Pain, obesity, adenosine salvage disruption, and smoking behavior mediate the effect of gut microbiota on sleep disorders: results from network Mendelian randomization and 16S rDNA sequencing.

Objectives: The objective of this study is to investigate the indirect causalities between gut microbiota and sleep disorders. Methods: In stage 1, we utilized 196 gut microbiota as the exposure factor and conducted a two-sample univariable Mendelian randomization (MR) analysis on five sleep disorders: insomnia, excessive daytime sleepiness (EDS), sleep-wake rhythm disorders (SWRD), obstructive sleep apnea (OSA), and isolated REM sleep behavior disorder (iRBD). In stage 2, we validated the MR findings by comparing fecal microbiota abundance between patients and healthy controls through 16S rDNA sequencing. In stage 3, we explored the indirect pathways by which the microbiota affects sleep, using 205 gut microbiota metabolic pathways and 9 common risk factors for sleep disorders as candidate mediators in a network MR analysis. Results: In stage 1, the univariable MR analysis identified 14 microbiota potentially influencing five different sleep disorders. In stage 2, the results from our observational study validated four of these associations. In stage 3, the network MR analysis revealed that the Negativicutes class and Selenomonadales order might worsen insomnia by increasing pain [mediation: 12.43% (95% CI: 0.47, 24.39%)]. Oxalobacter could raise EDS by disrupting adenosine reuptake [25.39% (1.84, 48.95%)]. Allisonella may elevate OSA risk via obesity promotion [36.88% (17.23, 56.54%)], while the Eubacterium xylanophilum group may lower OSA risk by decreasing smoking behavior [7.70% (0.66, 14.74%)]. Conclusion: Triangulation of evidence from the MR and observational study revealed indirect causal relationships between the microbiota and sleep disorders, offering fresh perspectives on how gut microbiota modulate sleep.

Fluorine-doped Carbon Support Enables Superfast Oxygen Reduction Kinetics by Breaking the Scaling Relationship.

It is well-established that Pt-based catalysts suffer from the unfavorable linear scaling relationship (LSR) between *OOH and *OH (ΔG(*OOH) = ΔG(*OH) + 3.2 ± 0.2 eV) for the oxygen reduction reaction (ORR), resulting in a great challenge to significantly reduced ORR overpotentials. Herein, we propose a universal and feasible strategy of fluorine-doped carbon supports, which optimize interfacial microenvironment of Pt-based catalysts and thus significantly enhance their reactive kinetics. The introduction of C-F bonds not only weakens the *OH binding energy, but also stabilizes the *OOH intermediate, resulting in a break of LSR. Furthermore, fluorine-doped carbon constructs a local super-hydrophobic interface that facilitates the diffusion of H2O and the mass transfer of O2. Electrochemical tests show that the F-doped carbon-supported Pt catalysts exhibit over 2-fold higher mass activities than those without F modification. More importantly, those catalysts also demonstrate excellent stability in both rotating disk electrode (RDE) and membrane electrode assembly (MEA) tests. This study not only validates the feasibility of tuning the electrocatalytic microenvironment to improve mass transport and to break the scaling relationship, but also provides a universal catalyst design paradigm for other gas-involving electrocatalytic reactions.

Sieving-type Electric Double Layer with Hydrogen Bond Interlocking to Stable Zinc Metal Anode.

The stability of aqueous zinc metal batteries is significantly affected by side reactions and dendrite growth on the anode interface, which primarily originate from water and anions. Herein, we introduce a multi H-bond site additive, 2, 2'-Sulfonyldiethanol (SDE), into an aqueous electrolyte to construct a sieving-type electric double layer (EDL) by hydrogen bond interlock in order to address these issues. On the one hand, SDE replaces H2O and SO42- anions that are adsorbed on the zinc anode surface, expelling H2O/SO42- from the EDL and thereby reducing the content of H2O/SO42- at the interface. On the other hand, when Zn2+ are de-solvated at the interface during the plating, the strong hydrogen bond interaction between SDE and H2O/SO42- can trap H2O/SO42- from the EDL, further decreasing their content at the interface. This effectively sieves them out of the zinc anode interface and inhibits the side reactions. Moreover, the unique characteristics of trapped SO42- anions can restrict their diffusion, thereby enhancing the transference number of Zn2+ and promoting dendrite-free deposition and growth of Zn. Consequently, utilizing an SDE/ZnSO4 electrolyte enables excellent cycling stability in Zn//Zn symmetrical cells and Zn//MnO2 full cells with lifespans exceeding 3500 h and 2500 cycles respectively.

