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.

Manganese sulfide-sulfur and limestone autotrophic denitrification system for deep and efficient nitrate removal: Feasibility, performance and mechanism.

Despite the great potential of sulfur-based autotrophic denitrification, an improvement in nitrate removal rate is still needed. This study used the desulfurized products of Mn ore to develop the MnS-S0-limestone autotrophic denitrification system (MSLAD). The feasibility of MSLAD for denitrification was explored and the possible mechanism was proposed. The nitrate (100 mg/L) was almost removed within 24 h in batch experiment in MSLAD. Also, an average TN removal of 98 % (472.0 mg/L/d) at hydraulic retention time of 1.5 h in column experiment (30 mg/L) was achieved. MnS and S0 could act as coupled electron donors and show synergistic effects for nitrate removal. γ-MnS with smaller particle size and lower crystallinity was more readily utilized by the bacterium and had higher nitrate removal efficiency than that of α-MnS. Thiobacillus and Sulfurimonas were the core functional bacterium in denitrification. Therefore, MnS-S0-limestone bio-denitrification provides an efficient alternative method for nitrate removal in wastewater.

Germline Cas9 promoters with improved performance for homing gene drive.

Gene drive systems could be a viable strategy to prevent pathogen transmission or suppress vector populations by propagating drive alleles with super-Mendelian inheritance. CRISPR-based homing gene drives convert wild type alleles into drive alleles in heterozygotes with Cas9 and gRNA. It is thus desirable to identify Cas9 promoters that yield high drive conversion rates, minimize the formation rate of resistance alleles in both the germline and the early embryo, and limit somatic Cas9 expression. In Drosophila, the nanos promoter avoids leaky somatic expression, but at the cost of high embryo resistance from maternally deposited Cas9. To improve drive efficiency, we test eleven Drosophila melanogaster germline promoters. Some achieve higher drive conversion efficiency with minimal embryo resistance, but none completely avoid somatic expression. However, such somatic expression often does not carry detectable fitness costs for a rescue homing drive targeting a haplolethal gene, suggesting somatic drive conversion. Supporting a 4-gRNA suppression drive, one promoter leads to a low drive equilibrium frequency due to fitness costs from somatic expression, but the other outperforms nanos, resulting in successful suppression of the cage population. Overall, these Cas9 promoters hold advantages for homing drives in Drosophila species and may possess valuable homologs in other organisms.

Polygonatum sibiricum polysaccharide ameliorates skeletal muscle aging via mitochondria-associated membrane-mediated calcium homeostasis regulation.

BACKGROUND: Sarcopenia, an age-related disease, is characterized by a gradual loss of muscle mass, strength, and function. It has been linked to abnormal organelle function in myotubes, including the mitochondria and endoplasmic reticulum (ER). Recent studies revealed that mitochondria-associated membranes (MAM), the sites connecting mitochondria and the ER, may be implicated in skeletal muscle aging. In this arena, the potential of Polygonatum sibiricum polysaccharide (PSP) emerges as a beacon of hope. PSP, with its remarkable antioxidant and anti-senescence properties, is on the cusp of a therapeutic revolution, offering a promising strategy to mitigate the impacts of sarcopenia. PURPOSE: The objective of this research is to explore the effects of PSP on age-related muscle dysfunction and the underlying mechanisms involved both in vivo and in vitro. METHODS: In this investigation, we used in vitro experiments using D-galactose (D-gal)-induced aging in C2C12 myotubes and in vivo experiments on aged mice. Key indices were assessed, including reactive oxygen species (ROS) levels, mitochondrial function, the expression of aging-related markers, and the key proteins of mitochondria and MAM fraction. Differentially expressed genes (DEGs) related to mitochondria and ER were identified, and bioinformatic analyses were performed to explore underlying mechanisms. Muscle mass and function were determined to evaluate the quantity and quality of skeletal muscle in vivo. RESULTS: PSP treatment effectively mitigated oxidative stress and mitochondrial malfunction caused by D-gal in C2C12 myotubes, preserving mitochondrial fitness and reducing MAM formation. Besides, PSP attenuated D-gal-induced increases in Ca2+ concentrations intracellularly by modulating the calcium-related proteins, which were also confirmed by gene ontology (GO) analysis of DEGs. In aged mice, PSP increased muscle mass and improved grip strength, hanging time, and other parameters while reducing ROS levels and increasing antioxidant enzyme activities in skeletal muscle tissue. CONCLUSION: PSP offers protection against age-associated muscle impairments. The proposed mechanism suggests that modulation of calcium homeostasis via regulation of the MAM results in a favorable functional outcome during skeletal muscle aging. The results of this study highlight the prospect of PSP as a curative intervention for sarcopenia and affiliated pathological conditions, warranting further investigation.

