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1.
Adv Sci (Weinh) ; : e2404506, 2024 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-39120001

RESUMO

In the development of lithium-ion batteries (LIBs), cheaper and safer solid polymer electrolytes are expected to replace combustible organic liquid electrolytes to meet the larger market demand. However, low ionic conductivity and inadequate cycling stability impede their commercial viability. Herein, a novel flexible conducting solid polymer electrolytes (CSPEs) based on polyvinyl alcohol (PVA) and ion-polarized diethylenetriaminepentaacetic acid (P-DETP) is developed for the first time and applied in LIBs. PVA and P-DETP form a compact polymer network through hydrogen bonding, enhancing the thermomechanical stability of CSPE while restricting the migration of larger anions. Furthermore, density functional theory calculations confirm that P-DETP can facilitate the dissociation of Li+-TFSI- via electrostatic attraction, resulting in increased mobility of lithium ions. Additionally, P-DETP contributes to the formation of a stable electrode-electrolyte interface layer, effectively suppressing the growth of lithium dendrites and improving antioxidant capacity. These synergistic effects enable CSPE to exhibit remarkable properties including high ionic conductivity (2.8 × 10-4 S cm-1), elevated electrochemical potential (5.1 V), and excellent lithium transference number (0.869). Notably, the P-DETP/LiTFSI CSPE demonstrates stable performance not only in LiFePO4 batteries but also adapts to high-nickel ternary LiNi0.88Co0.06Mn0.06O2 cathode, highlighting its immense potential for application in high energy density LIBs.

2.
Phys Rev Lett ; 132(25): 250204, 2024 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-38996245

RESUMO

The Hamiltonian, which determines the evolution of a quantum system, is fundamental in quantum physics. Therefore, it is crucial to implement high-precision generation and measurement of the Hamiltonian in a practical quantum system. Here, we experimentally demonstrate ultrahigh-precision Hamiltonian parameter estimation with a significant quantum advantage in a superconducting circuit via sequential control. We first observe the commutation relation for noncommuting operations determined by the system Hamiltonian, both with and without adding quantum control, verifying the commuting property of controlled noncommuting operations. Based on this control-induced commuting property, we further demonstrate Hamiltonian parameter estimation for polar and azimuth angles in superconducting circuits, achieving ultrahigh metrological gains in measurement precision exceeding the standard quantum limit by up to 16.0 and 16.1 dB at N=100, respectively.

3.
Neurosurg Rev ; 47(1): 384, 2024 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-39085721

RESUMO

"Low-lying" posterior communicating artery (PCoA) aneurysms require great attention in surgical clipping due to their distinct anatomical characteristics. In this study, we propose an easy method to immediately recognize "low-lying" PCoA aneurysms in neurosurgical practice. A total of 89 cases with "low-lying" PCoA aneurysms were retrospectively analyzed. All patients underwent preoperative digital subtraction angiography (DSA) examinations and microsurgical clipping. Cases were classified into the "low-lying" and regular groups based on intraoperative findings. The distance- and angle-relevant parameters that reflected the relative location of the aneurysms and tortuosity of the internal carotid artery were measured using 3D-DSA images. The data were sequentially integrated into a mathematical analysis to obtain the prediction model. Finally, we proposed a novel mathematical formula to preoperatively predict the existence of "low-lying" PCoA aneurysms with great accuracy. Neurosurgeons might benefit from this model, which enables them to directly identify "low-lying" PCoA aneurysms and make appropriate surgical decisions accordingly.


