Nuclear p62 condensates stabilize the promyelocytic leukemia nuclear bodies by sequestering their ubiquitin ligase RNF4.

Liquid-liquid phase separation has emerged as a crucial mechanism driving the formation of membraneless biomolecular condensates, which play important roles in numerous cellular processes. These condensates, found both in the nucleus and cytoplasm, are formed through multivalent, low-affinity interactions between various molecules. P62-containing condensates serve, among other functions, as proteolytic hubs for the ubiquitin-proteasome system. In this study, we investigated the dynamic interplay between nuclear p62 condensates and promyelocytic nuclear bodies (PML-NBs). We show that p62 condensates stabilize PML-NBs under both basal conditions and following exposure to arsenic trioxide which stimulates their degradation. We further show that this effect on the stability of PML-NBs is due to sequestration of their ubiquitin E3 ligase RNF4 in the p62 condensates with subsequent rapid degradation of the ligase. The sequestration of the ligase is made possible by association between the proline-rich domain of the PML protein and the PB1 domain of p62, which results in the formation of a PML-NB shell around the p62 condensates. Importantly, these hybrid structures do not undergo fusion and mixing of their contents which leaves unsolved the mechanism of sequestration of RNF4 in the condensates. These findings suggest an additional possible mechanism of PML-NB as a tumor suppressor which is mediated via interactions between different biomolecular condensates.

HBV integrations reshaping genomic structures promote hepatocellular carcinoma.

OBJECTIVE: Hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC), mostly characterised by HBV integrations, is prevalent worldwide. Previous HBV studies mainly focused on a few hotspot integrations. However, the oncogenic role of the other HBV integrations remains unclear. This study aimed to elucidate HBV integration-induced tumourigenesis further. DESIGN: Here, we illuminated the genomic structures encompassing HBV integrations in 124 HCCs across ages using whole genome sequencing and Nanopore long reads. We classified a repertoire of integration patterns featured by complex genomic rearrangement. We also conducted a clustered regularly interspaced short palindromic repeat (CRISPR)-based gain-of-function genetic screen in mouse hepatocytes. We individually activated each candidate gene in the mouse model to uncover HBV integration-mediated oncogenic aberration that elicits tumourigenesis in mice. RESULTS: These HBV-mediated rearrangements are significantly enriched in a bridge-fusion-bridge pattern and interchromosomal translocations, and frequently led to a wide range of aberrations including driver copy number variations in chr 4q, 5p (TERT), 6q, 8p, 16q, 9p (CDKN2A/B), 17p (TP53) and 13q (RB1), and particularly, ultra-early amplifications in chr8q. Integrated HBV frequently contains complex structures correlated with the translocation distance. Paired breakpoints within each integration event usually exhibit different microhomology, likely mediated by different DNA repair mechanisms. HBV-mediated rearrangements significantly correlated with young age, higher HBV DNA level and TP53 mutations but were less prevalent in the patients subjected to prior antiviral therapies. Finally, we recapitulated the TONSL and TMEM65 amplification in chr8q led by HBV integration using CRISPR/Cas9 editing and demonstrated their tumourigenic potentials. CONCLUSION: HBV integrations extensively reshape genomic structures and promote hepatocarcinogenesis (graphical abstract), which may occur early in a patient's life.

Role of oxidative stress in the concurrent development of osteoporosis and tendinopathy: Emerging challenges and prospects for treatment modalities.

Both osteoporosis and tendinopathy are widely prevalent disorders, encountered in diverse medical contexts. Whilst each condition has distinct pathophysiological characteristics, they share several risk factors and underlying causes. Notably, oxidative stress emerges as a crucial intersecting factor, playing a pivotal role in the onset and progression of both diseases. This imbalance arises from a dysregulation in generating and neutralising reactive oxygen species (ROS), leading to an abnormal oxidative environment. Elevated levels of ROS can induce multiple cellular disruptions, such as cytotoxicity, apoptosis activation and reduced cell function, contributing to tissue deterioration and weakening the structural integrity of bones and tendons. Antioxidants are substances that can prevent or slow down the oxidation process, including Vitamin C, melatonin, resveratrol, anthocyanins and so on, demonstrating potential in treating these overlapping disorders. This comprehensive review aims to elucidate the complex role of oxidative stress within the interlinked pathways of these comorbid conditions. By integrating contemporary research and empirical findings, our objective is to outline new conceptual models and innovative treatment strategies for effectively managing these prevalent diseases. This review underscores the importance of further in-depth research to validate the efficacy of antioxidants and traditional Chinese medicine in treatment plans, as well as to explore targeted interventions focused on oxidative stress as promising areas for future medical advancements.

