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Background: Robotic-assisted total knee arthroplasty (RATKA) has been reported to enhance operative decision-making. The purpose of this study was intended to assess the predictive accuracy of bone cuts, lower limb alignment, and component size of a novel system for RATKA preoperatively and intraoperatively. Methods: Preoperatively planned bone cuts, limb alignment, and component size were projected using a reconstructed 3D model. Intraoperative bone cuts and postoperative limb alignment were measured. Errors between planned and real bone cuts, limb alignment, and component size were compared. Results: The mean absolute errors for bone cuts and alignment were within 1.40mm/1.30° with a standard deviation (SD) of 0.96mm/1.12°. For all errors of bone cuts and alignment compared with the plan, there were no statistically significant differences except for the lateral distal of femoral cuts (P=0.004). The accuracy for predicting the femoral, tibial, and polyethylene component sizes was 100% (48/48), 90% (43/48), and 88% (42/48), respectively. Regarding all mean absolute errors of bone cuts and alignments, no significant differences were observed among surgeons. Conclusion: The novel robotically-assisted system for RATKA donated reliable operative decision-making based on the predictive accuracy regardless of the surgeon's level of experience.
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How organisms respond to environmental stress is a key topic in evolutionary biology. This study focused on the genomic evolution of Laburnicola rhizohalophila, a dark-septate endophytic fungus from roots of a halophyte. Chromosome-level assemblies were generated from five representative isolates from structured subpopulations. The data revealed significant genomic plasticity resulting from chromosomal polymorphisms created by fusion and fission events, known as dysploidy. Analyses of genomic features, phylogenomics, and macrosynteny have provided clear evidence for the origin of intraspecific diploid-like hybrids. Notably, one diploid phenotype stood out as an outlier and exhibited a conditional fitness advantage when exposed to a range of abiotic stresses compared with its parents. By comparing the gene expression patterns in each hybrid parent triad under the four growth conditions, the mechanisms underlying growth vigor were corroborated through an analysis of transgressively upregulated genes enriched in membrane glycerolipid biosynthesis and transmembrane transporter activity. In vitro assays suggested increased membrane integrity and lipid accumulation, as well as decreased malondialdehyde production under optimal salt conditions (0.3 M NaCl) in the hybrid. These attributes have been implicated in salinity tolerance. This study supports the notion that hybridization-induced genome doubling leads to the emergence of phenotypic innovations in an extremophilic endophyte.
Subject(s)
Diploidy , Plant Roots , Salt-Tolerant Plants , Plant Roots/microbiology , Salt-Tolerant Plants/microbiology , Salt-Tolerant Plants/genetics , Hybrid Vigor/genetics , Phylogeny , Genome, Fungal , Ascomycota/genetics , Ascomycota/metabolism , Gene Expression Regulation, Fungal , Endophytes/genetics , Endophytes/metabolism , Stress, Physiological/genetics , Phenotype , Salt Tolerance/genetics , Hybridization, GeneticABSTRACT
Objective: The oxidative balance score (OBS) is important for determining the cause of obesity and its complications. We aimed to evaluate the association between OBS and obesity and other segmental body composition parameters among young and middle-aged U.S. adults. Methods: 9,998 participants from the National Health and Nutrition Examination Survey 2011-2018 were included. Lean mass percentage (LM%) and FM% were evaluated by dual-energy x-ray absorptiometry. Obesity was defined as body FM% ≥25% in men and ≥ 35% in women. The OBS was scored by 5 pro-oxidant and 21 antioxidant factors. Associations of quartiles of OBS with obesity risk were estimated using multivariable logistic regression models. Multivariable linear regression was conducted to estimate the association between OBS and segmental body composition measures including the arm LM%, leg LM%, torso LM%, whole LM%, arm FM%, leg FM%, torso FM% and total FM%. Results: Compared to participants in the lowest quartile of OBS, those in the highest quartile of OBS were associated with a lower risk of BMI-defined obesity BMI-defined obesity [0.43 (0.36, 0.50)] and FM%-related obesity [0.43 (0.35, 0.52)]. Additionally, OBS was negatively associated with FM% of the limb and torso but positively associated with the percentage of lean mass (LM%) of the limb and trunk. Conclusion: OBS was negatively associated with the risk of obesity and segmental FM%, but was positively associated with segmental LM% among US adults, indicating that adhering to an anti-oxidative diet and lifestyle management may be beneficial for preventing segmental obesity.
