Search

Acute lung injury (ALI) or its more severe form, acute respiratory distress syndrome, is a life-threatening disease closely associated with an imbalance of M1/M2 macrophage polarization. However, current therapeutic strategies for ALI are controversial due to their side effects, restricted administration routes, or poor targeted delivery. The development of herbal medicine has uncovered numerous anti-inflammatory compounds potentially beneficial for ALI therapy. One such compound is the bergapten, a coumarin, which has been isolated from Ficus simplicissima Lour. However, it's been used as an anti-cancer drug and it's effects on ALI remain unexplored. The poor solubility and biodistribution of bergapten heavily limit its application. In this timely report, we developed a bioactive and lung-targeting lipid-nanomedicine by integrating bergapten and DPPC liposome, named as Ber-lipo. A comprehensive series of in vitro experiments confirmed the anti-inflammatory effects of Ber-lipo and its protective roles in maintaining the homeostasis of macrophage polarization and epithelial–endothelial integrity. In a lipopolysaccharide (LPS)-induced ALI mouse model, Ber-lipo can target inflamed lungs and significantly improve lung edema, tissue injury, and pulmonary function, relieve body weight loss, pulmonary permeability, and proinflammatory status, and especially maintain a balance of M1/M2 macrophage polarization. Furthermore, RNA sequencing analysis showed Ber-lipo's potential in effectively treating inflammatory lung diseases such as pneumonia, inhibiting proinflammatory signals, and altering the transcriptome of M1/M2 macrophages-associated genes in lung tissues. Molecular docking and Western blot analyses validated that Ber-lipo suppressed the activation of the TLR4/MyD88/NF-κB signaling axis responsible for ALI progression. In conclusion, this study demonstrates for the first time that new inhalable nanomedicine (Ber-lipo) can target inflamed lungs and ameliorates ALI by reprogramming macrophage polarization to an anti-inflammatory state via inactivating the TLR4/MyD88/NF-κB pathway, hence providing a promising strategy for enhanced ALI therapy in the clinic.

Abstract Background Echinococcosis is an infectious parasitic disease that is extremely harmful to human health. Albendazole is provided free of charge to patients requiring medication under the central government finance transfer payment scheme for echinococcosis control and prevention in China. Our aim is to monitor the state of patient medication and its therapeutic impact, which will help improve medication compliance and the therapeutic effect. Methods Random cluster sampling was used to select 10 echinococcosis-endemic counties in China, and all albendazole-treated patients in these counties were investigated. The chi-square and Kruskal–Wallis tests were used to compare two or more rates or constituent ratios, and multiple logistic regression analysis was used to identify the influencing factors. The records of patients were reviewed to obtain the initial diagnosis results as well as the most recent follow-up results and time, and efficacy was assessed. Results We examined 899 patient files treated with albendazole in 10 endemic counties. Of the 582 evaluable files, 7.9% did not take albendazole, and 69.2% did not take albendazole regularly. Only 22.9% took albendazole regularly. Of the 536 patients who took albendazole, 242 exhibited adverse reactions. Patients who were Tibetan, herdsmen, received no formal education, used emulsion, and exhibited adverse reactions demonstrated poor compliance. A total of 174 patients with cystic echinococcosis received their most recent imaging follow-up results within one year of the investigation date. Among them, 9 patients met the criteria for cure, accounting for 5.2%; 56 patients showed effectiveness, accounting for 32.2%; 105 patients were deemed ineffective, accounting for 59.8%; 5 patients experienced recurrence, accounting for 2.9%. Conclusions Albendazole medication compliance in patients with echinococcosis is not ideal. We must prioritize health education and promotion for Tibetans, herdsmen, and those without formal education. Patients who adhered to their medication regimen achieved higher rates of cure and effectiveness. To improve medication compliance and efficacy, it is particularly important to improve communication and medication guidance for patients receiving emulsions and those with adverse reactions after taking albendazole. Simultaneously strengthen patients' attention to follow-up and re-examination. Graphical Abstract

Spermiation is the process that releases mature spermatids from Sertoli cells into the lumen of the seminiferous tubule. Tubulobulbar complexes (TBCs) are elaborate cytoskeleton-related structures that are indispensable for spermiation. Despite well-defined ultrastructural events, the molecular regulation of TBCs during spermiation remains largely unknown. Here, we show that autophagy is active in TBC regions, and impaired autophagy in Sertoli cells affects spermiation. Further studies demonstrated that many TBC components bound to LC3 and could be selectively degraded through the autophagy-lysosome pathway. Perturbed autophagy impaired the degradation of some TBC components in Sertoli cells, such as VCL and CTTN, and led to the accumulation of TBC components surrounding the spermatid head, which may be associated with the sperm-releasing defect. Together, our results reveal that autophagy is essential for the TBC components degradation in mouse Sertoli cells and define a functional role of autophagy during spermiation.

Oxidative stress and inflammation are key drivers of osteoarthritis (OA) pathogenesis and disease progression. Herein we report the synthesis of poly(p-coumaric) nanoparticles (PCA NPs) from p-courmaic acid (p-CA), a naturally occurring phytophenolic acid, to be a multifunctional and drug-free therapeutic for temporomandibular joint osteoarthritis (TMJOA). Compared to hyaluronic acid (HA) that is clinically given as viscosupplementation, PCA NPs exhibited long-term efficacy, superior anti-oxidant and anti-inflammatory properties in alleviating TMJOA and repairing the TMJ cartilage and subchondral bone in a rat model of TMJOA. Notably, TMJ repair mediated by PCA NPs could be attributed to their anti-oxidant and anti-inflammatory properties in enhancing cell proliferation and matrix synthesis, while reducing inflammation, oxidative stress, matrix degradation, and chondrocyte ferroptosis. Overall, our study demonstrates a multifunctional nanoparticle, synthesized from natural p-coumaric acid, that is stable and possess potent antioxidant, anti-inflammatory properties and ferroptosis inhibition, beneficial for treatment of TMJOA.

Abstract Background The severe postpartum hemorrhage (SPPH) leads to dangerous maternal conditions, and its rate is still increasing and the trend in related risk factors is changing. Placenta-related problems remain the high-risk factor for SPPH. The object is to investigate the prevalence and the risk factors of the severe postpartum hemorrhage in pregnant women with placenta previa or low-lying placenta. Method A retrospective analysis of pregnant women with placenta previa or low-lying placenta after 28 weeks gestation from May 2018 to May 2023 in the Peking Union Medical College Hospital was conducted. The primary outcome was severe postpartum hemorrhage defined as blood loss ≥ 1000 mL within 24 h of childbirth, or with signs or symptoms of low blood volume requiring transfusion of ≥ 4U of red blood cells. Univariate and multivariate logistic regression were used to identify potential risk factors of severe postpartum hemorrhage and receiver operating curve to evaluate the prediction performance. Results Of the 14,964 women, 201 met the inclusive criteria. SPPH rate was 1.3% overall and 18.9% in women with placenta previa or low-lying placenta. Weight (aOR = 0.93, 95%CI 0.87–0.99), increta or percreta placenta (aOR = 7.93, 95%CI 2.53–24.77) were the risk factors. The area under the ROC curve was 0.69(95%CI 0.59–0.80) for increta or percreta placenta alone, and 0.72(95%CI 0.62–0.82) for the combination of times of cesarean sections and anterior placenta. Conclusions Placenta accreta spectrum was the key independent risk factor of SPPH in women with placenta previa or low-lying placenta. Antenatal risk assessment of SPPH in these population is highly desirable and optimal intervention could be planned.

Abstract The traditional airborne LiDAR point clouds vehicle recognition algorithms only utilize the contained geometric information and are not sufficient to recognize vehicles accurately, especially in complex urban scenes. And their applicability in super-high density UAV-LiDAR point clouds is unknown. Therefore, a 3-D algorithm combining geometric and intensity information from super-high density UAV-LiDAR point clouds is presented. The proposed algorithm firstly converts the original point clouds into a 3D multivalued image which fuses intensity, elevation and density information simultaneously. Thereafter, the potential vehicle voxels are extracted according to the intensity, elevation and density consistency of vehicles. Subsequently, individual vehicles are recognized using the potential vehicle voxel’s spatially connected set with vehicle size constraint. Finally, the quantified attribute information of each individual vehicle, containing the spatial location, type, and size, is determined. The results for recognized vehicles are evaluated using UAV-LiDAR data with different densities and demonstrate an average quality (Kappa coefficient) of 96.58% (96.04%) without being significantly affected by occlusion and the very close vehicle arrangement.

