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Abstract Metabolic reprogramming fuels cancer cell metastasis and remodels the immunosuppressive tumor microenvironment (TME). We report here that circPETH, a circular RNA (circRNA) transported via extracellular vesicles (EVs) from tumor-associated macrophages (TAMs) to hepatocellular carcinoma (HCC) cells, facilitates glycolysis and metastasis in recipient HCC cells. Mechanistically, circPETH-147aa, encoded by circPETH in an m6A-driven manner, promotes PKM2-catalyzed ALDOA-S36 phosphorylation via the MEG pocket. Furthermore, circPETH-147aa impairs anti-HCC immunity by increasing HuR-dependent SLC43A2 mRNA stability and driving methionine and leucine deficiency in cytotoxic CD8+ T cells. Importantly, through virtual and experimental screening, we find that a small molecule, Norathyriol, is an effective inhibitor that targets the MEG pocket on the circPETH-147aa surface. Norathyriol reverses circPETH-147aa-facilitated acquisition of metabolic and metastatic phenotypes by HCC cells, increases anti-PD1 efficacy, and enhances cytotoxic CD8+ T-cell function. Here we show that Norathyriol is a promising anti-HCC agent that contributes to attenuating the resistance of advanced HCC to immune checkpoint blocker (ICB) therapies.

Abstract The ovary is crucial for female reproduction and health, as it generates oocytes and secretes sex hormones. Transplantation of mesenchymal stem cells (MSCs) has been shown to alleviate pathological ovarian aging. However, it is unclear whether MSCs could benefit the naturally aging ovary. In this study, we first examined the dynamics of ovarian reserve of Chinese women during perimenopause. Using a naturally aging cynomolgus monkey (Macaca fascicularis) model, we found that transplanting human embryonic stem cells-derived MSC-like cells, which we called M cells, into the aging ovaries significantly decreased ovarian fibrosis and DNA damage, enhanced secretion of sex hormones and improved fertility. Encouragingly, a healthy baby monkey was born after M-cell transplantation. Moreover, single-cell RNA sequencing analysis and in vitro functional validation suggested that apoptosis, oxidative damage, inflammation, and fibrosis were mitigated in granulosa cells and stromal cells following M-cell transplantation. Altogether, these findings demonstrate the beneficial effects of M-cell transplantation on aging ovaries and expand our understanding of the molecular mechanisms underlying ovarian aging and stem cell-based alleviation of this process.

Rolling bearings are crucial components in industrial applications, forming the core of modern rotating machinery. The belief rule base with interval structure (IBRB-r) is a rule-based expert system designed to describe the causality of bearing faults. It is mainly applicable in situations where data within the intervals are relatively concentrated. However, in practical industrial applications, bearing operation data is often dispersed. This leads to uneven data distribution within the reference interval, affecting the model’s accuracy. Additionally, the interpretability of the parameters decreases after the IBRB-r model is optimized. To address these issues, an adaptive rule matching interval structured belief rule (IBRB-Di) is proposed for bearing fault diagnosis. First, a rule matching method that can be dynamically computed within an reference interval is introduced. Also, a new computation method for the weights of rules activation within an interval is presented. These methods adapt to the dispersion of data and simplify the number of rules. Second, the projected covariance matrix adaptive evolution strategy with expert constraints (P-CMA-ES) is adopted to optimize the model. This aims to balance accuracy and interpretability. Finally, the method is experimentally validated using the Case Western Reserve University bearing dataset. This verification confirms the effectiveness of the proposed method.

Abstract Background Prothrombin induced by vitamin K absence‐II (PIVKA‐II) and Alpha‐fetoprotein (AFP) have been widely used as diagnostic markers in hepatocellular carcinoma (HCC), but the prognostic values of the two serum markers and their clinical usefulness in patient selection for different surgical approaches remain largely unclear. Methods HCC patients received surgical treatment between 2015 and 2019 were included. Patients were divided into four statuses according to the serum PIVKA‐II and AFP secretion status: PIVKA‐II (−) AFP (−) (status 1); PIVKA‐II (+) AFP (−) (status 2); PIVKA‐II (−) AFP (+) (status 3); PIVKA‐II (+) AFP (+) (status 4). Kaplan–Meier analyses were conducted to compare the survivals of the four groups and the HCC patients received different surgical interventions; time‐dependent AUC curves were introduced to evaluate the prognostic value of the PIV‐AFP status; Cox regression model was used to identify prognostic indexes for overall survival (OS) and recurrence‐free survival (RFS). Results A total of 518 patients were included. Patients with PIVKA‐II (+) and APF (+) presented significantly decreased OS and RFS comparing to the other statuses. The areas under ROC curves of PIV‐AFP status in predicting OS and RFS were superior to the PIVKA‐II or the AFP alone. The HCC patients in early stages with PIVKA‐II (+) and APF (+) had worse RFS when received laparoscopic hepatectomy than those who received open hepatectomy, whereas there was no difference in other secretion statuses. The PIVKA‐II (+) and AFP (+) secretion status was an independent risk factor for OS, RFS. Conclusions The PIV‐AFP secretion status is of favorable clinical utility in predicting the OS and RFS of the HCC patients; extra caution is needed when applicated the laparoscopic approach in the HCC patients with PIVKA‐II (+) and AFP (+).

