Identification and genetic characterization of five novel bat coronaviruses from Yunnan, China.

BACKGROUND: Coronaviruses (CoVs) represent a serious threat to human health and have become a major transmissible, endemic, and causative pathogen in humans; they represent a major health concern, given their ability to cause infectious diseases. Bats are natural hosts for diverse viruses. Many transmission events of CoVs and identification of multiple novel CoVs in bats has increased attention towards their capacity to serve as hosts for zoonotic viruses. RESULTS: In this study, 61 bats from Yunnan Province were analyzed, identifying seven CoVs, including three α- and two ß-CoVs with full-genome sequences. Among the five identified alpha-CoVs, four belong to the Decacovirus subgenus and one to the Minunacovirus subgenus. Two beta-CoVs were also identified, both belonging to the Sarbecovirus subgenus.The genetic structures revealed similarities to known strains such as HKU10 and SARS-CoV-2, along with novel findings such as the Minunacovirus subgenus CoV YJ3c/f and unique ORF patterns. Our results demonstrated that strain JCC9 has a unique recombination pattern and shows a higher binding affinity to civet and pangolin ACE2 receptors, then the HpJC8xc strain transmits and recombines between hosts (bats), indicating a potential risk of crossing the interspecies barrier and infecting other animals. CONCLUSIONS: The CoVs detected in the bats studied in this research exhibit high diversity. Genomic analysis revealed that CoVs in bats undergo frequent recombination events. Furthermore, recombination patterns and evolutionary analyses suggest that alpha-CoVs are more prone to cross-species transmission across different bat families/genera, whereas beta-CoVs demonstrate host specificity and tend to co-evolve with their bat hosts.Our finding suggest that bats, as hosts of CoVs, be constantly monitored to prevent outbreaks of new infections caused by viruses passing across interspecies barriers, and consequently, viral diseases in humans or livestock.

PresRecRF: Herbal prescription recommendation via the representation fusion of large TCM semantics and molecular knowledge.

BACKGROUND: Herbal prescription recommendation (HPR) is a hotspot in the research of clinical intelligent decision support. Recently plentiful HPR models based on deep neural networks have been proposed. Owing to insufficient data, e.g., lack of knowledge of molecular, TCM theory, and herbal dosage in HPR modeling, the existing models suffer from challenges, e.g., plain prediction precision, and are far from real-world clinics. PURPOSE: To address these problems, we proposed a novel herbal prescription recommendation model with the representation fusion of large TCM semantics and molecular knowledge (termed PresRecRF). STUDY DESIGN AND METHODS: PresRecRF comprises three key modules. The representation learning module consists of two key components: a molecular knowledge representation component, integrating molecular knowledge into the herb-symptom-protein knowledge graph to enhance representations for herbs and symptoms; and a TCM knowledge representation component, leveraging BERT and ChatGPT to acquire TCM knowledge-enriched semantic representations. We introduced a representation fusion module to effectively merge molecular and TCM semantic representations. In the herb recommendation module, a multi-task objective loss is implemented to predict both herbs and dosages simultaneously. RESULTS: The experimental results on two clinical datasets show that PresRecRF can achieve the optimal performance. Further analysis of ablation, hyper-parameters, and case studies indicate the effectiveness and reliability of the proposed model, suggesting that it can help precision medicine and treatment recommendations. CONCLUSION: The entire process of the proposed PresRecRF model closely mirrors the actual diagnosis and treatment procedures carried out by doctors, which are better applied in real clinical scenarios. The source codes of PresRecRF is available at https://github.com/2020MEAI/PresRecRF.

Exploring the gut microbiota of healthy captive Asian elephants from various locations in Yunnan, China.