Background. People living with HIV (PWH) frequently have co-morbid substance use disorders that may have been impacted by the COVID-19 pandemic. This study examined associations between COVID-related stress and increased substance use among PWH in Washington State. Methods. Between August 2020 and March 2021, we conducted an online survey of 397 PWH in western Washington. Logistic regression was used to analyze associations between a COVID-19 stress score and four self-reported outcomes: increased alcohol use, increased cigarette smoking, increased marijuana use, and increased use of illicit substances. Results. Thirty-five (38.0%) of 92 participants who smoked, 61 (23.4%) of 261 participants who used alcohol, 15 (14.6%) of 103 participants who used marijuana, and 35 (33.0%) of 102 participants who used illicit substances reported increased use of these substances. Higher COVID-19 stress scores were associated with higher odds of increased cigarette smoking (adjusted odds ratio [aOR] = 1.15, 95% confidence interval [CI]: 1.04–1.27), even after adjustment for anxiety and depressive symptoms (aOR 1.14, 95%CI: 1.03–1.27). COVID-19 stress was not associated with an increased use of alcohol, marijuana, or illicit substances. Conclusions. COVID-19-related stress was associated with self-reported increased cigarette smoking among PWH in western Washington during the pandemic.

Background: Treatment options for patients with refractory inflammatory bowel disease (IBD) or concomitant IBD and extraintestinal manifestations (EIM) are often limited. Objective: This study aimed to examine the efficacy and safety of combining biologics or small molecules in patients with refractory IBD, active EIM, or active immune-mediated inflammatory disease (IMID). Design: This was a retrospective and multicenter study. Methods: We retrospectively collected demographics and disease characteristics from 47 patients with IBD who received dual-targeted therapy in 3 hospitals from January 2022 to June 2024. The primary endpoint was clinical remission based on the Harvey–Bradshaw index or patient-reported outcome 2 after at least 4 months of combination therapy. The secondary endpoints included clinical response, endoscopic response, and endoscopic remission, as well as all adverse events that occurred within the period of combination therapy. Results: In total, 47 IBD patients including 37 with refractory IBD, 5 with active EIM, and 5 with active IMID received dual-targeted therapy, of which 37 achieved clinical response (78.7%) and 27 achieved clinical remission (57.4%) at a median follow-up time of 13.0 months. Among these 47 patients, 29 patients underwent endoscopic follow-up, of which 15 (51.7%) achieved endoscopic response and 8 (27.6%) achieved endoscopic remission at a median follow-up time of 9.0 months. Mild and moderate adverse events were reported in 17 (36.2%) patients within the period of combination therapy, and serious adverse events requiring hospitalization occurred in 1 patient (2.1%). Conclusion: The combination therapy of biologics and small molecules for refractory IBD or those with concomitant EIM/IMID is effective and safe.

Acute hepatopancreatic necrosis (AHPND) is a bacterial disease caused by Vibrio bacteria that severely affects the Pacific white shrimp farming industry. Since AHPND was first identified in China and Vietnam in 2010, it was subsequently identified in Malaysia (2011), Thailand (2012), Mexico (2013), the Philippines (2014), South Korea (2016), Bangladesh (2017), the United States (US) (2017), and Japan (2020). AHPND causes significant economic losses of more than 7 billion US＄ annually to the global shrimp farming industry. It has severely restricted the development of the global shrimp farming industry. Many studies have shown that the pathogens of AHPND are Vibrio spp., including V. parahaemolyticus, V. owensii, V. campbellii, V. harveyi, V. punensis, and V. anguillarum. The virulence of these pathogenic strains was derived from a 70 kb virulent plasmid (pVA1-type plasmid). The pVA1-type plasmid carries pirAB genes encoding the binary toxin pirAB homologous to the insecticidal protein of Photobacterium phosphoreum. The pVA1-type plasmid has been confirmed to carry a novel trb type Ⅳ secretion system (T4SS). Trb-T4SS can mediate the conjugative transfer of the pVA1-type plasmid at high cell density for interspecific horizontal transfer.The quorum sensing (QS) system is also known as the density-sensing system. In the surrounding environment, the QS system allows bacteria to regulate the expression of multiple genes by sensing changes in the concentration of autoinducer signaling molecules. At high cell density, high concentrations of autoinducer signaling molecules bind to receptor proteins to inhibit phosphorylation cascades and high cell density master regulator OpaR is normally expressed. OpaR is involved in the regulation of various biological processes, such as biofilm-forming ability, motility, and the expression of the type Ⅲ and type Ⅳ secretion systems. Reportedly, high concentrations of signaling molecules in the QS system regulate the expression of key genes of the T4SS to increase the conjugative transfer efficiency of drug-resistant plasmids. However, the regulation of the T4SS by opaR in AHPND is not yet reported.In this study, OpaR, the high cell density master regulator of the QS system in V. parahaemolyticus, was selected to explore the relationship between the QS system and T4SS expression, as well as the conjugative transfer of the pVA1-type plasmid. The V. parahaemolyticus 20130629002S01::cat (Vp2S01::cat) strain, a pathogenic strain of AHPND, was used as the starting strain. The opaR gene was replaced with the erythromycin resistance gene (ermB) by homologous recombination and electroporation. The opaR mutant strain (Vp2S01::catΔopaR) was successfully constructed. The effects of OpaR on Vp2S01::cat were explored by performing growth curve and motility assays.Vp2S01::cat and Vp2S01::catΔopaR were cultured continuously for approximately 24 h in a shaking bed at 28 ℃ and 180 r/min. OD600 was measured every 2 h to compare the difference in growth. The results showed that there were no significant differences in the growth curves for Vp2S01::cat and Vp2S01::catΔopaR. Biofilm-forming ability was detected using a crystal violet staining assay. The results showed that the biofilm-forming ability of Vp2S01::catΔopaR was significantly reduced. Growth zone diameter was recorded in 0.3% (swimming) LB agar plates at 28 ℃ for 8 h to analyze the difference in swimming ability. We found that the swimming ability of Vp2S01::catΔopaR increased significantly by 2.67 times compared with that of Vp2S01::cat. Growth zone diameter was recorded in 1.5% (swarming) LB agar plates at 28 ℃ for 12 h to analyze the difference in swarming ability. The results showed that there was no significant difference in swarming ability between Vp2S01::cat and Vp2S01::catΔopaR. However, Vp2S01::catΔopaR had more missing colonies. Using VcLMB29 as the receptor strain, the conjugative transfer efficiency of Vp2S01::cat and Vp2S01::catΔopaR was compared at different time points. We found that the conjugative transfer efficiency of Vp2S01::catΔopaR increased after 12 and 24 h. The conjugative transfer efficiency after 24 h was increased by a factor of 265.43. RNA of Vp2S01::cat and Vp2S01::catΔopaR was extracted after 24 h of conjugative transfer and reverse-transcribed into cDNA for real-time quantitative fluorescence PCR (RT-qPCR). GyrB was used as the reference gene. AphA-qRT, opaR-qRT, and T4SS-qRT primers were used for RT-qPCR. The relative expression levels of genes were calculated using the 2–ΔΔCt method. The results showed that the relative expression levels of T4SS in the Vp2S01::catΔopaR experimental group were significantly increased by 1.13–3.21 times and that the relative expression levels of the key conjugative transfer genes traF, trbE, and traG were significantly increased by 1.96, 1.92, and 3.21 times, respectively.In conclusion, the opaR gene does not affect the growth and swarming motility but does affect the biofilm-forming and swimming ability of Vp2S01::cat. The high cell density master regulator OpaR may affect the conjugative transfer efficiency of the virulent plasmid by regulating the expression levels of T4SS. This study provides fundamental data for analyzing the mechanism by which the QS system regulates the expression of T4SS and the conjugative transfer of the pVA1-type plasmid in AHPND pathogenic bacteria, offering technical support for the control of the horizontal transfer of the virulent plasmid in AHPND-causing bacteria.

Objectives: The objective of the study was to investigate the clinical value of pelvic diameter in the evaluation of surgical difficulty and selection of the best surgical plan for exogenous cervical leiomyomas. Materials and Methods: Sixty-five patients with exogenous cervical leiomyomas admitted to our hospital from 2012 to 2021 were enrolled. All patients underwent pelvic magnetic resonance imaging examination before surgery and received surgical treatment within 1 week. Relevant clinical data were collected. According to the surgical approach, they were divided into two groups: the laparoscopic group and the laparotomy group. The clinical significance of the pelvic diameter line in the surgical selection of exogenous cervical leiomyomas was discussed by retrospective analysis of the correlation between the pelvic diameter line and the collected clinical indicators. Results: There was no significant difference in tumor location and pelvic diameter between the two groups (P > 0.05). However, there was a significant difference in tumor diameter and the ratio of tumor diameter line to pelvic diameter line (P < 0.05). In addition, the laparoscopic group underwent more myomectomy than hysterectomy and lost more blood during operation (P < 0.05).The postoperative index showed that patients in the laparotomy group had a higher proportion of full of cellular leiomyoma, higher postoperative temperature, and longer postoperative exhaust time (P < 0.05). Conclusion: The ratio of the tumor diameter line to the pelvic diameter line is correlated with the surgical plan selection of exogenous cervical leiomyomas, which may be used to evaluate the surgical difficulty of these patients and the selection of the suitable surgical plan.

