CircRNA circRREB1 promotes tumorigenesis and progression of breast cancer by activating Erk1/2 signaling through interacting with GNB4.

Current investigations have illuminated the essential roles played by circular RNAs (circRNAs) in driving breast cancer (BC) tumorigenesis. However, the functional implications and molecular underpinnings of most circRNAs in BC are not well characterized. Here, Circular RNA (circRNA) expression profiles were analyzed in four surgically resected BC cases along with adjacent non-cancerous tissues applying RNA microarray analysis. The levels and prognostic implications of circRREB1 in BC were subjected to quantitative real-time PCR (qRT-PCR) and in situ hybridization (ISH). Experimental manipulation of circRREB1 levels in both in vivo and in vitro settings further delineated its role in BC cell growth, invasion, and metastasis. The mechanical verification of circRREB1's interaction with GNB4 was established through RNA pull-down, mass spectrometry, Western blot analysis, RNA immunoprecipitation assays (RIP), fluorescence ISH (FISH), and rescue experiments. We found that circRREB1 exhibited significant upregulation in BC tissues and cells, implicating its association with an unfavorable prognosis in BC patients. CircRREB1 knockdown elicited anti-proliferative, anti-migratory, anti-invasive, and pro-apoptotic effects in BC cells, whereas its upregulation exerted opposing influences. Follow-up mechanistic examinations suggested that circRREB1 might interact with GNB4 directly, inducing the activation of Erk1/2 signaling and driving BC progression. Our findings collectively indicate that the interplay of circRREB1 with GNB4 promotes Erk1/2 signaling, thereby fostering BC progression, and positioning circRREB1 as a candidate therapeutic target for intervention in BC.

Effects of sleep disturbance, cancer-related fatigue, and psychological distress on breast cancer patients' quality of life: a prospective longitudinal observational study.

More attention has gone to researching the cancer-related fatigue (CRF)-sleep disturbance (SD)-psychological distress (PD) symptom cluster in breast cancer patients during the chemotherapy period, but the change trend and heterogeneous development track in the whole treatment stage remain unclear, and it is also unclear whether the appearance of and changes in one symptom cause changes in other symptoms and quality of life (QoL). This study, using breast cancer patients' data collected through a validated questionnaire, examined the relationships between SD, CRF, PD, and QoL using latent growth modeling analyses. CRF developmental trajectories showed an upward trend over five surveys (slope = 0.649, P < 0.001); PD showed a significant weakening trend (slope = - 0.583, P < 0.001); SD showed an increasing trend (slope = 0.345, P < 0.001), and QoL showed a statistically significant weakening trend (slope = - 0.373, P < 0.001). The initial CRF (coefficient = - 0.233, P < 0.01), PD (coefficient = - 0.296, P < 0.01), and SD (coefficient = - 0.388, P < 0.001) levels had a statistically significant negative effect on initial QoL level. The linear development rate of PD was statistically significant and negatively affected that of QoL (coefficient = - 0.305, P < 0.05), whereas the quadratic development rate of SD negatively affected that of QoL (coefficient = - 0.391, P < 0.05). Medical staff should identify the change characteristics of different variables based on SD, CRF, PD, and QoL change trajectories, and advance the intervention time, as changes in variables affect other variables' subsequent changes.

The burden and management competency of cardiomyopathies in China: a nationwide survey study.

