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Abstract Once considered unconventional cellular structures, membraneless organelles (MLOs), cellular substructures involved in biological processes or pathways under physiological conditions, have emerged as central players in cellular dynamics and function. MLOs can be formed through liquid-liquid phase separation (LLPS), resulting in the creation of condensates. From neurodegenerative disorders, cardiovascular diseases, aging, and metabolism to cancer, the influence of MLOs on human health and disease extends widely. This review discusses the underlying mechanisms of LLPS, the biophysical properties that drive MLO formation, and their implications for cellular function. We highlight recent advances in understanding how the physicochemical environment, molecular interactions, and post-translational modifications regulate LLPS and MLO dynamics. This review offers an overview of the discovery and current understanding of MLOs and biomolecular condensate in physiological conditions and diseases. This article aims to deliver the latest insights on MLOs and LLPS by analyzing current research, highlighting their critical role in cellular organization. The discussion also covers the role of membrane-associated condensates in cell signaling, including those involving T-cell receptors, stress granules linked to lysosomes, and biomolecular condensates within the Golgi apparatus. Additionally, the potential of targeting LLPS in clinical settings is explored, highlighting promising avenues for future research and therapeutic interventions.

Abstract dCTP pyrophosphatase 1 (DCTPP1) is widely expressed in tumors and the immune system and plays a critical role in human cancer progression. However, multi-omics characterization of DCTPP1 and its role in prognosis and immune microenvironment of tumor patients has not been explored. We collected data from 33 cancers and comprehensively analyzed the aberrant expression, prognostic role, pathway enrichment, immune microenvironment, and association with drug sensitivity of DCTPP1 in cancers, as well as the prediction of patients’ immunotherapeutic response to ICIs and targeted small molecule drugs. Finally, we experimentally confirmed the role of DCTPP1 in renal clear cell carcinoma. We discovered that DCTPP1 has a differentiable expression and a diagnostic biomarker significance in cancer. Additionally, we discovered that DCTPP1 is important for the tumor microenvironment and pan-cancer. TMB and MSI are frequent immunological checkpoints that are significantly correlated with DCTPP1 expression. Patients who express high levels of DCTPP1 have greater rates of survival and therapeutic response following immunotherapy. Ultimately, it was discovered that renal clear cell carcinoma cells’ invasion and proliferation were suppressed by DCTPP1 knockdown. Our findings demonstrate the significant potential of DCTPP1 as a biomarker for prognosis and immunotherapeutic response, which may pave the way for more investigation into the mechanism of tumor infiltration and DCTPP1’s potential for cancer therapy.

Abstract Mesenchymal–epithelial transition (MET) exon 14 (METex14) skipping mutation is a rare (3%–4%) driver mutation in non‐small cell lung cancer (NSCLC). Tepotinib, a selective MET inhibitor, has shown promise in treating METex14 skipping‐mutated NSCLC. However, its feasibility for perioperative application remains unclear. This report describes a 60‐year‐old man with stage IIIA (cT2N2M0) lung adenocarcinoma harboring a METex14 skipping mutation. After initial treatment with savolitinib was discontinued due to grade 4 transaminitis, the patient was switched to tepotinib, resulting in significant tumor regression. Six months later, further shrinkage was observed, and surgery revealed remarkable pathological response with no residual tumor in lymph nodes (ypT2N0M0, IB). Postoperative tepotinib continued, with no relapse at 6‐month follow‐up. This case highlights the potential of tepotinib as neoadjuvant therapy for resectable METex14 skipping‐mutated NSCLC, warranting further clinical trials.

Abstract Since chimeric antigen receptor T (CAR-T) cells were introduced three decades ago, the treatment using these cells has led to outstanding outcomes, and at the moment, CAR-T cell therapy is a well-established mainstay for treating CD19 + malignancies and multiple myeloma. Despite the astonishing results of CAR-T cell therapy in B-cell-derived malignancies, several bottlenecks must be overcome to promote its safety and efficacy and broaden its applicability. These bottlenecks include cumbersome production process, safety concerns of viral vectors, poor efficacy in treating solid tumors, life-threatening side effects, and dysfunctionality of infused CAR-T cells over time. Exosomes are nano-sized vesicles that are secreted by all living cells and play an essential role in cellular crosstalk by bridging between cells. In this review, we discuss how the existing bottlenecks of CAR-T cell therapy can be overcome by focusing on exosomes. First, we delve into the effect of tumor-derived exosomes on the CAR-T cell function and discuss how inhibiting their secretion can enhance the efficacy of CAR-T cell therapy. Afterward, the application of exosomes to the manufacturing of CAR-T cells in a non-viral approach is discussed. We also review the latest advancements in ex vivo activation and cultivation of CAR-T cells using exosomes, as well as the potential of engineered exosomes to in vivo induction or boost the in vivo proliferation of CAR-T cells. Finally, we discuss how CAR-engineered exosomes can be used as a versatile tool for the direct killing of tumor cells or delivering intended therapeutic payloads in a targeted manner.

Abstract This article provides an overview of recent progress in the achievement of non-contact intraoperative image control through the use of vision and sensor technologies in operating room (OR) environments. A discussion of approaches to improving and optimizing associated technologies is also provided, together with a survey of important challenges and directions for future development aimed at improving the use of non-contact intraoperative image access systems.

Abstract Purpose (1) to investigate the consecutive changes in hip muscle volume in patients with femoroacetabular impingement syndrome (FAIS) during the initial postoperative period, and (2) to determine the potential effect of the early changes in hip muscle volume on clinical outcomes. Methods Data between March 2021 and March 2022 was reviewed. Patients diagnosed with FAIS based on clinical symptoms and radiographic findings, and undergoing hip arthroscopic treatment were included. Exclusion criteria were incomplete MRI data, prior history of hip surgery, and concomitant hip conditions including hip osteoarthritis with a Tönnis grade > 1, avascular necrosis, Legg-Calvé-Perthes disease, osteoid osteoma, synovial chondromatosis, pigmented villonodular synovitis, and developmental dysplasia of the hip (DDH). MRI was performed preoperatively and 3, 6, 12-month postoperatively. Cross-sectional area (CSA) of hip muscles including rectus femoris (RF), iliocapsularis (IC), iliopsoas (IP), gluteus medius/minimus complex (G-med/min), and gluteus maximus (G-max) were collected on MRI. The CSA was corrected by body surface area (BSA). Preoperative and a minimum of 2-year postoperative patient-reported outcome (PRO) scores including Visual Analog pain Scale (VAS), modified Harris Hip Score (mHHS), and international Hip Outcome Tool, 12-component form (iHOT-12) were collected. A multivariate linear regression model was built to determine the influence of the potential factors on postoperative PROs. Results A total of 76 patients were included in the study. Compared to the preoperative level, decreased volume of RF and G-max, and increased IC/RF ratio were observed at postoperative 3 months (all with P

Abstract The D14 protein, an alpha/beta hydrolase, is a key receptor in the strigolactone (SL) signaling pathway. However, the response of VvD14 to SL signals and its role in grapevine root architecture formation remain unclear. This study demonstrated that VvD14c was highly expressed in grapevine tissues and fruit stages than other VvD14 isoforms. Application of GR24, an SL analog, enhanced the elongation and diameter of adventitious roots but inhibited the elongation and density of lateral roots (LRs) and increased VvD14c expression. Additionally, GR24 is nested within the VvD14c pocket and strongly bound to the VvD14c protein, with an affinity of 5.65 × 10−9 M. Furthermore, VvD14c interacted with grapevine MORE AXILLARY GROWTH 2 (VvMAX2) in a GR24-dependent manner. Overexpression of VvD14c in the d14 mutant and VvMAX2 in the max2 Arabidopsis mutant reversed the increased LR number and density, as well as primary root elongation. Conversely, homologous overexpression of VvD14c and VvMAX2 resulted in reduced LR number and density in grapevines. VvMAX2 directly interacted with LATERAL ORGAN BOUNDARY (VvLOB) and VvLBD19, thereby positively regulating LR density. These findings highlight the role of SLs in regulating grapevine root architecture, potentially via the VvD14c-VvMAX2-VvLOB/VvLBD19 module, providing new insights into the regulation of root growth and development in grapevines.

