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In order to study the influence characteristics of cored heat pipes on the temperature field of coal pile and the feasibility of preventing the spontaneous combustion of coal pile, the heat transfer law of two kinds of heat pipes with core and without core under different heat source temperature conditions was tested by experiments, and the heat transfer effect of different arrangement modes of cored heat pipes on large area coal pile was analyzed by numerical simulation. The results show that under different heat source temperature conditions, the maximum cooling range of cored heat pipe is 130.6 K, and the maximum cooling range of non-cored heat pipe is 118.6 K. The influence of heat pipes on the internal temperature field of coal pile can be divided into three regions according to the distance: high efficiency cooling zone, transition zone and slow cooling zone; the high temperature area inside the coal pile is smaller with triangular tube group arrangement; the best heat transfer effect is obtained when the spacing between tubes is 25 cm; compared with the tube group arrangement, the distance between tubes has more influence on the heat transfer effect of the core heat pipe.

Abstract Background Accurate breed identification is essential for the conservation and sustainable use of indigenous farm animal genetic resources. In this study, we evaluated the phylogenetic relationships and genomic breed compositions of 13 sheep breeds using SNP and InDel data from whole genome sequencing. The breeds included 11 Chinese indigenous and 2 foreign commercial breeds. We compared different strategies for breed identification with respect to different marker types, i.e. SNPs, InDels, and a combination of SNPs and InDels (named SIs), different breed-informative marker detection methods, and different machine learning classification methods. Results Using WGS-based SNPs and InDels, we revealed the phylogenetic relationships between 11 Chinese indigenous and two foreign sheep breeds and quantified their purities through estimated genomic breed compositions. We found that the optimal strategy for identifying these breeds was the combination of DFI_union for breed-informative marker detection, which integrated the methods of Delta, Pairwise Wright's FST, and Informativeness for Assignment (namely DFI) by merging the breed-informative markers derived from the three methods, and KSR for breed assignment, which integrated the methods of K-Nearest Neighbor, Support Vector Machine, and Random Forest (namely KSR) by intersecting their results. Using SI markers improved the identification accuracy compared to using SNPs or InDels alone. We achieved accuracies over 97.5% when using at least the 1000 most breed-informative (MBI) SI markers and even 100% when using 5000 SI markers. Conclusions Our results provide not only an important foundation for conservation of these Chinese local sheep breeds, but also general approaches for breed identification of indigenous farm animal breeds.

Abstract Objective This work aimed to investigate the potential correlation between chromosomal polymorphisms and various reproductive abnormalities. Methods We examined 21,916 patients affected by infertility who sought care at the Department of Reproductive Medicine, Affiliated Hospital of Shandong Second Medical University between January 2018 and December 2022. A total of 2227 individuals identified as chromosomal polymorphism carriers constituted the polymorphism group, and 2245 individuals with normal chromosome karyotypes were randomly selected to form a control group. Clinical manifestations, histories of spontaneous miscarriage, abnormal reproductive developments, fetal abnormalities, and male sperm quality anomalies were statistically compared between these two groups. Results Of the 21,916 patients analyzed, 2227 displayed chromosomal polymorphism, representing a 10.16% detection rate. Amongst the male patients, 1622 out of 10,827 exhibited polymorphisms (14.98%), whereas 605 out of 11,089 females showed polymorphisms (5.46%). Female carriers in the polymorphism group, showed statistically significant increased rates of spontaneous abortion (29.75% vs. 18.54%), fetal anomalies (1.32% vs. 0.81%), and uterine abnormalities compared with the control group (1.32% vs. 0.81%). Male carriers in the polymorphism group had higher rates of spontaneous abortion in partners (22.87% vs. 10.37%), fetal anomalies (1.97% vs. 0.25%), compromised sperm quality (41.74% vs. 7.18%), testicular underdevelopment (2.28% vs. 0.92%), and hypogonadotropic hypogonadism (0.62% vs. 0.37%) compared with the control group. Conclusion Chromosomal polymorphisms may have a certain negative effect on reproductive irregularities, including spontaneous abortions, fetal anomalies, and reduced sperm quality in males. Their clinical effects deserve further investigation.

ABSTRACT: Over 1 year, two KPC-producing and two non–KPC-producing Klebsiella pneumoniae strains were isolated from a patient. Genome and DNA hybridization analyses revealed the first three strains as a clonal lineage, with carbapenem resistance changes due to a Tn2-like transposon on an IncR/IncFII plasmid. The fourth strain, carrying three plasmids, caused a lethal infection and represented a different lineage. All strains belonged to the ST11-SL47-OL101 type. This study highlights the Tn2-like transposon's role in carbapenemase gene spread and the importance of distinguishing between bacterial colonization and infection.

Abstract Background R2R3-MYB transcription factors belong to one of the largest gene subfamilies in plants, and they are involved in diverse biological processes. However, the role of R2R3-MYB transcription factor subfamily genes in the response of rice (Oryza sativa L.) to salt stress has been rarely reported. Results In this study, we performed a genome-wide characterization and expression identification of rice R2R3-MYB transcription factor subfamily genes. We identified a total of 117 R2R3-MYB genes in rice and characterized their gene structure, chromosomal location, and cis-regulatory elements. According to the phylogenetic relationships and amino acid sequence homologies, the R2R3-MYB genes were divided into four groups. qRT-PCR of the R2R3-MYB genes showed that the expression levels of 10 genes significantly increased after 3 days of 0.8% NaCl treatment. We selected a high expression gene OsMYB2-115 for further analysis. OsMYB2-115 was highly expressed in the roots, stem, leaf, and leaf sheath. OsMYB2-115 was found to be localized in the nucleus, and the yeast hybrid assay showed that OsMYB2-115 has transcriptional activation activity. Conclusion This result provides important information for the functional analyses of rice R2R3-MYB transcription factor subfamily genes related to the salt stress response and reveals that OsMYB2-115 may be an important gene associated with salt tolerance in rice.

Abstract Background There is growing evidence for a relationship between gut microbiota and hepatic encephalopathy (HE). However, the causal nature of the relationship between gut microbiota and HE has not been thoroughly investigated. Method This study utilized the large-scale genome-wide association studies (GWAS) summary statistics to evaluate the causal association between gut microbiota and HE risk. Specifically, two-sample Mendelian randomization (MR) approach was used to identify the causal microbial taxa for HE. The inverse variance weighted (IVW) method was used as the primary MR analysis. Sensitive analyses were performed to validate the robustness of the results. Results The IVW method revealed that the genus Bifidobacterium (OR = 0.363, 95% CI: 0.139-0.943, P = 0.037), the family Bifidobacteriaceae (OR = 0.359, 95% CI: 0.133-0.950, P = 0.039), and the order Bifidobacteriales (OR = 0.359, 95% CI: 0.133-0.950, P = 0.039) were negatively associated with HE. However, no causal relationship was observed among them after the Bonferroni correction test. Neither heterogeneity nor horizontal pleiotropy was found in the sensitivity analysis. Conclusion Our MR study demonstrated a potential causal association between Bifidobacterium, Bifidobacteriaceae, and Bifidobacteriales and HE. This finding may provide new therapeutic targets for patients at risk of HE in the future.

