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Abstract Objective This study aimed to assess the efficacy and safety of bilateral superselective adrenal arterial embolization (SAAE) in patients with bilateral idiopathic hyperaldosteronism (IHA), a subtype of PA. Methods Ninety-eight patients with bilateral IHA underwent bilateral SAAE between August 2022 and August 2023. Sixty-eight patients were followed up for up to 12 months. The study outcomes were evaluated using the criteria provided by the Primary Aldosteronism Surgical Outcome (PASO) guidelines. Results The mean reductions in systolic and diastolic blood pressure were 27.4 ± 21.3 mmHg and 23.1 ± 17.4 mmHg, respectively (p

Abstract Hematopoietic stem cells (HSCs) exhibit significant functional and metabolic alterations within the lung cancer microenvironment, contributing to tumor progression and immune evasion by increasing differentiation into myeloid-derived suppressor cells (MDSCs). Our aim is to analyze the metabolic transition of HSCs from glycolysis to oxidative phosphorylation (OXPHOS) in lung cancer and determine its effects on HSC functionality. Using a murine Lewis Lung Carcinoma lung cancer model, we conducted metabolic profiling of long-term and short-term HSCs, as well as multipotent progenitors, comparing their metabolic states in normal and cancer conditions. We measured glucose uptake using 2-[N-(7-Nitrobenz-2-oxa-1,3-diazol-4-yl)Amino]-2-Deoxyglucose (2-NBDG) and assessed levels of lactate, acetyl-coenzyme A, and ATP. Mitochondrial functionality was evaluated through flow cytometry, alongside the impact of the glucose metabolism inhibitor 2-DG on HSC differentiation and mitochondrial activity. HSCs under lung cancer conditions showed increased glucose uptake and lactate production, with an associated rise in OXPHOS activity, marking a metabolic shift. Treatment with 2-DG led to decreased T-HSCs and MDSCs and an increased red blood cell count, highlighting its potential to influence metabolic and differentiation pathways in HSCs. This study provides novel insights into the metabolic reprogramming of HSCs in lung cancer, emphasizing the critical shift from glycolysis to OXPHOS and its implications for the therapeutic targeting of cancer-related metabolic pathways.

Abstract Introduction Despite improvement in the management of systemic lupus erythematosus (SLE) during the past two decades, 10–22% of patients with lupus nephritis (LN) will progress to end-stage renal disease (ESRD). Kidney transplantation is among the possible treatment for patients with SLE progressing to ESRD. However, the issue with kidney transplantation in patients with SLE is controversial. In this analysis, we aimed to compare the complications associated with kidney transplantation, causes of graft failure and causes of mortality following kidney transplantation in patients with SLE with ESRD. Methods The sources of data included http://www.ClinicalTrials.gov , EMBASE, MEDLINE, Google Scholar, Web of Science and the Cochrane database. Revman software version 5.4 was used for the data analysis whereby risk ratio (RR) with 95% confidence intervals (CI) were used to represent data following analysis. In addition, the Q statistic test and the I 2 statistic test were used to assess heterogeneity. A random effect statistical model was used and a subgroup outcome with a P-value less than 0.05 was considered statistically significant. Results A total number of 149,330 participants enrolled between the years 1968 and 2018 were included in this analysis with 7534 participants with SLE. Results of this analysis showed that mortality (RR 1.07, 95% CI 0.89–1.29; P = 0.45), graft failure (RR 1.22, 95% CI 0.99–1.55; P = 0.07) and delayed graft function (RR 1.01, 95% CI 0.44–2.34; P = 0.98) were not significantly higher in renal transplant patients with SLE versus a control group. When the causes of graft failure were analysed in renal transplant patients with SLE versus without SLE, acute graft rejection (RR 1.20, 95% CI 0.98–1.47; P = 0.07), chronic graft rejection (RR 0.76, 95% CI 0.57–1.03; P = 0.08), graft thrombosis (RR 1.47, 95% CI 0.83–2.63; P = 0.19), recurrence of disease (RR 3.08, 95% CI 1.00–9.47; P = 0.05) and chronic allograft nephropathy (RR 1.08, 95% CI 0.60–1.95; P = 0.80) were also not significantly higher in patients with SLE. On the basis of the analysis, mortality from any cardiac cause (RR 0.82, 95% CI 0.67–1.01; P = 0.06), sepsis (RR 1.19, 95% CI 0.93–1.53; P = 0.17), malignancy (RR 0.79, 95% CI 0.51–1.24; P = 0.31) and cerebrovascular attack (RR 0.76, 95% CI 0.44–1.30; P = 0.31) were not significantly different in kidney transplantation patients with versus without SLE. Conclusions Complications associated with kidney transplantation including mortality, graft failure and delayed graft function were not significantly higher in patients with SLE when compared with a control group. The causes of graft failure and mortality after kidney transplantation were also comparable in both groups. Therefore, kidney transplantation represents a promising treatment in patients with SLE with ESRD.

Abstract Background Pneumoconiosis has a significant impact on the quality of patient survival. This study aims to evaluate the performance and application value of improved Unet network technology in the recognition and segmentation of lesion areas of lung CT images in patients with pneumoconiosis. Methods A total of 1212 lung CT images of patients with pneumoconiosis were retrospectively included. The improved Unet network was used to identify and segment the CT image regions of the patients’ lungs, and the image data of the granular regions of the lungs were processed by the watershed and region growing algorithms. After random sorting, 848 data were selected into the training set and 364 data into the validation set. The experimental dataset underwent data augmentation and were used for model training and validation to evaluate segmentation performance. The segmentation results were compared with FCN-8s, Unet network (Base), Unet (Squeeze-and-Excitation, SE + Rectified Linear Unit, ReLU), and Unet + + networks. Results In the segmentation of lung CT granular region with the improved Unet network, the four evaluation indexes of Dice similarity coefficient, positive prediction value (PPV), sensitivity coefficient (SC) and mean intersection over union (MIoU) reached 0.848, 0.884, 0.895 and 0.885, respectively, increasing by 7.6%, 13.3%, 3.9% and 6.4%, respectively, compared with those of Unet network (Base), and increasing by 187.5%, 249.4%, 131.9% and 51.0%, respectively, compared with those of FCN-8s, and increasing by 14.0%, 31.2%, 4.7% and 9.7%, respectively, compared with those of Unet network (SE + ReLU), while the segmentation performance was also not inferior to that of the Unet + + network. Conclusions The improved Unet network proposed shows good performance in the recognition and segmentation of abnormal regions in lung CT images in patients with pneumoconiosis, showing potential application value for assisting clinical decision-making.

This article elucidates the concept of large model technology, summarizes the research status of large model technology both domestically and internationally, provides an overview of the application status of large models in vertical industries, outlines the challenges and issues confronted in applying large models in the oil and gas sector, and offers prospects for the application of large models in the oil and gas industry. The existing large models can be briefly divided into three categories: large language models, visual large models, and multimodal large models. The application of large models in the oil and gas industry is still in its infancy. Based on open-source large language models, some oil and gas enterprises have released large language model products using methods like fine-tuning and retrieval augmented generation. Scholars have attempted to develop scenario-specific models for oil and gas operations by using visual/multimodal foundation models. A few researchers have constructed pre-trained foundation models for seismic data processing and interpretation, as well as core analysis. The application of large models in the oil and gas industry faces challenges such as current data quantity and quality being difficult to support the training of large models, high research and development costs, and poor algorithm autonomy and control. The application of large models should be guided by the needs of oil and gas business, taking the application of large models as an opportunity to improve data lifecycle management, enhance data governance capabilities, promote the construction of computing power, strengthen the construction of “artificial intelligence + energy” composite teams, and boost the autonomy and control of large model technology.

