Climate-driven decline in water level causes earlier onset of hypoxia in a subtropical reservoir.

Hypoxia, especially in the bottom water, is occurring in deep and stratified reservoirs worldwide, threatening aquatic biodiversity, ecosystem functions and services. However, little is known about the timing of onset and ending of hypoxia, especially in subtropical reservoirs. Based on five-year (from April 2015 to January 2020) sampling of a subtropical monomictic deep reservoir (Tingxi Reservoir) in southeast China, we found the evidence of about 40 days earlier onset of hypolimnion hypoxia during low water level periods in dry years compared to wetter high water level years. We explored the effects of stratification and mixing conditions on hypoxia, cyanobacterial biomass, and nutrient dynamics; and revealed the physical and biochemical conditions that drove hypoxia. The results indicated that 1) The decline in water level increased the intensity of thermal stratification, resulting in 40 days earlier onset of hypolimnion hypoxia in dry years than in wet years; 2) The decline in water level expanded the extent of hypoxia by promoting nutrient accumulation and phytoplankton biomass growth; 3) Warmer climate and less precipitation (drought) significantly promoted the risk of hypoxic expansion and endogenous phosphorus release in subtropical reservoirs. We suggest that more attention needs to be paid to the early onset of hypoxia and its consequences on water quality in subtropical stratified reservoirs during low water level periods in a changing climate.

Direct Collapse Supermassive Black Holes from Relic Particle Decay.

We investigate the formation of high-redshift supermassive black holes (SMBHs) via the direct collapse of baryonic clouds, where the unwanted formation of molecular hydrogen is successfully suppressed by a Lyman-Werner (LW) photon background from relic particle decay. We improve on existing studies by dynamically simulating the collapse, accounting for the adiabatic contraction of the DM halo, as well as the in situ production of the LW photons within the cloud which reduce the impact of the cloud's shielding. We find a viable parameter space where the decay of either some of the dark matter or all of a subdominant decaying species successfully allows direct collapse of the cloud to a SMBH.

Transcriptomic analysis unveils alterations in the genetic expression profile of tree peony (Paeonia suffruticosa Andrews) infected by Alternaria alternata.

BACKGROUND: Black spot disease in tree peony caused by the fungal necrotroph A. alternata, is a primary limiting factor in the production of the tree peony. The intricate molecular mechanisms underlying the tree peony resistance to A. alternata have not been thoroughly investigated. RESULTS: The present study utilized high-throughput RNA sequencing (RNA-seq) technology to conduct global expression profiling, revealing an intricate network of genes implicated in the interaction between tree peony and A. alternata. RNA-Seq libraries were constructed from leaf samples and high-throughput sequenced using the BGISEQ-500 sequencing platform. Six distinct libraries were characterized. M1, M2 and M3 were derived from leaves that had undergone mock inoculation, while I1, I2 and I3 originated from leaves that had been inoculated with the pathogen. A range of 10.22-11.80 gigabases (Gb) of clean bases were generated, comprising 68,131,232 - 78,633,602 clean bases and 56,677 - 68,996 Unigenes. A grand total of 99,721 Unigenes were acquired, boasting a mean length of 1,266 base pairs. All these 99,721 Unigenes were annotated in various databases, including NR (Non-Redundant, 61.99%), NT (Nucleotide, 45.50%), SwissProt (46.32%), KEGG (Kyoto Encyclopedia of Genes and Genomes, 49.33%), KOG (clusters of euKaryotic Orthologous Groups, 50.18%), Pfam (Protein family, 47.16%), and GO (Gene Ontology, 34.86%). In total, 66,641 (66.83%) Unigenes had matches in at least one database. By conducting a comparative transcriptome analysis of the mock- and A. alternata-infected sample libraries, we found differentially expressed genes (DEGs) that are related to phytohormone signalling, pathogen recognition, active oxygen generation, and circadian rhythm regulation. Furthermore, multiple different kinds of transcription factors were identified. The expression levels of 10 selected genes were validated employing qRT-PCR (quantitative real-time PCR) to confirm RNA-Seq data. CONCLUSIONS: A multitude of transcriptome sequences have been generated, thus offering a valuable genetic repository for further scholarly exploration on the immune mechanisms underlying the tree peony infected by A. alternata. While the expression of most DEGs increased, a few DEGs showed decreased expression.