Abstract Load forecasting with distributed energy resources (DERs) behind‐the‐meter is more challenging owing to transformed data patterns. Traditional forecasting method which is only based on unmasked‐load could not suit the present limited masked‐load. To bridge the divergence between unmasked‐load and masked‐load, this article proposes a masked‐load forecasting (MLF) method based on transfer learning technique and Bayesian optimization, which is Maximum Mean Discrepancy‐Neural Network with Bayesian optimization (MMD‐NNb). At first, common feature vectors between unmasked‐load and masked‐load are extracted and an outcome predictor could be established based on feature vectors from historical unmasked‐load. The feature vectors from masked‐load could therefore accommodate to the outcome predictor, and the masked‐load could be forecast. Owing to the excessive hyperparameters involved in training, Bayesian optimization is adopted for hyperparameters fine‐tuning. MMD‐NNb was tested and compared with four related models. The improvements from MMD‐NNb were observed in all comparison scenarios. Also, MMD‐NNb was proved to have high resilience to the different DERs and not requiring additional DERs‐data.

Hydrophiine sea snakes represent ecologically significant and species-rich marine predatory reptiles, many of which inhabit marine environments throughout their entire lifecycles. However, due to morphological variability and limited molecular phylogenetic studies, the taxonomic relationships within this group remain unclear. In this study, we present the first complete mitochondrial genome of Aipysurus sea snakes, specifically Aipysurus eydouxii Gray 1849. The mitogenome comprises 17,228 base pairs and contains a total of 37 genes, plus a putative control region. This study provides valuable genetic data that will contribute to the future taxonomic classification and ecological protection of hydrophiine sea snakes.

Abstract Ocular metastasis is a rare type of distant metastasis of lung cancer. Limited information is available regarding ocular symptoms, diagnosis, treatment, and prognosis. We reported 16 patients diagnosed with ocular metastasis from lung cancer treated at our hospital from January 1988 to March 2024 and conducted a systematic review of 100 patients retrieved from the PubMed database from January 2014 to December 2023. A pooled analysis was performed using individual‐level patient data to generate the hazard ratio (HR) of the association between patient characteristics and overall survival. A total of 116 patients, 100 patients from the literature and 16 patients from our center, diagnosed with ocular metastasis from lung cancer were included in this study. Choroid metastasis was presented in 77 (66.4%) patients and was significantly associated with the onset of lung cancer with ocular symptoms and decreased vision; iris metastasis was significantly associated with small cell lung cancer (SCLC), high intraocular pressure, and ocular pain. Multivariate analyses revealed that males (HR, 2.488; 95% confidence interval [CI], 1.127–5.495), age ≥ 60 years (HR, 3.196; 95% CI, 1.391–7.341), and onset with ocular symptoms (HR, 4.312; 95% CI, 1.675–11.099) were significantly associated with overall survival. For non‐SCLC (NSCLC) patients, compared with chemotherapy, targeted therapy (HR, 0.238; 95% CI, 0.087–0.651) and combined therapy (HR, 0.133; 95% CI, 0.017–0.822) have greater therapeutic efficacy. Chemotherapy combined with immunotherapy and targeted therapy are more effective than chemotherapy alone for ocular metastatic NSCLC patients. For patients with targetable mutations, new‐generation tyrosine kinase inhibitors (TKIs) are preferred.

Abstract The study was to evaluate the clinical outcomes of azvudine versus nirmatrelvir-ritonavir against omicron strains of coronavirus disease 2019 infections and determine their comparative effectiveness. This retrospective study included 716 patients who received nirmatrelvir-ritonavir (NR group) or azvudine (FNC group) at Peking Union Medical College Hospital between 1 November 2022 and 27 February 2023. Patients in the FNC group (n = 304) were younger, exhibited less severe symptoms, started antiviral therapy later, received corticosteroids more frequently, and used tocilizumab less frequently than patients in the NR group (n = 412). Within 28 d of therapy, 40 (9.7%) and 20 (6.6%) deaths were in the NR and FNC groups, respectively. No differences were observed between drugs and mortality rates (odds ratio [OR] 0.78, 95% CI 0.40–1.5, P = 0.45), clinical improvement (OR 0.79, 95% CI 0.79–1.3, P = 0.38), and clinical progression (OR 1.0, 95% CI 0.58–1.8, P = 0.96). More patients in the NR group experienced platelet decline than those in the FNC group (17.6% vs. 8.9%, P = 0.034). This study indicated that the effectiveness and safety of azvudine were comparable to those of nirmatrelvir-ritonavir.

Abstract Male infertility is one of the most common reproductive dysfunctions. Despite oligospermia being a cause of infertility, few studies have been conducted on it. This study aimed to investigate differences in semen metabolic patterns in patients with oligospermia and to identify potential biomarkers associated with oligospermia. Semen samples from oligospermia patients (20 cases) and healthy controls (20 cases) were detected by high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS), and 72 and 89 metabolites were identified as potential markers in positive and negative ion modes, respectively. In addition, the results identified multiple metabolic pathways in patients with oligospermia, such as glycine serine and threonine metabolism, Synthesis and degradation of ketone bodies, Valine, leucine, and isoleucine degradation. These results described unique metabolic characteristics of semen in patients with oligospermia and provided novel insights into the mechanism of the semen disorder.

Abstract The systemic immune-inflammatory index (SII) has been identified as an independent prognostic factor for multiple diseases. However, the impact of SII on outcome of acute-on-chronic liver failure (ACLF) is scant. A retrospective study enrolled patients with ACLF treated with artificial liver support system. Restricted cubic spline (RCS) (knots at the 10th, 50th, and 90th percentiles) and Cox proportional hazards models were applied to investigate the relationship between SII and 90-day transplant-free survival and overall survival in patients with ACLF. A total of 258 patients with ACLF were included. The 90-day transplant-free survival rate and overall survival rate were 58.5% and 66.3%. The SII was 465.5 (277.3–804.4). Adjusted RCS models showed linear exposure–response relationship between SII and 90-day transplant-free survival (P for overall

Abstract While the critical role of NKX2-1 and its transcriptional targets in lung morphogenesis and pulmonary epithelial cell differentiation is increasingly known, mechanisms by which chromatin accessibility alters the epigenetic landscape and how NKX2-1 interacts with other co-activators required for alveolar epithelial cell differentiation and function are not well understood. Combined deletion of the histone methyl transferases Prdm3 and Prdm16 in early lung endoderm causes perinatal lethality due to respiratory failure from loss of AT2 cells and the accumulation of partially differentiated AT1 cells. Combination of single-cell RNA-seq, bulk ATAC-seq, and CUT&RUN data demonstrate that PRDM3 and PRDM16 regulate chromatin accessibility at NKX2-1 transcriptional targets critical for perinatal AT2 cell differentiation and surfactant homeostasis. Lineage specific deletion of PRDM3/16 in AT2 cells leads to lineage infidelity, with PRDM3/16 null cells acquiring partial AT1 fate. Together, these data demonstrate that NKX2-1-dependent regulation of alveolar epithelial cell differentiation is mediated by epigenomic modulation via PRDM3/16.

