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In this study, biodegradable Zn-Cu-Mn alloy stents were implanted into porcine coronary artery for 18 months, and the in vivo biosafety and efficacy as well as the degradation behavior were systematically studied. Results showed a rapid endothelialization of the target vessel was achieved at 1 month post-implantation. Although the lumen diameter loss and local inflammation were observed at the early stage, the stented blood vessel could gradually recover with time. The lumen diameter was already close to normal range at 12 months, indicating good bioefficacy of the stent. No adverse effect on blood indexes or local accumulation of Zn, Cu or Mn elements were found after implantation, neither the malapposition and thrombosis were observed, which exhibited good biosafety of the stents. The stent could maintain the basic structure and mechanical integrity at 6 months, and remained only approximately 26 % of the stent volume at 18 months, suggesting a desirable degradation rate. In general, the Zn-Cu-Mn alloy stent showed great advantages and prospects in clinical application.

Abstract Background The persistent accumulation of senescence cells is one of the characteristics of radiation-induced skin injury (RISI), leading to fibrosis and impaired healing. However, the reasons why these senescence cells are resistant to clearance remain unclear. Methods The mouse RISI model was established using an X-ray generator, and a shield was used to cover all areas except the skin of the right leg or back for protecting surrounding tissue. ScRNA sequencing, immunohistochemistry, immunofluorescence, qPCR, western blot, primary cell co-culture system and fluorescence microsphere phagocytosis assay were performed for the functional and mechanistic investigations. Results The dynamic changes of senescence cell levels and multiple immune cell levels during RISI were evaluated, we found that macrophages could remove senescence cells from the dermis, and the clearance ability gradually strengthens over time. ScRNA sequencing revealed that macrophages with high senescence clearance capacity exhibited increased NOD-like receptor family pyrin domain-containing 3 (NLRP3) expression compared to those with low senescence clearance capacity. Inhibition or conditional knockout of Nlrp3 in macrophages led to senescence cell clearance dysfunction and impaired healing. Further studies found that interleukin-33 secreted by senescence cells inhibited the expression of NLRP3 in macrophages and their ability to phagocytize senescence cells, especially in the early stages after radiation. In addition, Nocardia rubra cell wall skeleton (Nr-CWS), an approved immunomodulator, was found to activate macrophage NLRP3 expression, reduce senescence cell burden, and accelerate the healing of RISI. Conclusion This study underscored NLRP3 in macrophages as a critical intervention target for senescence cell immunosurveillance and emphasized Nr-CWS as a potential therapeutic agent for accelerating senescence cell clearance in RISI. Graphical Abstract

Abstract Background Methicillin resistant Staphylococcus aureus (MRSA) is one of the main causes of hospital-acquired infections, but the diagnosis of MRSA pseudomembranous enteritis has faded in recent years. Here, we reported a pseudomembranous enteritis case in a young male patient caused by ST5 MRSA. Methods Clinical data of the patient were collected from medical records. Mass spectrometry identification, antimicrobial susceptibility testing, whole genome sequencing, as well as resistance and virulence genes detection of MRSA strain were performed. Results A 27-year-old young man with acute pancreatitis and septic shock in the intensive care unit passed large volume of intestine-like “stool” with more than 200 centimetres in length. A large number of Gram-positive cocci was persistently found in the stool samples. Histopathological examination of the intestine-like stool revealed that this stool was actually pseudomembrane, consisting of fibrinous exudate, inflammatory cells and clusters of gram-positive cocci adjacent to the luminal border. The patient was suspected for diagnosis of pseudomembranous enteritis. Stool and gastric juice cultures were positive for MRSA. These strains belonged to ST5-SCCmec II-t311, and harbored abundant virulence genes, especially enterotoxin genes. They contained not only sea, sec3, sel, but an enterotoxin gene cluster (egc, seg, sei, sem, sen, seo, yent1 and yent2), which may serve as an enterotoxin gene nursery. Besides, the strains were related to the isolates of the same hospital between 2013 and 2015, and there may be nosocomial transmission. Conclusions The severe clinical symptoms in this patient and the described virulence genes all suggested that these ST5 strains belonged to a kind of hypervirulent MRSA lineage. At the same time, the analysis of cgMLST indicated that there might be nosocomial transmission, which required the society to pay more attention to this highly virulent nosocomial clone.

Abstract Background Cardiometabolic risk factors (CMRFs) related to metabolic dysfunction-associated steatotic liver disease (MASLD) comprised overweight/obesity, impaired glucose metabolism, hypertension, hypertriglyceridemia and low high-density lipoprotein cholesterol. We aimed to describe the overlap prevalence and synergistic interaction of the five CMRFs on MASLD and liver fibrosis. Methods Using data of 2017–2020 National Health and Nutrition Examination Survey, we included non-pregnant participants aged ≥ 20 years who completed vibration-controlled transient elastography examinations and had sufficient information to determine their metabolic status. Logistic and generalized linear regression models were performed to assess synergistic interaction between CMRFs on MASLD and identify the contributions to liver fibrosis. Results The overall estimated prevalence of MASLD was about 33.1%. More than 80% of patients had three or more CMRFs. For MASLD, synergistic interaction between pairs of overweight/obesity and other four CMRFs were higher than it between other CMRFs’ pairs [attributable proportion(AP): 40–50% vs 20–30%]. For liver fibrosis, overweight/obesity and impaired glucose metabolism or hypertension had significant synergistic interactions (AP: 50% or 30%, respectively). We identified 27 out of 31 possible CMRF combinations. Combinations including dyslipidemia were more frequent in men than women (77% vs 59%). Combinations including hypertension were less in Mexican Americans than other ethnicities (25% vs 45–57%). Most combinations with three or more CMRFs, regardless of overlap type, had significant associations with elevated liver stiffness value. Conclusions CMRF overlap was quite common and had additive interaction in patients with MASLD. Overlapping number may be more important than combination type in liver fibrosis development.

Abstract Fatty acid composition (FA) is an important indicator of meat quality in beef cattle. We investigated potential functional candidate genes for FA in beef cattle by integrating genomic and transcriptomic dataset through multiple strategies. In this study, we observed 65 SNPs overlapping with five candidate genes (CCDC57, FASN, HDAC11, ALG14, and ZMAT4) using two steps association based on the imputed sequencing variants. Using multiple traits GWAS, we further identified three significant SNPs located in the upstream of FASN and one SNP (chr19:50779529) was embedded in FASN. Of those, two SNPs were further identified as the cis-eQTL based on transcriptomic analysis of muscle tissues. Moreover, the knockdown of FASN yielded a significant reduction in intracellular triglyceride content in preadipocytes and impeded lipid droplet accumulation in adipocytes. RNA-seq analysis of preadipocytes with FASN interference revealed that the differentially expressed genes were enriched in cell differentiation and lipid metabolic pathway. Our study underscored the indispensable role of FASN in orchestrating adipocyte differentiation, and fatty acid metabolism. The integrative analysis with multiple strategies may contribute to the understanding of the genetic architecture of FA in farm animals.

Abstract Objective This study aimed to evaluate the clinical efficacy, safety, and feasibility of medical thoracoscopy combined with fibrinolytic therapy for the treatment of complicated parapneumonic effusions and empyema, with a focus on therapeutic outcomes and recovery duration. Methods A retrospective cohort study was conducted involving 108 patients treated at Zhongshan Hospital, Xiamen University, between January 2015 and May 2024. Patients were categorized into two groups: the medical thoracoscopy group (n = 33) and the traditional treatment group (n = 75). The thoracoscopy group underwent thoracoscopic adhesiolysis and loculation breakdown, followed by intrapleural urokinase administration. The traditional treatment group received pleural catheter drainage combined with urokinase therapy. Primary outcomes included changes in inflammatory markers (white blood cell count, C-reactive protein, and procalcitonin), imaging outcomes (resolution of pleural effusion, pulmonary inflammation, and the incidence of pleural thickening at three months), pulmonary function assessed by forced vital capacity (FVC), and in-hospital mortality. Secondary outcomes encompassed the duration of postoperative fever, drainage time, intravenous antibiotic use, complication rates, initial treatment failure, length of hospital stay, and hospitalization costs. Results Both groups demonstrated significant reductions in inflammatory markers post-treatment (P 0.05). Improvements in FVC were observed in both groups, with significantly greater gains in the thoracoscopy group (P 0.05). Conclusions Medical thoracoscopy combined with fibrinolytic therapy offers significant advantages in the management of complicated parapneumonic effusions and empyema. This approach effectively enhances inflammation control, improves pulmonary function, and accelerates recovery time without compromising safety or increasing costs, underscoring its potential for broader clinical application.

