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Prostate cancer (PCa) is a major health concern that necessitates appropriate diagnostic approaches for timely intervention. This review critically evaluates the role of liquid biopsy techniques, focusing on blood- and urine-based biomarkers, in overcoming the limitations of conventional diagnostic methods. The 4Kscore test and Prostate Health Index have demonstrated efficacy in distinguishing PCa from benign conditions. Urinary biomarker tests such as PCa antigen 3, MyProstateScore, SelectMDx, and ExoDx Prostate IntelliScore test have revolutionized risk stratification and minimized unnecessary biopsies. Emerging biomarkers, including non-coding RNAs, circulating tumor DNA, and prostate-specific antigen (PSA) glycosylation, offer valuable insights into PCa biology, enabling personalized treatment strategies. Advancements in non-invasive liquid biomarkers for PCa diagnosis may facilitate the stratification of patients and avoid unnecessary biopsies, particularly when PSA is in the gray area of 4 to 10 ng/mL.

Abstract Background Dysregulated energy metabolism has emerged as a defining hallmark of cancer, particularly evident in triple-negative breast cancer (TNBC). Distinct from other breast cancer subtypes, TNBC exhibits heightened glycolysis and aggressiveness. However, the transcriptional mechanisms of aerobic glycolysis in TNBC remains poorly understood. Methods The Cancer Genome Atlas (TCGA) cohort was utilized to identify genes associated with glycolysis. The role of FOSL1 in glycolysis and tumor growth in TNBC cells was confirmed through both loss-of-function and gain-of-function experiments. The subcutaneous xenograft model was established to evaluate the therapeutic potential of targeting FOSL1 in TNBC. Additionally, chromatin immunoprecipitation and luciferase reporter assays were employed to investigate the transcriptional regulation of glycolytic genes mediated by FOSL1. Results FOSL1 is identified as a pivotal glycolysis-related transcription factor in TNBC. Functional verification shows that FOSL1 enhances the glycolytic metabolism of TNBC cells, as evidenced by glucose uptake, lactate production, and extracellular acidification rates. Notably, FOSL1 promotes tumor growth in TNBC in a glycolysis-dependent manner, as inhibiting glycolysis with 2-Deoxy-D-glucose markedly diminishes the oncogenic effects of FOSL1 in TNBC. Mechanistically, FOSL1 transcriptionally activates the expression of genes such as SLC2A1, ENO1, and LDHA, which further accelerate the glycolytic flux. Moreover, FOSL1 is highly expressed in doxorubicin (DOX)-resistant TNBC cells and clinical samples from cases of progressive disease following neoadjuvant chemotherapy. Targeting FOSL1 proves effective in overcoming chemoresistance in DOX-resistant MDA-MB-231 cells. Conclusion In summary, FOSL1 establishes a robust link between aerobic glycolysis and carcinogenesis, positioning it as a promising therapeutic target, especially in the context of TNBC chemotherapy.

Abstract This paper proposes an optimal robust sizing model for distributed energy storage systems (DESSs) considering power quality management. The power conversion systems (PCSs) of DESSs with four‐quadrant operation characteristics can provide power quality management services to customers. To improve capacity utilization of the DESS, power quality management services are quantified and integrated into an optimal bi‐level sizing model, where the upper level addresses the sizing problem concerning battery and PCS capacities, while the lower level focuses on coordinating active/reactive power control of the DESS. A robust optimization approach for DESS scheduling is adopted to consider uncertainties of distributed photovoltaic (PV) power generation and power quality management requirements. The column and constraint generation (C&CG) algorithm is applied for efficient handling of this model. Ultimately, the effectiveness of the proposed approach is validated through comprehensive comparative analysis of four cases, resulting in a 12.44% increase in the net present value (NPV) over the entire lifecycle.

Abstract The efficacy of flipped classroom in ophthalmology education has not been well proved. This study aimed to investigate the efficacy of flipped classroom on diabetic retinopathy (DR) and glaucoma in ophthalmology education. Ninety-three medical students in Peking Union Medical College participated and were randomly assigned into two groups. Students in “Group A” participated in a flipped classroom on diabetic retinopathy (DR) and a regular course on glaucoma, while students in “Group B” had a flipped classroom on glaucoma and a regular one on DR. The primary outcome measure of this study was the exam score after class. The secondary outcome measure was the result of a post-classroom questionnaire. The final exam revealed numerically better scores for questions in the same section as flipped classroom that students joined with no statistical significance. The post-class questionnaire revealed an overall satisfaction rate of 93.48%. Most students thought the flipped classroom enhance personal abilities compared with the traditional lecture-based class. However, further amendments should also be made to improve defects such as students’ comprehension of basic knowledge and the overall degree of involvement of students. The concept of the flipped classroom could be applied to diabetic retinopathy and glaucoma with satisfactory results.

Abstract The debate about whether the capacity of working memory (WM) varies with the complexity of memory items continues. This study employed novel experimental materials to investigate the role of complexity in WM capacity. Across seven experiments, we explored the relationship between complexity and WM capacity. The results indicated that the complexity of memory items significantly affects WM capacity. However, given the non-linear relationship between complexity and WM capacity, we propose that WM may not allocate resources directly to each individual item. Instead, it might integrate these items to some extent before storage.