Introduction: The Asian elephant (Elephas maximus) is a giant herbivore classified as an endangered wildlife species by the International Union for Conservation of Threatened Species.This study aims to investigate and compare the core gut microbiota of captive Asian elephants from three different locations in Yunnan Province, China, to explore the impact of environmental and husbandry factors on microbial diversity. Methods: We collected fecal samples from 29 captive Asian elephants from three locations and performed full-length 16S rRNA gene sequencing. Microbial diversity was assessed using alpha diversity (Chao1 and Shannon indexes) and beta diversity (Bray-Curtis and Euclidean distance metrics). Principal coordinate analysis (PCoA) was used to visualize microbial variation among groups. Results: Alpha diversity analysis showed that the microbial diversity in the Yexianggu group was higher than that in the other groups. Bray-Curtis and Euclidean metrics revealed significant differences among the microbial communities. Bacteroidetes and Firmicutes, which are key cellulose-degrading bacteria, were the dominant phyla in all groups. Synergistaceae was the most abundant family in the Menghai group, while Lachnospiraceae and Pirellulaceae were more abundant in the Yexianggu and Yuantongshan groups, respectively. Genus p-1008-a5-gut-group was more abundant in Yexianggu, and Prevotella was predominant in Menghai. Discussion: These results indicate that habitat and husbandry practices significantly influence the gut microbiota of captive Asian elephants. The identification of bacterial species such as Lactobacillus fermentum, Clostridium neonatale, Enterococcus mundtii, Klebsiella huaxiensis, Corynebacterium nasicanis, and Streptococcus equinus highlights the potential role of specific microbes in maintaining host-microbial interactions. Promoting microbial diversity through improved captive conditions could enhance the health of these endangered animals.

A bibliometric analysis of the application of physical therapy in knee osteoarthritis from 2013 to 2022.

Background: Knee osteoarthritis (KOA) is one of the most common chronic joint diseases. Physical therapy, a non-invasive approach, is extensively used in its treatment. Although bibliometrics is a reliable method to evaluate the significance and impact of research fields, systematic bibliometric analyses in this area are lacking. This study aims to perform a bibliometric analysis covering 2013 to 2022, to highlight the current state, key focuses, and trends in physical therapy for KOA. Methods: This study utilizes the Web of Science Core Collection to gather relevant literature on physical therapy and KOA from 2013 to 2022. CiteSpace and VOSviewer software facilitated the visual analysis of the annual publications, geographic and institutional distributions, journals, authors, references, and keywords in this field. Results: The study analyzed 1,357 articles, showing an overall increase in publications over time from 71 countries and 2,302 institutions. The United States and Australia emerged as leaders in this field. The analysis identified 6,046 authors, with Kim L. Bennell as the most prolific and Bellamy N. receiving the most citations. BMC Musculoskeletal Disorders published the most articles, while Osteoarthritis and Cartilage received the most citations. High-impact articles were authored notably by McAlindon TE, Bannuru RR, Fernandes L, and Bennell KL. Keyword analysis highlighted a strong focus on patient self-management, exercise therapy, physical factor therapy, and remote rehabilitation. Conclusion: The bibliometric analysis confirms significant interest and ongoing research in physical therapy for KOA treatment from 2013 to 2022, indicating a growing field. Journals and authors in this area show influential and collaborative dynamics. Future research should focus on enhancing international and institutional collaboration and explore emerging trends like internet-guided treatments.

Distribution and genetic characterization of hantaviruses in bats and rodents from Yunnan.

Hemorrhagic fever with renal syndrome caused by hantaviruses has long been a serious public health issue in Yunnan Province. Hantaviruses exhibit a high extent of biodiversity in their natural hosts, particularly in mammalian hosts. This study was conducted to screen for hantaviruses in bats and rodents in Yunnan Province and elucidate their genetic characteristics and possible zoonotic disease risk. Hantaviruses were detected in 202 bats and 372 rodents with the positive rates 27.49% and 1.25% respectively. A novel lineage (named Lineage 10) of the Seoul virus (SEOV) from rodents and the geographic clustering of hantavirus in bats were identified using phylogenetic analyses of the full-length M- and S-segments. Our study suggest a high cross-species transmissibility of hantaviruses in bats and existence of a new lineage of SEOV in rodents differing significantly from other SEOVs. These results provide data to support the prevention and control of hantavirus-associated diseases in Yunnan Province.

Towards simulation optimization of subway station considering refined passenger behaviors.