Men who have sex with men (MSM) bear a disproportionate burden of HIV in China and are particularly vulnerable to mental health challenges. This study is phase one of a multi-phase project that aimed to identify unmet needs of MSM living with HIV to inform the development of a multi-level intervention. We interviewed 24 stakeholders through videoconferencing, including 15 MSM living with HIV, five staff from a community-based organization serving gender and sexual minority individuals, and four staff from the Centers for Disease Control and Prevention in Shanghai, China. We conducted content analysis using inductive and deductive coding and identified the following themes: 1) Navigating Turbulent Waters: multi-level stress currents; 2) Mapping Anchors: multifaceted support network; 3) Staying Afloat: Daily strategies and functioning; and 4) Charting New Courses: paths for intervention. Examining the stress and coping process among MSM living with HIV from a socio-ecological lens is especially important in the collective cultural context. The interactive nature of the stress from multiple socio-ecological levels, lack of individual coping skills, and scarcity of psychosocial services highlighted the importance of community-based, multi-level interventions to meet the needs of MSM living with HIV in China.

As the largest organic carbon input in the agroecosystems, crop residues can increase soil carbon sequestration and crop production in greenhouse vegetable fields (GVFs). However, the soil microbiological mechanisms driving straw decomposition in GVFs under different incubation temperatures and fertilization treatments are not clear. Thus, soil samples were collected from a long-term field experiment included chemical fertilizer application alone (CF), 2/4 fertilizer N+2/4 organic fertilizer N (CM), 2/4 fertilizer N+1/4 organic fertilizer N+1/4 straw N (CMS), 2/4 fertilizer N+2/4 straw N (CS), and incubated with 13C-labeled straw at different temperatures (15, 25, and 35°C) for 60 days. Organic-amended treatments (CM, CMS, and CS), especially CMS treatment, increased soil bacterial Alpha diversity before and after straw addition. Straw decomposition process was dominated by soil Proteobacteria, Actinobacteria, and Firmicutes for each treatments. The effect of incubation temperature on soil microbial community composition was higher than that of fertilization treatments. Soil Alphaproteobacteria and Actinomycetia were the most predominant class involved in straw decomposition. Gammaproteobacteria (Pseudomonas, Steroidobacter, Acidibacter, and Arenimonas) were the unique and predominant class involved in straw decomposition at medium and high temperatures as well as in the straw-amended treatments. Organic-amended treatments, especially straw-amended treatments, increased the relative abundance of glycosyl transferases (GT) and auxiliary activities (AA). Alphaproteobacteria, Actinomycetia, and Gammaproteobacteria had higher relative contribution to carbohydrase genes. In summary, the long-term organic-amended treatments altered the structure of soil microbial communities and increased soil bacterial diversity, with the CMS having a greater potential to enhance resistance to external environmental changes. Soil Alphaproteobacteria and Actinomycetia were responsible for the dominance of straw decomposition, and Gammaproteobacteria may be responsible for the acceleration of straw decomposition. Fertilization treatments promote straw decomposition by increasing the abundance of indicator bacterial groups involved in straw decomposition, which is important for isolating key microbial species involved in straw decomposition under global warming.

Abstract To compare the urine Congo‐red dot paper test (CRD) with dipstick urinalysis to screen preeclampsia (PE). A total of 409 paired spot urine samples were obtained prospectively from women with suspected pre‐eclampsia attending for routine hospital visits. Congo‐red dot paper test and dipstick urinalysis were examined and compared to screen pre‐eclampsia. The agreement between the two urinary test is modest (kappa coefficient = 0.28, 95% CI 0.14–0.42). The specificity of CRD was higher than urinalysis (97.4% vs. 90.4%, p

Abstract The Zika virus (ZIKV) is a serious global public health crisis. A major control challenge is its multiple transmission modes. This paper aims to simulate the transmission patterns of ZIKV using a dynamic process-based epidemiological model written in ordinary differential equations, which incorporates the human-to-mosquito infection by bites and sewage, mosquito-to-human infection by bites, and human-to-human infection by sex. Mathematical analyses are carried out to calculate the basic reproduction number and backward bifurcation, and prove the existence and stability of the equilibria. The model is validated with infection data by applying it to the 2015–2016 ZIKV epidemic in Brazil. The results indicate that the reproduction number is estimated to be 2.13, in which the contributions by mosquito bite, sex and sewage account for 85.7%, 3.5% and 10.8%, respectively. This number and the morbidity rate are most sensitive to parameters related to mosquito ecology, rather than asymptomatic or human-to-human transmission. Multiple transmission routes and suitable temperature exacerbate ZIKV infection in Brazil, and the vast majority of human infection cases were prevented by the intervention implemented. These findings may provide new insights to improve the risk assessment of ZIKV infection.

Shield tunnels are increasingly monitored using 3D laser scanning technology to generate high-resolution point cloud data, which serve as a critical foundation for precise deformation analysis. This study introduces an advanced methodology for analyzing tunnel cross-section displacements, leveraging point cloud data captured by the Self-Mobile Intelligent Laser Scanning System (SILSS), a Mobile Laser Scanning (MLS) platform capable of rapid and detailed 3D mapping of shield tunnels. The preprocessing pipeline includes the precise extraction of cross-sectional linings through local point density outlier removal techniques to enhance data accuracy. A custom segmentation algorithm partitions the tunnel cross-section linings into individual shield rings, enabling detailed and time-resolved displacement tracking. Aligned point clouds from different times were processed using the Iterative Closest Point (ICP) algorithm to achieve high-accuracy displacement analysis. Key displacement metrics, including average shield ring point cloud displacement and centerline shift, were computed to quantify displacement. Additionally, ovality analysis was employed to detect shield ring shape changes, providing critical insights into structural deformations. The findings are visualized in 3D, highlighting significant displacement areas in the tunnel cross-section. An analysis of the corresponding data obtained from the Leica Pegasus Two Ultimate scanner system shows that the data collected by SILSS are accurate. This methodology offers a robust tool for continuous tunnel monitoring, supporting the development of safer and more resilient underground infrastructure systems.

Exploring the temporal evolution dynamics of different soil organic nitrogen (N) components under different water–N management practices is a useful approach to accurately assessing N supply and soil fertility. This information can provide a scientific basis for precise water and N management methods for greenhouse vegetable production. The objective of this study was to investigate the effects of optimized irrigation and nitrogen management on the dynamics of soil organic nitrogen fractions, soil properties, and crop growth. This research was conducted from 2017 to 2023 in a greenhouse vegetable field in North China. Four treatments were applied: (1) high chemical N application with furrow irrigation (farmers’ practice, FP); (2) no chemical N application with drip irrigation (DN0); (3) 50% N of FP with drip irrigation (DN1); and (4) 75% N of FP with drip irrigation (DN2). The volume in drip irrigation is 70% of that in furrow irrigation. The results showed that in 2023 (after seven years of field trials), compared with FP, the soil organic carbon (SOC), total N, and water use efficiency of the DN1 and DN2 treatments increased by 15.9%, 11.4%, and 11.3% and 7.7%, 47.2% and 44.6%, respectively. However, there was no significant difference in the total crop yield except in the DN0 treatment. Soil organic N was mostly in the form of acid-hydrolyzed N (AHN). After seven years of optimized irrigation and N management, the DN1 treatment significantly increased the content of ammonium N (AN) and amino sugar N (ASN) in AHN compared with the FP treatment. The results of further analysis demonstrated that SOC was the main factor in regulating AHN and non-hydrolyzable N (NHN), while the main regulatory factors for amino acid N (AAN) and ASN in the AHN component were dry biomass and water use efficiency, respectively. From a time scale perspective, optimization of the water and N scheduling, especially in DN1 (reducing the total irrigation volume by 30% and the amount of N applied by 50%), is crucial for the sustainable improvement of soil fertility and the maintenance of vegetable production.

