Comparison between AWGC-cachexia and GLIM-malnutrition in patients with gastric cancer.

BACKGROUND: The newly released Asian Working Group for Cachexia (AWGC) criteria share similar diagnostic items with the Global Leadership Initiative on Malnutrition (GLIM) criteria. This study aims to compare the AWGC cachexia and GLIM malnutrition in patients with gastric cancer and investigate whether one diagnosis continues to be a prognostic factor in individuals diagnosed with the other condition. METHODS: Data of patients who underwent radical gastrectomy for gastric adenocarcinoma were prospectively collected from 2013 to 2019. The AWGC and GLIM criteria were applied to diagnosis cachexia and malnutrition, respectively. Univariate and multivariate logistic and Cox regression were used to verify the effect of relevant factors on postoperative complications and overall survival. RESULTS: A total of 1420 patients were included, among whom 174 (12.3 %) were diagnosed with AWGC-cachexia alone, 85 (6.0 %) were diagnosed with GLIM-malnutrition alone, and 324 (22.8 %) had both AWGC-cachexia and GLIM-malnutrition. Both AWGC-cachexia and GLIM-malnutrition were independent risk factors for complications and overall survival. When they coexisted, the odds ratios (OR) and hazard ratios (HR) tended to be higher. In the AWGC-cachexia subset, GLIM-malnutrition remained an independent risk factor (HR = 1.544, 95 % CI = 1.098-2.171, P = 0.012) for overall survival after the adjustment of confounding factors. Similarly, in the GLIM-malnutrition subset, AWGC-cachexia remained an independent risk factor for overall survival (HR = 1.697, 95 % CI = 1.087-2.650, P = 0.020). Patients with both cachexia and malnutrition had the worst overall survival. CONCLUSION: AWGC-cachexia and GLIM-malnutrition criteria were two non-redundancy tools in reflecting mortality risk in preoperative nutritional assessment.

Identification of hub genes and key pathways in arsenic-treated rice (Oryza sativa L.) based on 9 topological analysis methods of CytoHubba.

BACKGROUND: Arsenic is a toxic metalloid that can cause acute and chronic adverse health problems. Unfortunately, rice, the primary staple food for more than half of the world's population, is generally regarded as a typical arsenic-accumulating crop plant. Evidence indicates that arsenic stress can influence the growth and development of the rice plant, and lead to high concentrations of arsenic in rice grain. But the underlying mechanisms remain unclear. METHODS: In the present research, the possible molecules and pathways involved in rice roots in response to arsenic stress were explored using bioinformatics methods. Datasets that involving arsenic-treated rice root and the "study type" that was restricted to "Expression profiling by array" were selected and downloaded from Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) between the arsenic-treated group and the control group were obtained using the online web tool GEO2R. Gene Ontology (GO) function and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were performed to investigate the functions of DEGs. The protein-protein interactions (PPI) network and the molecular complex detection algorithm (MCODE) of DEGs were analyzed using STRING and Cystoscope, respectively. Important nodes and hub genes in the PPI network were predicted and explored using the Cytoscape-cytoHubba plug-in. RESULTS: Two datasets, GSE25206 and GSE71492, were downloaded from Gene Expression Omnibus (GEO) database. Eighty common DEGs from the two datasets, including sixty-three up-regulated and seventeen down-regulated genes, were then selected. After functional enrichment analysis, these common DEGs were enriched mainly in 10 GO items, including glutathione transferase activity, glutathione metabolic process, toxin catabolic process, and 7 KEGG pathways related to metabolism. After PPI network and MCODE analysis, 49 nodes from the DEGs PPI network were identified, filtering two significant modules. Next, the Cytoscape-cytoHubba plug-in was used to predict important nodes and hub genes. Finally, five genes [Os01g0644000, PRDX6 (Os07g0638400), PRX112 (Os07g0677300), ENO1(Os06g0136600), LOGL9 (Os09g0547500)] were verified and could serve as the best candidates associated with rice root in response to arsenic stress. CONCLUSIONS: In summary, we elucidated the potential pathways and genes in rice root in response to arsenic stress through a comprehensive bioinformatics analysis.