Assuntos
Angiografia Digital , Aneurisma Intracraniano , Procedimentos Neurocirúrgicos , Humanos , Aneurisma Intracraniano/cirurgia , Aneurisma Intracraniano/diagnóstico por imagem , Feminino , Masculino , Pessoa de Meia-Idade , Adulto , Angiografia Digital/métodos , Procedimentos Neurocirúrgicos/métodos , Estudos Retrospectivos , Idoso , Angiografia Cerebral/métodos , Modelos Teóricos , Artéria Carótida Interna/cirurgia , Artéria Carótida Interna/diagnóstico por imagem
4.
Toxicol Res ; 40(3): 431-440, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38911548

RESUMO

The Internet Data Center (IDC) is one of the most important infrastructures in the field of information technology. The cooling system for heat dissipation of IDC is indispensable due to it generates a large amount of heat during its calculation process, which may potentially harm its normal operation. Electronic fluorinated fluids have been widely used in cooling systems of IDC with stable physical and chemical properties. However, the biological toxicity of electronic fluorinated fluids has not been fully evaluated and there is a lack of unified safety standards, which may pose potential risks to the environment and human health. Here, hexafluoropropylene terpolymer (HFPT) as an example has been systematically studied, fully considering the application scenarios of data centers. Also, the emergency effects of fluorinated coolants in mammalian models from the perspectives of inhalation, skin contact, accidental entry into eyes, accidental ingestion, and chronic toxicity, are evaluated. Multiple in vivo experiments have proven that HFPT not only has stable physical and chemical properties, that can maintain the safe operation of IDC, but also has low physiological toxicity to mammals and can provide health benefits to data center staff and the assurance of surrounding environment. This study proves the good biological safety of electronic fluorinated fluids and provides a reference for environmental assessment and risk management of liquid cooling technology in IDC. Supplementary Information: The online version contains supplementary material available at 10.1007/s43188-024-00234-3.

5.
Sci Adv ; 10(26): eado1019, 2024 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-38924404

RESUMO

A kirigami-engineered composite hydrogel membrane is exploited for the construction of three dimensional (3D) solar-tracking evaporator arrays with outstanding evaporation performance and salt tolerance. The hybrid nanofiber network in the hydrogel membrane offers favorable water transport dynamics combined with excellent structural robustness, which are beneficial for the engineering of 3D dynamic structures. Periodic triangular cuts patterned into the membrane allow formation and reconfiguration of 3D conical arrays controlled by uniaxial stretching. With these structures, the tilt angles of the membrane surface are actively tuned to follow the solar trajectory, leading to a solar evaporation rate ~80% higher than that of static planar devices. Furthermore, the tapered 3D flaps and their micro-structured surfaces are capable of localized salt crystallization for prolonged solar desalination, enabling a stable evaporation rate of 3.4 kg m-2 hour-1 even in saturated brine. This versatile design may facilitate the implementation of solar evaporators for desalination and provide inspirations for other soft functional devices with dynamic 3D configurations.

6.
Ying Yong Sheng Tai Xue Bao ; 35(5): 1435-1446, 2024 May.
Artigo em Chinês | MEDLINE | ID: mdl-38886443

RESUMO

As regulators of the surface land processes, soil fauna communities are the vital foundations for healthy terrestrial ecosystems. Soil fauna have been studied in China for more than 70 years. Great progresses have been achieved in exploring soil fauna species composition and geographical distribution patterns. Soil fauna eco-geography, as a bridge between soil fauna geographic patterns and ecosystem services, has a new development opportunity with the deep recognition of soil fauna ecological functions. Soil fauna eco-geography research could be partitioned into four dimensions including the spatio-temporal patterns of: 1) the apparent characteristics of soil fauna community, such as species composition, richness and abundance; 2) the intrinsic characteristics of soil fauna community, such as dietary and habits; 3) soil fauna-related biotic and abiotic interactions especially those indicating drivers of soil fauna community structure or shaping the roles of soil fauna in ecosystems; and 4) soil fauna-related or -regulated key ecological processes. Current studies focus solely on soil fauna themselves and their geographical distributions. To link soil fauna geography more closely with ecosystem services, we suggested that: 1) converting the pure biogeography studies to those of revealing the spatio-temporal patterns of the soil fauna-related or regulated key relationships and ecological processes;2) expanding the temporal and spatial scales in soil fauna geographical research;3) exploring the integrated analysis approach for soil fauna-related data with multi-scales, multi-factors, and multi-processes;and 4) establishing standard reference systems for soil fauna eco-geographical researches. Hence, the change patterns of ecological niche of soil fauna communities could be illustrated, and precision mani-pulations of soil fauna communities and their ecological functions would become implementable, which finally contributes to ecosystem health and human well-being.