Abstract Residual antibiotics in chicken manure may interfere with the stability of anaerobic digestion (AD) and inhibit resource utilization efficiency. In this study, we aimed to enhance chicken manure bio-methanation in AD with high-concentration of sulfamethazine (SMZ) by adding metal (Fe, Co)-modified Enteromorpha-based hydrochar (Co-HC, Fe-HC). The results showed that Fe-HC and Co-HC increased the degree of acidogenesis by 1.25 times and 1.58 times, respectively. The maximum protein concentration in EPS was increased by 47.64% and 72.5% after adding Fe-HC and Co-HC. However, only Co-HC demonstrated notable improvements in both methane production and SMZ removal efficiency. Electrochemical analysis showed that Co-HC possessed a richer variety of oxygen and nitrogen functional groups, along with superior electron exchange capabilities compared to Fe-HC. Furthermore, microbiological assessments revealed that Co-HC enriched syntrophic bacteria (such as Syntrophomonas and Mesotoga), facilitating direct interspecies electron transfer (DIET) and subsequently enhancing biomethane production. The abundance of genes involved in electron transfer increased significantly with Co-HC, with a maximum increase of 75.86% in Co1.5-HC treatment. Additionally, the elimination of antibiotic resistance genes (sul1, sul2) increased by 65.66% in the Co1.5-HC treatment. This study offers a theoretical foundation and empirical support for the synergistic improvement of livestock and poultry manure containing high antibiotic concentrations, thereby helping to overcome challenges posed by recalcitrant substances. Graphical Abstract

Abstract Pest rodents persistently undermine crop yields and food security. Fertility control could be a viable alternative for managing rodent populations. This study investigates the antifertility effects of various concentrations of clarithromycin combined with 1.0 mg/kg quinestrol on male rodents to determine an effective contraceptive dose that minimizes quinestrol usage, addressing key concerns such as potential environmental residue, which may impact ecological balance, and poor palatability, which could reduce ingestion and limit the sterilant’s effectiveness. Male mice were divided into five groups and administered different doses of clarithromycin or clarithromycin and quinestrol for three consecutive days, while the control group received sunflower seed oil only. After seven days, organ weights, reproductive organ weights, sperm density, serum hormone levels, and CYP3A4 content in small intestinal and liver tissues were measured to assess persistent effects. Compared with the control group, all treatment groups had significant reductions in epididymal weight, seminal vesicle weight, and serum T and LH levels. Higher concentrations of clarithromycin (2 mg/kg and 10 mg/kg) significantly impacted reproductive metrics, including sperm density, organ weights, and serum LH and testosterone levels, though complete sterilization was not achieved, with more than 60 million cauda epididymal spermatozoa remaining. However, the combination demonstrated potential as an effective strategy for male fertility control. The combination of 2.0 mg/kg clarithromycin and quinestrol can mitigate organ enlargement seen with quinestrol alone. This combination also decreased total enzyme content, thereby diminishing quinestrol’s induction of CYP3A4, which may increase the sterilization effectiveness of the treatment.

Abstract Background Abnormal sensory perception, particularly pain insensitivity (PAI), is a typical symptom of autism spectrum disorder (ASD). Despite the role of myelin metabolism in the regulation of pain perception, the mechanisms underlying ASD-related PAI remain unclear. Methods The pain-associated gene sphingosine-1-phosphate receptor 1 (S1PR1) was identified in ASD samples through bioinformatics analysis. Its expression in the dorsal root ganglion (DRG) tissues of BTBR ASD model mice was validated using RNA-seq, western blot, RT-qPCR, and immunofluorescence. Pain thresholds were assessed using the von Frey and Hargreaves tests. Patch-clamp techniques measured KCNQ/M channel activity and neuronal action potentials. The expression of S1PR1, KCNQ/M, mitogen-activated protein kinase (MAPK), and cyclic AMP/protein kinase A (cAMP/PKA) signaling proteins was analyzed before and after inhibiting the S1P-S1PR1-KCNQ/M pathway via western blot and RT-qPCR. Results Through integrated transcriptomic analysis of ASD samples, we identified the upregulated gene S1PR1, which is associated with sphingolipid metabolism and linked to pain perception, and confirmed its role in the BTBR mouse model of ASD. This mechanism involves the regulation of KCNQ/M channels in DRG neurons. The enhanced activity of KCNQ/M channels and the decreased action potentials in small and medium DRG neurons were correlated with PAI in a BTBR mouse model of ASD. Inhibition of the S1P/S1PR1 pathway rescued baseline insensitivity to pain by suppressing KCNQ/M channels in DRG neurons, mediated through the MAPK and cAMP/PKA pathways. Investigating the modulation and underlying mechanisms of the non-opioid pathway involving S1PR1 will provide new insights into clinical targeted interventions for PAI in ASD. Conclusions S1PR1 may contribute to PAI in the PNS in ASD. The mechanism involves KCNQ/M channels and the MAPK and cAMP/PKA signaling pathways. Targeting S1PR1 in the PNS could offer novel therapeutic strategies for the intervention of pain dysesthesias in individuals with ASD.

Green synthesis of gold nanoparticles (AuNPs) using Ginkgo biloba leaf aqueous extract was optimized by response surface methodology to yield monodispersed, crystalline nanoparticles of 18 ± 4 nm diameter. Fourier transform infrared spectroscopy confirmed capping by flavonoids, terpenoids and polyphenols providing stability for over 6 months. The biosynthesized AuNPs exhibited promising in vitro dose and time-dependent antiproliferative effects against human nasopharyngeal carcinoma CNE1 cells with IC50 reducing from 65.7 to 39.2 μg/mL over 24–72 hrs. Distinct cytoplasmic damage was observed under microscope. Treatment with 50 μg/mL AuNPs for 48 hrs dramatically upregulated pro-apoptotic Bax, Caspase-3 and p53 by 8.7, 6.5 and 4.3 fold respectively while downregulating anti-apoptotic Bcl-2 by 11.2 fold, indicating apoptosis induction via mitochondrial intrinsic pathway. The green fabricated G. biloba AuNPs displayed preferential toxicity towards carcinoma cells compared to normal fibroblasts, indicating potential for targeted nasopharyngeal cancer therapy.

