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BACKGROUND AND OBJECTIVES: Mobility limitations has been linked to cognition. However, little is known about the relationship between mobility decline and cognitive decline. This study investigated the effect of mobility limitations and decline on cognitive decline in a population-based cohort of older adults. RESULT DESIGN AND METHODS: A population-based cohort of 9695 cognitively intact participants (mean age = 65.4 years, standard deviation [SD] = 10.4) was assessed. Mobility limitation scores ranging from 0-10 were assessed at baseline (wave 4) by using self-reporting difficulty in a set of 10 activities, and a higher score indicated worse mobility. A subset of 9250 participants underwent two mobility assessments at waves 3 and 4, and were categorized into normal mobility or mobility decline (defined as wave 4 - wave 3 > 1 SD of wave 3). Linear mixed models were used to assess the longitudinal contribution of mobility limitations and decline to cognitive decline. RESULTS: During a median follow-up period of 9.4 years (SD 1.8), the participants in the highest quartile of mobility scores displayed an accelerated cognitive decline (-0.191 SD/year, 95% CI = -0.223, -0.159) compared with those in the lowest quartile. Notably, individuals experiencing mobility decline exhibited a marked cognitive decline (-0.179 SD/year, 95% CI = -0.220, -0.139), potentially influenced by factors such as physical activity and depression. DISCUSSION AND IMPLICATIONS: Mobility limitations and decline significantly correlate with cognitive decline in older adults, highlighting that mobility-focused interventions in healthcare strategies to preserve cognition.
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Wide used guided bone regeneration (GBR) membrane materials, such as collagen, Teflon, and other synthesized polymers, present a great challenge in term of integrating the mechanical property and degradation rate when addressing critical bone defects. Therefore, inspired by the distinctive architecture of fish scales, this study utilized epigallocatechin gallate to modify decellularized fish scales following biomimetic mineralization to fabricate a GBR membrane that mimics the structure of lamellar bone. The structure, physical and chemical properties, and biological functions of the novel GBR membrane were evaluated. Results indicate that the decellularized fish scale with 5 remineralization cycles (5R-E-DCFS) exhibited a composite and structure similar to natural bone and had a special functionally gradient mineral contents character, demonstrating excellent mechanical properties, hydrophilicity, and degradation properties. In vitro, the 5R-E-DCFS membrane exhibited excellent cytocompatibility promoting Sprague-Dawley (SD) rat bone marrow mesenchymal stem cell proliferation and differentiation up-regulating the expression of osteogenic-related genes and proteins. Furthermore, in vivo, the 5R-E-DCFS membrane promoted the critical skull bone defects of SD rats repairment and regeneration. Therefore, this innovative biomimetic membrane holds substantial clinical potential as an ideal GBR membrane with mechanical properties for space-making and suitable degradation rate for bone regeneration to manage bone defects.
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OBJECTIVE: Gut microbiota was closely involved in the pathogenesis of depression, but the underlying molecular mechanisms in depression remained unclear. This study was conducted to investigate the relationship between neurotransmitters/inflammatory factors and gut microbiota in depressed mice. MATERIALS AND METHODS: A chronic social defeat stress (CSDS) depression model was established. Gut microbial composition was detected in faeces, neurotransmitters were detected in faeces, colon, blood and hippocampus, and inflammatory factors were detected in hippocampus. After a key neurotransmitter was identified, intervention experiment was conducted to explore whether it could improve depressive-like behaviours. RESULTS: Six differential genera in faeces, 14 differential neurotransmitters in gut-brain axis, and two differential inflammatory factors (interleukin-1 beta (IL-1ß) and interleukin-6 (IL-6)) in hippocampus were identified in depressed mice. There were significant correlations among differential genera, differential neurotransmitters and IL-1ß/IL-6. Among these differential neurotransmitters, 3-O-Methyldopa (3-OMDP) was found to be consistently decreased in faeces, colon, blood and hippocampus, and 3-OMDP was significantly correlated to Limosilactobacillus and IL-1ß. After receiving 3-OMDP, the depressive-like behaviours in depressed mice were improved and the increased IL-1ß/IL-6 levels were reversed. CONCLUSIONS: These results indicated that gut microbiota might affect host's inflammation levels in brain through regulating neurotransmitters, eventually leading to the onset of depression. 'Limosilactobacillus-3-OMDP-IL-1ß/IL-6' might be a potential pathway in the crosstalk of gut and brain, and 3-OMDP held the promise as a therapeutic target for depression.