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BACKGROUND: Acute pancreatitis (AP) is an inflammatory disorder of the exocrine pancreas, especially hyperlipidemia acute pancreatitis (HLAP) is the third leading cause of acute pancreatitis which is more severe with a greater incidence of persistent multiorgan failure. HLAP inflicts injury upon the organelles within the acinar cell, particularly mitochondria, the endolysosomal-autophagy system, and is accompanied by senescence-associated secretory phenotype (SASP). RAD, only two consists of Rhizoma Alismatis and Atractylodes macrocephala Rhizoma, which is best known for its ability to anti-inflammatory and lipid-lowering. Nevertheless, the mechanism by which RAD alleviates HLAP remains obscure, necessitating further investigation. PURPOSE: The study aimed to assess the effects of the RAD on HLAP and to elucidate the underlying mechanism in vivo and in vitro, offering a potential medicine for clinical treatment for HLAP. STUDY DESIGN AND METHODS: C57BL/6 mice with hyperlipidemia acute pancreatitis were induced by HFD and CER, then administrated with RAD. AR42J were stimulated by cerulein or conditioned medium and then cultured with RAD. Serums were analyzed to evaluate potential pancreas and liver damage. Furthermore, tissue samples were obtained for histological, and protein investigations by H&E, Oil red staining, and Western blot. In addition, western blot and immunofluorescent staining were utilized to estimate the effect of RAD on mitochondrial function, autophagy flux, and SASP. RESULTS: In vivo, RAD considerably alleviated systemic inflammation while attenuating TC, TG, AMY, LPS, inflammatory cytokines, histopathology changes, oxidative damage, mitochondrial fission, and autophagy markers in HLAP mice. Impaired autophagy flux and mitochondrial dysfunction resulted in a significant enhancement of NLRP3 and IL-1ß in the pancreas. RAD could reverse these changes. In vitro, RAD significantly restored mitochondrial membrane potential and oxidative phosphorylation levels. RAD decreased Beclin-1 and LC3-II expression and increased LAMP-1 and Parkin-Pink expression, which showed that RAD significantly ameliorated HLAP-induced damage to the mitochondria function by suppressing mitochondrial oxidative damage and enhancing autophagy flux and mitophagy to remove the damaged mitochondria. In addition, we found that RAD could up-regulate the expression of BAX, and Bad and down-regulate the expression of p16, and p21, indicating that RAD could promote damaged cell apoptosis and alleviate SASP. CONCLUSIONS: This study revealed that RAD ameliorates mitochondrial function to alleviate SASP through enhancing autophagy flux, mitophagy, and apoptosis which provided a molecular basis for the advancement and development of protection strategies against HLAP.
Subject(s)
Apoptosis , Autophagy , Hyperlipidemias , Mice, Inbred C57BL , Mitochondria , Pancreatitis , Animals , Pancreatitis/drug therapy , Autophagy/drug effects , Apoptosis/drug effects , Hyperlipidemias/drug therapy , Mitochondria/drug effects , Mitochondria/metabolism , Mice , Male , Atractylodes/chemistry , Drugs, Chinese Herbal/pharmacology , Pancreas/drug effects , Pancreas/pathology , Rhizome/chemistry , Disease Models, Animal , Alisma/chemistryABSTRACT
There is limited understanding regarding the changes in the ecological processes and the mechanisms of archaeal community in response to heavy metal contamination in the marine sediments. In this study, sediment samples were collected from 46 locations near harbors, and the concentration of heavy metals and the diversity of archaeal communities were investigated to understand the impact of Cd on archaeal communities. The results demonstrated a significant correlation between the diversity of archaeal community and Cd concentration, particularly showing a linear decrease in the species richness with rising Cd concentration. ANME-1b was identified as a significantly enriched archaeal taxon in the higher Cd environment. Null model and neutral community model indicated that the ecological assembly of archaeal communities in marine sediments was primarily governed by the stochastic processes, with dispersal limitation being the primary factor. The contribution of deterministic process to the assembly of archaeal communities in higher Cd environments increased clearly, accompanied by a notable reduction in species migration rates and widths of ecological niche of archaeal populations. Co-occurrence network analysis revealed an obvious increase in species interactions in higher Cd environments, with an apparent rise in the proportion of competitive relationships and an increase in the number of keystone species. Moreover, archaeal species formed a more complex and stable community to cope with Cd stress. This study provides new insights into the impacts of heavy metals on the ecological processes of marine microorganisms and the underlying mechanisms.