A small-molecule approach to restore female sterility phenotype targeted by a homing suppression gene drive in the fruit pest Drosophila suzukii.

CRISPR-based gene drives offer promising prospects for controlling disease-transmitting vectors and agricultural pests. A significant challenge for successful suppression-type drive is the rapid evolution of resistance alleles. One approach to mitigate the development of resistance involves targeting functionally constrained regions using multiple gRNAs. In this study, we constructed a 3-gRNA homing gene drive system targeting the recessive female fertility gene Tyrosine decarboxylase 2 (Tdc2) in Drosophila suzukii, a notorious fruit pest. Our investigation revealed only a low level of homing in the germline, but feeding octopamine restored the egg-laying defects in Tdc2 mutant females, allowing easier line maintenance than for other suppression drive targets. We tested the effectiveness of a similar system in Drosophila melanogaster and constructed additional split drive systems by introducing promoter-Cas9 transgenes to improve homing efficiency. Our findings show that genetic polymorphisms in wild populations may limit the spread of gene drive alleles, and the position effect profoundly influences Cas9 activity. Furthermore, this study highlights the potential of conditionally rescuing the female infertility caused by the gene drive, offering a valuable tool for the industrial-scale production of gene drive transgenic insects.

Predictive value of Global Leadership Initiative on Malnutrition criteria combined with handgrip strength for postoperative outcomes in overweight colorectal cancer patients.

BACKGROUND AND AIM: The Global Leadership Initiative on Malnutrition (GLIM) criteria are increasingly used to assess the nutritional status of hospitalized patients and predict the prognosis of patients with malignant tumors; however, malnutrition is often overlooked in overweight individuals, such as colorectal cancer patients. This study aimed to investigate the predictive value of the GLIM criteria combined with handgrip strength (HGS) in overweight colorectal cancer patients. METHODS: This retrospective study enrolled overweight patients who underwent radical resection for colorectal cancer at two centers between 2015 and 2021. Malnutrition was diagnosed based on the GLIM criteria. Skeletal muscle mass was assessed using the skeletal muscle index, and skeletal muscle function was assessed using the HGS test. The risk factors for complications and survival were also evaluated. RESULTS: A total of 850 patients were enrolled in the study. The incidence of malnutrition in the GLIM and HGS-GLIM groups was 12.4% and 6.4%, respectively. The incidence of total complications in both the malnutrition groups was significantly higher than that in the control group. Patients in the HGS-GLIM-malnutrition group had worse overall survival and disease-free survival. HGS-GLIM was independently associated with postoperative complications (P = 0.046), overall survival (P = 0.037), and disease-free survival (P = 0.047). CONCLUSION: The GLIM criteria combined with the HGS test is an effective tool for diagnosing malnutrition. Particularly, these modalities are applicable in overweight colorectal cancer patients. Compared with the standard GLIM criteria, this tool has a better predictive value for postoperative complications and long-term survival.

Heterojunction-Induced Rapid Transformation of Ni3+/Ni2+ Sites which Mediates Urea Oxidation for Energy-Efficient Hydrogen Production.

