei, R; Luo, JL ] C;Cent South Univ, Xiangya Hosp, Dept Oncol, Changsha 410008, Peoples R China.;Univ South China, Affiliated Hosp 2, Canc Res Inst, Hengyang Med Sch, Hengyang 421001, Peoples R China.;Hunan Prov Maternal & Child Hlth Care Hosp, Natl Hlth Commiss, Key Lab Birth Defect Res & Prevent, Changsha 410008, Peoples R China.
关键词：
FTSJ1;tumor promotor;CD8+T cell infiltration;triple-negative breast cancer
摘要：
Simple Summary In this study, we found that high FTSJ1 expression in triple-negative breast cancer patients was associated with poor prognosis and was associated with reduced infiltration of CD8+T cells in the tumor microenvironment. By knocking down FTSJ1, we observed an inhibitory effect on the proliferation and migration of triple-negative breast cancer, while inducing apoptosis and increasing the sensitivity of TNBC cells to T-cell-mediated cytotoxicity. This finding highlights the importance of FTSJ1 as a potential immunotherapy target in triple-negative breast cancer.Abstract FtsJ RNA 2 '-O-methyltransferase 1 (FTSJ1) is a member of the methyltransferase superfamily and is involved in the processing and modification of ribosomal RNA. We herein demonstrate that FTSJ1 favors TNBC progression. The knockdown of FTSJ1 inhibits TNBC cell proliferation and development, induces apoptosis of cancer cells, and increases the sensitivity of TNBC cells to T-cell-mediated cytotoxicity. Furthermore, the high expression of FTSJ1 in TNBC attenuates CD8+T cell infiltration in the tumor microenvironment (TME) correlated with poorer prognosis for clinical TNBC patients. In this study, we establish that FTSJ1 acts as a tumor promotor, is involved in cancer immune evasion, and may serve as a potential immunotherapy target in TNBC.
摘要：
AKG protects against CTX‐induced POI by inhibiting NLRP3‐mediated pyroptosis of granulosa cells, restoring the glycolysis and improving ovarian reserve function.(Created with BioRender.com). Scope Premature ovarian insufficiency (POI) is a common female infertility problem, with its pathogenesis remains unknown. The NOD‐like receptor family pyrin domain‐containing 3 (NLRP3)‐mediated pyroptosis has been proposed as a possible mechanism in POI. This study investigates the therapeutic effect of α‐ketoglutarate (AKG) on ovarian reserve function in POI rats and further explores the potential molecular mechanisms. Methods and results POI rats are caused by administration of cyclophosphamide (CTX) to determine whether AKG has a protective effect. AKG treatment increases the ovarian index, maintains both serum hormone levels and follicle number, and improves the ovarian reserve function in POI rats, as evidence by increased the level of lactate and the expression of rate‐limiting enzymes of glycolysis in the ovaries, additionally reduced the expression of NLRP3, Gasdermin D (GSDMD), Caspase‐1, Interleukin‐18 (IL‐18), and Interleukin‐1 beta (IL‐1β). In vitro, KGN cells are treated with LPS and nigericin to mimic pyroptosis, then treated with AKG and MCC950. AKG inhibits inflammatory and pyroptosis factors such as NLRP3, restores the glycolysis process in vitro, meanwhile inhibition of NLRP3 has the same effect. Conclusion AKG ameliorates CTX‐induced POI by inhibiting NLRP3‐mediated pyroptosis, which provides a new therapeutic strategy and drug target for clinical POI patients.
通讯机构：
[Jin, YP; Chen, G ; Wang, Y ; Xia, JL] W;[Xia, JL ] F;Wenzhou Med Univ, Affiliated Hosp 1, Dept Hepatobiliary Surg, Wenzhou 325035, Zhejiang, Peoples R China.;Wenzhou Med Univ, Affiliated Hosp 1, Key Lab Diag & Treatment Severe Hepatopancreat Dis, Wenzhou 325035, Zhejiang, Peoples R China.;Wenzhou Med Univ, Sch Publ Hlth & Management, Dept Epidemiol & Biostat, Wenzhou, Zhejiang, Peoples R China.