Abstract Visual observation and therapeutic intervention against tumors hold significant appeal for tumor treatment, particularly in meeting the demands of intraoperative navigation. From a clinical perspective, the naked‐eye visualization of tumors provides a direct and convenient approach to identifying tumors and navigating during surgery. Nevertheless, there is an ongoing need to develop effective solutions in this frontier. Genetically engineered microorganisms are promising as living therapeutics for combatting malignant tumors, leveraging precise tumor targeting and versatile programmed functionalities. Here, genetically modified Escherichia coli (E. coli) MG1655 bacterial cells are introduced, called MelaBac cells, designed to express tyrosinase continuously. This bioengineered melanogenesis produces melanin capable of pigmenting both subcutaneous CT26 xenografts and chemically induced colorectal cancer (CRC). Additionally, MelaBac cells demonstrate the initiation of photonic hyperthermia therapy and immunotherapy against tumors, offering promising selective therapeutic interventions with high biocompatibility.

The United Nations’ Sustainable Development Goals (SDGs) are significant in guiding modern scientific research. In recent years, scholars have paid much attention to MOFs materials as green materials. However, piezo catalysis of MOFs materials has not been widely studied. Piezoelectric materials can convert mechanical energy into electrical energy, while MOFs are effective photocatalysts for removing pollutants. Therefore, it is crucial to design MOFs with piezoelectric properties and photosensitivity. In this study, sulfur-functionalized metal–organic frameworks (S-MOFs) were prepared using organic sulfur-functionalized ligand (H2TDC) ultrasonic synthesis to enhance their piezoelectric properties and visible light absorption. The study demonstrated that the S-MOFs significantly enhanced the reduction of a 10 mg/L solution of hexavalent chromium to 99.4 % within 10 min, using only 15 mg of catalyst. The orbital energy level differences of the elements were analyzed using piezo response force microscopy (PFM) and X-ray photoelectron spectroscopy (XPS). The results showed that MOFs functionalized with sulfur atom ligands have a built-in electric field that facilitates charge separation and migration. This study presents a new approach to enhance the piezoelectric properties of MOFs, which broadens their potential applications in piezo catalysis and piezo-photocatalysis. Additionally, it provides a sustainable method for reducing hexavalent chromium, contributing to the achievement of sustainable development goals, specifically SDG-6, SDG-7, SDG-9, and SDG-12.

This study aimed to investigate the effects of germination and roasting on the flavor of quinoa. Firstly, the aroma of quinoa and germinated quinoa roasted under different conditions was analyzed using sensory evaluation and electronic nose (E-nose). Results showed that the best favorable aroma of quinoa and germinated quinoa was obtained when roasted at 160 °C for 15 min. Then, a total of 34 and 80 volatile organic compounds (VOCs) of quinoa and germinated quinoa roasted at 160 °C for 15 min were determined using headspace-gas chromatography-ion mobility spectrometry (HS-GC-IMS) and headspace solid-phase microextraction gas chromatography–mass spectrometry (HS-SPME-GC–MS), respectively. Germination and roasting effectively reduced the contents of VOCs that produced undesirable flavor. Moreover, germination improved the floral aromas, while roasting mainly produced caramel, cocoa, and roasted nut aromas of quinoa. This study indicated that germination and roasting treatments might serve as promising processing methods to improve the flavor of quinoa.

To study the formation and transformation mechanism of long-period stacked ordered (LPSO) structures, a systematic atomic scale analysis was conducted for the structural evolution of long-period stacked ordered (LPSO) structures in the Mg-Gd-Y-Zn-Zr alloy annealed at 300 °C∼500 °C. Various types of metastable LPSO building block clusters were found to exist in alloy structures at different temperatures, which precipitate during the solidification and homogenization process. The stability of Zn/Y clusters is explained by the first principles of density functional theory. The LPSO structure is distinguished by the arrangement of its different Zn/Y enriched LPSO structural units, which comprises local fcc stacking sequences upon a tightly packed plane. The presence of solute atoms causes local lattice distortion, thereby enabling the rearrangement of Mg atoms in the different configurations in the local lattice, and local HCP-FCC transitions occur between Mg and Zn atoms occupying the nearest neighbor positions. This finding indicates that LPSO structures can generate necessary Schockley partial dislocations on specific slip surfaces, providing direct evidence of the transition from 18R to 14H. Growth of the LPSO, devoid of any defects and non-coherent interfaces, was observed separately from other precipitated phases. As a result, the precipitation sequence of LPSO in the solidification stage was as follows: Zn/Ycluster+Mg layers→various metastable LPSO building block clusters→18R/24R LPSO; whereas the precipitation sequence of LPSO during homogenization treatment was observed to be as follows: 18R LPSO→various metastable LPSO building block clusters→14H LPSO. Of these, 14H LPSO was found to be the most thermodynamically stable structure.

Abstract The present study utilized the National Health and Nutrition Examination Survey (NHANES) database to examine the relationship between serum levels of heavy metals and Diabetic retinopathy (DR) in individuals aged over 30 years with type 2 diabetes mellitus (T2DM) in the United States. A cross-sectional analysis was conducted on 1583 individuals with T2DM from the NHANES 2011–2020, including 331 individuals in the DR group and 1252 individuals in the non-DR group. We collected data on serum levels of heavy metals, DR, and serum albumin for descriptive statistics, linear regression, and logistical regression analysis. After adjusting for age, gender, race and other factors, there was no statistically significant association between blood cadmium, selenium, mercury, or lead and DR. However, serum manganese (Mn) and DR had a significant negative association (β = − 0.2045, 95% CI = − 0.3484, − 0.0606). Serum albumin partially modulated the indirect influence of serum Mn on the incidence of DR, accounting for 12.80% of the association between serum Mn and DR. There was a negative association between serum Mn levels and the prevalence of DR in people with T2DM. Mn intake at least in this study has a little influence on the onset and development of DR.

In the air combat process, confrontation position is the critical factor to determine the confrontation situation, attack effect and escape probability of UAVs. Therefore, selecting the optimal confrontation position becomes the primary goal of maneuver decision-making. By taking the position as the UAV's maneuver strategy, this paper constructs the optimal confrontation position selecting games (OCPSGs) model. In the OCPSGs model, the payoff function of each UAV is defined by the difference between the comprehensive advantages of both sides, and the strategy space of each UAV at every step is defined by its accessible space determined by the maneuverability. Then we design the limit approximation of mixed strategy Nash equilibrium (LAMSNQ) algorithm, which provides a method to determine the optimal probability distribution of positions in the strategy space. In the simulation phase, we assume the motions on three directions are independent and the strategy space is a cuboid to simplify the model. Several simulations are performed to verify the feasibility, effectiveness and stability of the algorithm.

Abstract Acute kidney injury (AKI) is a common kidney disease associated with excessive reactive oxygen species (ROS). Unfortunately, due to the low kidney targeting and undesired side effects, the existing antioxidant and anti-inflammatory drugs are unavailable for AKI management in clinic. Therefore, it’s essential to develop effective nanodrugs with high renal targeting and biocompatibility for AKI treatment. Herein, we reported a novel nanodrug for AKI treatment, utilizing poly(ursolic acid) (PUA) as a bioactive nanocarrier and resveratrol (RES) as a model drug. The PUA polymer was synthesized form ursolic acid with intrinsic antioxidant and anti-inflammatory activities, and successfully encapsulated RES through a nanoprecipitation method. Subsequently, we systemically investigated the therapeutic potential of RES-loaded PUA nanoparticles (PUA NPs@RES) against AKI. In vitro results demonstrated that PUA NPs@RES effectively scavenged ROS and provided substantial protection against H2O2-induced cellular damage. In vivo studies revealed that PUA NPs significantly improved drug accumulation in the kidneys and exhibited favorable biocompatibility. Furthermore, PUA NPs alone exhibited additional anti-inflammatory and antioxidant effect, synergistically enhancing therapeutic efficacy in AKI mouse models when combined with RES. Overall, our study successfully developed an effective nanodrug using self-therapeutic nanocarriers, presenting a promising option for the treatment of AKI. Graphical abstract

Mobile laser scanning (MLS) has emerged as a pivotal tool for accurately collecting tunnel point cloud data and enabling the detection of tunnel deformation. This study introduces a novel approach for the precise monitoring of tunnel cross-section deformation, a critical factor in assessing stability and lining safety. The MLS system used in this study is the Self-mobile Intelligent Laser Scanning System (SILSS) for data acquisition. A comparison with corresponding data acquired by Leica P16 demonstrates that the data collected by SILSS are accurate. The methodology developed utilizes ellipticity parameters and deformation analysis indices based on the ellipse-fitting analysis of circular shield tunnel deformation. A key innovation is the robust denoising of data using the Random Sample Consensus (RANSAC) method, ensuring accurate ellipse fitting and extraction of tunnel lining. Subsequently, an algorithm segmented the tunnel cross-section lining into individual shield tunnels, enabling the calculation of ellipticity parameters for shield tunnels, which are the objects for deformation analysis. The experimental results underscore the novelty and effectiveness of this approach in monitoring deformation across different indices. The method proves to be a reliable tool for assessing tunnel health, providing a detailed evaluation of the cross-section’s condition through statistical and graphical visualization. This study significantly advances shield tunnel monitoring, offering a practical and precise methodology for tunnel deformation analysis based on MLS point cloud data.

