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1.
Chem Commun (Camb) ; 2024 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-38922126

RESUMO

Detailed photophysical processes of two AuCu14 clusters with different substituents (-F or -C(CH3)3) of the thiol ligand were studied in this work. The electronic effect of the substituents led to structural shrinkage, thus enhancing the luminous intensity. The internal conversion (IC) and intersystem crossing (ISC) rates in the AuCu14-C(CH3)3 crystal were slower compared with the AuCu14-F crystal, which was caused by the steric effect.

2.
Natl Sci Rev ; 11(7): nwae174, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38887544

RESUMO

Chemically modified superatoms have emerged as promising candidates in the new periodic table, in which Au13 and its doped M n Au13- n have been widely studied. However, their important counterpart, Ag13 artificial element, has not yet been synthesized. In this work, we report the synthesis of Ag13 nanoclusters using strong chelating ability and rigid ligands, that fills the gaps in the icosahedral superatomic metal clusters. After further doping Ag13 template with different degrees of Au atoms, we gained insight into the evolution of their optical properties. Theoretical calculations show that the kernel metal doping can modulate the transition of the excited-state electronic structure, and the electron transfer process changes from local excitation (LE) to charge transfer (CT) to LE. This study not only enriches the families of artificial superatoms, but also contributes to the understanding of the electronic states of superatomic clusters.

3.
Appl Ergon ; 120: 104333, 2024 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-38876003

RESUMO

The purpose of this study was to identify if workplace interventions, (i.e., mindfulness classes and monetary incentives for gym attendance), influenced workers' physical activity. Office-based participants were randomized into one of four intervention assignments: 1) CONTROL (no interventions) (n = 40), 2) MINDFULNESS (n = 33), 3) GYM INCENTIVE (n = 41), or 4) BOTH mindfulness and gym incentive (n = 31). Activity-tracker and self-reported metabolic expenditure and step counts were gathered between January 2020 and December 2020 whereas the eight-week long interventions were provided between January and March 2020, when the impact of COVID-19 pandemic started. While physical activity decreased during the follow-up months, percent changes of physical activity at 1-, 2-, and 9-month follow-ups compared to baseline show no significant differences between or across the four intervention assignments (p > 0.05). These results suggest that the intervention assignments had no effect on physical activity from baseline. The lack of effectiveness of these interventions on participant physical activity could be attributed to the influence of the COVID-19 pandemic, and any effects of the interventions could not outweigh the effects of the pandemic.

4.
Sci Rep ; 14(1): 13437, 2024 06 11.
Artigo em Inglês | MEDLINE | ID: mdl-38862601

RESUMO

The primary hurdles for small interference RNA (siRNA) in clinical use are targeted and cytosolic delivery. To overcome both challenges, we have established a novel platform based on phage display, called NNJA. In this approach, a lysosomal cathepsin substrate is engineered within the flexible loops of PIII, that is displaying a unique random sequence at its N-terminus. NNJA library selection targeting cell-expressed targets should yield specific peptides localized in the cytoplasm. That is because phage internalization and subsequent localization to lysosome, upon peptide binding to the cell expressed target, will result in cleavage of PIII, rendering phage non-infective. Such phage will be eliminated from the selected pool and only peptide-phage that escapes lysosomes will advance to the next round. Proof of concept studies with the NNJA library demonstrated cytosolic localization of selected peptide-phage and peptide-siRNA, confirmed through confocal microscopy. More importantly, conjugation of siHPRT to monomeric or multimeric NNJA peptides resulted in significant reduction in HPRT mRNA in various cell types without significant cytotoxicity. Sequence similarity and clustering analysis from NGS dataset provide insights into sequence composition facilitating cell penetration. NNJA platform offers a highly efficient peptide discovery engine for targeted delivery of oligonucleotides to cytosol.