Background: The public health burden of cardiomyopathies and competency in their management by health agencies in China are not well understood. Methods: This study adopted a multi-stage sampling method for hospital selection. In the first stage, nationwide tertiary hospital recruitment was performed. As a result, 88 hospitals with the consent of the director of cardiology and access to an established electronic medical records system, were recruited. In the second stage, we sampled 66 hospitals within each geographic-economic stratification through a random sampling process. Data on (1) the outpatient and inpatient visits for cardiomyopathies between 2017 and 2021 and (2) the competency in the management of patients with cardiomyopathies, were collected. The competency of a hospital to provide cardiomyopathy care was evaluated using a specifically devised scale. Findings: The outpatient and inpatient visits for cardiomyopathies increased between 2017 and 2021 by 38.6% and 33.0%, respectively. Most hospitals had basic facilities for cardiomyopathy assessment. However, access to more complex procedures was limited, and the integrated management pathway needs improvement. Only 4 (6.1%) of the 66 participating hospitals met the criteria for being designated as a comprehensive cardiomyopathy center, and only 29 (43.9%) could be classified as a primary cardiomyopathy center. There were significant variations in competency between hospitals with different administrative and economic levels. Interpretation: The health burden of cardiomyopathies has increased significantly between 2017 and 2021 in China. Although most tertiary hospitals in China can offer basic cardiomyopathy care, more advanced facilities are not yet universally available. Moreover, inconsistencies in the management of cardiomyopathies across hospitals due to differing administrative and economic levels warrants a review of the nation allocation of medical resources. Funding: This work was supported by the Chinese Academy of Medical Sciences (CAMS) Innovation Fund for Medical Sciences (2023-I2M-1-001) and the National High Level Hospital Clinical Research Funding (2022-GSP-GG-17).

The Emergence of Candida auris is Not Associated with Changes in Antifungal Prescription at Hospitals.

Purpose: This study describes the emergence of Candida auris in Hong Kong, focusing on the incidence and trends of different Candida species over time. Additionally, the study analyzes the relationship between C. auris and antifungal prescription, as well as the impact of outbreaks caused by C. auris. Patients and Methods: Data were collected from 43 public hospitals across seven healthcare networks (A to G) in Hong Kong, including Candida species culture and antifungal prescription information. Among 150,267 patients with 206,405 hospitalization episodes, 371,653 specimens tested positive for Candida species. Trends in Candida species and antifungal prescription were analyzed before (period 1: 2015 1Q to 2019 1Q) and after (period 2: 2019 2Q to 2023 2Q) the emergence of C. auris in Hong Kong. Results: Candida albicans was the most prevalent species, accounting for 57.1% (212,163/371,653) of isolations, followed by Candida glabrata (13.1%, 48,666), Candida tropicalis (9.2%, 34,261), and Candida parapsilosis (5.3%, 19,688). C. auris represented 2.0% of all Candida species isolations. Comparing period 2 to period 1, the trend of C. albicans remained stable, while C. glabrata, C. tropicalis, and C. parapsilosis demonstrated a slower increasing trend in period 2 than in period 1. Other species, including C. auris, exhibited a 1.1% faster increase in trend during period 2 compared to period 1. Network A, with the highest antifungal prescription, did not experience any outbreaks, while networks F and G had 40 hospital outbreaks due to C. auris in period 2. Throughout the study period, healthcare networks B to G had significantly lower antifungal prescription compared to network A, ranging from 54% to 78% less than that of network A. Conclusion: There is no evidence showing correlation between the emergence of C. auris and antifungal prescription in Hong Kong. Proactive infection control measures should be implemented to prevent nosocomial transmission and outbreak of C. auris.

Calcineurin regulates synaptic Ca2+-permeable AMPA receptors in hypothalamic presympathetic neurons via α2δ-1-mediated GluA1/GluA2 assembly.

