Impact of perioperative low-molecular-weight heparin therapy on clinical events of elderly patients with prior coronary stents implanted > 12 months undergoing non-cardiac surgery: a randomized, placebo-controlled trial.

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

Whole-genome metagenomic analysis of the oral microbiota in patients with obstructive sleep apnea.

PURPOSE: The oral microbiota is closely associated with systemic health, but few studies have investigated the oral microbiota in patients with obstructive sleep apnea (OSA). This study aimed to identify the variation of oral microbiota among patients with severe OSA, and the change of oral microbiota after treatment with continuous positive airway pressure (CPAP). METHODS: Participants were enrolled in the study from November 2020 to August 2021. Sleep parameters using full nocturnal polysomnography (PSG) were collected on healthy controls, patients with severe OSA, and patients with severe OSA after CPAP treatment for 3 months. Oral samples were also collected by rubbing disposable medical sterile swabs on the buccal mucosa. Routine blood tests and biochemical indicators were measured using the fully automated biochemical analyzer. Oral microbial composition of oral samples were determined using whole-genome metagenomic analysis in all participants. Correlations were analyzed between the oral microbiota and blood lipids. RESULTS: Study enrollment included 14 participants, 7 healthy controls and 7 patients with severe OSA. At the species level, the relative abundances of Prevotella, Alloprevotella, Bacteroides, Veillonella_tobetsuensis, Candidatus saccharimonas, and Leptotrichia in the groups with severe OSA were significantly lower than those in the healthy controls (P both < 0.05). The abundances of Capnocytophaga, Veillonella, Bacillus_anthracis, Eikenella, and Kingella were significantly higher whereas the abundances of Gordonia and Streptococcus were significantly lower in the group with severe OSA compared to the severe OSA-CPAP group (P < 0.05 for both). According to the Kyoto Encyclopedia of Genes and Genomes (KEGG), 4 pathways changed in the group with severe OSA compared with healthy controls (P both < 0.05). Pathways related to Novobiocin biosynthesis, 2-Oxocarboxylic acid metabolism, and Histidine metabolism were enriched in the patients with severe OSA. Nine pathways showed significant differences with regard to the relative abundances of phenylalanine metabolism; alanine, aspartate, and glutamate metabolism; one carbon pool by folate; monobactam biosynthesis; 2-oxocarboxylic acid metabolism; arginine biosynthesis and vitamin B6 metabolism; novobiocin biosynthesis; and arginine and proline metabolism, which were significantly higher in the group with severe OSA compared to the severe OSA-CPAP group (P both < 0.05). The Spearman correlation analysis between blood lipid parameters and oral microbiota components showed that negative correlations were observed between total cholesterol and Streptomyces (r = - 0.893, P = 0.007), and high-density lipoprotein cholesterol (HDL-C) and Gordonia (r = - 0.821, P = 0.023); positive correlations were observed between HDL-C and Candidatus saccharimonas (r = 0.929, P = 0.003), and low-density lipoprotein cholesterol (LDL-C) and Capnocytophaga (r = 0.893, P = 0.007). CONCLUSION: There was an apparent discrepancy of the oral microbiota and metabolic pathways between the group with severe OSA and controls, and CPAP significantly changed oral microbial abundance and metabolic pathways in patients with severe OSA. Correlation analysis showed that these oral bacteria were strongly correlated with the blood lipids level.

Optical microscope with a large tilt angle and a long focal length for a nano-size angle-resolved photoemission spectroscopy.

Angle-resolved photoemission spectroscopy with nanoscale spatial resolution (Nano-ARPES) is a powerful tool for the investigation of electronic structures of materials and their spatial configurations. In order to capture the area of interest in Nano-ARPES measurements effectively, an optical microscope can be used to provide real space optical images as a reference. In this work, a new type of optical microscope for Nano-APRES spectrometer with a large tilt angle of ∼30 degrees and a long focal length of ∼12 mm has been designed. Large magnifications by 7 × to 20 × and a spatial resolution of 3 um have been achieved, which can effectively assist optical alignment for Nano-ARPES. In addition, the strong boundary sensitivity observed in such a tilt design demonstrates its special capability in detecting the fine features of surface coarseness.

