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1.
Artigo em Inglês | MEDLINE | ID: mdl-38711173

RESUMO

Smart windows with synergetic light modulation have heightened demands for applications in smart cars and novel buildings. However, improving the on-demand energy-saving efficiency is quite challenging due to the difficulty of modulating sunlight with a broad bandwidth in an energy-saving way. Herein, a smart window with switchable near-infrared light transmittance and passive radiative cooling is prepared via a monomer design strategy and photoinduced polymerization. The effects of hydrogen bonds and fluorine groups in acrylate monomers on the electro-optical properties as well as microstructures of polymer-dispersed liquid crystal films have been systematically studied. Some films show a high contrast ratio of 90.4 or a low threshold voltage (Vth) of 2.0 V, which can be roll-to-roll processed in a large area. Besides, the film has a superior indoor temperature regulation ability due to its passive radiative cooling and controllable near-infrared light transmittance properties. Its radiative cooling efficiency is calculated to be 142.69 W/m2 and NIR transmittance could be switched to below 10%. The introduction of a carboxylic monomer and fluorinated monomer into the system endows the film with a highly efficient temperature management capability. The film has great potential for applications in fields such as flexible smart windows, camouflage materials, and so on.

2.
Biophys Rep ; 10(1): 31-40, 2024 Feb 29.
Artigo em Inglês | MEDLINE | ID: mdl-38737475

RESUMO

Soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNAER) family proteins are the engines of most intra-cellular and exocytotic membrane fusion pathways (Jahn and Scheller 2006). Over the past two decades, in-vitro liposome fusion has been proven to be a powerful tool to reconstruct physiological SNARE-mediated membrane fusion processes (Liu et al. 2017). The reconstitution of the membrane fusion process not only provides direct evidence of the capability of the cognate SNARE complex in driving membrane fusion but also allows researchers to study the functional mechanisms of regulatory proteins in related pathways (Wickner and Rizo 2017). Heretofore, a variety of delicate methods for in-vitro SNARE-mediated liposome fusion have been established (Bao et al. 2018; Diao et al. 2012; Duzgunes 2003; Gong et al. 2015; Heo et al. 2021; Kiessling et al. 2015; Kreye et al. 2008; Kyoung et al. 2013; Liu et al. 2017; Scott et al. 2003). Although technological advances have made reconstitution more physiologically relevant, increasingly elaborate experimental procedures, instruments, and data processing algorithms nevertheless hinder the non-experts from setting up basic SNARE-mediated liposome fusion assays. Here, we describe a low-cost, timesaving, and easy-to-handle protocol to set up a foundational in-vitro SNARE-mediated liposome fusion assay based on our previous publications (Liu et al. 2023; Wang and Ma 2022). The protocol can be readily adapted to assess various types of SNARE-mediated membrane fusion and the actions of fusion regulators by using appropriate alternative additives (e.g., proteins, macromolecules, chemicals, etc.). The total time required for one round of the assay is typically two days and could be extremely compressed into one day.

3.
Ecotoxicol Environ Saf ; 276: 116312, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38608383

RESUMO

The use of bisphenol A (BPA) has been restricted due to its endocrine-disrupting effects. As a widely used alternative to BPA today, environmental levels of bisphenol Z (BPZ) continue to rise and accumulate in humans. Oocyte quality is critical for a successful pregnancy. Nevertheless, the toxic impacts of BPZ on the maturation of mammalian oocytes remain unexplored. Therefore, the impacts of BPZ and BPA on oocyte meiotic maturation were compared in an in vitro mouse oocyte culture model. Exposure to 150 µM of both BPZ and BPA disrupted the assembly of the meiotic spindle and the alignment of chromosomes, and BPZ exerted stronger toxicological effects than BPA. Furthermore, BPZ resulted in aberrant expression of F-actin, preventing the formation of the actin cap. Mechanistically, BPZ exposure disrupted the mitochondrial localization pattern, reduced mitochondrial membrane potential and ATP content, leading to impaired mitochondrial function. Further studies revealed that BPZ exposure resulted in oxidative stress and altered expression of genes associated with anti-oxidative stress. Moreover, BPZ induced severe DNA damage and triggered early apoptosis in oocytes, accompanied by impaired lysosomal function. Overall, the data in this study suggest that BPZ is not a safe alternative to BPA. BPZ can trigger early apoptosis by affecting mitochondrial function and causing oxidative stress and DNA damage in oocytes. These processes disrupt cytoskeletal assembly, arrest the cell cycle, and ultimately inhibit oocyte meiotic maturation.