The growing global prevalence of chronic diseases has highlighted the limitations of conventional drug delivery methods, which often suffer from non-specific distribution, systemic toxicity, and poor bioavailability. Microscale and nanoscale materials have emerged as innovative solutions, offering enhanced targeting, controlled release, and the convergence of therapeutic and diagnostic functions, referred to as theranostics. This review explores the design principles, mechanisms of action, and clinical applications of various novel micro- and nanomaterials in diseases such as cancer, cardiovascular disorders, and infectious diseases. These materials enable real-time monitoring of therapeutic responses and facilitate precision medicine approaches. Additionally, this paper addresses the significant challenges hindering clinical translation, including biocompatibility, potential toxicity, and regulatory issues. Ongoing clinical trials demonstrate the potential of nanomaterials in theranostic applications, but further research is needed to overcome the barriers to widespread clinical adoption. This work aims to contribute to the acceleration of integrating nanomedicine into clinical practice, ultimately enhancing the efficacy and safety of therapeutic interventions.

Objective Preemptive multimodal analgesia is a frequently utilized method for controlling pain after total knee arthroplasty (TKA). So far, no studies have specifically examined the efficacy of adding acetaminophen to preemptive multimodal analgesia in TKA. The current work aimed to assess the efficacy of adding acetaminophen to preemptive multimodal analgesia for clinical pain management after TKA. Methods This was a double‐blinded randomized study including 80 cases randomized to the acetaminophen and control groups, respectively. The acetaminophen group was administered celecoxib at 400 mg, pregabalin at 150 mg, and acetaminophen at 300 mg 2 h before TKA. Control patients were administered celecoxib, pregabalin, and placebo. The primary outcome was postsurgical use of morphine hydrochloride for rescue analgesia. Secondary outcomes included the time to the initial rescue analgesia, postsurgical pain as determined by a visual analogue scale (VAS), functional recovery as reflected by the range of knee motion and ambulation distance, hospitalization duration, and complication rates. Continuous data with normal and skewed distributions were compared by the Student's t test and the Mann–Whitney U test, respectively. Categorical variables were compared by the Pearson's chi‐squared test. Results The control and acetaminophen groups were comparable in postoperative 0–24 h morphine consumption (11.3 ± 6.5 mg vs 12.3 ± 7.7 mg, P = 0.445) and total morphine consumption (17.3 ± 10.1 mg vs 19.3 ± 9.4 mg, P = 0.242). Additionally, time to the initial rescue analgesia, postoperative VAS score at any time point, postoperative functional recovery of the knee, and hospitalization duration were similar in both groups. Both groups also had similar occurrence rates of postoperative complications. Conclusions In this study, adding acetaminophen to preoperative preemptive multimodal analgesia did not decrease postoperative morphine use or ameliorate pain relief. The efficacy of adding acetaminophen to preemptive multimodal analgesia in TKA need to be further explored in future studies.

The bi-level programming coupling model of uncertainty constraints and interval parameter programming is developed to optimize the allocation of water resources and conduct a comprehensive analysis of water resource carrying capacity. The model uses an uncertainty credibility number set and interval value to deal with uncertain factors, and analyses the water resources allocation of Longchuan River in central Yunnan. The competition mechanism and polynomial variation improved algorithm are used to analyze the water consumption, economic benefits and satisfaction in different planning periods when λ = 0.7, 0.8, 0.9, 1.0. The results show that the uncertain bi-level coupling model can cause changes in water allocation, pollutant discharge, system efficiency, etc., and can also effectively balance the mutual constraints between economic benefits and environmental pollution discharge, ensuring a good development trend in the planning year. The water diversion from other basins such as the Central Yunnan Water Diversion Project was transferred to Longchuan River Basin to increase the water supply, and the carrying capacity was further improved, with an increase of water resources by 25.9%. The model research has certain practical and strategic significance for maintaining the sustainable development of the ecological environment in the Longchuan River Basin HIGHLIGHTS A bi-level programming coupling model of uncertainty-constrained programming and interval parameter programming is established.; Competition mechanism and polynomial mutation improved algorithm is introduced.; Select typical watersheds in central Yunnan, China, and solve the optimization model.; Through the comprehensive analysis of water resources carrying capacity, the ideal evaluation results are obtained.;

Summary: The role of neutrophils in tumor initiation stage is rarely reported because of the lack of suitable models. We found that neutrophils recruited in early tumor nodules induced by subcutaneous inoculation of B16 melanoma cells were able to attack tumor cells by trogocytosis. The anti-tumor immunotherapy like peritoneal injection with TLR9 agonist CpG oligodeoxynucleotide combined with transforming growth factor β2 inhibitor TIO3 could increase the trogocytic neutrophils in the nodules, as well as CD8+ T cells, natural killer (NK) cells, and their interferon-γ production. Local use of Cxcl2 small interfering RNA significantly reduced the number of neutrophils and trogocytic neutrophils in tumor nodules, as well as CD8+ T and NK cells, and also enlarged the nodules. These results suggest that neutrophils recruited early to the inoculation site of tumor cells are conducive to the establishment of anti-tumor immune microenvironment. Our findings provide a useful model system for studying the effect of neutrophils on tumors and anti-tumor immunotherapy.

BackgroundEchinococcosis is a natural focal, highly prevalent disease in China. Factors influencing the spread of echinococcosis are not only related to personal exposure but also closely related to the environment itself. The purpose of this study was to explore the influence of environmental factors on the prevalence of human echinococcosis and to provide a reference for prevention and control of echinococcosis in the future.MethodsData were collected from 370 endemic counties in China in 2018. By downloading Modis, DEM and other remote-sensing images in 2018. Data on environmental factors, i.e., elevation, land surface temperature (LST) and normalized difference vegetation index (NDVI) were collected. Rank correlation analysis was conducted between each environmental factor and the prevalence of echinococcosis at the county level. Negative binomial regression was used to analyze the impact of environmental factors on the prevalence of human echinococcosis at the county level.ResultsAccording to rank correlation analysis, the prevalence of human echinococcosis in each county was positively correlated with elevation, negatively correlated with LST, and negatively correlated with NDVI in May, June and July. Negative binomial regression showed that the prevalence of human echinococcosis was negatively correlated with annual LST and summer NDVI, and positively correlated with average elevation and dog infection rate. The prevalence of human cystic echinococcosis was inversely correlated with the annual average LST, and positively correlated with both the average elevation and the prevalence rate of domestic animals. The prevalence of human alveolar echinococcosis was positively correlated with both NDVI in autumn and average elevation, and negatively correlated with NDVI in winter.ConclusionThe prevalence of echinococcosis in the population is affected by environmental factors. Environmental risk assessment and prediction can be conducted in order to rationally allocate health resources and improve both prevention and control efficiency of echinococcosis.

Controllable contraception in male animals was demonstrated through the utilization of gold nanorods' photothermal effect to accomplish mild testicular hyperthermia. However, the challenges arising from testicular administration and the non-biodegradability of nanoparticles hinder further clinical implementation. Therefore, a straightforward, non-invasive, and enhanced contraception approach is required. This study explores the utilization of human heavy chain ferritin (HFn) nanocarriers loaded with aggregation-induced emission luminogens (AIEgens) for noninvasive, controllable male contraception guided by Near-Infrared-II (NIR-II) fluorescence imaging. The HFn-caged AIEgens (HFn@BBT) are delivered via intravenous injection and activated by near-infrared irradiation. Lower hyperthermia treatment induces partial damage to the testes and seminiferous tubules, reducing fertility indices by approximately 100% on the 7th day, which gradually recovers to 80% on the 60th day. Conversely, implementation of elevated hyperthermia therapy causes total destruction of both testes and seminiferous tubules, leading to a complete loss of fertility on the 60th day. Additionally, the use of AIEgens in NIR-II imaging offers improved fluorescence efficiency and penetration depth. The findings of this study hold significant promise for the advancement of safe and effective male contraceptive methods, addressing the need for noninvasive and controllable approaches to reproductive health and population control.