Abstract Background Glioma is a brain tumor and glioblastoma represents its most common type, accounting for almost 40% of primary tumors of the central nervous system, and is associated with the worst prognosis. Glioblastoma remains one of the major challenges in neurooncology. Recently, the Food and Drug Administration (FDA) has approved tumor treating fields (TTF) for the treatment of glioblastoma. In this analysis, we aimed to systematically assess the adverse outcomes associated with TTF when combined to temozolamide versus temozolamide alone for the treatment of glioblastoma. Methods MEDLINE (subset PubMed), EMBASE, Web of Science, Cochrane databases, Google scholar, and http://www.ClinicalTrials.gov were searched for publications comparing TTF in combination with temozolomide versus temozolomide alone for the treatment of glioblastoma. The adverse outcomes were considered as the endpoints in this analysis. The statistical analysis was carried out by the latest version of the RevMan software (version 5.4). Risk ratios (RR) with 95% confidence intervals (CI) were used to represent the data following assessment. A random effect model was used during the statistical analysis. Results A total number of 994 participants were included in this analysis whereby 572 participants were assigned to TTF + temozolomide, whereas 422 participants were assigned to temozolomide alone. All the studies were randomized trials. The majority of the participants were males (68.0–75.0%) with a mean age of the varying from 54.0 to 69.0 years. Results of this analysis showed that TTF in combination with temozolomide was not associated with significantly higher adverse outcomes related to blood and lymphatic system disorders (RR:0.87, 95% CI 0.30–2.48; P = 0.79), gastrointestinal disorders (RR: 0.83, 95% CI 0.14–4.72; P = 0.83), general deterioration and malaise (RR: 1.43, 95% CI 0.90–2.25; P = 0.13), infections and infestations (RR: 1.21, 95% CI 0.33–4.45; P = 0.78), injury/poison and procedural complications (RR: 1.78, 95% CI 0.88–3.61; P = 0.11), metabolic and nutritional disorders (RR: 0.61, 95% CI 0.34–1.08; P = 0.09), central nervous system disorders (RR: 1.14, 95% CI 0.89–1.46; P = 0.31), musculoskeletal and connective tissue disorders (RR: 0.99, 95% CI 0.48–2.07; P = 0.99), respiratory/thoracic/mediastinal disorders (RR: 0.85, 95% CI 0.44–1.62; P = 0.62), and psychiatric disorders (RR: 1.27, 95% CI 0.42–3.79; P = 0.67). Similar adverse effects were observed. Conclusion TTF in combination with temozolomide was not associated with significantly worse adverse outcomes for the treatment of patients with glioblastoma. Hence, future trials should focus on the cost-effectiveness of TTF for the treatment of glioblastoma.

Abstract Background A key challenge in the medical field is managing gallbladder polyps (GBP) > 10 mm, especially when their nature is uncertain. GBP with a diameter exceeding 10 mm are associated with an increased risk of gallbladder cancer, making the key to their management the differentiation between benign and malignant types. The current practice, due to the inability to predict accurately, leads to excessive surgeries and ineffective follow-ups, increasing patient risks and medical burdens. Purpose This study aims to establish an imaging radiomics model using clinical data and contrast-enhanced ultrasound (CEUS) to predict neoplastic GBP exceeding 10 mm in diameter preoperatively. Materials and methods Data from 119 patients with GBP > 10 mm of unknown origin were analyzed. A total of 1197 features were extracted from the GBP area using conventional ultrasound (US) and CEUS. Significant features were identified using the Mann–Whitney U test and further refined with a least absolute shrinkage and selection operator (LASSO) regression model to construct radiomic features. By integrating clinical characteristics, a radiomics nomogram was developed. The diagnostic efficacy of the preoperative logistic regression (LR) model was validated using receiver operating characteristic (ROC) curves, calibration plots, and the Hosmer–Lemeshow test. CEUS is an examination based on conventional ultrasound, and conventional two-dimensional ultrasound still poses significant challenges in differential diagnosis. CEUS has a high accuracy rate in diagnosing the benign or malignant nature of gallbladder space-occupying lesions, which can significantly reduce the preoperative waiting time for related examinations and provide more reliable diagnostic information for clinical practice. Results Feature selection via Lasso led to a final LR model incorporating high-density lipoprotein, smoking status, basal width, and Rad_Signature. This model, derived from machine learning frameworks including Support Vector Machine (SVM), Logistic Regression (LR), Multilayer Perceptron (MLP), k-Nearest Neighbors (KNN), and eXtreme Gradient Boosting (XGBoost) with fivefold cross-validation, showed AUCs of 0.95 (95% CI: 0.90–0.99) and 0.87 (95% CI: 0.72–1.0) in internal validation. The model exhibited excellent calibration, confirmed by calibration graphs and the Hosmer–Lemeshow test (P = 0.551 and 0.544). Conclusion The LR model accurately predicts neoplastic GBP > 10 mm preoperatively. Radiomics with CEUS is a powerful tool for analysis of GBP > 10 mm. The model not only improves diagnostic accuracy and reduces healthcare costs but also optimizes patient management through personalized treatment plans, enhancing clinical outcomes and ensuring resources are more precisely allocated to patients who need surgery.

Abstract RNA degradation using ribonuclease targeting chimeras (RiboTACs) is a promising approach for cancer therapy. However, potential off-target degradation is a serious issue. Here, a RiboTAC is designed for tumor microenvironment triggered activation. The tumor microenvironment activated RiboTAC (TaRiboTAC) incorporates two pre-miR-21 binders, a near-infrared fluorophore IR780, an RGD targeting peptide and a phenylboronic acid caged ribonuclease recruiter. The caged ribonuclease recruiter is embedded in the molecule and exposed in acidic pH, the phenylboronic acid cage is removed by H2O2 making the TaRiboTAC responsive to the acidic and high H2O2 levels in the tumor microenvironment. It is shown the TaRiboTAC targets tumor tissue and degrades pre-miR-21. The degradation of pre-miR-21 by TaRiboTACs significantly increases the radiotherapeutic susceptibility of cancer cells achieving efficient suppression of human lung adenocarcinoma A549 tumors in living mice.

Through-wall human pose reconstruction and behavior recognition have enormous potential in fields like intelligent security and virtual reality. However, existing methods for through-wall human sensing often fail to adequately model four-Dimensional (4D) spatiotemporal features and overlook the influence of walls on signal quality. To address these issues, this study proposes an innovative architecture for through-wall human sensing using a 4D imaging radar. The core of this approach is the ST2W-AP fusion network, which is designed using a stepwise spatiotemporal separation strategy. This network overcomes the limitations of mainstream deep learning libraries that currently lack 4D convolution capabilities, which hinders the effective use of multiframe three-Dimensional (3D) voxel spatiotemporal domain information. By preserving 3D spatial information and using long-sequence temporal information, the proposed ST2W-AP network considerably enhances the pose estimation and behavior recognition performance. Additionally, to address the influence of walls on signal quality, this paper introduces a deep echo domain compensator that leverages the powerful fitting performance and parallel output characteristics of deep learning, thereby reducing the computational overhead of traditional wall compensation methods. Extensive experimental results demonstrate that compared with the best existing methods, the ST2W-AP network reduces the average joint position error by 33.57% and improves the F1 score for behavior recognition by 0.51%.

Human pose estimation holds tremendous potential in fields such as human-computer interaction, motion capture, and virtual reality, making it a focus in human perception research. However, optical image-based pose estimation methods are often limited by lighting conditions and privacy concerns. Therefore, the use of wireless signals that can operate under various lighting conditions and obstructions while ensuring privacy is gaining increasing attention for human pose estimation. Wireless signal-based pose estimation technologies can be categorized into high-frequency and low-frequency methods. These methods differ in their hardware systems, signal characteristics, noise processing, and deep learning algorithm design based on the signal frequency used. This paper highlights research advancements and notable works in human pose reconstruction using millimeter-wave radar, through-wall radar, and WiFi. It analyzes the advantages and limitations of each signal type and explores potential research challenges and future developments in the field.

Since 2010, the utilization of commercial WiFi devices for contact-free respiration monitoring has garnered significant attention. However, existing WiFi-based respiration detection methods are susceptible to constraints imposed by hardware limitations and require the person to directly face the WiFi device. Specifically, signal reflection from the thoracic cavity diminishes when the body is oriented sideways or with the back toward the device, leading to complexities in respiratory monitoring. To mitigate these hardware-associated limitations and enhance robustness, we leveraged the signal-amplifying potential of Intelligent Reflecting Surfaces (IRS) to establish a high-precision respiration detection system. This system capitalizes on IRS technology to manipulate signal propagation within the environment to enhance signal reflection from the body, finally achieving posture-resilient respiratory monitoring. Furthermore, the system can be easily deployed without the prior knowledge of antenna placement or environmental intricacies. Compared with conventional techniques, our experimental results validate that this system markedly enhances respiratory monitoring across various postural configurations in indoor environments.

