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Abstract Background Metabolic abnormalities and immune inflammation are deeply involved in pulmonary vascular remodelling and the development of pulmonary hypertension (PH). However, the regulatory mechanisms of glycolysis in macrophages are still elusive. Cumulative evidence indicates that β-catenin plays a crucial role in metabolic reprogramming. This study aimed to investigate the effect of β-catenin on macrophage glycolysis in PH. Methods LPS-induced BMDMs were generated via in vitro experiments. A monocrotaline (MCT)-induced PH rat model was established, and the β-catenin inhibitor XAV939 was administered in vivo. The role of β-catenin in glycolysis was analysed. The degree of pulmonary vascular remodelling was measured. Results β-catenin was significantly increased in both in vitro and in vivo models. In LPS-induced BMDMs, β-catenin increased the levels of hexokinase 2 (HK2), phosphofructokinase (PFK), M2-pyruvate kinase (PKM2), lactate dehydrogenase (LDH), and lactate (LA) and the expression of inflammatory cytokines and promoted PASMC proliferation and migration in vitro. XAV939 decreased the level of glycolysis and downregulated the expression of inflammatory cytokines in vivo. MCT promoted pulmonary arterial structural remodelling and right ventricular hypertrophy, and XAV939 alleviated these changes. Conclusions Our findings suggest that β-catenin is involved in the development of PH by promoting glycolysis and the inflammatory response in macrophages. Inhibition of β-catenin could improve the progression of PH.

Chronic non-healing wounds induced by oxidative stress and inflammation can activate inflammatory cells and produce large amounts of inflammatory mediators, which fail to maintain homeostasis in the skin and delay the wound-healing process. To tackle this issue, heparin-loaded hierarchical composite scaffolds comprised of electrospun fibers and electrosprayed microspheres were prepared to act as an effective anti-inflammatory wound dressing. Microspheres with different electrosprayed densities were deposited into the surface of the electrospun fibers for the improvement of surface topographical cues and cellular activities. The results indicated that the electrospun fibers followed by electrosprayed for 3 ​min to fabricate the composite fiber/microsphere scaffolds contributed to the best performance in terms of promoting cellular activities, with no obvious cytotoxicity, good adhesion morphology, and the fastest cell migration rate. In addition, a suitable amount of heparin was added to the composite scaffolds to alleviate inflammation. The significant adsorption efficiency of heparin-loaded composite scaffolds on inflammatory mediator MCP-1 indicates a favorable anti-inflammation effect in vitro. Furthermore, the heparin-loaded hierarchical scaffolds accelerated the pace of inflammatory wound healing in vivo when compared to commercial 3 ​M Tegaderm and non-heparin-loaded scaffolds. Our work provided a facile strategy for fabricating heparin-loaded hierarchical fiber/microsphere scaffolds to modulate cellular activities via topographical cues and accelerating the inflammatory wound healing process by electrostatic interactions between heparin and MCP-1. These findings suggested that the heparin-loaded hierarchical scaffold was expected to be a promising dressing for inflammatory wound healing.

Background and objective Bone is a common site for metastasis in lung adenocarcinoma, but the mechanism behind lung adenocarcinoma bone metastasis is still unclear. And currently, there is a lack of easily traceable and stable lung adenocarcinoma bone metastasis cell models, which limits the research on the mechanism of lung adenocarcinoma bone metastasis. The establishment of human lung adenocarcinoma cell line that are highly metastatic to bone, labeled with green fluorescent proteins (GFP) and fireflies luciferase (LUC), along with transcriptomic characterization, would be beneficial for research on lung adenocarcinoma bone metastasis and provide new experimental methods. Methods The human lung adenocarcinoma cell line A549-GFP-LUC was injected into nude mice via the left ventricle to construct a bone metastasis model, and was domesticated in vivo for three consecutive times to obtain the human high bone metastasis lung adenocarcinoma cell line A549-GFP-LUC-BM3; cell counting kit-8 (CCK-8), colony formation assay, scratch wound assays, Transwell assay and Western blot were used to compare the proliferation and invasion abilities of A549-GFP-LUC-BM3 with the parental cells. A549-GFP-LUC-BM3 cells and parental cells were further analyzed by transcriptomic sequencing. Results Human high-bone metastatic lung adenocarcinoma cells A549-GFP-LUC-BM3 was successfully established. Compared to parental cells, this cells exhibited a significantly higher incidence of bone metastasis and enhanced in vitro proliferation, migration, and invasion abilities. Transcriptomic sequencing results revealed that the A549-GFP-LUC-BM3 cell line had 2954 differentially expressed genes compared to the parental cells, with 1021 genes up-regulated and 1933 genes down-regulated. Gene Ontology (GO) functional enrichment analysis indicated that the differentially expressed genes were primarily localized in cellular components such as the cell periphery. The molecular functions identified as significantly enriched included signaling receptor activity, calcium ion binding, and extracellular matrix structural constituent. Additionally, the biological processes found to be enriched were cell adhesion and biological adhesion. The enrichment analysis conducted using the Kyoto Encyclopedia of Genes and Genomes (KEGG) revealed that the differentially expressed genes were primarily involved in the metabolism of xenobiotics by cytochrome P450, retinol metabolism, drug metabolism-cytochrome P450, cell adhesion molecules, steroid hormone biosynthesis, and the nuclear factor kappa B (NF-κB) signaling pathway. Conclusion The highly bone-metastatic human lung adenocarcinoma cell line with GFP and luciferase double labeling was successfully established. The biological behavior and transcriptome sequencing of the cell line suggest that it has a high bone-metastatic potential.

Abstract Trivalent oral poliovirus vaccine (tOPV) has been withdrawn and instead an inactivated poliovirus vaccine (IPV) and bivalent type 1 and type 3 OPV (bOPV) sequential immunization schedule has been implemented since 2016, but no immune persistence data are available for this polio vaccination strategy. This study aimed to assess immune persistence following different polio sequential immunization schedules. Venous blood was collected at 24, 36, and 48 months of age from participants who had completed sequential schedules of combined IPV and OPV in phase III clinical trials. The serum neutralizing antibody titers against poliovirus were determined, and the poliovirus-specific antibody-positive rates were evaluated. A total of 1104 participants were enrolled in this study. The positive rates of poliovirus type 1- and type 3-specific antibodies among the sequential immunization groups showed no significant difference at 24, 36, or 48 months of age. The positive rates of poliovirus type 2-specific antibody in the IPV-IPV-tOPV group at all time points were nearly 100%, which was significantly higher than the corresponding rates in other immunization groups (IPV-bOPV-bOPV and IPV-IPV-bOPV). Immunization schedules involving one or two doses of IPV followed by bOPV failed to maintain a high positive rate for poliovirus type 2-specific antibody.

Abstract The African swine fever virus (ASFV) has caused severe economic losses in the pig industry. To monitor ASFV spread, the p30 protein has been identified as an ideal infection marker due to its early and long-term expression during the ASFV infection period. Timely monitoring of ASFV p30 enables the detection of ASFV infection and assessment of disease progression. Aptamers are an outstanding substitute for antibodies to develop an efficient tool for ASFV p30 protein detection. In this study, a series of aptamer candidates were screened by in vitro magnetic bead-based systematic evolution of ligands by exponential enrichment (MB-SELEX). An aptamer (Atc-20) finally showed high specificity and affinity (Kd = 140 ± 10 pM) against ASFV p30 protein after truncation and affinity assessment. Furthermore, an aptamer/antibody heterogeneous sandwich detection assay was designed based on Atc20, achieving a linear detection of ASFV p30 ranging from 8 to 125 ng/ml and a detection limit (LOD) of 0.61 ng/ml. This assay showed good analytical performances and effectively detected p30 protein in diluted serum samples, presenting promising potential for the development of ASFV biosensors.