Assuntos
Compostos Benzidrílicos , Dano ao DNA , Disruptores Endócrinos , Meiose , Mitocôndrias , Oócitos , Estresse Oxidativo , Fenóis , Animais , Fenóis/toxicidade , Oócitos/efeitos dos fármacos , Compostos Benzidrílicos/toxicidade , Meiose/efeitos dos fármacos , Mitocôndrias/efeitos dos fármacos , Camundongos , Estresse Oxidativo/efeitos dos fármacos , Feminino , Disruptores Endócrinos/toxicidade , Apoptose/efeitos dos fármacos , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Actinas/metabolismo
4.
Sci Bull (Beijing) ; 2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38670850

RESUMO

The merging of transition metal catalysis with electrochemistry has become a powerful tool for organic synthesis because catalysts can govern the reactivity and selectivity. However, coupling catalysts with alkyl radical species generated by anodic oxidation remains challenging because of electrode passivation, dimerization, and overoxidation. In this study, we developed convergent paired electrolysis for the coupling of nickel catalysts with alkyl radicals derived from photoinduced ligand-to-metal charge-transfer of cyclic alcohols and iron catalysts, providing a practical method for site-specific and remote arylation of ketones. The synergistic use of photocatalysis with convergent paired electrolysis can provide alternative avenues for metal-catalyzed radical coupling reactions.

5.
BMC Med ; 22(1): 171, 2024 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-38649992

RESUMO

BACKGROUND: Little is known about the safety and efficacy of discontinuing antiplatelet therapy via LMWH bridging therapy in elderly patients with coronary stents implanted for > 12 months undergoing non-cardiac surgery. This randomized trial was designed to compare the clinical benefits and risks of antiplatelet drug discontinuation via LMWH bridging therapy. METHODS: Patients were randomized 1:1 to receive subcutaneous injections of either dalteparin sodium or placebo. The primary efficacy endpoint was cardiac or cerebrovascular events. The primary safety endpoint was major bleeding. RESULTS: Among 2476 randomized patients, the variables (sex, age, body mass index, comorbidities, medications, and procedural characteristics) and percutaneous coronary intervention information were not significantly different between the bridging and non-bridging groups. During the follow-up period, the rate of the combined endpoint in the bridging group was significantly lower than in the non-bridging group (5.79% vs. 8.42%, p = 0.012). The incidence of myocardial injury in the bridging group was significantly lower than in the non-bridging group (3.14% vs. 5.19%, p = 0.011). Deep vein thrombosis occurred more frequently in the non-bridging group (1.21% vs. 0.4%, p = 0.024), and there was a trend toward a higher rate of pulmonary embolism (0.32% vs. 0.08%, p = 0.177). There was no significant difference between the groups in the rates of acute myocardial infarction (0.81% vs. 1.38%), cardiac death (0.24% vs. 0.41%), stroke (0.16% vs. 0.24%), or major bleeding (1.22% vs. 1.45%). Multivariable analysis showed that LMWH bridging, creatinine clearance < 30 mL/min, preoperative hemoglobin < 10 g/dL, and diabetes mellitus were independent predictors of ischemic events. LMWH bridging and a preoperative platelet count of < 70 × 109/L were independent predictors of minor bleeding events. CONCLUSIONS: This study showed the safety and efficacy of perioperative LMWH bridging therapy in elderly patients with coronary stents implanted > 12 months undergoing non-cardiac surgery. An alternative approach might be the use of bridging therapy with half-dose LMWH. TRIAL REGISTRATION: ISRCTN65203415.