Abstract C-C chemokine ligand 5 (CCL5) plays a crucial role in the advancement of human cancer. Nevertheless, little is known about the multi-omics characterisation of CCL5 and its significance for the immune microenvironment and prognosis of tumor patients. The basal expression levels of the CCL5 gene in normal human tissues, aberrant expression in disease, genomic alterations, prognostic roles, pathway enrichment, immune microenvironment, association with immune checkpoints, drug sensitivity, and the ability to predict patients’ immunotherapeutic response to immune checkpoint inhibitors (ICIs) and small molecule drugs were all thoroughly analyzed using data gathered from 33 cancers. Lastly, we were able to validate CCL5’s involvement in renal clear cell carcinoma by experimental means. We discovered that CCL5 has distinct expression patterns and a diagnostic biomarker significance in cancer. Furthermore, we discovered that CCL5 is essential for both the tumor microenvironment and pan-cancer. TMB and MSI are two frequent immunological checkpoints that are significantly correlated with CCL5, and patients who express high levels of CCL5 have stronger immunotherapeutic response and a better prognosis after immunotherapy. Eventually, molecular docking was used to find small molecule inhibitors that can specifically target CCL5. Ultimately, it was shown that CCL5 knockdown impeded renal clear cell carcinoma cells’ ability to proliferate and invade. Our findings demonstrate the significant potential of CCL5 as an immunotherapeutic response biomarker and prognostic indicator, which may pave the way for more studies on the mechanism of tumor infiltration and CCL5’s potential therapeutic applications in cancer.

Abstract Background Oxidative Balance Scores (OBS) is composite measures that assess the balance between pro-oxidant and antioxidant factors in an individual’s diet and lifestyle. Evidence on OBS and cardiovascular disease (CVD) in diabetic patients is scarce. This study investigates the potential association between OBS and CVD-prevalence and all-cause and CVD-related mortality in adult diabetic patients. Methods Participants were selected from the National Health and Nutrition Examination Survey (NHANES) 2007–2018. OBS-related data collection was initiated by linking the National Death Index to determine mortality due to all-cause and cardiovascular disease until December 31, 2019. Weighted logistic regression analyses explored the relationship between OBS and CVD. In addition, multivariable Cox proportional risk regression models and Kaplan–Meier curves were used to determine the correlation between OBS and mortality, with time to event as the time variable, as well as to estimate hazard ratios (HR) and 95% confidence interval (CI). Results A total of 3491 participants were included in the final analysis. Weighted logistic regression analysis of the relationship between OBS and CVD prevalence found that higher OBS was not associated with CVD prevalence compared with lower levels after fully adjustment in model 3 (OR: 0.82, 95% CI: 0.51–1.31, P = 0.39). During 3,491 person-years of follow-up, 408 deaths were recorded, of which 105 deaths were attributed to CVD. In fully adjusted model 3, participants in the highest quartile of OBS had significant reductions in all-cause mortality of 53% [HR: 0.47, 95% CI: 0.29–0.77), Ptrend= 0.002] and in cardiovascular disease mortality of 78% [HR: 0.22, 95% CI: 0.08–0.56), Ptrend= 0.004], compared with the lowest quartile groups of OBS. The Kaplan–Meier analysis results showed that participants in the highest quartile of OBS had the lowest risk of all-cause and CVD-related mortality and were statistically different (P

The development and creation of innovative therapeutic supplements and medications with extraordinary efficacy for addressing severe diabetes are of utmost importance to both developing and developed nations. A bio-inspired method has been documented for producing copper nanoparticles (CuNPs) using Pistacia atlantica leaf extract as a natural stabilizing agent. This approach is applicable, easy, and environmentally friendly, as it avoids using any toxic or harmful reagents. The CuNPs that were synthesized through biological processes underwent characterization using sophisticated physicochemical methods such as energy-dispersive X-ray spectroscopy, transmission electron microscopy, field emission-scanning electron microscopy, and Fourier-transformed infrared spectroscopy. It is confirmed that CuNPs exhibit a spherical structure, with an average size ranging from approximately 30 to 70 nm. Diabetes was induced in vivo through a fructose-enriched diet combined with streptozotocin. Half the subjects were administered CuNPs (100 µg/kg) via oral gavage. In contrast to the animals that were given regular food, the diabetic animals revealed an increase in serum fasting glucose level and a decrease in glucose tolerance. The administration of CuNPs had a significant impact on reducing glucose intolerance and fasting hyperglycemia. Additionally, it helped alleviate the negative effects of diabetes on cardiac output and work. Furthermore, utilizing CuNPs effectively hindered the rise in cardiac signal transducer and activator of transcription 3-phosphorylation caused by diabetes. The findings from this investigation provide evidence of the therapeutic benefits of CuNPs in mitigating diabetes-induced cardiac dysfunction in rats.

Abstract Endo-periodontal lesions (EPLs) involve both the periodontium and pulp tissue and have complicated etiologies and pathogenic mechanisms, including unique anatomical and microbiological characteristics and multiple contributing factors. This etiological complexity leads to difficulties in determining patient prognosis, posing great challenges in clinical practice. Furthermore, EPL-affected teeth require multidisciplinary therapy, including periodontal therapy, endodontic therapy and others, but there is still much debate about the appropriate timing of periodontal therapy and root canal therapy. By compiling the most recent findings on the etiology, pathogenesis, clinical characteristics, diagnosis, therapy, and prognosis of EPL-affected teeth, this consensus sought to support clinicians in making the best possible treatment decisions based on both biological and clinical evidence.

Let $ M $ be a compact connected orientable 3-manifold and $ F $ be a compact connected orientable surface properly embedded in $ M $. If $ F $ cuts $ M $ into two handlebodies $ X $ and $ Y $ (i.e., $ M = X\cup_FY $), then we say that $ F $ is an $ H' $-splitting surface for $ M $ and call $ X\cup_FY $ an $ H' $-splitting for $ M $. When the $ H' $-splitting surface $ F $ is incompressible in a handlebody $ H $, a characteristic of an $ H' $-splitting $ H_1\cup_F H_2 $ to denote $ H $ is already known. In the present paper, we generalize the above result as follows: Let $ H $ be a handlebody of genus $ g\geq 1 $, $ X\cup_F Y $ an $ H' $-splitting for $ H $. Then, either $ X\cup_F Y $ is stabilized, or there exists a reducing system $ \mathcal{J}_1\cup\mathcal{K}_1 $ of $ F $, such that $ \mathcal{J}_1 $ is quasi-primitive in $ Y $ and $ \mathcal{K}_1 $ is quasi-primitive in $ X $. Combining the result with the known result, we obtain a characteristic of an $ H' $-splitting $ H_1\cup_F H_2 $ to denote a handlebody.