Subject(s)
Archaea , Metals, Heavy , Archaea/genetics , Cadmium/analysis , Geologic Sediments , RNA, Ribosomal, 16S/analysis , Metals, Heavy/analysisABSTRACT
Introduction: Patients suffering from limb movement disorders require more complete rehabilitation treatment, and there is a huge demand for rehabilitation exoskeleton robots. Flexible and reliable motion control of exoskeleton robots is very important for patient rehabilitation. Methods: This paper proposes a novel exoskeleton robotic system for lower limb rehabilitation. The designed lower limb rehabilitation exoskeleton robot mechanism is mainly composed of the hip joint mechanism, the knee joint mechanism and the ankle joint mechanism. The forces and motion of the exoskeleton robot were analyzed in detail to determine its design parameters. The robot control system was developed to implement closed-loop position control and trajectory planning control of each joint mechanism. Results: Multiple experiments and tests were carried out to verify robot's performance and practicality. In the robot angular response experiments, the joint mechanism could quickly adjust to different desired angles, including 15°, 30°, 45°, and 60°. In the trajectory tracking experiments, the exoskeleton robot could complete tracking movements of typical actions such as walking, standing up, sitting down, go upstairs and go downstairs, with a maximum tracking error of ±5°. Robotic wearing tests on normal people were performed to verify the assistive effects of the lower limb rehabilitation exoskeleton at different stages. Discussion: The experimental results indicated that the exoskeleton robot has excellent reliability and practicality. The application of this exoskeleton robotic system will help paralyzed patients perform some daily movements and sports.
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BACKGROUND AND AIMS: Nonalcoholic fatty liver disease/nonalcoholic steatohepatitis (NASH) is one of the primary causes of chronic liver disease worldwide. Obeticholic acid (OCA), a potent farnesoid X nuclear receptor activator, has shown promise for treating NASH-related fibrosis due to its anti-fibrotic effects. This study aimed to examine the efficacy of OCA for patients with NASH as well as to investigate its impact on dyslipidemia. METHOD: A search of databases including PubMed, Embase, and Cochrane Library from January 1, 2010, to November 1, 2022, was conducted to identify systematic reviews of randomized controlled trials involving NASH patients. Inclusion criteria comprised randomized controlled trials that specifically addressed NASH as diagnosed through magnetic resonance imaging, computed tomography, or histology. The results were then categorized, with consideration given to both biochemical and histological outcomes. RESULT: Five NASH studies were ultimately selected for further analysis. In terms of biochemical indicators, patients receiving OCA treatment showed improvements in alanine transaminase (mean difference: -19.48, 95% confidence interval [CI]: -24.39 to 14.58; Pâ <â .05) and aspartate aminotransferase (mean difference: -9.22, 95% CI: -12.70 to 5.74; Pâ <â .05). As for histological improvement, OCA treatment reduced fibrosis (odds ratio [OR]: 1.95, 95% CI: 1.47-2.59; Pâ =â .001) and steatosis (OR: 1.95, 95% CI: 1.47-2.59; Pâ =â .001). No significant differences were observed regarding adverse events (1.44, 95% CI: 0.57-3.62; Pâ >â .001). Regarding dyslipidemia, mean differences between total cholesterol and low-density lipoprotein were found to be high (0.33, 95% CI: 0.01-0.64, Pâ <â .05; 0.39, 95% CI: 0.04-0.73, Pâ <â .05). In the case of pruritus, OCA achieved a high OR (3.22, 95% CI: 2.22-4.74) compared with placebo. CONCLUSION: OCA also reduced several liver test markers compared to placebo, including the biochemical indicators alanine transaminase, aspartate aminotransferase, alkaline phosphatase, and γ-glutamyl transpeptidase, and improved hepatocellular ballooning, fibrosis, steatosis, and lobular inflammation. Although the incidence of adverse events did not significantly differ between OCA and placebo groups among NASH patients, OCA treatment was found to elevate total cholesterol and low-density lipoprotein levels, and the reported severity of pruritus increased with higher doses of OCA.