Assuntos
Stents , Humanos , Masculino , Feminino , Idoso , Idoso de 80 Anos ou mais , Anticoagulantes/administração & dosagem , Anticoagulantes/efeitos adversos , Anticoagulantes/uso terapêutico , Inibidores da Agregação Plaquetária/administração & dosagem , Inibidores da Agregação Plaquetária/uso terapêutico , Inibidores da Agregação Plaquetária/efeitos adversos , Heparina de Baixo Peso Molecular/administração & dosagem , Heparina de Baixo Peso Molecular/uso terapêutico , Heparina de Baixo Peso Molecular/efeitos adversos , Dalteparina/administração & dosagem , Dalteparina/uso terapêutico , Dalteparina/efeitos adversos , Resultado do Tratamento , Procedimentos Cirúrgicos Operatórios/efeitos adversos , Hemorragia/induzido quimicamente , Placebos/administração & dosagem , Assistência Perioperatória/métodos
6.
Toxicol In Vitro ; 98: 105834, 2024 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-38657713

RESUMO

Triphenyltin chloride (TPTCL) is widely used in various industrial and agricultural applications. This study aimed to elucidate the mechanisms underlying the toxicological effects of TPTCL on oocytes. The obtained findings revealed that TPTCL exposure reduced polar body extrusion (PBE) and induced meiotic arrest. Mechanistically, TPTCL disrupted meiotic spindle assembly and chromosome alignment. Further analysis indicated a significant decrease in p-MAPK expression, and disturbances in the localization of Pericentrin and p-Aurora A in TPTCL exposed oocytes, which suggesting impaired microtubule organizing center (MTOC)function. Moreover, TPTCL exposure enhance microtubule acetylation and microtubule instability. Therefore, the spindle assembly checkpoint (SAC) remained activated, and the activity of the anaphase-promoting complex (APC) was inhibited, thereby preventing oocytes from progressing into the entering anaphase I (AI) stage. TPTCL exposure also augmented the actin filaments in the cytoplasm. Notably, mitochondrial function appeared unaffected by TPTCL, as evidenced indicated by stable mitochondrial membrane potential and ATP content. Furthermore, TPTCL treatment altered H3K27me2, H3K27me3 and H3K9me3 levels, suggesting changes in epigenetic modifications in oocytes. Taken together, our results suggest that TPTCL disrupts cytoskeleton assembly, continuously activates SAC, inhibits APC activity, and blocks meiotic progression, ultimately impair oocyte maturation.

7.
Epidemiology ; 2024 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-38534181

RESUMO

BACKGROUND: Artificial light at night, a well-recognized circadian clock disrupter, causes disturbances in endocrine homeostasis. However, the association of artificial light at night with polycystic ovary syndrome (PCOS) is still unknown. This study examines the effects of outdoor artificial light at night on sex hormones, glucose homeostasis markers, and PCOS prevalence in Anhui Province, China. METHODS: We recruited 20633 women of reproductive age from Anhui Medical University Reproductive Medicine Center. PCOS was diagnosed according to Rotterdam criteria. We estimated long-term (previous year) and short-term (previous month) artificial light at night values for residential addresses using 500-meter resolution satellite imagery. We fitted multivariable models, using both linear and logistic regression, to estimate the association of artificial light at night with sex hormones, glucose homeostasis markers, and PCOS prevalence. RESULTS: Both long-term and short-term exposure to outdoor artificial light at night were negatively associated with follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels, while positively associated with testosterone, fasting insulin, HOMA-IR, and HOMA-ß levels. The second-highest quintile of artificial light at night was associated with increased PCOS prevalence (OR long-term =1.4, 95% CI: 1.2,1.6); OR short-term =1.3, 95% CI: 1.1,1.5) compared to the lowest quintile. In addition, prevalence of PCOS was linearly associated with long-term exposure to artificial light at night, but non-linearly associated with short-term exposure. This association was more evident in younger, obese or overweight, moderately educated, rural women, and for the summer and fall seasons. CONCLUSIONS: Outdoor artificial light at night may be a novel risk factor for PCOS.