Water electrolysis is an environmentally-friendly strategy for hydrogen production but suffers from significant energy consumption. Substituting urea oxidation reaction (UOR) with lower theoretical voltage for water oxidation reaction adopting nickel-based electrocatalysts engenders reduced energy consumption for hydrogen production. The main obstacle remains strong interaction between accumulated Ni3+ and *COO in the conventional Ni3+-catalyzing pathway. Herein, a novel Ni3+/Ni2+ mediated pathway for UOR via constructing a heterojunction of nickel metaphosphate and nickel telluride (Ni2P4O12/NiTe), which efficiently lowers the energy barrier of UOR and avoids the accumulation of Ni3+ and excessive adsorption of *COO on the electrocatalysts, is developed. As a result, Ni2P4O12/NiTe demonstrates an exceptionally low potential of 1.313 V to achieve a current density of 10 mA cm-2 toward efficient urea oxidation reaction while simultaneously showcases an overpotential of merely 24 mV at 10 mA cm-2 for hydrogen evolution reaction. Constructing urea electrolysis electrolyzer using Ni2P4O12/NiTe at both sides attains 100 mA cm-2 at a low cell voltage of 1.475 V along with excellent stability over 500 h accompanied with nearly 100% Faradic efficiency.

Clinical impact of sarcopenia for overweight or obese patients with colorectal cancer.

BACKGROUND: Sarcopenia, overweight and obesity are all dynamic changes in body composition, which may have a negative effect on the prognosis for patients with colorectal cancer. The aim of this study was to investigate the predictive role of sarcopenia on overweight or obese patients with colorectal cancer. METHODS: We conducted an observative study on the population of overweight or obese patients with colorectal cancer who underwent curative surgeries in two centers between 2015 and 2021. They were grouped by the presence of sarcopenia. Propensity score match analysis was used to balance the baseline of clinicopathologic characteristics of the two groups. Then, the postoperative outcomes between the two groups were compared. Independent risk factors were evaluated for complications using univariate and multivariate analysis. RESULTS: Of 827 patients enrolled, 126 patients were matched for analysis. Patients with sarcopenia had a higher incidence of total complication and medical complications, a higher rate of laparoscopic surgery performed and higher hospitalization costs. Old age (≥65 years, P = 0.012), ASA grade (III, P = 0.008) and sarcopenia (P = 0.036) were independent risk factors for total complications. ASA grade (III, P = 0.002) and sarcopenia (P = 0.017) were independent risk factors for medical complications. CONCLUSIONS: Sarcopenia was prevalent among overweight or obese patients with colorectal cancer and was associated with negative postoperative outcomes. Early recognition of changes in body composition could help surgeons be well prepared for surgical treatment for overweight or obese patients.

Establishment and validation of novel nomograms to predict muscle quality in colorectal cancer patients.

OBJECTIVES: The skeletal muscle mass index and skeletal muscle radiodensity have promise as specific diagnostic indicators for muscle quality. However, the difficulties in measuring low skeletal muscle mass index and low skeletal muscle radiodensity limit their use in routine clinical practice, impeding early screening and diagnosis. The objective of this study is to develop a nomogram that incorporates preoperative factors for predicting low skeletal muscle mass index and low skeletal muscle radiodensity. METHODS: A total of 1692 colorectal cancer patients between 2015 and 2021 were included. The patients were randomly divided into a training cohort (n = 1353) and a validation cohort (n = 339). Nomogram models were calibrated using the area under the curve, calibration curves, and the Hosmer-Lemeshow test to assess their predictive ability. Finally, a decision curve was applied to assess the clinical usefulness. RESULTS: In a prediction model for low skeletal muscle mass index, age, body mass index, and grip strength were incorporated as variables. For low skeletal muscle radiodensity, age, sex, body mass index, serum hemoglobin level, and grip strength were included as predictors. In the training cohort, the area under the curve value for low skeletal muscle mass index was 0.750 (95% CI, 0.726-0.773), whereas for low skeletal muscle radiodensity, it was 0.763 (95% CI, 0.739-0.785). The Hosmer-Lemeshow test confirmed that both models fit well in both cohorts. Decision curve analysis was applied to assess the clinical usefulness of the model. CONCLUSIONS: The incorporation of preoperative factors into the nomogram-based prediction model represents a significant advancement in the muscle quality assessment. Its implementation has the potential to early screen patients at risk of low skeletal muscle mass index and low skeletal muscle radiodensity.

Effect of perioperative airway management on postoperative outcomes of colorectal cancer patients with sarcopenia.