Ligustilide alleviates oxidative stress during renal ischemia-reperfusion injury through maintaining Sirt3-dependent mitochondrial homeostasis.

BACKGROUND: Renal ischemia-reperfusion (I/R) injury is an inevitable complication during renal transplantation and is closely related to patient prognosis. Mitochondrial damage induced oxidative stress is the core link of renal I/R injury. Ligustilide (LIG), a natural compound extracted from ligusticum chuanxiong hort and angelica sinensis, has exhibited the potential to protect mitochondrial function. However, whether LIG can ameliorate renal I/R injury requires further investigation. Delving deeper into the precise targets and mechanisms of LIG's effect on renal I/R injury is crucial. PURPOSE: This study aimed to elucidate the specific mechanism of LIG's protective effect on renal I/R injury. METHODS: In this study, an in vivo model of renal ischemia-reperfusion (I/R) injury was developed in mice, along with an in vitro model of hypoxia-reoxygenation (H/R) using human proximal renal tubular epithelial cells (HK-2). To assess the impact of LIG on renal injury, various methods were employed, including serum creatinine (Cr) and blood urea nitrogen (BUN) testing, hematoxylin and eosin (HE) staining, and immunohistochemistry (IHC) for kidney injury molecule-1 (KIM-1). The effects of LIG on oxidative stress were examined using fluorescent probes dihydroethidium (DHE) and dichlorodihydrofluorescein diacetate (DCFH-DA), TdT-mediated dUTP Nick-End Labeling (TUNEL) staining, and flow cytometry. Additionally, the influence of LIG on mitochondrial morphology and function was evaluated through transmission electron microscopy (TEM), Mito Tracker Red CMXRos staining, adenosine triphosphate (ATP) concentration assays, and JC-1 staining. The potential mechanism involving LIG and Sirt3 was explored by manipulating Sirt3 expression through cell transfection. RESULTS: The results showed that LIG could provide protective function for mitochondria to alleviate oxidative stress induced by renal I/R. Further mechanistic studies indicated that LIG maintained mitochondrial homeostasis by targeting Sirt3. CONCLUSION: Our findings demonstrated that LIG alleviated oxidative stress during renal I/R injury through maintaining Sirt3-dependent mitochondrial homeostasis. Overall, our data raised the possibility of LIG as a novel therapy for renal I/R injury.

Correlates of symptom burden in renal dialysis patients: a systematic review and meta-analysis.

BACKGROUND: Patients receiving renal dialysis often experience a wide range of symptoms. These symptoms contribute to a significant symptom burden that significantly affects patients' quality of life and serves as a significant predictor of healthcare resource utilization and patient prognosis. It is necessary to synthesize existing evidence to draw reliable conclusions to deepen the understanding of symptom burden. OBJECTIVE: A systematic review and meta-analysis were conducted to identify the relevant factors of symptom burden in patients receiving renal dialysis. METHODS: The systematic review and meta-analysis was conducted by searching nine databases for studies reporting the correlates between symptom burden and demographic variables, disease factors, and psychosocial factors from inception to 24 June 2024. After two researchers independently conducted literature search, data extraction, and quality evaluation, meta-analysis was conducted using R Language and Stata 15.1 Software. This study has been registered in the PROSPERO. RESULTS: Sixty-two studies were included in this review. Results showed that the symptom burden of renal dialysis patients was positively correlated with age, gender, working status, medical cost, dialysis age, quality of sleep, nutritional status, comorbidities, depression, anxiety, disease uncertain, avoidance coping and resignation coping, and negatively correlated with marital status, income, serum sodium, quality of life, social support, subjective well-being, and self-management ability. CONCLUSIONS: Our findings reveal that many factors, including demographic, disease-related, and psychosocial variables, affect symptom burden. The results can supply information for health promotion and relief symptom burden for patients receiving renal dialysis.Registered number: CRD42024507577.

A new paradigm in intracellular immunology: Mitochondria emerging as leading immune organelles.