Assembly and comparative analysis of the complete mitochondrial genome of Fritillaria ussuriensis Maxim. (Liliales: Liliaceae), an endangered medicinal plant.

BACKGROUND: Fritillaria ussuriensis is an endangered medicinal plant known for its notable therapeutic properties. Unfortunately, its population has drastically declined due to the destruction of forest habitats. Thus, effectively protecting F. ussuriensis from extinction poses a significant challenge. A profound understanding of its genetic foundation is crucial. To date, research on the complete mitochondrial genome of F. ussuriensis has not yet been reported. RESULTS: The complete mitochondrial genome of F. ussuriensis was sequenced and assembled by integrating PacBio and Illumina sequencing technologies, revealing 13 circular chromosomes totaling 737,569 bp with an average GC content of 45.41%. A total of 55 genes were annotated in this mitogenome, including 2 rRNA genes, 12 tRNA genes, and 41 PCGs. The mitochondrial genome of F. ussuriensis contained 192 SSRs and 4,027 dispersed repeats. In the PCGs of F. ussuriensis mitogenome, 90.00% of the RSCU values exceeding 1 exhibited a preference for A-ended or U-ended codons. In addition, 505 RNA editing sites were predicted across these PCGs. Selective pressure analysis suggested negative selection on most PCGs to preserve mitochondrial functionality, as the notable exception of the gene nad3 showed positive selection. Comparison between the mitochondrial and chloroplast genomes of F. ussuriensis revealed 20 homologous fragments totaling 8,954 bp. Nucleotide diversity analysis revealed the variation among genes, and gene atp9 was the most notable. Despite the conservation of GC content, mitogenome sizes varied significantly among six closely related species, and colinear analysis confirmed the lack of conservation in their genomic structures. Phylogenetic analysis indicated a close relationship between F. ussuriensis and Lilium tsingtauense. CONCLUSIONS: In this study, we sequenced and annotated the mitogenome of F. ussuriensis and compared it with the mitogenomes of other closely related species. In addition to genomic features and evolutionary position, this study also provides valuable genomic resources to further understand and utilize this medicinal plant.

Agomir-122-loaded nanoparticles coated with cell membrane of activated fibroblasts to treat frozen shoulder based on homologous targeting.

As a common musculoskeletal disorder, frozen shoulder is characterized by thickened joint capsule and limited range of motion, affecting 2-5% of the general population and more than 20% of patients with diabetes mellitus. Pathologically, joint capsule fibrosis resulting from fibroblast activation is the key event. The activated fibroblasts are proliferative and contractive, producing excessive collagen. Albeit high prevalence, effective anti-fibrosis modalities, especially fibroblast-targeting therapies, are still lacking. In this study, microRNA-122 was first identified from sequencing data as a potential therapeutic agent to antagonize fibroblast activation. Then, Agomir-122, an analog of microRNA-122, was loaded into poly(lactic-co-glycolic acid) (PLGA) nanoparticles (Agomir-122@NP), a carrier with excellent biocompatibility for the agent delivery. Moreover, relying on the homologous targeting effect, we coated Agomir-122@NP with the cell membrane derived from activated fibroblasts (Agomir-122@MNP), with an attempt to inhibit the proliferation, contraction, and collagen production of abnormally activated fibroblasts. After confirming the targeting effect of Agomir-122@MNP on activated fibroblasts in vitro, we proved that Agomir-122@MNP effectively curtailed fibroblasts activation, ameliorated joint capsule fibrosis, and restored range of motion in mouse models both prophylactically and therapeutically. Overall, an effective targeted delivery method was developed with promising translational value against frozen shoulder.