Abstract Objectives To determine the value of periportal hyperintensity sign from gadobenate dimeglumine (Gd-BOPTA)-enhanced hepatobiliary phase (HBP) magnetic resonance imaging (MRI) for predicting clinical outcomes in patients with decompensated cirrhosis. Methods A total of 199 cirrhotic patients who underwent Gd-BOPTA-enhanced MRI were divided into control group (n = 56) and decompensated cirrhosis group (n = 143). The presence of periportal hyperintensity sign on HBP MRI was recorded. The Cox regression model was used to investigate the association between periportal hyperintensity sign and clinical outcomes. Results There was a significant difference in the frequency of periportal hyperintensity sign on HBP between compensated and decompensated cirrhotic patients (p < 0.05). After a median follow-up of 29.0 months (range, 1.0–90.0 months), nine out of 143 patients (6.2%) with decompensated cirrhosis died. Periportal hyperintensity sign on HBP MRI was a significant risk factor for death (hazard ratio (HR) = 23.677; 95% confidence interval (CI) = 4.759–117.788; p = 0.0001), with an area under the curve (AUC) of 0.844 (95% CI = 0.774–0.899). Thirty patients (20.9%) developed further decompensation. Periportal hyperintensity sign on HBP MRI was also a significant risk factor for further decompensation (HR = 2.594; 95% CI = 1.140–5.903; p = 0.023). Conclusions Periportal hyperintensity sign from Gd-BOPTA-enhanced HBP MRI is valuable for predicting clinical outcomes in patients with decompensated cirrhosis. Critical relevance statement Periportal hyperintensity sign from gadobenate dimeglumine-enhanced hepatobiliary phase magnetic resonance imaging is a new noninvasive method to predict clinical outcomes in patients with decompensated cirrhosis. Key points • There was a significant difference in the frequency of periportal hyperintensity sign on HBP between compensated and decompensated cirrhotic patients. • Periportal hyperintensity sign on the hepatobiliary phase was a significant risk factor for death in patients with decompensated cirrhosis. • Periportal hyperintensity sign on the hepatobiliary phase was a significant risk factor for further decompensation in patients with decompensated cirrhosis. Graphical Abstract

Abstract Understanding the stress state caused by a subsequent failure is crucial for successful refracturing. However, there are many differences between the stress reorientation phenomena of a multi-fracture horizontal well and that of a single fracture in a vertical well, including the interaction of multi-fractures. These factors can lead to a change in the stress field of multiple fractures, which is more complex than that of a single fracture. In this paper, based on the elastic theory of porous media and the mechanism of fluid–structure interaction, a finite element numerical model of multi-fracture stress fields is established. The net pressure loaded on the fracture wall was corrected using the fracture line model, which was solved using the separated coupling method with a staggered strategy, and a full coupling simulation of fluid flow and rock deformation was achieved. The results showed that with an increase in production time, the stress reorientation area around the fracture and at both ends first increased at a faster rate, then slowly decreased, and finally disappeared,indicating an optimal refracturing time window. This suggests that the greater the number of fractures, the greater the fracture inclination and fracture bending degree, and the more unfavorable it is for the formation and maintenance of the stress reorientation area near the fracture and at both ends of the fracture. The reorientation of the stress field between horizontal wells may lead to the fracture of the infill wells, causing bending and propagation towards the pressure-depletion area, thus reducing productivity.

Vegetable fields are often contaminated by heavy metals, and Spodoptera exigua is a major vegetable pest which is stressed by heavy metals mainly by feeding. In this study, cadmium accumulation in the tissues of S. exigua exposed to cadmium and its effects on the growth and development of the parents and the offspring were investigated. Under the stress of different concentrations of cadmium (0.2, 3.2, and 51.2 mg kg–1), the cadmium content in each tissue of S. exigua increased in a dose-dependent manner. At the larval stage, the highest cadmium accumulation was found in midgut in all three cadmium treatments, but at the adult stage, the highest cadmium content was found in fat body. In addition, the cadmium content in ovaries was much higher than in testes. When F1 S. exigua was stressed by cadmium and the F2 generation was not fed a cadmium-containing diet, the larval survival, pupation rate, emergence rate and fecundity of the F2 generation were significantly reduced in the 51.2 mg kg–1 treatment compared to the corresponding F1 generation. Even in the F2 generation of the 3.2 mg kg–1 treatment, the fecundity was significantly lower than in the parental generation. The fecundity of the only-female stressed treatment was significantly lower than that of the only-male stressed treatment at the 3.2 and 51.2 mg kg–1 cadmium exposure levels. When only mothers were stressed at the larval stage, the fecundity of the F2 generation was significantly lower than that of the F1 generation in the 51.2 mg kg–1 treatment, and it was also significantly lower than in the 3.2 and 0.2 mg kg–1 treatments. The results of our study can provide useful information for forecasting the population increase trends under different heavy metal stress conditions and for the reliable environmental risk assessment of heavy metal pollution.

Backgroud Li-Fraumeni syndrome is a hereditary tumor syndrome characterized by an elevated risk of malignancy, particularly acute lymphoblastic leukemia (ALL), which can be caused by the heterozygous germline mutation. TP53 gene germline mutation is considered a potential risk factor and crucial prognostic parameter for acute leukemia development and diagnosis, but rarely occurs in adults, and its specific pathogenic significance in acute leukemia is unclear.Case presentation We describes a case of a 45-year-old woman diagnosed with ALL. Whole-exome sequencing approach identified one of the TP53 germline mutations from her bone marrow sample with possible pathogenic significance, c.848G>A (p.Arg283His) heterozygous missense mutation located on exon 8, which was further verified in her hair, oral mucous and nail samples. Family pedigree screening revealed that the same TP53 genetic variant was present in the patient's father and non-donor son, whereas not in the donor. Digital PCR observed that this point mutation frequency dropped post-transplantation but remained low during maintenance therapy when the patient was leukemia-free.Conclusion This suspected Li-Fraumeni syndrome case report with a likely pathogenic heterozygous TP53 variant expands the cancer genetic spectrum. Screening her family members for mutations facilitates identifying the optimal relative donor and avoids unnecessary treatment by monitoring TP53 germline mutations for minimal residual disease following hematopoietic stem cell transplantation. Its potential roles in hematological malignant tumor development and clinical pathogenic implications necessitate further probing.

ABSTRACTObjectives T-cell acute lymphoblastic leukemia/lymphoblastic lymphoma (T-ALL/LBL) are highly malignant and aggressive hematologic tumors for which there is no standard first-line treatment. Chidamide, a novel histone deacetylase inhibitor, shows great promise. We assessed the efficacy and safety of an irradiation-containing conditioning regimen for allogeneic hematopoietic stem cell transplantation (allo-HSCT) and post-transplantation chidamide maintenance in patients with T-ALL/LBL.Methods We retrospectively analyzed the clinical data of six patients with T-ALL/LBL who underwent allo-HSCT with a radiotherapy-containing pretreatment regimen and post-transplant chidamide maintenance therapy. The endpoints were relapse, graft-versus-host disease (GVHD), transplant-related mortality (TRM), progression-free survival (PFS), overall survival (OS), and adverse events (AEs).Results All of the patients had uneventful post-transplant hematopoietic reconstitution, and all achieved complete molecular remission within 30 days. All six patients survived, and two relapsed with a median relapse time of 828.5 (170–1335) days. The 1-year OS rate was 100%, the 2-year PFS rate was 66.7%, and the TRM rate was 0%. After transplantation, two patients developed grade I-II acute GVHD (2/6); grade III-IV acute and chronic GVHD were not observed. The most common AEs following chidamide administration were hematological AEs, which occurred to varying degrees in all patients; liver function abnormalities occurred in two patients (grade 2), and symptoms of malaise occurred in one patient (grade 1).Conclusion Chidamide maintenance therapy after T-ALL/LBL transplantation is safe, but the efficacy needs to be further investigated.