Abstract Keratoconus (KC) is an irreversible blinding eye disease; therefore, early screening of KC suspects (KCS) is crucial for protecting patients’ quality of life. Scheimpflug imaging is a commonly used screening device in clinical practice. We aimed to evaluate the diagnostic ability of a Scheimpflug imaging device (Scansys) for KC and KCS and compared it with other Scheimpflug-based devices (Pentacam and Corvis ST). This prospective case-control study included 107 normal eyes, 72 KCS, and 57 KC. Scansys screening index Keratoconus probability (KCP) showed excellent performance in diagnosing KC at a cutoff value of 16.4 (area under the receiver operating characteristic [AUROC] = 1.000), with 100% sensitivity and 98.11% specificity. KCP had a better KCS diagnostic ability at a cutoff value of 8.9 (AUROC = 0.813) than Corvis biomechanical index (CBI, AUROC = 0.764), reaching 67.61% sensitivity and 85.85% specificity. Pentacam screening index Belin/Ambrósio enhanced ectasia display deviation (BAD-D) showed the best performance with 92.96% sensitivity and 89.62% specificity at a cutoff value of 1.525 (AUROC = 0.970) in diagnosing KCS. Scansys provides accurate KCP parameters in diagnosing KC; however, the efficiency of diagnosing KCS should be further optimized.

Abstract Background Polycystic ovary syndrome (PCOS) is a unity of endocrine and metabolic disorders, associated with PI3K/AKT/mTOR, autophagy, and gut microbiota. Quinoa is a valuable food source, which contains rich minerals, unsaturated fatty acids, and has a positive modulating effect on metabolic diseases. However, its effects and potential mechanisms on PCOS have not been reported yet. Therefore, the purpose of this study is to investigate the effect of quinoa on PCOS rats by regulating PI3K/AKT/mTOR, autophagy, and gut microbiota. Methods Ten–week-old female Sprague-Dawley (SD) rats have received letrozole for 24 days for induction of PCOS and subsequently were treated with a quinoa diet for 8 weeks. Vaginal smears were used to analyze the estrous cycle of rats. Hormone and biochemical indexes were analyzed by kit assays and glucometer. The pathological changes of ovary, pancreas, duodenum and colon were observed by HE staining. PI3K, AKT, mTOR and autophagy-related proteins in the ovary and colon were measured by western blot and immunohistochemistry staining. Tight junction proteins in colon were measured by immunohistochemistry staining. 16 s rDNA sequencing was used to detect the changes of intestinal microbiota in rats. Network pharmacology and molecular docking were used to study the possible targets and mechanisms of quinoa on PCOS. Spearman correlation analysis was used to study the relationship between intestinal microbial abundance and hormone levels of PCOS rats at the phylum and genus level. Results Quinoa significantly improved estrous cycle and biochemical parameters of PCOS-like rats, and the pathological state of ovary, pancreas, duodenum and colon tissues. Especially, quinoa significantly regulated the expression of PI3K, AKT, mTOR and autophagy-related proteins in the ovary. Quinoa may repair the intestinal barrier by upregulating the expression of tight junction proteins in the colon, and regulate autophagy-related factors in colon. Additionally, quinoa increased the abundance of Lactobacillu, Bacteroides and Oscillospira, and decreased the Firmicutes/Bacteroidetes ratio and the Blautia, and Prevotella, reversing the dysregulation of the gut microbiota. Correlation analysis showed that there is a strong correlation between gut microbiota with significant changes in abundance and hormone related to PCOS. Conclusion Our result indicated that effect of quinoa on PCOS maybe associated with activation of the PI3K/AKT/mTOR signaling pathway, inhibition of autophagy, and regulation of intestinal flora.

Abstract Objective Several antiseizure medications (ASMs) have been approved for the treatment of focal epilepsy. However, there is a paucity of evidence on direct comparison of ASMs. We evaluated the comparative efficacy and safety of all approved add‐on ASMs for the treatment of focal epilepsy using network meta‐analysis. Methods Data through extensive literature search was retrieved from PubMed, Embase, Cochrane, and ClinicalTrial.gov databases using predefined search terms from inception through March 2023. PRISMA reporting guidelines (CRD42023403450) were followed in this study. Efficacy outcomes assessed were ≥50%, ≥75%, and 100% responder rates. Patient retention rate and safety outcomes such as overall treatment‐emergent adverse events (TEAEs) and individual TEAEs were assessed. “Gemtc” 4.0.4 package was used to perform Bayesian analysis. Outcomes are reported as relative risks (RRs) and 95% confidence interval (CI). Results Literature search retrieved 5807 studies of which, 75 studies were included in the analysis. All ASMs showed significantly higher ≥50% responder rate compared with placebo. Except the ≥75% seizure frequency reduction for zonisamide (2.23; 95% CI: 1.00–5.70) and 100% for rufinamide (2.03; 95% CI: 0.54–11.00), all other interventions showed significantly higher ≥75% and 100% responder rates compared with placebo. Among treatments, significantly higher 100% responder rate was observed with cenobamate compared to eslicarbazepine (10.71; 95% CI: 1.56–323.9) and zonisamide (10.63; 95% CI: 1.37–261.2). All ASMs showed a lower patient retention rate compared to placebo, with the least significant value observed for oxcarbazepine (0.77; 95% CI: 0.7–0.84). Levetiracetam showed a lower risk of incidence (1.0; 95%CI: 0.94–1.1; SUCRA: 0.885067) for overall TEAE compared with other medications. Significance All approved ASMs were effective as add‐on treatment for focal epilepsy. Of the ASMs included, cenobamate had the greatest likelihood of allowing patients to attain seizure freedom. Plain Language Summary This article compares the efficacy and safety of antiseizure medications (ASMs) currently available to neurologists in the treatment of epileptic patients. Several newer generation ASMs that have been developed may be as effective or better than the older medications. We included 75 studies in the analysis. In comparison, all drugs improved ≥50%, ≥75% and 100% responder rates compared to control, except for Zonisamide and Rufinamide in the ≥75% and 100% responder rate categories. Retention of patients undergoing treatment was lower in drugs than placebo. All drugs were tolerated, the levetiracetam showed the best tolerability. Cenobamate more likely help completely to reduce seizures.