The decrease in Limosilactobacillus caused disturbances in peripheral and central 3-OMDP, which resulted in increased IL-6 and IL-1ß levels in brain, eventually leading to the onset of depression.3-OMDP could reverse the increased IL-6 and IL-1ß levels and improve the depressive-like behaviours in depressed mice.
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Depressão , Modelos Animais de Doenças , Microbioma Gastrointestinal , Hipocampo , Animais , Masculino , Camundongos , Comportamento Animal/efeitos dos fármacos , Eixo Encéfalo-Intestino/fisiologia , Depressão/tratamento farmacológico , Depressão/microbiologia , Depressão/metabolismo , Fezes/microbiologia , Microbioma Gastrointestinal/efeitos dos fármacos , Microbioma Gastrointestinal/fisiologia , Hipocampo/metabolismo , Interleucina-1beta/metabolismo , Interleucina-6/metabolismo , Interleucina-6/sangue , Camundongos Endogâmicos C57BL , Neurotransmissores/metabolismo , Estresse Psicológico/microbiologia , Estresse Psicológico/metabolismoRESUMO
BACKGROUND: Fever is a common side effect following thermal ablation in patients with hepatocellular carcinoma (HCC), yet its impact on prognosis remains unclear. MATERIALS AND METHODS: This retrospective study included initial HCC patients who underwent US-guided percutaneous microwave ablation at 13 hospitals between January 2006 and February 2021. All patients were categorized into afebrile, transient low-grade fever (TLF), and prolonged or high-grade fever (PHF) groups. Primary outcomes included very early recurrence (VER) and early recurrence (ER), secondary outcomes were disease-free survival (DFS) and overall survival (OS). Fever cut-offs for VER/ER were established using restrictive cubic splines and adjusted Cox model. Survival analyses used the Kaplan-Meier method. RESULTS: A total of 1458 initial HCC patients (mean age, 59±11[SD]; 1146 men). Compared to afebrile individuals, patients with TLF (temperatures ranging 37.0-38.8°C for 1-2 d), showed independent protective effects against VER (HR, 0.73; 95% CI: 0.57,0.95; P=0.02) and ER (HR, 0.66; 95% CI: 0.54,0.81; P<0.001), however, PHF showed no differences in VER (HR, 0.99; 95% CI: 0.76,1.30; P=0.96) and ER (HR, 0.86; 95% CI: 0.69,1.07; P=0.17). With a median follow-up of 47 months (IQR:26-79), the median DFS for TLF patients was 40 months, superior to afebrile (30 mo, P=0.019) and PHF patients (33 mo, P=0.049). The 5-year OS rate for TLF patients was 73.2%, higher than afebrile (69.3%, P=0.02) and PHF patients (66.7%, P=0.03). No significant difference was found in DFS and OS between afebrile and PHF patients (P=0.90 and 0.71). Notably, TLF patients exhibited the highest lymphocyte counts increasing median 7 days after ablation (P<0.001 vs. afebrile and P=0.01 vs. PHF). CONCLUSION: Transient low-grade fever following percutaneous microwave ablation in hepatocellular carcinoma patients demonstrated protection against early recurrence, possibly attributed to the short-term activation of lymphocytes.
