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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.

Abstract A power system can be regarded as a cyber‐physical system with physical power networks and a cyber system based on increasing engagement with information communication technologies for smart grid functionalities for more efficient operations and control. Non‐intrusive load monitoring (NILM), an emerging smart‐grid technology, can be used to better understand the electricity usage profile and composition of smart meters using advanced data analysis algorithms. Although NILM enables various smart grid services, wider applications of NILM require addressing the challenges regarding cyber security and data privacy risks. Anomaly detection in appliance data is one of the most effective measures against potential cyber intrusions from a data perspective. This study proposes a framework of anomaly detection‐based learning algorithms to identify the anomalous periods of electricity loading data, which may be a subject for potential cyber‐attacks. Comparison studies with the hidden Markov model are performed to validate the proposed approaches. The simulation results show that these anomaly detection‐based learning algorithms work well and can precisely determine anomalous loading periods. Moreover, these trained models perform well on the testing dataset without prior knowledge of the data, providing the possibility of the real‐time assessment of power‐ loading states. The proposed framework can also be used to develop protective measures to ensure secure system operation and user data privacy.

Abstract Developing superporous hemostatic sponges with simultaneously enhanced permeability and mechanical properties remains challenging but highly desirable to achieve rapid hemostasis for non-compressible hemorrhage. Typical approaches to improve the permeability of hemostatic sponges by increasing porosity sacrifice mechanical properties and yield limited pore interconnectivity, thereby undermining the hemostatic efficacy and subsequent tissue regeneration. Herein, we propose a temperature-assisted secondary network compaction strategy following the phase separation-induced primary compaction to fabricate the superporous chitosan sponge with highly-interconnected porous structure, enhanced blood absorption rate and capacity, and fatigue resistance. The superporous chitosan sponge exhibits rapid shape recovery after absorbing blood and maintains sufficient pressure on wounds to build a robust physical barrier to greatly improve hemostatic efficiency. Furthermore, the superporous chitosan sponge outperforms commercial gauze, gelatin sponges, and chitosan powder by enhancing hemostatic efficiency, cell infiltration, vascular regeneration, and in-situ tissue regeneration in non-compressible organ injury models, respectively. We believe the proposed secondary network compaction strategy provides a simple yet effective method to fabricate superporous hemostatic sponges for diverse clinical applications.

Abstract Bacteriophages (phages) represent a unique category of viruses with a remarkable ability to selectively infect host bacteria, characterized by their assembly from proteins and nucleic acids. Leveraging their exceptional biological properties and modifiable characteristics, phages emerge as innovative, safe, and efficient delivery vectors. The potential drawbacks associated with conventional nanocarriers in the realms of drug and gene delivery include a lack of cell-specific targeting, cytotoxicity, and diminished in vivo transfection efficiency. In contrast, engineered phages, when employed as cargo delivery vectors, hold the promise to surmount these limitations and attain enhanced delivery efficacy. This review comprehensively outlines current strategies for the engineering of phages, delineates the principal types of phages utilized as nanocarriers in drug and gene delivery, and explores the application of phage-based delivery systems in disease therapy. Additionally, an incisive analysis is provided, critically examining the challenges confronted by phage-based delivery systems within the domain of nanotechnology. The primary objective of this article is to furnish a theoretical reference that contributes to the reasoned design and development of potent phage-based delivery systems. Graphical abstract

Abstract Background Research into the acute kidney disease (AKD) after acute ischemic stroke (AIS) is rare, and how clinical features influence its prognosis remain unknown. We aim to employ interpretable machine learning (ML) models to study AIS and clarify its decision-making process in identifying the risk of mortality. Methods We conducted a retrospective cohort study involving AIS patients from January 2020 to June 2021. Patient data were randomly divided into training and test sets. Eight ML algorithms were employed to construct predictive models for mortality. The performance of the best model was evaluated using various metrics. Furthermore, we created an artificial intelligence (AI)-driven web application that leveraged the top ten most crucial features for mortality prediction. Results The study cohort consisted of 1633 AIS patients, among whom 257 (15.74%) developed subacute AKD, 173 (10.59%) experienced AKI recovery, and 65 (3.98%) met criteria for both AKI and AKD. The mortality rate stood at 4.84%. The LightGBM model displayed superior performance, boasting an AUROC of 0.96 for mortality prediction. The top five features linked to mortality were ACEI/ARE, renal function trajectories, neutrophil count, diuretics, and serum creatinine. Moreover, we designed a web application using the LightGBM model to estimate mortality risk. Conclusions Complete renal function trajectories, including AKI and AKD, are vital for fitting mortality in AIS patients. An interpretable ML model effectively clarified its decision-making process for identifying AIS patients at risk of mortality. The AI-driven web application has the potential to contribute to the development of personalized early mortality prevention.