Abstract Background Due to the high prevalence of multimorbidity and realistic health service demands for fall prevention, there is growing interest in the association between multimorbidity and falls. Our study aimed to identify multimorbidity patterns among Chinese older adults and explore the association between multimorbidity patterns and falls. Methods Data from 4,579 Chinese community-dwelling older adults was included in this analysis. Information regarding falls and 10 chronic conditions was collected. An exploratory factor analysis was performed to determine multimorbidity patterns. Regression models were fitted to explore the associations of individual chronic disease or multimorbidity patterns with falls. Results Among 4,579 participants, 368 (8.0%) were defined as fallers, including 92 (2.0%) frequent fallers, and multimorbidity affected 2,503 (54.7%) participants. Older adults with multimorbidity were more likely to be fallers [odds ratio (OR) = 1.3, P = 0.02] and frequent fallers (OR = 1.7, P = 0.04). Three multimorbidity patterns were identified (i.e., cardiovascular-metabolic diseases, psycho-cognitive diseases and organic diseases), and the associations between psycho-cognitive diseases/organic diseases and prevalent falls or frequent falls were found to be significant. Conclusions The psycho-cognitive disease pattern and organic disease pattern are significantly associated with falls. Therefore, more attention should be paid to patients with psycho-cognitive diseases and timely, targeted diagnostic and treatment services should be provided in fall prevention.

Abstract Schizophrenic patients’ brain tumor magnetic resonance imaging (MRI) images are important references for doctors to diagnose and treat schizophrenia. However, automatic segmentation of these images is a professional and tedious task. Existing methods suffer from problems such as large model parameters, long computation time, and inadequate image processing. To achieve more accurate segmentation of brain tumors, we propose brain tumor MRI images for automatic segmentation using self-supervised contrastive learning in schizophrenia patients (BTCSSSP). First, a denoising algorithm based on progressive principal component analysis approximation and adaptive clustering is designed to process the noisy MRI images. Second, a brightness-aware image enhancement algorithm is developed to address the problems of non-uniformity, unclear boundaries, and poor spatial resolution of the MRI images. Finally, a cross-scale U-Net network with selective feature fusion attention module is designed based on self-supervised contrastive learning to achieve automatic segmentation of brain tumor MRI images. The results show that the BTCSSSP method yields higher Recall and Precision than existing methods. The maximum recall is 95%, and the image segmentation precision is 95%, thus indicating good practical applicability.

Abstract During oxidative phosphorylation, mitochondria continuously produce reactive oxygen species (ROS), and untimely ROS clearance can subject mitochondria to oxidative stress, ultimately resulting in mitochondrial damage. Mitophagy is essential for maintaining cellular mitochondrial quality control and homeostasis, with activation involving both ubiquitin-dependent and ubiquitin-independent pathways. Over the past decade, numerous studies have indicated that different forms of regulated cell death (RCD) are connected with mitophagy. These diverse forms of RCD have been shown to be regulated by mitophagy and are implicated in the pathogenesis of a variety of diseases, such as tumors, degenerative diseases, and ischemia‒reperfusion injury (IRI). Importantly, targeting mitophagy to regulate RCD has shown excellent therapeutic potential in preclinical trials, and is expected to be an effective strategy for the treatment of related diseases. Here, we present a summary of the role of mitophagy in different forms of RCD, with a focus on potential molecular mechanisms by which mitophagy regulates RCD. We also discuss the implications of mitophagy-related RCD in the context of various diseases.

Abstract Purpose The relationship between delayed ambulation (DA) and postoperative adverse events (AEs) following transforaminal lumbar interbody fusion (TLIF) in elderly patients remains elusive. The aim of our study was to evaluate the effects of DA on the postoperative AEs including complications, readmission and prolonged length of hospital stay (LOS). Methods This was a retrospective analysis of a prospectively established database of elderly patients (aged 65 years and older) who underwent TLIF surgery. The early ambulation (EA) group was defined as patients ambulated within 48 h after surgery, whereas the delayed ambulation (DA) group was patients ambulated at a minimum of 48 h postoperatively. The DA patients were 1:1 propensity-score matched to the EA patients based on age, gender and the number of fused segments. Univariate analysis was used to compare postoperative outcomes between the two groups, and multivariate logistic regression analysis was used to identify risk factors for adverse events and DA. Results After excluding 125 patients for various reasons, 1025 patients (≤ 48 h: N = 659 and > 48 h: N = 366) were included in the final analysis. After propensity score matching, there were 326 matched patients in each group. There were no significant differences in the baseline data and the surgery-related variables between the two groups (p > 0.05). The patients in the DA group had a significant higher incidence of postoperative AEs (46.0% vs. 34.0%, p = 0.002) and longer LOS (p = 0.001). Multivariate logistic regression identified that age, operative time, diabetes, and DA were independently associated with postoperative AEs, whereas greater age, higher international normalized ratio, and intraoperative estimated blood loss were identified as independent risk factors for DA. Conclusions Delayed ambulation was an independent risk factor for postoperative AEs after TLIF in elderly patients. Older age, increased intraoperative blood loss and worse coagulation function were associated with delayed ambulation.

Abstract Benzodiazepines, commonly used for anxiolytics, hinder conditioned fear extinction, and the underlying circuit mechanisms are unclear. Utilizing remimazolam, an ultra-short-acting benzodiazepine, here we reveal its impact on the thalamic nucleus reuniens (RE) and interconnected hippocamposeptal circuits during fear extinction. Systemic or RE-specific administration of remimazolam impedes fear extinction by reducing RE activation through A type GABA receptors. Remimazolam enhances long-range GABAergic inhibition from lateral septum (LS) to RE, underlying the compromised fear extinction. RE projects to ventral hippocampus (vHPC), which in turn sends projections characterized by feed-forward inhibition to the GABAergic neurons of the LS. This is coupled with long-range GABAergic projections from the LS to RE, collectively constituting an overall positive feedback circuit construct that promotes fear extinction. RE-specific remimazolam negates the facilitation of fear extinction by disrupting this circuit. Thus, remimazolam in RE disrupts fear extinction caused by hippocamposeptal intermediation, offering mechanistic insights for the dilemma of combining anxiolytics with extinction-based exposure therapy.

Abstract Film capacitors are playing an increasingly important role in power‐related fields, driven by the continuous development of dielectric materials and practical needs. Long‐term accumulation has also led to an increasing wealth of data related to film capacitors. Sonification opens up a new way for people to make good use of data from film capacitors. A framework for sonifying film capacitors data based on TwoTone is presented. Based on the analysis and discussion, it is clear that the sonification results can easily represent the monotonic variation pattern of film capacitors data. What's more, the sonification results increase the possibility that people pay attention to the changing trend of film capacitors data when there is no significant difference in the visual perception of the data. In addition to providing a new way of music generation of electrical equipment, the method proposed is expected to contribute to theory reference in typical scenarios, such as factory calibration of film capacitors, monitoring of film capacitor operation status, and presentation of statistical data of film capacitors' dielectric materials, which will help us to better understand the distribution characteristics of polymer films.