Assuntos
Peptídeos Penetradores de Células , Biblioteca de Peptídeos , RNA Interferente Pequeno , Peptídeos Penetradores de Células/metabolismo , Peptídeos Penetradores de Células/química , Humanos , RNA Interferente Pequeno/genética , RNA Interferente Pequeno/metabolismo , Lisossomos/metabolismo , Técnicas de Visualização da Superfície Celular/métodos , Citosol/metabolismo
5.
Exp Cell Res ; 439(1): 114098, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38796136

RESUMO

The involvement of γδT cells, Th17 cells, and CD4+CD25+ regulatory T cells (Tregs) is crucial in the progression of pulmonary fibrosis (PF), particularly in maintaining immune tolerance and homeostasis. However, the dynamics of these cells in relation to PF progression, especially under pharmacological interventions, remains poorly understood. This study aims to unravel the interplay between the dynamic changes of these cells and the effect of pharmacological agents in a mouse model of PF induced by intratracheal instillation of bleomycin. We analyzed changes in lung histology, lung index, hydroxyproline levels, and the proportions of γδT cells, Th17 cells, and Tregs on the 3rd, 14th, and 28th days following treatment with Neferine, Isoliensinine, Pirfenidone, and Prednisolone. Our results demonstrate that these drugs can partially or dynamically reverse weight loss, decrease lung index and hydroxyproline levels, and ameliorate lung histopathological damage. Additionally, they significantly modulated the abnormal changes in γδT, Th17, and Treg cell proportions. Notably, on day 3, the proportion of γδT cells increased in the Neferine and Prednisolone groups but decreased in the Isoliensinine and Pirfenidone groups, while the proportion of Th17 cells decreased across all treated groups. On day 14, the Neferine group showed an increase in all three cell types, whereas the Pirfenidone group exhibited a decrease. In the Isoliensinine group, γδT and Th17 cells increased, and in the Prednisolone group, only Tregs increased. By day 28, an increase in Th17 cell proportion was observed in all treatment groups, with a decrease in γδT cells noted in the Neferine group. These shifts in cell proportions are consistent with the pathogenesis changes induced by these anti-PF drugs, suggesting a correlation between cellular dynamics and pharmacological interventions in PF progression. Our findings imply potential strategies for assessing the efficacy and timing of anti-PF treatments based on these cellular changes.


Assuntos
Bleomicina , Fibrose Pulmonar , Linfócitos T Reguladores , Células Th17 , Animais , Fibrose Pulmonar/induzido quimicamente , Fibrose Pulmonar/tratamento farmacológico , Fibrose Pulmonar/patologia , Fibrose Pulmonar/imunologia , Linfócitos T Reguladores/imunologia , Linfócitos T Reguladores/efeitos dos fármacos , Células Th17/efeitos dos fármacos , Células Th17/imunologia , Camundongos , Piridonas/farmacologia , Masculino , Prednisolona/farmacologia , Progressão da Doença , Camundongos Endogâmicos C57BL , Modelos Animais de Doenças , Pulmão/patologia , Pulmão/imunologia , Pulmão/efeitos dos fármacos , Subunidade alfa de Receptor de Interleucina-2/metabolismo , Isoquinolinas/farmacologia , Benzilisoquinolinas/farmacologia
6.
ACS Nano ; 18(22): 14403-14413, 2024 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-38775684

RESUMO

The highly reversible plating/stripping of Zn is plagued by dendrite growth and side reactions on metallic Zn anodes, retarding the commercial application of aqueous Zn-ion batteries. Herein, a distinctive nano dual-phase diamond (NDPD) comprised of an amorphous-crystalline heterostructure is developed to regulate Zn deposition and mechanically block dendrite growth. The rich amorphous-crystalline heterointerfaces in the NDPD endow modified Zn anodes with enhanced Zn affinity and result in homogeneous nucleation. In addition, the unparalleled hardness of the NDPD effectively overcomes the high growth stress of dendrites and mechanically impedes their proliferation. Moreover, the hydrophobic surfaces of the NDPD facilitate the desolvation of hydrate Zn2+ and prevent water-mediated side reactions. Consequently, the Zn@NDPD presents an ultrastable lifespan exceeding 3200 h at 5 mA cm-2 and 1 mAh cm-2. The practical application potential of Zn@NDPD is further demonstrated in full cells. This work exhibits the great significance of a chemical-mechanical synergistic anode modification strategy in constructing high-performance aqueous Zn-ion batteries.