From Skin to Gut: Understanding Microbial Diversity in Rana amurensis and R. dybowskii.

Amphibians face the threat of decline and extinction, and their health is crucially affected by the microbiota. Their health and ecological adaptability essentially depend on the diverse microbial communities that are shaped by unique host traits and environmental factors. However, there is still limited research on this topic. In this study, cutaneous (C) and gut (G) microbiota in Rana amurensis (A) and R. dybowskii (D) was analyzed through 16S amplicon sequencing. Groups AC and DC significantly differed in alpha diversity, while the gut groups (AG and DG) showed no such differences. Analyses of Bray-Curtis dissimilarity matrix and unweighted UniFrac distances showed significant differences in cutaneous microbiota between groups AC and DC, but not between groups AG and DG. Stochastic processes significantly influenced the assembly of cutaneous and gut microbiota in amphibians, with a notably higher species dispersal rate in the gut. The predominant phyla in the skin of R. amurensis and R. dybowskii were Bacteroidetes and Proteobacteria, respectively, with significant variations in Bacteroidota. Contrarily, the gut microbiota of both species was dominated by Firmicutes, Proteobacteria, and Bacteroidetes, without significant phylum-level differences. Linear discriminant analysis effect size (LEfSe) analysis identified distinct microbial enrichment in each group. Predictive analysis using phylogenetic investigation of communities by reconstruction of unobserved states 2 (PICRUSt2) revealed the significant functional pathways associated with the microbiota, which indicates their potential roles in immune system function, development, regeneration, and response to infectious diseases. This research underscores the critical impact of both host and environmental factors in shaping amphibian microbial ecosystems and emphasizes the need for further studies to explore these complex interactions for conservation efforts.

SN2 Reaction at the Amide Nitrogen Center Enables Hydrazide Synthesis.

Nucleophilic substitutions are fundamentally important transformations in synthetic organic chemistry. Despite the substantial advances in bimolecular nucleophilic substitutions (SN2) at saturated carbon centers, analogous SN2 reaction at the amide nitrogen atom remains extremely limited. Here we report an SN2 substitution method at the amide nitrogen atom with amine nucleophiles for nitrogen-nitrogen (N-N) bond formation that leads to a novel strategy toward biologically and medicinally important hydrazide derivatives. We found the use of sulfonate-leaving groups at the amide nitrogen atom played a pivotal role in the reaction. This new N-N coupling reaction allows the use of O-tosyl hydroxamates as electrophiles and readily available amines, including acyclic aliphatic amines and saturated N-heterocycles as nucleophiles. The reaction features mild conditions, broad substrate scope (>80 examples), excellent functional group tolerability, and scalability. The method is applicable to late-stage modification of various approved drug molecules, thus enabling complex hydrazide scaffold synthesis.

Photo-Triggered, Copper(II) Chloride-Catalyzed Radical Hydroalkylation and Hydrosilylation of Vinylboronic Esters To Access Alkylboronic Esters.

Alkyl boronic acids and their derivatives constitute vital building blocks in organic synthesis and are important motifs identified in medicinal chemistry. Herein, we present a phototriggered, CuCl2-catalyzed radical hydroalkylation and hydrosilylation of vinylboronic esters to alkylboronic esters. This approach exhibits mild reaction conditions, utilization of easily accessible reagents, and scalability up to a gram scale. Further synthetic transformations of the hydrosilylation products and mechanistic studies are also demonstrated.

Vertical connectivity of microbiome and metabolome reveals depth-dependent variations across a deep cold-seep water column.

Deciphering the vertical connectivity of oceanic microbiome and metabolome is crucial for understanding the carbon sequestration and achieving the carbon neutrality. However, we lack a systematic view of the interplay among particle transport, microbial community, and metabolic trait across depths. Through integrating the biogeochemical, microbial, and metabolic characteristics of a deep cold-seep water column (∼1989 m), we find the altered connectivity of microbial community and dissolved organic matter (DOM) across depths. Both the microbial communities (bacteria and protists) and DOM show a clear compositional connectivity from surface to the depth of 1000 m, highlighting the controls of sinking particle over microbial connectivity from the epipelagic to mesopelagic zone. However, due to the biological migration and ocean mixing, the fecal-associated bacteria and protistan consumers unexpectedly emerge and the degradation index of DOM substantially alters around 1000-1200 m. Collectively, we unveil the significance of multi-faceted particle dispersion, which supports the connectivity and variability of deep ocean microbial communities.