Perineuronal nets' role in metabolism.

Perineuronal nets (PNNs), specialized extracellular matrix structures that envelop neurons, have recently been recognized as key players in the regulation of metabolism. This review explores the growing body of knowledge concerning PNNs and their role in metabolic control, drawing insights from recent research and relevant studies. The pivotal role of PNNs in the context of energy balance and whole-body blood glucose is examined. The review also highlights novel findings, including the effects of astroglia, microglia, sex and gonadal hormones, nutritional regulation, circadian rhythms and age on PNNs dynamics. These findings illuminate the complex and multifaceted role of PNNs in metabolic health.

Public perceptions of international genetic information sharing for biomedical research in China: a case study of the social media debate on the article "A Pangenome Reference of 36 Chinese Populations" published in Nature.

BACKGROUND: The international disclosure of Chinese human genetic data continues to be a contentious issue in China, generating public debates in both traditional and social media channels. Concerns have intensified after Chinese scientists' research on pangenome data was published in the prestigious journal Nature. METHODS: This study scrutinized microblogs posted on Weibo, a popular Chinese social media site, in the two months immediately following the publication (June 14, 2023-August 21, 2023). Content analysis was conducted to assess the nature of public responses, justifications for positive or negative attitudes, and the users' overall knowledge of how Chinese human genetic information is regulated and managed in China. RESULTS: Weibo users displayed contrasting attitudes towards the article's public disclose of pangenome research data, with 18% positive, 64% negative, and 18% neutral. Positive attitudes came primarily from verified government and media accounts, which praised the publication. In contrast, negative attitudes originated from individual users who were concerned about national security and health risks and often believed that the researchers have betrayed China. The benefits of data sharing highlighted in the commentaries included advancements in disease research and scientific progress. Approximately 16% of the microblogs indicated that Weibo users had misunderstood existing regulations and laws governing data sharing and stewardship. CONCLUSIONS: Based on the predominantly negative public attitudes toward scientific data sharing established by our study, we recommend enhanced outreach by scientists and scientific institutions to increase the public understanding of developments in genetic research, international data sharing, and associated regulations. Additionally, governmental agencies can alleviate public fears and concerns by being more transparent about their security reviews of international collaborative research involving Chinese human genetic data and its cross-border transfer.

Stomach as the target organ of Rickettsia heilongjiangensis infection in C57BL/6 mice identified by click chemistry.

Spotted fever group rickettsiae (SFGR) are obligate intracellular bacteria that cause spotted fever. The limitations of gene manipulation pose great challenges to studying the infection mechanisms of Rickettsia. By combining bioorthogonal metabolism and click chemistry, we developed a method to label R. heilongjiangensis via azide moieties and achieved rapid pathogen localization without complex procedures. Moreover, we constructed a C57BL/6 mice infection model by simulating tick bites and discovered that the stomach is the target organ of R. heilongjiangensis infection through in vivo imaging systems, which explained the occurrence of gastrointestinal symptoms following R. heilongjiangensis infection in some cases. This study offers a unique perspective for subsequent investigations into the pathogenic mechanisms of SFGR and identifies a potential target organ for R. heilongjiangensis.

What influences the close contact between health care workers and patients? An observational study in a hospital dental outpatient department.