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Cardiomyocyte loss and myocardial fibrosis are major determinants of myocardial infarction (MI) pathological changes. Mesenchymal stem cell (MSC)-derived exosomes (exos) and Danshen decoction (DSY) have been demonstrated to mediate cardiac repair following MI. BM-MSCs exos or BM-MSCsDSY exos were intramuscularly injected into post-MI rats. On the 7th, 14th and 28th days, serum CK, LDH, α-HBDH, ALT, and AST were measured and electrocardiogram changes were monitored to identify cardiac function; Triphenyltetrazolium chloride staining, Hematein&Eosin staining, Masson trichrome staining and Transmission Electron Microscope were adopted to analyze infarct area, cardiac morphology, histopathology, and fibrosis and cardiomyocyte ultrastructure; TUNEL assay, real-time PCR and western blot were performed to detect cardiomyocyte apoptosis and autophagy. As a result, BMMSCsDSY exos are superior to BM-MSCs-exos in improvement of cardiac function, morphology, histopathology and cardiomyocyte ultrastructure, as well as in reduction of infarction area and cardiac fibrosis by inhibiting apoptosis and promoting autophagy of cardiomyocytes.
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S-Alkyl dithiocarbamates, as an important class of sulfur-containing compounds, play pivotal roles in diverse fields, yet methods for the synthesis that start from simple, readily available feedstocks and exhibit mild conditions and structurally diverse products are scarce. In this work, we developed an efficient approach for the synthesis of various S-alkyl dithiocarbamates via visible-light photocatalysis with readily available and structurally diverse alkyl carboxylic acids (primary, secondary, and tertiary acids, amino acids, etc.) and disulfide tetraalkylthiuram as the starting materials. This protocol features high efficiency, mild reaction conditions, a broad substrate scope, and good functional group tolerance. Potential applications are further demonstrated by a sunlight experiment, H2O as a solvent, gram-scale synthesis, and facile synthesis of bioactive molecules.
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BACKGROUND & AIMS: Frailty is associated with multiple morbidities. However, its effect on chronic liver diseases remains largely unexplored. This study evaluated the association of frailty with the risk of incident metabolic dysfunction-associated steatotic liver disease (MASLD), cirrhosis, liver cancer, and liver-related mortality. METHODS: A total of 339,298 participants without prior liver diseases from the UK Biobank were included. Baseline frailty was assessed by physical frailty and the frailty index, categorizing participants as non-frail, prefrail, or frail. The primary outcome was MASLD, with secondary outcomes, including cirrhosis, liver cancer, and liver-related mortality, confirmed through hospital admission records and death registries. RESULTS: During a median follow-up of 11.6 years, 4,667 MASLD, 1,636 cirrhosis, 257 liver cancer, and 646 liver-related mortality cases were identified. After multivariable adjustment, the risk of MASLD was found to be higher in participants with prefrailty (physical frailty: hazard ratio [HR] 1.66, 95% CI 1.40-1.97; frailty index: HR 2.01, 95% CI 1.67-2.42) and frailty (physical frailty: HR 3.32, 95% CI 2.54-4.34; frailty index: HR 4.54, 95% CI 3.65-5.66) than in those with non-frailty. Similar results were also observed for cirrhosis, liver cancer, and liver-related mortality. Additionally, the frail groups had a higher risk of MASLD, which was defined as MRI-derived liver proton density fat fraction >5%, than the non-frail group (physical frailty: odds ratio 1.64, 95% CI 1.32-2.04; frailty index: odds ratio 1.48, 95% CI 1.30-1.68). CONCLUSIONS: Frailty was associated with an increased risk of chronic liver diseases. Public health strategies should target reducing chronic liver disease risk in frail individuals. IMPACT AND IMPLICATIONS: While frailty is common and associated with a poor prognosis in people with MASLD (metabolic dysfunction-associated steatotic liver disease) and advanced chronic liver diseases, its impact on the subsequent risk of these outcomes remains largely unexplored. Our study showed that frailty was associated with increased risks of MASLD, cirrhosis, liver cancer, and liver-related mortality. This finding suggests that assessing frailty may help identify a high-risk population vulnerable to developing chronic liver diseases. Implementing strategies that target frailty could have major public health benefits for liver-related disease prevention.
