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Photocatalytic overall water splitting holds great promise for solar-to-hydrogen conversion. Maintaining charge separation is a major challenge but is key to unlocking this potential. Here we discovered a metal-organic framework (MOF) that shows suppressed charge recombination. This MOF features electronically insulated Zn2+ nodes and two chemically equivalent, yet crystallographically independent, linkers. These linkers behave as an electron donor-acceptor pair with non-overlapping band edges. Upon photoexcitation, the MOF undergoes a dynamic excited-state structural twist, inducing orbital rearrangements that forbid radiative relaxation and thereby promote a long-lived charge-separated state. As a result, the MOF achieves visible-light photocatalytic overall water splitting, in the presence of co-catalysts, with an apparent quantum efficiency of 3.09 ± 0.32% at 365 nm and shows little activity loss in 100 h of consecutive runs. Furthermore, the dynamic excited-state structural twist is also successfully extended to other photocatalysts. This strategy for suppressing charge recombination will be applicable to diverse photochemical processes beyond overall water splitting.
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BACKGROUND: For the treatment of coronoid process fractures, medial, lateral, anterior, anteromedial, and posterior approaches have been increasingly reported; however, there is no general consensus on the method of fixation of coronal fractures. Here, we present a highly-extensile minimally invasive approach to treat coronoid process fractures using a mini-plate that can achieve anatomic reduction, stable fixation, and anterior capsular repair. Further, the study aimed to determine the complication rate of the anterior minimally invasive approach and to evaluate functional and clinical patient-reported outcomes during follow-up. METHODS: Thirty-one patients diagnosed with coronoid fractures accompanied with a "terrible triad" or posteromedial rotational instability between April 2012 and October 2018 were included in the analysis. Anatomical reduction and mini-plate fixation of coronoid fractures were performed using an anterior minimally invasive approach. Patient-reported outcomes were evaluated using the Mayo Elbow Performance Index (MEPI) score, range of motion (ROM), and the visual analog score (VAS). The time of fracture healing and complications were recorded. RESULTS: The mean follow-up time was 26.7 months (range, 14-60 months). The average time to radiological union was 3.6 ± 1.3 months. During the follow-up period, the average elbow extension was 6.8 ± 2.9° while the average flexion was 129.6 ± 4.6°. According to Morrey's criteria, 26 (81%) elbows achieved a normal desired ROM. At the last follow-up, the mean MEPI score was 98 ± 3.3 points. There were no instances of elbow instability, elbow joint stiffness, subluxation or dislocation, infection, blood vessel complications, or nerve palsy. Overall, 10 elbows (31%) experienced heterotopic ossification. CONCLUSION: An anterior minimally invasive approach allows satisfactory fixation of coronoid fractures while reducing incision complications due to over-dissection of soft tissue injuries. In addition, this incision does not compromise the soft tissue stability of the elbow joint and allows the patient a more rapid return to rehabilitation exercises.