Elevated glucose metabolism is a prominent characteristic of fibroblast-like synoviocytes (FLS) in rheumatoid arthritis (RA). However, the efficacy of inhibiting a single target of glucose metabolism in FLS using small molecular inhibitors is limited for RA treatment. Herein, the synergistic inhibition of FLS’ survival, proliferation, and activation by combining two glucose metabolism inhibitors, diclofenac (DC) and lonidamine (LND) was first verified. Subsequently, DC and LND were individually conjugated to cystamine-modified hyaluronic acid (HA) to prepare two polymer-prodrug conjugates. A HAP-1 peptide-modified dual polymer-prodrug conjugates-assembled nanoparticles system (HAP−1NPDC+LND) was further tailored in the optimal synergistic ratio for targeted and synergistic metabolic modulation of FLS to alleviate RA symptoms. Upon targeted uptake by FLS in inflamed joints, HAP−1NPDC+LND released DC and LND within the intracellular reductive microenvironment, where DC hinders glucose uptake and LND suppresses glycolytic enzymes to eliminate FLS synergistically. Additionally, the secretion of lactic acid and pro-inflammatory factors from FLS were reduced, thereby disrupting the crosstalk between FLS and pro-inflammatory macrophages. Finally, HAP−1NPDC+LND demonstrated promising efficacy in a mouse model of collagen-induced arthritis (CIA). Overall, this research provides valuable insights into novel therapeutic strategies for the safe and effective of treatment RA through targeted and synergistic metabolic modulation of FLS.

In order to obtain a more protective phosphate conversion coating with a denser architecture, the nucleation kinetics of phosphate chemical conversion coating on Mg-Gd-Y-Zr magnesium alloy was tuned in this work. A pretreatment process was proposed and organic additives were incorporated, which aims at increasing the ionic produce (Jsp) at the interface for increasing σ, and decreasing the critical ionic product (JC,sp), respectively. Results prove that the pretreatment of bare alloys in a phosphate bath could increase the ion products of MgHPO4 / MnHPO4. The addition of benzalkonium chloride could neutralize the charges of crystals, and in turn promote the nucleation kinetics. A denser and more protective conversion coating could consequently be obtained.

Purpose: Assessing fluid responsiveness relying on central venous oxygen saturation (ScvO2) yields varied outcomes across several studies. This study aimed to determine the ability of the change in ScvO2 (ΔScvO2) to detect fluid responsiveness in ventilated septic shock patients and potential influencing factors. Methods: In this prospective, single-center study, all patients conducted from February 2023 to January 2024 received fluid challenge. Oxygen consumption was measured by indirect calorimetry, and fluid responsiveness was defined as an increase in cardiac index (CI) ≥ 10% measured by transthoracic echocardiography. Multivariate linear regression analysis was conducted to evaluate the impact of oxygen consumption, arterial oxygen saturation, CI, and hemoglobin on ScvO2 and its change before and after fluid challenge. The Shapiro-Wilk test was used for the normality of continuous data. Data comparison between fluid responders and non-responders was conducted using a two-tailed Student t-test, Mann Whitney U test, and Chi-square test. Paired t-tests were used for normally distributed data, while the Wilcoxon signed-rank test was used for skewed data, to compare data before and after fluid challenge. Results: Among 49 patients (31 men, aged (59 ± 18) years), 27 were responders. The patients had an acute physiology and chronic health evaluation II score of 24 ± 8, a sequential organ failure assessment score of 11 ± 4, and a blood lactate level of (3.2 ± 3.1) mmol/L at enrollment. After the fluid challenge, the ΔScvO2 (mmHg) in the responders was greater than that in the non-responders (4 ± 6 vs. 1 ± 3, p = 0.019). Multivariate linear regression analysis suggested that CI was the only independent influencing factor of ScvO2, with R2 = 0.063, p = 0.008. After the fluid challenge, the change in CI became the only contributing factor to ΔScvO2 (R2 = 0.245, p

Abstract Accurate and rapid segmentation of key parts of frozen tuna, along with precise pose estimation, is crucial for automated processing. However, challenges such as size differences and indistinct features of tuna parts, as well as the complexity of determining fish poses in multi-fish scenarios, hinder this process. To address these issues, this paper introduces TunaVision, a vision model based on YOLOv8 designed for automated tuna processing. TunaVision incorporates enhancements in instance segmentation through YOLOv8m-FusionSeg, improving the segmentation of small and complex targets by increasing channel depth and optimizing feature fusion. Additionally, the YOLOv8s RSF model improves feature extraction speed and accuracy, ensuring each fish is correctly identified and localized before segmentation and pose estimation. Furthermore, TunaVision employs a vector-based approach for pose estimation, utilizing detection and segmentation results to determine fish posture and orientation. Experiments show that YOLOv8m-FusionSeg achieves an mAP@0.5 of 93.3%, while YOLOv8s RSF achieves an mAP@0.5 of 96.1%, with a mean absolute error (MAE) of 1.81 degrees in angle estimation, significantly outperforming other methods. These findings highlight TunaVision’s effectiveness in segmenting, detecting, and estimating poses of frozen tuna, offering valuable insights for the development of automated processing systems.

Abstract Background Persistent infection with high-risk human papillomavirus (HPV) is a significant risk factor for cervical cancer. HPV typing and cytology are conducted in women of appropriate age to assess the risk of cervical lesions and to guide the need for further diagnostic procedures such as colposcopy, cervical biopsy, or treatment. This article explores methods to predict the risks of high-grade precancerous cervical lesions based on high-risk HPV typing. Methods We conducted a retrospective analysis of HPV typing data from 158,565 women, including 19,707 who underwent ThinPrep cytologic testing (TCT), 7,539 who had colposcopy examinations, and 4,762 who had biopsies. We evaluated the sensitivity, specificity, and risk parameters of high-grade lesions associated with high-risk HPV types. Results (1) The overall prevalence of HPV infection was 17.89%, with the most prevalent types being HPV52 (4.44%), HPV58 (2.10%), HPV53 (1.96%), HPV81 (1.85%), HPV42 (1.75%), and HPV16 (1.44%). (2) The sensitivity and specificity of detecting high-grade lesions in TCT, colposcopy, and biopsy, based on high-risk HPV typing, demonstrated a strong linear correlation with the infection rate of each type. (3) HPV16 was confirmed to have a higher risk of CIN2 + in biopsies using a self-defined risk parameter. (4) The top five HPV types with the highest PPVs and pathogenicity risks in biopsies were HPV45, HPV16, HPV58, HPV33, and HPV18. Conclusion In Changsha, China, HPV52, HPV58, and HPV53 were the most prevalent and contributed significantly to high-grade lesions. After adjusting for infection rates, a self-defined risk parameter was proposed as a measure of the intrinsic risks of high-grade lesions associated with high-risk HPV types. Focused monitoring of prevalent high-risk HPV types such as HPV45, HPV16, HPV58, HPV33, and HPV18, which show the highest pathogenicity risks, is recommended in our region.

Abstract Pyroptosis, a recently identified cellular demise regulated by gasdermin family proteins, is emerging as a promising avenue in cancer immunotherapy. However, the realm of light-controlled pyroptosis in cancer cells remains largely unexplored. In this study, we took a deliberate approach devoid of any chemical alterations to develop a novel photosensitizer called “pharmaceutical-dots (pharm-dots)” by combining nonemissive polymers (Poly (lactic-co-glycolic acid), PLGA) with nonfluorescent invisible molecules like curcumin, berberine, oridonin into PLGA nanoparticles (PLGA-NPs). Initially, our research commenced with a comprehensive mechanistic comparison study, consolidating fragmented information on optical mechanisms. This exploration revealed that surface passivation atoms play a dominant role in governing the fluorescence emission of PLGA-NPs. Remarkably, these new luminophores, composed of two non-inherently luminous components, exhibit a remarkable synergistic boost in photoluminescence through a “0 + 0 > 2” phenomenon. In-depth investigations uncovered that these luminous PLGA-NPs, capable of generating 1O2, induce pyroptosis under photoexcitation conditions through the caspase-3/gasdermin E (GSDME) pathway. Simultaneously, our findings highlight PLGA-NPs as a novel optical formulation suitable for imaging, displaying substantial biological activity when paired with photoirradiation. This discovery holds the potential to facilitate the application of light-controlled pyroptosis in antitumor therapy, marking a promising stride toward innovative approaches in cancer treatment. Graphical abstract

Abstract The involvement of B lymphocytes in the pathogenesis of rheumatoid arthritis (RA) is well-established, with their early and aberrant activation being a crucial factor. However, the mechanisms underlying this abnormal activation in RA remain incompletely understood. In this study, we identified a significant reduction in MAPK4 expression in both RA patients and collagen-induced arthritis (CIA) mouse models, which correlates with disrupted B cell activation. Using MAPK4 knockout (KO) mice, we demonstrated that MAPK4 intrinsically promotes the differentiation of marginal zone (MZ) B cells. Loss of MAPK4 in KO mice enhances proximal BCR signaling and activates the PI3K-AKT-mTOR pathway, leading to heightened B cell proliferation. Notably, B cells from MAPK4 KO mice produce significantly higher levels of IL-6, a key pro-inflammatory cytokine in RA. Furthermore, MAPK4 KO mice exhibit impaired T cell-independent humoral immune responses. Mechanistically, MAPK4 inhibits the activation of the PI3K signaling pathway in B cells by activating the IRF4-SHIP1 pathway. Treatment with the MAPK4 agonist Vacquinol-1 enhances MZ B cell differentiation in WT mice and reduces IL-6 secretion in CIA mouse models. In summary, this study reveals the diverse roles of MAPK4 in regulating of B cell functions, with potential implications for developing therapeutic strategies for RA and related autoimmune diseases.