As e-commerce continues to expand, understanding the factors that drive consumer traffic to business-to-consumer (B2C) websites is crucial. This study investigates the interplay between website technological sophistication, brand recognition, and business model innovation in influencing website traffic among Korean B2C companies. Drawing on data from 9003 companies across seven key sectors—finance, retail, healthcare, technology, food, education, and media—we employ Ordinary Least Squares (OLS) regression analysis to test our hypotheses. Our findings reveal that website technological sophistication is positively associated with monthly website visits. This relationship is particularly pronounced for companies with innovative business models, highlighting the synergistic effect of advanced website features and novel business strategies in attracting consumers. Conversely, the positive impact of website technological sophistication on traffic is less significant for well-established brands with high recognition levels, indicating that strong brand equity can mitigate the need for highly sophisticated websites. These results align with the Technology Acceptance Model (TAM), Innovation Diffusion Theory (IDT), and Signaling Theory (ST), providing a nuanced understanding of how technology, branding, and innovation intersect to drive online consumer behavior. Our study offers valuable insights for e-commerce firms seeking to optimize their digital presence and underscores the importance of investing in advanced website functionalities, particularly for lesser-known brands and companies with innovative business models. Future research should explore these dynamics in different cultural and industry contexts to enhance the generalizability of our findings.

The degradation of grasslands on the Qinghai–Tibet Plateau has severely impacted the region’s ecology and productivity, subsequently affecting the dietary niche of the region’s herbivores. Currently, little is known about the dietary strategies of plateau pikas (Ochotona curzoniae), an important species in the Qinghai–Tibet Plateau ecosystem, or freely grazing yaks (Bos grunniens) in response to grassland degradation. Fecal samples from plateau pikas and yaks were collected from degraded grasslands in the southwestern part of the plateau. The feeding habits and interactions between plateau pikas and yaks were investigated using chloroplast trnL-P6 amplification and sequencing technology to determine how these have changed given different levels of grassland degradation. The results indicated that alterations in food resources due to grassland degradation led to significant differences in the proportions of shared food types consumed by yaks and pikas; hence, these species adjusted their dietary breadths to mitigate the adverse effects of grassland degradation. As grassland degradation intensified, the proportion of shared food types between yaks and plateau pikas increased, suggesting that grassland degradation may increase dietary competition between these two species.

Re-emerging human adenovirus type 55 (HAdV55) has become a significant threat to public health due to its widespread circulation and the association with severe pneumonia, but an effective anti-HAdV55 agent remains unavailable. Herein, we report the generation of macaque-derived, human-like monoclonal antibodies (mAbs) protecting against HAdV55 infection with high potency. Using fluorophore-labelled HAdV55 virions as probes, we isolated specific memory B cells from rhesus macaques (Macaca mulatta) that were immunized twice with an experimental vaccine based on E1-, E3-deleted, replication-incompetent HAdV55. We cloned a total of 19 neutralizing mAbs, nine of which showed half-maximal inhibitory concentrations below 1.0 ng/ml. These mAbs recognized the hyper-variable-region (HVR) 1, 2, or 7 of viral hexon protein, or the fibre knob. In transgenic mice expressing human desmoglein-2, the major cellular receptor for HAdV55, a single intraperitoneal injection with hexon-targeting mAbs efficiently prevented HAdV55 infection, and mAb 29C12 showed protection at a dose as low as 0.004 mg/kg. Fibre-targeting mAb 28E8, however, showed protection only at a dose up to 12.5 mg/kg. In tree shrews that are permissive for HAdV55 infection and disease, mAb 29C12 effectively prevented HAdV55-caused pneumonia. Further analysis revealed that fibre-targeting mAbs blocked the attachment of HAdV55 to host cells, whereas hexon-targeting mAbs, regardless of their targeting HVRs, mainly functioned at post-attachment stage via inhibiting viral endosomal escape. Our results indicate that hexon-targeting mAbs have great anti-HAdV55 activities and warrant pre-clinical and clinical evaluation.

Objective: To investigate the source of infection in a patient with recurrent severe neck infections caused by Klebsiella pneumoniae and to analyze the virulence of isolates obtained from different sites of the patient. Methods: We collected preoperative neck abscess puncture fluid, intraoperative neck drainage fluid, sputum, intestinal fecal specimens, and blood samples from a patient who visited Wuxi Second People's Hospital twice between 2017 and 2018. We conducted isolation, identification, drug sensitivity tests, and string tests on the isolates. Capsule serotyping and virulence gene analysis were performed using PCR. The genetic relationship of different isolates was assessed by Multilocus Sequence Typing and virulence was evaluated using the Galleria mellonella infection model. Additionally, whole-genome sequencing was used to analyze the chromosomal and plasmid genes of one isolate. Results: Klebsiella pneumoniae was detected in the sputum and fecal specimens from both hospitalizations, as well as the preoperative ultrasound-guided puncture fluid and intraoperative drainage fluid from the first hospitalization, resulting in six isolates. These isolates were all K16 serotype, positive in the string test, and identified as ST660 by Multilocus Sequence Typing, indicating they belonged to the same clone. Virulence gene analysis showed that wcaG, iucB, iroNB, rmpA, rmpA2, Aer, kfuBC, ureA, fimH, mrkD, uge, and peg344 were positive, while allS, cf29a, and Wzy_K1 were negative. In the Galleria mellonella virulence assay, the lethality of different isolates was dose-dependent. The K16 group showed significantly higher larval mortality compared to other control groups (including K1, K2, K5, K20, and K57 groups). Genome sequencing revealed that plasmid p17388 carried numerous virulence genes and insertion sequences, particularly ISKPN74, and showed high homology with other Klebsiella plasmids. Conclusion: This study is the first to report severe cervical necrotizing fasciitis caused by the K16-ST660 Klebsiella pneumoniae Isolate. The high virulence of these isolates was confirmed by the Galleria mellonella virulence assay and the detection of numerous virulence genes. In-depth analysis of plasmid p17388 suggests that ISKPN74 may enhance stable integration of the plasmid into the bacterial chromosome through recombinases and transposases, thereby reducing the likelihood of plasmid loss and increasing bacterial virulence. Additionally, IS5 family insertion sequences may carry extra promoters or enhancers that, when inserted upstream of mucoviscosity-associated genes such as rmpA, may increase the transcription levels of downstream genes. This ISKPN74-mediated integration or insertion reveals a complex genetic mechanism that may contribute to the severity of infections caused by ST660 isolates. Our findings offer new insights into the virulence and structure of ST660-K16 Klebsiella pneumoniae, suggesting that further investigation into the specific mechanisms by which these insertion sequences enhance virulence could aid in developing novel infection management strategies.