Hypertension is a major adverse effect of calcineurin inhibitors, such as tacrolimus (FK506) and cyclosporine, used clinically as immunosuppressants. Calcineurin inhibitor-induced hypertension (CIH) is linked to augmented sympathetic output from the hypothalamic paraventricular nucleus (PVN). GluA2-lacking, Ca2+-permeable AMPA receptors (CP-AMPARs) are a key feature of glutamatergic synaptic plasticity, yet their role in CIH remains elusive. Here, we found that systemic administration of FK506 in rats significantly increased serine phosphorylation of GluA1 and GluA2 in PVN synaptosomes. Strikingly, FK506 treatment reduced GluA1/GluA2 heteromers in both synaptosomes and endoplasmic reticulum-enriched fractions from the PVN. Blocking CP-AMPARs with IEM-1460 induced a larger reduction of AMPAR-mediated excitatory postsynaptic current (AMPAR-EPSC) amplitudes in retrogradely labelled, spinally projecting PVN neurons in FK506-treated rats than in vehicle-treated rats. Furthermore, FK506 treatment shifted the current-voltage relationship of AMPAR-EPSCs from linear to inward rectification in labelled PVN neurons. FK506 treatment profoundly enhanced physical interactions of α2δ-1 with GluA1 and GluA2 in the PVN. Inhibiting α2δ-1 with gabapentin, α2δ-1 genetic knockout, or disrupting α2δ-1-AMPAR interactions with an α2δ-1 C terminus peptide restored GluA1/GluA2 heteromers in the PVN and diminished inward rectification of AMPAR-EPSCs in labelled PVN neurons induced by FK506 treatment. Additionally, microinjection of IEM-1460 or α2δ-1 C terminus peptide into the PVN reduced renal sympathetic nerve discharges and arterial blood pressure elevated in FK506-treated rats but not in vehicle-treated rats. Thus, calcineurin in the hypothalamus constitutively regulates AMPAR subunit composition and phenotypes by controlling GluA1/GluA2 interactions with α2δ-1. Synaptic CP-AMPARs in PVN presympathetic neurons contribute to augmented sympathetic outflow in CIH. KEY POINTS: Systemic treatment with the calcineurin inhibitor increases serine phosphorylation of synaptic GluA1 and GluA2 in the PVN. Calcineurin inhibition enhances the prevalence of postsynaptic Ca2+-permeable AMPARs in PVN presympathetic neurons. Calcineurin inhibition potentiates α2δ-1 interactions with GluA1 and GluA2, disrupting intracellular assembly of GluA1/GluA2 heterotetramers in the PVN. Blocking Ca2+-permeable AMPARs or α2δ-1-AMPAR interactions in the PVN attenuates sympathetic outflow augmented by the calcineurin inhibitor.

Multi-omics analysis provides new insights into the changes of important nutrients and fructose metabolism in loquat bud sport mutant.

Bud sport is a common and stable somatic variation in perennial fruit trees, and often leads to significant modification of fruit traits and affects the breeding value. To investigate the impact of bud sport on the main metabolites in the fruit of white-fleshed loquat, we conducted a multi-omics analysis of loquat fruits at different developmental stages of a white-fleshed bud sport mutant of Dongting loquat (TBW) and its wild type (TBY). The findings from the detection of main fruit quality indices and metabolites suggested that bud sport resulted in a reduction in the accumulation of carotenoids, fructose, titratable acid and terpenoids at the mature stage of TBW, while leading to the accumulation of flavonoids, phenolic acids, amino acids and lipids. The comparably low content of titratable acid further enhances the balanced and pleasent taste profile of TBW. Expression patterns of differentially expressed genes involved in fructose metabolism exhibited a significant increase in the expression level of S6PDH (EVM0006243, EVM0044405) prior to fruit maturation. The comparison of protein sequences and promoter region of S6PDH between TBY and TBW revealed no structural variations that would impact gene function or expression, indicating that transcription factors may be responsible for the rapid up-regulation of S6PDH before maturation. Furthermore, correlation analysis helped to construct a comprehensive regulatory network of fructose metabolism in loquat, including 23 transcription factors, six structural genes, and nine saccharides. Based on the regulatory network and existing studies, it could be inferred that transcription factors such as ERF, NAC, MYB, GRAS, and bZIP may promote fructose accumulation in loquat flesh by positively regulating S6PDH. These findings improve our understanding of the nutritional value and breeding potential of white-fleshed loquat bud sport mutant, as well as serve as a foundation for exploring the genes and transcription factors that regulate fructose metabolism in loquat.

Enhancing the emulsion properties and bioavailability of loaded astaxanthin by selecting the reaction sequence of ternary conjugate emulsifiers in nanoemulsions.

This study investigated the effects of the conjugate reaction sequences of whey protein concentrate (WPC), epigallocatechin gallate (EGCG) and dextran (DEX) on the structure and emulsion properties of conjugates and the bioaccessibility of astaxanthin (AST). Two types of ternary covalent complexes were synthesised using WPC, EGCG and DEX, which were regarded as emulsifiers of AST nanoemulsions. Results indicated that the WPC-DEX-EGCG conjugate (referred to as 'con') exhibits a darker SDS-PAGE dispersion band and higher contents of α-helix (6%), ß-angle (24%) and random coil (32%), resulting in a greater degree of unfolding structure and fluorescence quenching. These findings suggested WPC-DEX-EGCG con had the potential to exhibit better emulsification properties than WPC-EGCG-DEX con. AST encapsulation efficiency (76.22%) and bioavailability (31.89%) also demonstrated the superior performance of the WPC-DEX-EGCG con emulsifier in nanoemulsion delivery systems. These findings indicate that altering reaction sequences changes protein conformation, enhancing the emulsification properties and bioavailability of AST.