Abstract Breast cancer survivors face employment challenges. How to promote BC’s return to work is important for improving their quality of life and promoting recovery. Numerous studies have reported that BC survivors encounter employment challenges due to cognitive limitations, alongside factors. healthcare Professional has a good educational background and a good cognitive level and is also the closest combination of sociocultural tradition and healthcare systems, however, there is a lack of studies on their experience as BC survivors. A descriptive qualitative study was conducted to investigate the experiences of healthcare professionals returning to work following breast cancer diagnosis. 20 doctors and nurses were interviewed face-to-face with a semi-structured interview guide in three municipal hospitals. Four major themes and corresponding sub-themes were extracted from the collected data as follows: (1) Return to Work: Willingness and Conflicts; (2) Cancer Progression Anxiety; (3) Physical and Mental Re-Awareness, including (1) Decreased Physical Ability, (2) Frustration and Diminished Self-Esteem; 4. Reflection and Re-planning, including (1) Past Self-Questioning, (2) Active Life Re-planning, (3) Revitalizing Life’s Value, and (4) Career Changes: Coping and Adapting. This study revealed a positive reintegration into the workforce among participants in China’s healthcare professionals with a notably advanced medical understanding. It implies that, for BC survivors, a combination of rich medical knowledge, a stable work environment, substantial income, and robust support from colleagues and superiors play a positive role in enhancing their adaptability post a breast cancer diagnosis. Additionally, interviewees expressed guilt during sick leave, it was suggested that hospitals implement comprehensive support mechanisms related to leave, acknowledging the imperative need for adequate rest during the treatment period.

Abstract Genome-scale metabolic models (GSMM) are commonly used to identify gene deletion sets that result in growth coupling and pairing product formation with substrate utilization and can improve strain performance beyond levels typically accessible using traditional strain engineering approaches. However, sustainable feedstocks pose a challenge due to incomplete high-resolution metabolic data for non-canonical carbon sources required to curate GSMM and identify implementable designs. Here we address a four-gene deletion design in the Pseudomonas putida KT2440 strain for the lignin-derived non-sugar carbon source, p-coumarate (p-CA), that proved challenging to implement. We examine the performance of the fully implemented design for p-coumarate to glutamine, a useful biomanufacturing intermediate. In this study glutamine is then converted to indigoidine, an alternative sustainable pigment and a model heterologous product that is commonly used to colorimetrically quantify glutamine concentration. Through proteomics, promoter-variation, and growth characterization of a fully implemented gene deletion design, we provide evidence that aromatic catabolism in the completed design is rate-limited by fumarase hydratase (FUM) enzyme activity in the citrate cycle and requires careful optimization of another fumarate hydratase protein (PP_0897) expression to achieve growth and production. A double sensitivity analysis also confirmed a strict requirement for fumarate hydratase activity in the strain where all genes in the growth coupling design have been implemented. Metabolic cross-feeding experiments were used to examine the impact of complete removal of the fumarase hydratase reaction and revealed an unanticipated nutrient requirement, suggesting additional functions for this enzyme. While a complete implementation of the design was achieved, this study highlights the challenge of completely inactivating metabolic reactions encoded by under-characterized proteins, especially in the context of multi-gene edits.

With advancements in science and technology, collaborative and industrial robotic arms are increasingly gaining popularity. Enhancing the intelligence and autonomy of robot arms, particularly in autonomous grasping, has become one of the research hotspots in robotics research. To improve the efficiency and success rate of industrial robot arms in grasping target objects and avoiding obstacles, a three-finger pneumatic flexible clamp was selected, and a flexible grasping module was designed. Communication between the upper computer and the single-chip computer via a serial port enables clamping and loosening actions, constructing an autonomous grasping system based on the traditional Informed -RRT* algorithm. An improved info-RRT * algorithm (Grasping informed-RRT *, GI-RRT*) for the GR-ConvNet model is proposed. First, the maximum number of iterations and the adaptive function are pre-set to shorten the generation time of the manipulator’s motion trajectory and enhance sampling guidance and quality. Second, direct sampling of elliptical subsets constrains the position of sampling points, improving sampling efficiency. Finally, a greedy algorithm deletes redundant path points, and a cubic B-spline curve smoothly constrains the trajectory of the robot arm, shortening its length and improving flexibility. The generated residual convolutional neural network (GR-ConvNet) model predicts inputs from color and depth images captured by a depth camera, outputting the appropriate mapping grab pose of the object in the field of view. To verify the grasping effect of the robot arm, simulation and grasping experiments were conducted on the cooperative robot arm FR3. Simulation results show that, compared with the traditional Informed-RRT* algorithm, the improved algorithm shortens trajectory length by 10.11% and reduces trajectory generation time by 62.68%. The robot arm independently avoids obstacles and grasps target objects, meeting the requirements for autonomous grasping. Experiments with the cooperative robot arm demonstrate its ability to independently grasp objects independently and successfully avoid obstacles. This further validates the algorithm’s effectiveness on a real robot arm, bringing hope for its further development and use. It reduces the difficulty for operators to use the robot arm and accelerates the wide application of domestic robot arms in factories. This paper aims to promote the practical application of robot arms.

Abstract Iron alloys, including steels and magnetic functional materials, are widely used in capital construction, manufacturing, electromagnetic technology, etc. However, they face the long-standing challenge of high coefficient of thermal expansion (CTE), limiting the applications in high-precision fields. This work proposes a strategy involving the in-situ formation of a nano-scale lamellar/labyrinthine negative thermal expansion (NTE) phase within the iron matrix to tackle this problem. For example, a model alloy, Fe-Zr10-Nb6, was synthesized and its CTE is reduced to approximately half of the iron matrix. Meanwhile, the alloy possesses a strength-plasticity combination of 1.5 GPa (compressive strength) and 17.5% (ultimate strain), which outperforms other low thermal expansion (LTE) metallic materials. The magnetovolume effect of the NTE phase is deemed to counteract the positive thermal expansion in iron. The high stress-carrying hard NTE phase and the tough matrix synergistically contribute to the high mechanical properties. The interaction between the slip of lamellar microstructure and the slip-hindering of labyrinthine microstructure further enhances the strength-plasticity combination. This work shows the promise of offering a method to produce LTE iron alloys with high mechanical properties.

Despite the discovery of numerous oncogenes in colorectal cancer (CRC), the development of associated drugs is limited, posing a significant challenge for CRC treatment. Identification of novel druggable targets is therefore crucial for the therapeutic development of CRC. Here, we report the first investigation on therapeutics targeting the potent oncogene NUCKS1 to suppress cancer progression. NUCKS1-orientated bioinformatics screening of NUCKS1 inhibitors from our library of tRNA fragments originated from medicinal plants identified tRF-T36, a 5′ tRNA fragment of tRNAAsn(GUU) of Chinese yew (Taxus chinensis), exhibiting stronger inhibitory effects than taxol against CRC progression. Mechanistically, tRF-T36 binds directly to the 3′ UTR of NUCKS1 mRNA to downregulate its expressions via RNAi pathway. High-throughput RNA sequencing indicated that the downregulated NUCKS1 induced by tRF-T36 further inhibits PI3K/Akt pathway, as verified by the significantly efficacy decrease of tRF-T36 mimic in co-treatment with 740Y-P, an agonist of PI3K/Akt pathway. Collectively, our findings emphasize the importance of NUCKS1 as a promising druggable target for CRC. Furthermore, the present study provides the first siRNA sequence, tRF-T36 mimic, as small RNA drug candidate, thereby shedding light on CRC therapeutics.