The escalating passenger flow in subway systems presents significant challenges to station facilities during peak hours. Poorly designed station facilities can reduce passenger throughput efficiency and compromise passenger safety. This study conducts on-site investigations to extract refined parameters of passenger behaviors in security check and ticket checking areas. Using Beijing Subway Yizhuang Line Ciqunan Station as a case study, a microscopic simulation model is developed to replicate pedestrian flow within the subway station. By focusing on passenger demand and traffic organization, the layout of station facilities is regulated and optimized. After optimization, the passenger density in the security check and ticket inspection areas during the morning peak period decreased from 1.33 people/m2 to 1.00 people/m2; the longest queue length on the east side decreased from 15 people to 10 people, and the maximum queue length on the west side decreased from 7 people to 3 people. During peak hours, the dispersal time of passenger flow on the west side when entering the station decreased from 31.56 minutes to 30.04 minutes, and on the east side, it decreased from 36.12 minutes to 30.87 minutes. The optimization results effectively improved the efficiency of entering the station during peak hours.

The effects of mindfulness-based interventions on alleviating academic burnout in medical students: a systematic review and meta-analysis.

BACKGROUND: Mindfulness-based interventions have been tested to be the effective approach for preventing/reducing burnout in medical students. Therefore, this systematic review and meta-analysis aimed to synthesize the scientific evidence and quantify the pooled effect of MBIs on the burnout syndrome in medical students. METHODS: A comprehensive literature search was conducted in the databases, including PubMed, Embase, ERIC, PsycINFO, Scopus, Cochrane Central Register of Controlled Trials (CENTRAL), China National knowledge Information Database (CNKI) and WanFang Database from database inception to February 2023 using the terms of "mindfulness", "burnout" and "medical students". Two reviewers independently reviewed the studies, and extracted the data of the eligible studies, as well as assessed the risk of bias. A random-effects model was employed to calculate the standardized mean differences (SMD) with 95% confidence intervals (CI) of overall burnout and its sub-domains of burnout (i.e., emotional exhaustion, cynicism, and academic efficacy). RESULTS: Of 316 records in total, nine studies (with 810 medical students) were ultimately included. The four RCT studies demonstrated an overall judgment of some concerns risk of bias, and the overall risk of biases of the five qRCT studies were judged as serious. In term of the SORT, the RCT and qRCT studies were evaluated as level 2 evidence, and the overall strength of recommendation was classified as B (limited-quality patient-oriented evidence). The pooled analysis showed that MBIs were associated with significant small to moderate improvements for medical students' overall burnout (SMD=-0.64; 95% CI [-1.12, -0.16]; P = 0.009) in the included four RCTs, emotional exhaustion (SMD=-0.27; 95% CI [-0.50, -0.03]; P = 0.03) and academic efficacy (SMD = 0.43; 95% CI [0.20, 0.66]; P<0.001) in the four qRCTs. CONCLUSIONS: MBIs can serve as an effective approach for reducing burnout symptoms in medical students. Future high-quality studies with a larger sample size and robust randomized controlled trial methodologies should be obtained to reinforce the effectiveness of MBIs for reducing academic burnout in medical students.

LncRNA IRAIN overcomes imatinib resistance in chronic myeloid leukemia via NF-κB/CD44 pathway inhibition.

The development of tyrosine kinase inhibitors (TKIs) has revolutionarily increased the overall survival of patients with chronic myeloid leukemia (CML). However, drug resistance remains a major obstacle. Here, we demonstrated that a BCR-ABL1-independent long non-coding RNA, IRAIN, is constitutively expressed at low levels in CML, resulting in imatinib resistance. IRAIN knockdown decreased the sensitivity of CD34+ CML blasts and cell lines to imatinib, whereas IRAIN overexpression significantly increased sensitivity. Mechanistically, IRAIN downregulates CD44, a membrane receptor favorably affecting TKI resistance, by binding to the nuclear factor kappa B subunit p65 to reduce the expression of p65 and phosphorylated p65. Therefore, the demethylating drug decitabine, which upregulates IRAIN, combined with imatinib, formed a dual therapy strategy which can be applied to CML with resistance to TKIs.

Genome Characterization of a Tailam Virus Discovered in Brown Rats in Yunnan Province, China.