Endothelin-1-mediated Brainstem Glial Activation Produces Asthmatic Airway Vagal Hypertonia Via Enhanced ATP-P2X4 Receptor Signaling in Sprague-Dawley Rats.

The occurrence of major asthma symptoms is largely attributed to airway vagal hypertonia, of which the central mechanisms remain unclear. This study tests the hypotheses that endothelin-1-mediated brainstem glial activation produces asthmatic airway vagal hypertonia via enhanced action of adenosine 5'-triphosphate on neuronal purinergic P2X4 receptors. A rat model of asthma was prepared using ovalbumin. Airway vagal tone was evaluated by the recurrent laryngeal discharge and plethysmographic measurement of pulmonary function. The changes in the brainstem were examined using ELISA, Western blot, luciferin-luciferase, quantitative reverse transcription-polymerase chain reaction, enzyme activity assay and immunofluorescent staining, respectively. The results showed that in the medulla of rats, endothelin receptor type B and P2X4 receptors were primarily expressed in astrocytes and neurons, respectively, and both of which, along with endothelin-1 content, were significantly increased after ovalbumin sensitization. Ovalbumin sensitization significantly increased recurrent laryngeal discharge, which was blocked by acute intracisternal injection of P2X4 receptor antagonist 5-BDBD, knockdown of brainstem P2X4 receptors, and chronic intraperitoneal injection of endothelin receptor type B antagonist BQ788, respectively. Ovalbumin sensitization activated microglia and astrocytes and significantly decreased ecto-5'-nucleotidase activity in the medulla, and all of which, together with the increase of medullary P2X4 receptor expression and decrease of pulmonary function, were reversed by chronic BQ788 treatment. These results demonstrated that in rats, allergic airway challenge activates both microglia and astrocytes in the medulla via enhanced endothelin-1/endothelin receptor type B signaling, which subsequently causes airway vagal hypertonia via augmented adenosine 5'-triphosphate/P2X4 receptor signaling in central neurons of airway vagal reflex.

Digital transformation of the agricultural industry: Behavioral decision-making, influencing factors, and simulation practices in the Yunnan highlands.

Motivating the agricultural industry to engage in digital transformation is a challenge academically and socially. It is of great significance to study the choice of digital transformation mode of agricultural industrial organization and analyze its driving factors for promoting the sustainable development of agricultural industrial organization. This study adopts a bilateral evolutionary game to construct a decision-making model for behavioral decision-making during the digital transformation of the agricultural industry. The contingent-actual logical framework and multiple case studies of Yunnan highland agriculture are used to explore the impact of various factors on behavioral decision-making during the digital transformation of the agricultural industry. Additionally, a simulation analysis is used to verify the validity of the bilateral evolutionary game model. The results demonstrate that: (1) When the agricultural industry chooses "active transformation," behavioral decision-making during the digital transformation of the agricultural industry reaches a Nash equilibrium; (2) transformation costs, industry revenue, and reward and penalty mechanisms are the main driving factors for whether or not the agricultural industry chooses to actively engage in digital transformation; and (3) the probability of active digital transformation increases when agricultural industry organizations obtain higher returns at lower costs. Simultaneously, the higher the government's incentives, the greater the enthusiasm. However, when the penalty is excessive, the digital transformation takes the shape of either passive transformation or forced active transformation. Subsequently, it is necessary to improve the digital transformation planning of the agricultural industry, strengthen this field's cooperation mechanism, and formulate a reasonable reward and penalty system for digital transformation.

[Research Progress on Solidification and MICP Remediation of Soils in Heavy Metal Contaminated Site].