BACKGROUND: It is common for colorectal cancer patients to have sarcopenia as a comorbidity, which has been shown to have a negative impact on prognosis after surgery. This study explored whether implementing a novel care program could improve postoperative outcomes in colorectal cancer patients with sarcopenia. METHODS: We retrospectively analyzed the clinical data of patients diagnosed with sarcopenia before undergoing radical colorectal cancer surgery. We divided the patients into two groups according to the time point of program implementation and, compared the clinical characteristics and postoperative outcomes of these two groups. RESULTS: A total of 227 patients were included in the study. The baseline clinical characteristics of the two groups were similar. Compared with the control group, patients in the implementation group had a significantly lower rate of total complications (18.5% vs. 30.3%, P = 0.041), a significantly lower rate of pulmonary complications (2.8% vs. 10.9%, P = 0.017), and a significantly shorter postoperative hospital stay (12 days vs. 14 days, P = 0.001). Implementation of perioperative airway management (P = 0.018) was shown to be a protective factor against pulmonary complications in colorectal cancer patients with sarcopenia. CONCLUSION: The perioperative airway management program implemented at our center was easy to perform and can effectively improve short-term postoperative outcomes in colorectal cancer patients with sarcopenia.

Beneficial Effects of Bacillus amyloliquefaciens D1 Soy Milk Supplementation on Serum Biochemical Indexes and Intestinal Health of Bearded Chickens.

This study investigated the effects of dietary supplementation with Bacillus amyloliquefaciens D1 (B. amyloliquefaciens D1) on growth performance, serum anti-inflammatory cytokines, and intestinal microbiota composition and diversity in bearded chickens. To investigate the effects of Bacillus amyloliquefaciensa and fermented soy milk, 7-day-old broilers were orally fed different doses of Bacillus amyloliquefaciens D1 fermented soy milk for 35 days, with the unfermented soy milk group as the Placebo group. This study found that B. amyloliquefaciens D1 fermented soy milk improved the intestinal microbiota of broilers, significantly increasing the abundance of beneficial bacteria and decreasing the abundance of harmful bacteria in the gut. B. amyloliquefaciens D1 fermented soy milk also significantly reduced the serum lipopolysaccharide (LPS) content. The body weight and daily weight gain of broilers were increased. In conclusion, the results of this study are promising and indicate that supplementing the diets of bearded chickens with B. amyloliquefaciens D1 fermented soy milk has many beneficial effects in terms of maintaining intestinal microbiota balance and reducing inflammation in chickens.

Identification of a novel immune-related transcriptional regulatory network in sarcopenia.

BACKGROUND: Sarcopenia is highly prevalent in elderly individuals and has a significant adverse effect on their physical health and quality of life, but the mechanisms remain unclear. Studies have indicated that transcription factors (TFs) and the immune microenvironment play a vital role in skeletal muscle atrophy. METHODS: RNA-seq data of 40 muscle samples were downloaded from the GEO database. Then, differentially expressed genes (DEGs), TFs(DETFs), pathways(DEPs), and the expression of immune gene sets were identified with limma, edgeR, GO, KEGG, ORA, GSVA, and ssGSEA. Furthermore, the results above were integrated into coexpression analysis by Pearson correlation analysis (PCA). Significant coexpression patterns were used to construct the immune-related transcriptional regulatory network by Cytoscape and potential medicine targeting the network was screened by Connectivity Map. Finally, the regulatory mechanisms and RNA expression of DEGs and DETFs were identified by multiple online databases and RT‒qPCR. RESULTS: We screened 808 DEGs (log2 fold change (FC) > 1 or < - 1, p < 0.05), 4 DETFs (log2FC > 0.7 or < - 0.7, p < 0.05), 304 DEPs (enrichment scores (ES) > 1 or < - 1, p < 0.05), and 1208 differentially expressed immune genes sets (DEIGSs) (p < 0.01). Based on the results of PCA (correlation coefficient (CC) > 0.4 or < - 0.4, p < 0.01), we then structured an immune-related network with 4 DETFs, 9 final DEGs, 11 final DEPs, and 6 final DEIGSs. Combining the results of online databases and in vitro experiments, we found that PAX5-SERPINA5-PI3K/Akt (CC ≤ 0.444, p ≤ 0.004) was a potential transcriptional regulation axis, and B cells (R = 0.437, p = 0.005) may play a vital role in this signal transduction. Finally, the compound of trichostatin A (enrichment = -0.365, specificity = 0.4257, p < 0.0001) might be a potential medicine for sarcopenia based on the PubChem database and the result of the literature review. CONCLUSIONS: We first identified immune-related transcriptional regulatory network with high-throughput RNA-seq data in sarcopenia. We hypothesized that PAX5-SERPIAN5-PI3K/Akt axis is a potential mechanism in sarcopenia and that B cells may play a vital role in this signal transduction. In addition, trichostatin A might be a potential medicine for sarcopenia.