Prompt-driven Latent Domain Generalization for Medical Image Classification.

Deep learning models for medical image analysis easily suffer from distribution shifts caused by dataset artifact bias, camera variations, differences in the imaging station, etc., leading to unreliable diagnoses in real-world clinical settings. Domain generalization (DG) methods, which aim to train models on multiple domains to perform well on unseen domains, offer a promising direction to solve the problem. However, existing DG methods assume domain labels of each image are available and accurate, which is typically feasible for only a limited number of medical datasets. To address these challenges, we propose a unified DG framework for medical image classification without relying on domain labels, called Prompt-driven Latent Domain Generalization (PLDG). PLDG consists of unsupervised domain discovery and prompt learning. This framework first discovers pseudo domain labels by clustering the bias-associated style features, then leverages collaborative domain prompts to guide a Vision Transformer to learn knowledge from discovered diverse domains. To facilitate cross-domain knowledge learning between different prompts, we introduce a domain prompt generator that enables knowledge sharing between domain prompts and a shared prompt. A domain mixup strategy is additionally employed for more flexible decision margins and mitigates the risk of incorrect domain assignments. Extensive experiments on three medical image classification tasks and one debiasing task demonstrate that our method can achieve comparable or even superior performance than conventional DG algorithms without relying on domain labels. Our code is publicly available at https://github.com/SiyuanYan1/PLDG/tree/main.

Ferroptosis: a potential target for acute lung injury.

Acute lung injury (ALI) is caused by a variety of intrapulmonary and extrapulmonary factors and is associated with high morbidity and mortality. Oxidative stress is an important part of the pathological mechanism of ALI. Ferroptosis is a mode of programmed cell death distinguished from others and characterized by iron-dependent lipid peroxidation. This article reviews the metabolic regulation of ferroptosis, its role in the pathogenesis of ALI, and the use of ferroptosis as a therapeutic target regarding the pharmacological treatment of ALI.

OsUVR8b, rather than OsUVR8a, plays a predominant role in rice UVR8-mediated UV-B response.

UV RESISTANCE LOCUS 8 (UVR8) has been identified in Arabidopsis thaliana as the receptor mediating responses to UV-B radiation. However, UVR8-mediated UV-B signaling pathways in rice, which possesses two proteins (UVR8a and UVR8b) with high identities to AtUVR8, remain largely unknown. Here, UVR8a/b were found to be predominantly expressed in rice leaves and leaf sheaths, while the levels of UVR8b transcript and UVR8b protein were both higher than those of UVR8a. Compared to wild-type (WT) plants, uvr8b and uvr8a uvr8b rice mutants exposed to UV-B showed reduced UV-B-induced growth inhibition and upregulation of CHS and HY5 transcripts alongside UV-B acclimation. However, uvr8a mutant was similar to WT plants and exhibited changes comparable with WT. Overexpressing OsUVR8a/b enhanced UV-B-induced growth inhibition and acclimation to UV-B. UV-B was able to enhance the interaction between E3 ubiquitin ligase OsCOP1 and OsUVR8a/b, whereas the interaction of the homologous protein of Arabidopsis REPRESSOR OF UV-B PHOTOMORPHOGENESIS2 (AtRUP2) in rice with OsUVR8a/b was independent of UV-B. Additionally, OsUVR8a/b proteins were also found in the nucleus and cytoplasm even in the absence of UV-B. The abundance of OsUVR8 monomer showed an invisible change in the leaves of rice seedlings transferred from white light to that supplemented with UV-B, even though UV-B was able to weaken the interactions between OsUVR8a and OsUVR8b homo and heterodimers. Therefore, both OsUVR8a and OsUVR8b, which have different localization and response patterns compared with AtUVR8, function in the response of rice to UV-B radiation, whereas OsUVR8b plays a predominant role in this process.

High Performance Solar-Driven Power-Water Cogeneration for Practical Application: From Micro/Nano Materials to Beyond.