AIM: To investigate the morphological characteristics of retinal vessels in patients with different severity of diabetic retinopathy (DR) and in patients with or without diabetic macular edema (DME). METHODS: The 239 eyes of DR patients and 100 eyes of healthy individuals were recruited for the study. The severity of DR patients was graded as mild, moderate and severe non-proliferative diabetic retinopathy (NPDR) according to the international clinical diabetic retinopathy (ICDR) disease severity scale classification, and retinal vascular morphology was quantitatively analyzed in ultra-wide field images using RU-net and transfer learning methods. The presence of DME was determined by optical coherence tomography (OCT), and differences in vascular morphological characteristics were compared between patients with and without DME. RESULTS: Retinal vessel segmentation using RU-net and transfer learning system had an accuracy of 99% and a Dice metric of 0.76. Compared with the healthy group, the DR group had smaller vessel angles (33.68±3.01 vs 37.78±1.60), smaller fractal dimension (Df) values (1.33±0.05 vs 1.41±0.03), less vessel density (1.12±0.44 vs 2.09±0.36) and fewer vascular branches (206.1±88.8 vs 396.5±91.3), all P

Abstract Background The role of circRNAs in hepatocellular carcinoma (HCC) progression remains unclear. CircPIAS1 (circBase ID: hsa_circ_0007088) was identified as overexpressed in HCC cases through bioinformatics analysis. This study aimed to investigate the oncogenic properties and mechanisms of circPIAS1 in HCC development. Methods Functional analyses were conducted to assess circPIAS1’s impact on HCC cell proliferation, migration, and ferroptosis. Xenograft mouse models were employed to evaluate circPIAS1’s effects on tumor growth and pulmonary metastasis in vivo. Bioinformatics analysis, RNA immunoprecipitation, and luciferase reporter assays were utilized to elucidate the molecular pathways influenced by circPIAS1. Additional techniques, including RNA pulldown, fluorescence in situ hybridization (FISH), chromatin immunoprecipitation (ChIP), qPCR, and western blotting, were used to further explore the underlying mechanisms. Results CircPIAS1 expression was elevated in HCC tissues and cells. Silencing circPIAS1 suppressed HCC cell proliferation and migration both in vitro and in vivo. Mechanically, circPIAS1 overexpression inhibited ferroptosis by competitively binding to miR-455-3p, leading to upregulation of Nuclear Protein 1 (NUPR1). Furthermore, NUPR1 promoted FTH1 transcription, enhancing iron storage in HCC cells and conferring resistance to ferroptosis. Treatment with ZZW-115, an NUPR1 inhibitor, reversed the tumor-promoting effects of circPIAS1 and sensitized HCC cells to lenvatinib. Conclusion This study highlights the critical role of circPIAS1 in HCC progression through modulation of ferroptosis. Targeting the circPIAS1/miR-455-3p/NUPR1/FTH1 regulatory axis may represent a promising therapeutic strategy for HCC.

Abstract Traditional village toponyms contain rich vernacular geographical information, profound cultural connotations, and social group memories. Studying the meanings and spatial distribution characteristics of traditional village toponyms and their formation mechanism is significant for the sustainable development and protection of the intangible culture of traditional villages. However, previous studies mainly focused on qualitative description combined with geospatial analysis techniques to explore their spatial distribution and influencing factors, but there has yet to be an in-depth study on why such a pattern is formed. Thus, this study employs statistics, a GIS kernel density estimation method, a geodetector, and historical data to examine the spatial distribution, influence factors, and formation mechanisms of various toponyms in traditional villages in western Hunan, China. The results show that (1) the toponyms in traditional villages in western Hunan can be categorized into natural and cultural landscape toponyms. Natural landscape toponyms predominate in the northwest, whereas cultural landscape toponyms are more concentrated in the southeast, with Huayuan, Longshan, and Dong Autonomous Counties as the primary focal points; (2)Natural toponyms are shaped by terrain, river proximity, and vegetation, whereas cultural toponyms cluster due to natural features and historic trail influence, mirroring the historical migration and settlement patterns in the development of western Hunan; (3)Multiple influencing factors, regulatory powers, and curing processes reveal the formation mechanism of the spatial patterns of toponyms. This study offers a novel lens for recognizing and understanding the characteristics of human settlement environments and culture in traditional villages. Moreover, the results of this study can provide scientific guidance for the cultural protection of traditional villages on a cross-regional scale.

Abstract Background Impatiens is an important genus with rich species of garden plants, and its distribution is extremely extensive, which is reflected in its diverse ecological environment. However, the specific mechanisms of Impatiens’ adaptation to various environments and the mechanism related to lignin remain unclear. Results Three representative Impatiens species,Impatiens chlorosepala (wet, low degree of lignification), Impatiens uliginosa (aquatic, moderate degree of lignification) and Impatiens rubrostriata (terrestrial, high degree of lignification), were selected and analyzed for their anatomical structures, lignin content and composition, and lignin-related gene expression. There are significant differences in anatomical parameters among the stems of three Impatiens species, and the anatomical structure is consistent with the determination results of lignin content. Furthermore, the thickness of the xylem and cell walls, as well as the ratio of cell wall thickness to stem diameter have a strong correlation with lignin content. The anatomical structure and degree of lignification in Impatiens can be attributed to the plant's growth environment, morphology, and growth rate. Our analysis of lignin-related genes revealed a negative correlation between the MYB4 gene and lignin content. The MYB4 gene may control the lignin synthesis in Impatiens by controlling the structural genes involved in the lignin synthesis pathway, such as HCT, C3H, and COMT. Nonetheless, the regulation pathway differs between species of Impatiens. Conclusions This study demonstrated consistency between the stem anatomy of Impatiens and the results obtained from lignin content and composition analyses. It is speculated that MYB4 negatively regulates the lignin synthesis in the stems of three Impatiens species by regulating the expression of structural genes, and its regulation mechanism appears to vary across different Impatiens species. This study analyses the variations among different Impatiens plants in diverse habitats, and can guide further molecular investigations of lignin biosynthesis in Impatiens.

Abstract Ulcerative colitis (UC) is an idiopathic, chronic inflammatory condition of the colon, characterized by repeated attacks, a lack of effective treatment options, and significant physical and mental health complications for patients. The endoplasmic reticulum (ER) is a vital intracellular organelle in maintaining cellular homeostasis. Endoplasmic reticulum stress (ERS) is induced when the body is exposed to adverse external stimuli. Numerous studies have shown that ERS-induced apoptosis plays a vital role in the pathogenesis of UC. Mogroside V (MV), an active ingredient of Monk fruit, has demonstrated excellent anti-inflammatory and antioxidant effects. In this study, we investigated the therapeutic effects of MV on dextran sulfate sodium (DSS)-induced UC and its potential mechanisms based on ERS. The results showed that MV exerted a protective effect against DSS-induced UC in mice as reflected by reduced DAI scores, increased colon length, reduced histological scores of the colon, and levels of pro-inflammatory cytokines, as well as decreased intestinal permeability. In addition, the expression of ERS pathway including BIP, PERK, eIF2α, ATF4, CHOP, as well as the apoptosis-related protein including Caspase-12, Bcl-2 and Bax, was found to be elevated in UC. However, MV treatment significantly inhibited the UC and reversed the expression of inflammation signaling pathway including ERS and ERS-induced apoptosis. Additionally, the addition of tunicamycin (Tm), an ERS activator, significantly weakened the therapeutic effect of MV on UC in mice. These findings suggest that MV may be a therapeutic agent for the treatment of DSS-induced UC by inhibiting the activation of the ERS-apoptosis pathway, and may provide a novel avenue for the treatment of UC.