Assuntos
Biodiversidade , Ecossistema , Solo , China , Solo/química , Animais , Invertebrados/classificação , Invertebrados/crescimento & desenvolvimento , Geografia
8.
Open Forum Infect Dis ; 11(5): ofae238, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38770210

RESUMO

Varied seasonal patterns of respiratory syncytial virus (RSV) have been reported worldwide. We conducted a systematic review on articles identified in PubMed reporting RSV seasonality based on data collected before 1 January 2020. RSV seasonal patterns were examined by geographic location, calendar month, analytic method, and meteorological factors including temperature and absolute humidity. Correlation and regression analyses were conducted to explore the relationship between RSV seasonality and study methods and characteristics of study locations. RSV seasons were reported in 209 articles published in 1973-2023 for 317 locations in 77 countries. Regular RSV seasons were similarly reported in countries in temperate regions, with highly variable seasons identified in subtropical and tropical countries. Longer durations of RSV seasons were associated with a higher daily average mean temperature and daily average mean absolute humidity. The global seasonal patterns of RSV provided important information for optimizing interventions against RSV infection.

9.
Front Public Health ; 12: 1374522, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38584914

RESUMO

Background: Mobile phone addiction has adverse influences on the physical and mental health of college students. However, few studies shed light on the effect of fear of missing out on mobile phone addiction and the underlying mechanisms among college students. Methods: To explore their associations, the present study used the Fear of Missing Out Scales (FoMOS), Loneliness Scale (USL-8), Mobile Phone Addiction Index Scale (MPAI), and Depression-Anxiety-Stress Questionnaire (DASS-21) to investigate 750 college students. Results: The results suggested that fear of missing out significantly positively predicted mobile phone addiction. This direct effect could be mediated by depression, and the indirect effect of fear of missing out on mobile phone addiction could be moderated by loneliness. Specifically, the indirect effect was stronger for students with high levels of loneliness. Conclusion: This study provides a theoretical basis for developing future interventions for mobile phone addiction in higher education students.


Assuntos
Depressão , Solidão , Humanos , Medo , Estudantes , Dependência de Tecnologia
10.
Medicine (Baltimore) ; 103(14): e37683, 2024 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-38579075

RESUMO

Since the emergence of the Coronavirus Disease 2019 (COVID-19) outbreak, significant advancements has been made in research, from limited knowledge about the disease to the development of a vaccine. Although the severity of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) appears to be decreasing and the threat of COVID-19 is waning, there have been widespread concerns about persistent symptoms or sequelae experienced by some patients even after recovering from COVID-19. Traditional Chinese medicine (TCM) has shown favorable treatment outcomes during the onset of COVID-19, and extensive studies have been carried out to explore the efficacy of TCM interventions during the COVID-19 recovery period. The purpose of this review is to comprehensively analyze these studies and provide new insights for the prevention and treatment of the post-COVID-19 condition.