7.
Microbiol Spectr ; : e0379223, 2024 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-38809029

RESUMO

The entomopathogenic fungus Beauveria bassiana provides an eco-friendly substitute to chemical insecticides for mosquito control. Nevertheless, its widespread application has been hindered by its comparatively slow efficacy in eliminating mosquitoes. To augment the potency of B. bassiana against Aedes mosquitoes, a novel recombinant strain, Bb-Cyt1Aa, was developed by incorporating the Bacillus thuringiensis toxin gene Cyt1Aa into B. bassiana. The virulence of Bb-Cyt1Aa was evaluated against Aedes aegypti and Aedes albopictus using insect bioassays. Compared to the wild-type (WT) strain, the median lethal time (LT50) for A. aegypti larvae infected with Bb-Cyt1Aa decreased by 33.3% at a concentration of 1 × 108 conidia/mL and by 22.2% at 1 × 107 conidia/mL. The LT50 for A. aegypti adults infected with Bb-Cyt1Aa through conidia ingestion was reduced by 37.5% at 1 × 108 conidia/mL and by 33.3% at 1 × 107 conidia/mL. Likewise, the LT50 for A. aegypti adults infected with Bb-Cyt1Aa through cuticle contact decreased by 33.3% and 30.8% at the same concentrations, respectively. Furthermore, the Bb-Cyt1Aa strain also demonstrated increased toxicity against both larval and adult A. albopictus, when compared to the WT strain. In conclusion, our study demonstrated that the expression of B. thuringiensis toxin Cyt1Aa in B. bassiana enhanced its virulence against Aedes mosquitoes. This suggests that B. bassiana expressing Cyt1Aa has potential value for use in mosquito control. IMPORTANCE: Beauveria bassiana is a naturally occurring fungus that can be utilized as a bioinsecticide against mosquitoes. Cyt1Aa is a delta-endotoxin protein produced by Bacillus thuringiensis that exhibits specific and potent insecticidal activity against mosquitoes. In our study, the expression of this toxin Cyt1Aa in B. bassiana enhances the virulence of B. bassiana against Aedes aegypti and Aedes albopictus, thereby increasing their effectiveness in killing mosquitoes. This novel strain can be used alongside chemical insecticides to reduce dependence on harmful chemicals, thereby minimizing negative impacts on the environment and human health. Additionally, the potential resistance of B. bassiana against mosquitoes in the future could be overcome by acquiring novel combinations of exogenous toxin genes. The presence of B. bassiana that expresses Cyt1Aa is of significant importance in mosquito control as it enhances genetic diversity, creates novel virulent strains, and contributes to the development of safer and more sustainable methods of mosquito control.

8.
J Food Sci ; 2024 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-38778552

RESUMO

In this study, a series of collagen-chitosan-eugenol (CO-CS-Eu) flow-casting composite films were prepared using collagen from sturgeon skin, chitosan, and eugenol. The physicochemical properties, mechanical properties, microstructure, as well as antioxidant and antimicrobial activities of the composite membranes were investigated by various characterization techniques. The findings revealed that the inclusion of eugenol augmented the thickness of the film, darkened its color, reduced the transparency, and enhanced the ultraviolet light-blocking capabilities, with the physicochemical properties of the CO-CS-0.25%Eu film being notably favorable. Eugenol generates increasingly intricate matrices that disperse within the system, thereby modifying the optical properties of the material. Furthermore, the tensile strength of the film decreased from 70.97 to 20.32 MPa, indicating that eugenol enhances the fluidity and ductility of the film. Added eugenol also exhibited structural impact by loosening the film cross-section and decreasing its density. The Fourier transform infrared spectroscopy results revealed the occurrence of several intermolecular interactions among collagen, chitosan, and eugenol. Moreover, the incorporation of eugenol bolstered the antioxidant and antimicrobial capabilities of the composite film. This is primarily attributed to the abundant phenolic/hydroxyl groups present in eugenol, which can react with free radicals by forming phenoxy groups and neutralizing hydroxyl groups. Consequently, inclusion of eugenol substantially enhances the freshness retention performance of the composite film. PRACTICAL APPLICATION: ● The CO-CS-Eu film utilizes collagen from sturgeon skin, improving the use of sturgeon resources.● Different concentrations of eugenol altered its synergistic effect with chitosan.● The CO-CS-Eu film is composed of natural products with safe and edible properties.