Clinical Features of 85 Fatal Cases of COVID-19 from Wuhan. A Retrospective Observational Study.

Rationale: The global death toll from coronavirus disease (COVID-19) virus as of May 12, 2020, exceeds 286,000. The risk factors for death were attributed to advanced age and comorbidities but have not been accurately defined.Objectives: To report the clinical features of 85 fatal cases of COVID-19 in two hospitals in Wuhan.Methods: Medical records were collected of 85 fatal cases of COVID-19 between January 9, 2020, and February 15, 2020. Information recorded included medical history, exposure history, comorbidities, symptoms, signs, laboratory findings, computed tomographic scans, and clinical management.Measurements and Main Results: The median age of the patients was 65.8 years, and 72.9% were male. Common symptoms were fever (78 [91.8%]), shortness of breath (50 [58.8%]), fatigue (50 [58.8%]), and dyspnea (60 [70.6%]). Hypertension, diabetes, and coronary heart disease were the most common comorbidities. Notably, 81.2% of patients had very low eosinophil counts on admission. Complications included respiratory failure (80 [94.1%]), shock (69 [81.2%]), acute respiratory distress syndrome (63 [74.1%]), and arrhythmia (51 [60%]), among others. Most patients received antibiotic (77 [90.6%]), antiviral (78 [91.8%]), and glucocorticoid (65 [76.5%]) treatments. A total of 38 (44.7%) and 33 (38.8%) patients received intravenous immunoglobulin and IFN-α2b, respectively.Conclusions: In this depictive study of 85 fatal cases of COVID-19, most cases were males aged over 50 years with noncommunicable chronic diseases. The majority of the patients died of multiple organ failure. Early onset of shortness of breath may be used as an observational symptom for COVID-19 exacerbations. Eosinophilopenia may indicate a poor prognosis. A combination of antimicrobial drugs did not offer considerable benefit to the outcome of this group of patients.

Clinical Characteristics of COVID-19 Patients With Digestive Symptoms in Hubei, China: A Descriptive, Cross-Sectional, Multicenter Study.

OBJECTIVE: Since the outbreak of Coronavirus Disease 2019 (COVID-19) in December 2019, various digestive symptoms have been frequently reported in patients infected with the virus. In this study, we aimed to further investigate the prevalence and outcomes of COVID-19 patients with digestive symptoms. METHODS: In this descriptive, cross-sectional, multicenter study, we enrolled confirmed patients with COVID-19 who presented to 3 hospitals from January 18, 2020, to February 28, 2020. All patients were confirmed by real-time polymerase chain reaction and were analyzed for clinical characteristics, laboratory data, and treatment. Data were followed up until March 18, 2020. RESULTS: In the present study, 204 patients with COVID-19 and full laboratory, imaging, and historical data were analyzed. The average age was 52.9 years (SD ± 16), including 107 men and 97 women. Although most patients presented to the hospital with fever or respiratory symptoms, we found that 103 patients (50.5%) reported a digestive symptom, including lack of appetite (81 [78.6%] cases), diarrhea (35 [34%] cases), vomiting (4 [3.9%] cases), and abdominal pain (2 [1.9%] cases). If lack of appetite is excluded from the analysis (because it is less specific for the gastrointestinal tract), there were 38 total cases (18.6%) where patients presented with a gastrointestinal-specific symptom, including diarrhea, vomiting, or abdominal pain. Patients with digestive symptoms had a significantly longer time from onset to admission than patients without digestive symptoms (9.0 days vs 7.3 days). In 6 cases, there were digestive symptoms, but no respiratory symptoms. As the severity of the disease increased, digestive symptoms became more pronounced. Patients with digestive symptoms had higher mean liver enzyme levels, lower monocyte count, longer prothrombin time, and received more antimicrobial treatment than those without digestive symptoms. DISCUSSION: We found that digestive symptoms are common in patients with COVID-19. Moreover, these patients have a longer time from onset to admission, evidence of longer coagulation, and higher liver enzyme levels. Clinicians should recognize that digestive symptoms, such as diarrhea, are commonly among the presenting features of COVID-19 and that the index of suspicion may need to be raised earlier in at-risk patients presenting with digestive symptoms. However, further large sample studies are needed to confirm these findings.