Subject(s)
Chenodeoxycholic Acid/analogs & derivatives , Dyslipidemias , Non-alcoholic Fatty Liver Disease , Humans , Non-alcoholic Fatty Liver Disease/complications , Non-alcoholic Fatty Liver Disease/drug therapy , Alanine Transaminase , Randomized Controlled Trials as Topic , Chenodeoxycholic Acid/adverse effects , Fibrosis , Lipoproteins, LDL , Dyslipidemias/drug therapy , Pruritus/drug therapy , Aspartate Aminotransferases , CholesterolSubject(s)
Colon , Colonoscopy , Foreign Bodies , Animals , Humans , Male , Colon/surgery , Colonoscopy/methods , Foreign Bodies/surgery , Foreign Bodies/diagnostic imaging , AdultABSTRACT
PURPOSE: The aim of this study was to analyze the learning curve of total operative time, bone cutting accuracy, and limb alignment in total knee arthroplasty (TKA) using a Chinese image-based knee surgery robot known as HURWA. Additionally, a comparison was conducted with conventional TKA to ascertain the benefits of robotic-assisted TKA. METHODS: In this retrospective study, we analyzed a series of patients (n = 90) who underwent robotic-assisted total knee arthroplasty using the HURWA robot between December 2021 and October 2022. The procedures were performed by one of three orthopedic surgeons with varying levels of experience. As a control group, we selected the last 30 conventional TKA cases performed by each of these three surgeons. To determine the learning curve, we recorded the operative time, bone cutting error, and pre- and post-surgery radiographs. RESULTS: The study found no significant differences in total operative time, bone cutting accuracy, or limb alignment among the three surgeons. Of the three surgeons, surgeon 1, who had the most experience in joint arthroplasty, reached the learning curve in case 8, with the shortest bone cutting time and robot time. Surgeon 2 reached the learning curve in case 16, while surgeon 3 reached the learning curve in case 9. There was no observable learning curve effect for bone cutting accuracy and limb alignment. However, the percentage of cases where limb alignment differed from preoperative planning by 3° or less was higher in robotic-assisted TKA (77.97%) than in conventional TKA (47.19%). CONCLUSION: The study determined that the learning curve for robotic-assisted TKA using the HURWA knee surgery robot ranged from 8 to 20 cases. No observable learning curve effect was detected for bone cutting accuracy or limb alignment. Experienced surgeons using the HURWA robot for bone cutting took less time and reached the learning curve earlier. The HURWA robot achieved better limb alignment without depending on the experience of conventional TKA.
Subject(s)
Arthroplasty, Replacement, Knee , Osteoarthritis, Knee , Robotic Surgical Procedures , Humans , Arthroplasty, Replacement, Knee/methods , Knee Joint/surgery , Learning Curve , Osteoarthritis, Knee/diagnostic imaging , Osteoarthritis, Knee/surgery , Retrospective Studies , Robotic Surgical Procedures/methodsABSTRACT
Background: Klinefelter's syndrome (KS) was once considered infertile due to congenital chromosomal abnormalities, but the presence of focal spermatozoa changed this. The key to predict and promote spermatogenesis is to find targets that regulate focal spermatogenesis. Objective: To explore the trend of fertility changes in KS patients at different ages and identify potential therapeutic targets. Methods: Bibliometric analysis was used to collect clinical research data on KS from the Web of Science Core Collection (WoSCC) from 1992 to 2022. A cross-sectional study was conducted on 75 KS patients who underwent microscopic testicular sperm extraction (mTESE) from 2017 to 2022 in the real world. The reproductive hormones, testicular histopathology, androgen receptors, insulin-like factor 3 (INSL3) receptors and sperm recovery rate (SRR) were analyzed. Results: Male infertility, dysplasia, Sertoli cells, Leydig cells, testosterone and spermatogenesis were the research focuses related to KS. Luteinizing hormone (LH), testosterone, and INSL3 were evaluation indicators of Leydig cell function that fluctuate with age. Testosterone and LH peaked at ages 13-19 and 30-45, while INSL3 only peaked at ages 13-19. 27 patients (27/75) recovered sperm through mTESE and experienced SRR peaks at the ages of 20, 28, 34, and 37. The SRR of fibrosis patients was 46.15%, fatty degeneration was 7.14%, and melanosis was 40.00%. The INSL3 and androgen receptors were highly expressed and roughly balanced in focal spermatogenesis. Conclusion: Abnormal metabolism of Leydig cells led to imbalanced expression of INSL3 and androgen receptors, which might be a potential target for spermatogenesis in KS.