Abstract Colon cancer is a prevalent malignancy, while recent studies revealed the dys-regulation of Hippo signaling as the important driver for colon cancer progression. Several studies have indicated that post-translational modifications on YAP play crucial roles in both Hippo signaling activity and cancer progression. This raises a puzzling question about why YAP/TAZ, an auto-inhibitory pathway, is frequently over-activated in colon cancer, despite the suppressive cascade of Hippo signaling remaining operational. The protein stability of YAP is subject to a tiny balance between ubiquitination and deubiquitination processes. Through correlation analysis of DUBs (deubiquitinases) expression and Hippo target gene signature in colon cancer samples, we found JOSD1 as a critical deubiquitinase for Hippo signaling and colon cancer progression. JOSD1 could facilitate colon cancer progression and in colon cancer, inhibition of JOSD1 via shRNA has been demonstrated to impede tumorigenesis. Furthermore, molecular mechanism studies have elucidated that JOSD1 enhances the formation of the Hippo/YAP transcriptome by impeding K48-linked polyubiquitination on YAP. ChIP assays have shown that YAP binds to JOSD1’s promoter region, promoting its gene transcription. These results suggest that JOSD1 is involved in both activating and being targeted by the Hippo signaling pathway in colon cancer. Consequently, a positive regulatory loop between JOSD1 and Hippo signaling has been identified, underscoring their interdependence during colon cancer progression. Thus, targeting JOSD1 may represent a promising therapeutic approach for managing colon cancer.

Abstract Background Pectus carinatum (PC) mainly present at the growth spurt time of the early teenage years or the puberty. Poor outer appearance is a major reason for seeking help for surgeons to increase self-confidence and self-esteem. At present, minimally invasive repair (MIR) is one of effective ways to correct the chest wall deformity. Therefore, there is great practical significance to conduct clinical research on MIR about the adolescent PC. Methods We applied Abramson procedure in PC group or we applied Abramson procedure and Nuss procedure in PC/PE group. We retrospectively reviewed the results of 41 cases who underwent the surgical correction at our department from January 2020 to April 2023. Results All the procedures were successfully done without severe complications. The median operation Time was 80 min in PC group while was 130 min in PC/PE group. The median LOS were 4 days in PC group while 5 days in PC/PE group. The median compression depth was 32 mm in PC group while 12 mm in PC/PE group. Postoperatively, there are some complications. All Pneumothorax patients being treated conservatively were found in 9 patients in two groups. One patient suffered overcorrection after operation. There were 3 patients suffered steel wires breakage in two groups. One patient reoperation postoperatively for the dislocation of the bar secondary to steel wires breakage. Conclusions The Abramson procedure or Abramson procedure and Nuss procedure have good short-term results in repair PC and PC/PE. Select one or two procedures should be done individually based on whether the lower plane over depressed after Abramson procedure.

Abstract rAj-Tspin, a soluble recombinant peptide from Apostichopus japonicus, can inhibit the integrin β1 (ITGB1)/FAK/AKT signaling pathway in hepatocellular carcinoma (HCC) via cell epithelial–mesenchymal transition (EMT) and apoptosis. Zyxin (ZYX) is a focal adhesion protein that is considered a novel mediator of EMT and apoptosis. However, the inhibitory mechanisms of rAj-Tspin in HCC and whether it is related to ZYX are unclear. We examined the antitumor effect of rAj-Tspin on the Huh7 human HCC cell line and on a nude mouse model generated via subcutaneous injection or orthotopic intrahepatic transplantation of Huh7 cells. Our results revealed that rAj-Tspin strikingly reduced the viability and promoted the apoptosis of Huh7 cells and inhibited HCC tumor growth in nude mice. rAj-Tspin inhibited ITGB1 and ZYX protein expression in vivo and in vitro in a dose-dependent manner. Mechanistically, the FAK/AKT signaling pathway and the proliferation and invasion of HCC cells were suppressed upon ITGB1 and ZYX knockdown. Moreover, the effect of ITGB1 overexpression on the growth of HCC cells was inhibited by rAj-Tspin. In contrast, the promoting effect of ITGB1 overexpression could be inhibited by ZYX knockdown. ZYX knockdown had no effect on ITGB1 expression. These findings suggest that ZYX is required for the indispensable role of ITGB1 in rAj-Tspin‐alleviated HCC and provide an important therapeutic target for HCC. In summary, the anti-HCC effect of rAj-Tspin potentially involves the regulation of the ITGB1/ZYX/FAK/AKT pathway, which in turn impacts EMT and apoptosis. Graphical Abstract

Abstract Chordoma is a rare bone cancer with variable clinical outcomes. Here, we recruited 184 sporadic chordoma patients from the US and Canada and collected their clinical and treatment data. The average age at diagnosis was 45.5 years (Range 5–78) and the chordoma site distribution was 49.2% clivus, 26.2% spinal, and 24.0% sacral. Most patients (97.5%) received surgery as the primary treatment, among whom 85.3% also received additional treatment. Except for the most prevalent cancers like prostate, lung, breast, and skin cancer, there was no discernible enrichment for any specific cancer type among patients or their family members. Among a subset of patients (N = 70) with tumor materials, we conducted omics analyses and obtained targeted panel sequencing and SNP array genotyping data for 51 and 49 patients, respectively. The most recurrent somatic driver mutations included PIK3CA (12%), followed by chromatin remodeling genes PBRM1 and SETD2. Amplification of the 6q27 region, containing the chordoma susceptibility gene TBXT, was detected in eight patients (16.3%). Clival patients appeared to be less likely to carry driver gene mutations, chromosome arm level deletion events (e.g., 5p, 5p, and 9p), or 6q27 amplification compared to sacral patients. After adjusting for age, sex, tumor site, and additional treatment, patients with somatic deletions of 14q (OR = 13.73, 95% CI 1.96–96.02, P = 0.008) and 18p (OR = 13.68, 95% CI 1.77–105.89, P = 0.012) were more likely to have persistent chordoma. The study highlights genomic heterogeneity in chordoma, potentially linked to location and clinical progression.

Abstract Background Social anxiety symptoms are common and harmful psychological illness in college students. Although some studies have illustrated that physical activity could reduce social anxiety symptoms, the specific mechanism is still unclear. Based on theoretical studies on resilience and sleep, this study constructed a serial mediation model to explore whether they mediate between physical activity and social anxiety symptoms among college students. Methods This study surveyed 9,530 college students from three colleges in China to explore the mediating effect of physical activity and sleep problems between physical activity and social anxiety symptoms. Participants were investigated with the International Physical Activity Questionnaire, Connor-Davidson Resilience Scale, Sleep-related problems, and the Social Interaction Anxiety Scale and the Social Phobia Scale. Correlations between variables were analysed using Pearson correlation analysis and mediation analyses were performed using SPSS PROCESS macro 3.3 software. Result The study found that physical activity was negatively associated with social anxiety symptoms and sleep problems, but positively with psychological resilience. After controlling for sociodemographic variables, physical activity can not only indirectly alleviate social anxiety symptoms through the separate mediation of psychological resilience and sleep problems, but also through the serial mediation of psychological resilience and sleep problems. Conclusion These results suggest that improving physical activity levels could reduce social anxiety scores by increasing psychological resilience and sleep quality. This is of great reference significance for the prevention and intervention of college students’ mental health.

Abstract In light of the crucial role of marine ecosystems and the escalating environmental conservation challenges, it is essential to conduct marine monitoring to help implement targeted environmental protection measures efficiently. Energy harvesting technologies, particularly triboelectric nanogenerators (TENGs), have great potential for prolonging the lifespan and enhancing the reliability of sensors in remote areas. However, the high internal resistance, low current, and friction-induced abrasion issues of TENGs limit their performance in practical applications. This work presents a rolling mode triboelectric nanogenerator that utilizes multi-tunnel grating electrodes and the opposite-charge-enhancement mechanism to harvest wave energy efficiently. The device achieves significant instantaneous and root mean square power density of 185.4 W/(m3·Hz) and 10.92 W/(m3·Hz), respectively. By utilizing stacked devices and an exclusively designed power management module, a self-powered ocean sensing system including computing and long-range wireless communication (0.8 km) capabilities was developed. Laboratory and in-situ ocean tests were conducted to assess and validate the system. This work offers a potential solution for the challenging deployment of marine self-powered sensing nodes.