Abstract Prunus conradinae, a valuable flowering cherry belonging to the Rosaceae family subgenus Cerasus and endemic to China, has high economic and ornamental value. However, a high-quality P. conradinae genome is unavailable, which hinders our understanding of its genetic relationships and phylogenesis, and ultimately, the possibility of mining of key genes for important traits. Herein, we have successfully assembled a chromosome-scale P. conradinae genome, identifying 31,134 protein-coding genes, with 98.22% of them functionally annotated. Furthermore, we determined that repetitive sequences constitute 46.23% of the genome. Structural variation detection revealed some syntenic regions, inversions, translocations, and duplications, highlighting the genetic diversity and complexity of Cerasus. Phylogenetic analysis demonstrated that P. conradinae is most closely related to P. campanulata, from which it diverged ~ 19.1 million years ago (Mya). P. avium diverged earlier than P. cerasus and P. conradinae. Similar to the other Prunus species, P. conradinae underwent a common whole-genome duplication event at ~ 138.60 Mya. Furthermore, 79 MADS-box members were identified in P. conradinae, accompanied by the expansion of the SHORT VEGETATIVE PHASE subfamily. Our findings shed light on the complex genetic relationships, and genome evolution of P. conradinae and will facilitate research on the molecular breeding and functions of key genes related to important horticultural and economic characteristics of subgenus Cerasus.

Abstract The demand for larger and lighter mechanisms for next-generation space missions necessitates using deployable structures. High-strain fiber polymer composites show considerable promise for such applications due to their exceptional strength-to-weight ratio, manufacturing versatility, packaging efficiency, and capacity for self-deployment using stored strain energy. However, a significant challenge in using composite deployable structures for space applications arises from the unavoidable extended stowage periods before they are deployed into their operational configuration in orbit. During the stowage period, the polymers within the composites experience material degradation due to their inherent viscoelastic and/or plastic properties, causing stress relaxation and accumulation of plastic strains, thereby reducing the deployment capability and resulting in issues related to recovery accuracy. This paper aims to give a state-of-the-art review of recent advances in the design, modeling, and manufacturing of high-strain composites for deployable structures in space applications, emphasizing the long-term stowage effects. This review is intended to initiate discussion of future research to enable efficient, robust, and accurate design of composite deployable structures that account for the enduring challenges posed by long-term stowage effects.

In July 2021, a heavy rainstorm was sweeping across Henan Province, causing geological disasters such as floods, mudslides, and landslides, which seriously threatened the safety of human life and property. Precipitable water vapor (PWV) is related to the occurrence and scale of rainfall. Here, based on Global Navigation Satellite System (GNSS) observations, in-situ meteorological files (GMET), ephemeris products, ERA5 data, and weather station data, the relationship between PWV and rainstorm from July 1st to 30th was studied. The results show that GMET and ERA5 in July 2021 have high consistency in some stations, with a root mean square error (RMSE) for temperature below 1.6 °C, for pressure below 0.5 hPa, and for relative humidity below 9 %. During the week before the heavy rainstorm, the temperature dropped remarkably and the temperature difference decreased, while the relative humidity increased and the relative humidity difference decreased. Compared with ERA5 PWV, the RMSE of GNSS PWV retrieved using real-time ephemeris is 3.238 mm. Different from the normal rainfall, we found that the PWV variation during the Henan rainstorm experienced a unique “accumulation” period. We also observed a clear correlation between PWV and the rainstorm, both temporally and spatially. In addition, the PWV in the severely damaged area was 20 mm higher than the average value of the past decade. Ten days after the rainstorm, the surface of this area had subsided by 1.5–3 mm. Finally, we found that the topography of Henan, the low vortex, the north-biased subtropical high, and the double typhoons all played a role in the successful transport and deposition of water vapor.