BACKGROUND: Dental outpatient departments, characterized by close proximity and unmasked patients, present a considerable risk of respiratory infections for health care workers (HCWs). However, the lack of comprehensive data on close contact (<1.5m) between HCWs and patients poses a significant obstacle to the development of targeted control strategies. METHODS: An observation study was conducted at a hospital in Shenzhen, China, utilizing depth cameras with machine learning to capture close-contact behaviors of patients with HCWs. Additionally, questionnaires were administered to collect patient demographics. RESULTS: The study included 200 patients, 10 dental practitioners, and 10 nurses. Patients had significantly higher close-contact rates with dental practitioners (97.5%) compared with nurses (72.8%, P < .001). The reason for the visit significantly influenced patient-practitioner (P = .018) and patient-nurse (P = .007) close-contact time, with the highest values observed in prosthodontics and orthodontics patients. Furthermore, patient age also significantly impacted the close-contact rate with nurses (P = .024), with the highest rate observed in patients below 14 years old at 85% [interquartile range: 70-93]. CONCLUSIONS: Dental outpatient departments exhibit high HCW-patient close-contact rates, influenced by visit purpose and patient age. Enhanced infection control measures are warranted, particularly for prosthodontics and orthodontics patients or those below 14 years old.

Stroke volume variation induced by lung recruitment maneuver to predict fluid responsiveness in patients receiving mechanical ventilation: A systematic review and meta-analysis.

STUDY OBJECTIVE: The aim of this study was to evaluate the accuracy of lung recruitment maneuver induced stroke volume variation (ΔSVLRM) in predicting fluid responsiveness in mechanically ventilated adult patients by systematic review and meta-analysis. METHODS: A comprehensive electronic search of relevant literature was conducted in PubMed, Web of Science, Cochrane Library, Ovid Medline, Embase and Chinese databases (including China National Knowledge Infrastructure, Wanfang and VIP databases). Review Manager 5.4, Meta-DiSc 1.4 and STATA 16.0 were selected for data analysis, and QUADAS-2 tool was used for quality assessment. Data from selected studies were pooled to obtain sensitivity, specificity, diagnostic likelihood ratio (DLR) of positive and negative, diagnostic odds ratio (DOR), and summary receiver operating characteristic curve. RESULTS: A total of 6 studies with 256 patients were enrolled through March 2024. The risk of bias and applicability concerns for each included study were low, and there was no significant publication bias. There was moderate to substantial heterogeneity for the non-threshold effect, but not for the threshold effect. The combined sensitivity and specificity were 0.84 (95% CI, 0.77-0.90) and 0.79 (95% CI, 0.70-0.86), respectively. The DOR and the area under the curve (AUC) were 22.15 (95%CI, 7.62-64.34) and 0.90 (95% CI, 0.87-0.92), respectively. The positive and negative predictive values of DLR were 4.53 (95% CI, 2.50-8.18) and 0.19 (95% CI, 0.11-0.35), respectively. Fagan's nomogram showed that with a pre-test probability of 52%, the post-test probability reached 83% and 17% for the positive and negative tests, respectively. CONCLUSIONS: Based on the currently available evidence, ΔSVLRM has a good diagnostic value for predicting the fluid responsiveness in adult patients undergoing mechanical ventilation. Given the heterogeneity and limitations of the published data, further studies with large sample sizes and different clinical settings are needed to confirm the diagnostic value of ΔSVLRM in predicting fluid responsiveness. PROSPERO registration number: CRD42023490598.

Rationally Designed L12-Pt2RhFe Intermetallic Catalyst with High CO-Tolerance for Alkaline Methanol Electrooxidation.

It is a grand challenge to deep understanding of and precise control over functional sites for the rational design of highly efficient catalysts for methanol electrooxidation. Here, an L12-Pt2RhFe intermetallic catalyst with integrated functional components is demonstrated, which exhibits exceptional CO tolerance. The Pt2RhFe/C achieves a superior mass activity of 6.43 A mgPt -1, which is 2.23-fold and 3.53-fold higher than those of PtRu/C and Pt/C. Impressively, the Pt2RhFe/C exhibits a significant enhancement in durability owing to its high CO-tolerance and stability. Density functional theory calculations reveal that high performance of Pt2RhFe intermetallic catalyst arises from the synergistic effect: the strong OH binding energy (OHBE) at Fe sites induce stably adsorbed OH species and thus facilitate the dehydrogenation step of methanol via rapid hydrogen transfer, while moderate OHBE at Rh sites promote the formation of the transition state (Pt-CO···OH-Rh) with a low activation barrier for CO removal. This work provides new insights into the role of OH binding strength in the removal of CO species, which is beneficial for the rational design of highly efficient catalysts.