8.
Cardiovasc Diabetol ; 23(1): 108, 2024 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-38553738

RESUMO

BACKGROUND: Coronary inflammation plays crucial role in type 2 diabetes mellitus (T2DM) induced cardiovascular complications. Both glucose-lowering drug interventions (GLDIS) and glycemic control (GC) status potentially correlate coronary inflammation, as indicated by changes in pericoronary adipose tissue (PCAT) attenuation, and thus influence cardiovascular risk. This study evaluated the impact of GLDIS and GC status on PCAT attenuation in T2DM patients. METHODS: This retrospective study collected clinical data and coronary computed tomography angiography (CCTA) images of 1,342 patients, including 547 T2DM patients and 795 non-T2DM patients in two tertiary hospitals. T2DM patients were subgroup based on two criteria: (1) GC status: well: HbA1c < 7%, moderate: 7 ≤ HbA1c ≤ 9%, and poor: HbA1c > 9%; (2) GLDIS and non-GLDIS. PCAT attenuations of the left anterior descending artery (LAD-PCAT), left circumflex artery (LCX-PCAT), and right coronary artery (RCA-PCAT) were measured. Propensity matching (PSM) was used to cross compare PCAT attenuation of non-T2DM and all subgroups of T2DM patients. Linear regressions were conducted to evaluate the impact of GC status and GLDIS on PCAT attenuation in T2DM patients. RESULTS: Significant differences were observed in RCA-PCAT and LCX-PCAT between poor GC-T2DM and non-T2DM patients (LCX: - 68.75 ± 7.59 HU vs. - 71.93 ± 7.25 HU, p = 0.008; RCA: - 74.37 ± 8.44 HU vs. - 77.2 ± 7.42 HU, p = 0.026). Higher PCAT attenuation was observed in LAD-PCAT, LCX-PCAT, and RCA-PCAT in non-GLDIS T2DM patients compared with GLDIS T2DM patients (LAD: - 78.11 ± 8.01 HU vs. - 75.04 ± 8.26 HU, p = 0.022; LCX: - 71.10 ± 8.13 HU vs. - 68.31 ± 7.90 HU, p = 0.037; RCA: - 78.17 ± 8.64 HU vs. - 73.35 ± 9.32 HU, p = 0.001). In the linear regression, other than sex and duration of diabetes, both metformin and acarbose were found to be significantly associated with lower LAD-PCAT (metformin: ß coefficient = - 2.476, p=0.021; acarbose: ß coefficient = - 1.841, p = 0.031). CONCLUSION: Inadequate diabetes management, including poor GC and lack of GLDIS, may be associated with increased coronary artery inflammation in T2DM patients, as indicated by PCAT attenuation on CCTA, leading to increased cardiovascular risk. This finding could help healthcare providers identify T2DM patients with increased cardiovascular risk, develop improved cardiovascular management programs, and reduce subsequent cardiovascular related mortality.


Assuntos
Doença da Artéria Coronariana , Diabetes Mellitus Tipo 2 , Metformina , Placa Aterosclerótica , Humanos , Angiografia Coronária/métodos , Estudos Retrospectivos , Tecido Adiposo Epicárdico , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Acarbose , Hemoglobinas Glicadas , Doença da Artéria Coronariana/diagnóstico por imagem , Doença da Artéria Coronariana/terapia , Angiografia por Tomografia Computadorizada/métodos , Tecido Adiposo/diagnóstico por imagem , Inflamação/diagnóstico por imagem , Vasos Coronários/diagnóstico por imagem
10.
Nano Lett ; 24(14): 4150-4157, 2024 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-38529926