Abstract Previously a ring finger protein 20 (RNF20) is found to be essential for meiotic recombination and mediates H2B ubiquitination during spermatogenesis. However, its role in meiotic division is still unknown. Here, it is shown that RNF20 is localized at both centromeres and spindle poles, and it is required for oocyte acentrosomal spindle organization and female fertility. RNF20‐depleted oocytes exhibit severely abnormal spindle and chromosome misalignment caused by defective bipolar organization. Notably, it is found that the function of RNF20 in spindle assembly is not dependent on its E3 ligase activity. Instead, RNF20 regulates spindle assembly by recruiting tropomyosin3 (TPM3) to both centromeres and spindle poles with its coiled‐coil motif. The RNF20‐TPM3 interaction is essential for acentrosomal meiotic spindle assembly. Together, the studies uncover a novel function for RNF20 in mediating TPM3 recruitment to both centromeres and spindle poles during oocyte spindle assembly.

Backgroud: The co-administration of Chinese patent medicine with calcium channel blockers (CCBs) is a prevalent practice in China for treating essential hypertension (EH). However, robust evidence supporting the efficacy and safety of tailored combinations of different Chinese patent medicines with CCBs, according to individual patient conditions, is still limited. This study sought to elucidate the efficacy and safety of these combinations using a systematic review and network meta-analysis.Materials and methods: Relevant studies were sourced from established databases, incorporating randomized controlled trials published up to 1 February 2023. The ROB2 tool from the Cochrane Collaborative Network was employed to independently assess and cross-verify the quality of the included literature. A network meta-analysis was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) 2020 and PRISMA-Network Meta-Analyses (PRISMA-NMA) guidelines. A Bayesian network meta-analysis was utilized to gauge the efficacy and safety of distinct integrations of Chinese patent medicine and CCBs. Primary outcomes were interpreted using a paired fixed-effect meta-analysis. Publication bias was appraised through Egger’s test and represented with funnel plots. All statistical analyses were executed within the R statistical framework.Results: Following rigorous selection, data extraction, and bias evaluation, 36 articles were incorporated. Tianma Gouteng Granule, when combined with CCBs, displayed superior efficacy in reducing systolic blood pressure (SBP). In terms of diastolic blood pressure (DBP) reduction, Songling Xuemaikang Capsule combined with CCBs emerged as the most effective. Regarding enhancement of antihypertensive effective rates, Qinggan Jiangya Capsule paired with CCBs demonstrated optimal results. For diminishing Traditional Chinese Medicine syndrome scores, the Qiangli Dingxuan Tablet and CCBs combination proved most beneficial. When aiming to reduce total cholesterol (TC), triglycerides (TG), and low-density lipoprotein cholesterol (LDL-C) levels, Tianma Gouteng Granule and CCBs showcased superior results. In contrast, the combination of Songling Xuemaikang Capsule and CCBs was more effective in reducing LDL-C, tumor necrosis factor-alpha (TNF-α), and interleukin-6 (IL-6).Conclusion: This study underscores variability in outcomes from combining Chinese patent medicine and CCBs for hypertension, emphasizing the importance of personalized medicinal combinations, especially Tianma Gouteng Granule and Songling Xuemaikang Capsule. The results offer robust evidence to inform clinical guidelines for essential hypertention and significantly aid clinician in seleting appropriate Chinese patent medicines for treatment.

Abstract Hyperuricemia (HUA) makes a chronic inflammation status, which affects immune cells. The association between HUA and immune cells, such as monocytes and neutrophils, has been extensively studied. However, studies on HUA and lymphocytes are still limited. We selected 1543 healthy participants and 258 individuals with HUA to analyze the correlation between serum uric acid (SUA) levels and immune cells, and 98 healthy participants and 16 individuals with HUA were used to study the relationship between SUA levels and cytokine levels. Then, we used soluble UA to stimulate peripheral blood mononuclear cells in vitro and examined lymphocyte subset counts and activation by flow cytometry. The results revealed that the number of lymphocytes in the HUA group was significantly increased, particularly CD4+ T cell numbers, which were higher than those in the total population (P = 0.0019), females (P = 0.0142), and males (P = 0.0199) of the healthy control group. Concomitantly, interleukin (IL)-4 and IL-10 levels significantly increased in people with HUA (P = 0.0254; P = 0.0019). In vitro, soluble UA promoted the proliferation and activation of CD4+ T and CD19+ B cells. Thus, HUA is accompanied by elevated peripheral CD4+ T cells and may cause a Th2-dominant immune status.

Objectives Pericapsular nerve group (PENG) blocking is a novel nerve block modality for analgesia after total hip arthroplasty (THA); however, its analgesic efficacy is unclear. We aimed to compare the analgesic effect of ultrasound‐guided PENG blocking and periarticular local infiltration analgesia after THA. Methods This study involved patients undergoing unilateral primary THA at our institution between October 2022 and December 2022. Based on a prospective double‐blind, randomized approach, patients were randomly divided into two groups: the PENG and infiltration groups. The former received ultrasound‐guided pericapsular nerve block before surgery while the latter received local anesthesia and local infiltration analgesia during surgery. The primary outcome was the amount of morphine used for rescue analgesia within 48 h after surgery and the visual analog scale (VAS) pain score at 3, 6, 12, 24, and 48 h after surgery. Secondary outcomes consisted of postoperative hip function on the first and second postoperative days, including hip extension angle and flexion, as well as distance traveled by the patient. Tertiary outcomes included length of hospital stay and postoperative adverse reactions. The data were analyzed using SPSS 26.0. Using the appropriate statistical methodology, continuous and categorical data were analyzed, and p 0.05). However, the exercise VAS score in the PENG group was significantly higher than that in the infiltration group within 12 hours after surgery (6.1 + 1.2 vs. 5.4 + 1.0, p = 0.008). There was no significant difference in hip function, length of hospital stay, or incidence of complications between the two groups. Conclusion The analgesic effect and functional recovery of ultrasound‐guided pericapsular nerve block for THA was not superior to that of periarticular local infiltration analgesia.

Low-molecular-weight (LMW, wa (weighted average of O/C) and low H/Cwa. Conversely, such dialysates had numerous aliphatic chains with high H/Cwa and low O/Cwa compared to SRFA. In particular, LMW-DOM below 200 Da was identified by Orbitrap MS. This work provides an operational program for identifying LMW-DOM based on the SRFA standard and MS analysis.

Background: With the increasing global prevalence of hypertension, a condition that can severely affect multiple organs, there is a growing need for effective treatment options. Uncaria rhynchophylla-Alisma plantago-aquatica L. (UR-AP) is a traditional drug pair used for treating hypertension based on the liver-kidney synergy concept. However, the detailed molecular mechanisms underlying its efficacy remain unclear.Methods: This study utilized an integrative approach combining network pharmacology, cluster analysis, and molecular docking to uncover the bioactive components and targets of UR-AP in the treatment of hypertension. Initially, we extracted data from public databases to identify these components and targets. A Protein-Protein Interaction (PPI) network was constructed, followed by enrichment analysis to pinpoint the bioactive components, core targets, and pivotal pathways. Cluster analysis helped in identifying key sub-networks and hypothesizing primary targets. Furthermore, molecular docking was conducted to validate the interaction between the core targets and major bioactive components, thus confirming their potential efficacy in hypertension treatment.Results: Network pharmacological analysis identified 58 bioactive compounds in UR-AP, notably quercetin, kaempferol, beta-sitosterol (from Uncaria rhynchophylla), and Alisol B, alisol B 23-acetate (from Alisma plantago-aquatica L.), as pivotal bioactives. We pinpointed 143 targets common to both UR-AP and hypertension, highlighting MAPK1, IL6, AKT1, VEGFA, EGFR, and TP53 as central targets involved in key pathways like diastolic and endothelial function, anti-atherosclerosis, AGE-RAGE signaling, and calcium signaling. Cluster analysis emphasized IL6, TNF, AKT1, and VEGFA’s roles in atherosclerosis and inflammation. Molecular docking confirmed strong interactions between these targets and UR-AP’s main bioactives, underscoring their therapeutic potential.Conclusion: This research delineates UR-AP’s pharmacological profile in hypertension treatment, linking traditional medicine with modern pharmacology. It highlights key bioactive components and their interactions with principal targets, suggesting UR-AP’s potential as a novel therapeutic option for hypertension. The evidence from molecular docking studies supports these interactions, indicating the relevance of these components in affecting hypertension pathways. However, the study acknowledges its limitations, including the reliance on in silico analyses and the need for in vivo validation. These findings pave the way for future clinical research, aiming to integrate traditional medicine insights with contemporary scientific approaches for developing innovative hypertension therapies.