A Microscopically Heterogeneous Colloid Electrolyte for Extremely Fast-Charging and Long-Calendar-Life Silicon-Based Lithium-Ion Batteries.

Fast-charging capability and calendar life are critical metrics in rechargeable batteries, especially in silicon-based batteries that are susceptible to sluggish Li+ desolvation kinetics and HF-induced corrosion. No existing electrolyte simultaneously tackles both these pivotal challenges. Here we report a microscopically heterogeneous covalent organic nanosheet (CON) colloid electrolyte for extremely fast-charging and long-calendar-life Si-based lithium-ion batteries. Theoretical calculations and operando Raman spectroscopy reveal the fundamental mechanism of the multiscale noncovalent interaction, which involves the mesoscopic CON attenuating the microscopic Li+-solvent coordination, thereby expediting the Li+ desolvation kinetics. This electrolyte design enables extremely fast-charging capabilities of the full cell, both at 8C (83.1% state of charge) and 10C (81.3% state of charge). Remarkably, the colloid electrolyte demonstrates record-breaking cycling performance at 10C (capacity retention of 92.39% after 400 cycles). Moreover, benefiting from the robust adsorption capability of mesoporous CON towards HF and water, a notable improvement is observed in the calendar life of the full cell. This study highlights the role of microscopically heterogeneous colloid electrolytes in enhancing the fast-charging capability and calendar life of Si-based Li-ion batteries. Our work offers fresh perspectives on electrolyte design with multiscale interactions, providing insightful guidance for the development of alkali-ion/metal batteries operating under harsh environments.

High positive predictive value of CNVs detected by clinical exome sequencing in suspected genetic diseases.

BACKGROUND: Genetic disorders often manifest as abnormal fetal or childhood development. Copy number variations (CNVs) represent a significant genetic mechanism underlying such disorders. Despite their importance, the effectiveness of clinical exome sequencing (CES) in detecting CNVs, particularly small ones, remains incompletely understood. We aimed to evaluate the detection of both large and small CNVs using CES in a substantial clinical cohort, including parent-offspring trios and proband only analysis. METHODS: We conducted a retrospective analysis of CES data from 2428 families, collected from 2018 to 2021. Detected CNV were categorized as large or small, and various validation techniques including chromosome microarray (CMA), Multiplex ligation-dependent probe amplification assay (MLPA), and/or PCR-based methods, were employed for cross-validation. RESULTS: Our CNV discovery pipeline identified 171 CNV events in 154 cases, resulting in an overall detection rate of 6.3%. Validation was performed on 113 CNVs from 103 cases to assess CES reliability. The overall concordance rate between CES and other validation methods was 88.49% (100/113). Specifically, CES demonstrated complete consistency in detecting large CNV. However, for small CNVs, consistency rates were 81.08% (30/37) for deletions and 73.91% (17/23) for duplications. CONCLUSION: CES demonstrated high sensitivity and reliability in CNV detection. It emerges as an economical and dependable option for the clinical CNV detection in cases of developmental abnormalities, especially fetal structural abnormalities.

Up-Regulation of S100A8 and S100A9 in Pulmonary Immune Response Induced by a Mycoplasma capricolum subsp. capricolum HN-B Strain.

Mycoplasma capricolum subsp. capricolum (Mcc), a member of the Mycoplasma mycoides cluster, has a negative impact on the goat-breeding industry. However, little is known about the pathogenic mechanism of Mcc. This study infected mice using a previously isolated strain, Mcc HN-B. Hematoxylin and eosin staining, RNA sequencing, bioinformatic analyses, RT-qPCR, and immunohistochemistry were performed on mouse lung tissues. The results showed that 235 differentially expressed genes (DEGs) were identified. GO and KEGG enrichment analyses suggested that the DEGs were mainly associated with immune response, defensive response to bacteria, NF-kappa B signaling pathway, natural killer cell-mediated cytotoxicity, and T cell receptor signaling pathway. RT-qPCR verified the expression of Ccl5, Cd4, Cd28, Il2rb, Lck, Lat, Ptgs2, S100a8, S100a9, and Il-33. The up-regulation of S100A8 and S100A9 at the protein level was confirmed by immunohistochemistry. Moreover, RT-qPCR assays on Mcc HN-B-infected RAW264.7 cells also showed that the expression of S100a8 and S100a9 was elevated. S100A8 and S100A9 not only have diagnostic value in Mcc infection but also hold great significance in clarifying the pathogenic mechanism of Mcc. This study preliminarily elucidates the mechanism of Mcc HN-B-induced lung injury and provides a theoretical basis for further research on Mcc-host interactions.