9.
Synapse ; 78(3): e22293, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38779935

RESUMO

The differentiation of bone marrow stromal cells (BMSCs) into Schwann-like cells (SCLCs) has the potential to promote the structural and functional restoration of injured axons. However, the optimal induction protocol and its underlying mechanisms remain unclear. This study aimed to compare the effectiveness of different induction protocols in promoting the differentiation of rat BMSCs into SCLCs and to explore their potential mechanisms. BMSCs were induced using two distinct methods: a composite factor induction approach (Protocol-1) and a conditioned culture medium induction approach (Protocol-2). The expression of Schwann cells (SCs) marker proteins and neurotrophic factors (NTFs) in the differentiated cells was assessed. Cell proliferation and apoptosis were also measured. During induction, changes in miR-21 and Sprouty RTK signaling antagonist 2 (SPRY2) mRNA were analyzed. Following the transfection of BMSCs with miR-21 agomir or miR-21 antagomir, induction was carried out using both protocols, and the expression of SPRY2, ERK1/2, and SCs marker proteins was examined. The results revealed that NTFs expression was higher in Protocol-1, whereas SCs marker proteins expression did not significantly differ between the two groups. Compared to Protocol-1, Protocol-2 exhibited enhanced cell proliferation and fewer apoptotic and necrotic cells. Both protocols showed a negative correlation between miR-21 and SPRY2 expression throughout the induction stages. After induction, the miR-21 agomir group exhibited reduced SPRY2 expression, increased ERK1/2 expression, and significantly elevated expression of SCs marker proteins. This study demonstrates that Protocol-1 yields higher NTFs expression, whereas Protocol-2 results in stronger SCLCs proliferation. Upregulating miR-21 suppresses SPRY2 expression, activates the ERK1/2 signaling pathway, and promotes BMSC differentiation into SCLCs.


Assuntos
Diferenciação Celular , Proliferação de Células , Proteínas de Membrana , Células-Tronco Mesenquimais , MicroRNAs , Ratos Sprague-Dawley , Células de Schwann , Animais , Células de Schwann/metabolismo , Células de Schwann/citologia , MicroRNAs/metabolismo , MicroRNAs/genética , Diferenciação Celular/fisiologia , Ratos , Células-Tronco Mesenquimais/metabolismo , Células-Tronco Mesenquimais/citologia , Proteínas de Membrana/metabolismo , Proteínas de Membrana/genética , Proliferação de Células/fisiologia , Células Cultivadas , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Peptídeos e Proteínas de Sinalização Intracelular/genética , Apoptose/fisiologia , Fatores de Crescimento Neural/metabolismo , Fatores de Crescimento Neural/genética , Meios de Cultivo Condicionados/farmacologia , Proteínas do Tecido Nervoso
10.
Chem Commun (Camb) ; 60(41): 5447-5450, 2024 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-38687569

RESUMO

A Prussian blue analogue was synthesized using biomass leather waste as a precursor by doping with Co2+ ions. This material, demonstrates good performance in both the oxygen reduction reaction and oxygen evolution reaction, and exhibits excellent charge-discharge performance and stability in zinc-air batteries.

11.
Clin Infect Dis ; 2024 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-38636950

RESUMO

BACKGROUND: QUANTI-TAF aimed to establish tenofovir-diphosphate/emtricitabine-triphosphate (TFV-DP/FTC-TP) adherence benchmarks in dried blood spots (DBS) for persons with HIV (PWH) receiving tenofovir alafenamide/emtricitabine (TAF/FTC)-based antiretroviral therapy (ART). METHODS: During a 16-week pharmacokinetic study, PWH received TAF/FTC-based ART co-encapsulated with an ingestible sensor to directly measure cumulative (enrollment to final visit) and 10-day adherence. At monthly visits, intraerythrocytic concentrations of TAF/FTC anabolites (TFV-DP/FTC-TP) in DBS were quantified by LC-MS/MS and summarized at steady-state (week 12 or 16) as median (IQR). Linear mixed-effects models evaluated factors associated with TFV-DP/FTC-TP. RESULTS: 84 participants (86% male, 11% female, and 4% transgender), predominantly receiving bictegravir/TAF/FTC (73%) enrolled. 92% completed week 12 or 16 (94% receiving unboosted ART). TFV-DP for <85% (7/72), ≥85%-<95% (9/72), and ≥95% (56/72) cumulative adherence was 2696 (2039-4108), 3117 (2332-3339), and 3344 (2605-4293) fmol/punches. All participants with ≥85% cumulative adherence had TFV-DP ≥1800 fmol/punches. Adjusting for cumulative adherence, TFV-DP was higher with boosted ART, lower BMI, and in non-Blacks. FTC-TP for <85% (14/77), ≥85%-<95% (6/77), and ≥95% (57/77) 10-day adherence was 3.52 (2.64-4.48), 4.58 (4.39-5.06), and 4.96 (4.21-6.26) pmol/punches. All participants with ≥85% 10-day adherence had FTC-TP ≥2.5 pmol/punches. Low-level viremia (HIV-1 RNA ≥20-<200 copies/mL) occurred at 60/335 (18%) visits in 33/84 (39%) participants (range: 20-149 copies/mL), with similar TFV-DP (3177 [2494-4149] fmol/punches) compared with HIV-1 RNA <20 copies/mL visits (3279 [2580-4407] fmol/punches). CONCLUSIONS: We propose PK-based TFV-DP (≥1800 fmol/punches)/FTC-TP (≥2.5 pmol/punches) benchmarks in DBS for PWH receiving unboosted TAF/FTC-based ART with ≥85% adherence. In the setting of high adherence, low-level viremia was common.