Mitochondria, traditionally recognized as cellular 'powerhouses' due to their pivotal role in energy production, have emerged as multifunctional organelles at the intersection of bioenergetics, metabolic signaling, and immunity. However, the understanding of their exact contributions to immunity and inflammation is still developing. This review first introduces the innovative concept of intracellular immunity, emphasizing how mitochondria serve as critical immune signaling hubs. They are instrumental in recognizing and responding to pathogen and danger signals, and in modulating immune responses. We also propose mitochondria as the leading immune organelles, drawing parallels with the broader immune system in their functions of antigen presentation, immune regulation, and immune response. Our comprehensive review explores mitochondrial immune signaling pathways, their therapeutic potential in managing inflammation and chronic diseases, and discusses cutting-edge methodologies for mitochondrial research. Targeting a broad readership of both experts in mitochondrial functions and newcomers to the field, this review sets forth new directions that could transform our understanding of intracellular immunity and the integrated immune functions of intracellular organelles.

PV and SST neurons in the anterior cingulate cortex regulate social disorders in adulthood induced by sensory abnormalities in childhood.

OBJECTIVE: Childhood sensory abnormalities experience has a crucial influence on the structure and function of the adult brain. The underlying mechanism of neurological function induced by childhood sensory abnormalities experience is still unclear. Our study was to investigate whether the GABAergic neurons in the anterior cingulate cortex (ACC) regulate social disorders caused by childhood sensory abnormalities experience. METHODS: We used two mouse models, complete Freund's adjuvant (CFA) injection mice and bilateral whisker trimming (BWT) mice in childhood. We applied immunofluorescence, chemogenetic and optogenetic to study the mechanism of parvalbumin (PV) neurons and somatostatin (SST) neurons in ACC in regulating social disorders induced by sensory abnormalities in childhood. RESULTS: Inflammatory pain in childhood leads to social preference disorders, while BWT in childhood leads to social novelty disorders in adult mice. Inflammatory pain and BWT in childhood caused an increase in the number of PV and SST neurons, respectively, in adult mice ACC. Inhibiting PV neurons in ACC improved social preference disorders in adult mice that experienced inflammatory pain during childhood. Inhibiting SST neurons in ACC improved social novelty disorders in adult mice that experienced BWT in childhood. CONCLUSIONS: Our study reveals that PV and SST neurons of the ACC may play a critical role in regulating social disorders induced by sensory abnormalities in childhood.

Caspase-4/11 promotes hyperlipidemia and chronic kidney disease-accelerated vascular inflammation by enhancing trained immunity.

To determine whether hyperlipidemia and chronic kidney disease (CKD) have a synergy in accelerating vascular inflammation via trained immunity (TI), we performed aortic pathological analysis and RNA-Seq of high-fat diet-fed (HFD-fed) 5/6 nephrectomy CKD (HFD+CKD) mice. We made the following findings: (a) HFD+CKD increased aortic cytosolic LPS levels, caspase-11 (CASP11) activation, and 998 gene expressions of TI pathways in the aorta (first-tier TI mechanism); (b) CASP11-/- decreased aortic neointima hyperplasia, aortic recruitment of macrophages, and casp11-gasdermin D-mediated cytokine secretion; (c) CASP11-/- decreased N-terminal gasdermin D (N-GSDMD) membrane expression on aortic endothelial cells and aortic IL-1B levels; (d) LPS transfection into human aortic endothelial cells resulted in CASP4 (human)/CASP11 (mouse) activation and increased N-GSDMD membrane expression; and (e) IL-1B served as the second-tier mechanism underlying HFD+CKD-promoted TI. Taken together, hyperlipidemia and CKD accelerated vascular inflammation by promoting 2-tier trained immunity.

Dose-response relationship between weekly physical activity level and the frequency of colds in Chinese middle-aged and elderly individuals.