Abstract Osteogenesis imperfecta (OI) is a disorder of low bone mass and increased fracture risk due to a range of genetic variants that prominently include mutations in genes encoding type I collagen. While it is well known that OI reflects defects in the activity of bone-forming osteoblasts, it is currently unclear whether OI also reflects defects in the many other cell types comprising bone, including defects in skeletal vascular endothelium or the skeletal stem cell populations that give rise to osteoblasts and whether correcting these broader defects could have therapeutic utility. Here, we find that numbers of skeletal stem cells (SSCs) and skeletal arterial endothelial cells (AECs) are augmented in Col1a2 oim/oim mice, a well-studied animal model of moderate to severe OI, suggesting that disruption of a vascular SSC niche is a feature of OI pathogenesis. Moreover, crossing Col1a2 oim/oim mice to mice lacking a negative regulator of skeletal angiogenesis and bone formation, Schnurri 3 (SHN3), not only corrected the SSC and AEC phenotypes but moreover robustly corrected the bone mass and spontaneous fracture phenotypes. As this finding suggested a strong therapeutic utility of SHN3 inhibition for the treatment of OI, a bone-targeting AAV was used to mediate Shn3 knockdown, rescuing the Col1a2 oim/oim phenotype and providing therapeutic proof-of-concept for targeting SHN3 for the treatment of OI. Overall, this work both provides proof-of-concept for inhibition of the SHN3 pathway and more broadly addressing defects in the stem/osteoprogenitor niche as is a strategy to treat OI.

Abstract To explore the effect of different levels of systolic blood pressure (SBP) control on new-onset chronic kidney disease in hypertension multimorbidity. The hypertensive patients with multimorbidity information were enrolled from the Kailuan Study. The isolated hypertension patients undergoing physical examination during the same period were selected in a 1:1 ratio as control. Finally, 12,897 participants were divided into six groups: Group SBP

Abstract Dual emission from thermally activated delayed fluorescence (TADF) emitters is often difficult to observe, especially in solution, limited by Kasha’s rule. Two TADF dendrimers containing N-doped polycyclic aromatic hydrocarbons as acceptors are designed and synthesized. Compound 2GCzBPN, having a strongly twisted geometry, exhibits TADF, while 2GCzBPPZ, possessing a less twisted geometry, shows dual emission associated with the monomer and aggregate that is TADF. The demonstration reveals that 2GCzBPPZ can serve as a temperature sensor with excellent temperature sensitivity and remarkably wide emission color response in solution. By embedding 2GCzBPPZ in paraffin we demonstrate a spatial-temperature sensor that shows a noticeable emission shift from yellow to green and ultimately to blue as the temperature increases from 20 to 200 °C. We finally demonstrate the utility of these TADF dendrimers in solution-processed organic light-emitting diodes.

Abstract Lithium‐ion battery state‐of‐health (SOH) monitoring is essential for maintaining the safety and reliability of electric vehicles and efficiency of energy storage systems. When the SOH of lithium‐ion batteries reaches the end‐of‐life threshold, replacement and maintenance are required to avoid fire and explosion hazards. This paper provides a comprehensive literature review of lithium‐ion battery SOH estimation methods at the cell, module, and pack levels. Analysis and summary of the SOH definition based on the resistance, capacity, and energy indices are presented at each battery hierarchy level. A comparison of SOH indices in terms of modelling complexity, required measurement time, and accuracy is provided. To the best of knowledge, a comprehensive classification of SOH estimation methods at different battery hierarchy levels is presented for the first time in this review. In addition, SOH estimation methods are further classified based on the applied methodologies, including direct measurement, model‐based methods, data‐driven methods, and hybrid model‐data methods. Advantages and disadvantages of SOH estimation methods are summarized and compared across different battery hierarchy levels. A detailed summary of typical SOH estimation methods is presented along with the battery topology, operating conditions, and performance. The challenges and research prospects of lithium‐ion battery SOH estimation are discussed from the cell to pack levels.

Abstract Purpose To investigate the repeatability and reproducibility of a new method for centration analysis after small incision lenticule extraction (SMILE) and femtosecond laser-assisted LASIK (FS-LASIK). Methods This study comprised 29 eyes treated with SMILE and 24 with FS-LASIK. Decentrations were analyzed using tangential and pachymetry difference maps respectively. Both difference maps were generated with a Scheimpflug tomographer (Pentacam) for each eye, using preoperative and 3-month postoperative scans. Repeatability and reproducibility were evaluated by calculating the intraclass correlation coefficient (ICC), within-subject standard deviation (Sw), and coefficient of repeatability (CR). Results ICC, Sw, and CR showed good to excellent repeatability in locating the coordinates of the optical zone (OZ) center on both maps, with values ranging from 0.84 to 0.96, 0.03 to 0.13, and 0.08 to 0.36 respectively. The repeatability of the total decentration from the preoperative corneal vertex on the tangential curvature difference maps( $$d_{TC}$$ d TC ) and the pachymetry difference maps( $$d_{PC}$$ d PC ) were moderate and good, respectively. The ICC, Sw, and CR of $$d_{TC}$$ d TC were 0.63, 0.09, and 0.25, respectively. The ICC, Sw, and CR of $$d_{PC}$$ d PC were 0.77, 0.10, and 0.28, respectively. The reproducibility of the OZ center measurements was excellent for the tangential difference maps (ICC $$\ge 0.97$$ ≥ 0.97 ) and good for the pachymetry difference maps (ICC $$\ge$$ ≥ 0.86). ICC, Sw, and CR showed excellent reproducibility of $$d_{TC}$$ d TC , with values of 0.95, 0.03, and 0.08, respectively. ICC, Sw, and CR showed good reproducibility of $$d_{PC}$$ d PC , with values of 0.89, 0.06, and 0.17, respectively. Conclusion The centration analysis method used in this study showed good to excellent repeatability and reproducibility in locating the coordinates of the center of the OZ on the tangential and pachymetry difference maps.

Abstract The marine ecological red lines (MERLs) is an institutional innovation of the Chinese government to seek a balance between ecological protection and social development. China’s MERLs was designated in 2017, but there are problems such as insufficient consideration of areas of high ecological importance and lack of convergence with marine functional zoning. This paper carries out the adjustment of the MERLs in China by constructing the methods of marine ecological importance assessment and human activities disposal assessment, and the results show that after the adjustment, the type and distribution pattern of China’s MERLs is more reasonable, the areas of high ecological importance in the MERLs increases significantly, the intensity of human activities in the MERLs declines significantly, and the unification with the use of marine space is realized. China’s adjustment of the MERLs is based on scientific assessment and realizes the coordination of development and protection, which can provide a reference for global marine ecological protection.