Assuntos
COVID-19 , Medicamentos de Ervas Chinesas , Humanos , Medicina Tradicional Chinesa , SARS-CoV-2 , Medicamentos de Ervas Chinesas/uso terapêutico , Tratamento Farmacológico da COVID-19
11.
Cancer Cell Int ; 24(1): 131, 2024 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-38594722

RESUMO

Extensive exploration of the molecular subtypes of triple-negative breast cancer (TNBC) is critical for advancing precision medicine. Notably, the luminal androgen receptor (LAR) subtype has attracted attention for targeted treatment combining androgen receptor antagonists and CDK4/6 inhibitors. Unfortunately, this strategy has proven to be of limited efficacy, highlighting the need for further optimization. Using our center's comprehensive multiomics dataset (n = 465), we identified novel therapeutic targets and evaluated their efficacy through multiple models, including in vitro LAR cell lines, in vivo cell-derived allograft models and ex vivo patient-derived organoids. Moreover, we conducted flow cytometry and RNA-seq analysis to unveil potential mechanisms underlying the regulation of tumor progression by these therapeutic strategies. LAR breast cancer cells exhibited sensitivity to chidamide and enzalutamide individually, with a drug combination assay revealing their synergistic effect. Crucially, this synergistic effect was verified through in vivo allograft models and patient-derived organoids. Furthermore, transcriptomic analysis demonstrated that the combination therapeutic strategy could inhibit tumor progression by regulating metabolism and autophagy. This study confirmed that the combination of histone deacetylase (HDAC) inhibitors and androgen receptor (AR) antagonists possessed greater therapeutic efficacy than monotherapy in LAR TNBC. This finding significantly bolsters the theoretical basis for the clinical translation of this combination therapy and provides an innovative strategy for the targeted treatment of LAR TNBC.

12.
Nat Commun ; 15(1): 2939, 2024 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-38580630

RESUMO

Endplate sclerosis is a notable aspect of spine degeneration or aging, but the mechanisms remain unclear. Here, we report that senescent macrophages accumulate in the sclerotic endplates of lumbar spine instability (LSI) or aging male mouse model. Specifically, knockout of cdkn2a (p16) in macrophages abrogates LSI or aging-induced angiogenesis and sclerosis in the endplates. Furthermore, both in vivo and in vitro studies indicate that IL-10 is the primary elevated cytokine of senescence-related secretory phenotype (SASP). Mechanistically, IL-10 increases pSTAT3 in endothelial cells, leading to pSTAT3 directly binding to the promoters of Vegfa, Mmp2, and Pdgfb to encourage their production, resulting in angiogenesis. This study provides information on understanding the link between immune senescence and endplate sclerosis, which might be useful for therapeutic approaches.


Assuntos
Senescência Celular , Interleucina-10 , Animais , Masculino , Camundongos , Angiogênese , Células Endoteliais , Interleucina-10/genética , Macrófagos , Esclerose
13.
J Dev Orig Health Dis ; 15: e2, 2024 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-38450456

RESUMO

With the advancement of medical technology, there are increasing opportunities for new-borns, infants, and pregnant women to be exposed to general anaesthesia. Propofol is commonly used for the induction of anaesthesia, maintenance of general intravenous anaesthesia and sedation of intensive-care children. Many previous studies have found that propofol has organ-protective effects, but growing evidence suggests that propofol interferes with brain development, affecting learning and cognitive function. The purpose of this review is to summarize the latest progress in understanding the neurotoxicity of propofol. Evidence from case studies and clinical studies suggests that propofol has neurotoxicity on the developing brain. We classify the findings on propofol-induced neurotoxicity based on its damage mechanism. We end by summarizing the current protective strategies against propofol neurotoxicity. Fully understanding the neurotoxic mechanisms of propofol can help us use it at a reasonable dosage, reduce its side effects, and increase patient safety.


Assuntos
Anestesia , Propofol , Gravidez , Humanos , Feminino , Criança , Propofol/toxicidade , Anestésicos Intravenosos/efeitos adversos , Encéfalo , Cognição
14.
Glob Chang Biol ; 30(3): e17250, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38500362