Background: Engaging in appropriate physical activity can significantly lower the risk of various diseases among middle-aged and older adults. Investigating optimal levels of physical activity (PA) is crucial for enhancing the health of this demographic. This study aims to explore the dose-response relationship between weekly PA levels and the frequency of colds among Chinese middle-aged and elderly individuals, identifying the necessary PA level to effectively diminish the risk of colds. Methods: We conducted a cross-sectional study using a web-based survey targeting individuals aged 40 and older (n = 1, 683) in China. The survey collected information on PA and the frequency of colds. Data was analyzed using Kruskal-Wallis test and the χ2 test. We explored the dose-response relationship between weekly PA and cold frequency over the past year through an ordered multivariate logistic regression model and a restricted cubic spline model. Results: (1) Brisk walking emerged as the preferred physical exercise for those over 40. The findings suggest that engaging in moderate (odds ratio (OR) = 0.64, P < 0.001, 95% confidence interval (CI) [0.50-0.81]) and high (OR = 0.64, P < 0.001, 95% CI [0.51-0.79]) levels of PA weekly significantly reduces the risk of catching a cold. Individuals with one (OR = 1.47, P < 0.001, 95% CI [1.20-1.80]) or multiple chronic diseases (OR = 1.56, P < 0.001, 95% CI [1.21-2.00]) were at increased risk. Those residing in central (OR = 1.64, P < 0.001, 95% CI [1.33-02.01]) and western China (OR = 1.49, P = 0.008, 95% CI [1.11-02.00]) faced a higher risk compared to their counterparts in eastern China. (2) According to the restricted cubic spline model, adults who experienced one cold in the past year had a weekly PA level of 537.29 metabolic equivalent-minutes per week (MET-min/wk) with an OR value of 1. For those reporting two or more colds, the PA level was 537.76 MET-min/wk with an OR of 1. Conclusions: (1) Brisk walking is the most favored exercise among the Chinese middle-aged and elderly, with the prevalence of colds being affected by the number of chronic diseases and the geographic location. (2) Regular, moderate exercise is linked to a lower risk of colds. To effectively reduce cold frequency, it is recommended that middle-aged and elderly Chinese individuals engage in a minimum of 538 MET-min/wk of exercise.

Role of long non-coding RNA in inflammatory bowel disease.

Inflammatory bowel disease (IBD) is a group of recurrent chronic inflammatory diseases, including Crohn's disease (CD) and ulcerative colitis (UC). Although IBD has been extensively studied for decades, its cause and pathogenesis remain unclear. Existing research suggests that IBD may be the result of an interaction between genetic factors, environmental factors and the gut microbiome. IBD is closely related to non-coding RNAs (ncRNAs). NcRNAs are composed of microRNA(miRNA), long non-coding RNA(lnc RNA) and circular RNA(circ RNA). Compared with miRNA, the role of lnc RNA in IBD has been little studied. Lnc RNA is an RNA molecule that regulates gene expression and regulates a variety of molecular pathways involved in the pathbiology of IBD. Targeting IBD-associated lnc RNAs may promote personalized treatment of IBD and have therapeutic value for IBD patients. Therefore, this review summarized the effects of lnc RNA on the intestinal epithelial barrier, inflammatory response and immune homeostasis in IBD, and summarized the potential of lnc RNA as a biomarker of IBD and as a predictor of therapeutic response to IBD in the future.

Effects of 8 weeks parent-accompanied swimming on physical capacity and intelligence in preschool children.

This study aimed to explore the potential effects of 8-week parents-accompanied swimming on the physical capacity and intelligence of preschool children in China. Thirty-six boys (mean age 3.56 ± 0.27 years) were divided into three groups: the traditional physical exercise group (TP, n = 12), the accompanied swimming group (AS, n = 12) and the independent swimming group (IS, n = 12). Participants' physical capacity was assessed before and after the intervention using the following indicators: height, weight, distance of tennis ball throw, standing long jump distance, time for the 10-meter shuttle run, time for a two-legged continuous jump, sit-and-reach distance, and time on the walking balance beam. Intelligence was assessed at three points: pre-test, mid-test after 4 weeks, and post-test. Data were analyzed using a two-way repeated measures ANOVA, Bonferroni test (p < 0.05) and effect size. The time of the AS and IS groups to walk the balance beam was significantly lower than the TP group, with a difference of 1.81 s (p < 0.01, [95% CI -3.22 to -0.40], ES = 1.53) and 1.25 s (p < 0.05, [95% CI -2.66 to 0.16], ES = 0.81). At the mid-test, the IQ scores of the TP group were lower than the AS group (p < 0.05, [95% CI -12.45 to -0.96], ES = 0.89). Additionally, at post-test, the IQ scores of the TP group were significantly lower than those of both AS (p < 0.01, [95% CI -14.12 to -2.74], ES = 1.15) and IS groups (p < 0.01, [95% CI -12.53 to -3.31], ES = 1.21). Swimming enhances children's balance and IQ scores more than traditional physical exercises. Involving parents in swimming leads to a more significant increase in IQ scores within 4 weeks of initial swimming exercise.