Background and study aimThe klotho protein, a multifunctional protein, has been shown to be associated with a wide range of endocrine diseases and has been linked to thyroid tumourigenesis. However, the relationship between serum klotho levels and thyroid hormones remains poorly understood. This study aimed to explore the correlation between serum klotho levels and thyroid hormones.MethodsData was obtained from the NHANES cycles 2007-2008, 2009-2010, and 2011-2012. A total of 4674 participants were recruited for this study. Statistical analysis was using multiple linear regression analyses, and restricted cubic spline plots (RCS) to investigate the association between serum klotho levels and serum levels of thyroid hormones.ResultsIn the unadjusted covariate model, ln(klotho) significantly positively correlated with tT3, tT4, fT3, tT4/fT4, and tT3/fT3 (all PConclusionThere is an L-shaped nonlinear relationship between ln(klotho) and fT3, tT3, suggesting that klotho could be involved in the physiological regulation of thyroid function.

Leaf functional traits play critical roles in plant functioning. Although the functional traits of overstory trees have been extensively studied, minimal research has been conducted regarding understory species, despite the understory layer is an important component of temperate forests. Such insufficiency limit the broader understanding of processes and functions in forest ecosystems, particularly when under the increasing atmospheric nitrogen (N) deposition. Here, we investigated the responses of 18 leaf functional traits in six understory herbaceous species within young and mature stands (three species per stand) in larch (Larix principis-rupprechtii) plantations that subjected to 12 years of anthropogenic N addition. We found that N addition did not significantly impact the photosynthetic traits of understory herbaceous species in either stand; it only led to increased chlorophyll content in Geum aleppicum Jacq. Similarly, with the exception of decreases in the predawn leaf water potential of Sanguisorba officinalis L., N addition did not significantly affect leaf hydraulic traits. With the exception of changes to adaxial epidermis thickness in Potentilla chinensis Ser. (decreased) and G. aleppicum (increased), N addition had negligible effects on leaf anatomical traits and specific leaf area, however, interspecific variations in the plasticity of leaf anatomical traits were observed. Stable responses to N addition were also observed for nonstructural carbohydrates (NSC) and their components (soluble sugars and starch), with the exception of Polygonum divaricatum L., which exhibited increases in NSC. Overall, our results suggest that the functional traits of understory herbaceous species exhibit stability under conditions of long-term N enrichment in temperate plantations.

Abstract Colon-targeted oral drug delivery systems (CDDSs) are desirable for the treatment of ulcerative colitis (UC), which is a disease with high relapse and remission rates associated with immune system inflammation and dysregulation localized within the lining of the large bowel. However, the success of current available approaches used for colon-targeted therapy is limited. Budesonide (BUD) is a corticosteroid drug, and its rectal and oral formulations are used to treat UC, but the inconvenience of rectal administration and the systemic toxicity of oral administration restrict its long-term use. In this study, we designed and prepared colon-targeted solid lipid nanoparticles (SLNs) encapsulating BUD to treat UC by oral administration. A negatively charged surfactant (NaCS-C12) was synthesized to anchor cellulase-responsive layers consisting of polyelectrolyte complexes (PECs) formed by negatively charged NaCS and cationic chitosan onto the SLNs. The release rate and colon-specific release behavior of BUD could be easily modified by regulating the number of coated layers. We found that the two-layer BUD-loaded SLNs (SLN-BUD-2L) with a nanoscale particle size and negative zeta potential showed the designed colon-specific drug release profile in response to localized high cellulase activity. In addition, SLN-BUD-2L exhibited excellent anti-inflammatory activity in a dextran sulfate sodium (DSS)-induced colitis mouse model, suggesting its potential anti-UC applications.

Abstract Background Meiotic recombination is initiated by Spo11-dependent programmed DNA double-strand breaks (DSBs) that are preferentially concentrated within genomic regions called hotspots; however, the factor(s) that specify the positions of meiotic DSB hotspots remain unclear. Results Here, we examined the frequency and distribution of R-loops, a type of functional chromatin structure comprising single-stranded DNA and a DNA:RNA hybrid, during budding yeast meiosis and found that the R-loops were changed dramatically throughout meiosis. We detected the formation of multiple de novo R-loops in the pachytene stage and found that these R-loops were associated with meiotic recombination during yeast meiosis. We show that transcription-replication head-on collisions could promote R-loop formation during meiotic DNA replication, and these R-loops are associated with Spo11. Furthermore, meiotic recombination hotspots can be eliminated by reversing the direction of transcription or replication, and reversing both of these directions can reconstitute the hotspots. Conclusions Our study reveals that R-loops may play dual roles in meiotic recombination. In addition to participation in meiotic DSB processing, some meiotic DSB hotspots may be originated from the transcription-replication head-on collisions during meiotic DNA replication.

Abstract Background Although vaccination is one of the critical interventions to address global health issues, inadequate vaccination rates has become an international challenge. Vaccine hesitancy is the key to affecting inadequate vaccination rates. According to the WHO SAGE working group’s definition, vaccine hesitancy refers to delaying or refusing vaccination and has been ranked as one of the top 10 health threats. There has yet to be a scale that evaluates vaccination attitudes among Chinese adults. However, an attitude quantity, the adult vaccination attitude scale, has been developed to assess adult vaccination attitudes and reasons for vaccine hesitancy. Objective The Adult Attitudes to Vaccination Scale (ATAVAC) was initially developed by Professor Zoi Tsimtsiou et al. This study aimed to analyze the structure of the Chinese version of the ATAVAC and explore the relationship between adult vaccination attitudes, e-health literacy, and medical distrust. Methods After obtaining author permission for the initial scales, the study was translated using the Brislin back-translation method. 693 adults were enrolled to the study. To validate this hypothesis, participants finished the socio-demographic questionnaire, the Chinese version of the ATAVAC, the electronic Health Literacy Scale (e-HEALS) and the Medical Mistrust Index (MMI). The exploratory factor analysis (EFA) and confirmatory factor analysis (CFA) were used to examine the underlying structure of the factors of the Chinese version of the Adult Vaccination Attitude Scale and to measure its reliability and validity. Results The Cronbach’s alpha coefficient for the Chinese version of the ATAVAC was 0.885, with Cronbach’s alpha coefficients ranging from 0.850 to 0.958 for each dimension. The content validity index was 0.90, and the retest reliability was 0.943. The exploratory factor analysis (EFA) supported the 3-factor structure of the translation instrument, and the scale had good discriminant validity. The confirmatory factor analysis (CFA) revealed a degree of freedom of 1.219, a model fit index (GFI) of 0.979, a normative fit index (NFI) of 0.991, a Tucker-Lewis index (TLI) of 0.998, a comparability index (CFI) of 0.998 and a root mean square error of approximation (RMSEA) of 0.026. Conclusion The results show that the Chinese version of the ATAVAC has demonstrated good reliability and validity. Hence, it can be used as an effective tool to assess vaccination attitudes among Chinese adults.

Background During the promotion of category-based management for community healthcare institutions (class 1 institutions obtain the financial security, and class 2 institutions implement a performance management system), how to appropriately determine the security level and scientifically evaluate the performance is a difficulty to tackle for health administrative departments. Objective To assess the operational efficiency of community healthcare institutions with the data envelopment analysis (DEA) using the information of costs of these institutions calculated using the equivalent method, then attempt to develop an input and management model of integrating cost accounting and performance management for these institutions, providing a theoretical basis for accurate and scientific input of various resources into the community through cost measurement with equivalent method, and a data basis for performance assessment in communities with different characteristics through efficiency evaluation. Methods The real data (financial status and staffing) of 14 community healthcare institutions during 2019 to 2020 were collected from their financial reports, hospital information system, maternal and child healthcare information system, chronic disease management information system, as well as focus group interviews. The equivalent method was used to calculate the total costs of medical services and public health services. The super-efficiency DEA was used to evaluate and analyze the operational efficiency of the 14 sample institutions. Results (1) The average cost of one equivalent service (a general medical outpatient service lasting for 15 minutes was defined as one standard service equivalent unit) was 67.64 yuan in 2019 and 69.80 yuan in 2020 for the 14 institutions. The average cost of one equivalent essential medical service was higher than that of one equivalent public health service in both 2019 (167.14 yuan vs 18.86 yuan) and 2020 (215.43 yuan vs 19.78 yuan). The institutions demonstrated significant differences in the average cost of one equivalent essential medical service and the average cost of one equivalent public health service. (2) Each institution had its own peculiar characteristics. For example, S1 institution mainly provided essential medical services, and had higher total equivalent essential medical services and efficiency than other institutions, while S9 institution focused on providing public health services, and had the highest efficiency in delivering public health services. (3) In 2020, the 14 institutions provided 134 800 equivalent COVID-19-related services, with a cost of 1.037 8 million yuan. (4) In 2019 and 2020, only two institutions were relatively overall efficient, and ≥50.0% institutions were pure technically efficient. The institutions with overall operational inefficiency were mainly caused by scale inefficiency primarily due to increasing returns to scale. Conclusion The equivalent method provides a relatively unified "scale" to standardize the service efficiency of different types of community healthcare institutions, provides support for health administrative departments implementing category-based compensation for the institutions, benefiting the featured and high-level development of community healthcare institutions. Either institutions delivering essential medical services or those delivering public health services, mainly present increasing returns to scale, suggesting that the efficiency of these institutions can be improved by increasing the human/financial/material input into the institutions and providing precise compensation for them.