IntroductionKaryotyping and chromosome microarray analysis (CMA) are the two main prenatal diagnostic techniques currently used for genetic testing. We aimed to evaluate the value of chromosomal karyotyping and CMA for different prenatal indications.MethodsA total of 2084 amniocentesis samples from pregnant women who underwent prenatal diagnosis from 16 to 22 + 6 weeks of gestation between January 2021 and December 2022 were retrospectively collected. The pregnant women were classified according to different prenatal diagnostic indications and underwent CMA and karyotype analysis. Clinical data were collected, and the results of the CMA and karyotype analysis were statistically analyzed to compare the effects of the two diagnostic techniques.ResultsThe total detection rate of abnormal chromosomes was significantly higher using CMA than karyotype analysis. The detection rate of abnormal chromosomes using CMA was significantly higher than that using karyotyping for ultrasound abnormalities, high-risk serologic screening, adverse pregnancy history, positive noninvasive prenatal test (NIPT) screening, and ultrasound abnormalities combined with adverse pregnancy history indications. Among the fetuses with inconsistent results between the two testing methods, 144 had an abnormal CMA but a normal karyotype, with the highest percentage of pregnant women with ultrasound abnormalities at 38.89% (56/144). CMA had the highest detection rate for structural abnormalities combined with soft-index abnormalities among all ultrasound abnormalities. The highest detection rate of copy number variants in the group of structural abnormalities in a single system was in the genitourinary system (3/29, 10.34%).ConclusionCMA can improve the detection rate of chromosomal abnormalities in patients with ultrasound abnormalities, high-risk serologic screening, adverse maternal history, positive NIPT screening, and ultrasound abnormalities combined with adverse maternal history and can increase the detection rate of chromosomal abnormalities in karyotypic normality by 6.91% (144/2,084), this result is higher than similar studies. However, karyotype analysis remains advantageous over CMA regarding balanced chromosomal rearrangement and detection of low-level chimeras, and the combination of the two methods is more helpful in improving the detection rate of prenatal chromosomal abnormalities.

Abstract Bone-modifying agents (BMA) are extensively used in treating patients with prostate cancer with bone metastases. However, this increases the risk of medication-related osteonecrosis of the jaw (MRONJ). The safety of long-term BMA administration in clinical practice remains unclear. We aimed to determine the cumulative incidence and risk factors of MRONJ. One hundred and seventy-nine patients with prostate cancer with bone metastases treated with BMA at our institution since 2008 were included in this study. Twenty-seven patients (15%) had MRONJ during the follow-up period (median, 19 months; interquartile range, 9–43 months). The 2-year, 5-year, and 10-year cumulative MRONJ incidence rates were 18%, 27%, and 61%, respectively. Multivariate analysis identified denosumab use as a risk factor for MRONJ, compared with zoledronic acid use (HR 4.64, 95% CI 1.93–11.1). Additionally, BMA use at longer than one-month intervals was associated with a lower risk of MRONJ (HR 0.08, 95% CI 0.01–0.64). Furthermore, six or more bone metastases (HR 3.65, 95% CI 1.13–11.7) and diabetes mellitus (HR 5.07, 95% CI 1.68–15.2) were risk factors for stage 2 or more severe MRONJ. MRONJ should be considered during long-term BMA administration in prostate cancer patients with bone metastases.

Abstract Background Migratory birds exhibit heterogeneity in foraging strategies during wintering to cope with environmental and migratory pressures, and gut bacteria respond to changes in host diet. However, less is known about the dynamics of diet and gut fungi during the wintering period in black-necked cranes (Grus nigricollis). Results In this work, we performed amplicon sequencing of the trnL-P6 loop and ITS1 regions to characterize the dietary composition and gut fungal composition of black-necked cranes during wintering. Results indicated that during the wintering period, the plant-based diet of black-necked cranes mainly consisted of families Poaceae, Solanaceae, and Polygonaceae. Among them, the abundance of Solanaceae, Polygonaceae, Fabaceae, and Caryophyllaceae was significantly higher in the late wintering period, which also led to a more even consumption of various food types by black-necked cranes during this period. The diversity of gut fungal communities and the abundance of core fungi were more conserved during the wintering period, primarily dominated by Ascomycota and Basidiomycota. LEfSe analysis (P 2) found that Pyxidiophora, Pseudopeziza, Sporormiella, Geotrichum, and Papiliotrema were significantly enriched in early winter, Ramularia and Dendryphion were significantly enriched in mid-winter, Barnettozyma was significantly abundant in late winter, and Pleuroascus was significantly abundant in late winter. Finally, mantel test revealed a significant correlation between winter diet and gut fungal. Conclusions This study revealed the dynamic changes in the food composition and gut fungal community of black-necked cranes during wintering in Dashanbao. In the late wintering period, their response to environmental and migratory pressures was to broaden their diet, increase the intake of non-preferred foods, and promote a more balanced consumption ratio of various foods. Balanced food composition played an important role in stabilizing the structure of the gut fungal community. While gut fungal effectively enhanced the host’s food utilization rate, they may also faced potential risks of introducing pathogenic fungi. Additionally, we recongnized the limitations of fecal testing in studying the composition of animal gut fungal, as it cannot effectively distinguished between fungal taxa from food or soil inadvertently ingested and intestines. Future research on functions such as cultivation and metagenomics may further elucidate the role of fungi in the gut ecosystem.