Abstract Objective Neutrophil-to-lymphocyte ratio (NLR) has been shown to be an independent predictor for cardiovascular diseases and metabolic diseases. The role of NLR in metabolic syndrome (MS) has also been explored albeit with conflicting results. The objective of this study was to assess the predictive role of NLR in MS. Methods We conducted a meta-analysis of observational studies to evaluate the predictive role of NLR in MS. Cochrane library, PubMed, Medline, Embase, and Scopus were systematically searched from their inception to December 2023. The Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) guidelines was followed. The statistical analysis was performed using RevMan 5.3 software. A randomeffect model was used. Results Twenty six studies enrolling 70,937 individuals were included in this meta-analysis. Compared with the individuals without MS, NLR value was significantly higher in the patients of MS (mean difference (MD) 0.40, 95% confidence intervals (CI): 0.27–0.52, P

Abstract Background The present study aimed to investigate physicians’ perspectives on the diagnosis and treatment decisions for patients with non-small cell lung cancer (NSCLC) harbouring epidermal growth factor receptor (EGFR) exon 20 insertion (exon20ins) mutations in a real-world setting in China using an online questionnaire. Methods This study was performed via the CAPTRA-Lung collaboration between December 9, 2022 and March 6, 2023. The questionnaire was distributed digitally to physicians around China and was comprised of three sections: basic characteristics of surveyed physicians, diagnosis and treatment status of NSCLC patients with the EGFR exon20ins-mutation, and physicians’ perspectives on treatment options. Physicians who treat more than 10 patients with advanced NSCLC every month and who have treated patients with advanced EGFR exon20ins-mutant NSCLC in the past six months were involved in this study. Results A total of 53,729 questionnaires were distributed and 390 valid ones were collected. The EGFR mutation test was performed in 80.9% and 59.9% of patients receiving first-line or second-line therapy and beyond (hereinafter “second-line”)therapy, respectively. In terms of treatment options, chemotherapy plus antiangiogenic therapy was the most common treatment option (30.0% of patients in first-line settings; 25.0% of patients in second-line settings), and a certain proportion of patients received novel EGFR exon20ins-targeted agents (including tyrosine kinase inhibitors [TKIs] and bispecific antibodies) in first- or second-line settings, which accounted for 11.9% and 15.7% of all treated patients, respectively. Additionally, physicians reported the highest satisfaction score for the efficacy and safety of targeted agents. Most physicians believed that EGFR exon20ins-targeted TKIs represented the most promising treatment option (80.2% in first-line treatment and 73.3% in second-line treatment). Among several novel agents under study, sunvozertinib has received the highest recognition for efficacy and safety. Conclusions This study investigated the current diagnosis and treatment status and physicians’ perspective, of patients with EGFR exon20ins-mutant NSCLC. The results highlight significant unmet clinical needs in this subgroup of patients. EGFR exon20ins-targeted TKIs were recognized as the most promising treatment regimen and may benefit more patients considering their awareness and acceptance of targeted therapy.

Abstract Intertidal algae may adapt to environmental challenges by acquiring genes from other organisms and relying on symbiotic microorganisms. Here, we obtained a symbiont-free and chromosome-level genome of Pyropia haitanensis (47.2 Mb), a type of intertidal algae, by using multiple symbiont screening methods. We identified 286 horizontal gene transfer (HGT) genes, 251 of which harbored transposable elements (TEs), reflecting the importance of TEs for facilitating the transfer of genes into P. haitanensis. Notably, the bulked segregant analysis revealed that two HGT genes, sirohydrochlorin ferrochelatase and peptide-methionine (R)-S-oxide reductase, play a significant role in the adaptation of P. haitanensis to heat stress. Besides, we found Pseudomonas, Actinobacteria, and Bacteroidetes are the major taxa among the symbiotic bacteria of P. haitanensis (nearly 50% of the HGT gene donors). Among of them, a heat-tolerant actinobacterial strain (Saccharothrix sp.) was isolated and revealed to be associated with the heat tolerance of P. haitanensis through its regulatory effects on the genes involved in proline synthesis (proC), redox homeostasis (ggt), and protein folding (HSP20). These findings contribute to our understanding of the adaptive evolution of intertidal algae, expanding our knowledge of the HGT genes and symbiotic microorganisms to enhance their resilience and survival in challenging intertidal environments.

Abstract Background This study aimed to assess the effectiveness of the BOPPPS model (bridge-in, learning objective, pre-test, participatory learning, post-test, and summary) in otolaryngology education for five-year undergraduate students. Methods A non-randomized controlled trial was conducted with 167 five-year undergraduate students from Anhui Medical University, who were allocated to an experimental group and a control group. The experimental group received instruction using the BOPPPS model, while the control group underwent traditional teaching methods. The evaluation of the teaching effectiveness was performed through an anonymous questionnaire based on the course evaluation questionnaire. Students’ perspectives and self-evaluations were quantified using a five-point Likert scale. Furthermore, students’ comprehension of the course content was measured through a comprehensive final examination at the end of the semester. Results Students in the experimental group reported significantly higher scores in various competencies compared to the control group: planning work (4.27 ± 0.676 vs. 4.03 ± 0.581, P

Abstract Introduction Inflammatory and immunological responses are reported involved in the pathogenesis and progression of obstructive nephropathy (ON). This study was designed to investigate the characteristics of peripheral immunity in patients with upper urinary tract urolithiasis and analyze the underlying associations with renal function. Methods Patients with unilateral upper urinary tract urolithiasis meeting the operation indications were prospectively enrolled. Preoperative circulating immune cells and inflammatory cytokines were detected in our clinical laboratory, and the indicators of renal function and calculi related parameters were particularly recorded. Patients were sectionalized into subgroups on the basis of the lesion of calculi. Characteristics of peripheral immunity in each subgroup were investigated by statistical approaches, and the underlying correlations with the degree of hydronephrosis (HN) and renal function were discussed in corresponding group. Results Patients with ureteral calculi presented severer HN compared with renal calculi, especial middle ureteral calculi, acting as the chief culprit of ON, exhibiting the highest serum creatine and blood urea nitrogen, most impaired estimated glomerular filtration rate, and severest HN. In addition, serum interleukin-8 (IL-8) and IL-6 were demonstrated presenting statistical differences between ureteral calculi and renal calculi patients, exhibiting underlying values in comprehending ON. However, circulating immune cells were demonstrated no obvious differences among groups. Conclusions Circulating inflammatory cytokines, referred in particular to serum IL-8 and IL-6 were partially associated with kidney injury in patients with upper urinary tract urolithiasis. But the specific influences and mechanisms between them needed to be investigated furthermore.

To enhance the aerodynamic performance of aero engine blades, simulations and experiments regarding microtextures to reduce the flow loss on the blade surfaces were carried out. First, based on the axisymmetric characteristics of the impeller, a new simulation method was proposed to determine the aerodynamic parameters of the blade model through the comparison of flow field characteristics and simulation results. Second, the placement position and geometrical parameters (height, width, and spacing) of microtextures with lower energy loss were determined by our simulation of microtextures on the blade surface, and the drag reduction mechanism was analyzed. Triangular ribs with a height of 0.2 mm, a width of 0.3 mm, and a spacing of 0.2 mm exhibited the best drag reduction, reducing the energy loss coefficient and drag by 1.45% and 1.31% for a single blade, respectively. Finally, the blades with the optimal microtexture parameters were tested in the wind tunnel. The experimental results showed that the microtexture decreased energy loss by 3.7% for a single blade under 57° angle of attack and 136.24 m/s, which was favorable regarding the drag reduction performance of the impeller with 45 blades.