Solar-driven water-electricity cogeneration is a promising strategy for tackling water scarcity and power shortages. However, comprehensive reviews on performance, scalability, commercialization, and power density are lacking. This Perspective presents an overview of recent developments and insights into the challenges and future outlooks for practical applications in this area. We summarize recent advances in high-efficiency water production, focusing on rapid evaporation and condensation. Then we categorize power-water cogeneration systems by power generation mechanisms like steam, evaporation, salinity gradient, photovoltaics, and temperature gradient, providing a comprehensive summary of the performance and applicability of these systems in different scenarios. Finally, we highlight challenges in current systems, considering nanoscale mechanisms and large-scale manufacturing, while also exploring potential trends for future practical applications.

Engineered acetogenic bacteria as microbial cell factory for diversified biochemicals.

Acetogenic bacteria (acetogens) are a class of microorganisms with conserved Wood-Ljungdahl pathway that can utilize CO and CO2/H2 as carbon source for autotrophic growth and convert these substrates to acetate and ethanol. Acetogens have great potential for the sustainable production of biofuels and bulk biochemicals using C1 gases (CO and CO2) from industrial syngas and waste gases, which play an important role in achieving carbon neutrality. In recent years, with the development and improvement of gene editing methods, the metabolic engineering of acetogens is making rapid progress. With introduction of heterogeneous metabolic pathways, acetogens can improve the production capacity of native products or obtain the ability to synthesize non-native products. This paper reviews the recent application of metabolic engineering in acetogens. In addition, the challenges of metabolic engineering in acetogens are indicated, and strategies to address these challenges are also discussed.

The complete plastid genome of Abrus pulchellus subsp. mollis (Leguminosae): a medicinal plant in Southern China.

The subspecies Abrus pulchellus subsp. mollis exhibits pharmacological properties akin to the traditional Chinese medicinal plant Abri Herba (A. pulchellus subsp. cantoniensis (Hance) Verdc.). In this report, we unveil the plastid genome of A. pulchellus subsp. mollis. The genome spans 156,322 base pairs (bp), comprising a large single-copy (LSC) region of 86,633 bp, a small single-copy (SSC) region of 18,219 bp, and two distinct inverted repeat regions (IRs) of 25,735 bp each. Annotation process cataloged a total of 111 genes within this genome, including 77 protein-coding genes, 30 transfer RNA (tRNA) genes, and four ribosomal RNA (rRNA) genes. The overall guanine-cytosine (GC) content of the plastome is 35.5%. Phylogenetic analysis utilizing maximum-likelihood (ML) based on 16 complete plastid genomes reveals a close clustering of three Abrus taxa, namely A. pulchellus subsp. mollis, A. pulchellus subsp. cantoniensis, and A. precatorius. Notably, A. pulchellus subsp. cantoniensis clusters with A. precatorius as a sister group, distinct from A. pulchellus subsp. mollis. These findings highlight significant differences between the plastid genomes of the two subspecies, laying the foundation for future research on the identification of medicinal herbs and germplasm resources related to these subspecies.

Evaluation of artificial intelligence-powered screening for sexually transmitted infections-related skin lesions using clinical images and metadata.

BACKGROUND: Sexually transmitted infections (STIs) pose a significant global public health challenge. Early diagnosis and treatment reduce STI transmission, but rely on recognising symptoms and care-seeking behaviour of the individual. Digital health software that distinguishes STI skin conditions could improve health-seeking behaviour. We developed and evaluated a deep learning model to differentiate STIs from non-STIs based on clinical images and symptoms. METHODS: We used 4913 clinical images of genital lesions and metadata from the Melbourne Sexual Health Centre collected during 2010-2023. We developed two binary classification models to distinguish STIs from non-STIs: (1) a convolutional neural network (CNN) using images only and (2) an integrated model combining both CNN and fully connected neural network (FCN) using images and metadata. We evaluated the model performance by the area under the ROC curve (AUC) and assessed metadata contributions to the Image-only model. RESULTS: Our study included 1583 STI and 3330 non-STI images. Common STI diagnoses were syphilis (34.6%), genital warts (24.5%) and herpes (19.4%), while most non-STIs (80.3%) were conditions such as dermatitis, lichen sclerosis and balanitis. In both STI and non-STI groups, the most frequently observed groups were 25-34 years (48.6% and 38.2%, respectively) and heterosexual males (60.3% and 45.9%, respectively). The Image-only model showed a reasonable performance with an AUC of 0.859 (SD 0.013). The Image + Metadata model achieved a significantly higher AUC of 0.893 (SD 0.018) compared to the Image-only model (p < 0.01). Out of 21 metadata, the integration of demographic and dermatological metadata led to the most significant improvement in model performance, increasing AUC by 6.7% compared to the baseline Image-only model. CONCLUSIONS: The Image + Metadata model outperformed the Image-only model in distinguishing STIs from other skin conditions. Using it as a screening tool in a clinical setting may require further development and evaluation with larger datasets.