Safe CO2 threshold limits for indoor long-range airborne transmission control of COVID-19.

CO2-based infection risk monitoring is highly recommended during the current COVID-19 pandemic. However, the CO2 monitoring thresholds proposed in the literature are mainly for spaces with fixed occupants. Determining CO2 threshold is challenging in spaces with changing occupancy due to the co-existence of quanta and CO2 remaining from previous occupants. Here, we propose a new calculation framework for deriving safe excess CO2 thresholds (above outdoor level), C t, for various spaces with fixed/changing occupancy and analyze the uncertainty involved. We categorized common indoor spaces into three scenarios based on their occupancy conditions, e.g., fixed or varying infection ratios (infectors/occupants). We proved that the rebreathed fraction-based model can be applied directly for deriving C t in the case of a fixed infection ratio (Scenario 1 and Scenario 2). In the case of varying infection ratios (Scenario 3), C t derivation must follow the general calculation framework due to the existence of initial quanta/excess CO2. Otherwise, C t can be significantly biased (e.g., 260 ppm) when the infection ratio varies greatly. C t can vary significantly based on specific space factors such as occupant number, physical activity, and community prevalence, e.g., 7 ppm for gym and 890 ppm for lecture hall, indicating C t must be determined on a case-by-case basis. An uncertainty of up to 6 orders of magnitude for C t was found for all cases due to uncertainty in emissions of quanta and CO2, thus emphasizing the role of accurate emissions data in determining C t.

Cross-collection latent Beta-Liouville allocation model training with privacy protection and applications.

Cross-collection topic models extend previous single-collection topic models, such as Latent Dirichlet Allocation (LDA), to multiple collections. The purpose of cross-collection topic modeling is to model document-topic representations and reveal similarities between each topic and differences among groups. However, the restriction of Dirichlet prior and the significant privacy risk have hampered those models' performance and utility. Training those cross-collection topic models may, in particular, leak sensitive information from the training dataset. To address the two issues mentioned above, we propose a novel model, cross-collection latent Beta-Liouville allocation (ccLBLA), which operates a more powerful prior, Beta-Liouville distribution with a more general covariance structure that enhances topic correlation analysis. To provide privacy protection for the ccLBLA model, we leverage the inherent differential privacy guarantee of the Collapsed Gibbs Sampling (CGS) inference scheme and then propose a hybrid privacy protection algorithm for the ccLBLA model (HPP-ccLBLA) that prevents inferring data from intermediate statistics during the CGS training process without sacrificing its utility. More crucially, our technique is the first attempt to use the cross-collection topic model in image classification applications and investigate the cross-collection topic model's capabilities beyond text analysis. The experimental results for comparative text mining and image classification will show the merits of our proposed approach.

Engineering Bioactive M2 Macrophage-Polarized, Anti-inflammatory, miRNA-Based Liposomes for Functional Muscle Repair: From Exosomal Mechanisms to Biomaterials.

Severe inflammation and myogenic differentiation disorder are the major obstacles to skeletal muscle healing after injury. MicroRNAs (miRNAs) play an important role as regulatory molecules during the process of muscle healing, but the detailed mechanism of miRNA-mediated intercellular communication between myoblasts and macrophages remains unclear. Here, it is reported that myoblasts secrete miRNAs-enriched exosomes in the inflammatory environment, through which miR-224 is transferred into macrophages to inhibit M2 polarization. Further data demonstrate that WNT-9a may be a direct target of miR-224 for macrophage polarization. In turn, the secretome of M1 macrophages impairs myogenic differentiation and promotes proliferation. Single-cell integration analysis suggests that the elevation of exosome-derived miR-224 is caused by the activation of the key factor E2F1 in myoblasts and demonstrates the RB/E2F1/miR-224/WNT-9a axis. In vivo results show that treatment with antagomir-224 or liposomes containing miR-224 inhibitors suppresses fibrosis and improves muscle recovery. These findings indicate the importance of the crosstalk between myoblasts and macrophages via miRNA-containing exosomes in the regulation of macrophage polarization and myogenic differentiation/proliferation during muscle healing. This study provides a strategy for treating muscle injury through designing an M2 polarization-enabling anti-inflammatory and miRNA-based bioactive material.