RESUMO

Nitrogen (N) deposition affects ecosystem functions crucial to human health and well-being. However, the consequences of this scenario for soil ecosystem multifunctionality (SMF) in forests are poorly understood. Here, we conducted a long-term field experiment in a temperate forest in China, where N deposition was simulated by adding N above and under the canopies. We discover that canopy N addition promotes SMF expression, whereas understory N addition suppresses it. SMF was regulated by fungal diversity in canopy N addition treatments, which is largely due to the strong resistance to soil acidification and efficient resource utilization characteristics of fungi. While in understory N addition treatments, SMF is regulated by bacterial diversity, which is mainly because of the strong resilience to disturbances and fast turnover of bacteria. Furthermore, rare microbial taxa may play a more important role in the maintenance of the SMF. This study provides the first evidence that N deposition enhanced SMF in temperate forests and enriches the knowledge on enhanced N deposition affecting forest ecosystems. Given the divergent results from two N addition approaches, an innovative perspective of canopy N addition on soil microbial diversity-multifunctionality relationships is crucial to policy-making for the conservation of soil microbial diversity and sustainable ecosystem management under enhanced N deposition. In future research, the consideration of canopy N processes is essential for more realistic assessments of the effects of atmospheric N deposition in forests.


Assuntos
Ecossistema , Nitrogênio , Humanos , Nitrogênio/análise , Solo , Microbiologia do Solo , Florestas , Bactérias/metabolismo
15.
Chemphyschem ; 25(6): e202300835, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38372432

RESUMO

With the popularity and development of electronic devices, the demand for lithium batteries is increasing, which also puts high demands on the energy density, cycle life and safety of lithium batteries. Gel electrolytes achieve both of these requirements by curing the electrolytes to reduce the interfacial side reactions of lithium metal batteries. The ionic conductivity of the gel electrolytes prepared by in situ curing reach 8.0×10-4  S cm-1 , and the ionic mobility number is 0.53. Meanwhile, the gel electrolytes maintain a stable electrochemical window of 1.0-5.0 V. Benefited with the interfacial regulation of PEGDA gel electrolytes, the gel lithium metal batteries show better cycling stability, and achieved 97 % capacity retention after 200 cycles (0.2 C) with a lower increasing rate of impedance.

16.
Eur J Med Chem ; 265: 116079, 2024 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-38150962

RESUMO

In this work, a series of novel coumarin-based derivatives were designed and synthesized as tubulin polymerization inhibitors targeting the colchicine binding site, and their antiproliferative activities against MGC-803, HCT-116 and KYSE30 cells were evaluated. Among them, the compound I-3 (MY-1442) bearing a 6-methoxy-1,2,3,4-tetrahydroquinoline group exhibited most potent inhibitory activities on MGC-803 (IC50 = 0.034 µM), HCT-116 (IC50 = 0.081 µM) and KYSE30 cells (IC50 = 0.19 µM). Further mechanism studies demonstrated that compound I-3 (MY-1442) could directly bind to the colchicine binding site of ß-tubulin to inhibit tubulin polymerization and microtubules at the cellular level. The results of molecular docking indicated there were well binding interactions between compound I-3 (MY-1442) and the colchicine binding site of ß-tubulin. Compound I-3 (MY-1442) also exhibited effective anti-proliferation, pro-apoptosis, and anti-migration abilities against gastric cancer cells MGC-803. Additionally, compound I-3 (MY-1442) could regulate the expression of cell cycle- and apoptosis-related proteins. Importantly, compound I-3 (MY-1442) could significantly inhibit tumor growth in the MGC-803 xenograft tumor model with a TGI rate of 65.5 % at 30 mg/kg/day. Taken together, this work suggested that the coumarin skeleton exhibited great potential to be a key pharmacophore of tubulin polymerization inhibitors for the discovery of anticancer agents.