ADAM17 sheds EGFR/erbB ligands and triggers oncogenic pathways that lead to the progression of solid tumors. We targeted the ADAM17 disintegrin and cysteine rich domain region (D+C) to generate a panel of single-chain antibody fragments (scFvs) that selectively bind to the D or C domains of ADAM17, but not of ADAM10 or ADAM19. From the panel, we selected one scFv, referred to as C12, based on its high binding affinity towards the target, and re-formatted it to a full IgG for further studies. High-resolution cryo-electron microscopy studies documented that the mAb binds to the ADAM17 C-domain that in ADAM proteases, notably ADAM10 and ADAM17, is known to impart substrate-specificity. The C12 mAb significantly inhibited EGFR phosphorylation in cancer cell lines by hindering the cleavage of EGFR ligands tethered to the cell surface. This inhibition provides a mechanism for potential anti-tumor effects, and indeed C12 diminished the viability of a variety of EGFR-expressing cancer cell lines. Cell-based ELISA studies revealed that C12 preferentially bound to activated ADAM17 present on tumor cells, as compared to the autoinhibited ADAM17 that is the predominant form on HEK293 and other non-tumor cells. C12 also exhibited tumor growth inhibition in an ovarian cancer xenograft mouse model. Consistent with its selective tumor cell binding in vitro, radioimmuno PET (positron emission tomography) imaging with 89Zr-DFO-C12 in mouse xenograft models confirmed tumoral accumulation of the C12 mAb.

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.

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.

ABSTRACT Bacterial biofilms are the major etiology agent of peri-implant disease. Chemical decontamination is a promising treatment strategy against bacterial biofilms; however, its applications are limited by its low efficiency and poor biocompatibility. In contrast to three conventional cleaners (sterile saline, hydrogen peroxide, and chlorhexidine), this study used resveratrol and naringin solutions to remove mature Staphylococcus aureus and Porphyromonas gingivalis biofilm on sandblasted (with large grit and acid-etched (SLA) titanium surface. To determine changes in surface characteristics, the surface wettability and roughness were measured, and micromorphology was observed by scanning electron microscopy. With crystal violet (CV) and live/dead bacterial staining, residual plaque quantity and composition were measured. The biocompatibility was tested using pH and cytotoxicity, as well as by osteoblasts (MC3T3-E1) adhesion, proliferation, and differentiation, and fibroblasts (L-929) proliferation were also analyzed. It was found that resveratrol and naringin solutions were more effective in restoring surface characteristics and also showed that less plaque and viable bacteria were left. Naringin removed S. aureus biofilms better than chlorhexidine. Alkaline resveratrol and naringin solutions increased cell adhesion, proliferation, and osteogenic differentiation without any cytotoxicity. Resveratrol increased the expression of mRNA and protein associated with osteogenesis. In conclusion, resveratrol and naringin effectively restored SLA titanium surface characteristics and decontaminated the biofilm with good biocompatibility, suggesting their therapeutic potential as chemical decontaminants.IMPORTANCEBacterial biofilms are considered the primary etiology of peri-implant disease. Physical cleaning is the most common way to remove bacterial biofilm, but it can cause grooving, melting, and deposition of chemicals that alter the surface of implants, which may hamper biocompatibility and re-osseointegration. Chemical decontamination is one of the most promising treatments but is limited by low efficiency and poor biocompatibility. Our study aims to develop safer, more effective chemical decontaminants for peri-implant disease prevention and treatment. We focus on resveratrol and naringin, two natural compounds, which have shown to be more effective in decontaminating biofilms on dental implant surfaces and exerting better biocompatibility. This research is groundbreaking as it is the first exploration of natural plant extracts’ impact on mature bacterial biofilms on rough titanium surfaces. By advancing this knowledge, we seek to contribute to more effective and biocompatible strategies for combating peri-implant diseases, enhancing oral health, and prolonging implant lifespan.

Objective: In this study, to provide new methods for the treatment of Streptococcus pneumoniae infection, we aimed to describe the anti-inflammatory and antibacterial value of glycyrrhetinic acid on the basis of its inhibitory effect on bacterial growth (without killing the bacteria) and its reduction of the toxicity of S. pneumoniae. Methods: A mouse model was established via intranasal administration of Streptococcus pneumoniae D39, and glycyrrhetinic acid was subcutaneously injected for treatment. The wet‒dry ratio, bacterial flora content and inflammatory factor levels in the mouse lungs were determined. Cell experiments were used to evaluate glycyrrhetinic acid-mediated inhibition of PLY hemolysis and A549 cell death, and WB was used to measure glycyrrhetinic acid-mediated inhibition of PLY oligomerization. Results: Glycyrrhetinic acid reduced the levels of inflammatory factors, the dry‒wet ratio, the abundance of S. pneumoniae in the lungs of infected mice, pneumolysin-mediated A549 cell death, erythrocyte hemolysis and PLY oligoplasia. Conclusion: Glycyrrhetinic acid can reduce the virulence of S. pneumoniae by preventing the oligomerization of PLY.