Heavy metal pollution in soils of smelting sites is an important environmental problem to be solved urgently. Solidification technology has become one of the mainstream technologies for heavy metal remediation in contaminated sites owing to its shorter remediation time, low cost, and high treatment efficiency. On the basis of summarizing the latest research progress on the remediation of heavy metal pollution in sites by solidification in the past 10 years, this study focused on the mechanisms of solidification technology and analyzed the advantages and disadvantages of different mechanisms (mechanism of inorganic materials, mechanism of organic materials, mechanism of mechanical ball milling, and mechanism of microbial-induced carbonate mineralization (MICP)) and their scope of application. Then, according to the research focus and development trend presented by CiteSpace, the application prospects and limiting factors of MICP technology for the solidification and remediation of heavy metal pollution in sites were summarized from three aspects:the application of MICP in multi-metal remediation, the application of MICP composites in contaminated sites, and the influencing factors of MICP technology application. Finally, the prospects and challenges in solidification technology were put forward in order to provide reference for the future development.

Macrophage membrane-camouflaged pH-sensitive nanoparticles for targeted therapy of oral squamous cell carcinoma.

BACKGROUND: Oral cancer is the most common malignant tumor of the head and neck, and 90% of cases are oral squamous cell carcinoma (OSCC). Chemotherapy is an important component of comprehensive treatment for OSCC. However, the clinical treatment effect of chemotherapy drugs, such as doxorubicin (DOX), is limited due to the lack of tumor targeting and rapid clearance by the immune system. Thus, based on the tumor-targeting and immune evasion abilities of macrophages, macrophage membrane-encapsulated poly(methyl vinyl ether alt maleic anhydride)-phenylboronic acid-doxorubicin nanoparticles (MM@PMVEMA-PBA-DOX NPs), briefly as MM@DOX NPs, were designed to target OSCC. The boronate ester bonds between PBA and DOX responded to the low pH value in the tumor microenvironment, selectively releasing the loaded DOX. RESULTS: The results showed that MM@DOX NPs exhibited uniform particle size and typical core-shell structure. As the pH decreased from 7.4 to 5.5, drug release increased from 14 to 21%. The in vitro targeting ability, immune evasion ability, and cytotoxicity of MM@DOX NPs were verified in HN6 and SCC15 cell lines. Compared to free DOX, flow cytometry and fluorescence images demonstrated higher uptake of MM@DOX NPs by tumor cells and lower uptake by macrophages. Cell toxicity and live/dead staining experiments showed that MM@DOX NPs exhibited stronger in vitro antitumor effects than free DOX. The targeting and therapeutic effects were further confirmed in vivo. Based on in vivo biodistribution of the nanoparticles, the accumulation of MM@DOX NPs at the tumor site was increased. The pharmacokinetic results demonstrated a longer half-life of 9.26 h for MM@DOX NPs compared to 1.94 h for free DOX. Moreover, MM@DOX NPs exhibited stronger tumor suppression effects in HN6 tumor-bearing mice and good biocompatibility. CONCLUSIONS: Therefore, MM@DOX NPs is a safe and efficient therapeutic platform for OSCC.

Enhancing the Cooling Efficiency of Aluminum-Filled Epoxy Resin Rapid Tool by Changing Inner Surface Roughness of Cooling Channels.

In low-pressure wax injection molding, cooling time refers to the period during which the molten plastic inside the mold solidifies and cools down to a temperature where it can be safely ejected without deformation. However, cooling efficiency for the mass production of injection-molded wax patterns is crucial. This work aims to investigate the impact of varying surface roughness on the inner walls of the cooling channel on the cooling efficiency of an aluminum-filled epoxy resin rapid tool. It was found that the cooling time for the injection-molded products can be determined by the surface roughness according to the proposed prediction equation. Employing fiber laser processing on high-speed steel rods allows for the creation of microstructures with different surface roughness levels. Results demonstrate a clear link between the surface roughness of cooling channel walls and cooling time for molded wax patterns. Employing an aluminum-filled epoxy resin rapid tool with a surface roughness of 4.9 µm for low-pressure wax injection molding can save time, with a cooling efficiency improvement of approximately 34%. Utilizing an aluminum-filled epoxy resin rapid tool with a surface roughness of 4.9 µm on the inner walls of the cooling channel can save the cooling time by up to approximately 60%. These findings underscore the significant role of cooling channel surface roughness in optimizing injection molding processes for enhanced efficiency.

Deciphering Multidrug-Resistant Plasmids in Disinfection Residual Bacteria from a Wastewater Treatment Plant.