Hepatocellular carcinoma: An analysis of the expression status of stress granules and their prognostic value.

BACKGROUND: Hepatocellular carcinoma (HCC) is a global popular malignant tumor, which is difficult to cure, and the current treatment is limited. AIM: To analyze the impacts of stress granule (SG) genes on overall survival (OS), survival time, and prognosis in HCC. METHODS: The combined The Cancer Genome Atlas-Liver Hepatocellular Carcinoma (TCGA-LIHC), GSE25097, and GSE36376 datasets were utilized to obtain genetic and clinical information. Optimal hub gene numbers and corresponding coefficients were determined using the Least absolute shrinkage and selection operator model approach, and genes for constructing risk scores and corresponding correlation coefficients were calculated according to multivariate Cox regression, respectively. The prognostic model's receiver operating characteristic (ROC) curve was produced and plotted utilizing the time ROC software package. Nomogram models were constructed to predict the outcomes at 1, 3, and 5-year OS prognostications with good prediction accuracy. RESULTS: We identified seven SG genes (DDX1, DKC1, BICC1, HNRNPUL1, CNOT6, DYRK3, CCDC124) having a prognostic significance and developed a risk score model. The findings of Kaplan-Meier analysis indicated that the group with a high risk exhibited significantly reduced OS in comparison with those of the low-risk group (P < 0.001). The nomogram model's findings indicate a significant enhancement in the accuracy of OS prediction for individuals with HCC in the TCGA-HCC cohort. Gene Ontology and Gene Set Enrichment Analysis suggested that these SGs might be involved in the cell cycle, RNA editing, and other biological processes. CONCLUSION: Based on the impact of SG genes on HCC prognosis, in the future, it will be used as a biomarker as well as a unique therapeutic target for the identification and treatment of HCC.

PD-L1 siRNA hitched polyethyleneimine-elastase constituting nanovesicle induces tumor immunogenicity and PD-L1 silencing for synergistic antitumor immunotherapy.

BACKGROUND: PD-1/PD-L1 blockade has become a powerful method to treat malignant tumors. However, a large proportion of patients still do not benefit from this treatment, due to low tumor immunogenicity and low tumor penetration of the agents. Recently, neutrophil elastase has been shown to induce robust tumor immunogenicity, while the insufficient enzyme activity at the tumor site restricted its anti-tumor application. Here, we designed polyethyleneimine-modified neutrophil elastase (PEI-elastase) loaded with PD-L1small interfering RNA (PD-L1 siRNA) for improving enzymatic activity and delivering siRNA to tumor, which was expected to solve the above-mentioned problems. RESULTS: We first demonstrated that PEI-elastase possessed high enzymatic activity, which was also identified as an excellent gene-delivery material. Then, we synthesized anti-tumor lipopolymer (P-E/S Lip) by encapsulating PEI-elastase and PD-L1siRNA with pH-responsive anionic liposomes. The P-E/S Lip could be rapidly cleaved in tumor acidic environment, leading to exposure of the PEI-elastase/PD-L1 siRNA. Consequently, PEI-elastase induced powerful tumor immunogenicity upon direct tumor killing with minimal toxicity to normal cells. In parallel, PEI-elastase delivered PD-L1siRNA into the tumor and reduced PD-L1 expression. Orthotopic tumor administration of P-E/S Lip not only attenuated primary tumor growth, but also produced systemic anti-tumor immune response to inhibit growth of distant tumors and metastasis. Moreover, intravenous administration of P-E/S Lip into mice bearing subcutaneous tumors leaded to an effective inhibition of established B16-F10 tumor and 4T1 tumor, with histological analyses indicating an absence of detectable toxicity. CONCLUSIONS: In our study, a protease-based nanoplatform was used to cooperatively provoke robust tumor immunogenicity and down-regulate PD-L1 expression, which exhibited great potential as a combination therapy for precisely treating solid tumors.