Polar codes are considered as one of the most competitive channel coding schemes for the future wireless communication system. To improve the performance of polar codes with short code-length for control channels, a sphere decoding algorithm based on received value flipping is proposed in this paper. When a codeword fails the cyclic redundancy check, the algorithm flips the received value with low reliability and forms a new received sequence. Then, this new sequence is sent to the decoder for another decoding attempt. In addition, we also compare the performance of different flipping sets and evaluate the influence of the associated flipping set sizes. Simulation results show that, the proposed algorithm can achieve performance improvement over additive white Gaussian noise channel with acceptable complexity. For the (64, 16) polar code, the proposed algorithm can achieve about 0.23 dB performance gain at frame error rate = 10−3, compared to the conventional sphere decoding algorithm. Finally, we also verify the applicability of the proposed algorithm over Rayleigh fading channel and observe similar results.

Abstract Background Acute kidney injury (AKI) is a severe complication in critical patients receiving invasive mechanical ventilation (MV). However, AKI which occurs in the first 48 h after MV (early AKI) and thus likely associated with the MV settings is probably different from AKI occurring following 48 h (late AKI). This study is aimed at exploring the incidence of early and late AKI in elderly patients receiving MV and identifying their different risk factors and outcomes. Methods This retrospective, observational, multicenter cohort study consecutively included 3271 elderly patients (≥ 75 years) receiving invasive MV at four medical centers of Chinese PLA General Hospital from 2008 to 2020. The diagnosis of AKI was made following the 2012 KDIGO criteria and categorized into early (≤ 48 h) or late (> 48 h-7 days) according to the time from MV. Results There were totally 1292 cases enrolled for the final analysis. Among them, 376 patients (29.1%) developed early AKI versus 132 (10.2%) developed late AKI. The 28-day mortality rates of the non-AKI, early AKI, and late AKI patients were 14.4, 46.8, and 61.4%, respectively. After 90 days, mortality rates of three groups were 33.2, 60.6, and 72.7%, respectively. Risk factors for early AKI included PaO2/FIO2, serum creatinine, hemoglobin, and positive end-expiratory pressure at the beginning of MV, while those for late AKI were PaO2/FIO2, serum creatinine, and hemoglobin. In the multivariable adjusted analysis, both early AKI (HR = 4.035; 95% CI = 3.166–5.142; P

Abstract Purpose To compare the efficacy and safety of metformin, anti-obesity agents, and inositol with polycystic ovary syndrome (PCOS) undergoing in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI). Methods A comprehensive search was conducted in PubMed, Web of Science, Embase, Cochrane Library, and ClinicalTrials.gov for studies published in English up to October 26, 2024. Randomized controlled trials (RCTs) evaluating metformin, anti-obesity agents, and inositol were included. A network meta-analysis was performed using frequency statistical methods. Subgroup analyses were conducted based on controlled ovarian stimulation (COS) protocols and body mass index(BMI). The research protocol was registered with PROSPERO (registration code CRD42024502823). Results 20 RCTs were included with 1,827 patients assessed six different agents. Nineteen trials were rated low risk, with one rated moderate risk. Pairwise meta-analysis showed that metformin did not improve pregnancy outcomes but was associated with a reduced ovarian hyperstimulation syndrome (OHSS) risk (OR = 0.52, 95% CI 0.33–0.83), particularly in agonist protocols, along with lower E2 levels on the trigger day (SMD = -0.56, 95% CI -0.90 to -0.21) and increased side effects (OR = 6.85, 95% CI 4.32–10.86). Network meta-analysis confirmed no significant differences in pregnancy outcomes for these agents compared to controls, though both myoinositol and metformin reduced OHSS risk. Myoinositol was linked to a shorter gonadotropin duration (SMD = -1.21, 95% CI -2.03 to -0.38) and fewer side effects (OR = 0.23, 95% CI 0.06–0.83) compared to controls. Metformin led to lower E2 levels, a higher number of mature oocytes, and increased side effects (SMD = -376.52, 95% CI -610.83 to -142.22; SMD = 2.23, 95% CI 0.36–4.10; OR = 6.85, 95% CI 4.32–10.86) than controls. No studies reported an increased risk of fetal abnormalities. Conclusion Metformin and myoinositol may reduce OHSS risk in PCOS patients but did not significantly improve pregnancy outcomes. Metformin may lower OHSS risk in agonist protocol, reduce E2 levels on trigger day and increase mature oocytes but cause more side effects, while myoinositol may shorten gonadotropin duration with fewer side effects. Further robust RCTs are needed to confirm these findings.

Abstract Background The clinical manifestations of subacute combined degeneration of spinal cord (SCD) in children are complex and vary greatly. Notably, some SCD patients may be complicated with autoimmune diseases, leading to high early misdiagnosis and missed diagnosis rates. Case presentation In this study, a case involving an adolescent female with repetitive severe anemia, multiple joint swelling and pain in the left limbs, and paralysis of the bilateral lower limbs with serum vitamin B12 deficiency, polyglandular involvement, and various positive auto-antibodies (anti‑intrinsic factor antibody, anti‑parietal cell antibody, thyroid peroxidase antibody, thyroid globulin antibody and perinuclear anti‑neutrophil cytoplasmic antibody) is reported. The patient was diagnosed with SCD co-existing with autoimmune polyglandular syndrome type 3b (APS 3b) and undifferentiated connective tissue disease (UCTD) based on the symptoms and laboratory tests. However, treatment with high-dose intravenous methylprednisolone pulses, intravenous immunoglobulin, oral naproxen (changed to hydroxychloroquine after 2 weeks), vitamin B12, levothyroxine sodium tablets supplementation, blood transfusion, and rehabilitation significantly improved the patient’s condition. Conclusion Co-existence of APS 3b, UCTD, and SCD is rare in children with significantly different clinical manifestations. Nonetheless, early diagnosis and timely treatment of SCD are crucial for improving patient outcomes.

Abstract Influenza virus infections are a serious danger to people’s health worldwide as they are responsible for seasonal flu outbreaks. There is an urgent need to improve the effectiveness and durability longevity of the immune response to influenza vaccines. We synthesized the CpG HP021 and examined the impact of it on the immune response to an influenza vaccine. In BALB/c mice, hemagglutination inhibition (HI) titers to the vaccine were increased four- to eightfold against H1N1, H3N2, BV, and BY viruses by 3 μg IIV4 + 40 μg CpG HP021 compared with those of the non-adjuvanted IIV4 group, and the CpG HP021 group had a broader HI activity. Additionally, the immune response was directed towards Type 1 T helper (Th1) cells due to the CpG HP021 adjuvant. The CpG HP021-adjuvanted IIV4 induced a higher number of T cells secreting interferon gamma (IFN-γ) and tumor necrosis factor alpha (TNF-α), and increased the percentage of effector memory T cells in mice. In SD rats, the immune responses induced by IIV4 with CpG HP021 were similar to those in BALB/c mice. The development of CpG HP021 may expand the options for adjuvants in vaccines against infectious diseases.

Abstract Background Low-density lipoprotein cholesterol (LDL-C) is a well-recognized risk factor for cardiovascular diseases. However, several clinical studies demonstrated an inverse association between LDL-C and mortality risk in patients with acute myocardial infarction (AMI), known as the lipid paradox. This study aims to investigate the potential impact of inflammation on the association between LDL-C levels and mortality risks. Methods A total of 5244 patients with AMI from a large nationwide prospective cohort were included in our analysis. Patients were stratified according to LDL-C quartiles. The primary outcome was all-cause mortality, and the secondary endpoint was cardiac mortality. High-sensitive C-reactive protein (hsCRP) > 3 mg/L was defined as high inflammatory risk. Results During a median follow-up of 2.07 years, 297 mortality events (5.5%) and 227 cardiac mortality events (4.2%) occurred. Patients in the lowest LDL-C quartile had the highest incidence of all-cause mortality (7.3%) and cardiac mortality (5.8%). A U-shaped association between LDL-C levels and mortality risk was observed after multivariable adjustment, which persisted only in patients with high hsCRP levels. In contrast, a linear association between LDL-C and mortality risk was shown in patients with low hsCRP levels. Conclusions AMI patients with lower LDL-C levels had a higher risk of mortality. However, this association was only observed in those with high inflammatory risk. In contrast, the relationship between LDL-C and mortality risk was linear in patients with low inflammatory risk. This suggests the importance of considering inflammation when managing LDL-C levels in AMI patients.