Current disinfection processes pose an emerging environmental risk due to the ineffective removal of antibiotic-resistant bacteria, especially disinfection residual bacteria (DRB) carrying multidrug-resistant plasmids (MRPs). However, the characteristics of DRB-carried MRPs are poorly understood. In this study, qPCR analysis reveals that the total absolute abundance of four plasmids in postdisinfection effluent decreases by 1.15 log units, while their relative abundance increases by 0.11 copies/cell compared to investigated wastewater treatment plant (WWTP) influent. We obtain three distinctive DRB-carried MRPs (pWWTP-01-03) from postdisinfection effluent, each carrying 9-11 antibiotic-resistant genes (ARGs). pWWTP-01 contains all 11 ARGs within an ∼25 Kbp chimeric genomic island showing strong patterns of recombination with MRPs from foodborne outbreaks and hospitals. Antibiotic-, disinfectant-, and heavy-metal-resistant genes on the same plasmid underscore the potential roles of disinfectants and heavy metals in the coselection of ARGs. Additionally, pWWTP-02 harbors an adhesin-type virulence operon, implying risks of both antibiotic resistance and pathogenicity upon entering environments. Furthermore, some MRPs from DRB are capable of transferring and could confer selective advantages to recipients under environmentally relevant antibiotic pressure. Overall, this study advances our understanding of DRB-carried MRPs and highlights the imminent need to monitor and control wastewater MRPs for environmental security.

Unveiling the Dynamic Electrocatalytic Activity of Online Synthesized Bimetallic Nanocatalysts via Electrochemiluminescence Microscopy.

Effective bimetallic nanoelectrocatalysis demands precise control of composition, structure, and understanding catalytic mechanisms. To address these challenges, we employ a two-in-one approach, integrating online synthesis with real-time imaging of bimetallic Au@Metal core-shell nanoparticles (Au@M NPs) via electrochemiluminescence microscopy (ECLM). Within 120 s, online electrodeposition and in situ catalytic activity screening alternate. ECLM captures transient faradaic processes during potential switches, visualizes electrochemical processes in real-time, and tracks catalytic activity dynamics at the single-particle level. Analysis using ECL photon flux density eliminates size effects and yields quantitative electrocatalytic activity results. Notably, a nonlinear activity trend corresponding to the shell metal to Au surface atomic ratio is discerned, quantifying the optimal surface component ratio of Au@M NPs. This approach offers a comprehensive understanding of catalytic behavior during the deposition process with high spatiotemporal resolution, which is crucial for tailoring efficient bimetallic nanocatalysts for diverse applications.

Efficacy of recombinant human epidermal growth factor in pressure injury healing: evidence from Chinese randomized controlled trials.

OBJECTIVE: To evaluate the efficacy of recombinant human epidermal growth factor (rhEGF) in healing pressure injuries (PIs). METHODS: A meta-analysis was conducted of randomized controlled trials (RCTs) involving rhEGF in the treatment of PIs that were identified in PubMed, Web of Science, the Cochrane Library, and China National Knowledge Infrastructure (CNKI). The population, intervention, comparison, outcomes, study design (PICOS) strategy was applied to determine analysis eligibility. The Cochrane risk of bias tool was used, and statistical analysis, including sensitivity analysis, was performed of 3 outcomes indicators: the primary outcome was total efficacy of rhEGF in treating PIs, and the secondary outcomes were the proportion of complete healing and the time to complete healing. Total efficacy refers to the proportion of cases that have been cured, obviously effective, or effective. Complete healing refers to cases where the wound has healed, scabbed, and the scab has sloughed off. RESULTS: Sixteen RCTs were included, comprising a total of 1,206 patients. Study and control group size varied by outcomes. The total effective healing rate in rhEGF group was 97.18%, which was significantly higher than 83.38% in control group (OR: 5.69, [95% CI: 3.61, 8.97], z=7.49, P < .001). The proportion of complete healing in the rhEGF group was 73.30%, which was higher than 39.52% in control group (OR: 3.88, [95% CI: 3.01, 5.01], z=10.39, P < .001). Furthermore, the healing time using rhEGF was shorter (SMD: -2.14 days, [95% CI: -2.60, -1.67], z=9.07, P < .001). Sensitivity analyses indicated that the results were robust. CONCLUSIONS: The meta-analysis indicated that rhEGF was effective in healing PIs with few negative effects. Further research beyond Chinese populations involving larger studies and studies that distinguish between results found in using rhEGF alone or in combination are recommended.