LRIG2 regulates cell proliferation, migration and apoptosis of osteosarcoma.

BACKGROUND: Osteosarcoma (OS) is one of the malignant bone tumors with strong aggressiveness and poor prognosis. Leucine-rich repeats and immunoglobulin-like domains2 (LRIG2) is closely associated with the poor prognosis of a variety of tumors, but the role of LRIG2 in osteosarcoma and the underlying molecular mechanism remains unclear. OBJECTIVE: The aim of this study was to determine the function of LRIG2 in OS and the related molecular mechanism on cell proliferation, apoptosis and migration of OS. METHODS: The mRNA and protein expression of LRIG2 in OS tissues and cells was detected by qRT-PCR, western blot (WB) assay and immunohistochemistry (IHC). The cell counting Kit-8 (CCK-8), clone formation, transwell, TdT-mediated dUTP Nick-End Labeling (TUNEL) and WB assay were applied to determine the proliferation, migration and apoptosis abilities of OS cells and its molecular mechanisms. Spontaneous metastasis xenografts were established to confirm the role of LRIG2 in vivo. RESULTS: LRIG2 exhibited high expression in OS tissues and OS cell lines and the expression of which was significantly correlated with Enneking stage of patients, knockdown LRIG2 expression significantly inhibited OS cell proliferation, migration and enhanced apoptosis. Silencing LRIG2 also suppressed the growth of subcutaneous transplanted tumor in nude mice. Further, the mechanism investigation revealed that the protein level of cell proapoptotic proteins (Bax, caspase9 and caspase3) all increased attributed to LRIG2 deficiency, whereas expression of anti-apoptotic protein BCL2 decreased. LRIG2 silencing led to the decrease phosphorylation of AKT signaling, a decrease expression of vimentin and N-cadherin. Additionally, silencing LRIG2 significantly decreased the rate of tumor growth and tumor size. CONCLUSIONS: LRIG2 acts as an oncogene in osteosarcoma, and it might become a novel target in the treatment of human OS.

Evidence for Assimilatory Nitrate Reduction as a Previously Overlooked Pathway of Reactive Nitrogen Transformation in Estuarine Suspended Particulate Matter.

Suspended particulate matter (SPM) contributes to the loss of reactive nitrogen (Nr) in estuarine ecosystems. Although denitrification and anaerobic ammonium oxidation in SPM compensate for the current imbalance of global nitrogen (N) inputs and sinks, it is largely unclear whether other pathways for Nr transformation exist in SPM. Here, we combined stable isotope measurements with metagenomics and metatranscriptomics to verify the occurrence of dissimilatory nitrate reduction to ammonium (DNRA) in the SPM of the Pearl River Estuary (PRE). Surprisingly, the conventional functional genes of DNRA (nirBD) were abundant and highly expressed in SPM, which was inconsistent with a low potential rate. Through taxonomic and comparative genomic analyses, we demonstrated that nitrite reductase (NirBD) in conjunction with assimilatory nitrate reductase (NasA) performed assimilatory nitrate reduction (ANR) in SPM, and diverse alpha- and gamma-proteobacterial lineages were identified as key active heterotrophic ANR bacteria. Moreover, ANR was predicted to have a relative higher occurrence than denitrification and DNRA in a survey of Nr transformation pathways in SPM across the PRE spanning 65 km. Collectively, this study characterizes a previously overlooked pathway of Nr transformation mediated by heterotrophic ANR bacteria in SPM and has important implications for our understanding of N cycling in estuaries.

Incidences and reasons of postoperative surgical site infection after lumbar spinal surgery: a large population study.