Hepatocellular carcinoma (HCC) is the fifth most common malignancy and the third most common cause of cancer-related death worldwide. Due to asymptomatic patients in the early stage, most patients are diagnosed at an advanced stage and lose the opportunity for radical resection. In addition, for patients who underwent procedures with curative intent for early-stage HCC, up to 70% of patients may have disease recurrence within 5 years. With the advent of an increasing number of systemic therapy medications, we now have more options for the treatment of HCC. However, data from clinical studies show that with different combinations of regimens, the objective response rate is approximately 40%, and most patients will not respond to treatment. In this setting, biomarkers for predicting treatment response are of great significance for precise treatment, reducing drug side effects and saving medical resources. In this review, we summarized the existing and emerging biomarkers in the literature, with special emphasis on the pathways and mechanism underlying the prediction value of those biomarkers for systemic treatment response.

ObjectThe prediction of hepatocellular carcinoma (HCC) prognosis faced great challenge due to tumor heterogeneity. The purpose of this study was to explore the correlation between the immune infiltrate and prognosis. Moreover, we aimed to establish a risk prediction model for survival in HCC patients based on clinicopathological and immune indicators.MethodsIn this study, 316 patients with HCC who underwent radical resection in West China Hospital from 2009 to 2014 were included. Clinicopathological data and pathological specimens were collected. H&E staining and immunohistochemical staining were performed on the pathological tissue sections. The evaluation of tumor-infiltrating lymphocyte (TIL) density was based on H&E slices, and the assessment of the expressions of CD8, CD68, Lymphocyte activation gene-3 (LAG-3), T cell immunoglobulin domain and mucin domain-3 (TIM-3), Programmed Cell Death Protein 1 (PD-1), Programmed Cell Death Ligand 1 (PD-L1), OX40, CD66b, and Tryptase. was performed on the immunohistochemical slices. A risk prediction model for survival in HCC patients was established by integrating immune-related biomarkers and clinicopathological indicators.ResultsThe Barcelona Clinic Liver Cancer (BCLC) stage; the microvascular invasion status; the density of TILs; the expressing levels of CD66b, OX40, and PD-L1 in the immune cell; CD68; and CD8 were the predictors of patients’ overall survival (OS). The BCLC stage; the density of TILs; and the expressions of OX40, CD68, and CD8 were associated with disease-free survival (DFS). The expressions of CD66b, CD68, OX40, and CD8 had a cumulative effect on prognosis. The area under the curve of the prediction model for OS based on clinicopathological features was improved from 0.62 to 0.74 by adding to CD8, OX40, CD68, CD66b, and TILs, whereas it was improved from 0.59 to 0.73 for the DFS prediction model.ConclusionOur results, if confirmed, indicated that immune-related biomarkers should be taken into account or stratified in survival analysis for HCC.

Arterial degeneration, closely associated with cardiovascular diseases, is driven by aging-related vascular cell-specific transcriptomics changes. This study provides a single-cell transcriptomic atlas for senile aortic and coronary arteries and underscores FOXO3A-based the transcriptional network in vasoprotection during aging.

Abstract Blastocyst complementation by pluripotent stem cell (PSC) injection is believed to be the most promising method to generate xenogeneic organs. However, ethical issues prevent the study of human chimeras in the late embryonic stage of development. Primate embryonic stem cells (ESCs), which have similar pluripotency to human ESCs, are a good model for studying interspecies chimerism and organ generation. However, whether primate ESCs can be used in xenogenous grafts remains unclear. In this study, we evaluated the chimeric ability of cynomolgus monkey (Macaca fascicularis) ESCs (cmESCs) in pigs, which are excellent hosts because of their many similarities to humans. We report an optimized culture medium that enhanced the anti-apoptotic ability of cmESCs and improved the development of chimeric embryos, in which domesticated cmESCs (D-ESCs) injected into pig blastocysts differentiated into cells of all three germ layers. In addition, we obtained two neonatal interspecies chimeras, in which we observed tissue-specific D-ESC differentiation. Taken together, the results demonstrate the capability of D-ESCs to integrate and differentiate into functional cells in a porcine model, with a chimeric ratio of 0.001–0.0001 in different neonate tissues. We believe this work will facilitate future developments in xenogeneic organogenesis, bringing us one step closer to producing tissue-specific functional cells and organs in a large animal model through interspecies blastocyst complementation.

Achieving high detection accuracy of pavement cracks with complex textures under different lighting conditions is still challenging. In this context, an encoder-decoder network-based architecture named CrackResAttentionNet was proposed in this study, and the position attention module and channel attention module were connected after each encoder to summarize remote contextual information. The experiment results demonstrated that, compared with other popular models (ENet, ExFuse, FCN, LinkNet, SegNet, and UNet), for the public dataset, CrackResAttentionNet with BCE loss function and PRelu activation function achieved the best performance in terms of precision (89.40), mean IoU (71.51), recall (81.09), and F1 (85.04). Meanwhile, for a self-developed dataset (Yantai dataset), CrackResAttentionNet with BCE loss function and PRelu activation function also had better performance in terms of precision (96.17), mean IoU (83.69), recall (93.44), and F1 (94.79). In particular, for the public dataset, the precision of BCE loss and PRelu activation function was improved by 3.21. For the Yantai dataset, the results indicated that the precision was improved by 0.99, the mean IoU was increased by 0.74, the recall was increased by 1.1, and the F1 for BCE loss and PRelu activation function was increased by 1.24.