Subject(s)
Infertility, Male , Klinefelter Syndrome , Metabolic Diseases , Humans , Male , Leydig Cells/pathology , Klinefelter Syndrome/complications , Klinefelter Syndrome/genetics , Klinefelter Syndrome/drug therapy , Cross-Sectional Studies , Receptors, Androgen/genetics , Sperm Retrieval , Semen/chemistry , Spermatogenesis/physiology , Testosterone/therapeutic use , Luteinizing Hormone , Infertility, Male/genetics , Infertility, Male/drug therapy , Metabolic Diseases/drug therapyABSTRACT
BACKGROUND: There is little prospective evidence exists about whether adherence to a diabetes risk reduction diet (DRRD) is related to a significant reduction in renal cancer risk. We sought to clarify whether adherence to DRRD was associated with a reduced risk of renal cancer in a US population. METHODS: A population-based cohort of 101,755 American adults was identified from the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. A DRRD score was calculated to assess adherence to this dietary pattern, where increased scores indicated greater adherence. The relationship between DRRD score and risk of renal cancer was assessed based on the hazard ratios (HRs) and 95% confidence intervals (CIs), which were both calculated using Cox regression. Non-linear association was determined through restricted cubic spline regression. Potential effect modifiers were identified through subgroup analyses. RESULTS: Over a mean follow-up of 8.8 years, 446 renal cancers were detected. In this analysis, the fully adjusted model depicted a notable 29% reduction in the risk of renal cancer among individuals in the highest quartile of DRRD score in comparison with the lowest quartile individuals (HRQ4 vs. Q1: 0.71; 95% CI = 0.54, 0.94; Ptrend = 0.008). This association remained consistent across a series of sensitivity analyses. A non-linear inverse dose-response association between renal cancer risk with DRRD score was observed (Pnonlinearity = 0.026). Subgroup analyses showed that this favorable link was more prominent in participants with low Healthy Eating Index-2015 (Pinteraction = 0.015). Regarding the individual components of DRRD, a decrease in the risk of renal cancer was linked to increased intake of cereal fiber and whole fruit, and lower sugar-sweetened beverage consumption (all Ptrend < 0.05). CONCLUSIONS: Our findings indicate that individuals adhering to DRRD are associated with a reduction in the risk of renal cancer.
Subject(s)
Diabetes Mellitus , Kidney Neoplasms , Male , Adult , Humans , United States/epidemiology , Prospective Studies , Diet , Diet, Reducing , Kidney Neoplasms/epidemiology , Risk Reduction Behavior , Risk FactorsABSTRACT
Downregulation of endothelial Sirtuin1 (Sirt1) in insulin resistant states contributes to vascular dysfunction. Furthermore, Sirt1 deficiency in skeletal myocytes promotes insulin resistance. Here, we show that deletion of endothelial Sirt1, while impairing endothelial function, paradoxically improves skeletal muscle insulin sensitivity. Compared to wild-type mice, male mice lacking endothelial Sirt1 (E-Sirt1-KO) preferentially utilize glucose over fat, and have higher insulin sensitivity, glucose uptake, and Akt signaling in fast-twitch skeletal muscle. Enhanced insulin sensitivity of E-Sirt1-KO mice is transferrable to wild-type mice via the systemic circulation. Endothelial Sirt1 deficiency, by inhibiting autophagy and activating nuclear factor-kappa B signaling, augments expression and secretion of thymosin beta-4 (Tß4) that promotes insulin signaling in skeletal myotubes. Thus, unlike in skeletal myocytes, Sirt1 deficiency in the endothelium promotes glucose homeostasis by stimulating skeletal muscle insulin sensitivity through a blood-borne mechanism, and augmented secretion of Tß4 by Sirt1-deficient endothelial cells boosts insulin signaling in skeletal muscle cells.