A mechanistic analysis of metformin's biphasic effects on lifespan and healthspan in C. elegans: Elixir in youth, poison in elder.

Aging, a complex biological process influenced by genetic, environmental, and pharmacological factors, presents a significant challenge in understanding its underlying mechanisms. In this study, we explored the divergent impacts of metformin treatment on the lifespan and healthspan of young and old C. elegans, demonstrating a intriguing "elixir in youth, poison in elder" phenomenon. By scrutinizing the gene expression changes in response to metformin in young (day 1 of adulthood) and old (days 8) groups, we identified nhr-57 and C46G7.1 as potential modulators of age-specific responses. Notably, nhr-57 and C46G7.1 exhibit contrasting regulation patterns, being up-regulated in young worms but down-regulated in old counterparts following metformin treatment. Functional studies employing knockdown approaches targeting nhr-57, a gene under the control of hif-1 with a documented protective function against pore-forming toxins in C. elegans, and C46G7.1, unveiled their critical roles in modulating lifespan and healthspan, as well as in mediating the biphasic effects of metformin. Furthermore, deletion of hif-1 retarded the influence of metformin, implicating the involvement of hif-1/nhr-57 in age-specific drug responses. These findings underscored the necessity of deciphering the mechanisms governing age-related susceptibility to pharmacological agents to tailor interventions for promoting successful aging.

Cognatishimia coralii sp. nov., a marine bacterium isolated from seawater surrounding corals.

Coral reefs are declining due to the rising seawater temperature. Bacteria within and surrounding corals play key roles in maintaining the homeostasis of the coral holobiont. Research on coral-related bacteria could provide benefits for coral reef restoration. During the isolation of coral-associated bacteria, a Gram-stain-negative, motile bacterium (D5M38T) was isolated from seawater surrounding corals in Daya Bay, Shenzhen, PR China. Phylogenetic analysis revealed that strain D5M38T represents a novel species in the genus Cognatishimia. The temperature range for strain D5M38T growth was 10-40 °C, and the optimum temperature was 37 °C. The salinity range for the growth of this isolate was from 0 to 4.0 %, with an optimal salinity level of 0.5 %. The pH range necessary for strain D5M38T growth was between pH 5.0 and 9.0, with an optimal pH being 7.5. The predominant fatty acid was summed feature 8 (65.0 %). The major respiratory quinone was Q-10. The DNA G+C content was 56.8 %. The genome size was 3.88 Mb. The average nucleotide identity (ANI), average amino acid identity (AAI) and digital DNA-DNA hybridization (dDDH) values between strain D5M38T and its two closest neighbours, Cognatishimia activa LMG 29900T and Cognatishimia maritima KCTC 23347T, were 73.2/73.6%, 73.2/73.6% and 19.7/19.5%, respectively. Strain D5M38T was clearly distinct from its closest neighbours C. activa LMG 29900T and C. maritima KCTC 23347T, with 16S rRNA gene sequence similarity values of 97.5 and 97.3 %, respectively. The phylogenetic analysis, along with the ANI, AAI, and dDDH values, demonstrated that strain D5M38T is a member of the genus Cognatishimia, and is distinct from the other two recognized species within this genus. The physiological, biochemical and chemotaxonomic characteristics also supported the species novelty of strain D5M38T. Thus, strain D5M38T is considered to be classified as representing a novel species in the genus Cognatishimia, for which the name Cognatishimia coralii sp. nov. is proposed. The type strain is D5M38T (=MCCC 1K08692T=KCTC 8160T).