Objectives Burnout is common among medical personnel in China and may be related to excessive and persistent work-related stressors by different specialties. The aims of this study were to assess the prevalence of burnout, work overload and work-life imbalance according to different specialties and to explore the effect of specialty, work overload and work-life imbalance on burnout among medical personnel.Design A cross-sectional study.Setting This study was conducted in 1 tertiary general public hospital, 2 secondary general hospitals and 10 community health service stations in Liaoning, China.Participants A total of 3299 medical personnel participated in the study.Methods We used the 15-item Chinese version of the Maslach Burnout Inventory General Survey (MBI-GS) to measure burnout. Multivariable logistic regression models were used to explore the association between medical specialty, work overload, work-life imbalance and burnout.Results 3299 medical personnel were included in this study. The prevalence of burnout, severe burnout, work overload and work-life imbalance were 88.7%, 13.6%, 23.4% and 23.2%, respectively. Compared with medical personnel in internal medicine, working in obstetrics and gynaecology (OR=0.61, 95% CI 0.38, 0.99) and management (OR=0.45, 95% CI 0.28, 0.72) was significantly associated with burnout, and working in ICU （Intensive Care Unit）(OR=2.48, 95% CI 1.07, 5.73), surgery (OR=1.66, 95% CI 1.18, 2.35) and paediatrics (OR=0.24, 95% CI 0.07, 0.81) was significantly associated with severe burnout. Work overload and work-life imbalance were associated with higher ORs for burnout (OR=1.64, 95% CI 1.16, 2.32; OR=2.79, 95% CI 1.84, 4.24) and severe burnout (OR=4.33, 95% CI 3.43, 5.46; OR=3.35, 95% CI 2.64, 4.24).Conclusions Burnout, work overload and work-life imbalance were prevalent among Chinese medical personnel but varied considerably by clinical specialty. Burnout may be reduced by decreasing work overload and promoting work-life balance across different specialties.

IntroductionChronic obstructive pulmonary disease (COPD) is a chronic respiratory disease with high prevalence and mortality. In some acute exacerbations of COPD (AECOPD) in patients with no obvious signs of infection, early antibiotic treatment seems to clinically improve the disease, but more studies are needed to determine the prognostic impact of antibiotic treatment in AECOPD patients with no obvious signs of infection.PurposeTo clarify the impact of antibiotic treatment on the short-term and long-term prognoses of AECOPD patients without obvious signs of infection.MethodsThe impact of the two treatment methods on the prognosis of patients was compared at 30, 90, 180, and 360 days after discharge. A multicenter, randomized, parallel-controlled clinical trial was conducted in a department of respiratory and critical care medicine in Central China. All patients met the inclusion criteria for AECOPD, and the patients were randomly assigned to the antibiotic group or the nonantibiotic group at a 1:1 ratio. Patients in the antibiotic group were given moxifloxacin 400 mg/day intravenously for 7 days. Patients in the nonantibiotic group were intravenously injected with the same amount of normal saline as the amount of moxifloxacin given to those in the antibiotic group for 7 days.ResultsThere were 406 patients in the antibiotic group and 410 patients in the nonantibiotic group. During the short-term and long-term follow-ups, the acute exacerbation frequency, intensive care unit (ICU) treatment rate, mortality, and mMRC and CAT scores were not significantly different between the two groups (p > 0.05). At the 180- and 360-day follow-ups, the forced expiratory volume in 1 s (FEV1%) and peak expiratory flow (PEF) were not significantly different between the two groups (p > 0.05). The 30-day readmission rate was significantly lower in the antibiotic group than in the nonantibiotic group (p < 0.05). The time from discharge to the first acute exacerbation was not significantly different between the two groups (p > 0.05). The length of the first hospital stay after discharge was significantly lower in the antibiotic group (5.84 days) than in the nonantibiotic group (6.75 days) (p < 0.05). At the 30-day follow-up, the acute exacerbation frequency, age, C-reactive protein (CRP) level, and sputum viscosity were significantly greater in the nonantibiotic group than in the antibiotic group (p < 0.05). In addition, according to the receiver operating characteristic (ROC) analysis, the frequency of acute exacerbations at the 30-day follow-up was significantly greater in COPD patients aged >62.5 years, with a CRP level >12.56 mg/L or with a sputum viscosity >III, in the nonantibiotic group than in those in the antibiotic group, suggesting that the short-term prognosis was poor.ConclusionPatients who are >62.5 years of age, have a CRP concentration >12.56 mg/L, or have a sputum viscosity >III without obvious signs of infection should be treated with antibiotics to improve their short-term prognosis.Clinical Trial Registration:(https://www.chictr.org.cn), (ChiCTR1800018921)

BackgroundPrimary dysmenorrhea (PD) is one of the most common reasons that affect the life quality of women during childbearing age. This research aims to explore the efficacy and curative effect characteristics of oral contraceptives and low-power visible-light-activated photodynamic therapy (PDT). Besides investigating the possible mechanism of PDT, we expected to find a treatment model with better efficacy and fewer side effects.MethodIt was a multicenter, randomized, parallel-controlled study. Eligible participants were randomly assigned to three groups: placebo group, oral contraceptive (Marvelon) group, and the PDT group. They were treated continuously for three menstrual cycles and followed up for two cycles after treatment. The scores of the visual analog scale (VAS) and the concentration of pain-related small molecules in blood before and after treatment were recorded in each group, which can evaluate the therapeutic characteristics of different treatments.ResultBoth Marvelon and PDT were effective. The effect of Marvelon appears quickly which can significantly relieve symptoms at the beginning, while PDT shows a relatively slow role. There was no significant difference in the final efficacy two cycles after treatment. The therapeutic effect was achieved by reducing the concentrations of prostaglandin 2 (PGE2) and endothelin (ET) in the blood.ConclusionMarvelon and PDT are effective methods for the treatment of PD. The long-term efficacy of the two is similar, while the therapeutic characteristics and the side effects are different. Patients can choose the suitable way according to their individual needs.

Summary: Independently run single microgrids (MGs) encounter difficulties with inadequate self-consumption of local renewable energy and frequent power exchange with the grid. Combining numerous MGs to form a multi-microgrid (MMG) is a viable approach to enhance smart distribution networks' operational and financial performance. However, the correlation and coordination of intermittent power generation within each MG network pose many techno-economic challenges for energy sharing and trading. This review offers a comprehensive analysis of these challenges within the framework of MMG operations. It examines state-of-the-art methodologies for optimizing multi-energy dispatch and scrutinizes contemporary strategies within energy markets that contribute to the resilience of power systems. The discourse extends to the burgeoning role of blockchain technology in revolutionizing decentralized market frameworks and the intricacies of MMG coordination for reliable and cost-effective energy distribution. Overall, this study provides ample inspiration for theoretical and practical research to the new entrants and experts alike to develop new concepts for energy markets, scheduling and novel operating models for future resilient multi-energy networked systems/MMGs.