Abstract Background This study explores the correlation between nutritional status, as determined by the Geriatric Nutritional Risk Index (GNRI), and the incidence of postoperative delirium (POD) in patients undergoing gastric surgery. Methods Data were obtained from the MIMIC-IV 2.2 database for patients aged 18 years or older who underwent gastric surgery. Patients were categorized into the malnourished group (GNRI

Abstract Background This study aimed to construct, evaluate, and validate nomograms for breast cancer-specific survival (BCSS) and overall survival (OS) prediction in patients with HER2- overexpressing (HER2+) metastatic breast cancer (MBC). Methods The Surveillance, Epidemiology, and End Results (SEER) database was used to select female patients diagnosed with HER2 + MBC between 2010 and 2015. These patients were distributed into training and validation groups (7:3 ratio). Variables were screened using univariate and multivariate Cox regression analyses, and BCSS and OS nomograms were constructed to determine one-, three-, and five-year survival probabilities. The nomograms were evaluated and validated using the concordance index (C-index), time-dependent receiver operating characteristic (ROC) curves, calibration curves, and decision curve analysis. Stratification was evaluated using Kaplan–Meier curves and log-rank tests based on optimal total score cut-off values. We published web-based versions of these nomograms for clinical use. Results A total of 2,151 eligible patients were randomized into training (n = 1,505) and validation (n = 646) groups. Independent prognostic factors of BCSS and OS included: age; marital status; race; oestrogen receptor status; surgery; chemotherapy; and bone, brain, liver, and lung metastases. The C-indices for the BCSS and OS training groups were 0.707 and 0.702, respectively. The ROC, calibration, and decision curves demonstrated the strength of the nomograms. According to cut-off values, patients were categorized into low-, intermediate-, and high-risk groups, with significant differences in survival outcomes between them. Conclusion We constructed predictive nomograms and stratified risk to assess the prognosis of patients with HER2 + MBC, which could help inform therapeutic decisions. Trial registration Not applicable.

Abstract Background The body conformation traits of dairy cattle are closely related to their production performance and health. The present study aimed to identify gene variants associated with body conformation traits in Chinese Holstein cattle and provide marker loci for genomic selection in dairy cattle breeding. These findings could offer robust theoretical support for optimizing the health of dairy cattle and enhancing their production performance. Results This study involved 586 Chinese Holstein cattle and used the predicted transmitting abilities (PTAs) of 17 body conformation traits evaluated by the Council on Dairy Cattle Breeding in the USA as phenotypic values. These traits were categorized into body size traits, rump traits, feet/legs traits, udder traits, and dairy characteristic traits. On the basis of the genomic profiling results from the Genomic Profiler Bovine 100 K SNP chip, genotype data were quality controlled via PLINK software, and 586 individuals and 80,713 SNPs were retained for further analysis. Genome-wide association studies (GWASs) were conducted via GEMMA software, which employs both univariate linear mixed models (LMMs) and multivariate linear mixed models (mvLMMs). The Bonferroni method was used to determine the significance threshold, identifying gene variants significantly associated with body conformation traits in Chinese Holstein cattle. The single-trait GWAS identified 24 SNPs significantly associated with body conformation traits (P

Abstract Pneumonia is a key criterion for the severity of COVID-19. Whether COVID-19 symptoms are indicators of pneumonia in patients infected with SARS-CoV-2 Omicron variants is unclear. 6200 non-hospitalized patients with COVID-19 from three sites in three hospitals were divided into three cohorts: Cohort 1 (n = 1971, Outpatient Department), Cohort 2 (n = 1073, Emergency Department), and Cohort 3 (n = 3156, Fever Clinic). The association of COVID-19 symptoms with pneumonia in the patients were analysed. In Cohort 1, dry cough, expectoration, fever, muscle or body aches, sore throat, headache or dizziness, shortness of breath, and difficulty breathing were associated with pneumonia. For Cohort 2, expectoration, fatigue, congestion or runny nose, sore throat, headache or dizziness, chills, chest stuffiness, shortness of breath, and difficulty breathing were related to pneumonia. With Cohort 3, dry cough, expectoration, vomiting, chest stuffiness, shortness of breath, and difficulty breathing had associations with pneumonia. Moreover, duration of symptoms > 7 days was associated with pneumonia in all three cohorts. In the study, expectoration, shortness of breath, difficulty breathing, and duration of symptoms > 7 days were useful predictors of COVID-19 pneumonia in the patients infected with SARS-CoV-2 Omicron variants. Among these predictors, shortness of breath and difficulty breathing were high-risk early-warning factors for pneumonia, and duration of symptoms > 7 days was also a high-risk factor for pneumonia.

Abstract Renal ischemia-reperfusion injury (IRI) is an important cause of acute kidney injury (AKI). However, the pathophysiological changes and mechanisms during IRI-AKI progression remain unclear. This study aims toinvestigate the potential mechanisms in the progression of IRI-AKI by integrating metabolomics and transcriptomics data, providing a reference for the subsequent identification of biomarkers and therapeutic targets. IRI-AKI rat models with 30 min of ischemia and 24–72 h of reperfusion surgery simulating the progression of AKI were established. Compared to the control group underwent sham surgery (NC group), most of the differentially expressed metabolites (DEMs) in IRI-AKI 24 h and IRI-AKI 72 h decreased, mainly including amino acids, organic acids, and carnitines. Additionally, we found that DEMs were mainly enriched in amino acid-related pathways, among which valine, leucine, and isoleucine biosynthesis were dramatically altered in all comparisons. Transcriptomics revealed that differentially expressed genes (DEGs) were primarily involved in amino acid, lipid, and fatty acid metabolism. By integrating metabolomics and transcriptomics, we found valine, leucine, and isoleucine biosynthesis play key roles in IRI-AKI development. Our findings concluded that valine, leucine, and isoleucine pathways are hubs that potentially connect transcriptomes to metabolomes, providing new insights regarding the pathogenesis of IRI-AKI and its potential biomarkers and therapeutic strategies.

Abstract Cardiovascular diseases claim over 10 million lives annually, highlighting the critical need for long-term monitoring and early detection of cardiac abnormalities. Existing techniques like electrocardiograms (ECG) and Holter are accurate but suffer from discomfort caused by body-attached electrodes. While wearable devices using photoplethysmography offer more convenience, they sacrifice accuracy and are susceptible to environmental interference. Here we present a radio frequency (RF)-based (60 to 64 GHz) sensing system that monitors long-term heart rate variability (HRV) with clinical-grade accuracy. Our system successfully overcomes the orders-larger interference from respiration motion in far-field conditions without any model training. By identifying previously undiscovered frequency ranges (beyond 10-order heartbeat harmonics) where heartbeat information predominates over other motions, we generate prominent heartbeat patterns with harmonics typically considered detrimental. Extensive evaluations, including a large-scale outpatient setting involving 6,222 eligible participants and a long-term daily life scenario, where sleep data was collected over 5 separate random nights over two months and a continuous 21-night period, demonstrate that our system can monitor HRV and identify abnormalities with comparable performance to clinical-grade ECG-based systems. This RF-based HRV sensing system has the potential to support active self-assessment and revolutionize medical prevention with long-term and precise health monitoring.

Abstract Background Nuclear receptor subfamily 5 group A member 1 (NR5A1) plays pivotal roles in steroidogenesis and gonadal development. 46, XY disorder of sexual development (DSD) caused by NR5A1 mutations is a rare genetic condition. This study aimed to provide a comprehensive analysis of the clinical characteristics and molecular defects observed in 19 Chinese patients with NR5A1 variants, including assessing the deleterious effects of novel variants in vitro and evaluating their functional impact on the gonad and adrenal glands in vivo. Materials and methods Subjects with NR5A1 variants were identified from 223 Chinese 46, XY DSD patients via next-generation sequencing. In-silico analysis and functional assays were performed to evaluate the transcriptional activity, expression levels and nuclear localization of novel NR5A1 variants. The histological structure of the gonads was evaluated via immunohistochemistry (IHC). Results Patients with NR5A1 gene variants presented with serious conditions, including micropenis, cryptorchidism, azoospermia, and radiological abnormalities of the spleen. Five novel NR5A1 variants were identified, including heterozygous p.Y5*, p.Q42E and p.L359_L363del, as well as copy number variation (CNV) of chr9:127213317–127570245_del and an exon 6 duplication. A total of 63.2% (12/19) of patients harbored additional variants other than NR5A1. Defective transcriptional regulatory activities and abnormal protein expression levels were observed in NR5A1 variants. The reduced levels of DHEA-S and 11-oxygenated steroids indicate a mild impairment in adrenal function among certain patients. The IHC analysis of the testis revealed intact expression levels of SOX9 in Sertoli cells, while significant differences were observed in the expression pattern of CYP17A1 in Leydig cells among patients. The preserved maturation of adult Leydig cells in the patients may trigger spontaneous puberty. Conclusions Patients with NR5A1 mutations exhibit complex phenotypes. The observed clinical heterogeneity may be attributed to oligogenic mutations, dysregulated Leydig cell function, as well as the impaired ability to modulate the transcription of target genes.