Abstract Rosa roxburghii Tratt, a valuable plant in China with long history, is famous for its fruit. It possesses various secondary metabolites, such as L-ascorbic acid (vitamin C), alkaloids and poly saccharides, which make it a high nutritional and medicinal value. Here we characterized the chromosome-level genome sequence of R. roxburghii, comprising seven pseudo-chromosomes with a total size of 531 Mb and a heterozygosity of 0.25%. We also annotated 45,226 coding gene loci after masking repeat elements. Orthologs for 90.1% of the Complete Single-Copy BUSCOs were found in the R. roxburghii annotation. By aligning with protein sequences from public platform, we annotated 85.89% genes from R. roxburghii. Comparative genomic analysis revealed that R. roxburghii diverged from Rosa chinensis approximately 5.58 to 13.17 million years ago, and no whole-genome duplication event occurred after the divergence from eudicots. To fully utilize this genomic resource, we constructed a genomic database RroFGD with various analysis tools. Otherwise, 69 enzyme genes involved in L-ascorbate biosynthesis were identified and a key enzyme in the biosynthesis of vitamin C, GDH (L-Gal-1-dehydrogenase), is used as an example to introduce the functions of the database. This genome and database will facilitate the future investigations into gene function and molecular breeding in R. roxburghii.

Abstract Activation of the NF-κB pathway is strictly regulated to prevent excessive inflammatory and immune responses. In a well-known negative feedback model, IκBα-dependent NF-κB termination is a delayed response pattern in the later stage of activation, and the mechanisms mediating the rapid termination of active NF-κB remain unclear. Here, we showed IκBα-independent rapid termination of nuclear NF-κB mediated by CLK2, which negatively regulated active NF-κB by phosphorylating the RelA/p65 subunit of NF-κB at Ser180 in the nucleus to limit its transcriptional activation through degradation and nuclear export. Depletion of CLK2 increased the production of inflammatory cytokines, reduced viral replication and increased the survival of the mice. Mechanistically, CLK2 phosphorylated RelA/p65 at Ser180 in the nucleus, leading to ubiquitin‒proteasome-mediated degradation and cytoplasmic redistribution. Importantly, a CLK2 inhibitor promoted cytokine production, reduced viral replication, and accelerated murine psoriasis. This study revealed an IκBα-independent mechanism of early-stage termination of NF-κB in which phosphorylated Ser180 RelA/p65 turned off posttranslational modifications associated with transcriptional activation, ultimately resulting in the degradation and nuclear export of RelA/p65 to inhibit excessive inflammatory activation. Our findings showed that the phosphorylation of RelA/p65 at Ser180 in the nucleus inhibits early-stage NF-κB activation, thereby mediating the negative regulation of NF-κB.

AIM: To investigate systemic immune-inflammation index (SII), neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR) levels in patients with type 2 diabetes at different stages of diabetic retinopathy (DR). METHODS: This retrospective study included 141 patients with type 2 diabetes mellitus (DM): 45 without diabetic retinopathy (NDR), 47 with non-proliferative diabetic retinopathy (NPDR), and 49 with proliferative diabetic retinopathy (PDR). Complete blood counts were obtained, and NLR, PLR, and SII were calculated. The study analysed the ability of inflammatory markers to predict DR using receiver operating characteristic (ROC) curves. The relationships between DR stages and SII, PLR, and NLP were assessed using multivariate logistic regression. RESULTS: The average NLR, PLR, and SII were higher in the PDR group than in the NPDR group (P=0.011, 0.043, 0.009, respectively); higher in the NPDR group than in the NDR group (P

BackgroundNovel β-lactam antibiotics as well as other kinds of antibiotics have been used to treat complicated urinary tract infections (cUTIs); however, their efficacy and safety remain controversial.ObjectiveWe conducted a systematic review with meta-analysis to explore the efficacy and safety of novel β-lactam antibiotics versus other antibiotics against cUTIs.MethodsPubMed, Embase, and the Cochrane Central Register of Controlled Trials were searched systematically from inception through 15 March 2024 for clinical trials comparing novel β-lactam antibiotics with other antibiotics for treatment of cUTIs. Random-effects models were used to evaluate the impact of treatment on the risk ratio (RR) of clinical response, microbiologic response, adverse effects (AEs), serious adverse effects (SAEs). The quality of evidence was evaluated with the Cochrane Risk of Bias assessment tool. The review was registered in INPLASY (INPLASY202440054).ResultsTen randomized controlled trials involving 5, 925 patients met our inclusion criteria. Our meta-analysis revealed that there was no significant difference in overall clinical response (RR = 1.02), AEs (RR = 1.07), SAEs (RR = 1.20) between novel β-lactam antibiotics groups and other antibiotics groups. However, a significant difference was found in a subgroup of clinical cure rates at the end of treatment between novel β-lactam antibiotics groups and carbapenems groups, with low heterogeneity (RR = 1.02). A significant difference was observed in microbiologic response (RR = 1.11). Subgroup analysis revealed a significant difference in microbiologic response between novel BBL/BLS groups and carbapenems groups (RR = 1.13, I2 = 21%, P = 0.005). Differences was observed between novel BBL/BLS groups and piperacillin/tazobactam sodium groups (RR = 1.21, I2 = 70%, P = 0.02). Similar results were obtained from subgroup analysis of the difference in microbiologic response between novel β-lactam antibiotics groups and ertapenem groups (RR = 0.92, I2 = 0, P = 0.01).ConclusionNovel β-lactam antibiotics had similar overall clinical cure, AEs, SAE, to other antibiotics in the treatment of cUTIs. However, novel β-lactam antibiotics demonstrated superior clinical cure rates compared to carbapenems in a subgroup analysis, and exhibited better microbiologic response than other antibiotics.

IntroductionWith the goal of patient engagement, an initiative was formulated to equip each patient in the general wards with a tablet whereby they can access their health information and patient education materials and communicate with their healthcare team. This paper presented the methodology of the implementation efforts as well as an evaluation of the preliminary outcomes.MethodsThe process of hospital-wide implementation was shared using the implementation research logic model. The bedside tablets were rolled out hospital-wide in a step-wedge manner over 12 months. Barriers and facilitators to this implementation were discussed together with strategies to optimize the situation. Preliminary outcomes of the implementation were evaluated using the RE-AIM framework.ResultsThe initial adoption rate for the bedside tablet was low. Additional strategies, such as survey audits and provision of feedback, development of education materials for patients, facilitation, and purposefully re-examining the implementation strategies, were used to improve adoption. The trend of adoption increased over the course of 2 years from the start of implementation.DiscussionThe initial lower adoption rates may reflect Singapore's paternalistic healthcare culture. While this implementation was driven by the need to move away from paternalism and toward patient engagement, more time is required for significant cultural change.

Cyclophosphamide (CTX) is an anticancer medication that suppresses host immunity as well as adversely affects mucosal inflammation and gut microflora dysbiosis. The gut microflora is recognized as a substantial factor in host metabolism and immunological homeostasis. To improve immunity and inhibit cytotoxic and homeostatic imbalances triggered by CTX, it is essential to monitor immunoregulators. In this research, we assessed the impact of Octopus peptide hydrolysate (OPH) on immune modulation, intestinal integrity, and gut microbial composition in CTX-induced immune-deficient mice. The results revealed that OPH increased body weight, and immunological organ indices, and improved the histological changes in the colon, thymus, and spleen. The OPH stimulated the secretion of cytokines (IL-1β, IL-6, and TNF-α) and antibodies (IgM and IgA) while reducing the ratio of lipopolysaccharide (LPS) and diamine oxidase (DAO) in the serum. OPH further enhanced goblet cell and mucus production, upregulated the expression of gut tight-junction proteins (Occludin, Zonula Occludin-1, Mucin-2, and Claudin-1), and activated the TLR4/NF-κB cascade (p-IκBα, P65/p-p65). In addition, OPH treatment declined the Bacteroidetes/Firmicutes ratio, enhanced the relative ratio of Alistipes/Lachnospiraceae, and reversed the ecological equilibrium of the gut microflora. The findings revealed that OPH serves as a prebiotic to prevent CTX-mediated disruption in the intestinal barrier and boosts gut mucosal immunity by attenuating gut microflora imbalance, implying that OPH could be used as an immunological ingredient in nutritious foods to regulate the immune system and protect the gut from inflammatory diseases.