Abstract Background The efficacy of chloroquine treatment for vivax malaria has been rarely evaluated due to a lack of an appropriate testing method. The objective of this study was to conduct molecular monitoring of chloroquine resistance in Plasmodium vivax strains from vivax malaria patients in Yunnan Province, focusing on the analysis of polymorphism in the P. vivax chloroquine resistance transporter protein orthologous gene (pvcrt-o). Methods In accordance with the principles of a cohort study, blood samples were collected from malaria cases diagnosed with a P. vivax mono-infection in Yunnan Province from 2020 to 2022. Segmental PCR was used to amplify the whole pvcrt-o gene in the blood samples and their products were subsequently sequenced. The sequencing data were arranged to obtain the full coding DNA sequence (CDS) as well as the gene’s promoter region sequences. The CDSs were aligned with the reference sequence (XM_001613407.1) of the P. vivax SalI isolate to identify the mutant loci. Results From a total of 375 blood samples taken from vivax malaria cases, 272 both whole gene CDSs (1272–1275 bp) and promoter DNA sequences (707 bp) of pvcrt-o gene were obtained. Among the whole CDSs, there were 7 single nucleotide polymorphic sites in which c.7 A>G was the minor allele frequency (MAF) site with 4.4% (12/272) detection rate. The mutation detection rate showed a significant decrease from 9.8% (10/102) in 2020 to 1.1% (1/92) in 2021 and 1.3% (1/78) in 2022, indicating statistical significance (χ 2 = 11.256, P

Abstract The maternal-fetal interface shares similarities with tumor tissues in terms of the immune microenvironment. Normal pregnancy is maintained due to the immunosuppressed state, but pyroptosis induced by MITA can trigger the body’s immune response and disrupt the immunosuppressed state of the maternal-fetal interface, leading to abortion. In this study, we explored the role of MITA and TRIM38 in regulating pyroptosis and maintaining the immune tolerance of the maternal-fetal interface during pregnancy. Our findings show that the interaction between MITA and TRIM38 plays a crucial role in maintaining the immunosuppressed state of the maternal-fetal interface. Specifically, we observed that TRIM38-mediated K48 ubiquitination of MITA was higher in M2 macrophages, leading to low expression levels of MITA and thus inhibiting pyroptosis. Conversely, in M1 macrophages, the ubiquitination of K48 was lower, resulting in higher expression levels of MITA and promoting pyroptosis. Our results also indicated that pyroptosis played an important role in hindering the transformation of M1 to M2 and maintaining the immunosuppressed state of the maternal-fetal interface. These discoveries help elucidate the mechanisms that support the preservation of the immune tolerance microenvironment at the maternal-fetal interface, playing a vital role in ensuring successful pregnancy.

Abstract Left ventricular diastolic dysfunction (LVDD) is an early event associated with cardiovascular complications and poor prognosis in chronic kidney disease patients undergoing dialysis. In this study, we investigated whether diastolic dysfunction, measured by the E/E′ ratio, affects adverse outcomes in peritoneal dialysis (PD) patients (n = 148). Our results showed that patients with an E/E′ ratio ≥ 15 were more likely to be female, have a longer dialysis vintage, have significantly higher left atrial volume index and left atrial kinetic energy levels, have lower E′ levels and LV hypertrophy (LVH) degree, and have higher volume markers. Kaplan–Meier curves revealed that patients with a higher E/E′ ratio had worse survival and a higher risk of heart failure than those with a lower E/E′ ratio. Subgroup analysis demonstrated that non-diabetic patients with a higher E/E′ ratio had a higher risk of heart failure than those with a lower E/E′ ratio. Cox proportional hazard regression analysis indicated that the ECW/ICW ratio was strongly associated with LVDD and confirmed that the E/E′ ratio was an independent risk factor for overall death. Our study suggests that monitoring the E/E′ ratio in PD patients is important for improving their prognosis.

Chinese Olea europaea leaves, rich in verbascosides, were extracted using ultrasound-assisted extraction (UAE) and wall-breaking extraction (WBE) with deep eutectic solvents (Optimal UAE: 55 min, 200 mL/g liquid–solid ratio, 20% moisture, yielding 206.23 ± 0.58 mg GAE/g total phenolic content (TPC) and 1.59 ± 0.04% verbascoside yield (VAY); Optimal WBE: 140 s, 210 mL/g, 30% moisture, giving 210.69 ± 0.97 mg GAE/g TPC and 1.33 ± 0.2% VAY). HPLC analysis showed that young leaves accumulated higher TPC and phenolic compounds. Among the five olive varieties, Koroneiki and Chemlal showed the highest TPC in UAE, while Arbosana and Chemlal excelled in WBE. WBE yielded a higher TPC and rutin, whereas UAE marginally increased other phenolics. Additionally, the DPPH• assay showed that WBE-extracted verbascoside-rich extracts (VREs) of Chemlal exhibited high antioxidant activity (EC50 of 57 mg/mL), but Koroneiki-VREs exhibited lower activity against the ABTS•+ radical (EC50 of 134 mg/mL). Remarkably, the UAE/WBE-extracted Chemlal-VREs promoted the normal esophageal Het-1A cell line at 25 μg/mL for 24 h; yet, the esophageal cancer Eca-109 cells were sensibly inhibited, especially at 50 μg/mL; and the cell viability decreased dramatically. The results confirmed WBE as a relatively efficient method, and the Chemlal variety may be an excellent source of verbascoside.

Photovoltaic power generation and energy storage technology are current hotspots in the clean energy industry. As a core piece of equipment, an inverter is subjected to higher demands for its voltage regulation range and output performance. A differential boost inverter features a boosting function not found in traditional inverters, effectively widening the input voltage range, with characteristics of a single-stage structure and simple modulation. However, the differential boost inverter faces the issue of high common-mode voltage. Considering that the magnitude of the common-mode voltage changes with different modulation methods, a novel modulation strategy with a flexible common-mode voltage is proposed, which can effectively suppress the common-mode voltage under the same gain without affecting the output power quality. This article first introduces the topology, working principle, and traditional modulation methods of the differential boost inverter. Then, the new modulation strategy is defined, and the gain equation is derived. The new modulation method’s applicable scenarios are discussed and compared to other modulation methods based on the gain curve, concluding that the new method has advantages in terms of common-mode voltage amplitude and power quality under low boost gain. Finally, the effectiveness of the proposed method is verified through simulation and experiments.

Coastal ecosystems are facing critical water quality deterioration, while the most convenient passage to the South China Sea, Beibu Gulf, has been under considerable pressure to its ecological environment due to rapid development and urbanization. In this study, we characterized the spatiotemporal change in the water quality in Beibu Gulf and proposed a machine learning approach to predict the water pollution level in Beibu Gulf on the basis of 5-year (2018–2022) observation data of ten water quality parameters from ten selected sites. Random forest (rf) and linear algorithms were utilized. Results show that a high frequency of exceedance of water quality parameters was observed particularly in summer and autumn, e.g., the exceeding rate of Dissolved Inorganic Nitrogen (DIN) at GX01, GX03, GX06, and GX07 station were 28.2~78.1% (average is 52.0%), 6.0~21.7% (average is 52.0%), 23.0~44.7% (average is 31.9%), and 5.2~33.4% (average is 21.2%), respectively. With regard to the spatial distribution, the pH, Water Salinity (WS), and Dissolved Oxygen (DO) values of stations inside the bay were overall lower than those of corresponding stations at the mouth of the bay and stations outside the bay. The concentrations of Chlorophyll-a concentration (except QZB) and nutrient salts showed a clearly opposite trend compared with the above concerned three parameters. For instance, the average Chl-a value of station GX09 was 22.5% higher than that of GX08 and GX10 between 2018 and 2022. Correlation analysis among water quality factors shows a significant positive correlation (r > 0.85) between Dissolved Inorganic Nitrogen (DIN) and NO3-N, followed by NO2-N and NH4-N, indicating that the main component of DIN is NO3-N. The forecasting results with machine learning also demonstrate the possibility to estimate the water quality parameters, such as chl-a concentration, DIN, and NH4-N in a cost-effective manner with prediction accuracy of approximately 60%, and thereby could provide near-real-time information to monitor the water quality of the Beibu Gulf. Predicting models initiated in this study could be of great interest for local authorities and the tourism and fishing industries.