PURPOSE: The purpose of this study was to determine the incidences of postoperative acute surgical site infection (SSI) after lumbar spinal surgery and its possible reasons in our hospital during the past 9 years. METHODS: This is a retrospective study with a large sample size. The medical records of all included patients were reviewed, and patients with acute SSI were identified. The incidence and possible reasons of SSI were determined. RESULTS: A total of 7240 patients who underwent posterior lumbar spinal surgery were included in this study, and the total incidence of postoperative SSI was 1.53% (111/7240). Gram-negative bacteria were found to be dominant in postoperative wound infections after lumbar spinal surgery. And Escherichia coli were the most common pathogen in patients with SSI. The rate of postoperative SSI following lumbar spinal surgery was increased at first and then decreased during the past 9 years. Additionally, from 2011 to 2014, it was mainly deep infection in these patients, and then was mainly superficial infection from 2015 to 2019. Patients with lumbar spinal stenosis had the highest incidence of postoperative SSI (2.39%, P < 0.001). There was also a significant difference for the number of SSI cases among different surgeons. CONCLUSION: Based on a large population analysis, Gram-negative bacteria were the most common pathogen in postoperative SSI after lumbar spinal surgery. And patients with lumbar spinal stenosis had the highest incidence of SSI. Increasing the intervention of Gram-negative may be an important step to reduce the postoperative SSI after lumbar spinal surgery.

Role of pathogen-laden expiratory droplet dispersion and natural ventilation explaining a COVID-19 outbreak in a coach bus.

The influencing mechanism of droplet transmissions inside crowded and poorly ventilated buses on infection risks of respiratory diseases is still unclear. Based on experiments of one-infecting-seven COVID-19 outbreak with an index patient at bus rear, we conducted CFD simulations to investigate integrated effects of initial droplet diameters(tracer gas, 5 µm, 50 µm and 100 µm), natural air change rates per hour(ACH = 0.62, 2.27 and 5.66 h-1 related to bus speeds) and relative humidity(RH = 35% and 95%) on pathogen-laden droplet dispersion and infection risks. Outdoor pressure difference around bus surfaces introduces natural ventilation airflow entering from bus-rear skylight and leaving from the front one. When ACH = 0.62 h-1(idling state), the 30-min-exposure infection risk(TIR) of tracer gas is 15.3%(bus rear) - 11.1%(bus front), and decreases to 3.1%(bus rear)-1.3%(bus front) under ACH = 5.66 h-1(high bus speed).The TIR of large droplets(i.e., 100 µm/50 µm) is almost independent of ACH, with a peak value(∼3.1%) near the index patient, because over 99.5%/97.0% of droplets deposit locally due to gravity. Moreover, 5 µm droplets can disperse further with the increasing ventilation. However, TIR for 5 µm droplets at ACH = 5.66 h-1 stays relatively small for rear passengers(maximum 0.4%), and is even smaller in the bus middle and front(<0.1%). This study verifies that differing from general rooms, most 5 µm droplets deposit on the route through the long-and-narrow bus space with large-area surfaces(L∼11.4 m). Therefore, tracer gas can only simulate fine droplet with little deposition but cannot replace 5-100 µm droplet dispersion in coach buses.

Chinese expert recommendations on management of hepatocellular carcinoma during COVID-19 pandemic: a nationwide multicenter survey.

BACKGROUND: This study aimed to investigate the work status of clinicians in China and their management strategy alteration for patients with hepatocellular carcinoma (HCC) during the COVID-19 pandemic. METHODS: A nationwide online questionnaire survey was conducted in 42 class-A tertiary hospitals across China. Experienced clinicians of HCC-related specialties responded with their work status and management suggestions for HCC patients during the pandemic. RESULTS: 716 doctors responded effectively with a response rate of 60.1%, and 664 were included in the final analysis. Overall, 51.4% (341/664) of clinicians reported more than a 60% reduction of the regular workload and surgeons declared the highest proportion of workload reduction. 92.5% (614/664) of the respondents have been using online medical consultation to substitute for the "face-to-face" visits. Adaptive adjustment for the treatment strategy for HCC was made, including the recommendations of noninvasive and minimally invasive treatments such as transcatheter arterial chemoembolization for early and intermediate stage. Targeted therapy has been the mainstay for advanced stage and also as a bridge therapy for resectable HCC. DISCUSSION: During the COVID-19 pandemic, online medical consultation is recommended to avoid social contact. Targeted therapy as a bridge therapy is recommended for resectable HCC considering the possibility of delayed surgery.