RESUMO

Metallic Zn is considered as a promising anode material because of its abundance, eco-friendliness, and high theoretical capacity. However, the uncontrolled dendrite growth and side reactions restrict its further practical application. Herein, we proposed a ß-cyclodextrin-modified multiwalled carbon nanotube (CD-MWCNT) layer for Zn metal anodes. The obtained CD-MWCNT layer with high affinity to Zn can significantly reduce the transfer barrier of Zn2+ at the electrode/electrolyte interface, facilitating the uniform deposition of Zn2+ and suppressing water-caused side reactions. Consequently, the Zn||Zn symmetric cell assembled with CD-MWCNT shows a significantly enhanced cycling durability, maintaining a cycling life exceeding 1000 h even under a high current density of 5 mA cm-2. Furthermore, the full battery equipped with a V2O5 cathode displays an unparalleled long life. This work unveils a promising avenue toward the achievement of high-performance Zn metal anodes.

11.
Angew Chem Int Ed Engl ; 63(20): e202402910, 2024 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-38441480

RESUMO

The challenge of constructing a mechanically robust yet lightweight artificial solid-electrolyte interphase layer on lithium (Li) anodes highlights a trade-off between high battery safety and high energy density. Inspired by the intricate microstructure of the white sea urchin, we first develop a polyvinyl fluoride-hexafluoropropylene (PVDF-HFP) interfacial layer with a triple periodic minimal surface structure (TPMS) that could offer maximal modulus with minimal weight. This design endows high mechanical strength to an ordered porous structure, effectively reduces local current density, polarization, and internal resistance, and stabilizes the anode interface. At a low N/P ratio of ~3, using LiFePO4 as the cathode, Li anodes protected by TPMS-structured PVDF-HFP achieve an extremely low capacity-fading-rate of approximately 0.002 % per cycle over 200 cycles at 1 C, with an average discharge capacity of 142 mAh g-1. Meanwhile, the TPMS porous structure saves 50 wt % of the interfacial layer mass, thereby enhancing the energy density of the battery. The TPMS structure is conducive to large-scale additive manufacturing, which will provide a reference for the future development of lightweight, high-energy-density secondary batteries.

12.
Chem Asian J ; 19(9): e202301152, 2024 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-38469659

RESUMO

Wet-chemical synthesis refers to the bottom-up chemical synthesis in solution, which is among the most popular synthetic approaches towards functional two-dimensional (2D) materials. It offers several advantages, including cost-effectiveness, high yields,, precious control over the production process. As an emerging family of 2D materials, elemental 2D materials (Xenes) have shown great potential in various applications such as electronics, catalysts, biochemistry,, sensing technologies due to their exceptional/exotic properties such as large surface area, tunable band gap,, high carrier mobility. In this review, we provide a comprehensive overview of the current state-of-the-art in wet-chemical synthesis of Xenes including tellurene, bismuthene, antimonene, phosphorene,, arsenene. The current solvent compositions, process parameters utilized in wet-chemical synthesis, their effects on the thickness, stability of the resulting Xenes are also presented. Key factors considered involves ligands, precursors, surfactants, reaction time, temperature. Finally, we highlight recent advances, existing challenges in the current application of wet-chemical synthesis for Xenes production, provide perspectives on future improvement.