Subject(s)
Insulin Resistance , Sirtuin 1 , Animals , Male , Mice , Endothelial Cells , Endothelium , Glucose , Insulin , Muscle, Skeletal , Secretome , Sirtuin 1/geneticsABSTRACT
OBJECTIVES: This paper presented a detailed analysis of the epidemiology and molecular characteristics of staphylococcal food poisoning (SFP) that occurred in a hotel in Hangzhou. METHODS: A total of 46 guests at the hotel underwent an epidemiological survey. Samples of stool from patients, vomit, swabs from the kitchen, leftover food items, and anal swabs from food handlers were taken and investigated for the presence of potential pathogenic bacteria. Molecular techniques and whole genome sequencing were performed to track the evolution of Staphylococcus aureus associated with the outbreak of SFP. RESULTS: Forty-six individuals displayed gastrointestinal symptoms. Seventeen isolates of S. aureus were discovered to carry the seg, sei, sem, sen, seo, and selu genes found in a specific enterotoxin gene cluster (egc) operon, but without the presence of classical enterotoxins such as SEA â¼ SEE. All egc-positive isolates shared identical pulsed-field gel electrophoresis profiles and were classified under new ST7591 (Clonal Complex 72) with identical spa typing t148. In addition, some isolates of S. aureus obtained from food sources sold in Hangzhou over the past 3 years and carrying egc genes were grouped under the ST72 lineage (CC72). Through whole genome sequencing, a strong genetic connection was revealed between these egc-positive isolates and clinical ST72 S. aureus found in China. CONCLUSIONS: S. aureus with non-classical egc enterotoxins was suggested to be a potential cause of SFP in humans.
Subject(s)
Staphylococcal Food Poisoning , Staphylococcal Infections , Humans , Enterotoxins/genetics , Staphylococcus aureus/genetics , Staphylococcal Infections/epidemiology , Staphylococcal Food Poisoning/epidemiology , Staphylococcal Food Poisoning/genetics , Staphylococcal Food Poisoning/microbiology , Multigene Family , Disease Outbreaks , Food MicrobiologyABSTRACT
Background: Sulfur microbial diet (SMD), related to the enrichment of sulfur-metabolizing gut bacteria, has been confirmed to be linked to an elevated risk of early-onset colorectal adenoma in young females. However, it remains unclear whether SMD is associated with the risk of colorectal adenoma in older people, who are at greater risk for colorectal cancer. Methods: All data on participants in this study were retrieved from the intervention arm of the Prostate, Lung, Colorectal, and Ovarian (PLCO) cancer screening test. Participants' adherence to this dietary pattern was assessed using SMD score. Hazard ratios (HR) and 95% confidence intervals (CI) were adopted in Cox proportional hazards regression models to assess the link between SMD score and the incidence of colorectal adenoma in participants included in the study. Specific stratified analyses were constructed to assess whether this association changed in different conditions, whereas the robustness of the association was examined through sensitivity analyses. Results: The mean baseline age of participants was 62.1 (SD 5.2) years (range 54.0-75.0 years). During 19,468,589 person-years of follow-up, 992 colorectal adenoma cases were documented in a total of 17,627 included participants. In a fully adjusted model, an increased risk of colorectal adenoma was determined in participants in the highest quartile of SMD score in comparison with those in the lowest quartile (HRquartile4 vs. HRquartile1 = 1.23; 95% CI: 1.02, 1.47; p = 0.017 for trend). This positive association between SMD score and adenoma risk was more evident in participants who were current or former smokers (p = 0.029 for interaction). Conclusion: In this study, our results support a role for the SMD in the carcinogenicity of colorectal cancer precursors among older adults. Nevertheless, these results require validation through more research.