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BACKGROUND: Diabetes mellitus (DM) and sarcopenia are bidirectionally linked and commonly co-occur among middle-aged and elderly individuals. This study aims to examine the combined effect of DM and sarcopenia on depressive symptoms and cognitive function. METHODS: This was a nationwide cohort study using data from the China Health and Retirement Longitudinal Study. The definition of DM was self-reported and based on hemoglobin A1c (HbA1c) ≥ 6.5% or fasting blood glucose (FBG) ≥ 126 mg/dL. The diagnosis of sarcopenia was based on the Asian Working Group for Sarcopenia 2019 algorithm. The outcomes included depressive symptoms assessed using the 10-item Center for Epidemiologic Studies Depression Scale (CES-D-10) and cognitive function. Multi-adjusted linear and logistic regression models were conducted to evaluate the combined effect of DM and sarcopenia on depression and cognitive performance. RESULTS: 9148 participants were included in the longitudinal analysis, with 45.5% being men and an average age of 57.4 years. 6987 (76.4%) participants had neither DM nor sarcopenia, 1076 (11.8%) had DM only, 983 (10.8%) had sarcopenia only, and 102 (1.1%) had both DM and sarcopenia. In the cross-sectional analysis, the DM (+)/Sarcopenia (+) group exhibited the highest CES-D-10 score (ß: 2.23, 95% confidence interval (CI): 1.26, 3.19) and the lowest cognitive score (ß: - 1.02, 95% CI - 1.79, - 0.26) (P for trend < 0.05). In the longitudinal analysis, individuals in the DM (+)/Sarcopenia ( +) group had higher risks of moderate-to-severe depression (odds ratio (OR): 2.09, 95% CI 1.18, 3.71) and cognitive decline (OR: 1.87, 95% CI 1.19, 2.95) compared to the DM (-)/Sarcopenia (-) group. The population attributable fractions of DM and sarcopenia were 42.2% (95% CI 6.3, 90.4) for moderate-to-severe depression and 23.0% (95% CI 8.6, 39.3) for cognitive decline. CONCLUSION: DM and sarcopenia additively increase the risk of moderate-to-severe depression and cognitive impairment, highlighting the importance of vigilant monitoring and management of these conditions to preserve mental health in middle-aged and elderly individuals.
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OBJECTIVES: Intrinsic capacity (IC), a multidimensional construct encompassing mental and physical capacities, has been established in the aging framework by the World Health Organization. However, the detailed relationship between IC and Chinese sleep patterns (nighttime sleep and post-lunch naps) remains inadequately elucidated. METHODS: Participants in this study were individuals aged ≥45 years residing in China, included in the China Health and Retirement Longitudinal Study (CHARLS). We analyzed 4 years of CHARLS data from the first wave (May 2011-March 2012) to the second wave (July 2015-January 2016). Data from these waves were utilized for longitudinal analysis. Self-reported data included nighttime sleep and nap duration, along with other baseline characteristics. The IC evaluation involved physical examinations and blood tests. Initially, linear regression was used to assess the relationship between total sleep duration, nighttime sleep duration, nap duration, and IC change between the two waves that were determined by marginal effects (ME) and their corresponding 95% confidence intervals (CIs). Regression splines were employed to explore potential nonlinear associations. Subgroup and sensitivity analyses were conducted to investigate the heterogeneity of IC change under specific conditions and the robustness of our results. Mediation analysis was performed to identify potential factors mediating the relationship between sleep patterns and IC change. RESULTS: Both excessive (>10 h) (total, ME: -1.12; 95% CI: -1.61, -0.64; nighttime, ME: -1.44; 95% CI: -2.29, -0.59) and insufficient (<6 h) sleep duration (total, ME: -0.43; 95% CI: -0.68, -0.18; nighttime, ME: -0.50; 95% CI: -0.73, -0.27) negatively impacted IC change. Moderate naps (≤60 min) mitigated the decline in IC change (ME: 0.28; 95% CI: 0.07, 0.49). IC values decreased at the slowest rate when nap time constituted one-seventh of total sleep time. The onset of dyslipidemia partially mediated the association between naps (≤60 min) and IC change (P = 0.02). CONCLUSIONS: These findings suggest that maintaining a healthy sleep pattern of 6-8 h of nighttime or total sleep, along with a post-lunch nap of ≤60 min, helps preserve optimal IC or delay its decline. This is particularly beneficial for cognitive, psychological, and locomotion performance among middle-aged and older adults.