13.
J Agric Food Chem ; 72(10): 5439-5451, 2024 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-38412221

RESUMO

Increasing hydrogen peroxide (H2O2)-based systems have been developed to degrade various polysaccharides due to the presence of highly reactive free radicals, but published degradation mechanisms are still limited. Therefore, this study aimed to clarify the degradation mechanism of six typical glucosidic bonds from different disaccharides in an ultraviolet (UV)/H2O2 system. The results showed that the H2O2 concentration, disaccharide concentration, and radiation intensity were important factors affecting pseudo-first-order kinetic constants. Hydroxyl radical, superoxide radical, and UV alone contributed 58.37, 18.52, and 19.17% to degradation, respectively. The apparent degradation rates ranked in the order of cellobiose ≈ lactose > trehalose ≈ isomaltose > turanose > sucrose ≈ maltose. The reaction pathways were then deduced after identifying their degradation products. According to quantum chemical calculations, the cleavage of α-glycosidic bonds was more kinetically unfavorable than that of ß-glycosidic bonds. Additionally, the order of apparent degradation rates depended on the energy barriers for the formation of disaccharide-based alkoxyl radicals. Moreover, energy barriers for homolytic scissions of glucosidic C1-O or C7-O sites of these alkoxyl radicals ranked in the sequence: α-(1 → 2) ≈ α-(1 → 3) < α-(1 → 4) < ß-(1 → 4) < α-(1 → 6) < α-(1 → 1) glucosidic bonds. This study helps to explain the mechanisms of carbohydrate degradation by free radicals.


Assuntos
Álcoois , Peróxido de Hidrogênio , Poluentes Químicos da Água , Peróxido de Hidrogênio/química , Glucosídeos , Dissacarídeos/química , Maltose/metabolismo , Sacarose/química , Raios Ultravioleta , Oxirredução , Cinética , Poluentes Químicos da Água/química
14.
Environ Res ; 249: 118344, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38311200

RESUMO

More and more previously designed wastewater treatment plants (WWTPs) are upgraded to tertiary treatment to meet the higher effluent discharge standards of conventional pollutants. Contaminants of emerging concern (CECs) can cause adverse effects on organisms and usually flow into WWTPs along with urban sewage. How the retrofitted WWTPs targeting conventional pollutants will influence the treatment efficiency of CECs is seldom discussed. This study investigates the removal of CECs in two full-scale newly retrofitted WWTPs (CD and JM WWTPs), containing high-efficiency sedimentation tank and denitrification deep bed filter for enhancing total nitrogen removal. The overall CEC removal efficiencies in the CD and JM WWTPs were 73.79 % and 93.63 %, respectively. Mass balance results indicated that CD WWTP and JM WWTP release a total of 36.89 and 88.58 g/d of CECs into the environment through effluent and excess sludge, respectively. Analysis of the concentration of CECs along the treatment process revealed most CECs were removed in the biological treatment units. The incorporation of newly constructed tertiary treatment proved beneficial for CEC removal and removed 2.93 % and 2.36 % CECs, corresponding to CEC removal of 2.92 and 27.49 g/d in the CD and JM WWTPs, respectively. The data of this study were further used to evaluate the suitability of the SimpleTreat model for simulating the fate of CECs in WWTPs. The predicted fraction of CECs discharged through the biological treatment effluent were generally within ten-fold difference from the measured results, highlighting its potential for estimating CEC removal in WWTPs.


Assuntos
Nitrogênio , Eliminação de Resíduos Líquidos , Águas Residuárias , Poluentes Químicos da Água , Poluentes Químicos da Água/análise , Nitrogênio/análise , Eliminação de Resíduos Líquidos/métodos , Águas Residuárias/química , Águas Residuárias/análise
15.
EClinicalMedicine ; 69: 102468, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38361990