Abstract Background Prostate cancer is a worldwide health issue, and current prostate cancer care extends to the patient‒caregiver dyadic setting, where individuals are interdependent and interact with each other as well as possible negative psychological and behavioural outcomes. However, the impact of dyadic care interventions on health outcome indicators for prostate cancer patients and their informal caregivers has yet to be examined. Aim To describe the characteristics of dyadic interventions involving patients with prostate cancer and their informal caregivers and investigate their effects on psychosocial health, sexual health, and dyadic relationships. Methods Ten electronic databases (Web of Science, Cochrane Library, PsycINFO, PubMed, Embase, CINAHL, CNKI, Wanfang, VIP, and SinoMed) were thoroughly searched for related publications published between the database’s founding and April 2024. The risk of bias for the included studies was evaluated using the Cochrane risk-of-bias tool, and a meta-analysis was performed using RevMan 5.4. Results This study identified and evaluated 19 RCTs reporting 22 different interventions, as well as outcome indicators for the three aspects of psychosocial health, sexual health, and dyadic relationships in prostate cancer patients and informal caregivers. A meta-analysis of pooled data revealed that for prostate cancer patients, the intervention improved dyadic coping (SMD95% CI [95% CI] = 0.22 [0.01;0.42], p = 0.04), and for informal caregivers the dyadic care intervention reduced anxiety (SMD95% CI [95% CI] = -0.35 [-0.65;-0.06], p = 0.02), enhanced self-efficacy (SMD [95% CI] = 0.22 [0.01;0.43], p = 0.04), and improved sexual functioning (SMD [95% CI] = 0.29 [0.05;0.54], p = 0.02). No statistically significant overall effects were observed for the other outcome indicators. Conclusion The results of this review indicate that dyadic care interventions benefit prostate cancer patients and informal caregivers. However, given features such as research quality and sample size, further randomized controlled trials with excellent study designs are needed in the future to evaluate and validate the efficacy of dyadic care treatments for patients with prostate cancer. Trial registration The protocol for this study is registered in PROSPERO with registration number (CRD42024567542).

Abstract Metabolic syndrome (MetS) is a difficult-to-manage disease that poses a significant risk to human health. Here, we show that the supplementation of Lactobacillus reuteri ZJ617 ameliorates symptoms of MetS in mice induced by the high-fat diet. L. reuteri ZJ617 modulates host metabolism by interacting with the microbiome, resulting in the production of spermidine synthesized by the microbiota. L. reuteri ZJ617 serves as a source of substrates for the microbiota to synthesize spermidine, hence preventing the decline of bacteria responsible for spermidine production. Spermidine treatment mimics the metabolic effects of L. reuteri ZJ617, whereas pharmacological inhibition of spermidine biosynthesis in mice abolishes these benefits. Our findings reveal the mechanism by which L. reuteri ZJ617 alleviates MetS symptoms and provide support for its potential use as a probiotic for promoting metabolic health.

Abstract This paper presents an analytical examination of the small‐single stability (SSS) criterion of the permanent magnet synchronous generator (PMSG)‐based wind power delivery system via voltage source converter‐based high voltage direct current (VSC‐HVDC). First, a small‐signal model of the PMSG‐based WPDS is developed. Then, the SSS criterion, driven by the phase‐locked loop of the PMSG in the sub‐synchronous timescale, is derived. The derived SSS criterion provides analytical insights into why and how the loading condition, the grid connection, and the control parameters affect the system’s SSS. It is unambiguously revealed that increasing loading conditions of the PMSG or/and the grid connection of the WPDS to VSC‐HVDC shall bring about a higher risk of oscillatory instability. Hence, analytical derivation of the SSS criterion helps better understand the instability mechanism in the PMSG‐based WPDS via VSC‐HVDC. In addition, while the derivation of the SSS criterion presupposes identical dynamics among PMSGs, this derived criterion can still be approximately utilized to assess the SSS of the PMSG‐based WPDS via VSC‐HVDC, irrespective of whether the dynamics of the PMSGs are similar or different. Finally, the SSS criterion is demonstrated and evaluated through three examples of the PMSG‐based WPDS via VSC‐HVDC.