The rapid development of high-speed railways (HSR) worldwide has provided a fast, convenient, safe, and comfortable mode of transportation. It is also an important public transportation tool for green travel, contributing to the reduction of carbon emissions. HSR has a strong competitive advantage in long-distance passenger transportation, but it faces significant competition from the aviation industry. Airlines attract passengers with discounted fares and differentiated pricing strategies, apart from shorter travel times. Therefore, it is necessary for railway enterprises to enhance their competitiveness through differentiated pricing methods for HSR. In this study, we focus on optimizing a long-distance origin-destination (OD) pair and creating a competitive market environment by considering all operating trains and flights for the selected OD pair. We aim to improve the realism of the study by considering passengers’ fully rational travel choice behavior. To reduce the complexity of variables, passengers are grouped based on their expected departure time and income level. A mixed integer linear programing model is developed to address the problem, aiming to minimize overall travel costs for passengers while ensuring that the income of the railway enterprise does not fall below a specified value. By setting this specific value, the maximum revenue of HSR train tickets can be obtained.

This study investigated the effects of incorporating different levels of Euglena gracilis microalgae powder (MP) on the dough properties, rheology, and quality attributes of Chinese steamed bread (CSB) for the first time. Moderate levels of MP (2%) reinforced the gluten network and improved protein structure, while higher levels (4–8%) adversely affected the gluten network and rheological properties. The addition of MP decreased the specific volume, pore number, and pore density of CSB, but increased pore size, hardness, and chewiness. It also imparted a yellow color to the CSB and slowed down moisture loss during storage. Notably, MP effectively increased the protein and lipid content of CSB, enhancing its nutritional value. The results suggest that optimizing the MP level is crucial to achieve nutritional enhancement while maintaining desirable texture and sensory attributes. An addition of 2% MP can strike a balance between nutrition and the overall quality of the final product.

Background: A high body mass index (BMI) increases the risk of hypertension. However, little is known about the dose-dependent association between BMI and hypertension. Therefore, this study investigated the prevalence of hypertension in 7568 subjects from the Jiangsu Province, Eastern China, and analyzed the dose–response relationship between BMI and hypertension risk. Methods: The eligible subjects completed a structured questionnaire and clinical biochemical indicators were measured according to standardized protocols. Multivariate logistic regression models were used to evaluate the association between BMI and hypertension. Restricted cubic spline (RCS) analysis was used to analyze the dose–response relationship between BMI and hypertension risk. Moreover, sensitivity analysis was performed to verify the robustness of our findings. Results: The prevalence of hypertension was 35.3 % in the total population. BMI was significantly associated with systolic and diastolic blood pressure. The fully-adjusted odds ratio (OR) with 95 % confidence interval (CI) for hypertension was 1.17 (1.15, 1.19) for every 1 kg/m2 increase in BMI. Furthermore, the OR (95 % CI) for hypertension in the highest BMI group (Obesity) was 4.14 (3.45, 4.96) after adjusting for covariates compared with the normal group. Multivariable adjusted RCS analysis showed a positive and linear dose–response relationship between BMI and hypertension risk both in male and female populations (all P for non-linearity > 0.05). Conclusion: Our study demonstrated a positive and linear dose–response relationship between BMI and the risk of hypertension. The results of this study provide evidence for BMI-related clinical interventions to reduce the risk of hypertension.

2-amino-1-methyl-6-phenylimidazole [4, 5-b] pyridine (PhIP) is a prevalent heterocyclic amine (HAA) found in heated processed meat. This study investigated the inhibitory impact of eight different types of polyphenols containing m-dihydroxyl structure on PhIP formation through a chemical model system. The structure-activity relationship and potential sites of action of polyphenols containing m-dihydroxyl structure were also analyzed. Then, the mechanism of inhibiting PhIP formation by kaempferol, naringenin and quercetin was speculated by UPLC-MS. Results showed that 8 kinds of polyphenols containing m-dihydroxyl structure had significant (P