Pirfenidone alleviates lipopolysaccharide-induced lung injury by accentuating BAP31 regulation of ER stress and mitochondrial injury.

Pirfenidone has been widely used in the treatment of idiopathic pulmonary fibrosis (IPF). However, the role of pirfenidone in LPS-induced acute lung injury (ALI) remains unclear. This study aims to investigate the protective effects of pirfenidone in ALI and to explore its underlying mechanism. Pirfenidone clearly reduces LPS-triggered ALI as indicated by significant pathological alterations, reduced oxidative stress and inflammatory responses in vivo. Furthermore, pirfenidone also blocks apoptosis of LPS-induced alveolar epithelial type II (ATII) cells through inhibition of endoplasmic reticulum (ER) stress and mitochondrial injury in vivo and in vitro. A lower expression level of BAP31, an ER transmembrane protein, was found to be associated with ALI followed LPS challenge. The reintroduction of BAP31 blunted LPS induced ER stress and mitochondrial damage and therefore alleviated ATII cell apoptosis, which correlated with pirfenidone treatment. Knockdown of BAP31 expression in pirfenidone treated ATII cells re-activated ER stress, mitochondrial damage and followed cellular apoptosis. In summary, this study confirms the beneficial effect of pirfenidone on ER stress and mitochondrial dysfunction mediated apoptosis via upregulation of BAP31. Our results demonstrated that pirfenidone may be considered as a potential agent for the treatment of ALI in the future.

Comparative genomic analysis of Klebsiella pneumonia (LCT-KP214) and a mutant strain (LCT-KP289) obtained after spaceflight.

BACKGROUND: With the development of space science, it is important to analyze the relationship between the space environment and genome variations that might cause phenotypic changes in microbes. Klebsiella pneumoniae is commonly found on the human body and is resistant to multiple drugs. To study space-environment-induced genome variations and drug resistance changes, K. pneumoniae was carried into outer space by the Shenzhou VIII spacecraft. RESULTS: The K. pneumoniae strain LCT-KP289 was selected after spaceflight based on its phenotypic differences compared to the ground-control strain. Analysis of genomic structural variations revealed one inversion, 25 deletions, fifty-nine insertions, two translocations and six translocations with inversions. In addition, 155 and 400 unique genes were observed in LCT-KP214 and LCT-KP289, respectively, including the gene encoding dihydroxyacetone kinase, which generates the ATP and NADH required for microbial growth. Furthermore, a large number of mutant genes were related to transport and metabolism. Phylogenetic analysis revealed that most genes in these two strains had a dN/dS value greater than 1, indicating that the strain diversity increased after spaceflight. Analysis of drug-resistance phenotypes revealed that the K. pneumoniae strain LCT-KP289 was resistant to sulfamethoxazole, whereas the control strain, LCT-KP214, was not; both strains were resistant to benzylpenicillin, ampicillin, lincomycin, vancomycin, chloramphenicol and streptomycin. The sulfamethoxazole resistance may be associated with sequences in Scaffold7 in LCT-KP289, which were not observed in LCT-K214; this scaffold contained the gene sul1. In the strain LCT-KP289, we also observed a drug-resistance integron containing emrE (confers multidrug resistance) and ant (confers resistance to spectinomycin, streptomycin, tobramycin, kanamycin, sisomicin, dibekacin, and gentamicin). The gene ampC (confers resistance to penicillin, cephalosporin-ii and cephalosporin-i) was present near the integron. In addition, 30 and 26 drug-resistance genes were observed in LCT-KP289 and LCT-KP214, respectively. CONCLUSIONS: Comparison of a K. pneumoniae strain obtained after spaceflight with the ground-control strain revealed genome variations and phenotypic changes and elucidated the genomic basis of the acquired drug resistance. These data pave the way for future studies on the effects of spaceflight.