A novel insight into the key gene signature associated with the immune landscape in the progression of sarcopenia.

Sarcopenia is an age-related skeletal muscle disorder that causes falls, disability and death in the elderly, but its exact mechanism remains unknown. In this study, we merged three GEO datasets into the expression profiles of 118 samples and screened 22 differentially expressed genes (DEGs) as candidate genes. Pathway analysis demonstrated that the functional enrichment of DEGs is mainly in the cellular response to insulin stimulus, PPAR signaling pathway and other metabolism-related pathways. Then, we identified six key genes by machine learning, which were confirmed to be closely associated with sarcopenia by bioinformatics analysis. It was experimentally verified that SCD1 exhibits the most substantial alterations in the progression of sarcopenia with disturbed lipid metabolism and myosteatosis. In addition, the immune microenvironment of sarcopenia was found to be affected by these key genes, with Th17 cells down-regulated and NK cells up-regulated. Sarcopenic patients consequently presented a more significant systemic inflammatory state with higher CAR (p = 0.028) and PAR (p = 0.018). For the first time, we identified key genes in sarcopenia with high-throughput data and demonstrated that key genes can regulate the progression of sarcopenia by affecting the immune microenvironment. Among them, SCD1 may influence lipid metabolism and myosteatosis process. Screening of key genes and analyzing of immune microenvironment provide a more accurate target for treating sarcopenia.

Hollow-Particles Quasi-Solid-State Electrolytes with Biomimetic Ion Channels for High-Performance Lithium-Metal Batteries.

Solid-state electrolytes (SSEs) are the core material of solid-state lithium metal batteries (SLMBs), which are being researched urgently owing to their high energy and safety. Both high ionic conductivity and excellent cycling stability remain the primary goal of solid-state electrolytes. Herein, inspired by K+ /Na+ ion channels in cell membrane of eukaryotes, a novel hollow UiO-66 with biomimetic ion channels based on quasi-solid-state electrolytes (QSSEs) is designed. The hollow UiO-66 spheres containing biomimetic ion channels can spontaneously combine anions and incorporate more lithium ions, creating improved ionic conductivity (1.15 × 10-3 S cm-1 ) and lithium-ion transference number (0.70) at room temperature. The long-term cycling of symmetric batteries and COMSOL simulations demonstrate that this biomimetic strategy enables uniform ion flux to suppress Li dendrites. Furthermore, the Li metal full cells paired with LiFePO4 cathode exhibit excellent cycling stability and rate performance. Consequently, the strategy of designing biomimetic QSSEs opens up a new path for developing high-performance electrolytes for SLMBs.

Comparison of laparoscopic and open radical gastrectomy for gastric cancer patients with GLIM-defined malnutrition.