In this study, cattle bone collagen peptides–selenium chelate (CCP-Se) was prepared and its structure, oxidation resistance and stability were characterized. The selenium binding capacity was 33.65 ± 0.13 mg/g by optimized preparation conditions. Structural analysis showed that selenium ions bound mainly to the amino nitrogen, carboxyl oxygen and hydroxyl oxygen atoms of the cattle bone collagen peptide (CCP). The microstructure and particle size analyses showed that the particle size of CCP-Se was increased and formed a regular and compact crystal structure compared with CCP. Additionally, CCP-Se exhibited excellent antioxidant activity. Stability analysis showed that CCP-Se was stable in thermal processing, simulated in vitro digestion and acid/alkali tolerance tests. The intestinal selenium permeability of CCP-Se was significantly better than sodium selenite (p

Plasmid-mediated conjugative transfer of antibiotic resistance genes (ARGs) within the human and animal intestine represents a substantial global health concern. linoleic acid (LA) has shown promise in inhibiting conjugation in vitro, but its in vivo effectiveness in the mammalian intestinal tract is constrained by challenges in efficiently reaching the target site. Recent advancements have led to the development of waterborne polyurethane nanoparticles for improved drug delivery. In this study, we synthesized four waterborne polyurethane nanoparticles incorporating LA (WPU@LA) using primary raw materials, including N-methyldiethanolamine, 2,2'-(piperazine-1,4-diyl) diethanol, isophorone diisocyanate, castor oil, and acetic acid. These nanoparticles, identified as WPU0.89@LA, WPU0.99@LA, WPU1.09@LA, and WPU1.19@LA, underwent assessment for their pH-responsive release property and biocompatibility. Among these, WPU0.99@LA displayed superior pH-responsive release properties and biocompatibility towards Caco-2 and IPEC-J2 cells. In a mouse model, a dosage of 10 mg/kg/day WPU0.99@LA effectively reduced the conjugation of IncX4 plasmids carrying the mobile colistin resistance gene (mcr-1) by more than 45.1-fold. In vivo toxicity assessment demonstrated that 10 mg/kg/day WPU0.99@LA maintains desirable biosafety and effectively preserves gut microbiota homeostasis. In conclusion, our study provides crucial proof-of-concept support, demonstrating that WPU0.99@LA holds significant potential in controlling the spread of antibiotic resistance within the mammalian intestine.

IntroductionNutritional deficiencies (NDs) manifest in various forms and are widespread globally. However, a systematic evaluation of the epidemiology of NDs across all causes and age groups in different countries and regions has not been conducted.Materials and methodsThis study aimed to utilize data from the 2019 Global Burden of Disease (GBD) study to assess the burden and trends of NDs, including their incidence, prevalence, mortality, and disability-adjusted life years (DALYs). Additionally, the study evaluated health inequalities at global, regional, and national levels from 1990 to 2019.ResultIn 2019, the age-standardized incidence rate of NDs was 2,207.71 per 100,000 individuals (95% UI 1,863.04–2,604.67), and the age-standardized DALYs (ASR-DALYs) was 680.12 per 100,000 individuals (95% UI 507.21–894.89). Among the causes of NDs, dietary iron deficiency had the highest ASR-DALYs and exhibited minimal variation. Children under the age of 5 years faced the greatest risk of NDs. Sex disparity was evident, with males having lower rates than females. Although the gap in the burden of NDs between regions classified as poor and wealthy decreased, disparities persist.ConclusionThese findings provide critical insights for the development of global health strategies aimed at mitigating NDs and may guide policymakers in implementing effective and economically viable interventions.

ABSTRACT Growing evidence have indicated the crucial role of intratumor microbiome in a variety of solid tumor. However, the intratumoral microbiome in gynecological malignancies is largely unknown. In the present study, a total of 90 Han patients, including 30 patients with cancer in cervix, ovary, and endometrium each were enrolled, the composition of intratumoral microbiome was assessed by 16S rDNA amplicon high throughput sequencing. We found that the diversity and metabolic potential of intratumoral microbiome in all three cancer types were very similar. Furthermore, all three cancer types shared a few taxa that collectively take up high relative abundance and positive rate, including Pseudomonas sp., Comamonadaceae gen. sp., Bradyrhizobium sp., Saccharomonospora sp., Cutibacterium acnes, Rubrobacter sp., Dialister micraerophilus, and Escherichia coli. Additionally, Haemophilus parainfluenzae and Paracoccus sp. in cervical cancer, Pelomonas sp. in ovarian cancer, and Enterococcus faecalis in endometrial cancer were identified by LDA to be a representative bacterial strain. In addition, in cervical cancer patients, alpha-fetoprotein (AFP) (correlation coefficient = −0.3714) was negatively correlated (r = 0.4, 95% CI: 0.03 to 0.7) with Rubrobacter sp. and CA199 (correlation coefficient = 0.3955) was positively associated (r = 0.4, 95% CI: 0.03 to 0.7) with Saccharomonospora sp.. In ovarian cancer patients, CA125 (correlation coefficient = −0.4451) was negatively correlated (r = −0.4, 95% CI: −0.7 to −0.09) with Porphyromonas sp.. In endometrial cancer patients, CEA (correlation coefficient = −0.3868) was negatively correlated (r = −0.4, 95% CI: −0.7 to −0.02) with Cutibacterium acnes. This study promoted our understanding of the intratumoral microbiome in gynecological malignancies.IMPORTANCEIn this study, we found the compositional spectrum of tumor microbes among gynecological malignancies were largely similar by sharing a few taxa and differentiated by substantial species owned uniquely. Certain species, mostly unreported, were identified to be associated with clinical characteristics. This study prompted our understanding of gynecological malignancies and offered evidence for tumor microbes affecting tumor biology among cancers in the female reproductive system.

Investigating the composition of household dust can provide crucial insights into potential environmental and health implications. This study aimed to determine the concentration of selected metals in 30 household floor dust samples collected from two cities in Peninsular Malaysia, namely Melaka and Butterworth. The samples were collected using nylon socks attached to a vacuum cleaner nozzle during January-February 2021. All samples were sieved through a 200-µm sieve, acid-digested with aqua regia, and analyzed using inductively coupled plasma mass spectrometry (ICP-MS). Mean metal concentrations decreased in the order of Fe>Al>Mg>Zn>Mn>Ba>Cu>Cr>Pb. Cd was not detected in any samples. The median concentrations of Al, Ba, and Mg from Melaka were significantly higher than those from Butterworth. Hazard indexes for all metals were less than one, indicating a low noncarcinogenic risk of exposure to occupants via inhalation, dust ingestion, and skin absorption. Statistical analyses revealed that the levels of metals in household dust were influenced by factors such as the location and age of the house, the presence of air conditioning, and the time since the last paint. This study highlights the presence of metals in indoor settings of different cities in Malaysia, providing fundamental data for future research in the field.