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Placas Óseas , Articulación del Codo , Fijación Interna de Fracturas , Fracturas Conminutas , Rango del Movimiento Articular , Fracturas del Cúbito , Humanos , Masculino , Femenino , Fracturas del Cúbito/cirugía , Fracturas del Cúbito/diagnóstico por imagen , Fijación Interna de Fracturas/métodos , Fijación Interna de Fracturas/instrumentación , Persona de Mediana Edad , Adulto , Fracturas Conminutas/cirugía , Fracturas Conminutas/diagnóstico por imagen , Articulación del Codo/cirugía , Articulación del Codo/diagnóstico por imagen , Articulación del Codo/fisiopatología , Resultado del Tratamiento , Estudios Retrospectivos , Estudios de Seguimiento , Procedimientos Quirúrgicos Mínimamente Invasivos/métodos , Procedimientos Quirúrgicos Mínimamente Invasivos/instrumentación , Curación de Fractura , Anciano , Medición de Resultados Informados por el Paciente , Adulto JovenRESUMEN
Inspired by enzymatic catalysis, it is crucial to construct hydrogen-bonding-rich microenvironment around catalytic sites; unfortunately, its precise construction and understanding how the distance between such microenvironment and catalytic sites affects the catalysis remain significantly challenging. In this work, a series of metal-organic framework (MOF)-based single-atom Ru1 catalysts, namely, Ru1/UiO-67-X (X = -H, -m-(NH2)2, -o-(NH2)2), have been synthesized, where the distance between the hydrogen-bonding microenvironment and Ru1 sites is modulated by altering the location of amino groups. The -NH2 group can form hydrogen bonds with H2O, constituting a unique microenvironment that causes an increased water concentration around the Ru1 sites. Remarkably, Ru1/UiO-67-o-(NH2)2 displays a superior photocatalytic hydrogen production rate, â¼4.6 and â¼146.6 times of Ru1/UiO-67-m-(NH2)2 and Ru1/UiO-67, respectively. Both experimental and computational results suggest that the close proximity of amino groups to the Ru1 sites in Ru1/UiO-67-o-(NH2)2 improves charge transfer and H2O dissociation, accounting for the promoted photocatalytic hydrogen production.
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BACKGROUND: Gastric cancer is the fifth most common cancer and the fourth most common cause of cancer death worldwide, yet the prognosis of advanced disease remains poor. METHODS: This was a randomized, double-blinded, phase 2 trial (ClinicalTrials.gov: NCT04908813). Patients with locally advanced/metastatic HER2-positive gastric/gastroesophageal junction cancer and no prior systemic antitumor therapy were randomized 1:1:1 to 25 mg/kg HLX22 (a novel anti-HER2 antibody) + HLX02 (trastuzumab biosimilar) + oxaliplatin and capecitabine (XELOX) (group A), 15 mg/kg HLX22 + HLX02 + XELOX (group B), or placebo + HLX02 + XELOX (group C) in 3-week cycles. Primary endpoints were progression-free survival (PFS) and objective response rate (ORR) assessed by independent radiological review committee (IRRC). FINDINGS: Between November 29, 2021, and June 6, 2022, 82 patients were screened; 53 were randomized to group A (n = 18), B (n = 17), and C (n = 18). With 14.3 months of median follow-up, IRRC-assessed median PFS was prolonged with the addition of HLX22 (A vs. C, 15.1 vs. 8.2 months, hazard ratio [HR] 0.5 [95% confidence interval (CI) 0.17-1.27]; B vs. C, not reached vs. 8.2 months, HR 0.1 [95% CI 0.04-0.52]). Confirmed ORR was comparable among groups (A vs. B vs. C, 77.8% vs. 82.4% vs. 88.9%). Treatment-related adverse events (TRAEs) were observed in 18 (100%), 16 (94.1%), and 17 (94.4%) patients, respectively. One (5.6%) patient in group C reported a grade 5 TRAE. CONCLUSIONS: Adding HLX22 to HLX02 and XELOX prolonged PFS and enhanced antitumor response in the first-line treatment of HER2-positive gastric cancer, with manageable safety. FUNDING: Shanghai Henlius Biotech, Inc.