12.
Appl Ergon ; 118: 104276, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38569239

RESUMO

Previous studies on Human Factors and Ergonomics (HFE) have primarily examined the impact of Work-From-Home (WFH) on worker health and well-being, yet little research has examined the optimal implementation process of WFH programs. Work systems perspective suggests that organizational policies, leadership, and psychological factors collectively influence the success of organizational change efforts. Our study explored the roles of managerial/supervisory, psychological, and organizational policy factors in facilitating the relationship between employees' HFE awareness and their acceptance and satisfaction with the WFH arrangement. Using data from 3195 knowledge workers in the US who use computers as their primary work tool and have worked from home at least one day in the past 30 days, we employed structural equation modeling to test our hypotheses. Transformational HFE leadership and employees' general self-efficacy are pivotal in implementing ergonomic WFH arrangements. The combination of employees' HFE awareness, transformational HFE leadership, and adequate levels of self-efficacy may foster positive process outcomes (e.g., readiness for WFH arrangement, workspace design satisfaction) in WFH arrangements. Efforts that are coordinated across organizational levels determine the effectiveness of organizational change.


Assuntos
Ergonomia , Liderança , Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Local de Trabalho/psicologia , Autoeficácia , Política Organizacional , Teletrabalho , Satisfação no Emprego , Inovação Organizacional , Saúde Ocupacional
13.
Artigo em Inglês | MEDLINE | ID: mdl-38628818

RESUMO

Purpose: Results from studies of extended capecitabine after the standard adjuvant chemotherapy in early stage triple-negative breast cancer (TNBC) were inconsistent, and only low-dose capecitabine from the SYSUCC-001 trial improved disease-free survival (DFS). Adjustment of the conventional adjuvant chemotherapy doses affect the prognosis and may affect the efficacy of subsequent treatments. This study investigated whether the survival benefit of the SYSUCC-001 trial was affected by dose adjustment of the standard adjuvant chemotherapy or not. Patients and Methods: We reviewed the adjuvant chemotherapy regimens before the extended capecitabine in the SYSUCC-001 trial. Patients were classified into "consistent" (standard acceptable dose) and "inconsistent" (doses lower than acceptable dose) dose based on the minimum acceptable dose range in the landmark clinical trials. Cox proportional hazards model was used to investigate the impact of dose on the survival outcomes. Results: All 434 patients in SYSUCC-001 trial were enrolled in this study. Most of patients administered the anthracycline-taxane regimen accounted for 88.94%. Among patients in the "inconsistent" dose, 60.8% and 47% received lower doses of anthracycline and taxane separately. In the observation group, the "inconsistent" dose of anthracycline and taxane did not affect DFS compared with the "consistent" dose. Moreover, in the capecitabine group, the "inconsistent" anthracycline dose did not affect DFS compared with the "consistent" dose. However, patients with "consistent" taxane doses benefited significantly from extended capecitabine (P=0.014). The sufficient dose of adjuvant taxane had a positive effect of extended capecitabine (hazard ratio [HR] 2.04; 95% confidence interval [CI] 1.02 to 4.06). Conclusion: This study found the dose reduction of adjuvant taxane might negatively impact the efficacy of capecitabine. Therefore, the reduction of anthracycline dose over paclitaxel should be given priority during conventional adjuvant chemotherapy, if patients need dose reduction and plan for extended capecitabine.