Antioxidative, Anti-Inflammatory, Antibacterial, Photo-Cross-Linkable Hydrogel of Gallic Acid-Chitosan Methacrylate: Synthesis, In Vitro, and In Vivo Assessments.

Chitosan (CS)-based photo-cross-linkable hydrogels have gained increasing attention in biomedical applications. In this study, we grafted CS with gallic acid (GA) by carbodiimide chemistry to prepare the GA-CS conjugate, which was subsequently modified with methacrylic anhydride (MA) modification to obtain the methacrylated GA-CS conjugate (GA-CS-MA). Our results demonstrated that the GA-CS-MA hydrogel not only exhibited improved physicochemical properties but also showed antibacterial, antioxidative, and anti-inflammatory capacity. It showed moderate antibacterial activity and especially showed a more powerful inhibitory effect against Gram-positive bacteria. It modulated macrophage polarization, downregulated pro-inflammatory gene expression, upregulated anti-inflammatory gene expression, and significantly reduced reactive oxygen species (ROS) and nitric oxide (NO) production under lipopolysaccharide (LPS) stimulation. Subcutaneously implanted GA-CS-MA hydrogels induced significantly lower inflammatory responses, as evidenced by less inflammatory cell infiltration, thinner fibrous capsule, and predominately promoted M2 polarization. This study provides a feasible strategy to prepare CS-based photo-cross-linkable hydrogels with improved physicochemical properties for biomedical applications.

Construction of An Orthotopic Xenograft Model of Non-small Cell Lung Cancer Mimicking Disease Progression and Predicting Drug Activities.

Non-small cell lung cancer (NSCLC) is a highly lethal disease with a complex and heterogeneous tumor microenvironment. Currently, common animal models based on subcutaneous inoculation of cancer cell suspensions do not recapitulate the tumor microenvironment in NSCLC. Herein we describe a murine orthotopic lung cancer xenograft model that employs the intrapulmonary inoculation of three-dimensional multicellular spheroids (MCS). Specifically, fluorescent human NSCLC cells (A549-iRFP) were cultured in low-attachment 96-well microplates with collagen for 3 weeks to form MCS, which were then inoculated intercostally into the left lung of athymic nude mice to establish the orthotopic lung cancer model. Compared with the original A549 cell line, MCS of the A549-iRFP cell line responded similarly to anticancer drugs. The long-wavelength fluorescent signal of the A549-iRFP cells correlated strongly with common markers of cancer cell growth, including spheroid volume, cell viability, and cellular protein level, thus allowing dynamic monitoring of the cancer growth in vivo by fluorescent imaging. After inoculation into mice, the A549-iRFP MCS xenograft reliably progressed through phases closely resembling the clinical stages of NSCLC, including the expansion of the primary tumor, the emergence of neighboring secondary tumors, and the metastases of cancer cells to the contralateral right lung and remote organs. Moreover, the model responded to the benchmark antilung cancer drug, cisplatin with the anticipated toxicity and slower cancer progression. Therefore, this murine orthotopic xenograft model of NSCLC would serve as a platform to recapitulate the disease's progression and facilitate the development of potential anticancer drugs.

Composite Aerogel Scaffolds Containing Flexible Silica Nanofiber and Tricalcium Phosphate Enable Skin Regeneration.

Poor hemostatic ability and less vascularization at the injury site could hinder wound healing as well as adversely affect the quality of life (QOL). An ideal wound dressing should exhibit certain characteristics: (a) good hemostatic ability, (b) rapid wound healing, and (c) skin appendage formation. This necessitates the advent of innovative dressings to facilitate skin regeneration. Therapeutic ions, such as silicon ions (Si4+) and calcium ions (Ca2+), have been shown to assist in wound repair. The Si4+ released from silica (SiO2) can upregulate the expression of proteins, including the vascular endothelial growth factor (VEGF) and alpha smooth muscle actin (α-SMA), which is conducive to vascularization; Ca2+ released from tricalcium phosphate (TCP) can promote the coagulation alongside upregulating the expression of cell migration and cell differentiation related proteins, thereby facilitating the wound repair. The overarching objective of this study was to exploit short SiO2 nanofibers along with the TCP to prepare TCPx@SSF aerogels and assess their wound healing ability. Short SiO2 nanofibers were prepared by electrospinning and blended with varying proportions of TCP to afford TCPx@SSF aerogel scaffolds. The TCPx@SSF aerogels exhibited good cytocompatibility in a subcutaneous implantation model and manifested a rapid hemostatic effect (hemostatic time 75 s) in a liver trauma model in the rabbit. These aerogel scaffolds also promoted skin regeneration and exhibited rapid wound closure, epithelial tissue regeneration, and collagen deposition. Taken together, TCPx@SSF aerogels may be valuable for wound healing.