Diagnostic algorithm based on ratio of ascites-serum tumor markers is superior to tumor markers in the differentiation of benign ascites from malignant ascites.

BACKGROUND: Differential diagnosis between benign ascites and malignant ascites remains challenging in clinical practice, the aim of our study is to determine the differential value of the ratio of ascitic-serum tumor markers between benign ascites and malignant ascites. METHODS: 418 patients with new-onset ascites were retrospectively enrolled in this study. The pertinent data of patients enrolled were collected; diagnostic value of tumor markers, ascites-serum tumor marker ratio, and diagnostic algorithm based on ascitic tumor markers and ascites-serum tumor marker ratio in patients with ascites were investigated. RESULTS: 81.25% of the patients with benign ascites had low (<1) ratio of ascites-serum tumor markers (Max [A/S CEA, A/S CA15-3, A/S CA19-9]); and 91.88 % of patients with benign ascites had the ratio of ascites-serum tumor marker less than 1.5. On the other hand, 94.96% of the patients with malignant ascites had high (≥1) ratio of ascites-serum tumor markers; and 97.29% of patients with malignant ascites had the ratio of ascites-serum tumor markers more than 0.67. Finally, diagnostic algorithm based on ascitic tumor markers and ascites-serum tumor marker ratio showed 96.37% of the sensitivity, and 94.37% of the accuracy in the diagnosis of malignant ascites, while ascitic tumor markers with a sensitivity of 78.29%, and an accuracy of 84.93%. CONCLUSIONS: Diagnostic algorithm based on ascitic tumor markers and ascites-serum tumor marker ratio exhibited an excellent performance in distinguishing benign and malignant ascites, which should be recommended in patients with new-onset ascites in clinical practice.

Tobacco exposure and alcohol drinking prevalence and associations with hypertension in rural southwest China: A cross-sectional study.

INTRODUCTION: This study examined the prevalence of tobacco exposure and drinking and ascertained the relationships between tobacco exposure, alcohol drinking, concurrent smoking and drinking, and hypertension in rural southwestern China. METHODS: Data were collected from a cross-sectional health interview and examination survey, which included 7572 adults aged ≥35 years, in rural China. Participant demographic characteristics, smoking habits, exposure to secondhand smoke (SHS), and alcohol drinking habits were obtained using a standard questionnaire. Blood pressure (BP), height, weight, and waist circumference were measured for each participant. RESULTS: The overall prevalence of smoking, SHS exposure, drinking, concurrent smoking and drinking, concurrent exposure to SHS and drinking, and hypertension was 37.7%, 27.4%, 16.2%, 12.6%, 1.6%, and 41.3%, respectively. Males had a significantly higher prevalence of smoking (74.1% vs 2.2%, p<0.01), drinking (31.1% vs 1.7%, p<0.01), and concurrent smoking and drinking than females (25.3% vs 0.3%, p<0.01). However, females had a higher prevalence of SHS exposure than males (30.2% vs 20.6%, p<0.01). Ethnic minorities had a higher prevalence of SHS exposure, drinking, and concurrent smoking and drinking, than Han participants (p<0.01). Participants with a higher education level had a higher prevalence of smoking, drinking, and concurrent smoking and drinking than their counterparts (p<0.01). In contrast, participants with a lower education level had a higher prevalence of SHS exposure than their counterparts (p<0.01). Multivariate logistic regression analysis found that smokers (AOR=1.31; 95% CI: 1.13-1.51), individuals exposed to SHS (AOR=1.24; 95% CI: 1.11-1.43), drinkers (AOR=1.31; 95%: CI: 1.15-1.50), and concurrent smokers and drinkers (AOR=1.45; 95% CI: 1.25-1.67) all had a higher probability of having hypertension (p<0.01). Additionally, concurrent smoking and drinking had the strongest association with the prevalence of hypertension (AOR=1.45; 95% CI: 1.25-1.67; p<0.01). CONCLUSIONS: Socioeconomic factors play an important role in influencing the prevalence of smoking, exposure to SHS, and drinking in rural southwest China. Interventions to prevent and reduce hypertension should, in particular, focus on smokers, individuals exposed to SHS, drinkers, and, in particular, concurrent smokers and drinkers.