Whole-genome resequencing uncovers diversity and selective sweep in Kazakh cattle.

The Kazakh cattle in the Xinjiang Uygur Autonomous Region of China are highly adaptable and have multiple uses, including milk and meat production, and use as draft animals. They are an excellent original breed that could be enhanced by breeding and hybrid improvement. However, the genomic diversity and signature of selection underlying the germplasm characteristics require further elucidation. Herein, we evaluated 26 Kazakh cattle genomes in comparison with 103 genomes of seven other cattle breeds from regions around the world to assess the Kazakh cattle genetic variability. We revealed that the relatively low linkage disequilibrium at large SNP distances was strongly correlated with the largest effective population size among Kazakh cattle. Using population structural analysis, we next demonstrated a taurine lineage with restricted Bos indicus introgression among Kazakh cattle. Notably, we identified putative selected genes associated with resistance to disease and body size within Kazakh cattle. Together, our findings shed light on the evolutionary history and breeding profile of Kazakh cattle, as well as offering indispensable resources for germplasm resource conservation and crossbreeding program implementation.

Identification of cellular senescence-associated genes as new biomarkers for predicting the prognosis and immunotherapy response of non-small cell lung cancer and construction of a prognostic model.

Background: Globally, lung carcinoma remains the leading cause of death, with its associated morbidity and mortality rates remaining elevated. Despite the slow advancement of treatment, the outlook remains bleak. Cellular senescence represents a halt in the cell cycle, encompassing a range of physiological and pathological activities, along with diverse phenotypic alterations, including variations in secretory phenotype, macromolecular harm, and metabolic disturbances. Research has revealed its vital function in the formation and growth of tumors. This study aimed to examine cellular senescence-related mRNAs linked to the outlook of non-small cell lung cancer (NSCLC) and to formulate a predictive risk framework for NSCLC. Methods: We acquired the NSCLC expression data from The Cancer Genome Atlas (TCGA) to examine mRNAs linked to cellular senescence. Both single-variable and multiple-variable cox proportion risk assessments were utilized to determine the traits of cellular senescence-related mRNAs linked to NSCLC prognosis. Subsequently, the prognostic model for cellular senescence-related mRNAs was integrated with clinical-pathological characteristics to create a prognostic nomogram. Furthermore, the study delved into the risk-oriented predictive model, examining immune infiltration and responses to immunotherapy among both high and low-risk categories. Results: Utilizing both univariate and multivariate Cox proportion risk assessments, a risk model comprising 12 mRNAs associated with cellular aging was ultimately developed: IGFBP1, TLR3, WT1, ID1, PTTG1, ERRFI1, HEPACAM, MAP2K3, RAD21, NANOG, PRKCD, SOX5. Univariate analysis and multivariate analysis illustrated that the risk score served as a standalone indicator for prognosis, and the hazard ratio (HR) of the risk score were 1.182 (1.139-1.226) (p < 0.001) and 1.162 (1.119 - 1.206) (p < 0.001), respectively. Individual prognoses were forecasted using nomogram, c-index, and principal component analysis (PCA). Furthermore, the risk-oriented model revealed notable statistical variances in immune infiltration and response to immunotherapy among the high and low risk categories. Conclusions: This study shows that mRNAs related to cell senescence associated with prognosis are reliable predictors of NSCLC immunotherapy reaction and prognosis.

Landscape of plasmids encoding ß-lactamases in disinfection residual Enterobacteriaceae from wastewater treatment plants.