Abstract Background Upper urinary tract urothelial carcinoma (UTUC) is a rare and highly aggressive malignancy characterized by poor prognosis, making the accurate identification of high-grade (HG) UTUC essential for subsequent treatment strategies. This study aims to develop and validate a nomogram model using computed tomography urography (CTU) images to predict HG UTUC. Methods A retrospective cohort study was conducted to include patients with UTUC who underwent radical nephroureterectomy and received a CTU examination prior to surgery. In the CTU images, tumor lesions located in the renal calyces, renal pelvis and ureter were segmented, and radiomics features from the unenhanced, medullary, and excretory phases were extracted. The maximum relevance minimum redundancy algorithm, least absolute shrinkage and selection operator, and various machine learning (ML) algorithms—including random forest, support vector machine, and eXtreme gradient boosting—were employed to select radiomics features and calculate radiomics scores. Logistic regression (LR) analysis was performed to identify the independent influencing factors of clinical baseline characteristics. Multiple datasets of radiomics features were constructed by integrating single-phase radiomics features with the most significant independent factor. Both LR and ML algorithms were utilized to develop predictive models. The area under the receiver operating characteristic curve (AUC values), accuracy, sensitivity, and specificity were assessed for model performance evaluation. Decision curve analysis was conducted to evaluate the clinical net benefits. Results A total of 167 patients were enrolled in this study. Among them, 56 were diagnosed with low-grade UTUC (including papillary urothelial neoplasms with low malignant potential and low-grade urothelial carcinoma) as confirmed by postoperative pathological examination results, and 111 were of HG. These patients were randomly allocated to the training set and the validation set at a ratio of 7:3. The training set comprised 116 patients with a mean age of 63.5 ± 9.38 years and 38 males. The validation set comprised 51 patients with a mean age of 65.6 ± 11.1 years and 18 males. Hydronephrosis was identified as the most significant independent factor in the clinical baseline features. Models that include mixed-phase development achieve better performance compared to models that rely simply on single-phase development. The nomogram model had excellent predictive ability for HG UTUC, with AUC values of 0.844 and an accuracy of 0.793 in the validation sets. The nomogram model can enhance accuracy by 14.1% (79.3% vs. 65.2%) and sensitivity by 32.8% (93.2% vs. 60.4%) compared to urinary cytology. Conclusions This study developed a nomogram model, which significantly improved the diagnostic ability for HG UTUC compared to urinary cytology. Furthermore, the results of the decision curve analysis showed that the model had a net benefit and could provide a non-invasive and potentially diagnostic reference tool for HG UTUC.

Abstract In recent years, many meta‐heuristic algorithms have been investigated to estimate the parameters of photovoltaic (PV) models. However, the accuracy of the estimated parameters still needs to be concerned, especially for some complex PV models with many unknown parameters. In order to estimate the unknown parameters of the PV models more precisely and reliably, an efficient hybrid algorithm based on particle swarm optimisation and teaching‐learning‐based optimisation (PSOTLBO) is proposed in this paper. In PSOTLBO, inspired by the learner phase of teaching‐learning‐based optimisation (TLBO), an improved learner phase is designed and introduced into the basic PSO to enhance the global search ability and the ability to get rid of local optimum. The improved learner phase divides the population into four groups according to three values, which are the average fitness values of the overall population, the population in the first half of the fitness ranking and the population in the second half of the fitness ranking. Typically, each group has its particular movement pattern concentrating on exploration or exploitation respectively to improve the search efficiency of the algorithm. Furthermore, to deal with individuals beyond the boundary, a new designed probabilistic rebound strategy is introduced, which increases the diversity of population and avoids population aggregation at the search boundary. Then, the proposed PSOTLBO is applied to estimate the parameters of the single diode model, double diode model and PV module model. The comparative results between PSOTLBO and other 14 advanced algorithms show that the average root mean square error values of different PV models obtained by PSOTLBO are 9.86021878E−04, 9.82630511E−04, 2.42507487E−03, 1.72981371E−03, and 1.66006031E−02, respectively, which indicate that PSOTLBO can provide more accurate and stable parameter estimation results than other compared algorithms. Furthermore, the convergence experimental results demonstrate that PSOTLBO has outstanding performance in convergence speed and stability.

Metal matrix self-lubricating materials lie at the core of cutting-edge aerospace, mechanical, and electrical industries, which demand technological performances that cannot be met by traditional liquid lubricants. Rapid innovation in nanocarbon materials in recent years enabled rapid development of advanced nanocomposites for applications in structural engineering and functional devices. Carbonous materials (e.g., graphite, graphene and carbon nanotubes), exhibit a wide range of unique electrical, mechanical, and thermal properties, which are also considered ideal lubricating reinforcements for metal matrix nanocomposites (MMCs) with superior mechanical and tribological properties. In this review, we first showcase the distinctive features of the constituents commonly employed in self-lubricating MMCs, encompassing the high-strength metallic matrix and nano-carbonous reinforcement. Then, we present a comprehensive overview of the recent advancements in preparation techniques for these advanced MMCs, followed by an in-depth discussion on their corresponding tribological properties and wear mechanisms. We close this review by outlining key problems to be solved and the future trend of the development in self-lubricating MMCs.

ABSTRACT: Breastfeeding by mothers with gestational diabetes mellitus (GDM) has been shown to reduce maternal insulin demands and diminish the risks of diabetes in infants, leading to improved long-term health outcomes. Milk fat globule membrane (MFGM) proteins play a crucial role in influencing the immunity and cognitive development of infants. Understanding the alterations in MFGM proteins in breast milk from mothers with GDM is essential for enhancing their self-efficacy and increase breastfeeding rates. The objective of this study is to investigate and compare MFGM proteins in milk from mothers with and without GDM based on tandem mass tag (TMT) labeling and liquid chromatography–tandem MS techniques. A total of 5,402 proteins were identified, including 4 upregulated proteins and 24 downregulated proteins. These significantly altered proteins were found to be associated with human diseases, cellular processes, and metabolism pathways. Additionally, the oxidative phosphorylation pathway emerged as the predominant pathway through Gene Set Enrichment Analysis involving all genes.