摘要：
Metastasis causes most cancer-related deaths, and the role and mechanism of periostin (POSTN) in the metastasis of hepatocellular carcinoma (HCC) remain undiscovered. In this study, DEN and HTVi HCC models were performed in hepatic-specific Postn ablation and Postn knock-in mouse to reveal the role of POSTN in HCC metastasis. Furthermore, POSTN was positively correlated with circulating EPCs level and promoted EPC mobilization and tumour infiltration. POSTN also mediated the crosstalk between HCC and EPCs, which promoted metastasis ability and upregulated CD36 expression in HCC through indirect crosstalk. Chemokine arrays further revealed that hepatic-derived POSTN induced elevated CCL2 expression and secretion in EPCs, and CCL2 promoted prometastatic traits in HCC. Mechanistic studies showed that POSTN upregulated CCL2 expression in EPCs via the αvβ3/ILK/NF-κB pathway. CCL2 further induced CD36 expression via the CCR2/STAT3 pathway by directly binding to the promoter region of CD36. Finally, CD36 was verified to have a prometastatic role in vitro and to be correlated with POSTN expression, metastasis and recurrence in HCC in clinical samples. Our findings revealed that crosstalk between HCC and EPCs is mediated by periostin/CCL2/CD36 signalling which promotes HCC metastasis and emphasizes a potential therapeutic strategy for preventing HCC metastasis.
摘要：
A huge solid cystic mass located in the mediastinum was found in a 15‐year‐old youngster suffering shortness of breath. The synovial sarcoma was diagnosed by tissue of emergency surgery. One month later, the mediastinum lesion of patient relapsed. The next‐generation sequencing was performed and revealed BRCA2 c.968dupT mutation. Eventually, the pazopanib plus nivolumab was administered with progression‐free survival of 14 months. Abstract Pericardial synovial sarcomas (PSS) have a low incidence rate and are highly invasive with a dismal prognosis. Standard treatment includes surgery, radiotherapy and chemotherapy but with limited response. Here, we report the case of a 15‐year‐old nonsmoking youngster diagnosed with PSS who developed disease relapsed from surgery after 1 month. Next‐generation sequencing (NGS) using baseline tissue was performed, and BRCA2 c.968dupT was detected. Then pazopanib (a multitargeted inhibitor) plus nivolumab (an immune checkpoint inhibitor) was administered, with a partial response and progression‐free survival of 14 months. BRCA2 c.968dupT has not previously been reported in PSS and its response to targeted combination immunotherapy are not well characterized. Here, we report the efficacy of pazopanib combined with nivolumab in a PSS patient harboring BRCA2 c.968dupT and also provide the clinical evidence of the utility of NGS in exploring actionable mutations for solid tumor. Combination therapy based on immunotherapy may be a potential treatment choice for PSS harboring BRCA2 mutation.
摘要：
This study proposes and develops a novel ionic concentration gradient electric generator (i‐CGEG) based on the evaporation rate difference of electrolytes. The i‐CGEG with PVA–Na electrolyte achieves a thermovoltage greater than 200 mV and an energy density of 77.94 J m−2 at a temperature of 323 K. Wearable devices and their corresponding cell modules are also developed to recycle body heat. Abstract Constructing concentration differences between anions and cations at the ends of an ionic conductor is an effective strategy in electricity generation for powering wearable devices. Temperature gradient or salinity gradient is the driving force behind such devices. But their corresponding power generation devices are greatly limited in actual application due to their complex structure and harsh application conditions. In this study, a novel ionic concentration gradient electric generator based on the evaporation difference of the electrolyte is proposed. The device can be constructed without the need for semipermeable membranes, and operation does not need to build a temperature difference. As a demonstration, a PVA–Na ionic hydrogel is prepared as an electrolyte for the device and achieved a thermovoltage of more than 200 mV and an energy density of 77.94 J m−2 at 323 K. Besides, the device exhibits the capability to sustain a continuous voltage output for a duration exceeding 1500 min, as well as enabling charging and discharging cycles for 100 iterations. For practical applications, a module comprising 16 sub‐cells is constructed and successfully utilized to directly power a light‐emitting diode. Wearable devices and their corresponding cell modules are also developed to recycle body heat.
摘要：
Mining can provide abundant resources, but it also causes heavy metal wastewater pollution, which poses a serious threat to aquatic ecosystems. In this study, Cypridopsis vidua was used as the test organism to investigate the single and combined acute toxicity of common heavy metals (such as chromium (Cr) and nickel (Ni)) in mining wastewater. Then, a random forest model (RF model) was used to predict the combined toxicity of chromium and nickel. Single acute toxicity experiments showed that the 96 h-LC(50 )values of the Cr and Ni for Cypridopsis vidua were 0.81 mg/L and 4.3 mg/L, respectively. aCr was more toxic than Ni. Furthermore, the combined acute toxicity experiments demonstrated that the toxicity of Cr-Ni was higher than Ni but lower than Cr. The predicted results of the RF model were highly consistent with the experimental results of the Cr-Ni combined acute toxicity. So, the model has accurate toxicity prediction ability.