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BACKGROUND: Trastuzumab and pertuzumab combination has been approved for the treatment of patients with HER2-positive metastatic breast cancer. However, trastuzumab and pertuzumab combination did not show improvement in overall survival in patients with HER2-positive metastatic gastric cancer. METHODS: We developed a new HER2-targeted monoclonal antibody, HLX22, targeting HER2 subdomain IV as trastuzumab but with non-overlapping epitopes. We examined the antitumor effects of this novel HER2-antibody in gastric cell lines and cell line-derived xenograft (CDX) and patient-derived xenograft (PDX) models. RESULTS: HLX22 in combination with HLX02 (trastuzumab biosimilar) induced enhancement of HER2/HER2 homodimers and HER2/EGFR heterodimers internalization, which ultimately led to the reduction in signal transductions involving STAT3, P70 S6, and AKT; gene expressions of FGF-FGFR-PI3K-MTOR, EGF-EGFR-RAS, TGF-ß-SMAD, PLCG and cell cycle progression related pathways that favor tumor development, proliferation, progression, migration and survival in gastric cancer cell line NCI-N87 were also reduced. These differing but complementary actions contributed to the synergistic antitumor efficacy of the HLX22 and HLX02 combination in gastric cancer cell lines, CDX and PDX. In addition, HLX22 in combination with HLX02 demonstrated stronger antitumor efficacy than HLX02 and HLX11 (a potential pertuzumab biosimilar) combination treatment both in vitro and in vivo. CONCLUSIONS: These results suggested that the application of non-competing antibodies HLX22 and HLX02 targeting HER2 subdomain IV together may be of substantial benefit to gastric cancer patients who currently respond suboptimal to trastuzumab therapy.
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Epítopos , Receptores ErbB , Receptor ErbB-2 , Neoplasias Gástricas , Ensayos Antitumor por Modelo de Xenoinjerto , Neoplasias Gástricas/tratamiento farmacológico , Neoplasias Gástricas/patología , Neoplasias Gástricas/metabolismo , Humanos , Receptor ErbB-2/metabolismo , Línea Celular Tumoral , Animales , Receptores ErbB/metabolismo , Multimerización de Proteína/efectos de los fármacos , Transducción de Señal/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Dominios Proteicos , Femenino , Ratones , Anticuerpos Monoclonales/farmacología , Anticuerpos Monoclonales/uso terapéutico , Antineoplásicos/farmacología , Antineoplásicos/uso terapéuticoRESUMEN
Sophora alopecuroides has important uses in medicine, wind breaking, and sand fixation. The CHY-zinc-finger and RING-finger (CHYR) proteins are crucial for plant growth, development, and environmental adaptation; however, genetic data regarding the CHYR family remain scarce. We aimed to investigate the CHYR gene family in S. alopecuroides and its response to abiotic stress, and identified 18 new SaCHYR genes from S. alopecuroides whole-genome data, categorized into 3 subclasses through a phylogenetic analysis. Gene structure, protein domains, and conserved motifs analyses revealed an exon-intron structure and conserved domain similarities. A chromosome localization analysis showed distribution across 12 chromosomes. A promoter analysis revealed abiotic stress-, light-, and hormone-responsive elements. An RNA-sequencing expression pattern analysis revealed positive responses of SaCHYR genes to salt, alkali, and drought stress. SaCHYR4 overexpression considerably enhanced alkali and drought tolerance in Arabidopsis thaliana. These findings shed light on SaCHYR's function and the resistance mechanisms of S. alopecuroides, presenting new genetic resources for crop resistance breeding.
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Regulación de la Expresión Génica de las Plantas , Familia de Multigenes , Filogenia , Proteínas de Plantas , Sophora , Estrés Fisiológico , Estrés Fisiológico/genética , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Sophora/genética , Arabidopsis/genética , Genoma de Planta , Sequías , Cromosomas de las Plantas/genéticaRESUMEN
Aim: Liquid biopsies analyzing cell-free DNA (cfDNA) methylation in plasma offer a noninvasive diagnostic for diseases, with the potential of aging biomarkers underexplored. Methods: Utilizing enzymatic methyl-seq (EM-seq), this study assessed cfDNA methylation patterns in aging with blood from 35 healthy individuals. Results: It found aging signatures, including higher cfDNA levels and variations in fragment sizes, plus approximately 2000 age-related differentially methylated CpG sites. A biological age predictive model based on 48 CpG sites showed a strong correlation with chronological age, verified by two datasets. Age-specific epigenetic shifts linked to inflammation were revealed through differentially methylated regions profiling and Olink proteomics. Conclusion: These findings suggest cfDNA methylation as a potential aging biomarker and might exacerbate immunoinflammatory reactivity in older individuals.