Conventional disinfection processes, such as chlorination and UV radiation, are ineffective in controling antibiotic-resistant bacteria, especially disinfection residual Enterobacteriaceae (DRE) encoding ß-lactamases, some of which have been classified as "critical priority pathogens" by the World Health Organization. However, few studies have focused on the transferability, phenotype, and genetic characteristics of DRE-derived plasmids encoding ß-lactamases, especially extended-spectrum ß-lactamases and carbapenemases. In this study, we isolated 10 typical DRE harboring plasmid-mediated blaNDM, blaCTX-M, or blaTEM in post-disinfection effluent from two wastewater treatment plants (WWTPs), with transfer frequency ranging from 1.69 × 10-6 to 3.02 × 10-5. According to genomic maps of plasmids, all blaNDM and blaTEM were cascaded with IS26, and blaCTX-M was adjacent to ISEcp1 or IS26, indicating the important role of these elements in the movement of ß-lactamase-encoding genes. The presence of intact class 1 integrons on pWTPN-01 and pWTPC-03 suggested the ability of these DRE-derived plasmids to integrate other exogenous antibiotic resistance genes (ARGs). The coexistence of antibiotic, disinfectant, and heavy metal resistance genes on the same plasmid (e.g., pWTPT-03) implied the facilitating role of disinfectants and heavy metals in the transmission of DRE-derived ARGs. Notably, two plasmid transconjugants exhibited no discernible competitive fitness cost, suggesting a heightened environmental persistence. Furthermore, enhanced virulence induced by ß-lactamase-encoding plasmids in their hosts was confirmed using Galleria mellonella infection models, which might be attributed to plasmid-mediated virulence genes. Overall, this study describes the landscape of ß-lactamase-encoding plasmids in DRE, and highlights the urgent need for advanced control of DRE to keep environmental and ecological security.

Mitochondria-associated membranes contribution to exercise-mediated alleviation of hepatic insulin resistance: Contrasting high-intensity interval training with moderate-intensity continuous training in a high-fat diet mouse model.

OBJECTIVE: Mitochondria-associated membranes (MAMs) serve pivotal functions in hepatic insulin resistance (IR). Our aim was to explore the potential role of MAMs in mitigating hepatic IR through exercise and to compare the effects of different intensities of exercise on hepatic MAMs formation in high-fat diet (HFD) mice. METHODS: Male C57BL/6J mice were fed an HFD and randomly assigned to undergo supervised high-intensity interval training (HIIT) or moderate-intensity continuous training (MICT). IR was evaluated using the serum triglyceride/high-density lipoprotein cholesterol ratio (TG/HDL-C), glucose tolerance test (GTT), and insulin tolerance test (ITT). Hepatic steatosis was observed using hematoxylin-eosin (H&E) and oil red O staining. The phosphatidylinositol 3-kinase/protein kinase B/glycogen synthase kinase 3 beta (PI3K-AKT-GSK3ß) signaling pathway was assessed to determine hepatic IR. MAMs were evaluated through immunofluorescence (colocalization of voltage-dependent anion-selective channel 1 [VDAC1] and inositol 1,4,5-triphosphate receptor [IP3R]). RESULTS: After 8 weeks on an HFD, there was notable inhibition of the hepatic PI3K/Akt/GSK3ß signaling pathway, accompanied by a marked reduction in hepatic IP3R-VDAC1 colocalization levels. Both 8-week HIIT and MICT significantly enhanced the hepatic PI3K/Akt/GSK3ß signaling and colocalization levels of IP3R-VDAC1 in HFD mice, with MICT exhibiting a stronger effect on hepatic MAMs formation. Furthermore, the colocalization of hepatic IP3R-VDAC1 positively correlated with the expression levels of phosphorylation of protein kinase B (p-AKT) and phosphorylation of glycogen synthase kinase 3 beta (p-GSK3ß), while displaying a negative correlation with serum triglyceride/high-density lipoprotein cholesterol levels. CONCLUSION: The reduction in hepatic MAMs formation induced by HFD correlates with the development of hepatic IR. Both HIIT and MICT effectively bolster hepatic MAMs formation in HFD mice, with MICT demonstrating superior efficacy. Thus, MAMs might wield a pivotal role in exercise-induced alleviation of hepatic IR.

Effects of vitamin family members on insulin resistance and diabetes complications.

The following letter to the editor highlights the article "Effects of vitamin D supplementation on glucose and lipid metabolism in patients with type 2 diabetes mellitus and risk factors for insulin resistance" in World J Diabetes 2023 Oct 15; 14 (10): 1514-1523. It is necessary to explore the role of vitamin family members in insulin resistance and diabetes complications.