14.
Genes (Basel) ; 15(2)2024 01 23.
Artigo em Inglês | MEDLINE | ID: mdl-38397131

RESUMO

PURPOSE: The purpose of this study was to screen the genes and pathways that are involved in spermatogonia stem cell (SSC) differentiation regulation during the transition from Aundiff to A1. Methods: RNA sequencing was performed to screen differentially expressed genes at 1 d and 2 d after SSC differentiation culture. KEGG pathway enrichment and GO function analysis were performed to reveal the genes and pathways related to the initiation of early SSC differentiation. RESULTS: The GO analysis showed that Rpl21, which regulates cell differentiation initiation, significantly increased after 1 day of SSC differentiation. The expressions of Fn1, Cd9, Fgf2, Itgb1, Epha2, Ctgf, Cttn, Timp2 and Fgfr1, which are related to promoting differentiation, were up-regulated after 2 days of SSC differentiation. The analysis of the KEGG pathway revealed that RNA transport is the most enriched pathway 1 day after SSC differentiation. Hspa2, which promotes the differentiation of male reproductive cells, and Cdkn2a, which participates in the cell cycle, were significantly up-regulated. The p53 pathway and MAPK pathway were the most enriched pathways 2 days after SSC differentiation. Cdkn1a, Hmga2, Thbs1 and Cdkn2a, microRNAs that promote cell differentiation, were also significantly up-regulated. CONCLUSIONS: RNA transport, the MAPK pathway and the p53 pathway may play vital roles in early SSC differentiation, and Rpl21, Fn1, Cd9, Fgf2, Itgb1, Epha2, Ctgf, Cttn, Timp2, Fgfr1, Hspa2, Cdkn2a, Cdkn1a, Hmga2 and Thbs1 are involved in the initiation of SSC differentiation. The findings of this study provide a reference for further revelations of the regulatory mechanism of SSC differentiation.


Assuntos
Fator 2 de Crescimento de Fibroblastos , Proteína Supressora de Tumor p53 , Masculino , Humanos , Fator 2 de Crescimento de Fibroblastos/metabolismo , Proteína Supressora de Tumor p53/genética , Espermatogônias/metabolismo , Diferenciação Celular/genética , Perfilação da Expressão Gênica
15.
Zhonghua Wei Zhong Bing Ji Jiu Yi Xue ; 36(1): 106-109, 2024 Jan.
Artigo em Chinês | MEDLINE | ID: mdl-38404284

RESUMO

At present, the major public health challenges caused by novel coronavirus infection have gradually subside. However, a large number of people are still suffering from long-novel coronavirus syndrome or post-novel coronavirus syndrome. The clinical manifestations of long coronavirus syndrome are related to multiple systems, such as respiratory, circulatory, nervous, digestive and musculoskeletal systems, with various long-term persistent symptoms after novel coronavirus infection. At the same time, the infection of the novel coronavirus is an important cause of frailty and sarcopenia in the elderly population. However, at present, the scholars have not paid enough attention to the skeletal muscle weakness caused by the novel coronavirus. Therefore, this paper focuses on the long-novel coronavirus syndrome and sarcopenia to explore the pathological mechanism of skeletal muscle attenuation caused by the SARS-CoV-2 mediated "cytokine storm", mitochondrial damage, hypoxia state and other links,so as to raise the attention of clinical and academic researchers and improve the clinical strategy of frailty and sarcopenia after novel coronavirus infection.


Assuntos
COVID-19 , Fragilidade , Sarcopenia , Idoso , Humanos , SARS-CoV-2 , Músculo Esquelético
16.
Chemistry ; 30(17): e202304371, 2024 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-38412422

RESUMO

The Diels-Alder reaction stands as one of the most pivotal transformations in organic chemistry. Its efficiency, marked by the formation of two carbon-carbon bonds and up to four new stereocenters in a single step, underscores its versatility and indispensability in synthesizing natural products and pharmaceuticals. The most significant stereoselectivity feature is the "endo rule". While this rule underpins the predictability of the stereochemical outcomes, it also underscores the challenges in achieving the opposite diastereoselectivity, making the exo-Diels-Alder reactions often considered outliers. This review delves into recent examples of exo-Diels-Alder reactions, shedding light on the factors inverting the intrinsic tendency. We explore the roles of steric, electrostatic, and orbital interactions, as well as thermodynamic equilibriums in influencing exo/endo selectivity. Furthermore, we illustrate strategies to manipulate these factors, employing approaches such as bulky substituents, s-cis conformations, transient structural constraints, and innovative control physics. Through these analyses, our aim is to provide a comprehensive understanding of how to predict and design exo-Diels-Alder reactions, paving the way for new diastereoselective catalyst systems and expanding the chemical scope of Diels-Alder reactions.