PURPOSE: Malnutrition is common in the patients with gastric cancer. Radical gastrectomy remained the primary strategy of curable treatment for gastric cancer. This study is performed to explore the effect of laparoscopic radical gastrectomy on clinical outcomes in gastric cancer patients with malnutrition. METHODS: Gastric cancer patients with GLIM-defined malnutrition between 2014 and 2019 at our center were enrolled. The patients were divided into two groups according to the different type of surgery. Propensity score match analysis was used to balance the clinicopathologic characteristics of two groups. Postoperative outcomes and survival were compared. Multivariate analysis was used to independent risk factors of complication, overall survival (OS), and disease-free survival (DFS). RESULTS: Compared with patients underwent open radical gastrectomy, patients who underwent laparoscopic radical gastrectomy had lower rate of total, surgical and severe complications. They also had shorter postoperative hospital stay with better OS and DFS. Hypoalbuminemia (P = 0.003) was the independent risk factor of complications. Old age (≥75, P = 0.035) and TNM stage (III: P < 0.001, II: P = 0.015) were the independent risk factors of OS. Combined resection (P = 0.003) and TNM stage (III: P < 0.001, II: P = 0.001) posed independent risk factors of lacking DFS. Laparoscopic surgery proved to be the independent protective factor of complications (P = 0.014), OS (P < 0.001) and DFS (P < 0.001). CONCLUSION: Laparoscopic radical gastrectomy was relative safe and showed favorable outcomes in malnourished gastric cancer patients.

Isolation and Purification of Bacillus amyloliquefaciens D1 Protease and Its Application in the Fermentation of Soybean Milk to Produce Large Amounts of Free Amino Acids.

In this study, a strain of Bacillus amyloliquefaciens D1, with a notably high production of neutral protease, was isolated from Morchella crassipes. The protease was purified to 10.4-fold with a specific activity of 4542.9 U/mg and 2.7% recovery. The enzyme was purified by 70% (NH4)2SO4 and DEAE-Cellulose-52 column. The estimated molecular mass of the purified protease obtained by SDS-PAGE was approximately 40 kDa. The enzyme was optimally active at pH 6.0 and 50 °C. Furthermore, the maximum hydrolysis rate (Vmax) and apparent Michaelis-Menten constant (Km) values of the purified protease were 8.2 mg/mL and 65.7 µg/(min mL). The enzymatic properties and rapid and efficient purification of Bacillus amyloliquefaciens D1 provide the basis for its potential commercialization and industrial development. Moreover, more essential amino acids, such as isoleucine, leucine, and phenylalanine, would be released when the strain fermented soybean milk, and then a better amino acid profile would be formed in soybean milk. Results suggest that this strain exhibits great potential in fermented soybean milk, and the enzyme could lay a foundation for its industrial application and further research.

Ginsenoside Rb1 Prevents Oxidative Stress-Induced Apoptosis and Mitochondrial Dysfunction in Muscle Stem Cells via NF-κB Pathway.

Sarcopenia, featured by the progressive loss of skeletal muscle function and mass, is associated with the impaired function of muscle stem cells (MuSCs) caused by increasing oxidative stress in senescent skeletal muscle tissue during aging. Intact function of MuSCs maintains the regenerative potential as well as the homeostasis of skeletal muscle tissues during aging. Ginsenoside Rb1, a natural compound from ginseng, exhibited the effects of antioxidation and against apoptosis. However, its effects of restoring MuSC function during aging and improving age-related sarcopenia remained unknown. In this study, we investigated the role of Rb1 in improving MuSC function and inhibiting apoptosis by reducing oxidative stress levels. We found that Rb1 inhibited the accumulation of reactive oxygen species (ROS) and protected the cells from oxidative stress to attenuate the H2O2-induced cytotoxicity. Rb1 also blocked oxidative stress-induced apoptosis by inhibiting the activation of caspase-3/9, which antagonized the decrease in mitochondrial content and the increase in mitochondrial abnormalities caused by oxidative stress via promoting the protein expression of genes involved in mitochondrial biogenesis. Mechanistically, it was proven that Rb1 exerted its antioxidant effects and avoided the apoptosis of myoblasts by targeting the core regulator of the nuclear factor-kappa B (NF-κB) signal pathway. Therefore, these findings suggest that Rb1 may have a beneficial role in the prevention and treatment of MuSC exhaustion-related diseases like sarcopenia.

Mutagenesis and Resistance Development of Bacteria Challenged by Silver Nanoparticles.