Changes in the recent three decades and survey on the current status of surgical treatment for esophageal cancer in China.

BACKGROUND: To review the changes and survey on status quo of the surgical treatment for esophageal cancer in China. The differences in diagnosis and treatment for esophageal cancer among hospitals in different regions across China were also investigated. METHODS: We sent questionnaires to 46 hospitals across China, investigating the volume of esophageal cancer surgeries, surgical procedures, and perioperative management under the guidance of esophageal surgery chiefs. RESULTS: A total of 46 questionnaires were sent out and collected. The survey results showed that in the past 5 years, the volume of surgeries for esophageal cancer remained stable by 23.9% of those hospitals, increased by 30.4%, and decreased by 45.7%. Of those patients treated by surgery, 19.1% were in the early stages, and 80.9% were in locally advanced stages. In terms of surgical procedures, 73.4% of the patients were treated by minimally invasive surgery and 85.7% of esophageal substitutes were a gastric conduit, 93.1% of the substitutes were pulled to the neck through the esophageal bed. For the lymph node dissection, 78.5% of the patients had a complete two-field lymph node dissection including the para-recurrent laryngeal nerve lymph nodes. Of the patients with neoadjuvant therapy, 53.5% received chemotherapy or chemotherapy plus immunotherapy (47.0%), and 43.5% had chemoradiation. CONCLUSIONS: Currently, in China, minimally invasive surgery-oriented multimodality treatment, including complete two-field lymph node dissection, has become the standard approach for esophageal cancer management. Over the past decade, this standardized approach has significantly improved prognosis compared to previous decades.

Microplastic detection and remediation through efficient interfacial solar evaporation for immaculate water production.

Freshwater scarcity and microplastics (MPs) pollution are two concerning and intertwined global challenges. In this work, we propose a "one stone kills two birds" strategy by employing an interfacial solar evaporation platform (ISEP) combined with a MPs adsorbent. This strategy aims to produce clean water and simultaneously enhance MPs removal. Unlike traditional predecessors, our ISEP generates condensed water free from MPs contamination. Additionally, the photothermally driven interfacial separation process significantly improves the MPs removal performance. We observed a removal ratio increase of up to 5.5 times compared to previously reported MPs adsorbents. Thus, our rationally-designed ISEP holds promising potential to not only mitigate the existing water scarcity issue but also remediate MPs pollution in natural water environments.

The Effects of External Interfaces on Hydrophobic Interactions I: Smooth Surface.

External interfaces, such as the air-water and solid-liquid interfaces, are ubiquitous in nature. Hydrophobic interactions are considered the fundamental driving force in many physical and chemical processes occurring in aqueous solutions. It is important to understand the effects of external interfaces on hydrophobic interactions. According to the structural studies on liquid water and the air-water interface, the external interface primarily affects the structure of the topmost water layer (interfacial water). Therefore, an external interface may affect hydrophobic interactions. The effects of interfaces on hydrophobicity are related not only to surface molecular polarity but also to the geometric characteristics of the external interface, such as shape and surface roughness. This study is devoted to understanding the effects of a smooth interface on hydrophobicity. Due to hydrophobic interactions, the solutes tend to accumulate at external interfaces to maximize the hydrogen bonding of water. Additionally, these can be demonstrated by the calculated potential mean forces (PMFs) using molecular dynamic (MD) simulations.

Large potential of strengthening the land carbon sink in China through anthropogenic interventions.