Paramyxoviridae is one of the most well known and largest virus families, including some animal and human pathogens, such as the Hendra, Nipah, and Rinderpest viruses, with a high potential for the emergence of human diseases. Based on recent phylogenetic analyses, two new genera (Narmovirus and Jeilongvirus) have been described. The newly recognized genus Jeilongvirus has rapidly increased in number and has grown to 15 species from 7 a few years ago. However, little is known about the diversity, host range, or evolution of Jeilongvirus. As a well-known host reservoir for many pathogens, rodents have always been the focus for characterizing their pathogenic potential. In this study, we isolated a Tailam virus strain (RN-JH-YN-2022-1) belonging to the genus Jeilongvirus from Rattus norvegicus in Yunnan Province, China. The virus presented a near-complete genome (19,046 nucleotides). Similar to other members of the genus Jeilongvirus, the genome of RN-JH-YN-2022-1 contains eight basic genes (3'-N-P/V/C-M-F-SH-TM-G-L-5') with 88.88% sequence identity to Tailam virus (TL8K). Additionally, we discuss the pattern of genus Jeilongvirus diversity and the possible route of spread of the Tailam virus, which could provide new clues into the host range, virus diversity, and geographical distribution of the genus Jeilongvirus.

Metabarcode insights into the airborne fungal diversity in the indoor and outdoor environments in archives from Yunnan, Southwestern China.

Monitoring dynamics of airborne fungal species and controlling of harmful ones are of vital importance to conservation of cultural relics. However, the evaluation of air quality and the community structure characteristics of microorganisms, especially fungi, in the atmosphere of archives is in a stage of continuous exploration though more than 4,000 archives were constructed in China. Seventy-two air samples were collected in this study under different spatial and weather conditions from the archives of Kunming Medical University, located in the Kunming metropolitan area, Yunnan province, southwestern China. A total of 22 airborne fungal classes, 160 genera and 699 ASVs were identified, the species diversity is on the rise with the strengthening of air circulation with the outside space, and thus the intensive energy metabolism and activity were found in the spaces with window and sunny weather, except for the higher lipid synthesis of indoor samples than that of outdoor ones. Furthermore, there were significant differences in fungal community composition and abundance between sunny and rainy weathers. A considerable number of species have been identified as indicator in various environmental and weather conditions of the archives, and temperature and humidity were thought to have significant correlations with the abundance of these species. Meanwhile, Cladosporium and Alternaria were the dominant genera here, which may pose a threat to the health of archive professionals. Therefore, monitoring and controlling the growth of these fungal species is crucial for both conservation of paper records and health of archive professionals.

The 25-kDa linear polyethylenimine exerts specific antiviral activity against pseudorabies virus through interferencing its adsorption via electrostatic interaction.

Pseudorabies virus (PRV) is the causative agent of Aujeszky's disease, which is responsible for enormous economic losses to the global pig industry. Although vaccination has been used to prevent PRV infection, the effectiveness of vaccines has been greatly diminished with the emergence of PRV variants. Therefore, there is an urgent need to develop anti-PRV drugs. Polyethylenimine (PEI) is a cationic polymer and has a wide range of antibacterial and antiviral activities. This study found that a low dose of 1 µg/mL of the 25-kDa linear PEI had significantly specific anti-PRV activity, which became more intense with increasing concentrations. Mechanistic studies revealed that the viral adsorption stage was the major target of PEI without affecting viral entry, replication stages, and direct inactivation effects. Subsequently, we found that cationic polymers PEI and Polybrene interfered with the interaction between viral proteins and cell surface receptors through electrostatic interaction to exert the antiviral function. In conclusion, cationic polymers such as PEI can be a category of options for defense against PRV. Understanding the anti-PRV mechanism also deepens host-virus interactions and reveals new drug targets for anti-PRV.IMPORTANCEPolyethylenimine (PEI) is a cationic polymer that plays an essential role in the host immune response against microbial infections. However, the specific mechanisms of PEI in interfering with pseudorabies virus (PRV) infection remain unclear. Here, we found that 25-kDa linear PEI exerted mechanisms of antiviral activity and the target of its antiviral activity was mainly in the viral adsorption stage. Correspondingly, the study demonstrated that PEI interfered with the virus adsorption stage by electrostatic adsorption. In addition, we found that cationic polymers are a promising novel agent for controlling PRV, and its antiviral mechanism may provide a strategy for the development of antiviral drugs.

Diversity of astroviruses in wild animals in Yunnan province, China.