Abstract The large scale deployment of modern wind turbines and the yearly increase of installed capacity have drawn attention to their operation and maintenance issues. The development of highly reliable and low‐maintenance wind turbines is an urgent demand in order to achieve the low‐carbon goals, and the arrival of fault diagnosis provides assurance for its satisfactory operation and maintenance. Numerous statistical studies have pointed out that generator failures are a main cause of wind turbine system downtime. The generator, as one of the core components, converts rotating mechanical energy into electrical energy. However, the generators can hardly operate reliably towards the end of the turbine life owing to the variable‐speed conditions and harsh electromagnetic environments. This article first provides a comprehensive and up‐to‐date review of the electrical and mechanical failures of various parts (stator, rotor, air gap and bearings) of the generator. Then the fault characteristics and diagnostic processes of generators are investigated, and the principles and processes of fault diagnosis are discussed. Finally, the application of four categories of model‐based, signal‐based, knowledge‐based and hybrid approaches to wind turbine generator fault diagnosis is summarized. The comprehensive review shows that the hybrid approach is now the leading and most accurate tool for real‐time fault diagnosis for wind turbine generators. A qualitative and quantitative assessment of algorithm performance using false alarm rates is proposed. The methodology can subsequently be applied to the wind industry.

Abstract Objective To discuss the differences in the effectiveness and security of kidney stones in overweight or obese patients by mini percutaneous nephrolithotomy (MiniPCNL) and retrograde intrarenal surgery (RIRS). Materials and methods We exhaustively searched numerous databases, including PubMed, Embase, Web of Science, Cochrane Library, and CNKI, covering all records from their initiation date until September 2023. This included controlled trials focusing on the use of MiniPCNL and RIRS in the treatment of kidney stones in overweight or obese patients. The gathered data was then analyzed using the Review Manager 5.4 software. Results 9 studies including 1122 patients were included. Meta-analysis showed that: The MiniPCNL group had higher overall complications, grade I complications, length of hospital stay(LOS), first stone-free rate (SFR), and final SFR in obese patients, with no significant difference between the two groups in terms of operative time(OT), hemoglobin drop, and grade II complication rate. There were more overall complications, grade I complications, final SFR, and LOS with MiniPCNL in patients with stones > 2 cm compared to no significant difference in grade II complications. MiniPCNL performed in the prone position had higher final SFR, less OT, hemoglobin drop, and no statistically significant difference in overall complications or LOS. Sheaths using > 14 F had higher overall complication rates, final SFR, and LOS, and no statistical differences in OT and first SFR between the two modalities. In the MiniPCNL subgroup aged ≤ 50 years, there were higher first SFR, final SFR, and shorter OT, and in the MiniPCNL subgroup aged > 50 years, there were more OT, LOS, and hemoglobin drop, with no statistical difference in overall complications between the two groups. Conclusion Our study showed that MiniPCNL in obese patients had higher initial SFR and final SFR, fewer procedures, but more postoperative complications, LOS, and grade I complications compared with RIRS. Similar results were seen in patients in the prone position, with stones > 2 cm and age ≤ 50 years. Systematic review registration [ https://www.crd.york.ac.uk/PROSPERO/ ], identifier PROSPERO (CRD42023467284).

Abstract Interfacial hole transfer from a photoexcited semiconductor to surface adsorbates is pivotal for initiating solar-to-chemical energy conversion, yet the atomic-level transfer kinetics remains elusive. Using the methoxy/TiO2(110) system as an archetype, here we elucidate the hole transfer mechanism from hole-trapping lattice oxygen to the methoxy adsorbate at gas/solid and liquid/solid interfaces through molecular dynamics simulations and static minimum energy path calculations. Instead of direct nonadiabatic hopping, we uncover an adiabatic migration pathway adapted to local substrate relaxation, driven by a bond-stretching mechanism supported by stronger Ti-O stretching vibrations. Notably, this mechanism persists at the aqueous methoxy/TiO2(110) interface, albeit hindered by interfacial water and coadsorbates. Surprisingly, the hole transfer barriers across various photoexcited adsorbate/TiO2 interfaces correlate more closely with the vertical excitation energies of the adsorbates rather than their redox potentials, indicating an early-type transition-state nature. These insights deepen our understanding of elementary hole transfer kinetics in surface photochemistry.