Our bodies undergo many changes as we age, some of which might affect our health. To better understand these changes, scientists study something called 'cell-free DNA' (cfDNA) in our blood. This cfDNA can give us clues about our health and the risk of diseases like cancer or heart conditions.In our research, we analyzed cfDNA from the blood of 35 people to identify patterns associated with aging. We discovered that approximately 2000 specific spots in our DNA change in a way that's linked to aging. These changes might help us figure out someone's biological age essentially, how old their body seems based on various health factors, which can differ from their actual age.We also found that these DNA changes could indicate how aging might make the body's defense system which fights off diseases react more intensely. Understanding this could be crucial for managing health as we get older.Our study suggests that cfDNA could be a useful marker for aging, offering a new approach to understanding and possibly managing the health effects associated with growing older.
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Envejecimiento , Ácidos Nucleicos Libres de Células , Islas de CpG , Metilación de ADN , Epigénesis Genética , Inflamación , Humanos , Envejecimiento/genética , Ácidos Nucleicos Libres de Células/sangre , Ácidos Nucleicos Libres de Células/genética , Femenino , Inflamación/genética , Masculino , Anciano , Persona de Mediana Edad , Adulto , Biomarcadores/sangre , Anciano de 80 o más AñosRESUMEN
BACKGROUND: Whether or not the addition of immunotherapy to current standard-of-care treatments can improve efficacy in proficient mismatch repair (pMMR)/microsatellite-stable (MSS) metastatic colorectal cancer (mCRC), the predominant type of mCRC, is unclear. METHODS: This randomized, double-blind, phase 2 part of a phase 2/3 trial was conducted at 23 hospitals across China (ClinicalTrials.gov: NCT04547166). Patients with unresectable metastatic/recurrent colorectal adenocarcinoma and no prior systemic therapy were randomly assigned 1:1 to receive every-3-weeks intravenous serplulimab (300 mg) plus HLX04 (7.5 mg/kg) and XELOX (serplulimab group) or placebo (300 mg) plus bevacizumab (7.5 mg/kg) and XELOX (placebo group). The primary endpoint was independent radiology review committee (IRRC)-assessed progression-free survival (PFS). Secondary endpoints included other efficacy endpoints and safety. FINDINGS: Between July 16, 2021, and January 20, 2022, 114 patients were enrolled and randomly assigned to the serplulimab (n = 57) or placebo (n = 57) group. All patients had stage IV CRC, and 95.7% of the patients with available microsatellite instability (MSI) status were MSS. With a median follow-up duration of 17.7 months, median PFS was prolonged in the serplulimab group (17.2 vs. 10.7 months; hazard ratio [HR], 0.60; 95% confidence interval [CI], 0.31-1.14). Although the median overall survival (OS) was not reached for either group, a trend of an OS benefit was observed for the serplulimab group (HR, 0.77; 95% CI, 0.41-1.45). 36 (65.5%) and 32 (56.1%) patients in the serplulimab and placebo groups had grade ≥3 treatment-related adverse events, respectively. CONCLUSIONS: Serplulimab plus HLX04 and XELOX exhibits promising efficacy and is safe and tolerable in patients with treatment-naive mCRC. FUNDING: This work was funded by Shanghai Henlius Biotech, Inc.
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OBJECTIVE: This study aims to conduct an in-depth genomic analysis of a carbapenem-resistant Proteus mirabilis strain to uncover the distribution and mechanisms of its resistance genes. METHODS: The research primarily utilized whole-genome sequencing to analyze the genome of the Proteus mirabilis strain. Additionally, antibiotic susceptibility tests were conducted to evaluate the strain's sensitivity to various antibiotics, and related case information was collected to analyze the clinical distribution characteristics of the resistant strain. RESULTS: Study on bacterial strain WF3430 from a tetanus and pneumonia patient reveals resistance to multiple antibiotics due to extensive use. Whole-genome sequencing exposes a 4,045,480 bp chromosome carrying 29 antibiotic resistance genes. Two multidrug-resistant (MDR) gene regions, resembling Tn6577 and Tn6589, were identified (MDR Region 1: 64.83 Kb, MDR Region 2: 85.64 Kbp). These regions, consist of integrative and conjugative elements (ICE) structures, highlight the intricate multidrug resistance in clinical settings. CONCLUSION: This study found that a CR-PMI strain exhibits a unique mechanism for acquiring antimicrobial resistance genes, such as blaNDM-1, located on the chromosome instead of plasmids. According to the results, there is increasing complexity in the mechanisms of horizontal transmission of resistance, necessitating a comprehensive understanding and implementation of targeted control measures in both hospital and community settings.