Abstract Background Acute gouty arthritis (AGA) is classified as ‘arthritis’ in traditional Chinese medicine (TCM) theory. Shirebi granules (SGs), derived from the classic prescription SiMiaoWan, exerts satisfying therapeutic efficacy in ameliorating AGA clinically. However, the underlying mechanisms of SGs against AGA remain unclarified. Methods AGA-related biological processes, signal pathways and biomarker genes were mined from the GEO database through bioinformatics. SGs components were systematically recognized using the UPLC-Q-TOF–MS/MS. A correlation network was established based on the biomarker genes and the chemical components, from which the signal pathway used for further study was selected. Finally, we established an AGA model using SD rats injected with monosodium urate (MSU) in the ankle joint for experimental validation. A combination of behavioral tests, H&E, safranin O- fast green, western blotting, and immunofluorescence were employed to reveal the mechanism of action of SGs on AGA. Results The deterioration of AGA was significantly related to the imbalance between immunity and inflammation, neutrophil chemotaxis and inflammatory factor activation. HDAC5, PRKCB, NFκB1, MPO, PRKCA, PIK3CA were identified to be the candidate targets of SGs against AGA, associated with neutrophil extracellular traps (NETs) signal pathway. Animal experiments demonstrated that SGs effectively repaired cartilage damage, blocked TLR4 activation, and inhibited the expression of NETs indicators and inflammatory factors. In addition, SGs prominently alleviated joint redness and swelling, improved joint dysfunction, inhibited inflammatory infiltration of AGA rats. Conclusion Our data reveal that SGs may effectively alleviate the disease severity of AGA by suppressing NETs-promoted imbalance between immunity and inflammation.

Abstract Nonalcoholic fatty liver disease (NAFLD) is a serious threat to public health, but its underlying mechanism remains poorly understood. In screening important genes using Gene Importance Calculator (GIC) we developed previously, ribosomal modification protein rimK-like family member A (RIMKLA) was predicted as one essential gene but its functions remained largely unknown. The current study determined the roles of RIMKLA in regulating glucose and lipid metabolism. RIMKLA expression was reduced in livers of human and mouse with NAFLD. Hepatic RIMKLA overexpression ameliorated steatosis and hyperglycemia in obese mice. Hepatocyte-specific RIMKLA knockout aggravated high-fat diet (HFD)-induced dysregulated glucose/lipid metabolism in mice. Mechanistically, RIMKLA is a new protein kinase that phosphorylates betaine-homocysteine S-methyltransferase 1 (BHMT1) at threonine 45 (Thr45) site. Upon phosphorylation at Thr45 and activation, BHMT1 eliminated homocysteine (Hcy) to inhibit the activity of transcription factor activator protein 1 (AP1) and its induction on fatty acid synthase (FASn) and cluster of differentiation 36 (CD36) gene transcriptions, concurrently repressing lipid synthesis and uptake in hepatocytes. Thr45 to alanine (T45A) mutation inactivated BHMT1 to abolish RIMKLA’s repression on Hcy level, AP1 activity, FASn/CD36 expressions, and lipid deposition. BHMT1 overexpression rescued the dysregulated lipid metabolism in RIMKLA-deficient hepatocytes. In summary, RIMKLA is a novel protein kinase that phosphorylates BHMT1 at Thr45 to repress lipid synthesis and uptake. Under obese condition, inhibition of RIMKLA impairs BHMT1 activity to promote hepatic lipid deposition.

In this study, the mucosa of porcine small intestine was used as the raw material to optimize the optimal process for the extraction of heparin (Hep) by high hydrostatic pressure enzymatic hydrolysis by response surface test, to study the adsorption conditions of Hep purified by macroporous resin, and to explore the stability of Hep (pH, temperature, and light). The results showed that the optimal enzymatic process was alkaline protease, 3.1 h, 55 ℃, pH9.5, pressure 100 MPa, enzyme addition 9%, salt concentration 2.0%, the actual average concentration of Hep was measured to be 11.56±0.12 U/mL. The purification of Hep was carried out by using the D958 resin, with the up-sampling flow rate of 1.5 BV/h, the concentration of the eluent of 4 mol/L NaCl, and the elution flow rate of 1.5 BV/h, the purity of Hep could reach 68.75% after purification, and the electrophoretic purity achieved. In the stability study, Hep had the best stability at pH7.5, better stability at 40 ℃, and light had no effect on the stability of Hep. This study can greatly improve the extraction effect of Hep and provide theoretical and technical support for the high value processing and utilization of pig small intestine.

Abstract Non-small cell lung cancer (NSCLC) is characterized by a high incidence rate and poor prognosis worldwide. A deeper insight into the pathogenesis of NSCLC and identification of novel therapeutic targets are essential to improve the prognosis of NSCLC. In this study, we revealed that fibrinogen-like protein 1 (FGL1) promotes proliferation, migration, and invasion of NSCLC cells. Mechanistically, we found that Stat3 acts as a transcription factor and can be recruited to the FGL1 promoter, enhancing FGL1 promoter activity. Lysine-specific demethylase 4A (KDM4A) interacts with Stat3 and facilitates the removal of methyl groups from H3K9me3, thereby enhancing Stat3-mediated transcription of FGL1. Furthermore, we observed that Stat3 and KDM4A promote NSCLC cell proliferation, migration, and invasion partly by upregulating FGL1 expression. Additionally, the expression of FGL1 was significantly higher in cancer tissues (n = 90) than in adjacent non-cancerous tissues (n = 90). Furthermore, patients with high FGL1 expression had a shorter overall survival (OS) compared to those with low FGL1 expression. We measured the expression levels of FGL1 on circulating tumor cells (CTCs) in 65 patients and found that patients with a dynamic decrease in FGL1 expression on CTCs exhibited a better therapeutic response. These findings suggest that the dynamic changes in FGL1 expression can serve as a potential biomarker for predicting treatment efficacy in NSCLC. Overall, this study revealed the significant role and regulatory mechanisms of FGL1 in the development of NSCLC, suggesting its potential as a therapeutic target for patients with NSCLC. Future studies should provide more personalized and effective treatment options for patients with NSCLC to improve clinical outcomes.

Abstract Hypertension is a disease associated with epigenetic aging. However, the pathogenic mechanism underlying this relationship remains unclear. We aimed to characterize the shared genetic architecture of hypertension and epigenetic aging, and identify novel risk loci. Leveraging genome-wide association studies (GWAS) summary statistics of hypertension (129,909 cases and 354,689 controls) and four epigenetic clocks (N = 34,710), we investigated genetic architectures and genetic overlap using bivariate casual mixture model and conditional/conjunctional false discovery rate methods. Functional gene-sets pathway analyses were performed by functional mapping and gene annotation (FUMA) protocol. Hypertension was polygenic with 2.8 K trait-influencing genetic variants. We observed cross-trait genetic enrichment and genetic overlap between hypertension and all four measures of epigenetic aging. Further, we identified 32 distinct genomic loci jointly associated with hypertension and epigenetic aging. Notably, rs1849209 was shared between hypertension and three epigenetic clocks (HannumAge, IEAA, and PhenoAge). The shared loci exhibited a combination of concordant and discordant allelic effects. Functional gene-set analyses revealed significant enrichment in biological pathways related to sensory perception of smell and nervous system processes. We observed genetic overlaps with mixed effect directions between hypertension and all four epigenetic aging measures, and identified 32 shared distinct loci with mixed effect directions, 25 of which were novel for hypertension. Shared genes enriched in biological pathways related to olfaction.

Fermented fruit and vegetable products are an important part of traditional fermented food in China. During production, fresh vegetables and fruits are used as raw materials. The fermentation is conducted by the interactions between microorganisms including lactic acid bacteria and fungi which are naturally carried by raw materials. After fermentation, the composition and quantity of microorganisms in fruits and vegetables tend to become out of control, which often leads to post-acidification, softening, spoilage and other problems. Therefore, the development of sterilization technology suitable for fermented fruit and vegetable products has important industrial value. Compared with the destructive effect of traditional heat sterilization, the non-thermal sterilization technology without heating can not only kill the spoilage and pathogenic microorganisms, but also reduce the impact on probiotics, and greatly alleviate the deterioration of fermented fruit and vegetable products. Therefore, non-thermal sterilization technologies have gradually become one of the research hotspots in the field of fermented fruit and vegetable products sterilization. In this paper, the application progress of common non-thermal sterilization technologies in fermented fruit and vegetable products is reviewed. The sterile effect and influencing factors of non-thermal sterilization technologies in fermented fruit and vegetable products are summarized. Its influence on quality and safety attributes of products is discussed. The aim of this study is to provide a theoretical basis for the large-scale application of non-thermal sterilization technologies in the industrial production of fermented fruit and vegetable products.