Abstract Antennas that can operate across multiple communication standards have remained a challenge. To address these limitations, we propose a Field-Programmable Radio Frequency Surface (FPRFS), which is based on manipulating current flow on its surface to achieve desirable RF characteristics. In this work, we demonstrate that substantial enhancements in radiation efficiency can be achieved while preserving the high reconfigurability of antenna structures implemented on the FPRFS. This is accomplished by utilizing an asymmetric excitation, directing the excitation to the low-loss contiguous surface, and dynamically manipulating the imaged return current on a segmented ground plane by switches. This important insight allows for adaptable antenna performance that weakly depends on the number of RF switches or their loss. We experimentally validate that FPRFS antennas can achieve efficiencies comparable to traditionally implemented antenna counterparts. This permits the FPRFS to be effectively utilized as a productive antenna and impedance-matching network with real-time reconfigurability.

High concentrations of harmful metal(loid)s and extreme acidity are persistent environmental concerns in acidic pit lakes. In this study, we examine Cueva de la Mora (CM), a meromictic pit lake in the Iberian Pyrite Belt, Spain, as a model system. Our research aims to explore potential bioremediation strategies to mitigate the impacts of metal(loid)s and acidity in such environments. The major strategy applied in this research is to biologically stimulate sulfate reduction (i.e., biosulfidogenesis) in the deep layer of the lake to promote the formation of low-solubility sulfide minerals. Previous omics-based studies of CM have shown that several sulfate-reducing bacteria (SRB) taxa are present in the deep layer. However, their activities are likely limited by the availability of electron donors for sulfide production. Therefore, different amendments (glycerol, elemental sulfur, and glycerol + elemental sulfur) were tested to promote sulfide production and enrich acid-tolerant sulfide-producing microbes. Our results showed that glycerol stimulated dissimilatory sulfate reduction much faster than elemental sulfur alone, suggesting that electron donor limitations control sulfide production. Furthermore, the combined addition of glycerol and elemental sulfur (S(0)) resulted in the highest level of sulfide production. This indicates that S(0) can play a significant role as an electron acceptor in further promoting sulfide production when a suitable electron donor is present. Microbial community analysis revealed that Desulfosporosinus acididurans, a previously discovered acid-tolerant SRB, was enriched and became the dominant species in incubations with glycerol only (~76–96% abundance) or the combination of glycerol and S(0) (~93–99% abundance).

The excessive application and loss of pesticides poses a great risk to the ecosystem, and the environmental safety assessment of pesticides is time-consuming and expensive using traditional animal toxicity tests. In this work, a pesticide acute toxicity dataset was created for silkworm integrating extensive experiments and various common pesticide formulations considering the sensitivity of silkworm to adverse environment, its economic value in China, and a gap in machine learning (ML) research on the toxicity prediction of this species, which addressed the previous limitation of only being able to predict toxicity classification without specific toxicity values. A new comprehensive voting model (CVR) was developed based on ML, combined with three regression algorithms, namely, Bayesian Ridge (BR), K Neighbors Regressor (KNN), Random Forest Regressor (RF) to accurately calculate lethal concentration 50 % (LC50). Three conformal models were successfully constructed, marking the first combination of conformal models with confidence intervals to predict silkworm toxicity. Further, the mechanism by analyzing structural alerts was summarized, and identified 25 warning structures, 24 positive compounds and 14 negative compounds. Importantly, a novel comprehensive prediction system was constructed that can provide LC50 and confidence intervals, structural alerts analysis, lipid-water partition coefficient (LogP) and similarity analysis, which can comprehensively evaluate the ecological toxicity risk of substances to make up for the incomplete toxicity data of new pesticides. The validity and generalization of the CVR model were verified by an external validation set. In addition, five new, low-toxic and green pesticide alternatives were designed through 50,000 cycles. Moreover, our software and ST Profiler can provide low-cost information access to accelerate environmental risk assessment, which can predict not only a single chemical, but also batches of chemicals, simply by inputting the SMILES / CAS / (Chinese / English) name of chemicals.

The developmental toxicity and human health risks of triazole fungicides (TFs) have attracted worldwide attention due to the ability to enter the human body in a variety of ways. Nevertheless, the specific mechanism by which TFs exert remains incompletely understood. Given that retinoic acid (RA) signaling pathway are closely related to development, this study aimed to screen and identify developmentally disabled chemicals in commonly used TFs and to reveal the potential effects of TFs on developmental retardation through the RA signaling pathway in mouse embryonic stem cells (mESCs). Specifically, six typical TFs (myclobutanil, tebuconazole, hexaconazole, propiconazole, difenoconazole, and flusilazole) were exposed through the construction of an embryoid bodies (EBs)-based in vitro global differentiation models. Our results clarified that various TFs disturbed lineage commitment during early embryonic development. Crucially, the activation of RA signaling pathway, which alters the expression of key genes and interferes the transport and metabolism of retinol, may be responsible for this effect. Furthermore, molecular docking, molecular dynamics simulations, and experiments using a retinoic acid receptor α inhibitor provide evidence supporting the potential modulatory role of the retinoic acid signaling pathway in developmental injury. The current study offers new insights into the TFs involved in the RA signaling pathway that interfere with the differentiation process of mESCs, which is crucial for understanding the impact of TFs on pregnancy and early development.