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Antibacterianos , Proteínas Bacterianas , Farmacorresistencia Bacteriana Múltiple , Pruebas de Sensibilidad Microbiana , Infecciones por Proteus , Proteus mirabilis , Secuenciación Completa del Genoma , beta-Lactamasas , Proteus mirabilis/genética , Proteus mirabilis/efectos de los fármacos , Proteus mirabilis/enzimología , Proteus mirabilis/aislamiento & purificación , beta-Lactamasas/genética , Humanos , Farmacorresistencia Bacteriana Múltiple/genética , Antibacterianos/farmacología , Infecciones por Proteus/microbiología , Proteínas Bacterianas/genética , Cromosomas Bacterianos/genética , Genoma Bacteriano/genética , Carbapenémicos/farmacologíaRESUMEN
Directly coupling N2 and CO2 to synthesize urea by photocatalysis paves a sustainable route for urea synthesis, but its performance is limited by the competition of photogenerated electrons between N2 and CO2, as well as the underutilized photogenerated holes. Herein, we report an efficient urea synthesis process involving photogenerated electrons and holes in respectively converting CO2 and N2 over a redox heterojunction consisting of WO3 and Ni single-atom-decorated CdS (Ni1-CdS/WO3). For the photocatalytic urea synthesis from N2 and CO2 in pure water, Ni1-CdS/WO3 attained a urea yield rate of 78â µM h-1 and an apparent quantum yield of 0.15 % at 385â nm, which ranked among the best photocatalytic urea synthesis performance reported. Mechanistic studies reveal that the N2 was converted into NO species by â OH radicals generated from photogenerated holes over the WO3 component, meanwhile, the CO2 was transformed into *CO species over the Ni site by photogenerated electrons. The generated NO and *CO species were further coupled to form *OCNO intermediate, then gradually transformed into urea. This work emphasizes the importance of reasonably utilizing photogenerated holes in photocatalytic reduction reactions.
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The underlying mechanism of the ongoing seismic swarm in the Noto Peninsula, Japan, which generates earthquakes at 10 times the average regional rate, remains elusive. We capture the evolution of the subsurface stress state by monitoring changes in seismic wave velocities over an 11-year period. A sustained long-term increase in seismic velocity that is seasonally modulated drops before the earthquake swarm. We use a three-dimensional hydromechanical model to quantify environmentally driven variations in excess pore pressure, revealing its crucial role in governing the seasonal modulation with a stress sensitivity of 6 × 10-9 per pascal. The decrease in seismic velocity aligns with vertical surface uplift, suggesting potential fluid migration from a high-pore pressure zone at depth. Stress changes induced by abnormally intense snow falls contribute to initiating the swarm through subsequent perturbations to crustal pore pressure.