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Phenformin, a biguanide compound, has attracted increased attention due to its prominent antitumor activity. As a multitarget agent, the antitumor effects of phenformin involve a wide range of factors, including inhibition of mitochondrial complex I, activation of AMPactivated protein kinase, impact on the tumor microenvironment, suppression of cancer stem cells and others. In addition, phenformin has been shown to markedly augment the effectiveness of various clinical treatment methods, including radiotherapy, chemotherapy, targeted therapy and immunotherapy. It is noteworthy that breakthrough progress has been made in the treatment of cancer with phenformin with application in clinical trials for the treatment of melanoma. Phenformin not only reduces the lesion area of patients, but also enhances the efficacy of dalafinib/trimetinib. In the present review, the novel breakthroughs in the antitumor effects and mechanisms of phenformin were discussed. In addition, the current review focuses on the clinical development value of phenformin, striving to provide new insights into the future research direction of phenformin in the field of tumor treatment.
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Neoplasias , Fenformin , Microambiente Tumoral , Humanos , Fenformin/farmacologia , Fenformin/uso terapêutico , Microambiente Tumoral/efeitos dos fármacos , Neoplasias/tratamento farmacológico , Antineoplásicos/uso terapêutico , Antineoplásicos/farmacologia , Células-Tronco Neoplásicas/efeitos dos fármacos , Animais , Melanoma/tratamento farmacológicoRESUMO
Sinonasal squamous cell carcinoma (SNSCC) is an aggressive cancer affecting the nasal and sinus regions, with its progression factors, particularly genetic ones, not yet fully understood. Here, we first conducted a retrospective study with 219 SNSCC patients to identify clinical factors affecting SNSCC prognosis. Additionally, we mined a vast literature dataset to uncover genetic factors associated with SNSCC progression. Based on this data, we constructed SNSCC prognosis pathways and performed a gene set enrichment analysis (GSEA). Clear operative margins were linked to a 73.5-86.3% improvement in overall survival and a 73.5-88.9% lower risk of recurrence. Nasal cavity-originated cases exhibited a 67.6-97.4% decrease in mortality and an 80.7-96.7% lower recurrence rate. Patients at T1-2 staging had a 65.0-80.6% reduced risk of death and recurrence compared to those at T3 stage. Additionally, we identified 53 genes associated with SNSCC, with 14 also implicated in primary tumor site, T stage, and operative margin. These genes, including EGFR, PIK3CA, ERBB2, PTEN, BCL2, BRAF, KRAS, and PRL, form a complex SNSCC-prognosis pathway and were significantly enriched in 42 KEGG pathways and Gene Ontology (GO) terms (FDR-corrected p-value < 0.001), influencing cell growth, apoptosis, and oncogenic signaling pathways. Our study suggests that three clinical parameters (operative margin type, primary tumor site, and T-stage) and 14 genetic factors may influence SNSCC prognosis post-surgery. These findings deepen our understanding of SNSCC and offer potential avenues to enhance its treatment and outcomes.