BACKGROUND: Astroviruses (AstVs) are single-stranded RNA viruses that have been detected in a wide range of mammals and birds. They are associated with numerous interspecies transmissions and viral recombination events, posing a threat to human and animal health. METHODS: We collected 1,333 samples from wild animals, including bats, rodents, wild boars, and birds, from various states and cities in the Yunnan Province, China, between 2020 and 2023 to investigate the presence of AstVs. AstVs were detected using a polymerase chain reaction targeting the RdRp gene. Finally, the Molecular Evolutionary Genetics Analysis software was used to construct the phylogenetic tree. RESULTS: The overall positivity rate for AstVs was 7.12% in four species, indicating their widespread occurrence in the region. High genetic diversity among AstVs was observed in different animal species, suggesting the potential for interspecies transmission, particularly among rodents and birds. Additionally, we identified a novel AstV strain and, for the first time, provided information on the presence of bastroviruses in Yunnan, China. CONCLUSIONS: The widespread distribution and high genetic diversity of AstVs, along with the observed potential for interspecies transmission, highlight the importance of further investigation and surveillance in the region. The findings emphasize the need for increased attention to AstVs and their potential impact on human and animal health in Yunnan and other regions.

Diffusion-weighted Imaging Detection of Acute Ischemia Brain Lesions in Spontaneous Intracerebral Hemorrhage Associated with White Matter Hyperintensities, Enlarged Perivascular Spaces and Diabetes Mellitus.

OBJECTIVE: Diffusion-weighted imaging (DWI) is commonly detected after spontaneous intracerebral hemorrhage (sICH) and is associated with poor functional outcomes. However, the etiology and significance of DWI lesions remain unclear. Thus, our study aimed to explore the prevalence and risk factors of acute ischemic lesions in sICH and discussed the possible mechanisms. METHODS: We conducted a retrospective review of a consecutive cohort of 408 patients from June 2013 to October 2019 with sICH, who had brain computed tomography (CT) and magnetic resonance imaging (MRI) within 14 days of symptoms onset. Acute ischemic lesions were assessed on MRI using DWI lesions. We compared the clinical and imaging characteristics of patients with and without DWI lesions. The data were analyzed by univariate and multivariate logistic regression. RESULTS: Among the enrolled 408 patients, the mean age was 56.8 ± 14.5 years, 68 (16.7%) of them had been diagnosed with diabetes mellitus (DM). DWI lesions were observed in 89 (21.8%) patients, and most of them had a history of lacunar infarctions, which were located in cortical or subcortical. In multivariate logistic regression analysis, DM (odds ratio (OR) 3.962, p <0.001), severe deep white matter hypertensities (DWMH) (OR 2.463, p =0.001) and severe centrum semiovale enlarged perivascular spaces (CSO-EPVS) (OR 2.679, p =0.001) were independently associated with the presence of DWI lesions. CONCLUSION: In our cohort, we found DM, severe DWMH and severe CSO-EPVS were the independent risk factors in sICH patients with DWI lesions.

Second haploidentical bone marrow transplantation with antithymocyte antibody-containing conditioning regimen for graft failure in eight patients with severe aplastic anemia.

The effects of a second haploidentical bone marrow transplantation with an antithymocyte antibody-containing conditioning regimen after graft failure in patients with severe aplastic anemia remain unclear. Eight severe aplastic anemia patients with graft failure with a median age of 12.5 (range, 3-22) years were retrospectively reviewed. At the second transplantation, they received a median mononuclear cell number of 15.7 (range, 11.2-20.9) × 108/kg or a median CD34+ cell number of 6.2 (range, 2.5-17.5) × 106/kg. They were all successfully engrafted, with a median time of 12.5 (range, 11-16) days for neutrophils and 24 (range, 14-50) days for platelets. Three patients developed skin acute graft-versus-host disease Grades I-II, and another 3 developed limited chronic graft-versus-host disease. All patients successfully recovered after treatment with methylprednisolone (0.5-1 mg/kg/day) and tacrolimus. One patient each died of respiratory failure caused by multidrug-resistant Klebsiella pneumoniae at 8 months and invasive fungal disease at 23 months after transplantation. Six patients survived with a 5-year estimated overall survival of 75% and a median follow-up time of 61 (range, 8-129) months. A second haploidentical bone marrow transplantation with an antithymocyte antibody-containing conditioning regimen was feasible for saving severe aplastic anemia patients with graft failure.

RNA virus diversity in rodents.