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OBJECTIVE: To explore the efficacy of serplulimab plus chemotherapy in esophageal squamous cell carcinoma (ESCC) patients with liver metastases. METHODS: A post hoc exploratory analysis of ASTRUM-007 study was performed, focusing on the association between the liver metastases status and the clinical outcomes. A systematic literature search of electronic databases was conducted to identify eligible randomized controlled trials for the meta-analysis. Study-level pooled analyses of hazard ratios (HRs) for PFS according to liver metastases were performed. RESULTS: The post hoc analysis of ASTRUM-007 showed that although patients with liver metastases had a worse prognosis comparing with the non-liver metastases patients in both treatment arms (serplulimab plus chemotherapy arm: median PFS, 5.7 vs. 6.6 months, HR 1.57 [95% CI, 1.15-2.13]; median OS, 13.7 vs. 15.3 months, HR 1.48 [95% CI, 1.09-1.98]; placebo plus chemotherapy arm: median PFS, 4.3 vs. 5.5 months, HR 1.58 [95% CI, 1.01-2.39]; median OS, 10.3 vs. 11.2 months, HR 1.32 [95% CI, 0.84-2.00]), OS and PFS benefits derived from serplulimab plus chemotherapy versus placebo plus chemotherapy in this study were observed in both patients with liver metastases (HR of PFS: 0.60; 95% CI, 0.37-0.97; HR of OS: 0.68; 95% CI, 0.43-1.11) and the non-liver metastases patients (HR of PFS: 0.62; 95% CI, 0.49-0.80; HR of OS: 0.69; 95% CI, 0.55-0.87) with similar magnitude. Three randomized controlled trials were included in the meta-analysis. Pooled HRs demonstrated that the addition of anti-PD-1 antibodies significantly improved PFS compared to chemotherapy alone regardless of liver metastases status. CONCLUSIONS: This study reveals that the presence of liver metastases is a poor prognostic factor but does not affect the improvements in both PFS and OS brought by adding PD-1 blockade to chemotherapy in ESCC patients. Predictive biomarkers for survival in these patients warrant further investigation.
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Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias Esofágicas , Carcinoma de Células Escamosas de Esófago , Neoplasias Hepáticas , Humanos , Neoplasias Hepáticas/secundario , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/mortalidad , Carcinoma de Células Escamosas de Esófago/tratamiento farmacológico , Carcinoma de Células Escamosas de Esófago/secundario , Carcinoma de Células Escamosas de Esófago/mortalidad , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Esofágicas/tratamiento farmacológico , Neoplasias Esofágicas/patología , Neoplasias Esofágicas/mortalidad , Masculino , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Femenino , Persona de Mediana Edad , Ensayos Clínicos Controlados Aleatorios como Asunto , Anciano , Resultado del Tratamiento , Anticuerpos Monoclonales Humanizados/uso terapéutico , Anticuerpos Monoclonales Humanizados/administración & dosificaciónRESUMEN
Background: Platelet hyperreactivity is a risk factor for thrombosis in elderly patients with cardiovascular diseases. However, the mechanism of platelet hyperactivation has not been elucidated. This study aims to investigate alterations in the proteomes of platelets and their correlation with platelet hyperreactivity among elderly individuals. Methods: This study included 10 young (28.1 ± 1.9 years), 10 middle-aged (60.4 ± 2.2 years), and 10 old (74.2 ± 3.0 years) subjects. Washed platelets were used in the present study. Platelet samples were analysed by using data-independent acquisition (DIA) quantitative mass spectrometry (MS). Results: The results showed that the platelet proteomic profile exhibited high similarity between the young and middle-aged groups. However, there were significant differences in protein expression profiles between the old group and the young group. By exploring the dynamic changes in the platelet proteome with ageing, clusters of proteins that changed significantly with ageing were selected for further investigation. These clusters were related to the initial triggering of complement, phagosome and haemostasis based on enrichment analysis. We found that platelet degranulation was the major characteristic of the differentially expressed proteins between the old and young populations. Moreover, complement activation, the calcium signalling pathway and the nuclear factor-κB (NF-κB) signalling pathway were enriched in differentially expressed proteins. Conclusions: The present study showed that there are obvious differences in the protein profiles of the elderly compared with young and middle-aged populations. The results provide novel evidence showing changes in platelet hyperactivity and susceptibility to thrombosis in the elderly population.