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Carcinoma de Células Escamosas , Humanos , Masculino , Feminino , Prognóstico , Pessoa de Meia-Idade , Idoso , Estudos Retrospectivos , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/cirurgia , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/mortalidade , Neoplasias dos Seios Paranasais/genética , Neoplasias dos Seios Paranasais/cirurgia , Neoplasias dos Seios Paranasais/patologia , Neoplasias dos Seios Paranasais/mortalidade , Recidiva Local de Neoplasia/genética , Estadiamento de Neoplasias , Adulto , Idoso de 80 Anos ou mais , Regulação Neoplásica da Expressão GênicaRESUMO
National Medical Products Administration released the Special provisions on the administration of registration of traditio-nal Chinese medicine(TCM) in February 2023, encouraging high-quality human use experience(HUE) study in TCM clinical practice to obtain sufficient evidence for TCM registration support. The provisions suggested that the HUE study should meet the relevant requirements and accept the drug registration verification. This paper aims to standardize the HUE study, obtain high-quality HUE data to support registration applications, and promote the standardization of research. In accordance with the relevant laws and regulations of the state and the requirements of the technical guidelines for the HUE study in the drug review center of the National Medical Products Administration, the clinical characteristics of TCM were considered, and the Clinical Evaluation Committee of Traditional Chinese Me-dicine of the Chinese Pharmaceutical Association organized and formulated the Guidelines for quality control of human use experience study on traditional Chinese medicine,including the conditions of medical institutions carrying out HUE study, researchers, sponsors, key information and requirements of pharmacy, research programs, key points of ethical review, requirements of the research implementation process, risk management, and subject protection of HUE study. After several rounds of consultation with experts, a guideline document suitable for supporting drug registration and guiding HUE study on TCM was finally formed.
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Medicamentos de Ervas Chinesas , Medicina Tradicional Chinesa , Controle de Qualidade , Humanos , Medicina Tradicional Chinesa/normas , Medicamentos de Ervas Chinesas/normas , ChinaRESUMO
Introduction: Viruses are among the main pathogens causing diarrhoea in calves. The current study found that bovine norovirus (BNoV) is one of the principal viruses causing diarrhoea in calves in Xinjiang, China. Material and Methods: A total of 974 calf faecal samples from six regions in Xinjiang were tested for BNoV using reverse-transcriptase PCR. The genomic characteristics of BNoV and the genetic evolution of the VP1 gene, protein three-dimensional structure characteristics and amino acid variation were analysed using bioinformatics methods. Results: Epidemiological survey results showed that the infection rate of BNoV was 19.82%, and all samples tested positive in five regions. The results of the genetic evolution analysis showed that BNoV strains from Tacheng of northern Xinjiang and Kashgar of southern Xinjiang both belonged to the GIII.2 genotype of BNoV but were not on the same cluster of evolutionary branches. Additionally, the amino acid variation of the VP1 protein was not observed to significantly affect its spatial structure. Conclusion: This study is the first to report the genetic characteristics of the BNoV complete genome sequence in Xinjiang and provides a scientific basis for BNoV vaccine development and pathogenesis research.
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Aim: Comparing the safety, effectiveness, and mid-term survival rates of robot-assisted minimally invasive esophagectomy (RAMIE) and video-assisted minimally invasive esophagectomy (VAMIE). Methods: A total of 842 patients undergoing minimally invasive esophagectomy were analyzed, including 694 patients in VAMIE group and 148 in RAMIE group. PSM analysis was applied to generate matched pairs for further comparison. Operative outcomes, postoperative complications and Mid-term outcomes were compared between all patients in matched groups. Results: After 1:4 PSM, 148 patients in the RAMIE and 592 patients in the VAMIE. Compared to VAMIE, RAMIE exhibited earlier removal of chest and neck drainage tubes, shorter postoperative hospital stays, and a higher number of lymph node dissections. However, the surgical duration of RAMIE was longer than that of VAMIE. Postoperative complications were no statistically significant between the RAMIE and VAMIE groups. There was no statistically significant difference in the 3-year OS and DFS between the two groups. Conclusion: Compared to VAMIE, RAMIE emerges as a viable and safe surgical approach and suggests RAMIE as a potential alternative to minimally invasive esophagectomy.