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The microbial community assembly processes and underlying mechanisms in response to heavy metal accumulation in coastal sediments remain underexplored. In this study, the heavy metal concentration in samples were found below the marine sediment quality standards. Through partial Mantel tests and linear regression analysis, Cd was identified as the major influencing factor, displaying strongest correlation with the bacterial community in the sediments. The class Desulfuromonadia was identified as a biomarker which showed enrichment in the sediments with high Cd content. Additionally, the results of null model and the neutral community model demonstrated the prominent role of stochastic processes in the assembly of bacterial community. However, with the increase in Cd concentration, the influence of selection processes intensified, resulting in a decline in species migration rate and subsequent reduction in ecological niche width. Furthermore, the intensified competition and an increase in keystone species among bacterial populations further enhanced the stability of the microbial co-occurrence network in response to high Cd concentration. This study offers an insight into the effects of heavy metal on microbial assembly and coexistence, which are conducive to marine ecosystem management and conservation.
Subject(s)
Cadmium , Microbiota , Geologic Sediments , Linear Models , Microbial ConsortiaABSTRACT
Elucidating the cellular organization of the cerebral cortex is critical for understanding brain structure and function. Using large-scale single-nucleus RNA sequencing and spatial transcriptomic analysis of 143 macaque cortical regions, we obtained a comprehensive atlas of 264 transcriptome-defined cortical cell types and mapped their spatial distribution across the entire cortex. We characterized the cortical layer and region preferences of glutamatergic, GABAergic, and non-neuronal cell types, as well as regional differences in cell-type composition and neighborhood complexity. Notably, we discovered a relationship between the regional distribution of various cell types and the region's hierarchical level in the visual and somatosensory systems. Cross-species comparison of transcriptomic data from human, macaque, and mouse cortices further revealed primate-specific cell types that are enriched in layer 4, with their marker genes expressed in a region-dependent manner. Our data provide a cellular and molecular basis for understanding the evolution, development, aging, and pathogenesis of the primate brain.
Subject(s)
Cerebral Cortex , Macaca , Single-Cell Analysis , Transcriptome , Animals , Humans , Mice , Cerebral Cortex/cytology , Cerebral Cortex/metabolism , Macaca/metabolism , Transcriptome/geneticsABSTRACT
BACKGROUND: Despite the possible contribution of dairy products to the development or prevention of cancers, there is a lack of epidemiological evidence linking low-fat dairy consumption to the risk of developing lung cancer. This research was conducted to fill this knowledge gap. METHODS: The data for this research were collected from the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial. The Cox proportional risk model was employed to evaluate the link between low-fat dairy consumption and the risk of developing lung cancer. Hazard ratios (HRs) and 95% confidence intervals (CIs) were measured in both unadjusted and adjusted models. A series of predefined subgroup analyses were performed to identify potential effect modifiers, and several sensitivity analyses were conducted to assess the stability of the findings. RESULTS: The study included data from 98,459 individuals. During a total of 869,807.9 follow-up person-years, 1642 cases of lung cancer were observed, with an incidence of 0.189 cases for every 100 person-years. In the fully adjusted model, participants in the highest quartile of low-fat dairy consumption had a significantly decreased risk of lung cancer compared to the ones in the lowest quartile (HRquartile 4 vs. 1 : 0.769, 95% CI: 0.664, 0.891, ptrend = 0.005). The restricted cubic spline plot revealed an inverse nonlinear dose-response relationship between low-fat dairy consumption and lung cancer risk (pnonlinearity = 0.008). Subgroup analyses demonstrated that the inverse association was stronger among participants with higher daily caloric intake (pinteraction = 0.031). Various sensitivity analyses produced consistent results. CONCLUSION: Consuming more low-fat dairy products is significantly linked to a reduced risk of developing lung cancer, indicating that an appropriate increase in the use of low-fat dairy products may help prevent lung cancer.