Abstract Objective The accessibility issue of orphan drugs in China is prominent. Based on real-world data from a tier-one city in Northeast China, this study aims to analyze the current usage and affordability of orphan drugs for rare diseases. Methods The data was sourced from the health insurance claims data of a certain city from 2018 to 2021, including a total of 16 orphan drugs. The utilization of orphan drugs is assessed using four indicators: frequency of medical insurance claims, medication cost, defined daily doses (DDDs), and defined daily drug cost (DDDc). Affordability is measured using the concept of catastrophic health expenditure (CHE). Results Between January 2018 and December 2021, there were a total of 2,851 medical insurance claims in the city, with a total medication costs of $3.08 million. Overall, during the study, there was a year-on-year increase in the utilization frequency of individual rare disease drugs in the city, with DDDs rising from 140.22 in 2018 to 3983.63 in 2021. Additionally, the annual medication costs of individual drugs showed a consistent upward trend, increasing from $10,953.53 in 2018 to $120,491.36 in 2021. However, the DDDc of individual drugs decreased from $398.12 in 2018 to $96.65 in 2021.The number of sales and the amount of sales for orphan drugs in community pharmacies have significantly increased. Prior to medical insurance coverage, out of the 16 orphan drugs, 9 drugs had annual treatment costs exceeding CHE for urban residents, and 15 drugs had annual treatment costs exceeding CHE for rural residents. After medical insurance coverage, there were no drugs with out-of-pocket costs exceeding CHE for urban residents, while 8 drugs had out-of-pocket costs exceeding CHE for rural residents. Furthermore, both before and after medical insurance coverage, the four treatment drugs for idiopathic pulmonary arterial hypertension were more affordable compared to the four treatment drugs for multiple sclerosis. Conclusion The usage frequency of orphan drugs in a certain city increased gradually, but the disease burden remained heavy. More policy support should be provided to the priority rare disease populations, and the rare disease medical security and diagnosis and treatment systems should be improved.

Abstract Background Malnutrition is common in patients with chronic cardiovascular disease and is associated with significantly higher all-cause mortality. Approximately one-third of patients with heart failure are malnourished. However, the relationship between malnutrition and idiopathic pulmonary arterial hypertension (IPAH) remains unclear. This study aimed to clarify the prognostic value of malnutrition in patients with IPAH. Methods A total of 432 consecutive participants with IPAH were included in this study between March 2013 and August 2021. Three common malnutrition assessment tools, including the geriatric nutritional risk index (GNRI), prognostic nutritional index (PNI), and controlling nutritional status (CONUT) score, were used to evaluate the nutritional status of patients with IPAH. The relationships between the malnutrition tools and long-term adverse outcomes were determined using restricted cubic splines and multivariate Cox regression models. Results During a mean follow-up of 3.1 years, 158 participants experienced clinical worsening or all-cause death. Patients were stratified into the low-, intermediate- and high-risk groups based on the European Society of Cardiology (ESC) risk stratification, and the PNI (55.9 ± 5.7 vs. 54.4 ± 7.2 vs. 51.1 ± 7.1, P = 0.005) and CONUT score (2.1 ± 0.9 vs. 2.5 ± 1.2 vs. 3.3 ± 1.1, P

Abstract Objective To examine the influences and mechanisms of MicroRNA-19a-3p (miR-19a-3p) on endothelial dysfunction in atherosclerosis. Methods An analysis of miR-19a expression was carried out using the Gene Expression Omnibus (GEO) database. The effect of miR-19a-3p on endothelial function in HUVECs was evaluated by miR-19a-3p overexpression under TNF-α treatment. Luciferase assays were performed to explore the potential target genes. Overexpression of junctional protein associated with coronary artery disease (JCAD) was used to examine the effects of miR-19a-3p on cell adhesion, and proliferation. Results MiR-19a-3p expression in endothelial cells decreased after exposure to TNF-α and/or oscillatory flow, consistent with the expression change of miR-19a-3p found in atherosclerotic plaques. Additionally, endothelial cell dysfunction and inflammation were significantly diminished by miR-19a-3p overexpression but markedly exacerbated by miR-19a-3p inhibition. MiR-19a-3p transfection significantly decreased the expression of JCAD by binding to the 3’-UTR of JCAD mRNA. Furthermore, the protective effect of miR-19a-3p against endothelial cell dysfunction and inflammation was achieved by regulating JCAD and was closely linked to the Hippo/YAP signaling pathway. Conclusion MiR-19a-3p expression is a crucial molecular switch in the onset of atherosclerosis and miR-19a-3p overexpression is a possible pharmacological therapeutic strategy for reversing the development of atherosclerosis.

Abstract This study assessed the knowledge, attitude, and practice (KAP) of non-ophthalmic medical staff towards myopia-related fundus lesions. This multicenter, cross-sectional study enrolled non-ophthalmic medical staff of Suining City between January and May 2023 using a self-designed questionnaire. A total of 505 (93.19%) valid questionnaires were included. Their mean KAP scores were 8.10 ± 2.32 (range: 0–12), 20.27 ± 2.68 (range: 0–24), and 17.77 ± 5.04 (range: 0–28), respectively. Structural equation modeling indicated that knowledge has a positive effect on attitude (β = 0.307, P

Abstract Background Transvaginal Natural Orifice Transluminal Endoscopy (vNOTES) is regarded as a challenging surgical technique to learn but is promising in reducing perioperative pain and significantly improves the cosmetic outcomes. Previous studies on the learning curve analysis of vNOTES mainly focuses on the hysterectomy approach, while the vNOTES ovarian cystectomy’s learning curve was merely reported though more frequently performed than vNOTES hysterectomy. Therefore, this study seeks to analyze the learning curve of three surgeons with varying levels of experience in performing endoscopic surgery and vaginal surgeries for the treatment of ovarian cysts using vNOTES. Methods A total of 127 patients with ovarian cysts of a variety of pathological types were treated by ovarian vNOTES performed by three surgeons of different levels of endoscopic and transvaginal surgical experience. Each surgeon’s learning curve was plotted using the Cumulative Sum method and divided into three or four phases of technique learning at the turning point of the learning curve. The sociodemographic and clinical features of patients in each phase were then compared and factors potentially associated with operation time were also screened. Results The learning curve was presented in four phases. The operation time (OT) was significantly shorter in phases II (53.66 ± 16.55 min) and IV (54.39 ± 23.45 min) as compared with phases I (68.74 ± 15.85) and III (75.93 ± 30.55) (p

Abstract Purpose To investigate the impact of antibiotic treatment for chronic endometritis (CE) on the pregnancy outcome of frozen-thawed embryo transfer (FET) cycles and the relevant clinical risk factors associated with CE. Methods A retrospective cohort analysis was conducted on 1352 patients who underwent hysteroscopy and diagnostic curettage at Nanjing Maternal and Child Health Hospital from July 2020 to December 2021. All patients underwent CD138 immunohistochemical (IHC) testing to diagnose CE, and a subset of them underwent FET after hysteroscopy. Patient histories were collected, and reproductive prognosis was followed up. Results Out of 1088 patients, 443 (40.7%) were diagnosed with CE. Univariate and multivariate binary logistic regression analyses revealed that parity ≥ 2, a history of ectopic pregnancy, moderate-to-severe dysmenorrhea, hydrosalpinx, endometrial polyps, a history of ≥ 2 uterine operations, and RIF were significantly associated with an elevated risk of CE (P 0.05). Conclusion Infertile patients with a history of parity ≥ 2, hydrosalpinx, a history of ectopic pregnancy, moderate-to-severe dysmenorrhea, endometrial polyps, a history of ≥ 2 uterine operations, and RIF are at an increased risk of CE; these patients should be recommended to undergo hysteroscopy combined with CD138 examination before embryo transfer. Antibiotic treatment can improve the reproductive outcomes of FET in patients with CE, especially those with RIF.

Abstract Background Non-syndromic tooth agenesis (NSTA) is a type of ectodermal dysplasia (ED) in which patients with non-syndromic oligodontia may only affect teeth. No pathological findings were found in other tissues of the ectodermal. Herein, we report a case of a NSTA patient with severe dental anxiety and poor oral health. Case presentation A 5-year-old boy without systemic diseases presented as a patient with oligodontia, extensive caries, and periapical periodontitis. Molecular genetic analysis found a mutation in the Ectodysplasin A (EDA) gene, confirming the diagnosis of NSTA. Conclusion Tooth agenesis (TA) is the most common ectodermal developmental abnormality in humans. Non-syndromic oligodontia patients often seek treatment in the department of stomatology. Because of their complex oral conditions, these patients should be provided with a systematic and personalized treatment plan.