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Prostate-specific antigen (PSA) is a key marker for a prostate cancer diagnosis. The low sensitivity of traditional lateral flow immunoassay (LFIA) methods makes them unsuitable for point-of-care testing. Herein, we designed a nanozyme by in situ growth of Prussian blue (PB) within the pores of dendritic mesoporous silica (DMSN). The PB was forcibly dispersed into the pores of DMSN, leading to an increase in exposed active sites. Consequently, the atom utilization is enhanced, resulting in superior peroxidase (POD)-like activity compared to that of cubic PB. Antibody-modified DMSN@PB nanozymes serve as immunological probes in an enzymatic-enhanced colorimetric and photothermal dual-signal LFIA for PSA detection. After systematic optimization, the LFIA based on DMSN@PB successfully achieves a 4-fold amplification of the colorimetric signal within 7 min through catalytic oxidation of the chromogenic substrate by POD-like activity. Moreover, DMSN@PB exhibits an excellent photothermal conversion ability under 808 nm laser irradiation. Accordingly, photothermal signals are introduced to improve the anti-interference ability and sensitivity of LFIA, exhibiting a wide linear range (1-40 ng mL-1) and a low PSA detection limit (0.202 ng mL-1), which satisfies the early detection level of prostate cancer. This research provides a more accurate and reliable visualization analysis methodology for the early diagnosis of prostate cancer.
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Colorimetría , Ferrocianuros , Nanocompuestos , Antígeno Prostático Específico , Antígeno Prostático Específico/análisis , Ferrocianuros/química , Inmunoensayo/métodos , Humanos , Nanocompuestos/química , Masculino , Límite de Detección , Neoplasias de la Próstata/diagnóstico , Dióxido de Silicio/química , PorosidadRESUMEN
Corticotropin releasing factor (CRF) network in the oval nucleus of bed nuclei of the stria terminalis (ovBNST) is generally indicated in stress, but its role in female-biased susceptibility to anxiety is unknown. Here, we established a female-biased stress paradigm. We found that the CRF release in ovBNST during stress showed female-biased pattern, and ovBNST CRF neurons were more prone to be hyperexcited in female mice during stress in both in vitro and in vivo studies. Moreover, optogenetic modulation to exchange the activation pattern of ovBNST CRF neurons during stress between female and male mice could reverse their susceptibility to anxiety. Last, CRF receptor type 1 (CRFR1) mediated the CRF-induced excitation of ovBNST CRF neurons and showed female-biased expression. Specific knockdown of the CRFR1 level in ovBNST CRF neurons in female or overexpression that in male could reverse their susceptibility to anxiety. Therefore, we identify that CRFR1-mediated hyperexcitation of ovBNST CRF neurons in female mice encode the female-biased susceptibility to anxiety.
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Ansiedad , Hormona Liberadora de Corticotropina , Neuronas , Receptores de Hormona Liberadora de Corticotropina , Animales , Femenino , Masculino , Ratones , Ansiedad/metabolismo , Reacción de Prevención/fisiología , Conducta Animal , Hormona Liberadora de Corticotropina/metabolismo , Neuronas/metabolismo , Receptores de Hormona Liberadora de Corticotropina/metabolismo , Receptores de Hormona Liberadora de Corticotropina/genética , Núcleos Septales/metabolismo , Estrés Psicológico/metabolismoRESUMEN
Alzheimer's disease (AD) is a neurodegenerative disease characterized by memory loss and cognitive impairment. ß-amyloid (Aß) is one of the typical pathological features of AD, and its accumulation leads to neuronal death from oxidative stress. Here, we found that hederagenin (HG), a natural product, exhibits anti-tumor, anti-inflammatory, anti-depressant, anti-neurodegenerative biological activities. However, whether HG has anti-Aß activity remains unclear. Based on the characteristics of HG, it is hypothesized that HG has biological activity against Aß injury. Therefore, Aß-injured SH-SY5Y cells were constructed, and the protective effect of HG against Aß injury was further evaluated using C. elegans. The results showed that HG increased superoxide dismutase activity, effectively reduced Aß-induced oxidative damage, and reduced apoptosis via the PI3â K/Akt signaling pathway. HG inhibited Aß deposition and delayed senescence and paralysis in the C. elegans strain, CL4176. HG showed inhibitory effects on Aß; therefore, more natural active products are expected to be applied in AD therapy.