Subject(s)
Dairy Products , Lung Neoplasms , Male , Humans , Prospective Studies , Risk Factors , Dairy Products/adverse effects , Diet, Fat-Restricted , Lung Neoplasms/epidemiology , Lung Neoplasms/etiology , Lung Neoplasms/prevention & controlABSTRACT
Background: Dietary approaches to stop hypertension (DASH) eating pattern is linked to anti-inflammatory responses and antioxidation, which overlap with the pathogenesis of lung cancer. However, there is insufficient epidemiological evidence to link this dietary pattern to lung cancer risk conclusively. Aim: To determine if adherence to the DASH diet is linked to a lower risk of developing lung cancer in a large prospective study. Methodology: The data of participants were retrieved from the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial. A DASH score was calculated based on 8 dietary components to reflect adherence to DASH, with greater scores representing higher adherence. Three Cox proportional hazards models were constructed to analyze the association between DASH scores and lung cancer risk, including an unadjusted model and two adjusted models (model 1 for demographics and model 2 for fully confounding factors). A restricted cubic spline plot was utilized to illustrate the likelihood of developing lung cancer across the entire range of DASH scores. The association between each of the 8 DASH components and the risk of lung cancer was assessed separately. Several subgroup analyses were conducted to identify potential modifiers, and several sensitivity analyses were performed to verify the robustness of the findings. Results: The study involved 98,459 individuals in total. The mean (standard deviation) DASH score was 24.00 (4.62) points, along with the mean follow-up period of 8.84 (1.94) years. Lung cancer was identified in 1642 cases over 869807.9 person-years of follow-up, and the overall incidence rate was 0.189 cases/100 person-years. Participants in the highest quartile in the fully adjusted model had a relatively decreased risk of developing lung cancer in comparison to those in the lowest quartile (HRquartile 4 versus 1: 0.647; 95% CI: 0.557, 0.752; Ptrend < 0.001). The restricted cubic spline plot demonstrated that DASH score and lung cancer risk were inversely associated and had a linear dose-response relationship (Pnon-linear = 0.944). According to subgroup analyses, those who were current or former smokers had a stronger inverse connection than those who never smoked (Pinteraction = 0.013). The results remained robust after several sensitivity analyses. Conclusion: The risk of lung cancer was inversely associated with DASH scores in the US population. This suggests that following the DASH pattern can help prevent lung cancer, especially for current or former smokers. More epidemiological evidence from other regions and populations is needed to confirm our findings.
ABSTRACT
This study investigates the role and mechanisms by which the myokine musclin promotes exercise-induced cardiac conditioning. Exercise is one of the most powerful triggers of cardiac conditioning with proven benefits for healthy and diseased hearts. There is an emerging understanding that muscles produce and secrete myokines, which mediate local and systemic "crosstalk" to promote exercise tolerance and overall health, including cardiac conditioning. The myokine musclin, highly conserved across animal species, has been shown to be upregulated in response to physical activity. However, musclin effects on exercise-induced cardiac conditioning are not established. Following completion of a treadmill exercise protocol, wild type (WT) mice and mice with disruption of the musclin-encoding gene, Ostn, had their hearts extracted and exposed to an ex vivo ischemia-reperfusion protocol or biochemical studies. Disruption of musclin signaling abolished the ability of exercise to mitigate cardiac ischemic injury. This impaired cardioprotection was associated with reduced mitochondrial content and function linked to blunted cyclic guanosine monophosphate (cGMP) signaling. Genetic deletion of musclin reduced the nuclear abundance of protein kinase G (PKGI) and cyclic adenosine monophosphate (cAMP) response element binding (CREB), resulting in suppression of the master regulator of mitochondrial biogenesis, peroxisome proliferator-activated receptor γ coactivator 1α (PGC1α), and its downstream targets in response to physical activity. Synthetic musclin peptide pharmacokinetic parameters were defined and used to calculate the infusion rate necessary to maintain its plasma level comparable to that observed after exercise. This infusion was found to reproduce the cardioprotective benefits of exercise in sedentary WT and Ostn-KO mice. Musclin is essential for exercise-induced cardiac protection. Boosting musclin signaling might serve as a novel therapeutic strategy for cardioprotection.