Abstract Prostate cancer (PCa), with high heterogeneity and poor prognosis, is one of the most common malignant tumors in men. Circular RNAs (circRNAs) have been identified in tumor progression and resistance to medication in numerous studies. However, the role of circ_0001047 in PCa is unclear. In this research, we found that circ_0001047 had low expression in PCa cells and tissues and was negatively correlated with testosterone secretion in vivo. Overexpression of circ_0001047 inhibited the proliferation, migration, invasion, and anti-apoptotic abilities of human PCa cells in vitro. Mechanistically, circ_0001047 promoted the expression of FKBP5 through sponge adsorption of miR-122-5p and then inhibited the proliferation, anti-apoptotic migration, and invasion abilities of PCa cells. In addition, overexpression of circ_0001047 enhanced the sensitivity of PCa cells to abiraterone by inhibiting AKT phosphorylation activation through upregulation of FKBP5/PHLPP1. This study revealed a novel mechanism by which circ_0001047 regulates PCa progression and treatment sensitivity via the miR-122-5p/FKBP5/PHLPP1/AKT axis. These findings deepen our comprehension of the molecular mechanisms in latent PCa progression and treatment resistance. Graphical Abstract

Abstract Introduction Urine-derived exosomes could potentially be biomarkers for bladder cancer (BC) diagnosis. This study aimed to systematically evaluate the diagnostic worth of urine-derived exosomes in BC patients through a meta-analysis of diverse studies. Methods A systematic search was carried out in PubMed, Web of Science, Embase, Cochrane, and CNKI databases to obtain the literature concerning the diagnosis of BC via urine-derived exosomes. A literature retrieval strategy was devised to pick articles and extract needed data from the literature. QUADS-2 was used to evaluate the quality of the included literatures, and the aggregated diagnostic effect was assessed by calculating the area under the aggregated SROC curve. All statistical analyses and plots were conducted with STATA 14.0 and RevMan5.3. Results A total of 678 articles were retrieved by means of the search strategy of the online database. Through screening, 21 articles were obtained, involving 3348 participants and 77 studies. The meta-analysis of the results indicated that urinary exosomes had a combined sensitivity of 0.75, a specificity of 0.77, and a combined AUC of 0.83 for the diagnosis of BC, suggesting that urine-derived exosomes have a relatively satisfactory diagnostic effect in the detection of BC. Among the subgroups classified by biomarker, long non-coding RNAs (lncRNAs) had the highest comprehensive sensitivity (SEN = 0.78), and miRNAs had the highest comprehensive specificity (SPN = 0.81). In other subgroup analyses, the biomarker panel for multiple exosomes combined diagnosis demonstrated the best diagnostic efficacy, with a combined the area under the curve ( AUC) of 0.87. Conclusions As a novel biomarker, urine-derived exosomes have significant diagnostic prospects in the diagnosis of BC. Nevertheless, their application in clinical settings still demands a considerable number of clinical trials to confirm their clinical feasibility and practicability.

Abstract In heavy oil reservoirs, favorable reservoir properties have a positive impact on the production performance during CO2 huff-n-puff. It is significant to study the screening method of applicable conditions for CO2 huff-n-puff in actual reservoirs. To solve these problems, this paper introduced the orthogonal design method to analyze the main factors based on numerical simulation. The technical analysis and the economic evaluation were both employed to obtain the applicable conditions of selecting oil layers or injection wells during CO2 huff-n-puff. And a new algorithms of machine learning, the random forest algorithm, was introduce to find the weighted factors and the scoring standards that were suitable for CO2 huff-n-puff. Finally, a set of method for screening suitable reservoir conditions was established. Based on the introduction of orthogonal analysis method and random forest algorithm, a software was established to achieve the purpose of analyzing the feasibility of CO2 huff-n-puff considering different reservoir geological parameters. This method increased the accuracy and efficiency in screening reservoir conditions that was suitable for CO2 huff-n-puff.

Objective: Investigate the effects of Lonicera caerulea anthocyanin complex liquid preparation (compound made of Lonicera caerulea L., Polygonatum sibiricum, Inonotus obliquus, LPI) on glucose and lipid metabolism in type 2 diabetes mellitus (T2D) mice. Methods: T2D model in mice was constructed by high-fat feeding combined with streptozotocin. The mice were randomly divided into 6 groups: Blank control group, diabetes model group, low, middle and high dose sample group and metformin positive control group. After continuous intervention for 28 days, the body mass data and physiological and biochemical indexes of mice were measured and recorded, and the pathological observation of the organs of mice was performed. Results: Each dose group of LPI could increase the weight of T2D mice, improve the symptoms of organ injury, significantly reduce serum insulin level (P

Abstract Background Diabetic nephropathy (DN) is a common complication of diabetes mellitus, and Prolyl 4-Hydroxylase Subunit Beta (P4HB) expression is increased in high glucose (HG)-induced renal tubular epithelial cells (TECs). But it’s role in HG-induced TECs remains to be elucidated. Methods The HK-2 cells were induced using HG and transfected with SiRNA-P4HB. DCFH-DA staining was utilized for the detection of cellular levels of ROS. WB and immunofluorescence were utilized to detect the expression of P4HB, epithelial-mesenchymal transition (EMT), fibrosis, and TGFβ/SMAD3-related proteins in HK-2 cells. Online databases were utilized for predicting the interaction target of P4HB, and immunoprecipitation (IP) experiments were employed to validate the binding of P4HB with the target. SiRNA and overexpression vectors of target gene were used to verify the mechanism of action of P4HB. Results HG induced an increase in the expression of P4HB and TGFβ, p-SMAD3, and ROS in HK-2 cells. Furthermore, HG downregulated the expression of E-cadherin and upregulated the expression of N-cadherin, Vimentin, α-SMA, Fibronectin, Collagen IV, SNAIL, and SLUG in HK-2 cells. Interfering with P4HB significantly reversed the expression of these proteins. Database predictions and IP experiments showed that P4HB interacts with PRMT1, and the expression of PRMT1 was increased in HG-induced HK-2 cells. Interfering with PRMT1 inhibited the changes in expression of EMT and fibrosis related proteins induced by HG. However, overexpression of PRMT1 weakened the regulatory effect of P4HB interference on the EMT, fibrosis, and TGFβ/SMAD3-related proteins in HK-2 cells. Conclusion P4HB regulated the TGFβ/SMAD3 signaling pathway through PRMT1 and thus participates in HG-induced EMT and fibrosis in HK-2 cells.