RESUMO

Background: Azvudine and nirmatrelvir/ritonavir are approved to treat mild-to-moderate coronavirus disease 2019 (COVID-19) in adults with a high risk for progression to severe infection. We sought to compare the antiviral effectiveness and clinical outcomes of elderly severe patients with COVID-19 receiving these two antiviral agents. Methods: In this observational study, we identified 249 elderly patients with severe COVID-19 infection who were admitted to the Second Medical Center of the People's Liberation Army General Hospital from December 2022 to January 2023, including 128 azvudine recipients, 66 nirmatrelvir/ritonavir recipients and 55 patients not received antiviral treatments. We compared the cycle threshold (Ct) value dynamic change of all three groups. The primary outcome was a composite outcome of disease progression, including all-cause death, intensive care unit admission, and initiation of invasive mechanical ventilation. The outcomes of all enrolled patients were followed up from the electronic medical record system. Kaplan-Meier and Cox risk proportional regression analyses were used to compare the clinical outcomes of all three groups. To more directly compare the effectiveness of the two antiviral drugs, we performed propensity-score matching between the two antiviral groups and compared antiviral efficacy and clinical outcomes in the matched population. Findings: Among 249 patients (mean age, 91.41 years), 77 patients died during the follow-up period. When compared to patients who did not receive any antivirals, neither nirmatrelvir/ritonavir nor azvudine demonstrated a survival benefit. The Cox analysis of the all-cause death of the three groups showed that the risk of death was 0.730 (0.423-1.262) in the azvudine group 0.802 (0.435-1.480) and in the nirmatrelvir/ritonavir group compared with the non-antiviral group. After propensity score matching, we included 58 azvudine recipients and 58 nirmatrelvir/ritonavir recipients. The fitted curve of the Ct value after matching illustrated that the rate of viral decline in the early stage of nirmatrelvir/ritonavir treatment seems to surpass that of azvudine, but there was no statistical significance. Azvudine was seemly associated with a lower risk of composite outcomes (HR:1.676, 95% CI:0.805-3.488) and short-term all-cause death (HR: 1.291, 95%CI: 0.546-3.051). Interpretation: Patients who received azvudine have a similar antiviral effectiveness and survival curve trend compared to nirmatrelvir/ritonavir. In this limited series, antiviral treatment was not associated with a significant clinical benefit. This lack of clinical benefit might be attributed to potential bias. Funding: This study was supported by the "National Key R&D Program of China" (Funding No. 2020YFC2008900) and the National Defense Science and Technology Innovation Special Zone Project (223-CXCY-N101-07-18-01).

16.
Cell Res ; 34(2): 151-168, 2024 02.
Artigo em Inglês | MEDLINE | ID: mdl-38182888

RESUMO

Autophagosome-lysosome fusion mediated by SNARE complexes is an essential step in autophagy. Two SNAP29-containing SNARE complexes have been extensively studied in starvation-induced bulk autophagy, while the relevant SNARE complexes in other types of autophagy occurring under non-starvation conditions have been overlooked. Here, we found that autophagosome-lysosome fusion in selective autophagy under non-starvation conditions does not require SNAP29-containing SNARE complexes, but requires the STX17-SNAP47-VAMP7/VAMP8 SNARE complex. Further, the STX17-SNAP47-VAMP7/VAMP8 SNARE complex also functions in starvation-induced autophagy. SNAP47 is recruited to autophagosomes following concurrent detection of ATG8s and PI(4,5)P2 via its Pleckstrin homology domain. By contrast, SNAP29-containing SNAREs are excluded from selective autophagy due to inactivation by O-GlcNAcylation under non-starvation conditions. These findings depict a previously unknown, default SNARE complex responsible for autophagosome-lysosome fusion in both selective and bulk autophagy, which could guide research and therapeutic development in autophagy-related diseases.


Assuntos
Autofagossomos , Lisossomos , Proteínas SNARE , Autofagia/fisiologia , Fusão de Membrana/fisiologia , Humanos
17.
Int J Mol Sci ; 25(2)2024 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-38279241

RESUMO

We previously discovered WS-6 as a new antidepressant in correlation to its function of stimulating neurogenesis. Herein, several different scaffolds (stilbene, 1,3-diphenyl 1-propene, 1,3-diphenyl 2-propene, 1,2-diphenyl acrylo-1-nitrile, 1,2-diphenyl acrylo-2-nitrile, 1,3-diphenyl trimethylamine), further varied through substitutions of twelve amide substituents plus the addition of a methylene unit and an inverted amide, were examined to elucidate the SARs for promoting adult rat neurogenesis. Most of the compounds could stimulate proliferation of progenitors, but just a few chemicals possessing a specific structural profile, exemplified by diphenyl acrylonitrile 29b, 32a, and 32b, showed better activity than the clinical drug NSI-189 in promoting newborn cells differentiation into mature neurons. The most potent diphenyl acrylonitrile 32b had an excellent brain AUC to plasma AUC ratio (B/P = 1.6), suggesting its potential for further development as a new lead.