[Preliminary analysis on the treatment of ventilator-associated pneumonia caused by pandrug-resistant Acinetobacter baumannii].

OBJECTIVE: To analyze the clinical features of pandrug-resistant Acinetobacter baumannii (PDR-Ab) in the Chinese PLA General Hospital and compare the efficacies of different antibiotic treatments in aged patients with ventilator-associative pneumonia (VAP) caused by PDR-Ab. METHODS: Data were collected from all isolated PDR-Ab strains in our hospital from April 2009 to April 2010. The clinical features, treatment, and outcomes were retrospectively reviewed. RESULTS: PDR-Ab was found to be the dominant pathogen in 42 of 126 aged VAP patients. Cefoperazone/sulbactam plus minocycline showed good efficacy in 20 patients with PDR-Ab VAP, showing a clinical cure rate of 65% (13/20) and a bacterial eradication rate of 40% (8/20). Another 22 patients were treated with other antimicrobial drugs, achieving a clinical cure rate of 22.7% (5/22) and a bacterial eradication rate of 13.6% (3/22). The factors influencing bacterial clearance were prolonged length of hospital stay and mechanical ventilation prior to positive culture (all P<0.01). CONCLUSION: Cefoperazone/sulbactam plus minocycline can be an effective treatment for VAP caused by PDR-Ab.

The Effect of Visual Word Segmentation Cues in Tibetan Reading.

BACKGROUND/OBJECTIVES: In languages with within-word segmentation cues, the removal or replacement of these cues in a text hinders reading and lexical recognition, and adversely affects saccade target selection during reading. However, the outcome of artificially introducing visual word segmentation cues into a language that lacks them is unknown. Tibetan exemplifies a language that does not provide visual cues for word segmentation, relying solely on visual cues for morpheme segmentation. Moreover, previous studies have not examined word segmentation in the Tibetan language. Therefore, this study investigated the effects of artificially incorporated visual word segmentation cues and basic units of information processing in Tibetan reading. METHODS: We used eye-tracking technology and conducted two experiments with Tibetan sentences that artificially incorporated interword spaces and color alternation markings as visual segmentation cues. CONCLUSIONS: The results indicated that interword spaces facilitate reading and lexical recognition and aid in saccade target selection during reading. Color alternation markings facilitate reading and vocabulary recognition but do not affect saccade selection. Words are more likely to be the basic units of information processing and exhibit greater psychological reality than morphemes. These findings shed light on the nature and rules of Tibetan reading and provide fundamental data to improve eye movement control models for reading alphabetic writing systems. Furthermore, our results may offer practical guidance and a scientific basis for improving the efficiency of reading, information processing, and word segmentation in Tibetan reading.

Urolithin A promotes the degradation of TMSB10 to deformation F-actin in non-small-cell lung cancer.

BACKGROUND: Lung cancer is one of the most frequently diagnosed cancers and non-small-cell lung cancer (NSCLC) poses major diagnoses. Urolithin A (UA) is a natural compound produced by the gut microbiota through the metabolism of polyphenol ellagitannins (ETs) and ellagic acid (EA), which has been found to inhibit epithelial-mesenchymal transition (EMT) in lung cancer cell lines. However, the mechanism of UA function in NSCLC remains elusive. PROPOSE: This study aimed to investigate the potential effectiveness of UA in NSCLC therapeutic and uncovering its underlying mechanisms. METHODS: Effects of UA treatment, TMSB10 gene knockdown or overexpression on NSCLC cell phenotype were evaluated by availability, transwell assays. The downstream factors and pathways of UA were investigated by proteomics. TMSB10 expression in NSCLC tissues was detected by bioinformatics analysis as well as immunohistochemistry. Confocal imaging, GST pull-down and western blotting investigated the mechanism of UA induced TMSB10 degradation. RESULTS: In the present study, we demonstrated that UA shows an inhibitory role in NSCLC cell proliferation, migration, and invasion. This inhibition is attributed to the accelerated degradation of TMSB10, a biomarker among various cancers, via the autophagy-lysosome pathway. Additionally, knocked down of TMSB10 showed a similar phenotype with UA treatment. The reduction of TMSB10 protein level following decreased ATP level inhibits the F-actin formation for cell migration, thereby disrupting the equilibrium between G-actin-TMSB10 and G-actin-ATP interactions in A549 cells. CONCLUSION: Our results reveal that UA is potential for NSCLC therapeutics through reducing the protein level of TMSB10 to deformation the F-actin.