Patients with the target gene mutation frequently derive significant clinical benefits from target therapy. However, differences in the abundance level of mutations among patients resulted in varying survival benefits, even among patients with the same target gene mutations. Currently, there is a lack of rational and interpretable models to assess the risk of treatment failure. In this study, we investigated the underlying coupled factors contributing to variations in medication sensitivity and established a statistically interpretable framework, named SAFE-MIL, for risk estimation. We first constructed an effectiveness label for each patient from the perspective of exploring the optimal grouping of patients’ positive judgment values and sampled patients into 600 and 1,000 groups, respectively, based on multi-instance learning (MIL). A novel and interpretable loss function was further designed based on the Hosmer-Lemeshow test for this framework. By integrating multi-instance learning with the Hosmer-Lemeshow test, SAFE-MIL is capable of accurately estimating the risk of drug treatment failure across diverse patient cohorts and providing the optimal threshold for assessing the risk stratification simultaneously. We conducted a comprehensive case study involving 457 non-small cell lung cancer patients with EGFR mutations treated with EGFR tyrosine kinase inhibitors. Results demonstrate that SAFE-MIL outperforms traditional regression methods with higher accuracy and can accurately assess patients’ risk stratification. This underscores its ability to accurately capture inter-patient variability in risk while providing statistical interpretability. SAFE-MIL is able to effectively guide clinical decision-making regarding the use of drugs in targeted therapy and provides an interpretable computational framework for other patient stratification problems. The SAFE-MIL framework has proven its effectiveness in capturing inter-patient variability in risk and providing statistical interpretability. It outperforms traditional regression methods and can effectively guide clinical decision-making in the use of drugs for targeted therapy. SAFE-MIL offers a valuable interpretable computational framework that can be applied to other patient stratification problems, enhancing the precision of risk assessment in personalized medicine. The source code for SAFE-MIL is available for further exploration and application at https://github.com/Nevermore233/SAFE-MIL.

Investigating the composition of household dust can provide crucial insights into potential environmental and health implications. This study aimed to determine the concentration of selected metals in 30 household floor dust samples collected from two cities in Peninsular Malaysia, namely Melaka and Butterworth. The samples were collected using nylon socks attached to a vacuum cleaner nozzle during January-February 2021. All samples were sieved through a 200-µm sieve, acid-digested with aqua regia, and analyzed using inductively coupled plasma mass spectrometry (ICP-MS). Mean metal concentrations decreased in the order of Fe>Al>Mg>Zn>Mn>Ba>Cu>Cr>Pb. Cd was not detected in any samples. The median concentrations of Al, Ba, and Mg from Melaka were significantly higher than those from Butterworth. Hazard indexes for all metals were less than one, indicating a low noncarcinogenic risk of exposure to occupants via inhalation, dust ingestion, and skin absorption. Statistical analyses revealed that the levels of metals in household dust were influenced by factors such as the location and age of the house, the presence of air conditioning, and the time since the last paint. This study highlights the presence of metals in indoor settings of different cities in Malaysia, providing fundamental data for future research in the field.

Hyperthyroidism and thyroid cancer significantly impact health, and often require Radioactive Iodine (RAI) therapy. Anxiety is common in patients undergoing RAI, particularly related to dietary compliance. This study aimed to assess the effectiveness of the mobile health application, DietLens in reducing anxiety and increasing satisfaction in patients preparing for RAI therapy, focusing on low-iodine diet (LID). A quasi-experimental study was conducted in a Singapore tertiary hospital outpatient department from March 13, 2019 to March 27, 2020, involving patients scheduled for their first RAI treatment. Participants were divided into a control group receiving standard care and an intervention group using DietLens alongside standard care. Anxiety levels were assessed using the Zung Self-Rating Anxiety Scale, and satisfaction levels were measured through self-reported questionnaires. In the study, 56 participants were initially divided into control (n = 28) and intervention (n = 28) groups. After accounting for dropouts, 50 participants finished the study, with each group comprising 25 individuals. Anxiety levels were similar between groups pre-intervention. Post-intervention, the intervention group displayed a significant decrease in anxiety levels compared to the control group (independent t-test: t (48) = 2.50, p = 0.02). The multivariate linear regression analysis indicated that being in the intervention group was significantly associated with a decrease in post-intervention anxiety score (β = −4.03, 95 % CI: −7.33 to −0.72, p = 0.02). Fisher's Exact Test revealed a borderline significant difference in satisfaction with educational materials and the overall treatment process, with 100 % of the intervention group expressing satisfaction compared to 80 % in the control group, resulting in a p-value of 0.052 in both instances. DietLens was effective in reducing anxiety and enhancing satisfaction related to RAI therapy preparation, particularly in managing a LID, highlighting a beneficial role for digital interventions in healthcare settings.

Abstract Background Gamithromycin is an effective therapy for bovine and swine respiratory diseases but not utilized for rabbits. Given its potent activity against respiratory pathogens, we sought to determine the pharmacokinetic profiles, antimicrobial activity and target pharmacokinetic/pharmacodynamic (PK/PD) exposures associated with therapeutic effect of gamithromycin against Pasteurella multocida in rabbits. Results Gamithromycin showed favorable PK properties in rabbits, including high subcutaneous bioavailability (86.7 ± 10.7%) and low plasma protein binding (18.5–31.9%). PK analysis identified a mean plasma peak concentration (Cmax) of 1.64 ± 0.86 mg/L and terminal half-life (T1/2) of 31.5 ± 5.74 h after subcutaneous injection. For P. multocida, short post-antibiotic effects (PAE) (1.1–5.3 h) and post-antibiotic sub-inhibitory concentration effects (PA-SME) (6.6–9.1 h) were observed after exposure to gamithromycin at 1 to 4× minimal inhibitory concentration (MIC). Gamithromycin demonstrated concentration-dependent bactericidal activity and the PK/PD index area under the concentration-time curve over 24 h (AUC24h)/MIC correlated well with efficacy (R2 > 0.99). The plasma AUC24h/MIC ratios of gamithromycin associated with the bacteriostatic, bactericidal and bacterial eradication against P. multocida were 15.4, 24.9 and 27.8 h in rabbits, respectively. Conclusions Subcutaneous administration of 6 mg/kg gamithromycin reached therapeutic concentrations in rabbit plasma against P. multocida. The PK/PD ratios determined herein in combination with ex vivo activity and favorable rabbit PK indicate that gamithromycin may be used for the treatment of rabbit pasteurellosis.

Abstract Silent information regulator 2 (Sir2) proteins typically catalyze NAD+-dependent protein deacetylation. The recently identified bacterial Sir2 domain-containing protein, defense-associated sirtuin 2 (DSR2), recognizes the phage tail tube and depletes NAD+ to abort phage propagation, which is counteracted by the phage-encoded DSR anti-defense 1 (DSAD1), but their molecular mechanisms remain unclear. Here, we determine cryo-EM structures of inactive DSR2 in its apo form, DSR2–DSAD1 and DSR2–DSAD1–NAD+, as well as active DSR2–tube and DSR2–tube–NAD+ complexes. DSR2 forms a tetramer with its C-terminal sensor domains (CTDs) in two distinct conformations: CTDclosed or CTDopen. Monomeric, rather than oligomeric, tail tube proteins preferentially bind to CTDclosed and activate Sir2 for NAD+ hydrolysis. DSAD1 binding to CTDopen allosterically inhibits tube binding and tube-mediated DSR2 activation. Our findings provide mechanistic insight into DSR2 assembly, tube-mediated DSR2 activation, and DSAD1-mediated inhibition and NAD+ substrate catalysis in bacterial DSR2 anti-phage defense systems.