Assuntos
Acrilonitrila , Alcenos , Compostos de Bifenilo , Ratos , Animais , Acrilonitrila/farmacologia , Neurogênese , Hipocampo , Nitrilas/farmacologia , Amidas
18.
Stem Cells Dev ; 33(1-2): 1-10, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37847179

RESUMO

The health of hair is directly related to people's health and appearance. Hair has key physiological functions, including skin protection and temperature regulation. Hair follicle (HF) is a vital mini-organ that directly impacts hair growth. Besides, various signaling pathways and molecules regulate the growth cycle transition of HFs. Hair and its regeneration studies have attracted much interest in recent years with the increasing rate of alopecia. Mesenchymal stem cells (MSCs), as pluripotent stem cells, can differentiate into fat, bone, and cartilage and stimulate regeneration and immunological regulation. MSCs have been widely employed to treat various clinical diseases, such as bone and cartilage injury, nerve injury, and lung injury. Besides, MSCs can be used for treatment of hair diseases due to their regenerative and immunomodulatory abilities. This review aimed to assess MSCs' treatment for alopecia, pertinent signaling pathways, and new material for hair regeneration in the last 5 years.


Assuntos
Cabelo , Células-Tronco Mesenquimais , Humanos , Cabelo/fisiologia , Folículo Piloso/metabolismo , Alopecia/metabolismo , Alopecia/terapia , Transdução de Sinais
19.
Bioorg Chem ; 143: 106983, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38016396

RESUMO

RNA polymerase is an essential enzyme involved in bacterial transcription, playing a crucial role in RNA synthesis. However, it requires the association with sigma factors to initiate this process. In our previous work, we utilized a structure-based drug discovery approach to create benzoyl and benzyl benzoic acid compounds. These compounds were designed based on the amino acid residues within the key binding site of sigma factors, which are crucial for their interaction with RNA polymerase. By inhibiting bacterial transcription, these compounds exhibited notable antimicrobial activity, and we coined them as sigmacidins to highlight their resemblance to sigma factors and the benzoic acid structure. In this study, we further modified the compound scaffolds and developed a series of sulfonamidyl benzoic acid derivatives. These derivatives displayed potent antimicrobial activity, with minimum inhibitory concentrations (MICs) as low as 1 µg/mL, demonstrating their efficacy against bacteria. Furthermore, these compounds demonstrated low cytotoxicity, indicating their potential as safe antimicrobial agents. To ascertain their mechanism of action in interfering with bacterial transcription, we conducted biochemical and cellular assays. Overall, this study showcases the effectiveness of sulfonamidyl benzoic acid derivatives as antimicrobial agents by targeting protein-protein interactions involving RNA polymerase and sigma factors. Their strong antimicrobial activity and low cytotoxicity implicate their potential in combating antibiotic-resistant bacteria.


Assuntos
Antibacterianos , Anti-Infecciosos , Antibacterianos/farmacologia , Antibacterianos/química , Fator sigma/metabolismo , RNA Polimerases Dirigidas por DNA/metabolismo , Bactérias/metabolismo , Ácido Benzoico/farmacologia , Testes de Sensibilidade Microbiana
20.
Urol Case Rep ; 52: 102634, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38148853

RESUMO

Upper tract urothelial carcinoma (UTUC) is a relatively rare malignant neoplasm of the urinary system. Due to its highly aggressiveness, the tumor has already undergone invasive growth when most UTUC patients are diagnosed. In addition, the most common cause of fever in cancer patients is infection, and cancer patients with neoplastic fever are relatively rare. We reported a 58-year-old man with invasive high-grade UTUC accompanied by hyperthermia.

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