Differentially expressed genes of esophageal tissue in male acute and chronic sleep deprivation mice.

Gastroesophageal reflux disease (GERD) is associated with sleep disturbances. However, mechanisms underlying these interactions remain unclear. Male acute and chronic sleep deprivation (SD) mice were used for this study. Mice in the chronic SD group exhibited anxiety- and depression-like behaviors. We further performed high-throughput genome sequencing and bioinformatics analysis to screen for featured differentially expressed genes (DEGs) in the esophageal tissue. The acute SD group, comprised 25 DEGs including 14 downregulated and 11 upregulated genes. Compared with the acute SD group, more DEGs were present in the chronic SD group, with a total of 169 DEGs, including 88 downregulated and 81 upregulated genes. Some DEGs that were closely related to GERD and associated esophageal diseases were significantly different in the chronic SD group. Quantitative real-time polymerase chain reaction verified the downregulation of Krt4, Krt13, Krt15 and Calml3 and upregulation of Baxl1 and Per3. Notably, these DEGs are involved in biological processes, which might be the pathways of the neuroregulatory mechanisms of DEGs expression.

Collaborative Modeling to Compare Different Breast Cancer Screening Strategies: A Decision Analysis for the US Preventive Services Task Force.

Importance: The effects of breast cancer incidence changes and advances in screening and treatment on outcomes of different screening strategies are not well known. Objective: To estimate outcomes of various mammography screening strategies. Design, Setting, and Population: Comparison of outcomes using 6 Cancer Intervention and Surveillance Modeling Network (CISNET) models and national data on breast cancer incidence, mammography performance, treatment effects, and other-cause mortality in US women without previous cancer diagnoses. Exposures: Thirty-six screening strategies with varying start ages (40, 45, 50 years) and stop ages (74, 79 years) with digital mammography or digital breast tomosynthesis (DBT) annually, biennially, or a combination of intervals. Strategies were evaluated for all women and for Black women, assuming 100% screening adherence and "real-world" treatment. Main Outcomes and Measures: Estimated lifetime benefits (breast cancer deaths averted, percent reduction in breast cancer mortality, life-years gained), harms (false-positive recalls, benign biopsies, overdiagnosis), and number of mammograms per 1000 women. Results: Biennial screening with DBT starting at age 40, 45, or 50 years until age 74 years averted a median of 8.2, 7.5, or 6.7 breast cancer deaths per 1000 women screened, respectively, vs no screening. Biennial DBT screening at age 40 to 74 years (vs no screening) was associated with a 30.0% breast cancer mortality reduction, 1376 false-positive recalls, and 14 overdiagnosed cases per 1000 women screened. Digital mammography screening benefits were similar to those for DBT but had more false-positive recalls. Annual screening increased benefits but resulted in more false-positive recalls and overdiagnosed cases. Benefit-to-harm ratios of continuing screening until age 79 years were similar or superior to stopping at age 74. In all strategies, women with higher-than-average breast cancer risk, higher breast density, and lower comorbidity level experienced greater screening benefits than other groups. Annual screening of Black women from age 40 to 49 years with biennial screening thereafter reduced breast cancer mortality disparities while maintaining similar benefit-to-harm trade-offs as for all women. Conclusions: This modeling analysis suggests that biennial mammography screening starting at age 40 years reduces breast cancer mortality and increases life-years gained per mammogram. More intensive screening for women with greater risk of breast cancer diagnosis or death can maintain similar benefit-to-harm trade-offs and reduce mortality disparities.

FAM53B promotes pancreatic ductal adenocarcinoma metastasis by regulating macrophage M2 polarization.