17.
Angew Chem Int Ed Engl ; 63(13): e202318030, 2024 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-38308534

RESUMO

The specific states of aggregation of metal atoms in sub-nanometer-sized gold clusters are related to the different quantum confinement volumes of electrons, leading to novel optical and electronic properties. These volumes can be tuned by changing the relative positions of the gold atoms to generate isomers. Studying the isomeric gold core and the electron coupling between the basic units is fundamentally important for nanoelectronic devices and luminescence; however, appropriate cases are lacking. In this study, the structure of the first staggered di-superatomic Au25 -S was solved using single-crystal X-ray diffraction. The optical properties of Au25 -S were studied by comparing with eclipsed Au25 -E. From Au25 -E to Au25 -S, changes in the electronic structures occurred, resulting in significantly different optical absorptions originating from the coupling between the two Au13 modules. Au25 -S shows a longer electron decay lifetime of 307.7 ps before populating the lowest triplet emissive state, compared to 1.29 ps for Au25 -E. The experimental and theoretical results show that variations in the geometric isomerism lead to distinct photophysical processes owing to isomerism-dependent electronic coupling. This study offers new insights into the connection between the geometric isomerism of nanosized building blocks and the optical properties of their assemblies, opening new possibilities for constructing function-specific nanomaterials.

18.
Hum Genet ; 143(2): 185-195, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38302665

RESUMO

PURPOSE: Miscarriage, often resulting from a variety of genetic factors, is a common pregnancy outcome. Preconception genetic carrier screening (PGCS) identifies at-risk partners for newborn genetic disorders; however, PGCS panels currently lack miscarriage-related genes. In this study, we evaluated the potential impact of both known and candidate genes on prenatal lethality and the effectiveness of PGCS in diverse populations. METHODS: We analyzed 125,748 human exome sequences and mouse and human gene function databases. Our goals were to identify genes crucial for human fetal survival (lethal genes), to find variants not present in a homozygous state in healthy humans, and to estimate carrier rates of known and candidate lethal genes in various populations and ethnic groups. RESULTS: This study identified 138 genes in which heterozygous lethal variants are present in the general population with a frequency of 0.5% or greater. Screening for these 138 genes could identify 4.6% (in the Finnish population) to 39.8% (in the East Asian population) of couples at risk of miscarriage. This explains the cause of pregnancy loss in approximately 1.1-10% of cases affected by biallelic lethal variants. CONCLUSION: This study has identified a set of genes and variants potentially associated with lethality across different ethnic backgrounds. The variation of these genes across ethnic groups underscores the need for a comprehensive, pan-ethnic PGCS panel that includes genes related to miscarriage.


Assuntos
Aborto Espontâneo , Feminino , Recém-Nascido , Humanos , Gravidez , Animais , Camundongos , Aborto Espontâneo/genética , Genes Letais , Triagem de Portadores Genéticos , Etnicidade , Biologia Computacional
19.
Sci Adv ; 10(9): eadk5047, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38416835

RESUMO

Modern synthetic technology generally invokes high temperatures to control the hydration level of ceramics, but even the state-of-the-art technology can still only control the overall hydration content. Magically, natural organisms can produce bioceramics with tailorable hydration profiles and crystallization traits solely from amorphous precursors under physiological conditions. To mimic the biomineralization tactic, here, we report pressure-controlled hydration and crystallization in fabricated ceramics, solely from the amorphous precursors of purely inorganic gels (PIGs) synthesized from biocompatible aqueous solutions with most common ions in organisms (Ca2+, Mg2+, CO32-, and PO43-). Transparent ceramic tablets are directly produced by compressing the PIGs under mild pressure, while the pressure regulates the hydration characteristics and the subsequent crystallization behaviors of the synthesized ceramics. Among the various hydration species, the moderately bound and ordered water appears to be a key in regulating the crystallization rate. This nature-inspired study offers deeper insights into the magic behind biomineralization.

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