Long non-coding RNA MFAT1 promotes skeletal muscle fibrosis by modulating the miR-135a-5p-Tgfbr2/Smad4 axis as a ceRNA.

Fibrosis after skeletal muscle injury is common in sports and can cause irreversible damage to the biomechanical properties of skeletal muscle. Long non-coding RNAs (lncRNAs) have been validated to act as important modulators in the fibrosis of various organs. Here, we reported a novel lncRNA (the skeletal muscle fibrosis-associated transcript 1, lnc-MFAT1), which was highly expressed in skeletal muscle fibrosis. We demonstrate that lnc-MFAT1 knockdown can reduce TGFß-induced fibrosis in vitro and attenuate skeletal muscle fibrosis after acute contusion in mice. Further study showed that lnc-MFAT1 acted as a competitive endogenous RNA of miR-135a-5p. Besides, the miR-135a-5p inhibition obviously promoted TGFß-induced fibrosis in vitro via enhancing its target genes Tgfbr2/Smad4. Moreover, we discovered that lnc-MFAT1 regulates Tgfbr2/Smad4 expression by sponging miR-135a-5p to exert competing endogenous RNA function, resulting in TGFß pathway activation. In conclusion, our study identified a crucial role of lnc-MFAT1-miR-135a-Tgfbr2/Smad4 axis in skeletal muscle fibrosis, providing a promising treatment option against skeletal muscle fibrosis.

Impact of COVID-19 lockdown on NO2 and PM2.5 exposure inequalities in London, UK.

Amid the COVID-19 pandemic, a nationwide lockdown was imposed in the United Kingdom (UK) on March 23, 2020. These sudden control measures led to radical changes in human activities in the Greater London Area (GLA). During this lockdown, transportation use was significantly reduced and non-key workers were required to work from home. This study aims to understand how population exposure to PM2.5 and NO2 changed spatially and temporally across London, in different microenvironments, following the lockdown period relative to the previous three-year average in the same calendar period. Our research shows that population exposure to NO2 declined significantly (52.3% ± 6.1%), while population exposure to PM2.5 showed a smaller relative reduction (15.7% ± 4.1%). Changes in population activity had the strongest relative influence on exposure levels during morning rush hours, when prior to the lockdown a large percentage of people would normally commute or be at the workplace. In particular, a very high exposure decrease was observed for both pollutants (approximately 66% for NO2 and 19% for PM2.5) at 08:00am, consistent with the radical changes in population commuting. The infiltration of outdoor air pollution into housing modifies the degree of exposure change both temporally and spatially. Moreover, this study shows that the impacts on air pollution exposure vary across groups with different socioeconomic status (SES), with a disproportionate positive effect on the areas of the city home to more economically deprived communities.

The impact of indoor thermal stratification on the dispersion of human speech droplets.

Exhaled jets from an infected person are found to be locked at a certain height when thermal stratification exists in rooms, causing a potential high risk of disease transmission. This work is focused on the theoretical analysis of the dynamic characteristics of human speech droplets and the residual droplet nuclei in both thermally uniform and stratified environments. Results show that most droplets generated from human speaking can totally evaporate or deposit to the ground within 1.5-2 m. For small droplets of < 80µm, thermal stratification shows a more significant impact on their residues. The lock-up height of the droplet nuclei is a function of droplet size and the temperature gradient, and within this lock-up layer, these droplet nuclei can travel a long distance, much more than 2m. For medium droplets of 80-180 µm, thermal stratification can weaken the evaporation and accelerate the deposition processes, equivalent to a higher relative humidity (RH). Accordingly, more droplets can deposit to the ground, reducing the exposure to large droplets in close proximity to the source. Large droplets of > 180µm show no dependence on stratification and RH. These findings can have implications for developing effective engineering methods to limit the spread of infectious disease.