As urbanization advances, the issue of urban heat islands (UHIs) grows increasingly serious, with UHIs gradually transitioning into regional urban heat islands. There is still a lack of research on the evolution and drivers of the thermal environment in urban agglomerations; therefore, in this study, we used trend analysis methods and spatial statistical analysis tools to investigate these issues in the Beijing–Tianjin–Hebei (BTH) urban agglomeration. The results demonstrated the following: (1) The land surface temperature (LST) exhibited low fluctuation, while the relative land surface temperature (RLST) fluctuated significantly. In Zhangjiakou and Chengde, the LST and RLST evolution trends were complex, and the results differed between daytime and nighttime, as well as between the annual and seasonal scales. In other regions, the trends of LST and RLST evolution were more obvious. (2) During the daytime, the high UHI clusters centered on “BJ–TJ–LF” and “SJZ–XT–HD” formed gradually; during the nighttime, the high UHI clusters were mainly observed in built-up areas. The distribution range and direction of UHIs showed greater degrees of evolution during the daytime in summer. (3) The total UHI area showed an increasing trend, and the intensity of heat stress suffered by the BTH agglomeration was increasing. (4) In BTH and Hebei, aerosol optical depth, surface solar radiation, population density, and gross domestic product were the dominant factors influencing UHIs; moreover, in Beijing and Tianjin, all factors showed an basically equal impact. The methodology and findings of this study hold significant implications for guiding urban construction, optimizing urban structure, and improving urban thermal comfort in the BTH urban agglomeration.

PurposeVector flow mapping and treadmill exercise stress echocardiography were used to evaluate and explore changes in the left ventricular (LV) flow field of patients with nonobstructive coronary artery disease.MethodsOverall, 34 patients with nonobstructive (

As a traditional Chinese herbal medicine, Corni Fructus (CF) possesses varieties of pharmacological functions including anti-diabetes, anti-oxidation, anti-inflammatory, and hepatoprotective properties. However, the most commonly used forms of CF are pills and decoctions in the type 2 diabetes (T2DM) medical treatment. Until now, it remains unclear whether and how nano-powder CF (NPCF) improves T2DM. Here, we prepared NPCF via ball milling nanotechnology. NPCF significantly improved the symptoms of T2DM mice through alleviating hepatic inflammation and oxidative stress, reducing hyperglycemic and hyperlipidemic, and restoring pancreatic and liver damages. Network pharmacology screening was utilized to obtain 293 NPCF active ingredient targets and 1235 T2DM targets, and 195 cross-targets were obtained by crossover. Mechanistically, NPCF may enhance glucose transport, promote glycogen synthesis, and improve insulin resistance by acting on insulin receptor (INSR)/phosphatidylinositol 3-kinase (PI3K/AKT)/glucose transporter 4 (GLUT4) signaling pathways. Therefore, NPCF may be a potential dosage form of CF for T2DM treatment.

Background: Cisplatin (DDP) is the principal agent used for chemotherapy in patients with non-small cell lung cancer (NSCLC). Nevertheless, DDP resistance is an essential cause for a worse prognosis of patient. Therefore, this study proposes to discover features of miR-424-5p in DDP resistance of NSCLC. Method: After exogenous modulation of miR-424-5p expression, A549 cell activity was measured using CCK-8 and flow cytometry. A549/DDP and A549/DDP-associated subcutaneous tumor model were constructed to investigate the effect of miR-424-5p on DDP resistance in NSCLC in vivo. TargetScan and JASPAR databases predicted the potential molecular mechanism of miR-424-5p. A549-and A549/DDP-derived exosomes were isolated and characterized using a transmission electron microscope and nanoparticle tracking analysis. Result: Overexpression of miR-424-5p facilitated proliferation and DDP resistance in A549 cells, and knockdown of miR-424-5p did the opposite. Knockdown of miR-424-5p enhanced DDP restriction on tumor weight and volume. Moreover, SOCS5 and SOCS56 (SOCS5/6) were downstream targets of miR-424-5p. miR-424-5p down-regulated SOCS5/6 expression to activate JAK2/STAT3 and PI3K/AKT pathways. Notably, tumor protein p53 (TP53) is a transcription factor for the miR-424-5p host gene, as confirmed by the dual-luciferase reporter gene. Cellular and animal experiments indicated that TP53 limited the regulatory function of miR-424-5p on NSCLC growth, DDP resistance, and related molecules. Interestingly, miR-424-5p was markedly enriched in A549/DDP cell-derived exosomes than in A549 cell-derived exosomes, and TP53 down-regulated miR-424-5p expression in A549/DDP cell-derived exosomes. Conclusion: DDP-resistant cell-derived exosome miR-424-5p contributes to NSCLC growth and DDP resistance by targeting SOCS5 and SOCS6 to activate JAK2/STAT3 and PI3K/AKT pathways, which are blocked by TP53.

Introduction: This paper presents a spatial effect model to examine the impact of industrial agglomeration and international R&D capital technology spillover on air pollution.Methods: The study utilizes spatial panel data from 30 provinces and cities in China spanning the period 2008 to 2022, allowing for the decomposition of both direct and indirect spillover effects.Results: Additionally, the research investigates the threshold effect of industrial agglomeration and international research and development capital and technology spillover on air pollution, considering independent research and development as the threshold variable. The findings reveal evident spatial autocorrelation and spatial dependence between industrial agglomeration, international R&D capital, and air pollution. Importantly, both international R&D capital technology spillover and industrial agglomeration exhibit a single threshold effect. This implies that surpassing the threshold value leads to a more pronounced positive impact of international R&D capital technology spillover on reducing air pollution, while the impact of industrial agglomeration on air pollution tends to be positive.Discussion: The findings of this study have significant theoretical and practical implications for the promotion of sustainable economic development, particularly in China.

Pigments derived from red pepper fruits are widely used in food and cosmetics as natural colorants. Nitrogen (N) is a key nutrient affecting plant growth and metabolism; however, its regulation of color-related metabolites in pepper fruit has not been fully elucidated. This study analyzed the effects of N supply (0, 250, and 400 kg N ha-1) on the growth, fruit skin color, and targeted and non-target secondary metabolites of field-grown pepper fruits at the mature red stage. Overall, 16 carotenoids were detected, of which capsanthin, zeaxanthin, and capsorubin were the dominant ones. N application at 250 kg ha-1 dramatically increased contents of red pigment capsanthin, yellow-orange zeaxanthin and β-carotene, with optimum fruit yield. A total of 290 secondary metabolites were detected and identified. The relative content of most flavonoids and phenolic acids was decreased with increasing N supply. Correlation analysis showed that color parameters were highly correlated with N application rates, carotenoids, flavonoids, phenolic acids, lignans, and coumarins. Collectively, N promoted carotenoid biosynthesis but downregulated phenylpropanoid and flavonoid biosynthesis, which together determined the spectrum of red color expression in pepper fruit. Our results provide a better understanding of the impact of N nutrition on pepper fruit color formation and related physiology, and identification of target metabolites for enhancement of nutritional quality and consumer appeal.

Magnetic microrobots have gained significant attention in the biomedical field due to their wireless actuation, strong controllability, fast response, and minimal impact on the environment. As the task complexity keeps increasing in the clinical applications of magnetic microrobots, more geometric structures and magnetization profiles have been included in the designs of magnetic microrobots, posing significant challenges to the fabrication of magnetic microrobots. Microassembly is a fabrication method that can create convoluted structures with small‐scale modules. It can accurately control the position and orientation of each magnetic module, resulting in a magnetic microrobot with arbitrary 3D geometries and magnetization profiles. This article reviews recent advanced assembly‐based fabrication methods of magnetic microrobots, including microassembly driven by contact mechanical forces and noncontact field forces. The principles, fabrication processes, and the advantages and disadvantages of each assembly‐based fabrication method are summarized. The existing challenges and future development of fabricating magnetic microrobots by assembly are discussed in detail. It is believed that this review will provide a methodological reference and inspire new ideas for manufacturing powerful magnetic microrobots in future biomedical applications.