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Background: COVID-19 began in December 2019, rapidly spreading worldwide. China implemented a dynamic zero-COVID strategy and strict control measures after the outbreak. However, Guangzhou city ended closed-off management by the end of November 2022, leading to exposure to SARS-CoV-2. Despite most hospitalized patients being infected or co-infected with SARS-CoV-2, some remained uninfected. We report two cases of bacterial pneumonia with elevated globulin levels not infected with SARS-CoV-2, aiming to identify protection factors of SARS-CoV-2 infection and provide a scientific basis for SARS-CoV-2 prevention. Case presentation: Case 1, a 92-year-old male, admitted on October 21, 2022, developed worsening cough and sputum after aspiration, diagnosed with bacterial pneumonia with Pseudomonas aeruginosa, Escherichia coli (CRE) and carbapenem-resistant Acinetobacter baumannii (CRAB) infections. He was treated with imipenem anti-infective therapy and mechanical ventilation, then switched to a combination of meropenem, voriconazole and amikacin anti-infective therapy due to recurrent infections and septic shock, and died of sepsis on 8 January 2023. Case 2 is an 82-year-old male admitted on 30 September 2022, with recurrent cough, sputum, and shortness of breath, diagnosed with bacterial pneumonia with carbapenem-resistant Klebsiella pneumoniae (CRKP) and Mycobacterium pneumoniae infections. He was treated with ventilator-assisted ventilation, meropenem, amikacin, tigecycline and mucomycin nebulization and discharged with improvement on 26 October. He was readmitted on 21 November 2022 and diagnosed with bacterial pneumonia. He was treated with cefoperazone sulbactam, amikacin, meropenem and fluconazole and discharged on 31 December. Neither patient was infected with SARS-CoV-2 during hospitalization. Notably, their globulin levels were elevated before SARS-CoV-2 exposure, gradually decreasing afterward. Conclusions: Patients with bacterial pneumonia with high globulin levels likely have large amounts of immunoglobulin, and that immunoglobulin cross-reactivity causes this protein to be involved in clearing SARS-CoV-2 and preventing infection. Therefore, bacterial pneumonia patients with high globulin levels included in this study were not infected with SARS-CoV-2. After exposure to SARS-CoV-2, the amount of globulin in the patient's body was reduced because it was used to clear SARS-CoV-2. The results of this study are expected to provide a theoretical basis for the study of the mechanism of prevention and treatment of SARS-CoV-2 infection.
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COVID-19 , Pneumonia Bacteriana , SARS-CoV-2 , Humanos , Masculino , COVID-19/complicações , Pneumonia Bacteriana/tratamento farmacológico , Pneumonia Bacteriana/diagnóstico , Idoso de 80 Anos ou mais , Antibacterianos/uso terapêuticoRESUMO
In-vehicle information system (IVIS) use is prevalent among young adults. However, their interaction with IVIS needs to be better understood. Therefore, an on-road study aims to explore the effects of input modalities and secondary task types on young drivers' secondary task performance, driving performance, and visual glance behavior. A 2 × 4 within-subject design was undertaken. The independent variables are input modalities (auditory-speech and visual-manual) and secondary task types (calls, music, navigation, and radio). The dependent variables include secondary task performance (task completion time, number of errors, and SUS), driving performance (average speed, number of lane departure warnings, and NASA-TLX), and visual glance behavior (average glance duration, number of glances, total glance duration, and number of glances over 1.6 s). The statistical analysis result showed that the main effect of input modalities is significant, with more distraction during visual-manual than auditory-speech. The main impact of secondary task types was also substantial across most metrics, aside from average speed and average glance duration. Navigation and music were the most distracting, followed by calls, and radio came in last. The distracting effect of input modalities is relatively stable and generally not moderated by the secondary task types, except radio tasks. The findings practically benefit the driver-friendly human-machine interface design, preventing IVIS-related distraction.