Abstract Background Although ROX index is frequently used to assess the efficacy of high-flow nasal cannula treatment in acute hypoxemic respiratory failure (AHRF) patients, the relationship between the ROX index and the mortality remains unclear. Therefore, a retrospective cohort study was conducted to evaluate the ability of the ROX index to predict mortality risk in patients with AHRF. Method Patients diagnosed with AHRF were extracted from the MIMIC-IV database and divided into four groups based on the ROX index quartiles. The primary outcome was 28-day mortality, while in-hospital mortality and follow-up mortality were secondary outcomes. To investigate the association between ROX index and mortality in AHRF patients, restricted cubic spline curve and COX proportional risk regression were utilized. Result A non-linear association (L-shaped) has been observed between the ROX index and mortality rate. When the ROX index is below 8.28, there is a notable decline in the 28-day mortality risk of patients as the ROX index increases (HR per SD, 0.858 [95%CI 0.794–0.928] P

Abstract As an important forestry pest, Coronaproctus castanopsis (Monophlebidae) has caused serious damage to the globally valuable Gutianshan ecosystem, China. In this study, we assembled the first chromosome-level genome of the female specimen of C. castanopsis by merging BGI reads, HiFi long reads and Hi-C data. The assembled genome size is 700.81 Mb, with a scaffold N50 size of 273.84 Mb and a contig N50 size of 12.37 Mb. Hi-C scaffolding assigned 98.32% (689.03 Mb) of C. Castanopsis genome to three chromosomes. The BUSCO analysis (n = 1,367) showed a completeness of 91.2%, comprising 89.2% of single-copy BUSCOs and 2.0% of multicopy BUSCOs. The mapping ratio of BGI, second-generation RNA, third-generation RNA and HiFi reads are 97.84%, 96.15%, 97.96%, and 99.33%, respectively. We also identified 64.97% (455.3 Mb) repetitive elements, 1,373 non-coding RNAs and 10,542 protein-coding genes. This study assembled a high-quality genome of C. castanopsis, which accumulated valuable molecular data for scale insects.

Abstract Despite the central role of human leukocyte antigen class I (HLA-I) in tumor neoantigen presentation, quantitative determination of presentation capacity remains elusive. Based on a pooled pan-cancer genomic dataset of 885 patients treated with immune checkpoint inhibitors (ICIs), we developed a score integrating the binding affinity of neoantigens to HLA-I, as well as HLA-I allele divergence, termed the HLA tumor-Antigen Presentation Score (HAPS). Patients with a high HAPS were more likely to experience survival benefit following ICI treatment. Analysis of the tumor microenvironment indicated that the antigen presentation pathway was enriched in patients with a high HAPS. Finally, we built a neural network incorporating factors associated with neoantigen production, presentation, and recognition, which exhibited potential for differentiating cancer patients likely to benefit from ICIs. Our findings highlight the clinical utility of evaluating HLA-I tumor antigen presentation capacity and describe how ICI response may depend on HLA-mediated immunity.

Coronary restenosis is an important cause of poor long-term prognosis in patients with coronary heart disease. Here, we show that lysine methyltransferase SMYD2 expression in the nucleus is significantly elevated in serum- and PDGF-BB-induced vascular smooth muscle cells (VSMCs), and in tissues of carotid artery injury-induced neointimal hyperplasia. Smyd2 overexpression in VSMCs (Smyd2-vTg) facilitates, but treatment with its specific inhibitor LLY-507 or SMYD2 knockdown significantly inhibits VSMC phenotypic switching and carotid artery injury-induced neointima formation in mice. Transcriptome sequencing revealed that SMYD2 knockdown represses the expression of serum response factor (SRF) target genes and that SRF overexpression largely reverses the inhibitory effect of SMYD2 knockdown on VSMC proliferation. HDAC3 directly interacts with and deacetylates SRF, which enhances SRF transcriptional activity in VSMCs. Moreover, SMYD2 promotes HDAC3 expression via tri-methylation of H3K36 at its promoter. RGFP966, a specific inhibitor of HDAC3, not only counteracts the pro-proliferation effect of SMYD2 overexpression on VSMCs, but also inhibits carotid artery injury-induced neointima formation in mice. HDAC3 partially abolishes the inhibitory effect of SMYD2 knockdown on VSMC proliferation in a deacetylase activity-dependent manner. Our results reveal that the SMYD2-HDAC3-SRF axis constitutes a novel and critical epigenetic mechanism that regulates VSMC phenotypic switching and neointimal hyperplasia.

Impatiens is rich in germplasm resources, with more than 260 species in China. A study on the pollen micromorphology of Impatiens by scanning electron microscopy (SEM) showed that the pollen characteristics were richly diverse, and there was some correlation among the characteristics. In addition, the micromorphological index can be used for an effective cluster analysis of Impatiens. However, there was high interspecific similarity in some Impatiens, and the classification of Impatiens cannot be accurate to the species using pollen characteristics. Based on the classification conditions of Impatiens, the characteristics of the pollen structure were found to be useful to classify Impatiens into subgenera or smaller groups. The macroscopic characteristics and the number of sepals (NS) were used as references, which enabled the conclusion that there were 11 indices in the pollen micromorphological index, and the taxonomic effect was greater than the NS. In summary, the pollen micromorphology of Impatiens plays an important role in the classification of Impatiens. The purpose of this study was to explore this characteristic of Impatiens, which has some reference significance to supplement the pollen characteristics and palynological classification of Impatiens. The goal for this research was to aid in the interspecific identification and genetic breeding of Impatiens.

Objectives COVID-19 had significant influences on everyone’s lives. This study aimed to explore impacts of COVID-19 on mental and sexual health and access to health services among gay, bisexual and other men who have sex with men (GBMSM) in Singapore. Methods This qualitative study recruited 16 self-identified GBMSM via purposive sampling and semi-structured individual interviews were conducted. Three themes and seven sub-themes were derived from analysis done using the framework method. Results Participants shared how COVID-19 led to negative emotions and experiences at an intrapersonal level and interpersonal level (with families or partners), which were also worsened by prevailing stigma that GBMSM already face in Singapore and within their social networks. Sexual behaviours associated with HIV and other sexually transmitted infections risk and substance use were seen to be maladaptive coping methods of social isolation due to COVID-19. These dynamics were all exacerbated by the closure of “non-essential” services, which included many important services for mental and sexual health that were relevant to the GBMSM community. Conclusions Changes in policies and community efforts should be explored to improve these areas, enhancing the psychosocial and sexual well-being of GBMSM.

Objective To assess the feasibility, efficacy, and safety of microwave ablation in treating follicular thyroid neoplasms and suspicious follicular thyroid neoplasms.Methods In this retrospective study, the data of patients treated with microwave ablation for follicular neoplasms from December 2016 to January 2024 were summarized. The changes in nodule size, volume, technical success rate, disease progression, complete tumor resolution, thyroid function, and complications post-ablation were evaluated.Results Seventy-four patients (15 men, 59 women; mean age 46.3 ± 15.2 years) with follicular neoplasms were included. Over a median follow-up of 13 months, complete ablation was achieved, giving a 100% technical success rate. At the first month post-ablation, the maximum diameter of nodules showed no significant change (p = 0.287). From the third month, both maximum diameter and volume significantly decreased (p 0.05). The complication and side effect rates were 8.1% and 4.1%, respectively.Conclusions Initial findings suggest microwave ablation is an effective and safe treatment for follicular neoplasms, with low incidences of disease progression and complications, while maintaining thyroid function.