Pre-treatment processing technology plays a crucial role in the overall freshwater fish processing procedure, and automatic head and tail cutting stands out as a significant pre-treatment technique within the industry. The system for removing the head and tail of freshwater fish comprised a Cartesian coordinate manipulator, a fish transfer device, a control system, and an image acquisition device. In the vision system, five image segmentation methods were utilized for fish head and tail image segmentation comparison tests. These methods include U-Net (U-shaped Deep Neural Network), DeeplabV3, PSPNet (Pyramid Scene Parsing Network), FastSCNN (Fast Semantic Segmentation Network), and ICNet (Image Cascade Network), all of which were employed to evaluate their performance. Among the tested segmentation methods, the ICNet demonstrated the most excellent segmentation capability. The experimental results indicated a segmentation accuracy of 99.01%, a mean intersection over union (MIoU) of 82.50%, and an image processing time of 15.25 ms. The results showed that the fish head and tail were successfully cut off using this model for recognition with a circular knife. Consequently, the segmentation model employed in the machine vision system within this study has demonstrated successful applicability in automatically cutting the heads and tails of freshwater fish of various sizes.

Conger myriaster has a high price on the international market and occupies an important position in aquatic product export in China, and it is widely distributed in the Yellow Sea, the Bohai Sea, the East China Sea, the coastal waters of Japan from southern Hokkaido to northern Okinawa, and the sea near the Korean Peninsula. The experimental aquaculture techniques of C. myriaster include pond culture, industrialized open-flowing water culture, and industrialized recirculating aquaculture. No report has been published on the morphological characteristics or the effects of various morphological traits on the body weight and net body weight of C. myriaster in an industrialized open-flowing water culture. In this study, C. myriaster was collected under this industrialized culture mode and assessed using traditional measurement methods, statistical analysis, and other means to systematically measure and analyze morphological traits. A total of 90 C. myriaster were collected equally from three aquaculture companies along the coast of the Yellow Sea. The body weight (BW), net body weight (NW), total length (TL), body length (BL), body height (BH), soma width (SW), head length (HL), head height (HH), head width (HW), proboscis length (PL), proboscis width (PW), eye diameter (ED), vertical eye diameter (VED), and distance between eyes (DE) were measured individually using an electronic balance, a ruler, and a Vernier caliper. We analyzed the relationships between morphological traits and constructed a truss network diagram of morphological traits. The effects of the morphological traits on BW and NW were studied by correlation analysis, path analysis, multiple regression analysis, and curve fitting. The correlation analysis showed that the correlations of BW with TL, BL, BH, SW, HH, and HW were extremely significant (P < 0.01), with correlation coefficient values of 0.818, 0.829, 0.611, 0.697, 0.667, and 0.642, respectively. The correlations of NW with TL, BL, BH, SW, HH, HW, and VED were extremely significant (P < 0.01), with correlation coefficients of 0.848, 0.857, 0.574, 0.591, 0.617, 0.564, and 0.519, respectively. Path analysis revealed that the path coefficients between BW and three morphological traits (namely BL, BH, and SW) were larger than those for other morphological traits, at 0.631, 0.204, and 0.374, respectively. The path coefficients between NW and these three morphological traits (BL, BH, and SW) were larger than those for other morphological traits, at 0.703, 0.213, and 0.239, respectively. Through determination coefficient analysis, it was observed that the determination coefficient for BL to BW was the largest, with a value of 0.398. The combination of SW and BL had the largest determination coefficient for BW, with a value of 0.162. This indicated that BL was a core morphological trait to determine the BW, and the SW was an important morphological trait to determine the BW. The determination coefficient of BL to NW was the largest at 0.494. The combination of SW and TL had the largest coefficient of determination for NW, with a value of 0.116. This showed that the BL was the core morphological trait to determine the NW, and SW was an important morphological trait to determine the NW. A stepwise regression method was used to establish a regression equation in which the three morphological traits were independent variables and the BW or NW was the dependent variable. The multiple regression equation of the important morphological traits for BW was BW = –642.699 + 1.086 × BL + 3.874 × BH + 7.917 × SW (P < 0.01). The multiple regression equation of the important morphological traits for NW was NW = -526.995 + 1.033 × BL + 3.438 × BH + 4.317 × SW (P < 0.01). Further curve fitting was performed for each morphological trait with BW and NW in the equation. The best fitting models of BL, BH, and SW for BW were the logarithmic function, logarithmic function, and power function, respectively, and the model equations were BW = -3, 542.357 + 608.061lnBL (R2 = 0.929), BW = 14.313BH0.941 (R2 = 0.908), and BW = -1, 028.49 + 416.452lnSW (R2 = 0.920), respectively. The best-fitting models of BL, BH, and SW for NW were the logarithmic, linear, and logarithmic functions, respectively. The model equations were NW = -2, 983.881 + 516.411lnBL (R2 = 0.930), NW = -22.252 + 11.392BH (R2 = 0.914), and NW = -774.583 + 329.017lnSW (R2 = 0.921), respectively. In summary, BL was the core morphological trait affecting the BW and NW of C. myriaster in an industrialized culture model. BH and SW were important morphological traits affecting the BW and NW of C. myriaster in the industrialized culture model. These results provide a theoretical basis for the future identification of germplasm characteristics, genetic breeding, and healthy aquaculture of C. myriaster.

Abstract Background Genomic mating (GM) can effectively control the growth rate of inbreeding in population and achieve long-term sustainable genetic progress. However, the design of GM method and assessment of its effects during long-term selection have not been fully explored in beef cattle breeding. Results In this study, we constructed a simulated population based on the real genotypes of Huaxi cattle, where five generations of simulated breeding were carried out using the genomic optimal contribution selection (GOCS), genetic algorithms strategy and three traditional mating strategies. During the breeding process, genetic parameters including average genomic estimated breeding value (GEBV), genetic gain values ( $$\Delta G$$ Δ G ), the rate of inbreeding values ( $$\Delta F$$ Δ F ) were calculated and compared across generations. Our results showed that the GM method could significantly improve the genetic gain while effectively controlling the inbreeding accumulation within the population. When using the GM method, there was an increase in genetic gain for Huaxi cattle ranging from 1.1% to 25.6% compared to traditional mating strategy, with inbreeding decreasing in the range of 5.8% to 36.2%. Validation using the real dataset from Huaxi cattle further confirmed our findings from the simulated study, offspring populations using the GM strategy exhibited a 7.3% increase in genetic gain compared to positive assortative mating. Conclusions These findings suggest that the GM method shows potential for achieving sustainable genetic gain and could be utilized during long-term selection in beef cattle breeding.

Abstract Background Effective screening for colorectal cancer (CRC) enables earlier diagnosis and intervention to improve patient survival. Methods In this study, we prospectively conducted a blood-based CRC screening program for community residents in Hanjiang District, Yangzhou City, and evaluated the screening efficacy of a blood-based multi-locus DNA methylation assay (ColonAiQ). The ColonAiQ-positive rate and colonoscopy participation rate of the population, detection rate of intestinal lesions, and positive predictive value (PPV) of CRC and advanced adenoma (AA) were calculated, and the associated factors were explored. Results A total of 105,285 participants were enrolled from January 2021 to December 2022, all of whom completed the ColonAiQ assay, yielding a positive rate of 6.42% (6759/105,285). The colonoscopy compliance rate was 48.56% (3282/6759). Intestinal lesions were detected in 1773 individuals (54.02%), including 63 cases of CRCs (predominately early-stage), 1195 adenomas (441 cases of AAs), 327 polyps, and 188 other benign lesions. CRC patients exhibited higher ColonAiQ scores and more positive loci compared to healthy individuals. The PPVs were 1.92% for CRC and 13.44% for AA. Among participants, 66,121 (62.8%) completed questionnaires graded by the Asia–Pacific Colorectal Screening score, with 12,139 (18.36%) classified in the high-risk tier. High-risk participants had a higher ColonAiQ-positive rate (11.07%) and PPVs for CRC (3.46%) and AA (22.18%). Factors associated with increased detection rates for CRC and AA included male gender, older age, a history of alcohol consumption, and prior polyps. Conclusions Our study demonstrated that ColonAiQ assay effectively identifies high-risk population. These findings strongly suggest that the ColonAiQ assay represents a promising strategy for the early detection of CRC and AA in individuals at average risk. Trial registration Registered at ClinicalTrials.gov (NCT05336539).