Assuntos
Antineoplásicos , Neoplasias Gástricas , Humanos , Colchicina/farmacologia , Tubulina (Proteína)/metabolismo , Moduladores de Tubulina/química , Simulação de Acoplamento Molecular , Neoplasias Gástricas/tratamento farmacológico , Polimerização , Proliferação de Células , Sítios de Ligação , Cumarínicos/farmacologia , Antineoplásicos/farmacologia , Antineoplásicos/química , Ensaios de Seleção de Medicamentos Antitumorais
17.
J Cancer ; 14(18): 3496-3507, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38021164

RESUMO

Background: Neuroblastoma (NB) is a cancer that arises from neural-crest-derived sympathoadrenal lineage. Less is known about the pathogenesis and molecular characteristics of MYCN non-amplified (MYCN-NA) NB. Methods: We constructed a signature model targeting mucin family according to RNA sequencing data from GSE49710 dataset, and validated the prognostic performance. We also analyzed the gene expression matrix using DESeq2 R packages to screen the most differential mucin in high-risk NB samples. We further assessed its prognostic value, particularly in MYCN-NA NB samples. Moreover, we performed functional experiments to evaluate the impact of MUC15 overexpression on the migration of MYCN-NA NB cell lines. Results: The 8-mucin signature model showed good prognostic performance in the GSE49710 dataset. Among the mucin genes, MUC15 was significantly upregulated in the high-risk NB cohort and was associated with poor prognosis, especially in MYCN-NA NB samples. Furthermore, MUC15 overexpression and exogenous MUC15 protein enhanced the migration of MYCN-NA NB cell lines. Mechanistically, MUC15 promoted the phosphorylation of focal adhesion kinase (FAK) by inhibiting the expression of MYCT1, a target of c-Myc. Conclusions: Our findings suggested a potential network in controlling NB cell metastasis. Targeting MUC15 in MYCN-NA NB patients could be a promising therapeutic strategy.

18.
Internet Interv ; 34: 100690, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38023965

RESUMO

Purpose: This meta-analysis aims to evaluate the impact of Internet-based self-help interventions on the mental health of adolescents and college students. Methods: We conducted a systematic review of randomized controlled trials (RCTs) that investigated Internet-based self-help interventions aiming to mitigate mental health symptoms such as anxiety and depression, as well as managing high levels of stress, among adolescents and college students. Our search spanned databases including Web of Science, PubMed, Cochrane Library, and Embase, up until November 1st, 2022. It is essential to emphasize that our focus was the evaluation of symptoms (continuous outcomes), rather than the diagnosis of specific mental disorders. The meta-analysis was performed using the R version 4.3.1. The effect size measure was the standardized mean difference (SMD), and random-effects models were used to pool data from eligible RCTs. Subgroup analyses were carried out to examine variations in intervention effects based on factors such as sample type, intervention modality, guidance type, and intervention duration. Results: The meta-analysis was based on 25 comparisons involving a total of 4480 participants. In comparison to the control group (n = 2125), participants receiving interventions (n = 2355) reported significant reductions in symptoms of anxiety, depression, and stress, along with a significant improvement in quality of life. Specifically, for depression, we observed moderate intervention effects (SMD = -0.42, 95 % CI: -0.56, -0.27), and a similar pattern was seen for quality of life (SMD = 0.36, 95%CI: 0.22, 0.49). Small intervention effects were found for anxiety (SMD = -0.35, 95 % CI [-0.48, -0.22]) and stress (SMD = -0.35, 95 % CI [-0.51, -0.20]). Given significant heterogeneity, subgroup analyses were conducted for anxiety and depression, considering factors such as sample type, intervention method, and intervention duration. Notably, college students experienced more significant benefits in both anxiety and depression alleviation compared to adolescents. Longer interventions (>8 weeks) were particularly effective in reducing anxiety and depression. Additionally, third-wave cognitive-behavioral therapy (CBT) showed pronounced intervention effects in both outcome measures, while the presence of guidance did not notably influence results. Conclusion: This meta-analysis underscores the positive impact of Internet-based self-help programs in alleviating the symptoms of psychological disorders among adolescents and college students. However, it is crucial to acknowledge that the available evidence exhibits inconsistencies and limitations. Therefore, further research utilizing rigorous methodologies is necessary to verify and broaden the findings of this meta-analysis.