The Barrier Disruption and Pyroptosis of Intestinal Epithelial Cells Caused by Perfringolysin O (PFO) from Clostridium perfringens.

Clostridium perfringens (C. perfringens), a Gram-positive bacterium, produces a variety of toxins and extracellular enzymes that can lead to disease in both humans and animals. Common symptoms include abdominal swelling, diarrhea, and intestinal inflammation. Severe cases can result in complications like intestinal hemorrhage, edema, and even death. The primary toxins contributing to morbidity in C. perfringens-infected intestines are CPA, CPB, CPB2, CPE, and PFO. Amongst these, CPB, CPB2, and CPE are implicated in apoptosis development, while CPA is associated with cell death, increased intracellular ROS levels, and the release of the inflammatory factor IL-18. However, the exact mechanism by which PFO toxins exert their effects in the infected gut is still unidentified. This study demonstrates that a C. perfringens PFO toxin infection disrupts the intestinal epithelial barrier function through in vitro and in vivo models. This study emphasizes the notable influence of PFO toxins on intestinal barrier integrity in the context of C. perfringens infections. It reveals that PFO toxins increase ROS production by causing mitochondrial damage, triggering pyroptosis in IPEC-J2 cells, and consequently resulting in compromised intestinal barrier function. These results offer a scientific foundation for developing preventive and therapeutic approaches against C. perfringens infections.

Application of Recombinant Lactic Acid Bacteria (LAB) Live Vector Oral Vaccine in the Prevention of F4+ Enterotoxigenic Escherichia coli.

Enterotoxigenic Escherichia coli (ETEC) causes severe diarrhea in piglets. The current primary approach for ETEC prevention and control relies on antibiotics, as few effective vaccines are available. Consequently, an urgent clinical demand exists for developing an effective vaccine to combat this disease. Here, we utilized food-grade Lactococcus lactis NZ3900 and expression plasmid pNZ8149 as live vectors, together with the secreted expression peptide Usp45 and the cell wall non-covalent linking motif LysM, to effectively present the mutant LTA subunit, the LTB subunit of heat-labile enterotoxin, and the FaeG of F4 pilus on the surface of recombinant lactic acid bacteria (LAB). Combining three recombinant LAB as a live vector oral vaccine, we assessed its efficacy in preventing F4+ ETEC infection. The results demonstrate that oral immunization conferred effective protection against F4+ ETEC infection in mice and piglets lacking maternal antibodies during weaning. Sow immunization during late pregnancy generated significantly elevated antibodies in colostrum, which protected piglets against F4+ ETEC infection during lactation. Moreover, booster immunization on piglets during lactation significantly enhanced their resistance to F4+ ETEC infection during the weaning stage. This study highlights the efficacy of an oral LAB vaccine in preventing F4+ ETEC infection in piglets by combining the sow immunization and booster immunization of piglets, providing a promising vaccination strategy for future prevention and control of ETEC-induced diarrhea in piglets.

Antimicrobial Resistance and Genomic Characteristics of Escherichia coli Strains Isolated from the Poultry Industry in Henan Province, China.