To investigate the role of the HvnAnt2 gene in the formation of different qingke barley grain colours, HvnAnt2 was isolated from the leaves of the White 91-97-3 (white), Blue qingke (blue), Kunlun 17 (black), and Purple qingke (purple). The HvnAnt2 gene encodes a hydrophilic unstable protein consisting of 561 amino acids, without a transmembrane structure and without a signal peptide, with one bHLH-MYC_N and one HLH domain at amino acids 22-204 and 387-436, respectively. The HvnAnt2 of qingke barley was most closely related to Hordeum vulgare and most distantly related to Triticum monococcum; it was mainly related to light responsiveness and methyl jasmonate responsiveness. The Ant2 gene was highly expressed in Kunlun 17 and Purple qingke barley grains during the later stage of development. The protein interaction prediction showed that flavonoid 3'-monooxygenase, anthocyanin biosynthesis gene regulators, and key enzymes in folate metabolism interacted with the Ant2 protein. This study provides a reference for further analysis of the Ant2 gene in the anthocyanin synthesis pathways of qingke barley with different grain colours.

Abstract Background Expanding the number of biomarkers is imperative for studying the etiology and improving venous thromboembolism prediction. In this study, we aimed to identify promising biomarkers or targeted therapies to improve the detection accuracy of early-stage deep vein thrombosis (DVT) or reduce complications. Methods Quantibody Human Cytokine Antibody Array 440 (QAH-CAA-440) was used to screen novel serum-based biomarkers for DVT/non-lower extremity DVT (NDVT). Differentially expressed proteins in DVT were analyzed using bioinformatics methods and validated using a customized array. Diagnostic accuracy was calculated using receiver operating characteristics, and machine learning was applied to establish a biomarker model for evaluating the identified targets. Twelve targets were selected for validation. Results Cytokine profiling was conducted using a QAH-CAA-440 (RayBiotech, USA) quantimeter array. Cross-tabulation analysis with Venn diagrams identified common differential factors, leading to the selection of 12 cytokines for validation based on their clinical significance. These 12 biomarkers were consistent with the results of previous array analysis: FGF-6 (AUC = 0.956), Galectin-3 (AUC = 0.942), EDA-A2 (AUC = 0.933), CHI3L1 (AUC = 0.911), IL-1 F9 (AUC = 0.898), Dkk-4 (AUC = 0.88), IG-H3 (AUC = 0.876), IGFBP (AUC = 0.858), Gas-1 (AUC = 0.858), Layilin (AUC = 0.849), ULBP-2 (AUC = 0.813)and FGF-9 (AUC = 0.773). These cytokines are expected to serve as biomarkers, targets, or therapeutic targets to differentiate DVT from NDVT. Conclusions EDA-A2, FGF-6, Dkk-4, IL-1 F9, Galentin-3, Layilin, Big-h3, CHI3L1, ULBP-2, Gas-1, IGFBP-5, and FGF-9 are promising targets for DVT diagnosis and treatment.

Abstract To analyze the differential expression genes of polycystic ovary syndrome (PCOS), clarify their functions and pathways, as well as the protein–protein interaction network, identify HUB genes, and explore the pathological mechanism. PCOS microarray datasets were screened from the GEO database. Common differentially expressed genes (co-DEGs) were obtained using GEO2R and Venn analysis. Enrichment and pathway analyses were conducted using the DAVID online tool, with results presented in bubble charts. Protein–protein interaction analysis was performed using the STRING tool. HUB genes were identified using Cytoscape software and further interpreted with the assistance of the GeneCards database. A total of two sets of co-DEGs (108 and 102), key proteins (15 and 55), and hub genes (10 and 10) were obtained. The co-DEGs: (1) regulated inflammatory responses and extracellular matrix, TNF, and IL-17 signaling pathways; (2) regulated ribosomes and protein translation, ribosome and immune pathways. The key proteins: (1) regulated inflammation, immunity, transcription, matrix metabolism, proliferation/differentiation, energy, and repair; (2) regulated ubiquitination, enzymes, companion proteins, respiratory chain components, and fusion proteins. The Hub genes: (1) encoded transcription factors and cytokines, playing vital roles in development and proliferation; (2) encoded ribosomes and protein synthesis, influencing hormone and protein synthesis, associated with development and infertility. The dysregulated expression of inflammation and protein synthesis genes in PCOS may be the key mechanism underlying its onset and progression.

Abstract This study explores migrasomes' role in neuroblastoma, a common malignant tumor in children, and their potential impact on tumor formation. We analyzed neuroblastoma RNA-seq datasets from public databases, including GSE62564, GSE181559, target, and fwr144. Through data normalization and unsupervised classification using migrasome-specific molecular markers, Differentially Expressed Genes were identified, followed by functional enrichment analysis. Our novel migrasome-associated machine learning model, MigScore, was developed using ten algorithms and 101 combinations, validated on two single-cell datasets. This enabled immune infiltration assessment and drug compatibility prediction, highlighting the utility of MS275, a histone deacetylase inhibitor. Results showed a significant inverse relationship between MigScore and favorable clinical outcomes, elucidating the link between migrasome pathways and tumor immunogenicity. These findings suggest that migrasomes are crucial in neuroblastoma prognosis, leading to the possibility of personalized treatment strategies and improved outcomes.

Abstract With the continuous expansion of saline soils under climate change, understanding the eco-evolutionary tradeoff between the microbial mitigation of carbon limitation and the maintenance of functional traits in saline soils represents a significant knowledge gap in predicting future soil health and ecological function. Through shotgun metagenomic sequencing of coastal soils along a salinity gradient, we show contrasting eco-evolutionary directions of soil bacteria and archaea that manifest in changes to genome size and the functional potential of the soil microbiome. In salt environments with high carbon requirements, bacteria exhibit reduced genome sizes associated with a depletion of metabolic genes, while archaea display larger genomes and enrichment of salt-resistance, metabolic, and carbon-acquisition genes. This suggests that bacteria conserve energy through genome streamlining when facing salt stress, while archaea invest in carbon-acquisition pathways to broaden their resource usage. These findings suggest divergent directions in eco-evolutionary adaptations to soil saline stress amongst microbial clades and serve as a foundation for understanding the response of soil microbiomes to escalating climate change.

Abstract Purpose To evaluate the availability, cost, affordability of anti-cancer medicines in Nanjing, Jiangsu. Methods A longitudinal tracking investigation study was performed to collect information about 24 essential anti-cancer medicines (EAMs) and 17 innovative anti-cancer medicines (IAMs) in 26 healthcare institutions in Nanjing from 2016 to 2020. The availability, cost, drug utilization and affordability of EAMs and IAMs were investigated. Results The availability of EAMs showed no significant changes in Nanjing, but the availability of IAMs showed a significant increase in 2018 and 2019 and tended to stabilize in 2020. For EAMs, the DDDc(Defined Daily Dose cost) of LPGs (Lowest-Priced Generics) showed no significant changes, and the DDDc of OBs (Originator Brands) and IAMs significantly decreased. The DDDs(Defined Daily Doses) of EAMs (LPGs) showed a decreasing trend since 2016 and rose again in 2019. Overall, the DDDs of EAMs (LPGs) decreased by 25.18% between 2016 and 2020, but the proportion selected for clinical treatment remained at 67.35% in 2020. The DDDs of EAMs (OBs) and IAMs both showed an increasing trend year by year, with a proportional increase of 207.72% and 652.68%, respectively; but the proportion selected for clinical treatment was only 16.09% and 16.56% respectively in 2020. EAMs (LPGs) had good affordability for urban residents but poor affordability for rural residents; the affordability of EAMs (OBs) and IAMs was poor for both urban and rural residents. Conclusions There were no significant changes in the availability and cost of EAMs (LPGs), whose lower prices showed better affordability. Although their relative change in drug utilization showed a decreasing trend, they still dominated clinical treatment. Driven by the national drug price negotiation (NDPN) policy, the availability of IAMs was on the rise. It is necessary to further develop and strengthen policies for essential medicines procurement assessment to improve the accessibility of EAMs.