19.
Artigo em Inglês | MEDLINE | ID: mdl-38028893

RESUMO

Background: Hong Kong experienced four epidemic waves caused by the ancestral strain of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in 2020-2021 and a large Omicron wave in 2022. Few studies have assessed antibacterial prescribing for coronavirus disease 2019 (COVID-19) inpatients throughout the pandemic. Objectives: To describe inpatient antibacterial prescribing and explore factors associated with their prescription. Methods: Electronic health records of patients with COVID-19 admitted to public hospitals in Hong Kong from 21 January 2020 to 30 September 2022 were used to assess the prevalence and rates of inpatient antibacterial drug use (days of therapy/1,000 patient days [DOT/1,000 PD]). We used multivariable logistic regression to investigate potential associations between patients' baseline characteristics and disease severity and prescription of an antibacterial drug during hospital admission. Results: Among 65,810 inpatients with COVID-19, 54.0% were prescribed antibacterial drugs (550.5 DOT/1,000 PD). Compared to waves 1-2 (46.7%; 246.9 DOT/1,000 PD), the prescriptions were lowest during wave 4 (28.0%; 246.9; odds ratio (OR): 0.39, 95% CI: 0.31-0.49) and peaked in early wave 5 (64.6%; 661.2; 0.82, 0.65-1.03). Older age (≥80 years: OR 2.66, 95% CI, 2.49-2.85; 60-79 years: 1.59, 1.51-1.69, compared with 20-59 years), more severe disease (fatal: 3.64, 3.2-4.16; critical: 2.56, 2.14-3.06, compared with severe), and COVID-19 vaccine doses (two doses: 0.74, 0.69-0.78; three doses: 0.69, 0.64-0.74; four doses: 0.52, 0.44-0.62, compared with unvaccinated) were associated with inpatient antibacterial drug use. Conclusions: Antibacterial prescribing changed over time for hospitalized patients with confirmed COVID-19 and was potentially related to patients' demographics, medical conditions, and COVID-19 vaccination status as well as healthcare capacity during epidemic waves.

20.
Biotechnol Biofuels Bioprod ; 16(1): 161, 2023 Oct 27.
Artigo em Inglês | MEDLINE | ID: mdl-37891680

RESUMO

BACKGROUND: The well-known industrial fungus Trichoderma reesei has an excellent capability of secreting a large amount of cellulases and xylanases. The induced expression of cellulase and xylanase genes is tightly controlled at the transcriptional level. However, compared to the intensive studies on the intricate regulatory mechanism of cellulase genes, efforts to understand how xylanase genes are regulated are relatively limited, which impedes the further improvement of xylanase production by T. reesei via rational strain engineering. RESULTS: To identify transcription factors involved in regulating xylanase gene expression in T. reesei, yeast one-hybrid screen was performed based on the promoters of two major extracellular xylanase genes xyn1 and xyn2. A putative transcription factor named XTR1 showing significant binding capability to the xyn1 promoter but not that of xyn2, was successfully isolated. Deletion of xtr1 significantly increased the transcriptional level of xyn1, but only exerted a minor promoting effect on that of xyn2. The xylanase activity was increased by ~ 50% with XTR1 elimination but the cellulase activity was hardly affected. Subcellular localization analysis of XTR1 fused to a green fluorescence protein demonstrated that XTR1 is a nuclear protein. Further analyses revealed the precise binding site of XTR1 and nucleotides critical for the binding within the xyn1 promoter. Moreover, competitive EMSAs indicated that XTR1 competes with the essential transactivator XYR1 for binding to the xyn1 promoter. CONCLUSIONS: XTR1 represents a new transcriptional repressor specific for controlling xylanase gene expression. Isolation and functional characterization of this new factor not only contribute to further understanding the stringent regulatory network of xylanase genes, but also provide important clues for boosting xylanase biosynthesis in T. reesei.

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