Abstract Background Parent-child separation poses a significant challenge for left-behind children (LBC). However, limited empirical evidence exists regarding the correlation between left-behind characteristics and the psychological symptoms of LBC. This study investigated psychological symptoms among LBC and explored associations between left-behind characteristics and those symptoms. Methods Using stratified cluster sampling, 1,832 LBC aged 13–18 years from three cities in East China were selected for analysis. Participants’ depression and anxiety symptoms were assessed with the Patient Health Questionnaire 9 and the General Anxiety Disorder 7, respectively. Chi-square tests were used to compare differences in detection rates of psychological symptoms among LBC in different groups. Binary logistic regression analysis was used to infer associations between left-behind characteristics and psychological symptoms. Results Depression and anxiety symptoms were detected in 32.86% and 33.24%, respectively, of participating LBC. Univariate analysis showed statistically significant differences in detection rates of depression symptoms by sex, grade, and timing of parent-child separation. Statistically significant differences were observed in anxiety symptom rates by sex, grade, type of caregiver, and timing of mother-child separation. Multivariate analysis indicated a positive association between LBC’s anxiety symptoms and mother-child separation that occurred during post-primary school, and type of caregiver (father only or mother only). Our findings confirm a positive association between left-behind characteristics and anxiety symptoms among LBC. Conclusion The timing of mother-child separation and type of caregiver are potential risk factors for the development of anxiety symptoms in this population.

Abstract Purpose Cutaneous metastasis (CM) accounts for 5–30% of patients with breast cancer (BC) and presents unfavorable response to treatment and poor prognosis. A better understanding of the molecular alterations involved in metastasis is essential, which would help identify diagnostic and efficacy biomarkers for CM. Materials : We retrospectively reviewed a total of 13 patients with histological or cytological diagnosis of breast cancer and CM. Clinical information was extracted from the medical records. The mutational landscape of matched primary tumors with their lymph nodes or CM tissues were analyzed using next-generation sequencing (NGS) of 425 cancer-relevant genes. All tissues were also analyzed by immunohistochemistry (IHC). The association of prognosis with various clinical and molecular factors was also evaluated. Results More than half of the patients were Ki67 low ( 50%) showed significantly shorter T1 than the Ki67 low group (≤ 50%) (median 12.5 vs. 50.0 months, P = 0.036). TP53, PIK3CA mutations, and TERT amplification group were associated with inferior T2 (median 11 vs. 36 months, P = 0.065; 8 vs. 36 months, P = 0.013, 7 vs. 36 months, P = 0.003, respectively). All p values were not adjusted. Conclusion We compared the genomic features of primary breast cancer tissues with their corresponding CM tissues and discussed potential genes and pathways that may contribute to the skin metastasis of advanced breast cancers patients. TP53, PIK3CA mutant, and TERT amplification may serve as biomarkers for poor prognosis for CM patients.

ARID1A deletion mutation contributes to improved treatment of several malignancies with immune checkpoint inhibitors (ICIs). However, its role in modulating of tumor immune microenvironment (TIME) of gastric cancer (GC) remains unclear. Here, we report an increase of CD8+ T cells infiltration in GC patients with ARID1A-mutation (MUT), which enhances sensitivity to ICIs. Kaplan-Meier survival analysis showed that ARID1A-mutation patients with gastrointestinal malignancies benefit from immunotherapy. Transcriptome analysis implicated that ARID1A regulates STAT5 downstream targets to inhibit T-cell mediated toxicity. Integrated dual luciferase assay and ChIP-qPCR analyses indicated that ARID1A coordinated with STAT5 to facilitate the transcription of the immunosuppressive factors TGF-β1 and NOX4. ARID1A recruited canonical BAF complex (cBAF) subunits, including SMARCB1 and SMARCD1, to sustain DNA accessibility. Downregulation of ARID1A reduced chromatin remodeling into configurations which make GC more sensitive to ICIs. In addition, targeting STAT5 effectively improved anti-PD-1 efficiency in ARID1A-wild type (WT) GC patients. Taken together, ARID1A is a coactivator of STAT5, function as a chromatin organizer in GC ICIs resistance, and targeting STAT5 is an effective strategy to improve the efficiency of ICIs in GC.

Cold patched asphalt mixture plays a crucial role in road maintenance, providing flexibility and the ability to quickly recover from harsh weather conditions. This article conducts in-depth research on the performance of cold patched asphalt mixture through multiple experiments, with special attention paid to the influence of diluent content and curing conditions on its performance. The experimental results show that using a mixture of green curing agents is feasible, and the diluent content is one of the main factors affecting the physical properties of cold patched asphalt. The optimal content of asphalt diluent was determined to be 25 % through mass evaporation experiments and rotational viscosity experiments. Meanwhile, it was found that single component polyurethane prepolymers and SBS curing agents have a negative impact on the adhesion of cold patched asphalt, but have an improving effect on its strength, high-temperature resistance, and water stability. After comparing the performance of cold patched asphalt mixtures under different curing conditions, it was found that the performance of cold patched materials with long-term curing was better. Finally, this study determined the optimal dosage ratio of base asphalt, bio oil diluent, and single component polyurethane prepolymer as 100:25:12, providing technical support for the design and application of cold patched asphalt concrete pavement under high adverse weather conditions.

Study region: Xinjiang is located in the mid-latitude region of Eurasia in northwestern China. Precipitation is predominantly concentrated in northern Xinjiang, while southern Xinjiang remains comparatively arid. Summer precipitation accounts for 54.4 % of the annual total. Study focus: This study aims to develop a machine learning model to predict summer precipitation (June–August) in XJ and explore the key variables contributing to summer precipitation in this region. The SHapley Additive exPlanations method was integrated with an extreme tree model to quantify the contributions of variables towards precipitation. Artificial neural networks, support vector machines, and extreme gradient boosting were considered to predict summer precipitation. To train the ML model, we used precipitation data from 1961 to 2012, whilst the forecast results from 2013 to 2017 were used for validation. New hydrological insights for the regions: The results demonstrated that the ANN model achieved robust performance during both the training and validation periods. For Northern and Southern XJ, the Mean Absolute Error and Root Mean Square Error of the ANN model were 15.34 (20.40) and 23.21 (30.01), respectively. The SHAP analysis showed that in the context of Northern Xinjiang, the Niño B Sea Surface Temperature Anomaly, Western Pacific Subtropical High Intensity, Pacific Subtropical High Intensity, and Multivariate ENSO Index play crucial roles in the prediction of summer precipitation. In Southern Xinjiang, the South China Sea Subtropical High Intensity, South China Sea Subtropical High Area, Western Pacific Warm Pool Strength, and Atlantic multidecadal oscillation have emerged as key variables affecting summer precipitation forecasting.

Freezing storage is a common preservation method for industrialized duck meat. However, both the frozen storage and thawing processes of meat can affect meat quality. Therefore, appropriate thawing methods are crucial for maintaining good meat quality. In this study, a pulsed electric field (PEF) was used for thawing zhijiang duck meat and the freshed duck meats were used as control. Optimization of the PEF-assisted thawing process and its effect on the quality of zhijiang duck meat were analyzed. Our data showed that the shear force in the 2 kV/cm PEF-assisted thawing group was the lowest in PEF-assisted thawing groups. The color of zhijiang duck meat in the 2 kV/cm PEF-assisted thawing group was optimal. The 2 kV/cm PEF-assisted thawing could improve the texture characteristics of zhijiang duck meat and enhance water holding capacity of zhijiang duck meat. PEF-assisted thawing could better maintain the microstructure of zhijiang duck meat. Our data showed that if the intensity or duration of PEF treatment is too high, the quality of duck meat will actually decrease. Therefore, appropriate parameters should be selected in practical applications, which will provide a reference for the application of PEF-assisted thawing on the market.