BACKGROUND: Our study investigated the role of FAM53B in regulating macrophage M2 polarization and its potential mechanisms in promoting pancreatic ductal adenocarcinoma (PDAC) metastasis. AIM: To further investigate the role of FAM53B in regulating macrophage M2 polarization and its potential mechanism in promoting PDAC metastasis. Our goal is to determine how FAM53B affects macrophage M2 polarization and to define its underlying mechanism in PDAC metastasis. METHODS: Cell culture and various experiments, including protein analysis, immunohistochemistry, and animal model experiments, were conducted. We compared FAM53B expression between PDAC tissues and healthy tissues and assessed the correlation of FAM53B expression with clinical features. Our study analyzed the role of FAM53B in macrophage M2 polarization in vitro by examining the expression of relevant markers. Finally, we used a murine model to study the role of FAM53B in PDAC metastasis and analyzed the potential underlying mechanisms. RESULTS: Our research showed that there was a significant increase in FAM53B levels in PDAC tissues, which was linked to adverse tumor features. Experimental findings indicated that FAM53B can enhance macrophage M2 polarization, leading to increased anti-inflammatory factor release. The results from the mouse model further supported the role of FAM53B in PDAC metastasis, as blocking FAM53B prevented tumor cell invasion and metastasis. CONCLUSION: FAM53B promotes PDAC metastasis by regulating macrophage M2 polarization. This discovery could lead to the development of new strategies for treating PDAC. For example, interfering with the FAM53B signaling pathway may prevent cancer spread. Our research findings also provide important information for expanding our understanding of PDAC pathogenesis.

Brisk walking improves motor function and lower limb muscle strength in Chinese women aged 80 years and older.

This study investigates the effects of a 12-week brisk walking exercise regimen on motor function improvements in elderly women. Twenty-six elderly women, aged 84.2 ± 3.2 years, participated in a 12-week brisk walking exercise program. Fitness assessments and blood biomarker analyses (including CHO, HDLC, LDLC, TC) were conducted pre- and post-intervention. Additionally, targeted metabolomics was employed to measure short-chain fatty acids, amino acids, and vitamin metabolites. The intervention led to significant enhancements in participants' flexibility (p < 0.05), lower limb muscle strength (p < 0.01), and cardiorespiratory endurance (p < 0.01), while muscle mass showed no significant changes. Fifteen significant differential metabolites were identified (VIP > 1.0, FC > 1.2 or < 0.8, and p < 0.05), with arginine, ornithine, aspartic acid, glutamine, phenylalanine, tyrosine, and pantothenic acid playing key roles across seven metabolic pathways. A 12-week brisk walking exercise program significantly enhanced flexibility, lower limb muscle strength, and cardiorespiratory endurance among elderly women. These improvements did not extend to muscle mass or upper limb muscle strength. The observed enhancement in exercise capacity may be attributed to improved regulation of neurotransmitters.

PTPLAD1 Regulates PHB-Raf Interaction to Orchestrate Epithelial-Mesenchymal and Mitofusion-Fission Transitions in Colorectal Cancer.

Colorectal cancer (CRC) remains one of the leading causes of cancer-related death worldwide. The poor prognosis of this malignancy is attributed mainly to the persistent activation of cancer signaling for metastasis. Here, we showed that protein tyrosine phosphatase-like A domain containing 1 (PTPLAD1) is down-regulated in highly metastatic CRC cells and negatively associated with poor survival of CRC patients. Systematic analysis reveals that epithelial-to-mesenchymal transition (EMT) and mitochondrial fusion-to-fission (MFT) transition are two critical features for CRC patients with low expression of PTPLAD1. PTPLAD1 overexpression suppresses the metastasis of CRC in vivo and in vitro by inhibiting the Raf/ERK signaling-mediated EMT and mitofission. Mechanically, PTPLAD1 binds with PHB via its middle fragment (141-178 amino acids) and induces dephosphorylation of PHB-Y259 to disrupt the interaction of PHB-Raf, resulting in the inactivation of Raf/ERK signaling. Our results unveil a novel mechanism in which Raf/ERK signaling activated in metastatic CRC induces EMT and mitochondrial fission simultaneously, which can be suppressed by PTPLAD1. This finding may provide a new paradigm for developing more effective treatment strategies for CRC.