Abstract Background Hulless barley (Hordeum vulgare L. var. nudum Hook. f.) is a significant cereal crop and a substantial source of forage for livestock. Long non-coding RNAs (lncRNAs) and metabolites play crucial roles in the nutrient accumulation and regeneration of hulless barley plants following mowing. The study aimed to identify differentially expressed lncRNAs and metabolites in hulless barley plants by analyzing transcriptomic and metabolomic datasets at 2 h, 24 h, and 72 h following mowing. Results The study revealed that 190, 90, and 438 lncRNA genes were differentially expressed at the 2 h, 24 h, and 72 h time points compared to the non-mowing control. We identified 14 lncRNA genes—11 downregulated and 3 upregulated—showing consistently significant differential expression across all time points after mowing. These differentially expressed lncRNAs target genes involved in critical processes such as cytokinin signaling, cell wall degradation, storage protein accumulation, and biomass increase. In addition, we identified ten differentially expressed metabolites targeting diverse metabolic pathways, including plant hormones, alkaloids, and flavonoids, before and after mowing at various time points. Endogenous hormone analysis revealed that cytokinin most likely played a crucial role in the regeneration of hulless barley after mowing. Conclusions This study created a comprehensive dataset of lncRNAs, metabolites, and hormones in hulless barley after mowing, revealing valuable insights into the functional characteristics of lncRNAs, metabolites, and hormones in regulating plant regeneration. The results indicated that cytokinin plays a significant role in facilitating the regeneration process of hulless barley after mowing. This comprehensive dataset is an invaluable resource for better understanding the complex mechanisms that underlie plant regeneration, with significant implications for crop improvement.

Abstract Background The canine influenza virus (CIV) outbreak has garnered considerable attention as it poses a significant threat to dog health. During the H3N2 CIV evolution in beagles, the virus formed a new clade after 2019 and gradually became more adaptable to other mammals. Therefore, successfully elucidating the biological characteristics and constructing a canine influenza infection model is required for CIV characterization. Methods We performed genetic analyses to examine the biological characteristics and infection dynamics of CIV. Results The genotype of our H3N2 CIV strain (from 2019 in Shanghai) belonged to the 5.1 clade, which is now prevalent in China. Using MDCK cells, we investigated viral cytopathic effects. Virus size and morphology were observed using transmission electron microscopy. Beagles were also infected with 104, 105, and 106 50% egg-infectious doses (EID50). When compared with the other groups, the 106 EID50 group showed the most obvious clinical symptoms, the highest virus titers, and typical lung pathological changes. Our results suggested that the other two treatments caused mild clinical manifestations and pathological changes. Subsequently, CIV distribution in the 106 EID50 group was detected by hematoxylin and eosin (H&E) and immunofluorescence (IF) staining, which indicated that CIV primarily infected the lungs. Conclusions The framework established in this study will guide further CIV prevention strategies.

Abstract Background Based on our previous research, a full-length cDNA sequence of HvANS gene was isolated from purple and white Qingke. The open reading frame (ORF) in the purple variety Nierumuzha was 1320 base pairs (bp), encoding 439 amino acids, while the ORF in the white variety Kunlun 10 was 1197 bp, encoding 398 amino acids. A nonsynonymous mutation was found at the position of 1195 bp (T/C) in the coding sequence (CDS) of the HvANS gene. We carried out a series of studies to further clarify the relationship between the HvANS gene and anthocyanin synthesis in Qingke. Results The conservative structural domain prediction results showed that the encoded protein belonged to the PLN03178 superfamily. Multiple comparisons showed that this protein had the highest homology with Hordeum vulgare, at 88.61%. The approximately 2000 bp promoter sequence of the HvANS gene was identical in both varieties. The real-time fluorescence PCR (qRT-PCR) results revealed that HvANS expression was either absent or very low in the roots, stems, leaves, and awns of Nierumuzha. In contrast, the HvANS expression was high in the seed coats and seeds of Nierumuzha. Likewise, in Kunlun 10, HvANS expression was either absent or very low, indicating a tissue-specific and variety-specific pattern for HvANS expression. The subcellular localization results indicated that HvANS was in the cell membrane. Metabolomic results indicated that the HvANS gene is closely related to the synthesis of three anthocyanin substances (Idaein chloride, Kinetin 9-riboside, and Cyanidin O-syringic acid). Yeast single hybridization experiments showed that the HvANS promoter interacted with HvANT1, which is the key anthocyanin regulatory protein. In a yeast two-hybrid experiment, we obtained two significantly different proteins (ZWY2020 and POMGNT2-like) and verified the results by qRT-PCR. Conclusions These results provide a basis for further studies on the regulatory mechanism of HvANS in the synthesis of anthocyanins in Qingke purple grains.

Abstract Background Pneumoconiosis has a significant impact on the quality of patient survival due to its difficult staging diagnosis and poor prognosis. This study aimed to develop a computer-aided diagnostic system for the screening and staging of pneumoconiosis based on a multi-stage joint deep learning approach using X-ray chest radiographs of pneumoconiosis patients. Methods In this study, a total of 498 medical chest radiographs were obtained from the Department of Radiology of West China Fourth Hospital. The dataset was randomly divided into a training set and a test set at a ratio of 4:1. Following histogram equalization for image enhancement, the images were segmented using the U-Net model, and staging was predicted using a convolutional neural network classification model. We first used Efficient-Net for multi-classification staging diagnosis, but the results showed that stage I/II of pneumoconiosis was difficult to diagnose. Therefore, based on clinical practice we continued to improve the model by using the Res-Net 34 Multi-stage joint method. Results Of the 498 cases collected, the classification model using the Efficient-Net achieved an accuracy of 83% with a Quadratic Weighted Kappa (QWK) score of 0.889. The classification model using the multi-stage joint approach of Res-Net 34 achieved an accuracy of 89% with an area under the curve (AUC) of 0.98 and a high QWK score of 0.94. Conclusions In this study, the diagnostic accuracy of pneumoconiosis staging was significantly improved by an innovative combined multi-stage approach, which provided a reference for clinical application and pneumoconiosis screening.

The unique flavor properties and rich nutrients of traditional fermented food are closely related to its complex and variable microbial structure, which also makes it difficult to control the quality of final fermented product. In order to explore the changes of microbial structure and sensory property and nutritional property in the process of food fermentation and the internal relationship between them, the data analysis process is a key step. Therefore, it is necessary to establish a fast and accurate data analysis method for quality control of fermented food. Machine learning has the advantages of high-dimensional simplification rate, large data throughput and high prediction accuracy, showing great application potential in the field of quality control of fermented food. Hence, machine learning has become one of the research hotspots. This paper reviews the application of machine learning in the quality control of fermented food. On the basis of an overview of common models of machine learning, this paper systematically summarizes the application of machine learning in the prediction of microbial structure evolution, flavor compound composition analysis and customization of personalized consumption in the process of food fermentation. The problems and developmental trends in the application of machine learning to quality control of traditional fermented food are summarized and prospected. Although the application of machine learning in fermented food is still confined by the problems such as insufficient general applicability of the model, limited quality indicators, and limited personalized consumption scenario, etc., with the iterative update of the technical model, the adaptation for multi-factors and whole process, and the application expansion in the background of personalized consumption, machine learning will show a greater value for practical application in the field of fermented food. The purpose of this study is to provide guidance for the further application of machine learning in the standardized and controllable production of traditional fermented food.

Abstract Keratoconus, a disorder characterized by corneal thinning and weakening, results in vision loss. Corneal crosslinking (CXL) can halt the progression of keratoconus. The development of accelerated corneal crosslinking (A-CXL) protocols to shorten the treatment time has been hampered by the rapid depletion of stromal oxygen when higher UVA intensities are used, resulting in a reduced cross-linking effect. It is therefore imperative to develop better methods to increase the oxygen concentration within the corneal stroma during the A-CXL process. Photocatalytic oxygen-generating nanomaterials are promising candidates to solve the hypoxia problem during A-CXL. Biocompatible graphitic carbon nitride (g-C3N4) quantum dots (QDs)-based oxygen self-sufficient platforms including g-C3N4 QDs and riboflavin/g-C3N4 QDs composites (RF@g-C3N4 QDs) have been developed in this study. Both display excellent photocatalytic oxygen generation ability, high reactive oxygen species (ROS) yield, and excellent biosafety. More importantly, the A-CXL effect of the g-C3N4 QDs or RF@g-C3N4 QDs composite on male New Zealand white rabbits is better than that of the riboflavin 5’-phosphate sodium (RF) A-CXL protocol under the same conditions, indicating excellent strengthening of the cornea after A-CXL treatments. These lead us to suggest the potential application of g-C3N4 QDs in A-CXL for corneal ectasias and other corneal diseases.