ObjectiveBacillus cereus (B. cereus) can be used as a probiotic or produce a variety of toxins that are pathogenic to humans and animals. Environmental stressors can affect the growth process of B. cereus and the expression of its virulence genes. Due to the limitations of methods such as pharmacological disinfection methods (there are limits to the use of antibiotics) and chemical disinfection methods (chemical methods may produce residues), attempts can be made to remove and reduce B. cereus infections through environmental stress factors.MethodsIn this study, the expression of four virulence genes (nheA, hblD, cytK, and entFM) of bovine-origin lethal B. cereus was investigated by qPCR under the effect of different environmental stressors. The extent of pathological damage to various organs of mice by B. cereus was observed by pathological sections.ResultsThe results showed that high temperature could inhibit the expression of B. cereus virulence genes. Expression of B. cereus virulence genes was affected under the influence of pH. Different salt concentrations could make the B. cereus virulence genes show low expression. Under a single environmental stressors, nheA, hblD, cytK, and entFM had the lowest expression at 40°C, pH 8.0, and were lowly expressed at all salt concentrations except the control group. The action of multiple environmental stressors affect the expression of virulence genes. Under multiple environmental stressors, nheA, hblD and cytK were least expressed at a temperature of 40°C, pH 6.0, and salt concentration of 3.0%, and entFM was least expressed at a temperature of 20°C, pH 8.0, and salt concentration of 1.5%. Animal pathogenicity tests have shown that environmental stressors affect the virulence of B. cereus.ConclusionThe level of virulence gene expression in B. cereus can be reduced by environmental stress factors, thus further reducing the risk of B. cereus to human health. This study provides some reference for the prevention and control of B. cereus disease.

ObjectiveIn January 2023, China implemented the “Class B Management” policy, marking a new phase in COVID-19 control. As new SARS-CoV-2 variants continue to emerge, some have shown significant immune evasion, posing challenges to epidemic control efforts. To manage the pandemic effectively, Henan Province launched a surveillance program for SARS-CoV-2 variants, systematically analyzing their clinical characteristics and epidemiological patterns.MethodsThis study collected genomic sequence data from 5,965 COVID-19 cases between January 1, 2023, and March 17, 2024, using the Henan Province SARS-CoV-2 variant surveillance system. Genome sequence analysis was performed with CLC Genomics Workbench, and genotyping and sequence alignment were carried out using the Nextclade platform. The clinical severity of different variants was assessed in relation to patient sex, age, clinical classification, and vaccination status.ResultsBetween Week 1 of 2023 and Week 11 of 2024, a total of 5,965 complete SARS-CoV-2 genome sequences were obtained, including 3,004 male (50.36%) and 2,961 female (49.64%) cases. The majority of cases were mild (5,451 cases, 91.38%), followed by moderate (311 cases, 5.21%) and severe or critical cases (203 cases, 3.4%). The predominant variants included BA.5.2, XBB, and BA.2.86. BA.5.2 was dominant until April 2023, after which it was gradually replaced by XBB. From December 2023, BA.2.86 began to increase and became the predominant variant by January 2024. The XBB variant exhibited a significantly lower rate of severe cases, with most infections being mild (P < 0.05). Male patients, the elderly, and certain variants (e.g., BA.5.2) were associated with more severe outcomes, while XBB and BA.2.86 showed lower pathogenicity, with a marked reduction in severe and fatal cases (P < 0.05).ConclusionAs SARS-CoV-2 variants evolve, the incidence of severe cases has progressively decreased. Both XBB and BA.2.86 variants exhibit lower pathogenicity. This study provides vital scientific evidence on the epidemiological features, clinical manifestations, and control strategies of SARS-CoV-2 variants. It underscores the importance of continuous viral surveillance and genomic sequencing to guide public health decision-making.

Antibiotic resistance is a critical global public health issue. The gut microbiome acts as a reservoir for numerous antibiotic resistance genes (ARGs), which influence both existing and future microbial populations within a community or ecosystem. However, the differences in ARG expression between fresh and composted feces remain poorly understood. In this study, we collected eight samples from a farm in Kaifeng City, China, comprising both fresh and composted pig manure. Using a high-throughput quantitative PCR array, we analyzed differences in ARG expression between these two types of manure. Our findings revealed significant differences in ARG profiles, as demonstrated by principal coordinate analysis (PCoA). Further analysis identified 39 ARGs (log2FC > 1, p < 0.05) in composted pig manure, with 25 genes downregulated and 14 upregulated. Notably, tetB-01, blaOCH, and blaOXY were the most abundant in composted pig manure compared to fresh manure. Additionally, 16S rRNA species profiling revealed that the composting process significantly altered the microbial community structure, with an increased abundance of Firmicutes and a decreased abundance of Bacteroidetes in composted pig manure. In summary, composting substantially transforms both the microbial community structure and the ARG profile in pig manure, underscoring its potential role in modulating the dynamics of ARGs in agricultural environments.