Aim Comparing the anxiety and depression severity and their impact on subsequent birth outcomes in pregnant women before and during Omicron wave in Shanghai in 2022.Methods The depression-anxiety symptoms networks were compared between the pregnant women during the outbreak period (outbreak group; n = 783) and a matched control group of pregnant women before the outbreak (pre-outbreak group; n = 783). The impact of baseline mental state on follow-up pregnancy and neonatal outcomes was also explored by logistic regression.Findings Levels of depression and anxiety between the two groups were not significant different. Network analysis showed that central symptom "trouble relaxing" and bridge symptom "depressed mood" shared by both groups. Different symptom associations in different periods of the pandemic. Total scores and sub-symptom scores of prenatal depressive and anxious severities increased the odds ratios of maternal and neonatal syndromes. The influence of mental state on gestational and neonatal outcomes differed across different pandemic periods.Conclusion The Omicron wave did not have a significant negative impact on the depressive and anxious mood in pregnant women. Targeting central and bridge symptoms intervention may be effective in reducing their adverse effects on co-occurring of anxious and depressive mood and birth outcomes.

ABSTRACTThis study employed sero-epidemiological methods to estimate the incidence of pertussis within a healthy population located in eastern China. The aim was to gain deeper insights into the epidemiological characteristics and burden of pertussis within the country. Blood samples were collected from healthy individuals in Jiangsu Province between June 2019 and December 2022. The levels of IgG antibodies against pertussis toxin (anti-PT) and filamentous hemagglutinin (anti-FHA) in the serum were quantitatively measured using enzyme-linked immunosorbent assay (ELISA). Additionally, pertussis case data reported in Jiangsu Province were collected from the China Information System for Disease Control and Prevention and compared with the results of this study. In 2022, the reported incidence of pertussis stood at 1.0 per 100,000 individuals, marking the highest rate observed in the past two decades. Among 1,909 patients examined, the geometric mean concentration (GMC) of anti-PT IgG antibody was 20.2 (18.5–21.9) IU/ml, while that of anti-FHA IgG antibody was 27.0 (25.4–28.7) IU/ml. The IgG-PT and IgG-FHA seropositivity rate (>20.0 IU/ml) was highest in the 1 ~ 2 y old group and decreased rapidly to the lowest in the 3 ~ 4 y old group and then increased gradually with age. The estimated rate of pertussis infection based on seroprevalence was approximately 25,625‐fold higher than the reported notification rate in the ≥15 year age group. Our findings highlight decreased immunity post-vaccination, stressing the importance of additional booster shots for adolescents and adults to maintain immunity and reduce severe illness. Additionally, they offer vital guidance for policymakers to enhance immunization strategies.

This study aimed to investigate the correlation between ultrafiltration rate (UFR) and hemoglobin levels and erythropoietin (EPO) response in patients receiving maintenance hemodialysis (MHD). 225 MHD patients were divided into three groups according to the UFR: < 10 ml/h/kg, 10–13 ml/h/kg, and >13 ml/h/kg. Clinical parameters and prognosis were compared among the groups. Multiple linear correlation and regression analyses were conducted. SPSS 26.0 (IBM, Chicago, IL, USA) was used to analyze all statistics. The UFR < 10 ml/h/kg group was older than the other groups (p 13 ml/h/kg group had the highest SpKt/V (p

This research delves into unexplored territories of Foreign Language Anxiety (FLA), going beyond the traditional focus on language proficiency. We examined the nuanced roles of language exposure and individual differences in cognitive control abilities in shaping FLA. By engaging 46 English learners in a comprehensive assessment, our analysis uncovered significant yet distinct contributions of these factors to various aspects of FLA. Notably, proficiency predicted communication and overall anxiety, exposure influenced evaluation anxiety, while inhibition and mental set shifting abilities significantly predicted communication and test anxiety respectively. These findings illuminate the complexity of FLA, revealing that it stems from a multifaceted interplay of language proficiency, exposure, and cognitive control. This holistic understanding offers valuable insights for educators and learners alike, emphasizing the importance of tailored strategies that address not just language proficiency but also exposure opportunities and cognitive strengths.

Introduction: With advancements in detection equipment and an increase in the frequency of examinations, thyroid nodules and goiter in children have garnered attention. Objective: This study aims to determine the effects of high iodine and fluoride exposure on thyroid nodules and goiter in school-aged children. Methods: We recruited children aged 8 to 12 from rural Jiangsu, China, based on the concentrations of iodine and fluoride in local drinking water and urine. Participants were divided into four groups: a group with high fluoride and iodine (HFHI), a group with high fluoride (HF), a group with high iodine (HI), and a control group (CONTROL). Fluoride levels in both drinking water and urine samples were measured using the ion-selective electrode method. Urinary iodine (UI) was assessed using inductively coupled plasma mass spectrometry, and children's thyroids were examined with portable ultrasound equipment equipped with a linear 7.5-MHz probe. Results: The detection rates of thyroid nodules in the HFHI, HF, HI, and CONTROL groups were 10.4 %, 6.5 %, 7.7 %, and 2.8 %, respectively. The goiter detection rates were 3.8 %, 2.9 %, 3.8 %, and 1.1 %, respectively. In the HFHI group, statistically significant correlations were found between urinary fluoride (UF) and thyroid nodules (P = 0.011, adjusted OR and 95 % CIs were 2.29 [1.21, 4.32]), as well as between UI and thyroid nodules (P = 0.038, adjusted OR and 95 % CIs were 1.58 [1.04, 2.40]), and between UI and goiter (P = 0.014, adjusted OR and 95 % CI were 2.31 [1.19, 4.48]). In the HI group, there was a statistically significant link between UI and goiter (P = 0.005, adjusted OR and 95 % CI were 2.45 [1.31, 4.58]). Conclusions: Combined high iodine and fluoride exposure may have an adverse effect on thyroid nodules in school-age children.

Summary: Background: The influence of the gut microbiota on long-term immune checkpoint inhibitor (ICI) efficacy and immune-related adverse events (irAEs) is poorly understood, as are the underlying mechanisms. Methods: We performed gut metagenome and metabolome sequencing of gut microbiotas from patients with lung cancer initially treated with anti-PD-1/PD-L1 therapy and explored the underlying mechanisms mediating long-term (median follow-up 1167 days) ICI responses and immune-related adverse events (irAEs). Results were validated in external, publicly-available datasets (Routy, Lee, and McCulloch cohorts). Findings: The ICI benefit group was enriched for propionate (P = 0.01) and butyrate/isobutyrate (P = 0.12) compared with the resistance group, which was validated in the McCulloch cohort (propionate P

Summary: Obstructive sleep apnea (OSA) leads to chronic intermittent hypoxia (CIH) and is not well addressed by current therapies. The genioglossus (GG) is the largest upper airway dilator controlling OSA pathology, making its repair a potential treatment. This study investigates dental pulp stem cells (DPSCs) in repairing GG injury in a CIH mouse model. We induced DPSCs to myogenic lineage cells (iDPSCs) and transplanted them into GG of CIH mice. DPSCs/iDPSCs grafts improved EMGGG and muscle type transitions while reducing tumor necrosis factor α (TNF-α), alanine aminotransferase (ALT), lactate dehydrogenase (LDH), and creatine kinase (CK) levels, improving body weight. Moreover, iDPSCs increased Pax7+/Ki67+ and human-derived STEM121 cells in the GG compared with DPSCs. DPSCs/iDPSCs enhanced Desmin+ myotube formation in myoblasts under hypoxia in vitro, with iDPSCs increased human-derived myogenic markers and nuclei in myotubes. These results indicate that iDPSCs, beyond their paracrine effects like DPSCs, directly participate in myogenic differentiation, supporting the potential use of DPSCs for OSA treatment.