To improve the mechanical properties of casting aluminum-copper alloy, the mixed rare earth (RE) was added to ZL206 and its properties and the enhanced mechanism of alloy were researched. The results showed that the strength and hardness of the composite were improved by 10.2% and 6.2%, respectively. After adding mixed RE, which was led by the heterogeneous enrichment area blocking the growth of the α-Al phase and making grain refinement during the solidification process. The simulation results of RE surface adsorption models by first principles also showed that the elastic constant calculation improved the bulk modulus, shear modulus, and Young's modulus of the material. The addition of mixed RE enhances the strength and hardness, although it adversely affects toughness and reduces the machining index. Also, the work function decreased, and the Fermi level increased, reflecting that the electron locality on each band was strong and the bonding state of the alloy system was covalent, which showed that the corrosion resistance was enhanced after adding mixed RE. It provides a new method for the mechanism of RE-modified aluminum-copper alloys and expands the direction of cast aluminum-copper alloy modification.

The recent proliferation of Fifth-Generation (5G) networks and Sixth-Generation (6G) networks has given rise to Vehicular Crowd Sensing (VCS) systems which solve parking collisions by effectively incentivizing vehicle participation. However, instead of being an isolated module, the incentive mechanism usually interacts with other modules. Based on this, we capture this synergy and propose a Collision-free Parking Recommendation (CPR), a novel VCS system framework that integrates an incentive mechanism, a non-cooperative VCS game, and a multi-agent reinforcement learning algorithm, to derive an optimal parking strategy in real time. Specifically, we utilize an LSTM method to predict parking areas roughly for recommendations accurately. Its incentive mechanism is designed to motivate vehicle participation by considering dynamically priced parking tasks and social network effects. In order to cope with stochastic parking collisions, its non-cooperative VCS game further analyzes the uncertain interactions between vehicles in parking decision-making. Then its multi-agent reinforcement learning algorithm models the VCS campaign as a multi-agent Markov decision process that not only derives the optimal collision-free parking strategy for each vehicle independently, but also proves that the optimal parking strategy for each vehicle is Pareto-optimal. Finally, numerical results demonstrate that CPR can accomplish parking tasks at a 99.7% accuracy compared with other baselines, efficiently recommending parking spaces.

Abstract Background Extracellular adenosine triphosphate (ATP) is an important signal molecule. In previous studies, intensive research had revealed the crucial roles of family with sequence similarity 3 member A (FAM3A) in controlling hepatic glucolipid metabolism, islet β cell function, adipocyte differentiation, blood pressure, and other biological and pathophysiological processes. Although mitochondrial protein FAM3A plays crucial roles in the regulation of glucolipid metabolism via stimulating ATP release to activate P2 receptor pathways, its mechanism in promoting ATP release in hepatocytes remains unrevealed. Methods db/db, high-fat diet (HFD)-fed, and global pannexin 1 (PANX1) knockout mice, as well as liver sections of individuals, were used in this study. Adenoviruses and adeno-associated viruses were utilized for in vivo gene overexpression or inhibition. To evaluate the metabolic status in mice, oral glucose tolerance test (OGTT), pyruvate tolerance test (PTT), insulin tolerance test (ITT), and magnetic resonance imaging (MRI) were conducted. Protein–protein interactions were determined by coimmunoprecipitation with mass spectrometry (MS) assays. Results In livers of individuals and mice with steatosis, the expression of ATP-permeable channel PANX1 was increased (P

Reservoirs play a critical role in terrestrial hydrological systems, but the contribution of small and medium-sized ones is rarely considered and recorded. Particularly in developing countries, there is a rapid increase of such reservoirs due to their quick construction. Accurately identifying these reservoirs is important for understanding social and economic development, but distinguishing them from other natural water bodies poses a significant challenge. Thus, we propose a method to identify reservoirs using high-resolution satellite images and deep learning algorithms. We trained models with various parameters and network structures, and You Only Look Once version 7 (YOLOv7) outperformed other algorithms and was selected to build the final model. The method was applied to a region in northwestern Iran, characterized by an abundance of reservoirs of various sizes. Evaluation results indicated that our method was highly accurate (mAP: 0.79, Recall: 0.76, Precision: 0.82). The YOLOv7 model was able to automatically identify 650 reservoirs in the entire study region, indicating that the proposed method can accurately detect reservoirs and has the potential for broader-scale surveys, even global applications.

Abstract The carbon capture‐transportation‐utilization (C‐CTU) chain strengthens the coupling between terminal energy consumption and renewable energy resources (RES), achieving carbon emission reduction in power generation sectors. However, the dynamic operation of the C‐CTU chain and the uncertainties induced by RES output pose new challenges for the low‐carbon operation. To address above challenges, the nonlinear dynamic operation model of C‐CTU chain is first proposed in this study. It is further incorporated into the day‐ahead operation scheme of the electricity‐carbon integrated system considering the stochastic nature of wind power. This scheme is treated as a two‐stage stochastic integer programming (TS‐SIP) problem with a mixed‐integer nonlinear recourse. By means of the polyhedral envelope‐based linearization method, this recourse is reformulated into its linear counterpart. To further improve the computational performance of classical decomposition algorithms, a novel Benders decomposition framework with hybrid cutting plane strategies is proposed to obtain better feasible solutions within a limited time. Simulations are conducted on two power system test cases with the C‐CTU chain. Numerical results indicate that the engagement of C‐CTU chain promotes the low‐carbon economic operation of the power system. Also, the proposed decomposition algorithm shows a superior solution capability to handle large‐scale TS‐SIP than state‐of‐the‐art commercial solvers.

Abstract Objective The objective of this study was to conduct a comprehensive analysis of the molecular transmission networks and transmitted drug resistance (TDR) patterns among individuals newly diagnosed with HIV-1 in Nanjing. Methods Plasma samples were collected from newly diagnosed HIV patients in Nanjing between 2019 and 2021. The HIV pol gene was amplified, and the resulting sequences were utilized for determining TDR, identifying viral subtypes, and constructing molecular transmission network. Logistic regression analyses were employed to investigate the epidemiological characteristics associated with molecular transmission clusters. Results A total of 1161 HIV pol sequences were successfully extracted from newly diagnosed individuals, each accompanied by reliable epidemiologic information. The analysis revealed the presence of multiple HIV-1 subtypes, with CRF 07_BC (40.57%) and CRF01_AE (38.42%) being the most prevalent. Additionally, six other subtypes and unique recombinant forms (URFs) were identified. The prevalence of TDR among the newly diagnosed cases was 7.84% during the study period. Employing a genetic distance threshold of 1.50%, the construction of the molecular transmission network resulted in the identification of 137 clusters, encompassing 613 nodes, which accounted for approximately 52.80% of the cases. Multivariate analysis indicated that individuals within these clusters were more likely to be aged ≥ 60, unemployed, baseline CD4 cell count ≥ 200 cells/mm3, and infected with the CRF119_0107 (P

Abstract Herein, we aimed to identify blood biomarkers that compensate for the poor specificity of D-dimer in the diagnosis of deep vein thrombosis (DVT). S100A8 was identified by conducting protein microarray analysis of blood samples from patients with and without DVT. We used ELISA to detect S100A8, VCAM-1, and ICAM-1 expression levels in human blood and evaluated their correlations. Additionally, we employed human recombinant protein S100A8 to induce human umbilical vein endothelial cells and examined the role of the TLR4/MAPK/VCAM-1 and ICAM-1 signaling axes in the pathogenic mechanism of S100A8. Simultaneously, we constructed a rat model of thrombosis induced by inferior vena cava stenosis and detected levels of S100A8, VCAM-1, and ICAM-1 in the blood of DVT rats using ELISA. The associations of thrombus tissue, neutrophils, and CD68-positive cells with S100A8 and p38MAPK, TLR4, and VCAM-1 expression levels in vein walls were explored. The results revealed that blood S100A8 was significantly upregulated during the acute phase of DVT and activated p38MAPK expression by combining with TLR4 to enhance the expression and secretion of VCAM-1 and ICAM-1, thereby affecting the occurrence and development of DVT. Therefore, S100A8 could be a potential biomarker for early diagnosis and screening of DVT.