Escherichia coli (E. coli) is an important foodborne pathogen and a biomarker for monitoring antimicrobial resistance. Investigating the prevalence of E. coli in the poultry industry holds great importance, particularly in Henan province, a major poultry-producing region in China. Here, we investigated the antimicrobial resistance (AMR) phenotypes of E. coli strains obtained from the poultry industry in Henan, China. A total of 344 E. coli strains were isolated from 638 samples collected from seven farms, three slaughterhouses, and ten terminal markets. Approximately 96.4%, 81.7%, and 52.5% of the isolates from the farms, slaughterhouses, and terminal markets exhibited multidrug resistance. Whole-genome sequencing was performed on 169 strains to reveal their genomic characteristics. The sequence type (ST) analysis revealed that ST10 and ST156 were the most frequent types within the poultry supply chain, whereas ST10 and ST162 were commonly found across the farms, slaughterhouses, and terminal markets. Fourteen ST10 E. coli strains belonged to phylogenetic group A, while fifteen ST165 and six ST162 E. coli strains belonged to phylogenetic group B1. In addition, several antimicrobial resistance genes and virulence factor genes were identified. The blaNDM-5 gene mediated carbapenem resistance in two E. coli strains, while mcr-1-mediated colistin resistance was detected in nine E. coli strains. Phylogenetic group A exhibited fewer virulence genes compared to other groups of E. coli. Plasmid replicons, such as IncFIB (AP001918), IncX1, IncFIC (FII), and IncFII (pHN7A8), were frequently observed. These findings provide valuable insights into the current AMR profiles of E. coli strains isolated from the poultry industry in Central China and highlight the need to implement good manufacturing practices and reduce antibiotic usage to mitigate potential risks associated with E. coli.

A multifunctional smart field-programmable radio frequency surface.

Antennas that can operate across multiple communication standards have remained a challenge. To address these limitations, we propose a Field-Programmable Radio Frequency Surface (FPRFS), which is based on manipulating current flow on its surface to achieve desirable RF characteristics. In this work, we demonstrate that substantial enhancements in radiation efficiency can be achieved while preserving the high reconfigurability of antenna structures implemented on the FPRFS. This is accomplished by utilizing an asymmetric excitation, directing the excitation to the low-loss contiguous surface, and dynamically manipulating the imaged return current on a segmented ground plane by switches. This important insight allows for adaptable antenna performance that weakly depends on the number of RF switches or their loss. We experimentally validate that FPRFS antennas can achieve efficiencies comparable to traditionally implemented antenna counterparts. This permits the FPRFS to be effectively utilized as a productive antenna and impedance-matching network with real-time reconfigurability.

Antiviral effectiveness and survival correlation of azvudine and nirmatrelvir/ritonavir in elderly severe patients with COVID-19: a retrospective real-world study.

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

A multi-omic analysis of an Enterococcus faecium mutant reveals specific genetic mutations and dramatic changes in mRNA and protein expression.

BACKGROUND: For a long time, Enterococcus faecium was considered a harmless commensal of the mammalian gastrointestinal (GI) tract and was used as a probiotic in fermented foods. In recent decades, E. faecium has been recognised as an opportunistic pathogen that causes diseases such as neonatal meningitis, urinary tract infections, bacteremia, bacterial endocarditis and diverticulitis. E. faecium could be taken into space with astronauts and exposed to the space environment. Thus, it is necessary to observe the phenotypic and molecular changes of E. faecium after spaceflight. RESULTS: An E. faecium mutant with biochemical features that are different from those of the wild-type strain was obtained from subculture after flight on the SHENZHOU-8 spacecraft. To understand the underlying mechanism causing these changes, the whole genomes of both the mutant and the WT strains were sequenced using Illumina technology. The genomic comparison revealed that dprA, a recombination-mediator gene, and arpU, a gene associated with cell wall growth, were mutated. Comparative transcriptomic and proteomic analyses showed that differentially expressed genes or proteins were involved with replication, recombination, repair, cell wall biogenesis, glycometabolism, lipid metabolism, amino acid metabolism, predicted general function and energy production/conversion. CONCLUSION: This study analysed the comprehensive genomic, transcriptomic and proteomic changes of an E. faecium mutant from subcultures that were loaded on the SHENZHOU-8 spacecraft. The implications of these gene mutations and expression changes and their underlying mechanisms should be investigated in the future. We hope that the current exploration of multiple "-omics" analyses of this E. faecium mutant will provide clues for future studies on this opportunistic pathogen.

Examining the extraction of parafoveal semantic information in Tibetan.