Objective: Acute lower gastrointestinal bleeding is a common emergency in gastroenterology. Currently, there is insufficient information to predict adverse outcomes in patients with acute lower gastrointestinal bleeding. Our study aimed to compare the effectiveness of the clinical risk scores currently utilized and their ability to predict significant outcomes in lower gastrointestinal bleeding. Methods: We conducted a prognostic study of patients hospitalized for acute lower gastrointestinal bleeding who underwent colonoscopy or angiography at a single-center hospital between January 2015 and October 2023. Adverse outcomes associated with ALGIB included rebleeding, blood transfusion, hemostatic interventions, and in-hospital death. We calculated three risk scores at admission (Oakland, Birmingham, SALGIB). We measured the accuracy of these scores using the area under the receiver operating characteristic curve (AUC) and compared them with DeLong's test. Results: 222 patients with confirmed lower gastrointestinal bleeding (aged 64 years, 53–75) were finally included. The most common diagnoses were colorectal cancer (28 %) and hemorrhoids (14 %). The Oakland score, Birmingham score, and SALGIB score displayed comparable performance in predicting any adverse outcome (AUC = 0.54, 0.53, 0.55). However, none of the scores were able to sufficiently discriminate rebleeding, blood transfusion, or hemostatic intervention. Using the Youden index, cutoff points for predicting undesired results were identified for the Oakland score at 13, Birmingham score at 3, and SALGIB score at 2. Conclusions: None of the three scores demonstrated satisfactory discrimination for adverse outcomes. Therefore, it is necessary to develop novel risk stratification scores with higher performance to improve risk stratification in acute lower gastrointestinal bleeding.

ObjectiveMild cognitive impairment (MCI) is a common non-motor manifestation of Parkinson’s disease, commonly referred to as PD-MCI. However, there is a lack of comprehensive data regarding the role of glial cell line-derived neurotrophic factor (GDNF) and cerebral white matter damage in the pathogenesis of PD-MCI. The objective of this study is to investigate the association between alterations in GDNF levels and cerebral white matter damage in individuals diagnosed with PD-MCI, as well as to explore their potential involvement in cognitive progression.MethodsNeuropsychological assessments were conducted on 105 patients with Parkinson’s disease and 45 healthy volunteers to examine various cognitive domains. An enzyme-linked immunosorbent assay (ELISA) was employed to measure serum levels of GDNF. Additionally, all participants underwent 3.0T magnetic resonance imaging (MRI) to acquire diffusion tensor images (DTI), and a voxel-based analysis (VBA) approach was utilized to compare the fractional anisotropy (FA) values of white matter in the brain.ResultsThere was a significant correlation between the right corpus callosum, right cingulate gyrus, and the Digit Span Backward Test (DSB-T) as well as the Trail Making Test A (TMT-A), both of which assess attention and working memory functions. The left internal capsule exhibited a significant correlation with the Trail Making Test B (TMT-B) and the Clock Drawing Test (CDT), which evaluate executive function. Additionally, the right cingulate gyrus showed a significant association with scores on the Auditory Verbal Learning Test-HuaShan (AVLT-H), assessing memory function. Abnormal fiber structures that demonstrated significant correlations with serum GDNF levels included the left internal capsule, left corticospinal tract, right corpus callosum, and right cingulate gyrus.ConclusionThe decrease in serum GDNF levels among PD-MCI patients exhibiting impairments in attention and working memory function was significantly correlated with alterations in the corpus callosum (knee) and posterior cingulate gyrus. Furthermore, the reduction of serum GDNF levels in PD-MCI patients with impaired executive function is associated with changes in the internal capsule (forelimb) projection fibers. Additionally, the decline of serum GDNF levels in PD-MCI patients experiencing memory function impairment is related to alterations in the right cingulate gyrus.

Hemoperfusion is one of the most important therapies for progressive chronic kidney disease (CKD) and is effective at removing toxins from the blood. Increasing the efficiency of adsorbents applied in hemoperfusion is crucial. In the present study, shell of areca nut, one of the most common waste Chinese herb medicine residue with a porous structure was carbonized and activated at different temperatures to obtain two kinds of porous materials. The biocompatibility of the as-prepared porous materials was estimated via a hemolytic test, and the removal efficiency of the materials toward toxins was tested via an adsorption experiment in solution and blood samples from CKD patients, simulated hemoperfusion and in vivo hemoperfusion. After 4 h of adsorption, free and protein-bound toxins in solution were efficiently removed by the prepared porous materials, and the removal efficiency was better than that of commonly used hemoperfutor adsorbents. Most of the tested toxins can be removed from CKD blood samples and simulated hemoperfusion samples. Blood uremic toxins from CKD mice were also efficiently and safely removed after in vivo hemoperfusion using the as-prepared adsorbent. This work highlights promising adsorbents for hemoperfusion that could increase the therapeutic efficacy in patients with progressive CKD.

This case report describes a rare instance of extrarenal clear cell renal cell carcinoma (ccRCC) in a 48-year-old woman who presented with a loss of consciousness. Abdominal CT revealed a 24 × 31 mm mass in the left adrenal region, with no kidney involvement. The mass was surgically excised, and histopathological examination confirmed the diagnosis of ccRCC. Immunohistochemical analysis revealed positive markers, including CA9, CD10, PAX-8, and vimentin. The patient did not undergo adjuvant therapy, and a 6-month follow-up showed no signs of recurrence or metastasis. This case emphasizes the importance of considering extrarenal ccRCC in differential diagnoses of adrenal masses.

Despite the transformative impact of anti-PD-1/PD-L1 therapies, challenges such as low response rates persist. The stimulator of interferon genes (STING) pathway, a crucial element of innate immunity, emerges as a strategic target to overcome these limitations. Understanding its multifaceted functions in cancer, including antigen presentation and response to DNA damage, provides valuable insights. STING agonists, categorized into cyclic dinucleotides (CDNs) and non-CDNs, exhibit promising safety and efficacy profiles. Innovative delivery systems, including antibody-drug conjugates, nanocarriers, and exosome-based therapies, address challenges associated with systemic administration and enhance targeted tumor delivery. Personalized vaccines, such as DT-Exo-STING, showcase the adaptability of STING agonists for individualized treatment. These advancements not only offer new prospects for combination therapies but also pave the way for overcoming resistance mechanisms. This review focuses on the potential of targeting STING pathway to enhance cancer immunotherapy. The integration of STING agonists into cancer immunotherapy holds promise for more effective, personalized, and successful approaches against malignancies, presenting a beacon of hope for the future of cancer treatment.