ObjectiveThe aim of this study was to investigate the clinical effectiveness of a perforator flap from the ulnar palm in repairing soft tissue defects in the palm and fifth digit following severe Dupuytren's contracture.MethodsA retrospective study was conducted between March 2013 and January 2023. In total, 25 patients with soft tissue defects that occurred after severe Dupuytren's contracture release were treated using a perforator flap from the ulnar palm. Improvements in symptoms and functionality were assessed and compared before and after surgery. Data regarding the degree of contracture, two-point discrimination, and the total active motion (TAM) scale of the affected hand were collected by the same physician at the specified time points (preoperative, postoperative, and final follow-up), along with an evaluation of the donor and recipient areas of the flap. Concurrently, patients completed the visual analog scale (VAS) and disability of arm, shoulder, and hand (DASH) questionnaires.ResultsAll 25 flaps survived uneventfully, and the wound healed primarily. The follow-up time was 15–26 months (average, 20.48 months). At the final follow-up, the patient satisfaction score related to flap appearance ranged from 4 to 5 (mean, 4.72). The average two-point discrimination value of the flap was 5.52 ± 0.97 mm. The contracture of the affected hand was improved with a mean TAM of 229° ± 16.75°. Furthermore, the degree of pain and functional status of the affected hand had improved (P

The protection of the ecological environment and the scarcity of renewable resources are increasingly concerning global issues. To address these challenges, efforts have been made to use desert sand and fly ash in the preparation of building materials. This study attempts to replace river sand with desert sand and cement with fly ash to create an environmentally friendly and economical building material—desert sand dry-mixed mortar (DSDM). Through preliminary mix ratio experiments, five grades of DSDM were developed, and their durability in the saline soil regions of northwest China was studied. The study conducted macro-performance tests on the five strength grades of DSDM after sulfate dry-wet cycles (DWCs), analyzing changes in appearance, mass loss rate, compressive strength loss rate, and flexural strength loss rate. Using SEM, XRD, and NMR testing methods, the degradation mechanisms of the DSDM samples were analyzed. Results indicate that sulfate ions react with hydration products to form ettringite and gypsum, leading to sulfate crystallization. In the initial stages of DWCs, these erosion products fill the pores, increasing density and positively impacting the mortar's performance. However, as the number of cycles increases, excessive accumulation of erosion products leads to further expansion of pores and cracks within the DSDM, increasing the proportion of harmful and more harmful pores, degrading performance, and ultimately causing erosion damage to the mortar. Among the samples, DM5 exhibited the poorest erosion resistance, fracturing after 30 cycles with a mass loss of 43.57 %. DM10 experienced failure after 60 cycles, with its compressive strength retention dropping to 78.86 %. In contrast, DM15, DM20, and DM25 showed the best erosion resistance, with compressive strength retention above 75 % after 120 cycles. Finally, the Wiener random probability distribution was used to predict the remaining life of DSDM samples under different degradation indicators, with flexural strength being the most sensitive indicator. Based on the flexural strength loss rate, the maximum sulfate DWCs for DM5, DM10, DM15, DM20, and DM25 were 132, 118, 78, 52, and 35 cycles, respectively. This study provides a theoretical basis for the promotion and use of DSDM in desert fringe areas.

ABSTRACTThe mechanisms of how host-microbe mutualistic relationships are established at weaning contingently upon B-cell surveillance remain inadequately elucidated. We found that CD138+ plasmacyte (PC)-mediated promotion of IgA response regulates the symbiosis between Bacteroides uniformis (B. uniformis) and the host during the weaning period. The IgA-skewed response of CD138+ PCs is essential for B. uniformis to occupy a defined gut luminal niche, thereby fostering stable colonization. Furthermore, B. uniformis within the natural gut niche was perturbed in the absence of IgA, resulting in exacerbated gut inflammation in IgA-deficient mice and weaned piglets. Thus, we propose that the priming and maintenance of intestinal IgA response from CD138+ PCs are required for host-microbial symbiosis, whereas the perturbation of which would enhance inflammation in weaning process.

The aim of this study was to analyze the effects of non-genetic factors on the estimation of genetic parameters of early growth traits in hybrid mutton sheep using ASReml software, in order to provide theoretical basis for screening the optimal hybriding combinations and accelerating the breeding process of new breeds of specialized housed-feeding mutton sheep. We selected the wellgrown hybrid Southhu (Southdown × Hu sheep) and Dorhu (Dorset × Hu sheep) sheep as the research objects, constructed weight correction formulae for SH and DH sheep at 60 and 180 days; and used ASReml software to investigate the effects of non-genetic factors on the estimation of genetic parameters of early growth traits in hybrid sheep. The results showed that the birth month and birth type were found significant for all traits (p