Observational studies have shown an association between liver dysfunction and hepatocellular carcinoma (HCC), but the causality relationship between them is unclear. We aimed to determine whether there is a bidirectional causal relationship between liver function indicators (alanine aminotransferase, ALT; aspartate aminotransferase, AST; alkaline phosphatase, ALP; γ-glutamyltransferase, GGT) and HCC. Our two-sample Mendelian randomization (MR) study acquired single nucleotide polymorphisms (SNPs) associated with liver function indicators (ALT, n = 134,182; AST, n = 134,154; GGT, n = 118,309; ALP, n = 105,030) and with HCC (n = 197,611) from publicly available genome-wide association studies (GWAS) of East Asian ancestry in Japan (BioBank Japan, BBJ). Univariable MR analyses were performed to identify whether the genetic evidence of exposure was significantly associated with outcome. Multivariable MR analysis was conducted to estimate the independent effects of exposures on outcome. Univariable MR analysis indicated that the level of ALT, AST, and GGT was the risk factor for HCC incidence. Meanwhile, multivariable MR analysis revealed that AST was an independent risk factor for HCC. The hazard ratio (HR) of the probability of HCC was 3.045 [95% confidence interval (95%CI), 1.697–5.463, p = 0.003] for AST. The results of reverse MR analyses showed that gene-predictive HCC incidence could increase the levels of AST (HR = 1.031, 95%CI: 1.009–1.054, p = 2.52 × 10−4) and ALT (HR = 1.040, 95%CI: 1.019–1.063, p = 0.005). Meanwhile, HCC may be negatively correlated with ALP levels (HR = 0.971, 95%CI: 0.947–0.995, p = 0.018). This study provides evidence to support that genetically predicted higher levels of AST are related to increased risk of HCC, with no strong evidence of a causal effect of genetically predicted ALP, ALP, and GGT on HCC. In addition, genetic predisposition to HCC could influence blood concentration of ALT, AST, and ALP. Thus, this may create a vicious cycle.

Abstract Background Diets rich in plant-based foods are associated with lower risks of non-alcoholic fatty liver disease (NAFLD), while the prospective evidence is limited. We aimed to examine longitudinal associations of plant-based diets and genetic susceptibility with NAFLD risk. Methods This longitudinal cohort study included 159,222 participants (58.0 ± 8.0 years old, 55.7% female) free of NAFLD in the UK Biobank. We calculated the overall plant-based diet index (PDI), the healthful plant-based diet index (hPDI), and the unhealthful plant-based diet index (uPDI). New-onset NAFLD was the primary outcome. The weighted polygenic risk score was calculated based on risk variants associated with NAFLD. Hazard ratios (HR) and 95% confidential intervals (CI) were estimated by Cox proportional hazards model. Magnetic resonance imaging-derived proton density fat fraction (MRI-PDFF) measured liver fat content in a subsample of 20,692 participants (57.5 ± 7.4 years old, 52.6% female) was the secondary outcome. The associations between plant-based diet indices and MRI-PDFF were evaluated using generalized linear models. Results During a median follow-up of 9.5 years, 1541 new-onset NAFLD cases were documented. Compared to the lowest quintile, multivariable-adjusted hazard ratios (HRs) of NAFLD in the highest quintile were 0.78 (95% confidential intervals [CI], 0.66–0.93, p-trend =0.02), 0.74 (95% CI, 0.62–0.87, p-trend

Abstract Background During endotracheal intubation, extubation, tracheotomy, and tracheotomy tube replacement, the splashed airway secretions of patients will increase the risk of transmission of SARS-CoV‐2 and many other potential viral and bacterial diseases, such as influenza virus, adenovirus, respiratory syncytial virus, rhinovirus, Middle East respiratory coronavirus syndrome (MERS-CoV), Streptococcus pneumoniae, and Mycobacterium tuberculosis. Therefore, it is necessary to establish a barrier between patients and medical workers to reduce the risk of operators’ infection with potentially pathogenic microorganisms. Methods We designed a “safety cap” that can be connected to the opening of an endotracheal tube or tracheotomy tube to reduce the diffusion area of respiratory secretions during the process of endotracheal intubation, extubation and tracheotomy tube replace, so as to reduce the infection risk of medical workers. Results Through a series of hydrodynamic simulation analysis and experiments, we demonstrated that the use of “safety cap” can substantially limit the spatter of airway secretions, so as to improve the hospital sanitation. Conclusion The “safety cap” can effectively limit the dissemination of patients’ respiratory secretions, thus reducing the risk of potential diseases transmission and may have certain application prospects.

Abstract Retinopathy of Prematurity (ROP) is a multifactorial disease characterized by abnormal retinal vascular growth in premature infants, which is one of the leading causes of childhood blindness. Lactic acid metabolism may play an imperative role in the development of ROP, but there are still few relevant studies. Our team use a dataset GSE158799 contained 284 genes in 3 P17_OIR mice and 3 P30_OIR mice to identify 41 potentially differentially expressed lactate metabolism-related genes (LMRGs) related to ROP. Then through bioinformatics analysis, we strive to reveal the interaction, the enriched pathways and the immune cell infiltration among these LMRGs, and predict their functions and internal mechanisms. These DEGs may regulate lactate metabolism, leading to the changes of metabolism and immunity, thereby inducing the development of ROP. Our results will expand our understanding of the intrinsic mechanism of ROP and may be helpful for the directions for treatment of ROP in the future.

Stem color is an important agronomic trait of wax gourds. However, its regulatory genes have not been identified. In this study, 105 inbred lines constructed from two parents (GX-71 and MY-1) were sequenced and quantitative trait loci sequencing was used to mine the genes that regulate stem color in wax gourds. The results identified two quantitative trait loci related to stem color, qSC5 and qSC12, located on Chr05 (11,134,567–16,459,268) and Chr12 (74,618,168–75,712,335), respectively. The qSC5 had a phenotypic variation rate of 36.9% and a maximum limit of detection of 16.9. And the qSC12 had a phenotypic variation rate of 20.9%, and a maximum limit of detection of 11.2. Bch05G003950 (named BchAPRR2) and Bch12G020400 were identified as candidate genes involved in stem color regulation in wax gourds. The chlorophyll content and expression of BchAPRR2 and Bch12G020400 were significantly higher in green-stemmed wax gourds than in white-stemmed ones. Therefore, BchAPRR2 and Bch12G020400 were considered the main and secondary regulatory genes for wax gourd stem color, respectively. Finally, InDel markers closely linked to BchAPRR2 were developed to validate the prediction of wax gourd stem color traits in 55 germplasm lines, with an accuracy of 81.8%. These findings lay the foundation for exploring the genetic regulation of wax gourd stem color and future research on wax gourd breeding.

Traditional single nucleic acid assays can only detect one target while multiple nucleic acid assays can detect multiple targets simultaneously, providing comprehensive and accurate information. Fluorescent microspheres in multiplexed nucleic acid detection offer high sensitivity, specificity, multiplexing, flexibility, and scalability advantages, enabling precise, real-time results and supporting clinical diagnosis and research. However, multiplexed assays face challenges like complexity, costs, and sample handling issues. The review explores the recent advancements and applications of fluorescent microspheres in multiple nucleic acid detection. It discusses the versatility of fluorescent microspheres in various fields, such as disease diagnosis, drug screening, and personalized medicine. The review highlights the possibility of adjusting the performance of fluorescent microspheres by modifying concentrations and carrier forms, allowing for tailored applications. It emphasizes the potential of fluorescent microsphere technology in revolutionizing nucleic acid detection and advancing health, disease treatment, and medical research.