Background Statins are widely used for treating patients with ischemic stroke at risk of secondary cerebrovascular events. It is unknown whether Asian populations benefit from more intensive statin‐based therapy for stroke recurrence. Therefore, in the present study we evaluated the effectiveness and safety of high‐dose and moderate‐dose statins for patients who had experienced mild ischemic stroke during the acute period. Methods and Results This multicenter prospective study included patients with mild ischemic stroke who presented within 72 hours of symptom onset. The outcomes of patients in the high‐intensity and moderate‐intensity statin treatment groups were compared, with the main efficacy outcome being stroke recurrence and the primary safety end point being intracranial hemorrhage. The propensity score matching method was employed to control for imbalances in baseline variables. Subgroup analyses were conducted to evaluate group differences. In total, the data of 2950 patients were analyzed at 3 months, and the data of 2764 patients were analyzed at 12 months due to loss to follow‐up. According to the multivariable Cox analyses adjusted for potential confounders, stroke recurrence occurred similarly in the high‐intensity statin and moderate‐intensity statin groups (3 months: adjusted hazard ratio [HR], 1.12 [95% CI, 0.85–1.49]; P=0.424; 12 months: adjusted HR, 1.08 [95% CI, 0.86–1.34]; P=0.519). High‐intensity statin therapy was associated with an increased risk of intracranial hemorrhage (3 months: adjusted HR, 1.81 [95% CI, 1.00–3.25]; P=0.048; 12 months: adjusted HR, 1.86 [95% CI, 1.10–3.16]; P=0.021). The results from the propensity score‐matched analyses were consistent with those from the Cox proportional hazards analysis. Conclusions Compared with moderate‐intensity statin therapy, high‐dose statin therapy may not decrease the risk of mild, noncardiogenic ischemic stroke recurrence but may increase the risk of intracranial hemorrhage. Registration URL: www.chictr.org.cn/. Unique Identifier: ChiCTR1900025214.

Background: Colon adenocarcinoma (COAD) is one of the most common malignant tumors. The interplay involving ferroptosis between tumor and immune cells plays a crucial in cancer progression. However, the biological basis of this interplay in COAD development remains elusive. Methods: Transcriptome data of COAD samples were obtained from The Cancer Genome Atlas and National Center for Biotechnology Information databases. Using single-sample gene set enrichment analysis, we calculated the ferroptosis score (FS) and immune cell infiltration levels for each sample, leveraging the expression levels of genes related to ferroptosis and various immune cell types. Samples with FSs greater than the 75th percentile were classified into the high-FS subgroup, while those below the 25th percentile were categorized as the low-FS subgroup. Moreover, tumor tissue samples and adjacent normal tissue samples were collected from twenty colon patients. Using real-time quantitative polymerase chain reaction, we validated the expression of certain genes in these samples. Results: The COAD samples with high FSs experienced favorable survival probability and heightened sensitivity to anticancer drugs, with FSs negatively associated with the pathological stages. Moreover, the up-regulated genes in high-FS subgroup exhibited enrichment in immune-related pathways, suggesting a correlation between immunity and ferroptosis. Importantly, we discovered a key lncRNA-mRNA co-expression network linking tumor cell ferroptosis and immune infiltration (e.g., neutrophil) in the progression and classification of COAD. Further analysis identified several ferroptosis-related lncRNAs (e.g., RP11-399O19.9) within this network, indicating their potential roles in COAD progression and deserving in-depth study. Conclusions: Our findings provide novel insights into the underlying biological basis, particularly involving lncRNAs, at gene expression level associated with ferroptosis in COAD and cancer therapy. Nevertheless, further analysis and validation are required to expand the findings.

MicroRNAs (miRNAs) are small noncoding RNAs of 18–25 bases. miRNAs are also important new biomarkers that can be used for disease diagnosis in the future. Studies have shown that miR-124 levels are significantly elevated during acute myocardial infarction (AMI) and play a key role in the cardiovascular system. A variety of methods have been established to detect myocardial infarction-related miRNAs. However, most require complex miRNA extraction and isolation, and these methods are virtually undetectable when RNA levels are low in the sample. It may lead to biased results. Thus, it is necessary to develop a technique that can detect miRNA without extracting it, which means that intracellular detection is of great significance. Here, we improved the traditional silicon spheres and obtained a biosensor that could effectively capture and detect specific noncoding nucleic acids through the layer-by-layer assembly method. The sensor is protected by hyaluronic acid so it can successfully escape the lysosome into the cell and achieve detection. With the help of a full-featured microplate reader, we determined that the detection limit of the biosensor could reach 1 fM, meeting the needs of intracellular detection. At the same time, we prepared an oxidative stress cardiomyocyte infarction model and successfully captured the overexpressed miR-124 in the infarcted cells to achieve in situ detection. This study could provide a new potential tool to develop miRNAs for sensitive diagnosis in AMI, and the proposed strategy implies its potential for biomedical research.

Summary: Background: Mapping gut microecological features to serum metabolites (SMs) will help identify functional links between gut microbiome and cardiometabolic health. Methods: This study encompassed 836-1021 adults over 9.7 year in a cohort, assessing metabolic syndrome (MS), carotid atherosclerotic plaque (CAP), and other metadata triennially. We analyzed mid-term microbial metagenomics, targeted fecal and serum metabolomics, host genetics, and serum proteomics. Findings: Gut microbiota and metabolites (GMM) accounted for 15.1% overall variance in 168 SMs, with individual GMM factors explaining 5.65%–10.1%, host genetics 3.23%, and sociodemographic factors 5.95%. Specifically, GMM elucidated 5.5%–49.6% variance in the top 32 GMM-explained SMs. Each 20% increase in the 32 metabolite score (derived from the 32 SMs) correlated with 73% (95% confidence interval [CI]: 53%–95%) and 19% (95% CI: 11%–27%) increases in MS and CAP incidences, respectively. Among the 32 GMM-explained SMs, sebacic acid, indoleacetic acid, and eicosapentaenoic acid were linked to MS or CAP incidence. Serum proteomics revealed certain proteins, particularly the apolipoprotein family, mediated the relationship between GMM-SMs and cardiometabolic risks. Interpretation: This study reveals the significant influence of GMM on SM profiles and illustrates the intricate connections between GMM-explained SMs, serum proteins, and the incidence of MS and CAP, providing insights into the roles of gut dysbiosis in cardiometabolic health via regulating blood metabolites. Funding: This study was jointly supported by the National Natural Science Foundation of China, Key Research and Development Program of Guangzhou, 5010 Program for Clinical Research of Sun Yat-sen University, and the ‘Pioneer' and ‘Leading goose' R&D Program of Zhejiang.

Copper, an indispensable micronutrient, is implicated in numerous vital biological processes and is essential for all physiological activities. Recently, the discovery of a novel type of copper-dependent cell death, known as cuproptosis, has shed light on its role in cancer development. Extensive research is currently underway to unravel the mechanisms underlying cuproptosis and its correlation with various cancer types. In this review, we summarize the findings regarding the roles and mechanisms of cuproptosis in various cancer types, including colorectal cancer, lung cancer, gastric cancer, breast cancer, liver cancer and cutaneous melanoma. Furthermore, the effects of copper-related agents such as copper chelators and copper ionophores on cell proliferation, apoptosis, angiogenesis, tumor immunity, and chemotherapy resistance have been explored in cancer preclinical and clinical trials. These insights provide promising avenues for the development of prospective anticancer drugs aimed at inducing cuproptosis.