摘要：
In this paper, we presented a novel technique called extended modified auxiliary equation mapping technique, which we used to analyze the combined Chen-Lee-Liu derivative nonlinear Schrodinger equation (MCLL-NLSE) analytically. With the help of three parameters, we were able to use our proposed method to produce newer, broader sets of exact solutions, including bright, periodic, semi half bright, dark, combined, semi half dark, doubly periodic, doubly bright, half bright, and half dark. This is the main distinction between our method and others currently in use. To develop the theoretical fluid dynamics, nonlinear fiber optics, electromagnetism, mathematical physics, bio-mathematics, soliton dynamics, plasma physics, industrial studies, quantum mechanics, nuclear physics and many other natural and physical sciences has been greatly impacted by recently discovered solutions. We have presented the newly discovered solutions in graphs in various dimensions using Mathematica 10.4 to provide a better clear picture of the dynamic properties of the solutions. Additionally, we conducted stability tests on the obtained solutions and presented them as a table.
摘要：
Radiation encephalopathy (RE) refers to radiation-induced brain necrosis and is a life-threatening complication in patients with nasopharyngeal carcinoma (NPC) after radiotherapy (RT), and radiation-induced pre-symptomatic glymphatic alterations have not yet been investigated. We used diffusion tensor image analysis along the perivascular space (DTI-ALPS) index to examine the pre-symptomatic glymphatic alterations in NPC patients following RT. A total of 109 patients with NPC consisted of Pre-RT (n = 35) and Post-RT (n = 74) cohorts were included. The post-RT NPC patients, with normal-appearing brain structure at the time of MRI, were further divided into Post-RT-RE- (n = 58) and Post-RT-RE+ (n = 16) subgroups based on the detection of RE in follow-up. We observed lower DTI-ALPS (left) index, DTI-ALPS (right) index and DTI-ALPS (whole brain) index in post-RT patients than that in pre-RT patients (p < 0.05). We further found that post-RT-RE+ patients demonstrated significantly lower DTI-ALPS (right) (p = 0.013), DTI-ALPS (whole brain) (p = 0.011) and marginally lower DTI-ALPS (left) (p = 0.07) than Post-RT (non-RE) patients. Significant negative correlations were observed between the maximum dosage of radiation-treatment (MDRT) and DTI-ALPS (left) index (p = 0.003) as well as DTI-ALPS (whole brain) index (p = 0.004). Receiver operating characteristic (ROC) curve analysis showed that DTI-ALPS (whole brain) index exhibited good performance (AUC = 0.706) in identifying patients more likely developing RE. We concluded that glympathic function was impaired in NPC patients following RT and DTI-ALPS index may serve as a novel imaging biomarker for diagnosis of RE.
摘要：
Background: Triple-negative breast cancer (TNBC) is a subtype of BC with high rates of mortality. The mechanism of PTPRG-AS1 in ferroptosis of TNBC was investigated. Methods: Chromatin immunoprecipitation and dual-luciferase reporter assays were used to measure intermolecular relationships. MTT and colony formation assays detected cell viability and proliferation. Kits detected Fe2+ and reactive oxygen species levels. The role of PTPRG-AS1 in tumor growth was analyzed in vivo. Results: PTPRG-AS1 was increased in TNBC tissues and cells. PTPRG-AS1 silencing increased the reduction of glutathione and GPX4, increased Fe2+ and reactive oxygen species in erastin-treated cells and inhibited proliferation. POU2F2 transcriptionally upregulated PTPRG-AS1. PTPRG-AS1 targeted miR-376c-3p to upregulate SLC7A11. PTPRG-AS1 knockdown suppressed tumor growth in vivo. Conclusion: POU2F2 transcriptionally activates PTPRG-AS1 to modulate ferroptosis and proliferation by miR-376c-3p/SLC7A11, promoting TNBC. Tweetable abstract: Triple-negative breast cancer is the most malignant subtype of BC. POU2F2 transcriptionally upregulated PTPRG-AS1. PTPRG-AS1 targeted miR-376c-3p to increase SLC7A11 expression. POU2F2 upregulated PTPRG-AS1 to inhibit ferroptosis in triple-negative breast cancer by miR-376c-3p/SLC7A11. Plain language summary: Triple-negative breast cancer (TNBC) is a kind of breast cancer with high recurrence and low survival rates. Activation of the ferroptosis pathway can inhibit BC proliferation and distant metastasis. Therefore, identifying effective biomarkers and molecular mechanisms of ferroptosis in TNBC is important for its earlier detection and therapy. PTPRG-AS1 is a new type of lncRNA discovered in recent years that is increased in various diseases and is related to prognosis. In the present study, the authors found that POU2F2 promoted PTPRG-AS1 transcription. PTPRG-AS1 knockdown activated ferroptosis in TNBC and inhibited proliferation. Mechanistically, PTPRG-AS1 targeted miR-376c-3p to upregulate SLC7A11, thereby inhibiting ferroptosis and promoting TNBC development. These results indicate that PTPRG-AS1 is a possible therapeutic target in TNBC.