Background: Fine particulate matter (PM2.5) exposure is an important environmental risk for maternal and children's health, with peak exposures especially those derived from primary combustion hypothesized to pose greater risk. Identifying PM2.5 peaks and their contributions to personal exposure remains challenging. This study measured personal PM2.5 exposure, characterized primary combustion peaks, and investigated their determinants during and after pregnancy and among Hispanic women in Los Angeles, CA. Methods: Continuous personal PM2.5 exposure, Global Positioning System geolocation, and ecological momentary assessment surveys were collected from 63 women for 4 consecutive days in their 1st trimester, 3rd trimester and 4–6 months postpartum. Based on the shape of PM2.5 time-series, primary combustion peaks were identified, characterized (number, duration, area under the curve [AUC]), and linked with locations they occurred in. Zero-inflated generalized mixed-effect models were used to examine the spatial and temporal determinants of PM2.5 peak exposures. Results: A total of 490 PM2.5 peaks were identified from 618 person-days of monitoring. Spending an additional minute at parks and open spaces was related to smaller (AUC decreased 3.1 %, 95 % CI: 1.5 %–4.6 %) and shorter (duration decreased 1.7 %, 0.5 %–2.9 %) PM2.5 peak exposure. An additional minute in vehicular trips also related to smaller and shorter peak exposure (AUC and duration decreased 2.5 %, 1.2 %–3.7 % and 1.8 %, 1.0 %–2.6 %, respectively). However, an additional minute at industrial locations was associated with greater number (3.6 %, 2.0 %–5.2 %), AUC (1.6 %, 0.1 %–3.2 %) and duration (1.0 %, 0.0 %–2.1 %) of personal PM2.5 peak exposure. Conclusions: This study demonstrates the potential to statistically identify exposure to primary combustion PM2.5 peaks and understand their determinants from personal monitoring data. Results suggest that visits to parks and open spaces may minimize PM2.5 peak exposures, while visiting industrial locations may increase them in and around pregnancy.

BackgroundAcute kidney injury (AKI) is a common adverse outcome following nephrectomy. The progression from AKI to acute kidney disease (AKD) and subsequently to chronic kidney disease (CKD) remains a concern; yet, the predictive mechanisms for these transitions are not fully understood. Interpretable machine learning (ML) models offer insights into how clinical features influence long-term renal function outcomes after nephrectomy, providing a more precise framework for identifying patients at risk and supporting improved clinical decision-making processes. ObjectiveThis study aimed to (1) evaluate postnephrectomy rates of AKI, AKD, and CKD, analyzing long-term renal outcomes along different trajectories; (2) interpret AKD and CKD models using Shapley Additive Explanations values and Local Interpretable Model-Agnostic Explanations algorithm; and (3) develop a web-based tool for estimating AKD or CKD risk after nephrectomy. MethodsWe conducted a retrospective cohort study involving patients who underwent nephrectomy between July 2012 and June 2019. Patient data were randomly split into training, validation, and test sets, maintaining a ratio of 76.5:8.5:15. Eight ML algorithms were used to construct predictive models for postoperative AKD and CKD. The performance of the best-performing models was assessed using various metrics. We used various Shapley Additive Explanations plots and Local Interpretable Model-Agnostic Explanations bar plots to interpret the model and generated directed acyclic graphs to explore the potential causal relationships between features. Additionally, we developed a web-based prediction tool using the top 10 features for AKD prediction and the top 5 features for CKD prediction. ResultsThe study cohort comprised 1559 patients. Incidence rates for AKI, AKD, and CKD were 21.7% (n=330), 15.3% (n=238), and 10.6% (n=165), respectively. Among the evaluated ML models, the Light Gradient-Boosting Machine (LightGBM) model demonstrated superior performance, with an area under the receiver operating characteristic curve of 0.97 for AKD prediction and 0.96 for CKD prediction. Performance metrics and plots highlighted the model’s competence in discrimination, calibration, and clinical applicability. Operative duration, hemoglobin, blood loss, urine protein, and hematocrit were identified as the top 5 features associated with predicted AKD. Baseline estimated glomerular filtration rate, pathology, trajectories of renal function, age, and total bilirubin were the top 5 features associated with predicted CKD. Additionally, we developed a web application using the LightGBM model to estimate AKD and CKD risks. ConclusionsAn interpretable ML model effectively elucidated its decision-making process in identifying patients at risk of AKD and CKD following nephrectomy by enumerating critical features. The web-based calculator, found on the LightGBM model, can assist in formulating more personalized and evidence-based clinical strategies.