Because of their extremely broad spectrum and strong biocidal power, nanoparticles of metals, especially silver (AgNPs), have been widely applied as effective antimicrobial agents against bacteria, fungi, and so on. However, the mutagenic effects of AgNPs and resistance mechanisms of target cells remain controversial. In this study, we discover that AgNPs do not speed up resistance mutation generation by accelerating genome-wide mutation rate of the target bacterium Escherichia coli. AgNPs-treated bacteria also show decreased expression in quorum sensing (QS), one of the major mechanisms leading to population-level drug resistance in microbes. Nonetheless, these nanomaterials are not immune to resistance development by bacteria. Gene expression analysis, experimental evolution in response to sublethal or bactericidal AgNPs treatments, and gene editing reveal that bacteria acquire resistance mainly through two-component regulatory systems, especially those involved in metal detoxification, osmoregulation, and energy metabolism. Although these findings imply low mutagenic risks of nanomaterial-based antimicrobial agents, they also highlight the capacity for bacteria to evolve resistance.

Coexistence of GLIM-defined malnutrition and sarcopenia have negative effect on the clinical outcomes in the elderly gastric cancer patients after radical gastrectomy.

Background: Malnutrition and sarcopenia are common in elderly gastric cancer patients, which are also interrelated and affect each other. We aimed to determine the characteristics of coexistence of malnutrition and sarcopenia in the elderly gastric cancer patients and investigate the predictive roles of malnutrition and sarcopenia on clinical outcomes. Methods: Between 2014 and 2019, a total of 742 elderly gastric cancer patients were enrolled. Malnutrition and sarcopenia were diagnosed according to the most recent diagnostic criteria. Patients were divided into four groups according to presence of these two symptoms. Clinical characteristics, short- and long-term outcomes were compared among four groups. The independent risk factors for complications and survival were evaluated using univariate and multivariate analyses. Results: Of all patients, 34.8% were diagnosed with malnutrition and 34.0% were diagnosed with sarcopenia. Patients with both malnutrition and sarcopenia had the highest rate of total (P < 0.001), surgical (P = 0.003), and medical complications (P = 0.025), and the highest postoperative hospital stays (P < 0.001) and hospitalization costs (P < 0.001). They also had the worst overall survival (P < 0.0001) and disease-free survival (P < 0.0001). Sarcopenia and Charlson Comorbidity Index (≥2) were independent risk factors for total complications. Hypoalbuminemia and malnutrition were non-tumor-related independent risk factors for overall survival and disease-free survival. Conclusions: Malnutrition and sarcopenia had superimposed negative effects on elderly gastric cancer patients. Preoperative geriatric evaluation including screening for malnutrition and sarcopenia are recommended for all elderly gastric cancer patients for accurate treatment strategy.

Prognostic significance of postoperative loss of skeletal muscle mass in patients underwent coronary artery bypass grafting.

Background: Increasing life expectancy of coronary artery bypass grafting (CABG) remains to be the major concern of cardiac surgeons. However, few studies have investigated the effect of postoperative skeletal muscle index (SMI) loss on prognosis. This study aims to evaluate the prognostic role of postoperative SMI loss ≥ 5% after CABG, in order to develop a novel nomogram to predict overall survival (OS). Methods: Patients underwent CABG via midline sternotomy from December 2015 to March 2021 were recruited in this study. Preoperative and postoperative 3 months chest computed tomography (CT) images were compared to assess changes in SMI at T12 level. Based on this, patients were classified into the presence or absence of SMI loss ≥ 5%. The association between postoperative SMI loss ≥ 5% and OS was then analyzed by the Kaplan-Meier curves and Cox model. A novel nomogram incorporating independent clinical prognostic variables was also developed. Results: The study enrolled 506 patients receiving CABG, of whom 98 patients experienced T12 SMI loss ≥ 5% and had a significantly worse OS (P < 0.0001). Multivariate regression analysis showed that T12 SMI per cent change (%T12 SMI-change) was an independent prognostic factor for OS (HR = 0.809, 95% CI = 0.749-0.874). The nomogram incorporating %T12 SMI-change with other variables was accurate for predicting OS. Besides, we also found that postoperative oral nutritional supplement (ONS) can rescue T12 SMI loss. Conclusion: Postoperative SMI loss can predict survival outcome after CABG. The nomogram incorporating changes in SMI provides a superior performance than existing systems.