Semantic segmentation of high-resolution multispectral remote sensing image has been intensely studied. However, the shadow occlusions, or the similar color and textures, between the categories influence the segmentation accuracy. Concomitantly, the size of targets in the remote sensing images is diverse and the network cannot balance their segmentation. This paper introduces a network, Transformer-based Multi-modal Fusion Network (TMFNet), which fuses the multi-modal features and incorporates height features from the digital surface model (DSM) to supplement the extra different features between each category. Particularly, we introduce two parallel encoders to extract the features from different modalities, a Multi-Modal fusion model based on the Transformer (MMformer) to complete the multi-modal fusion, and a Border Region Attention based multi-level Fusion Module (BRAFM) to integrate the cross-level features and enhance the small target segmentation by utilizing the details around the border. The experiment results on the ISPRS Vaihingen and Potsdam benchmark datasets indicate that the proposed TMFNet outperforms the SOTA methods on the segmentation performance.

The global economy is accelerating its transformation from an industrial economy to a digital economy, and the digital transformation of the manufacturing industry has become an important trend worldwide. Based on China’s provincial panel data from 2004 to 2020, this study uses a dynamic panel model to investigate the role of digitization in the transformation and upgrading of the manufacturing industry. The empirical results show that digitalization has significantly improved the green total factor productivity (GTFP) of the manufacturing industry, while it has significantly inhibited investment in fixed assets. The analysis of regional heterogeneity shows that in areas with scarce labor, abundant human capital, and areas with high innovation investment, digitalization has a larger effect on promoting productivity and inhibiting the expansion of investment scale. In the regions with more outward foreign direct investment, the effect of digitalization on improving productivity is insignificant, and the effect on inhibiting the expansion of investment scale is larger, implying that there is a risk of industrial hollowing out. Further analysis finds that digitalization improves the GTFP of regional manufacturing through mechanisms such as enhancing innovation capabilities, promoting industrial upgrading, and improving investment efficiency, and reduces manufacturing fixed asset investment through channels such as human capital upgrades and rising labor costs.

Nevoid basal cell carcinoma syndrome is a rare autosomal dominant disorder characterized by a diverse clinical presentation, which includes developmental abnormalities and tumorigenesis that can impact multiple organ systems. Basal cell carcinoma is the most common and characteristic clinical presentation in patients with NBCCS. There are three identified causative genes for this disease, the PTCH1 gene located at 9q22-31, the PTCH2 gene at 1p32-34, and the SUFU gene at 10q24.32. In this paper, we report a case of multiple nevoid basal cell carcinoma. The mutated gene in this patient was determined to be the ELP1 gene located on chromosome 9. This patient’s ELP1 gene mutation may contribute to the development of multiple nevoid basal cell carcinomas on the face.

PurposeAgainst the background of population aging challenges in China, focusing on health, security, and social participation as core elements of positive aging, this study aims to formulate strategies for promoting the health of the older adults and reveal the pathways and trends of social participation in promoting health.MethodThe study analyzed 1,015 randomly selected older adults individuals living at home in Beijing using household survey questionnaires. Drawing on group dynamics theory and structural equation modeling, the study proposed hypotheses regarding the relationships between social participation, group cohesion, and health status.ResultsFirst, the triangular path model of social participation, group cohesion, and health status among the older adults was established. The direct path coefficient of social participation on health status was 0.15, that of social participation on group cohesion was 0.56, and that of group cohesion on health status was 0.32. The indirect path coefficient of social participation on health status through group cohesion was calculated at 0.56 × 0.32 = 0.18. Second, of the older adults age groups—younger, middle, and older—social participation’s direct path effects on health status were present only in the older age group. Social participation’s indirect path effects on health status through group cohesion were relatively high in all three groups, with a slight increase in the older age group.ConclusionFirst, just the older adults participation in social activities serves as a benign stimulus to physical and mental health. Additionally, group cohesion formed through interaction with others during social activities encourages self-improvement behaviors, indirectly promoting health. In fact, indirect pathways of health promotion through group cohesion are stronger than direct pathways, highlighting the importance of group cohesion during social participation. Second, participation in activities alone can provide only sufficient benign stimuli for the older adults aged 80 and above, with the direct path effect of social participation on health beginning to appear only with increasing age. With age, selectivity of interaction with others decreases, and dependence increases; social participation’s indirect path effect on health through group cohesion continues to grow slightly.

The application of high-density and high-performance micro thermoelectric devices is still in its infancy, mainly restricted by the low performance of Bi2Te3-based thick film as well as the limited device integration. In this study, we proposed a dynamic regulation strategy to simultaneously strengthen the thermoelectric and mechanical properties for n-type Bi2Te3-based thick films. The effects of growth temperature and time on thermoelectric properties have been firstly explored. As the thermoelectric properties exhibit consistent degradation with increasing thickness at static growth temperature, an effective rising temperature method is introduced to dynamically regulate the nucleation rate and growing diffusion ability. Thus, the grain refinement with compact texture structure leads to a relatively large carrier mobility (77.1 cm2·V−1·s−1) and appropriate concentration (5.25 × 1019 cm−3) as well as further 12% improvement of power factor with an average value up to 12.0 μW·cm−1·K−2 over a wide temperature ranging from 313 K to 453 K. Furthermore, significant enhancement of mechanical property is also achieved with high elastic modules (56.03 GPa), hardness (0.63 GPa) and large energy dissipation capacity to prevent micro-cracks. This study provides a practical solution with dynamic temperature control to fabricate high-performance Bi2Te3 thick films with enhanced mechanical property and processing feasibility for micro thermoelectric devices.