This paper introduces the election optimization algorithm (EOA), a meta-heuristic approach for engineering optimization problems. Inspired by the democratic electoral system, focusing on the presidential election, EOA emulates the complete election process to optimize solutions. By simulating the presidential election, EOA introduces a novel position-tracking strategy that expands the scope of effectively solvable problems, surpassing conventional human-based algorithms, specifically, the political optimizer. EOA incorporates explicit behaviors observed during elections, including the party nomination and presidential election. During the party nomination, the search space is broadened to avoid local optima by integrating diverse strategies and suggestions from within the party. In the presidential election, adequate population diversity is maintained in later stages through further campaigning between elite candidates elected within the party. To establish a benchmark for comparison, EOA is rigorously assessed against several renowned and widely recognized algorithms in the field of optimization. EOA demonstrates superior performance in terms of average values and standard deviations across the twenty-three standard test functions and CEC2019. Through rigorous statistical analysis using the Wilcoxon rank-sum test at a significance level of 0.05, experimental results indicate that EOA consistently delivers high-quality solutions compared to the other benchmark algorithms. Moreover, the practical applicability of EOA is assessed by solving six complex engineering design problems, demonstrating its effectiveness in real-world scenarios.

The objective of this study was to investigate how nitrogen and slow-release fertilizers affect the traits of leaf senescence and quinoa production in order to explore the optimal slow-release fertilizer and nitrogen fertilizer ratios suitable for quinoa production, as well as to provide theoretical references for the planting of quinoa fertilization methods and fertilizer amount. In this experiment, the main local strain Quinoa 77 was selected as the experimental material, and six treatments were set up: CK: no nitrogen fertilizer; T1: 100% urea (N); T2: 100% slow-release fertilizer (C); T3: 5:5 (C5N5); T4: 3:7 (C3N7); and T5: 7:3 (C7N3). This was done in order to investigate how various treatments affect the activities of catalase (CAT), peroxidase (POD), and superoxide dismutase (SOD); malondialdehyde (MDA) content; and yield of quinoa leaves. The findings revealed the following: (1) As the reproductive period progressed, the activities of CAT, POD, and SOD in quinoa leaves treated differently showed a tendency to increase and subsequently decrease, and they reached the peak value at the early stage of filling. The activity of CAT, POD, and SOD in the T3 treatment was the highest, and the average activities were 3148.74 U·g−1, 2197.84 U·g−1, and 118.51 U·g−1, respectively, which increased by 78.90%, 101.99%, and 108.14%, respectively, compared with CK. The content of MDA continued to increase with the progress of fertility. The average T3 treatment was 36.41 nmol·g−1, which was 46.87% lower than that of CK. (2) Out of all the treatments, T3 had the highest yield with an average of 3829.43 kg·hm−2, T5 the second with an average of 3313.52 kg·hm−2, and T4 the third with 2847.47 kg·hm−2, which increased yields by 96.18%, 69.75%, and 45.87%, respectively, compared with CK. (3) Yield was highly significantly and positively correlated with thousand kernel weight; number of grains per spike per plant; and the early filling stages of CAT, POD, and SOD sports, and it had a negative, extremely significant correlation with MDA content. Comprehensive analysis showed that slow-release fertilizer and nitrogen fertilizer can improve the antioxidant enzyme activity of quinoa leaves, inhibit MDA content, improve the physiological characteristics of quinoa, and delay the purpose of leaf senescence, with a better effect of yield and income, of which the T3 treatment had the high-quality impact of increasing yields and was a more scientific and reasonable fertilization method.

Quinoa (Chenopodium quinoa Willd.) is gaining recognition as a pseudocereal due to its nutritional attributes and adaptability to challenging conditions and marginal soils. However, understanding the optimal fertilization for quinoa growth remains a challenge. This study investigates the effects of nitrogen fertilization (0, 90, 120, and 150 kg using urea) on quinoa phenology, growth, and photosynthesis in the Loess Plateau region of China, a critical area facing soil erosion and ecological degradation. The results showed that nitrogen fertilization significantly influenced quinoa phenology, prompting early flowering and shorter growth at an optimum rate of 120 kg ha−1. Nitrogen application enhanced growth traits such as plant height, stem diameter, and chlorophyll content, particularly at the heading and flowering stages. Photosynthesis-related parameters, including net photosynthesis rate, transpiration rate, stomatal conductance, and intercellular CO2 concentration, were affected by nitrogen application, with higher values observed at 120 kg ha−1. Non-photochemical quenching was significantly increased by nitrogen application, indicating the efficient dissipation of excess energy. The study demonstrated a positive correlation between grain yield and growth traits, photosynthesis-related traits, and chlorophyll content. In conclusion, quinoa yield could be significantly improved at the Loess Plateau region under rainfed conditions by an optimal nitrogen fertilizer rate of 120 kg ha−1, which reduces the growth duration while increasing photosynthesis traits.

Abstract Background Chloroquine (CQ) has been the preferred clinical treatment for vivax malaria in Yunnan Province since 1958, with over 300,000 patients. This study aimed to help make trend predictions regarding variations the in anti-malarial drug susceptibility of Plasmodium vivax distributed in Yunnan Province and effectively implement monitoring measures on the efficacy of anti-malarial drugs for vivax malaria. Methods Blood samples collected from patients with mono-P. vivax infections were employed in this study based on the principle of cluster sampling. The whole gene of P. vivax multidrug resistance 1 protein gene (pvmdr1) was amplified by nested-PCR techniques and the PCR amplification produce were sequenced by Sanger bidirectional sequencing. The mutant loci and haplotypes of coding DNA sequence (CDS) were identified by comparison with the reference sequence (NC_009915.1) of the P. vivax Sal I isolate. Parameters such as Ka/Ks ratio were calculated using MEGA 5.04 software. Results A total of 753 blood samples from patients infected with mono-P. vivax were collected, of which 624 blood samples yielded the full gene sequence (4392 bp) of the pvmdr1 gene, with 283, 140, 119, and 82 sequences from 2014, 2020, 2021 and 2022, respectively. A total of 52 single nucleotide polymorphic (SNP) loci were detected for the 624 CDSs, of which 92.3% (48/52), 34.6% (18/52), 42.3% (22/52), and 36.5% (19/52) SNPs were detected in 2014, 2020, 2021 and 2022, respectively. All of 624 CDSs were defined for a total of 105 mutant haplotypes, with CDSs of 2014, 2020, 2021, and 2022 containing 88, 15, 21, and 13 haplotypes, respectively. Of the 105 haplotypes, the threefold mutant haplotype (Hap_87) was the starting point for stepwise evolution, and the most drastic tenfold mutations were Hap_14 and Hap_78, and the fivefold, sixfold, sevenfold, and eightfold mutations. Conclusions In the majority of vivax malaria cases in Yunnan Province, most of them were infected with strains carrying demonstrating highly mutated in pvmdr1 genes. However, the dominant mutation strains types varied from year to year, which warrants further exploration in order to confirm the correlation between with phenotypic changes in P. vivax strains and their susceptibility to anti-malarial drugs such as chloroquine.