The terrestrial ecosystem in China mitigates 21%-45% of the national contemporary fossil fuel CO2 emissions every year. Maintaining and strengthening the land carbon sink is essential for reaching China's target of carbon neutrality. However, this sink is subject to large uncertainties due to the joint impacts of climate change, air pollution, and human activities. Here, we explore the potential of strengthening land carbon sink in China through anthropogenic interventions, including forestation, ozone reduction, and litter removal, taking advantage of a well-validated dynamic vegetation model and meteorological forcings from 16 climate models. Without anthropogenic interventions, considering Shared Socioeconomic Pathways (SSP) scenarios, the land sink is projected to be 0.26-0.56 Pg C a-1 at 2060, to which climate change contributes 0.06-0.13 Pg C a-1 and CO2 fertilization contributes 0.08-0.44 Pg C a-1 with the stronger effects for higher emission scenarios. With anthropogenic interventions, under a close-to-neutral emission scenario (SSP1-2.6), the land sink becomes 0.47-0.57 Pg C a-1 at 2060, including the contributions of 0.12 Pg C a-1 by conservative forestation, 0.07 Pg C a-1 by ozone pollution control, and 0.06-0.16 Pg C a-1 by 20% litter removal over planted forest. This sink can mitigate 90%-110% of the residue anthropogenic carbon emissions in 2060, providing a solid foundation for the carbon neutrality in China.

SH-Alb inhibits phenotype remodeling of pro-fibrotic macrophage to attenuate liver fibrosis through SIRT3-SOD2 axis.

Albumin has a variety of biological functions, such as immunomodulatory and antioxidant activity, which depends largely on its thiol activity. However, in clinical trials, the treatment of albumin by injection of commercial human serum albumin (HSA) did not achieve the desired results. Here, we constructed reduced modified albumin (SH-Alb) for in vivo and in vitro experiments to investigate the reasons why HSA did not achieve the expected effects. SH-Alb was found to delay the progression of liver fibrosis in mice by alleviating liver inflammation and oxidative stress. Although R-Alb also has some of the above roles, the effect of SH-Alb is more remarkable. Mechanism studies have shown that SH-Alb reduces the release of pro-inflammatory and pro-fibrotic cytokine through the mitogen-activated protein kinase (MAPK) signaling pathway. In addition, SH-Alb deacetylates SOD2, a key enzyme of mitochondrial reactive oxygen species (ROS) production, by promoting the expression of SIRT3, thereby reducing the accumulation of ROS. Finally, macrophages altered by R-Alb or SH-Alb can inhibit the activation of hepatic stellate cells and endothelial cells, further delaying the progression of liver fibrosis. These results indicate that SH-Alb can remodel the phenotype of macrophages, thereby affecting the intrahepatic microenvironment and delaying the process of liver fibrosis. It provides a good foundation for the application of albumin in clinical treatment.

The Dependence of Hydrophobic Interactions on the Shape of Solute Surface.

According to our recent studies on hydrophobicity, this work is aimed at understanding the dependence of hydrophobic interactions on the shape of a solute's surface. It has been observed that dissolved solutes primarily affect the structure of interfacial water, which refers to the top layer of water at the interface between the solute and water. As solutes aggregate in a solution, hydrophobic interactions become closely related to the transition of water molecules from the interfacial region to the bulk water. It is inferred that hydrophobic interactions may depend on the shape of the solute surface. To enhance the strength of hydrophobic interactions, the solutes tend to aggregate, thereby minimizing their surface area-to-volume ratio. This also suggests that hydrophobic interactions may exhibit directional characteristics. Moreover, this phenomenon can be supported by calculated potential mean forces (PMFs) using molecular dynamics (MD) simulations, where different surfaces, such as convex, flat, or concave, are associated with a sphere. Furthermore, this concept can be extended to comprehend the molecular packing parameter, commonly utilized in studying the self-assembly behavior of amphiphilic molecules in aqueous solutions.

Synthesis and Preclinical Evaluation of Novel 68Ga-DOTA-RBB as Potential PET Radiotracer for Imaging CDK4/6 in Tumors.

Many malignant tumors, including breast cancer, exhibit amplification and overexpression of cyclin-dependent kinase 4 and 6 (CDK4/6). Ribociclib, approved and used in clinical treatment, acts as a highly selective CDK4/6 inhibitor for ER+/HER2- breast cancer. By modifying ribociclib with the chelator DOTA, we designed and synthesized a novel CDK4/6-positive PET imaging agent, which was radiolabeled by 68Ga for radioactive tagging. The radiotracer demonstrates high radiochemical purity, excellent stability in vitro and in vivo, and favorable pharmacokinetic characteristics. Cell uptake experiments using MCF-7 cells indicate that an excess of ribociclib (RBB) can inhibit cellular uptake of 68Ga-DOTA-RBB. Imaging and biodistribution experiments in MCF-7 tumor-bearing nude mice show significant radioactive accumulation in the tumor. However, preadministration of excess ribociclib results in a substantial reduction in radioactive accumulation within the tumor. On the basis of our explorations, 68Ga-DOTA-RBB, as a targeted imaging agent for CDK4/6-positive tumors, holds significant potential application values.