作者机构：
[Huang, Haobo; Wu, Mingxin; Liu, Zhican; Zeng, Jianping; Zhang, Lingling; Zhu, Yunlong] Xiangtan Cent Hosp, Dept Cardiol, Xiangtan 411100, Peoples R China.;[Wu, Mingxin; Liu, Zhican; Zeng, Jianping; Zhu, Yunlong] Univ South China, Grad Collaborat Training Base Xiangtan Cent Hosp, Hengyang Med Sch, Hengyang 421001, Hunan, Peoples R China.;[Zhu, Yunlong] Cent South Univ, Dept Cardiol, Xiangya Hosp 2, Changsha 410011, Hunan, Peoples R China.;[Peng, Ke] Xiangtan Cent Hosp, Dept Sci Res, Xiangtan 411100, Peoples R China.;[Yang, Wenbin] Xiangtan Cent Hosp, Med Dept, Xiangtan 411100, Peoples R China.
通讯机构：
[Wu, MX ; Zhang, LL; Peng, K ] X;Xiangtan Cent Hosp, Dept Cardiol, Xiangtan 411100, Peoples R China.;Univ South China, Grad Collaborat Training Base Xiangtan Cent Hosp, Hengyang Med Sch, Hengyang 421001, Hunan, Peoples R China.;Xiangtan Cent Hosp, Dept Sci Res, Xiangtan 411100, Peoples R China.
摘要：
This study aimed to clarify the existence of the mild obesity paradox in patients with ST-segment elevation myocardial infarction (STEMI) and assess the impact of mild obesity on the prognosis of STEMI. A retrospective cohort study was conducted on STEMI patients who underwent percutaneous coronary intervention at Xiangtan Central Hospital from January 1, 2020 to July 31, 2022. After excluding individuals with a body mass index (BMI) of no less than 35kg/m(2), subjects were divided into the mildly obese group (BMI, 30-35kg/m(2)) and non-obese group (BMI < 30kg/m(2)). The cardiovascular events and death were deemed the composite endpoints and were employed as the outcome event. The study recruited 664 patients with STEMI, including 515 males and 149 females. The mildly obese group of male patients exhibited a lower incidence of composite endpoints than the non-obese group (22.4% vs. 41.3%, P < 0.001). For female patients, no significant difference was observed in the incidence of composite endpoints between the two groups (43.6% vs. 43.8%, P = 0.987). After adjusting for confounding factors, the multivariable Cox regression analysis revealed mild obesity as an independent protective factor for male patients [hazard ratio (HR) 0.47; 95% confidence interval (CI) 0.32-0.69; P < 0.001]. Nevertheless, mild obesity was not associated with the prognosis of female patients (HR 0.96; 95% CI 0.47-1.94; P = 0.9). In male STEMI patients, mild obesity presented a paradoxical effect in improving the prognosis and functioned as an independent protective factor for the prognosis of STEMI. However, no association between mild obesity and prognosis was found in female patients, possibly due to distinct physiological and metabolic characteristics between male and female patients, which deserved further investigation and validation.
作者机构：
[Chen, Nan; Yuan, Tie-chui; Li, Zhi-you] Cent South Univ, State Key Lab Powder Met, Changsha 410083, Peoples R China.;[Teng, Hao; Chen, Long-wei] Univ South China, Coll Mech Engn, Hengyang 421001, Peoples R China.
通讯机构：
[Li, ZY ] C;[Teng, H ] U;Cent South Univ, State Key Lab Powder Met, Changsha 410083, Peoples R China.;Univ South China, Coll Mech Engn, Hengyang 421001, Peoples R China.
摘要：
With high-energy wet ball milling M2 high-speed steel (HSS) powder and ferrovanadium alloy, an in-situ synthesized core-shell MC carbides reinforced M2 HSS was prepared via vacuum sintering. The phase, morphology and composition distribution of the milled composite powders, and the evolution of the sintered microstructure with the temperature and the associated mechanical properties before and after heat treatment were investigated. The ground powders were fully refined into lamellae and aggregates with V-element evenly distributed inside. Almost full densification (similar to 99.2% relative density) of the modified M2 steel was achieved at 1180 degree celsius by supersolidus liquid phase sintering. Near-spherical MC carbides and irregular M6C carbides were dispersed within the HSS matrix, and the MC developed a core-shell structure due to the solidification of the sintering liquid. Both the matrix grains and carbides of the sintered alloy had been refined by heat treatment, reaching satisfactory bending strength of 3580 MPa and hardness of HRC58, and enhancing the scratch resistance significantly.