Many zoonotic disease emergencies are associated with RNA viruses in rodents that substantially impact public health. With the widespread application of meta-genomics and meta-transcriptomics for virus discovery over the last decade, viral sequences deposited in public databases have expanded rapidly, and the number of novel viruses discovered in rodents has increased. As important reservoirs of zoonotic viruses, rodents have attracted increasing attention for the risk of potential spillover of rodent-borne viruses. However, knowledge of rodent viral diversity and the major factors contributing to the risk of zoonotic epidemic outbreaks remains limited. Therefore, this study analyzes the diversity and composition of rodent RNA viruses using virus records from the Database of Rodent-associated Viruses (DRodVir/ZOVER), which covers the published literatures and records in GenBank database, reviews the main rodent RNA virus-induced human infectious diseases, and discusses potential challenges in this field.

Metal organic layers enabled cell surface engineering coupling biomembrane fusion for dynamic membrane proteome profiling.

Systematically dissecting the highly dynamic and tightly communicating membrane proteome of living cells is essential for the system-level understanding of fundamental cellular processes and intricate relationship between membrane-bound organelles constructed through membrane traffic. While extensive efforts have been made to enrich membrane proteins, their comprehensive analysis with high selectivity and deep coverage remains a challenge, especially at the living cell state. To address this problem, we developed the cell surface engineering coupling biomembrane fusion method to map the whole membrane proteome from the plasma membrane to various organelle membranes taking advantage of the exquisite interaction between two-dimensional metal-organic layers and phospholipid bilayers on the membrane. This approach, which bypassed conventional biochemical fractionation and ultracentrifugation, facilitated the enrichment of membrane proteins in their native phospholipid bilayer environment, helping to map the membrane proteome with a specificity of 77% and realizing the deep coverage of the HeLa membrane proteome (5087 membrane proteins). Furthermore, membrane N-phosphoproteome was profiled by integrating the N-phosphoproteome analysis strategy, and the dynamic membrane proteome during apoptosis was deciphered in combination with quantitative proteomics. The features of membrane protein N-phosphorylation modifications and many differential proteins during apoptosis associated with mitochondrial dynamics and ER homeostasis were found. The method provided a simple and robust strategy for efficient analysis of membrane proteome, offered a reliable platform for research on membrane-related cell dynamic events and expanded the application of metal-organic layers.

Porcine IGFBP3 promotes porcine circovirus type 2 replication via PERK/eIF2α mediated DNA damage.

The infection of porcine circovirus type 2 (PCV2) triggers activation of the protein kinase RNA-like endoplasmic reticulum kinase (PERK) pathway and leads to DNA damage. Insulin-like growth factor-binding protein 3 (IGFBP3) may interact with the endoplasmic reticulum (ER). It remains unclear whether IGFBP3 regulates DNA damage via ER stress to mediate PCV2 replication. In this study, we observed an upregulation of porcine IGFBP3 expression during PCV2 infection, and overexpression of IGFBP3 enhanced the expression of PCV2 Cap protein, PCV2 DNA copy number, and viral titers in PK-15 B6 cells and 3D4/21 cells. Additionally, overexpression of IGFBP3 induced an increase in the DNA damage marker γH2AX by activating the PERK/eIF2α pathway without concomitant activation of ATF4, IRE1α, and ATF6α/GRP78 pathways in PK-15 B6 cells and 3D4/21 cells. Knockdown of IGFBP3 had a reverse effect on PCV2 replication in PK-15 B6 cells and 3D4/21 cells. Furthermore, treatment with etoposide enhanced PCV2 replication while KU57788 decreased it. GSK2606414 and salubrinal limited both DNA damage and viral replication. Therefore, our findings suggest that porcine IGFBP3 promotes PCV2 replication through the PERK/eIF2α pathway-mediated induction of DNA damage in PK-15 B6 cells and 3D4/21 cells. Our study provides a basis for exploring novel antiviral strategies via the extensive understanding of the relationships between host cellular proteins and viral replication.

Alleviation of ischemia-reperfusion induced renal injury by chemically modified SOD2 mRNA delivered via lipid nanoparticles.