The effects of lactic acid bacteria fermentation and in vitro simulated digestion on phenolic bioavailability, phenolic bioavailability, and antioxidant activity of purple sweet potato juice (PSPJ) were investigated. The PSPJ was fermented by Lactobacillus rhamnosus and Streptococcus thermophilus. The viable bacterial count, phenolic components, antioxidant activity, phenolic bioaccessibility, and phenolic bioavailability of PSPJ were analyzed during the simulated digestion process in vitro. The data displayed that lactic acid bacteria fermentation increased total α-glucosidase inhibition, total flavonoid content, and ratephenolic content. The antioxidant activities were improved after in vitro simulated digestion due to the biotransformation of phenolic substances by lactic acid bacteria fermentation. The bioaccessibility and bioavailability of phenols in PSPJ were improved with fermentation of lactic acid bacteria. Furthermore, the viable bacteria count of the two strains was significantly improved (>7 log CFU/mL) after simulated digestion in vitro.

Background: Restless legs syndrome (RLS) is a common sensorimotor sleep disorder that affects sleep quality of life. Much effort has been made to make progress in RLS pharmacotherapy; however, patients with RLS still report poor long-term symptom control. Methods: Comprehensive Mendelian randomization (MR) was performed to search for potential causal genes and drug targets using the cis-pQTL and RLS GWAS data. Robustness was validated using the summary-based Mendelian randomization (SMR) method and co-localization analysis. Further evidence of pleiotropy of the target genes and their potential side effects was provided by phenome-wide MR analysis (MR-PheWAS). Finally, molecular docking simulations were conducted on drug candidates corresponding to these targets, which revealed promising binding affinities and interaction patterns and underscored the druggable potential of the target gene. All of the analyses above were conducted in the context of Homo sapiens. Results: MAN1A2 showed a statistically significant result in the MR analysis, which was validated through SMR and co-localization analysis. The MR-PheWAS showed a low probability of pleiotropy and prospective side effects. Molecular docking was used to visualize the binding structure and fine affinity for MAN1A2 and the drugs predicted by DSigDB. Conclusions: Our study provides comprehensive evidence supporting MAN1A2 as a promising causal gene and therapeutic target for RLS, offering insights into the underlying molecular mechanisms and paving the way for future drug development efforts.

Objectives: This study explores whether sex differences in reactive aggression (RA) and proactive aggression (PA) are attributable to sex, gender role orientation, or their interaction and explores the neuroanatomical characteristics of these sex differences. Methods: In a sample of 108 males and 126 females, we examined the sex-by-gender role orientation interaction on RA, PA, and brain gray matter volume (GMV). Then, we explored the relationship between aggression and regional GMV. Results: When the effects of sex and gender role orientation on aggression were disentangled, there were no sex differences in RA, regardless of gender role orientation. However, sex differences (male > female) in PA were observed within the masculine group but not within the feminine group. Brain imaging results revealed sex differences (male > female) on the right inferior frontal gyrus GMV, a region involved in cognitive control, within the masculine group. Moreover, a negative association between PA and the right inferior frontal gyrus GMV was observed in masculine females rather than masculine males. Conclusions: These findings indicate that gender role orientation has a more significant effect on aggression than sex, particularly with regard to PA, and hint that the goal of cognitive control involved in displaying PA differs in masculine males and masculine females.

Background/Objectives: Chronic Limb-Threatening Ischemia (CLTI) is a chronic limb ischemic disease caused by vascular lesions, characterized by pain, ulcers, and gangrene, which can be life-threatening in severe cases. The objective of this study is to explore whether Berbamine (BBM) can protect against and repair ischemic muscle tissue in the lower limbs; Methods: Using a mouse hindlimb ischemia (HLI) model, 36 C57BL6 mice were divided into sham, HLI, and HLI+BBM treatment groups. Results: Our findings indicate that BBM can restore motor function and muscle tissue pathology in mice, potentially by inhibiting the nuclear translocation of nuclear factor kappa-B (NF-κB), thereby alleviating tissue inflammation caused by chronic ischemia, reducing muscle cell apoptosis, inhibiting M1 macrophage polarization, and promoting angiogenesis. Conclusions: Our research suggests that BBM has the potential to protect against ischemic damage in lower limb muscle tissue, providing a new approach to the treatment of CLTI.

This study investigates whether ketoconazole, a CYP3A4 inhibitor, can enhance the suppressive effects of quinestrol on reproductive capacity, potentially allowing for a reduced quinestrol dosage while maintaining its efficacy. A total of 104 healthy adult male mice were divided into two groups, assessed at 10 and 30 days. Within each group, six treatment categories were tested: the control (CK), quinestrol alone (Q1, Q5), and quinestrol combined with varying doses of ketoconazole (Q1 + K0.4, Q1 + K2, Q5 + K0.4). The key parameters measured included internal and reproductive organ weights, sperm density, sperm motility, sperm abnormalities, and CYP3A4 enzyme content in intestinal and liver tissues. After 10 days, the combination of a low dose of quinestrol with ketoconazole (Q1 + K0.4) showed the most significant pronounced effects in reducing reproductive potential, with notable reductions in epididymal weight, sperm density, sperm abnormality rate and vitality, serum hormone levels, and CYP3A4 content in the small intestine and liver. Although some reproductive parameters returned to near-baseline levels after 30 days, the Q1 + K0.4 regimen continued to exhibit reduced seminal vesicle weight and testosterone levels. Importantly, the combination did not significantly increase CYP3A4 enzyme content, indicating effective metabolic inhibition. The combination of quinestrol and ketoconazole, especially the Q1 + K0.4 regimen, demonstrated the most noticeable impact on reducing reproductive capacity. This regimen significantly reduced key reproductive parameters and showed strong metabolic inhibition, suggesting that ketoconazole substantially enhances the efficacy of quinestrol in fertility control.