PE/PPE mutations in the transmission of Mycobacterium tuberculosis in China revealed by whole genome sequencing.

OBJECTIVE: This study aims to examine the impact of PE/PPE gene mutations on the transmission of Mycobacterium tuberculosis (M. tuberculosis) in China. METHODS: We collected the whole genome sequencing (WGS) data of 3202 M. tuberculosis isolates in China from 2007 to 2018 and investigated the clustering of strains from different lineages. To evaluate the potential role of PE/PPE gene mutations in the dissemination of the pathogen, we employed homoplastic analysis to detect homoplastic single nucleotide polymorphisms (SNPs) within these gene regions. Subsequently, logistic regression analysis was conducted to analyze the statistical association. RESULTS: Based on nationwide M. tuberculosis WGS data, it has been observed that the majority of the M. tuberculosis burden in China is caused by lineage 2 strains, followed by lineage 4. Lineage 2 exhibited a higher number of transmission clusters, totaling 446 clusters, of which 77 were cross-regional clusters. Conversely, there were only 52 transmission clusters in lineage 4, of which 9 were cross-regional clusters. In the analysis of lineage 2 isolates, regression results showed that 4 specific gene mutations, PE4 (position 190,394; c.46G > A), PE_PGRS10 (839,194; c.744 A > G), PE16 (1,607,005; c.620T > G) and PE_PGRS44 (2,921,883; c.333 C > A), were significantly associated with the transmission of M. tuberculosis. Mutations of PE_PGRS10 (839,334; c.884 A > G), PE_PGRS11 (847,613; c.1455G > C), PE_PGRS47 (3,054,724; c.811 A > G) and PPE66 (4,189,930; c.303G > C) exhibited significant associations with the cross-regional clusters. A total of 13 mutation positions showed a positive correlation with clustering size, indicating a positive association. For lineage 4 strains, no mutations were found to enhance transmission, but 2 mutation sites were identified as risk factors for cross-regional clusters. These included PE_PGRS4 (338,100; c.974 A > G) and PPE13 (976,897; c.1307 A > C). CONCLUSION: Our results indicate that some PE/PPE gene mutations can increase the risk of M. tuberculosis transmission, which might provide a basis for controlling the spread of tuberculosis.

Transcriptome profiling of fast/glycolytic and slow/oxidative muscle fibers in aging and obesity.

Aging and obesity pose significant threats to public health and are major contributors to muscle atrophy. The trends in muscle fiber types under these conditions and the transcriptional differences between different muscle fiber types remain unclear. Here, we demonstrate distinct responses of fast/glycolytic fibers and slow/oxidative fibers to aging and obesity. We found that in muscles dominated by oxidative fibers, the proportion of oxidative fibers remains unchanged during aging and obesity. However, in muscles dominated by glycolytic fibers, despite the low content of oxidative fibers, a significant decrease in proportion of oxidative fibers was observed. Consistently, our study uncovered that during aging and obesity, fast/glycolytic fibers specifically increased the expression of genes associated with muscle atrophy and inflammation, including Dkk3, Ccl8, Cxcl10, Cxcl13, Fbxo32, Depp1, and Chac1, while slow/oxidative fibers exhibit elevated expression of antioxidant protein Nqo-1 and downregulation of Tfrc. Additionally, we noted substantial differences in the expression of calcium-related signaling pathways between fast/glycolytic fibers and slow/oxidative fibers in response to aging and obesity. Treatment with a calcium channel inhibitor thapsigargin significantly increased the abundance of oxidative fibers. Our study provides additional evidence to support the transcriptomic differences in muscle fiber types under pathophysiological conditions, thereby establishing a theoretical basis for modulating muscle fiber types in disease treatment.