Abstract Background To investigate whether adding magnesium sulfate to a periarticular infiltration analgesia (PIA) cocktail could improve pain control and functional outcomes in patients undergoing total knee arthroplasty (TKA). Methods Ninety patients were randomly assigned to the magnesium sulfate and control groups, with 45 patients in each group. In the magnesium sulfate group, patients were given a periarticular infusion of a cocktail of analgesics consisting of epinephrine, ropivacaine, magnesium sulfate, and dexamethasone. The control group received no magnesium sulfate. The primary outcomes consisted of visual analogue scale (VAS) pain scores, postoperative morphine hydrochloride consumption for rescue analgesia, and time to first rescue analgesia. Secondary outcomes were postoperative inflammatory biomarkers (IL-6 and CRP), postoperative length of stay, and knee functional recovery (assessed by knee range of motion, quadriceps strength, daily mobilization distance, and time to first straight-leg raising). Tertiary outcomes included the postoperative swelling ratio and complication rates. Results Within 24 h of surgery, patients in the magnesium sulfate group had markedly lower VAS pain scores during motion and at rest. After the addition of magnesium sulfate, the analgesic effect was dramatically prolonged, leading to a reduction in morphine dosage within 24 h and the total morphine dosage postoperatively. Postoperative inflammatory biomarker levels were significantly reduced in the magnesium sulfate group compared with the control. There were no considerable differences between the groups in terms of the postoperative length of stay and knee functional recovery. Both groups had similar postoperative swelling ratios and incidences of complications. Conclusions The addition of magnesium sulfate to the analgesic cocktail for PIA can prolong postoperative analgesia, decrease the consumption of opioids, and effectively alleviate early postoperative pain after TKA. Trial registration: Chinese Clinical Trial Registry, ChiCTR2200056549. Registered on 7 February 2022, https://www.chictr.org.cn/showproj.aspx?proj=151489 .

Abstract Aims/Introduction In this study, we aimed to investigate the relationships between gamma‐glutamyl transferase (GGT) and fasting blood glucose (FBG) during a 6‐year follow‐up study of participants, and to determine whether GGT is a risk factor for FBG. Materials and Methods A total of 1,369 individuals from the health examination survey in the urban area of Xuzhou, central China, were followed up for 6 years. The patients were divided into four groups based on their baseline GGT levels (in quartiles). The one‐way analysis of variance (anova) method was used to compare the differences between the variables and baseline. The relationship between GGT and FBG levels was investigated using repeated measurements anova. Results The grouping of baseline GGT levels affected the changes in blood glucose during the 6‐year follow‐up study. In the GGT quartile subgroups, the annual mean increase in FBG levels showed a positive relationship with baseline GGT levels. This trend was even more aggregated in the highest baseline GGT group. Interactions among time course, baseline FBG and GGT groups in different participants together affected the change of FBG levels during the follow‐up period. The repeated measures anova suggested that different baseline GGT groups were still significantly associated with increased FBG levels. GGT is a risk factor that affects FBG levels(P

Abstract Purpose Despite the poor prognosis of triple-negative breast cancer (TNBC), it has been demonstrated that neoadjuvant immunotherapy in combination with chemotherapy can improve the pathologic complete response (pCR) rate and/or long-term outcome of TNBC. However, there have been no real-world studies reporting on the effectiveness of neoadjuvant checkpoint inhibitors in early TNBC. Methods Between November 2019 and December 2021, 63 early TNBC patients treated with anti-PD-1 antibodies (pembrolizumab or camrelizumab) or anti-PD-L1 antibody (atezolizumab) in combination with chemotherapy at seven institutions were included. PCR1 defined as ypT0/Tis and ypN0 was the primary endpoint. Secondary endpoints included pCR2 defined as ypT0/Tis, overall response rate (ORR), disease-free survival (DFS), drug-related adverse events (AEs) and biomarkers. Results Among the patients in the current study, 34.9% of patients were able to achieve pCR1, and 47.6% of patients had achieved pCR2. The ORR was 82.5%. 33 patients with non-pCR2 tumors were found to have a median DFS of 20.7 months (95% CI 16.3 months-not reached). The DFS of patients with pCR2 and non-pCR2 after neoadjuvant therapy was significantly different (HR = 0.28, 95% CI 0.10–0.79; P = 0.038). The most common AEs were nausea (63.4%), fatigue (42.7%), leucopenia (30.0%) and elevated transaminase (11.7%). Conclusion It is possible to achieve a meaningful pCR rate and DFS by combining neoadjuvant checkpoint blockade with chemotherapy in patients with high-risk TNBC. Compared to clinical trials, however, there was a slightly lower pCR rate in this multicentered real-world study.

Infertility affects 10%–20% of the population in most countries, with approximately half of those cases resulting from male infertility. Although millions of infertile men are able to have children with the assistance of reproductive technology, individuals with non-obstructive azoospermia (NOA) syndrome are unable to do so because they lack functional sperm. Therefore, some other strategies for infertile NOA men are still urgently needed. Our current study uses an NOA-like mouse model to optimize microinjection and a subsequent electroporation method to test potential treatment strategies. We showed that the spermatogenetic process could be partially rescued in young Stra8-Rnf20−/− mice with microinjection and subsequent electroporation of Rnf20 plasmids into the testes. All meiotic prophase I stages could be identified, and programmed DNA double-strand break repair factors could successfully be recruited to Stra8-Rnf20−/− spermatocytes after electroporation. Moreover, by including an autophagy inhibitor in the treatment, electroporation significantly improved the spermatogenetic rescue efficiency of adult Stra8-Rnf20−/− mice. Most importantly, infertility caused by Rnf20 depletions could be overcome by electroporation coupled with intracytoplasmic sperm injection. Our studies establish a relative safe and efficient testis electroporation system and provide a promising therapeutic strategy for patients with NOA.

Background Obstructive sleep apnoea (OSA) is the most common sleep-related breathing disorder, yet it remains undiagnosed in a large proportion of adults.Objective This study aims to investigate the status of patient delay and provider delay in OSA patients and examine related factors affecting patient delay in OSA individuals in China.Methods A cross-sectional design was conducted on a sample of 309 OSA patients (aged from 18 to 76, median age of 47 years, 84.8% male) in Northeast China. Participants were required to complete the sociodemographic questionnaire, the symptom characteristics questionnaire, the help-seeking attitude scale (HSAS), the social support rating scale and the chronic disease self-efficacy scales (CDSES) to test the hypothesis. Binary logistic regression analysis was conducted to explore factors that account for the patient delay.Results The median patient delay among OAS patients in this study was 22 months, the median provider delay was one month, and the median total delay was 26 months. As shown by multivariate analysis results, patients who have snored for over 6 years (OR = 3.377, 95%CI: 1.175–9.702) were more likely to experience prolonged patient delays. Per capita monthly family income above 3000 RMB (OR = 0.172, 95%CI: 0.052–0.571), taking up residence in cities or towns (OR = 0.484, 95%CI: 0.248–0.946), higher self-recognition of the disease (OR = 0.793, 95%CI: 0.647–0.972), higher objective support (OR = 0.825, 95%CI: 0.739–0.921) and stronger self-efficacy (OR = 0.674, 95%CI: 0.525–0.867) were significantly associated with shorter patient delays.Conclusion Patient delay is common in Chinese OSA patients. The upstream factors affecting the patient delay in individuals with OSA include income, place of residence, and objective support; midstream factors include self-recognition of the disease and self-efficacy; downstream factors include years of snoring.KEY MESSAGESDespite being a high-prevalence disease, many obstructive sleep apnoea (OSA) patients are not clearly diagnosed and treated.The factors affecting the delay in seeking medical treatment in individuals with OSA included income, place of residence, objective support, self-recognition of the disease, self-efficacy and years of snoring.Investigations into OSA patients’ care-seeking behaviours can better reflect the secondary prevention of OSA, and it is crucial to pay attention to the delayed phase of patients.