Abstract The prevalence of obesity-associated precocious puberty is gradually increasing, but the relationship between gut flora and obesity-associated precocious puberty remains unclear.We analysed the gut flora characteristics of a clinical sample of 30 girls aged 5–8 years using 16s rRNA sequencing. An obesity rat model and a rat model of gut flora transplantation were also constructed. Body weight, body length, abdominal girth, food intake, vulva opening time, and gonadal index were monitored. The secretion levels of estradiol (E2), total cholesterol (TC), follicle-stimulating hormone (FSH), luteinizing hormone (LH), and thyroglobulin (Tg) were analyzed by ELISA. In addition, ovarian and uterine development was observed by HE staining. The mRNA and protein levels of kisspeptin-1 (Kiss-1) and gonadotropin-releasing.We found that the relative abundance of Dialister, Bacteroides, Bifidobacterium, Collinsella, and Romboutsia may be associated with obesity-associated precocious puberty. Obesity promotes gonadal development, and the gut flora of patients with obesity and obesity-associated precocious puberty regulated the gene and protein expression of Kiss-1 and GnRH, promoting precocious puberty and hypothalamic-gonadal axis hormone secretion in rats. In contrast, probiotic intervention slowed gonadal development, reduced hormone secretion, and attenuated hypothalamic-gonadal axis activity. Gut flora promoted obesity-associated precocious puberty by influencing the hypothalamic-gonadal axis, and probiotics have a therapeutic and preventive role in obesity-associated precocious puberty, which may be associated with the Kiss-1/GnRH pathway. These findings may provide some new strategies for clinical treatment and prevention of obesity-associated precocious puberty in girls.

Abstract To address the issues of node interaction power overrun and high carbon emissions that may arise during distributed optimization in multi‐energy parks (MEPs), this paper proposes a distributed low‐carbon and economic operation method for multi‐energy parks based on a cloud platform that considers network transmission capacity.The proposed method achieves maximun profit by designing a two layer collaborative architecture for distributed optimization operations. At the top level, cloud platform services are utilized to build a model for checking network transport capacity and carbon emission quotas, optimizing network node over‐limit inspection . The bottom layer constructs a distributed optimization model for multi‐energy complementation in each park, taking into account the information privacy and individual interests of each multi‐energy park. An improved alternating direction multiplier method (ADMM) is proposed to effectively solve the two‐layer framework. The case studies show that the distributed optimization method under cloud platform services proposed in this paper can achieve maximum revenue for integrated energy service provider while ensuring the safe operation of multi‐energy parks, and reasonably allocate the benefits of collaborative operation among various parks while promoting carbon emission reduction.

Abstract Chronic pain is a prevalent health condition that imposes a significant burden on the global health system. Health literacy is a determinant of the quality of pain management which directly impacts public and individual health. However, the existing health literacy measurements have predominantly focused on medical models stemmed from Western culture and the knowledge of non-Western health models has largely been neglected. This review scopes refereed health literacy publications with regard to traditional Chinese medicine and chronic pain to explore and identify 1) the conceptual basis underlying the development of traditional Chinese medicine health literacy in this area, and 2) measurement tools used in this area and their associated psychometric qualities. Twenty-eight journal articles were assessed and the results showed that most studies’ conceptual frameworks were unable to cover three key health literacy aspects defined by the World Health Organization (access, understand, and apply). Furthermore, the identified health literacy measurement tools generally lacked rigorous psychometric evaluation. Future studies should focus on exploring a comprehensive model that encompasses various health models and developing measurement tools with more culturally representative psychometric assessments.

Abstract Background With the continuous advancement of modern medical technology, the survival rate of premature infants has significantly increased. Klebsiella pneumoniae (K. pneumoniae) is one of the most common pathogens causing neonatal infections, particularly posing a serious risk to premature infants. This study aimed to analyze the clinical characteristics, antibiotic susceptibility profiles, and treatment outcomes of K. pneumoniae infections in these infants. Methods We retrospectively compared cases of K. pneumoniae infection in premature and term infants admitted in a tertiary hospital from January 2017 to December 2022 in China. Clinical and microbiological characteristics were evaluated. Data analysis was performed using the Statistical Package for the Social Sciences (SPSS), with statistical significance defined as P

Abstract Background Hepatocellular carcinoma (HCC) is one of the most prevalent and lethal cancers worldwide, with death rates increasing by approximately 2–3% per year. The high mortality and poor prognosis of HCC are primarily due to inaccurate early diagnosis and lack of monitoring when liver transplantation is not feasible. Fatty acid (FA) metabolism is a critical metabolic pathway that provides energy and signaling factors in cancer, particularly in HCC, and promotes malignancy. Therefore, it is essential to explore specific FA metabolism-related diagnostic and prognostic signatures that can enable the effective early diagnosis and monitoring of HCC. Methods In this study, we used genes associated with FA metabolism pathway and weighted gene co-expression network analysis (WGCNA) to establish a gene co-expression network and identify hub genes related to HCC (disease WGCNA) and FA clusters (cluster WGCNA). A diagnostic model was constructed using data downloaded from the Gene Expression Omnibus database (GSE25097), and a prognostic model was established using The Cancer Genome Atlas cohort, in which Univariate Cox regression analysis, multivariate Cox risk model, and LASSO Cox regression analysis were applied. The immune infiltration of HCC cells was evaluated using CIBERSORT. The function of the key SLC22A1 gene was experimentally verified in vitro and in vivo. Results Twelve overlapping genes (CPEB3, ASPDH, DEPDC7, ETFDH, UGT2B7, GYS2, F11, ANXA10, CYP2C8, GLYATL1, C6, and SLC22A1) from disease and cluster WGCNA were identified as key genes and used in the construction of the diagnostic and prognostic models. The RF model had the highest area under the ROC curve (AUC) of 0.994 was identified as the most effective for distinguishing patients with HCC with different features. The top five important genes (C6, UGT2B7, SLC22A1, F11, and CYP2C8) from the RF model were selected as diagnostic genes for further analysis (ROC curves: AUC value = 0.986, 95% confidence interval [95% CI] = 0.967–0.999). Moreover, a risk score formula consisting of four genes (GYS2, F11, ANXA10 and SLC22A1) was established and its independent prognostic ability was further demonstrated (univariate Cox regression analysis: hazard ratio [HR] = 3.664%, 95% CI = 2.033–6.605, P

Abstract Background Ferroptosis, a form of cell death characterized by lipid peroxidation, plays a crucial role in tumor suppression, offering novel avenues for cancer therapy. Previous studies have indicated that high levels of cyclin-dependent kinase subunit 2 (CKS2) promote the progression of various cancers. However, the potential interplay between CKS2 and ferroptosis in colon cancer (CC) remains unclear. Methods Bioinformatics and RNA-seq analyses were employed to study genes associated with the ferroptosis signaling pathway. CKS2 expression was evaluated using quantitative reverse transcription polymerase chain reaction (qRT-PCR) and Western blot (WB). The in vitro and in vivo effects of CKS2 on CC cells were assessed through the CCK-8 assay, colony formation assay, propidium iodide (PI) staining, BODIPY staining, DCFH-DA staining, and animal experiments. Additionally, the impact of CKS2 on autophagy and glutathione (GSH) metabolism was investigated using a transmission electron microscope (TEM), immunofluorescence (IF) assays, WB experiments, and relevant assay kits. Results CKS2 expression was elevated in CC, indicating a poor clinical outcome. Knockdown of CKS2 significantly enhanced Erastin-induced ferroptosis in CC cells, leading to reduced GSH metabolism. Conversely, CKS2 overexpression produced opposite effects. Mechanistically, CKS2-induced autophagy reinforced GSH metabolism, thereby increasing resistance to ferroptosis in CC cells. Furthermore, inhibiting CKS2 promoted tumor ferroptosis by downregulating GPX4 expression. Additionally, CKS2 knockdown effectively increased sorafenib-induced ferroptosis both in vitro and in vivo. Conclusion CKS2 suppresses ferroptosis in CC by modulating GSH metabolism in both in vitro and in vivo settings. These findings offer new insights into targeting CKS2 for CC treatment and shed light on the mechanism of ferroptosis in CC.

Abstract Background This study aims to construct predicting models using radiomic and clinical features in predicting first-line vascular endothelial growth factor receptor-tyrosine kinase inhibitor (VEGFR-TKI) early resistance in metastatic clear cell renal cell carcinoma (mccRCC) patients. We also aim to explore the correlation of predicting models with short and long-term survival of mccRCC patients. Materials and methods In this retrospective study, 110 mccRCC patients from 2009 to 2019 were included and assigned into training and test sets. Radiomic features were extracted from tumor 3D-ROI of baseline enhanced CT images. Radiomic features were selected by Lasso method to construct a radiomic score. A combined nomogram was established using the combination of radiomic score and clinical factors. The discriminative abilities of the radiomic, clinical and combined nomogram were quantified using ROC curve. Cox regression analysis was used to test the correlation of nomogram score with progression-free survival (PFS) and overall survival (OS). PFS and OS were compared between different risk groups by log-rank test. Results The radiomic, clinical and combined nomogram demonstrated AUCs of 0.81, 0.75, and 0.83 in training set; 0.79, 0.77, and 0.88 in test set. Nomogram score ≥ 1.18 was an independent prognostic factor of PFS (HR 0.22 (0.10, 0.47), p