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Male fertility has been declining in recent decades, and a growing body of research points to environmental and lifestyle factors as the cause. The widespread use of radiation technology may result in more people affected by male infertility, as it is well established that radiation can cause reproductive impairment in men. This article provides a review of radiation-induced damage to male reproduction, and the effects of damage mechanisms and pharmacotherapy. It is hoped that this review will contribute to the understanding of the effects of radiation on male reproduction, and provide information for research into drugs that can protect the reproductive health of males.
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Reproducción , Masculino , Humanos , Reproducción/efectos de la radiación , Reproducción/efectos de los fármacos , Infertilidad Masculina/prevención & control , Infertilidad Masculina/etiología , Genitales Masculinos/efectos de la radiación , AnimalesRESUMEN
Optically active poly(naphthalene-1,4-diyl) was prepared through helix-sense-selective polymerization of the corresponding monomers and also through circularly polarized light (CPL) irradiation, resulting in distinctive circular dichroism (CD) spectral patterns. Chirality of the helix-sense-selective polymerization -based polymer is ascribed to preferred-handed helicity while that of the CPL-based polymer to a non-helical, chiral conformation ('biased-dihedral conformation') with preferred-handedness which was stable only in the solid state. The helix of the helix-sense-selective polymerization-based polymer gradually racemized in tetrahydrofuran while it was stabilized by aggregate formation in a hexane-dichloromethane solution. Both helix-sense-selective polymerization- and CPL-based polymers exhibited efficient circularly polarized luminescence.
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In the realm of molecular detection, the surface-enhanced Raman scattering (SERS) technique has garnered increasing attention due to its rapid detection, high sensitivity, and non-destructive characteristics. However, conventional rigid SERS substrates are either costly to fabricate and challenging to prepare over a large area, or they exhibit poor uniformity and repeatability, making them unsuitable for inspecting curved object surfaces. In this work, we present a flexible SERS substrate with high sensitivity as well as good uniformity and repeatability. First, the flexible polydimethylsiloxane (PDMS) substrate is manually formulated and cured. SiO2/Ag layer on the substrate can be obtained in a single process by using ion beam sputtering. Then, reactive ion etching is used to etch the upper SiO2layer of the film, which directly leads to the desired densely packed nanostructure. Finally, a layer of precious metal is deposited on the densely packed nanostructure by thermal evaporation. In our proposed system, the densely packed nanostructure obtained by etching the SiO2layer directly determines the SERS ability of the substrate. The bottom layer of silver mirror can reflect the penetrative incident light, the spacer layer of SiO2and the top layer of silver thin film can further localize the light in the system, which can realize the excellent absorption of Raman laser light, thus enhancing SERS ability. In the tests, the prepared substrates show excellent SERS performance in detecting crystalline violet with a detection limit of 10-11M. The development of this SERS substrate is anticipated to offer a highly effective and convenient method for molecular substance detection.
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Reducing the silver film to 10 nm theoretically allows higher transparency but in practice leads to degraded transparency and electrical conductivity because the ultrathin film tends to be discontinuous. Herein, we developed a thinning-back process to address this dilemma, in which silver film is first deposited to a larger thickness with high continuity and then thinned back to a reduced thickness with an ultrasmooth surface, both implemented by a flood ion beam. Contributed by the shallow implantation of silver atoms into the substrate during deposition, the thinness of silver films down to 4.5 nm can be obtained, thinner than ever before. The atomic-level surface smooth permits excellent visible transparency, electrical conductivity, and the lowest haze among all existing transparent conductors. Moreover, the ultrathin silver film exhibits the unique robustness of mechanical flexibility. Therefore, the ion-beam thinning-back process presents a promising solution towards the excellent transparent conductor for flexible optoelectronic devices.