Chromosomal-scale genome assembly of the Mediterranean mussel Mytilus galloprovincialis.

The Mediterranean mussel, Mytilus galloprovincialis, is a significant marine bivalve species that has ecological and economic importance. This species is robustly resilient and highly invasive. Despite the scientific and commercial interest in studying its biology and aquaculture, there remains a need for a high-quality, chromosome-scale reference genome. In this study, we have assembled a high-quality chromosome-scale reference genome for M. galloprovincialis. The total length of our reference genome is 1.41 Gb, with a scaffold N50 sequence length of 96.9 Mb. BUSCO analysis revealed a 97.5% completeness based on complete BUSCOs. Compared to the four other available M. galloprovincialis assemblies, the assembly described here is dramatically improved in both contiguity and completeness. This new reference genome will greatly contribute to a deeper understanding of the resilience and invasiveness of M. galloprovincialis.

A pan-respiratory antiviral chemotype targeting a transient host multi-protein complex.

We present a novel small molecule antiviral chemotype that was identified by an unconventional cell-free protein synthesis and assembly-based phenotypic screen for modulation of viral capsid assembly. Activity of PAV-431, a representative compound from the series, has been validated against infectious viruses in multiple cell culture models for all six families of viruses causing most respiratory diseases in humans. In animals, this chemotype has been demonstrated efficacious for porcine epidemic diarrhoea virus (a coronavirus) and respiratory syncytial virus (a paramyxovirus). PAV-431 is shown to bind to the protein 14-3-3, a known allosteric modulator. However, it only appears to target the small subset of 14-3-3 which is present in a dynamic multi-protein complex whose components include proteins implicated in viral life cycles and in innate immunity. The composition of this target multi-protein complex appears to be modified upon viral infection and largely restored by PAV-431 treatment. An advanced analog, PAV-104, is shown to be selective for the virally modified target, thereby avoiding host toxicity. Our findings suggest a new paradigm for understanding, and drugging, the host-virus interface, which leads to a new clinical therapeutic strategy for treatment of respiratory viral disease.

Hypoalbuminemia contributes to ascites formation via sodium and water retention: Evidence from clinical date and albumin deficient mice.

Albumin infusions improve circulatory and renal function in patients with decompensated cirrhosis. However, there is no convincing evidence that hypoalbuminemia contributes to ascites formation in liver cirrhosis. The aim of our study is to determine the exact role of hypoalbuminemia in the formation of ascites caused by liver cirrhosis and its underlying mechanism. Clinical profiles of patients with liver cirrhosis retrospectively analyzed. The details of albumin involved in ascites formation were investigated in rat model and murine model. Statistical analysis demonstrated hypoalbuminemia was an independent risk factor for ascites formation in patients with liver cirrhosis (OR = 0.722, P < 0.001). In carbon tetrachloride (CCl4)-induced rat model of liver cirrhosis, a significant reduction in serum albumin was observed in rats with ascites (13.37 g/L) compared with rats without ascites (21.43 g/L, P < 0.001). In thioacetamide (TAA)-treated mice, ascites amount of heterozygous albumin (Alb+/-) mice (112.0 mg) was larger than that of wild-type (Alb+/+) mice (58.46 mg, P < 0.001). In CCl4-induced chronic liver injury, ascites amounts of Alb+/- or Alb+/+ mice were 80.00 mg or 48.46 mg (P = 0.001). Further study demonstrated 24-h urinary sodium excretion in Alb+/- mice was lower than that of Alb+/+ mice in TAA/CCl4-induce murine models of liver cirrhosis. Additionally, serum sodium concentration of Alb+/- mice was lower than that of Alb+/+ mice. In cirrhotic mice, higher level of antidiuretic hormone was observed in Alb+/- mice compared with the control; and renal aquaporin (AQP2) expression in Alb+/- mice was significantly higher than that of WT mice. These revealed hypoalbuminemia contributed to the occurrence of ascites in liver cirrhosis through sodium and water retention.