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Condução de Veículo , Análise e Desempenho de Tarefas , Humanos , Masculino , Feminino , Adulto Jovem , Adulto , Direção Distraída , Atenção/fisiologia , AdolescenteRESUMO
Introduction: Breeding rice with drought tolerance for harsh environments is crucial for agricultural sustainability. Understanding the genetic underpinnings of drought tolerance is vital for developing resilient rice varieties. Genome-wide association studies (GWAS) have emerged as pivotal tools in unravelling the complex genetic architecture of traits like drought tolerance, capitalizing on the natural genetic diversity within rice germplasm collections. Methods: In this study, a comprehensive panel of 210 rice varieties was phenotyped over ten days in controlled conditions, subjected to simulated drought stress using 20% PEG 6000 in petri dishes. Throughout the stress period, crucial traits such as germination percentage (GP), germination rate index (GRI), mean germination time (MGT), and seedling percentage (SP) were meticulously monitored. Results: The GWAS analysis uncovered a total of 38 QTLs associated with drought tolerance traits, including novel loci like qMGT-5.2, qSP-3, qSP7.2, and qGP-5.2. Additionally, RNA-seq analysis identified ten genes with significant expression differences under drought stress conditions. Notably, haplotype analysis pinpointed elite haplotypes in specific genes linked to heightened drought tolerance. Discussion: Overall, this study underscores the importance of GWAS in validating known genes while unearthing novel loci to enrich the genetic resources for enhancing drought tolerance in rice breeding programs.
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Despite the widespread utilizable value of 3-oxazolines, mild and efficient access to such a class of unique structures still remains, to date, a challenge. Herein, we present a [3 + 2] annulation strategy, guided by the retrosynthetic principle of [CO + CCN], that utilizes vinyl azides as the CCN module and aldehydes as the CO module. This approach enables the efficient construction of the 3-oxazoline framework with remarkable features, including operational simplicity, environmental friendliness, and high efficiency. Notably, it solely requires the addition of inexpensive and readily available N-hydroxyphthalimide (NHPI) and air oxygen to obtain the desired product. It also provides a new way to generate the hydroxyl radical, which is produced by the homolysis of peroxycarboxylic acid. In addition, control experiments, X-ray crystallographic analysis, high-resolution mass spectrometry (HRMS), and density functional theory (DFT) calculations afford evidence for the key intermediates (hydroxyl radical, carboxyl radical, imine radical, hydroxyl substituted amide derivatives), further confirming the path for realization of 3-oxazolines.
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It is time- and man-power intensive to craft various fish species for underwater animations and games. Even professionals spend hours to days for one. Therefore, we propose Procedural Fish Generation, which presents an innovative and automatic approach to generate 3D fish models with one lateral image. The core lies in parameterizing the ray-finned fish with curves and optimizing them with textures to fit the input using differentiable rendering, greatly reducing the manual modeling work. It presents advantages over multi-image reconstruction in requiring single image, while state-of-the-art methods suffer from such a scenario to achieve informative reconstruction. Also, our method outputs a polygon mesh, widely compatible with modern graphics hardware and software, thus facilitating further editing. Furthermore, we fine tune the prompts for Stable Diffusion while users can type a name to find high-quality lateral images. Extensive ablation studies and comparisons have proved its effectiveness and efficiency for experts and non-experts.
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In the investigation of heterotrimeric G protein-mediated signal transduction in planta, their roles in the transmittance of low K+ stimuli remain to be elucidated. Here, we found that the primary root growth of wild-type Arabidopsis was gradually inhibited with the decrease of external K+ concentrations, while the primary root of the mutants for G protein ß subunit AGB1 and γ subunits AGG1, AGG2 and AGG3 could still grow under low K+ conditions (LK). Exogenous NAA application attenuated primary root elongation in agb1 and agg1/2/3 but promoted the growth in wild-type seedlings under LK stress. Using ProDR5:GFP, ProPIN1:PIN1-GFP and ProPIN2:PIN2-GFP reporter lines, a diminishment in auxin concentration at the radicle apex and a reduction in PIN1and PIN2 efflux carrier abundance were observed in wild-type roots under LK, a phenomenon not recorded in the agb1 and agg1/2/3. Further proteolytic and transcriptional assessments revealed an enhanced degradation of PIN1 and a suppressed expression of PIN2 in the wild-type background under LK, contrasting with the stability observed in the agb1 and agg1/2/3 mutants. Our results indicate that the G protein ß and γ subunits play pivotal roles in suppressing of Arabidopsis root growth under LK by modulating auxin redistribution via alterations in PIN1 degradation and PIN2 biosynthesis.