Abstract Background Papillary thyroid carcinoma (PTC) is globally prevalent and associated with an increased risk of lymph node metastasis (LNM). The role of cancer-associated fibroblasts (CAFs) in PTC remains unclear. Methods We collected postoperative pathological hematoxylin–eosin (HE) slides from 984 included patients with PTC to analyze the density of CAF infiltration at the invasive front of the tumor using QuPath software. The relationship between CAF density and LNM was assessed. Single-cell RNA sequencing (scRNA-seq) data from GSE193581 and GSE184362 datasets were integrated to analyze CAF infiltration in PTC. A comprehensive suite of in vitro experiments, encompassing EdU labeling, wound scratch assays, Transwell assays, and flow cytometry, were conducted to elucidate the regulatory role of CD36+CAF in two PTC cell lines, TPC1 and K1. Results A significant correlation was observed between high fibrosis density at the invasive front of the tumor and LNM. Analysis of scRNA-seq data revealed metastasis-associated myoCAFs with robust intercellular interactions. A diagnostic model based on metastasis-associated myoCAF genes was established and refined through deep learning methods. CD36 positive expression in CAFs can significantly promote the proliferation, migration, and invasion abilities of PTC cells, while inhibiting the apoptosis of PTC cells. Conclusion This study addresses the significant issue of LNM risk in PTC. Analysis of postoperative HE pathological slides from a substantial patient cohort reveals a notable association between high fibrosis density at the invasive front of the tumor and LNM. Integration of scRNA-seq data comprehensively analyzes CAF infiltration in PTC, identifying metastasis-associated myoCAFs with strong intercellular interactions. In vitro experimental results indicate that CD36 positive expression in CAFs plays a promoting role in the progression of PTC. Overall, these findings provide crucial insights into the function of CAF subset in PTC metastasis.

Abstract Background Laparoscopic sleeve gastrectomy combined with fundoplication (LSGFD) can significantly control body weight and achieve effective anti-reflux effects. The aim of this study is to investigate the correlation between the alteration in Ghrelin levels and weight loss following SGFD, and to compare Ghrelin levels, weight loss and metabolic improvements between SG and SGFD, with the objective of contributing to the existing body of knowledge on SGFD technique in the management of patients with obesity and gastroesophageal reflux disease (GERD). Methods A retrospective analysis was conducted on the clinical data of 115 obese patients who underwent bariatric surgery between March 2023 and June 2023 at the Department of Minimally Invasivew Surgery, Hernia and Abdominal Wall Surgery, People’s Hospital of Xinjiang Uygur Autonomous Region. The subjects were divided into two groups based on surgical methods: sleeve gastrectomy group (SG group, 93 cases) and sleeve gastrectomy combined with fundoplication group (SGFD group, 22 cases). Clinical data, such as ghrelin levels before and after the operation, were compared between the two groups, and the correlation between changes in ghrelin levels and weight loss effectiveness after the operation was analyzed. Results: Three months after the operation, there was no significant difference in body mass, BMI, EWL%, fasting blood glucose, triglyceride, cholesterol, and uric acid levels between the SG and SGFD groups (P > 0.05). However, the SGFD group exhibited a significant decrease in body weight, BMI, and uric acid levels compared to preoperative levels (P 0.05). Logistic regression analysis indicated that ghrelin levels three months after the operation were influential in postoperative weight loss. Conclusion The reduction of plasma Ghrelin level in patients after SGFD is not as obvious as that in patients after SG, but it can make obese patients get the same good weight loss and metabolic improvement as patients after SG. Ghrelin level at the third month after operation is the influencing factor of postoperative weight loss.

Abstract The neuropeptide 26RFa, a member of the RF-amide peptide family, activates the pyroglutamylated RF-amide peptide receptor (QRFPR), a class A GPCR. The 26RFa/QRFPR system plays critical roles in energy homeostasis, making QRFPR an attractive drug target for treating obesity, diabetes, and eating disorders. However, the lack of structural information has hindered our understanding of the peptide recognition and regulatory mechanism of QRFPR, impeding drug design efforts. In this study, we determined the cryo-EM structure of the Gq-coupled QRFPR bound to 26RFa. The structure reveals a unique assembly mode of the extracellular region of the receptor and the N-terminus of the peptide, and elucidates the recognition mechanism of the C-terminal heptapeptide of 26RFa by the transmembrane binding pocket of QRFPR. The study also clarifies the similarities and distinctions in the binding pattern of the RF-amide moiety in five RF-amide peptides and the RY-amide segment in neuropeptide Y. These findings deepen our understanding of the RF-amide peptide recognition, aiding in the rational design of drugs targeting QRFPR and other RF-amide peptide receptors.

Abstract Background PCSK9 inhibitors are a novel class of lipid-lowering drugs that have demonstrated favorable efficacy and safety. Evolocumab and alirocumab have been added to China’s National Reimbursement Drug List through the National Drug Price Negotiation (NDPN) policy. This study aims to evaluate the impact of the NDPN policy on the utilization and accessibility of these two PCSK9 inhibitors. Methods The procurement data of evolocumab and alirocumab were collected from 1,519 hospitals between January 2021 and December 2022. We determined the monthly availability, utilization, cost per daily defined dose (DDDc), and affordability of the two medicines. Single-group interrupted time series (ITS) analysis was performed to assess the impact of the NDPN policy on each drug, and multiple-group ITS analysis was performed to compare the differences between them. Results The NDPN policy led to a significant and sudden increase in the availability and utilization of PCSK9 inhibitors, along with a decrease in their DDDc. In the year following the policy implementation, there was an increase in the availability, utilization, and spending, and the DDDc remained stable. The affordability of PCSK9 inhibitors in China have been significantly improved, with a 92.97% reduction in out-of-pocket costs. The availability of both PCSK9 inhibitors was similar, and the DDDc of alirocumab was only $0.23 higher after the intervention. The market share of evolocumab consistently exceeded that of alirocumab. Regional disparities in utilization were observed, with higher utilization in the eastern region and a correlation with per capita disposable income. Conclusions The NDPN policy has successfully improved the accessibility and utilization of PCSK9 inhibitors in China. However, regional disparities in utilization indicate the need for further interventions to ensure equitable medicine access.

Abstract Wheat is one of the major food crops worldwide. Stripe rust can cause a great loss of wheat yield, especially when the disease is prevalent. Chemical control not only causes the loss of resistance to stripe rust but also has a serious impact on the human body and environment. Therefore, the most economical measure to control wheat stripe rust is to cultivate resistant varieties. Rapid variation of stripe rust races often leads to rapid "loss" of resistance to stripe rust disease; therefore, breeders and researchers have to continuously explore new stripe rust resistance genes to provide new resistance sources for the rapid variation of stripe rust races. Previous studies have confirmed that PI660076, a spring wheat line, showed stripe rust resistance under natural conditions at the adult stage, which has great value in breeding programs. In this study, a recombinant inbred lines (RIL) population was constructed by crossing the wheat line PI660076 with the stripe rust-susceptible line AvS. Genotyping of the population was performed using a wheat 15 K SNP array. Three QTLs were identified using phenotypic data over four years across three environments. The resistance type of each QTL was determined by inoculating the RIL lines with single and homozygous QTL during the seedling and adult stages under controlled conditions. The all-stage resistance (ASR) QTL, QYr076.jaas-2A (flanked by SNP marker AX-11048464 and Kompetitive Allele-Specific PCR (KASP) marker KASP_4940) explained 7.13–16.58% and 6.95–7.25% of infection type (IT) and disease severity (DS), respectively. The adult-plant resistance (APR) resistance QTL, QYr076.jaas-4D.1 (flanked by KASP marker KASP_0795 and SNP marker AX-111567243,) explained 6.85–12.70% and 7.94–17.26% of IT and DS, respectively. The APR resistance QTL, QYr076.jaas-4D.2 flanked by KASP markers KASP_9130 and KASP_6535, explained 7.97–39.19% and 8.77–20.55% of the phenotypic variation in IT and DS, respectively. All the three QTLs are likely to be new. The obtained results lay a foundation for further utilization of the stripe rust-resistant line PI660076, as well as for fine mapping and molecular marker-assisted selection breeding. Graphical Abstract