This study conducted two experiments to investigate the extraction of semantic preview information from the parafovea in Tibetan reading. In Experiment 1, a single-factor (preview type: identical vs. semantically related vs. unrelated) within-subject experimental design was used to investigate whether there is a parafoveal semantic preview effect (SPE) in Tibetan reading. Experiment 2 used a 2 (contextual constraint: high vs. low) × 3 (preview type: identical vs. semantically related vs. unrelated) within-subject experimental design to investigate the influence of contextual constraint on the parafoveal semantic preview effect in Tibetan reading. Supporting the E-Z reader model, the experimental results showed that in Tibetan reading, readers could not obtain semantic preview information from the parafovea, and contextual constraint did not influence this process. However, comparing high- and low-constrained contexts, the latter might be more conducive to extracting semantic preview information from the parafovea.

Occurrence, distribution, and potential ecological risks of antibiotics in a seasonal freeze-thaw basin.

Antibiotics have gained increasing attention as pharmaceuticals widely existing in human society. Under low temperature conditions, antibiotics tend to have higher environmental persistence, which poses a potential threat to ecological environment, but research on antibiotics in low-temperature basins is still lacking. Therefore, for investigating occurrence, spatio-temporal distributions, and ecological risks of antibiotics in a seasonal freeze-thaw basin, rivers in Tumen River basin were selected and sampled, including 25 samples during the river-freezing season and 27 samples during the non-freezing season. Overall, climate characteristics of different latitudes and renewal frequency of antibiotics are important factors that lead to diversity of antibiotics in basins. Eleven target antibiotics were detected and their average concentrations during the river-freezing season (0.83-27.5 ng L-1) were lower than that during the non-freezing season (2.80-45.30 ng L-1), severely impacted by river flow, ice sealed-melting, and local feeding practices. In addition, total antibiotic concentrations are usually highest in downstream areas of human settlements, receiving input from husbandry and sewage, respectively. Through ecological risk assessment, norfloxacin and amoxicillin posed high risks to algae, which were identified as high-risk pollutants in basin.

Brain Structural and Functional Alterations in Native Tibetans Living at High Altitude.

Tibetans have adapted to high altitude environments. However, the genetic effects in their brains have not been identified. Twenty-five native Tibetans living in Lhasa (3650 m) were recruited for comparison with 20 Han immigrants who originated from lowlands and had been living in Lhasa for two years. The physiological characteristics, brain structure and neuronal spontaneous activity were investigated. Compared with Han immigrants, Tibetans showed higher peripheral oxygen saturation (SpO2), and lower heart rate, red blood cell counts, hematocrit, and hemoglobin. Tibetans showed increased gray matter volume in the visual cortex, hippocampus, and rectus; increased the amplitudes of low-frequency fluctuations (ALFF) values in the left putamen and left fusiform gyrus; and decreased voxel-mirrored homotopic connectivity (VMHC) values in the precentral gyrus. Moreover, Tibetans have decreased functional connectivity (FC) between the left precentral gyrus and the frontal gyrusand right precuneus. In Tibetans and Han immigrants, hemoglobin and hematocrit were negatively correlated with total gray matter volume in males, SpO2 was also positively correlated with ALFF in the left fusiform gyrus, while hemoglobin, and hematocrit were positively correlated with VMHC in the precentral gyrus and FC in the precentral gyrus with other brain regions, SpO2 was also found to be negatively correlated with VMHC in the precentral gyrus, and hemoglobin and hematocrit were negatively correlated with ALFF in the left putamen and left fusiform gyrus. In summary, genetic mutations may result in modulation of some brain regions, which was further confirmed by the identification of correlations with hemoglobin and hematocrit in these regions.

Draft genome sequence of Pseudomonas aeruginosa strain ATCC 27853.

Pseudomonas aeruginosa is a common bacterium that can cause disease. The versatility of Pseudomonas aeruginosa enables the organism to infect damaged tissues or those with reduced immunity which cause inflammation and sepsis. Here we report the genome sequence of the strain ATCC 27853.