Ischemia-reperfusion injury (IRI) is a major cause of acute kidney injury, which is a serious clinical condition with no effective pharmacological treatment. Mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) significantly alleviate kidney IRI; however, the underlying mechanisms and key molecules conferring renoprotection remain elusive. In this study, we characterized the protein composition of MSC-EVs using a proteomics approach and found that mitochondrial protein superoxide dismutase 2 (SOD2) was enriched in MSC-EVs. Using lipid nanoparticles (LNP), we successfully delivered chemically modified SOD2 mRNA into kidney cells and mice with kidney IRI. We demonstrated that SOD2 mRNA-LNP treatment decreased cellular reactive oxygen species (ROS) in cultured cells and ameliorated renal damage in IRI mice, as indicated by reduced levels of serum creatinine and restored tissue integrity compared with the control mRNA-LNP-injected group. Thus, the modulation of mitochondrial ROS levels through SOD2 upregulation by SOD2 mRNA-LNP delivery could be a novel therapeutic method for ischemia-reperfusion-induced acute kidney injury.

Comparative analysis of the intestinal microbiome in Rattus norvegicus from different geographies.

Rat species Rattus norvegicus, also known as the brown street rat, is the most abundant mammal after humans in urban areas, where they co-exist with humans and domestic animals. The reservoir role of R. norvegicus of zoonotic pathogens in cities among rodent-borne diseases that could endanger the lives of humans and other mammals. Therefore, understanding the normal microbiome of R. norvegicus is crucial for understanding and preventing zoonotic pathogen transmission to humans and animals. We investigated the intestinal microbiome of free-living R. norvegicus collected from the Ruili, Nujiang, and Lianhe regions of Yunnan, China, using 16S rRNA gene sequence analysis. Proteobacteria, followed by Firmicutes, and Bacteroidetes were abundant in the intestines of R. norvegicus; however, bacterial compositions varied significantly between samples from different locations. Following a similar trend, Gammaproteobacteria, Bacilli, and Clostridia were among the top bacterial classes in most intestinal samples. The situation differed slightly for the Lianhe and Nujiang samples, although Phyla Bacteroidota and Spirochaetota were most prevalent. The Alpha diversity, Chao1, and Simpson indexes revealed microbial richness among the R. norvegicus samples. A slight variation was observed among the samples collected from Ruili, Nujiang, and Lianhe. At species levels, several opportunistic and zoonotic bacterial pathogens, including Lactococcus garvieae, Uruburuella suis, Bartonella australis, Clostridium perfringens, Streptococcus azizii, Vibrio vulnificus, etc., were revealed in the R. norvegicus intestines, implying the need for a regular survey to monitor and control rodent populations. In conclusion, we explored diverse microbial communities in R. norvegicus intestines captured from different regions. Further, we identified several opportunistic and potential bacterial pathogens, which still need to be tested for their underlying pathogenesis. The findings of our current study should be considered a warning to the health authorities to implement rat control and surveillance strategies globally.

Cerebral Microbleeds Are Associated with Widespread Blood-Brain Barrier Leakage.

INTRODUCTION: The pathogenesis of cerebral microbleeds (CMBs) is incompletely understood, but blood-brain barrier (BBB) leakage may play a key role. This study aimed to investigate the relationship between compromised BBB integrity and CMBs as well as cognitive function. METHODS: Ninety-seven participants were enrolled in this cross-sectional study, involving 24 CMB patients. Dynamic contrast-enhanced-magnetic resonance imaging was used to measure BBB permeability, and cognitive function was assessed by Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA). RESULTS: Compared with participants without CMBs, CMB patients had higher volume transfer constant (Ktrans, all p < 0.01) and area under the concentration curve (AUC, all p < 0.05) in normal-appearing white matter (NAWM), white matter hyperintensities (WMH), cortical gray matter (CGM), and deep gray matter (DGM). Multivariable linear regression analyses revealed that CMB patients had significantly higher Ktrans in NAWM and AUC in NAWM, WMH, and CGM after adjustment for age, sex, vascular risk factors, and cognitive scores. MMSE and MoCA scores decreased with increasing Ktrans in WMH and DGM as well as AUC in WMH after adjustment for age, sex, CMB group, and education length. CONCLUSION: This study demonstrated that widespread BBB leakage was prevalent in CMB patients, suggesting that compromised BBB integrity may play a key role in the pathogenesis of CMBs and could lead to cognitive impairment.