Abstract. Background:. Pneumonia-like primary pulmonary lymphoma (PPL) was commonly misdiagnosed as infectious pneumonia, leading to delayed treatment. The purpose of this study was to establish a computed tomography (CT)-based radiomics model to differentiate pneumonia-like PPL from infectious pneumonia. Methods:. In this retrospective study, 79 patients with pneumonia-like PPL and 176 patients with infectious pneumonia from 12 medical centers were enrolled. Patients from center 1 to center 7 were assigned to the training or validation cohort, and the remaining patients from other centers were used as the external test cohort. Radiomics features were extracted from CT images. A three-step procedure was applied for radiomics feature selection and radiomics signature building, including the inter- and intra-class correlation coefficients (ICCs), a one-way analysis of variance (ANOVA), and least absolute shrinkage and selection operator (LASSO). Univariate and multivariate analyses were used to identify the significant clinicoradiological variables and construct a clinical factor model. Two radiologists reviewed the CT images for the external test set. Performance of the radiomics model, clinical factor model, and each radiologist were assessed by receiver operating characteristic, and area under the curve (AUC) was compared. Results:. A total of 144 patients (44 with pneumonia-like PPL and 100 infectious pneumonia) were in the training cohort, 38 patients (12 with pneumonia-like PPL and 26 infectious pneumonia) were in the validation cohort, and 73 patients (23 with pneumonia-like PPL and 50 infectious pneumonia) were in the external test cohort. Twenty-three radiomics features were selected to build the radiomics model, which yielded AUCs of 0.95 (95% confidence interval [CI]: 0.94–0.99), 0.93 (95% CI: 0.85–0.98), and 0.94 (95% CI: 0.87–0.99) in the training, validation, and external test cohort, respectively. The AUCs for the two readers and clinical factor model were 0.74 (95% CI: 0.63–0.83), 0.72 (95% CI: 0.62–0.82), and 0.73 (95% CI: 0.62–0.84) in the external test cohort, respectively. The radiomics model outperformed both the readers' interpretation and clinical factor model (P

Type II deiodinase (DIO2) is thought to provide triiodothyronine (T3) to the nucleus to meet intracellular needs by deiodinating the prohormone thyroxine. DIO2 is expressed widely in many tissues and plays an important role in a variety of physiological processes, such as controlling T3 content in developing tissues (e.g., bone, muscles, and skin) and the adult brain, and regulating adaptive thermogenesis in brown adipose tissue (BAT). However, the identification and cloning of DIO2 have been challenging. In recent years, several clinical investigations have focused on the Thr92Ala polymorphism, which is closely correlated with clinical syndromes such as type 2 diabetes, obesity, hypertension, and osteoarthritis. Thr92Ala-DIO2 was also found to be related to bone and neurodegenerative diseases and tumors. However, relatively few reviews have synthesized research on individual deiodinases, especially DIO2, in the past 5 years. This review summarizes current knowledge regarding the physiological functions of DIO2 in thyroid hormone signaling and adaptive thermogenesis in BAT and the brain, as well as the associations between Thr92Ala-DIO2 and bone and neurodegenerative diseases and tumors. This discussion is expected to provide insights into the physiological functions of DIO2 and the clinical syndromes associated with Thr92Ala-DIO2.

Abstract Postoperative nausea and vomiting (PONV) can lead to various postoperative complications. The risk assessment model of PONV is helpful in guiding treatment and reducing the incidence of PONV, whereas the published models of PONV do not have a high accuracy rate. This study aimed to collect data from patients in Sichuan Provincial People’s Hospital to develop models for predicting PONV based on machine learning algorithms, and to evaluate the predictive performance of the models using the area under the receiver characteristic curve (AUC), accuracy, precision, recall rate, F1 value and area under the precision-recall curve (AUPRC). The AUC (0.947) of our best machine learning model was significantly higher than that of the past models. The best of these models was used for external validation on patients from Chengdu First People’s Hospital, and the AUC was 0.821. The contributions of variables were also interpreted using SHapley Additive ExPlanation (SHAP). A history of motion sickness and/or PONV, sex, weight, history of surgery, infusion volume, intraoperative urine volume, age, BMI, height, and PCA_3.0 were the top ten most important variables for the model. The machine learning models of PONV provided a good preoperative prediction of PONV for intravenous patient-controlled analgesia.

Objective To investigate the effect of exenatide treatment on the composition of intestinal flora and metabolic pathways in patients with obesity with polycystic ovary syndrome.Methods Patients with obesity with polycystic ovary syndrome (PCOS) were distributed to two groups: one received exenatide combined with metformin (COM group, n = 14) and the other used metformin alone (MF group, n = 15). Fresh fecal specimens from the participants, including 29 patients with obesity with PCOS and 6 healthy controls, were collected for metagenomic sequencing. The effect of exenatide combination with metformin or metformin alone on the composition and function of intestinal flora in patients with obesity with PCOS were compared by bioinformatics analysis.Results The level of BMI, TT, HbA1c, and HDL-c was significantly improved in both groups. The MF and COM groups were abundant in Firmicutes, Bacteroidetes, Uroviricota, Actinobacteria, and Proteobacteria. Abundance of Bacteroidetes, Proteobacteria, Hungatella, and certain probiotics like Phocaeicola and Anaerobutyricum significantly increased in both groups after treatment. Enriched microbial species in the MF and COM group were different. Clostridium, Fusobacterium, and Oxalobacter were the main bacteria in the post-MF group, while Lactococcus_garvieae, Clostridium_perfringens, and Coprococcus_sp_AF16_5 were the main bacteria in the post-COM group. The post-COM group had more probiotic species including Bifidobacterium, Prevotella, and Anaerobutyricum after treatment.Conclusion Both exenatide combined with metformin and metformin monotherapy can improve metabolic and endocrine markers, and the diversity and abundance of gut microbiota in patients with obesity with PCOS. The effects of the combination and monotherapy agents on intestinal flora were consistent to some extent but also unique respectively.

Background: Vitiligo stands as a challenging skin disorder with limited treatment options available. LiuWei DiHuang formula (LDF), a renowned Traditional Chinese medicine, has exhibited promising results in treating vitiligo over an extended period. However, the precise underlying mechanism of its action remains elusive. Methods: Employing a comprehensive network pharmacology approach, this study identified active compounds and their corresponding targets within LDF, while also pinpointing vitiligo-associated targets sourced from the TCMSP database, OMIM, DisGenNET, and Genecards. A network was established to illustrate the connections between active compounds and targets, alongside a protein-protein interaction network. Further analyses, encompassing Gene Ontology (GO) function and KEGG pathway enrichment, were conducted using the DAVID platform. Molecular docking simulations were performed utilizing AutoDockTools and AutoDockVina software. To validate the outcomes of the systematic pharmacological investigation, experiments were conducted using juvenile zebrafish. Results: The collective effort of the network pharmacology approach yielded a compilation of 41 compounds and 192 targets. Molecular docking simulations notably revealed the lowest binding energies for CAT-quercetin and CAT-Kaempferol interactions. The utilization of juvenile zebrafish experiments highlighted a significant increase in melanocyte count following methoxsalen and LDF treatment. Notably, LDF prominently augmented the expression levels of proteins related to melanogenesis. Additionally, LDF showcased the capacity to enhance CAT and SOD levels while concurrently reducing ROS and MDA activity. In contrast to the model group, substantial increases in protein and mRNA levels of Nrf2 and HO-1 were observed in response to LDF treatment (P

The utility's utilization of communication technology and renewable energy sources has paved the path for self-sustaining microgrids (MGs). However, the intermittency of solar and wind energies raises concerns about meeting demand effectively. To ensure optimal performance of distributed MGs, an efficient energy management system (EMS) is crucial to tackle this uncertainty. Historically, MGs have primarily achieved operational cost reduction through optimal functioning. Integrating demand response (DR) into the EMS could further enhance operational efficiency and peak reduction. This research work addresses this challenge by incorporating DR programs into grid-connected MGs' energy management. Stochastic programming is employed to account for the unpredictable solar and wind behaviours. Flexible price elasticity is used to calculate price elasticity coefficients, portraying customer responses effectively. The implemented research work compares the Dragon Fly Algorithm with other heuristic approaches, resulting in a 12.42 % reduction in overall operating costs and the efficacy of the proposed algorithm is shown.. Using the Analytic Hierarchy Process (AHP), the User Satisfaction Index is assessed, revealing that the CPP demand response initiative tops the satisfaction scale with a score of 0.92881.. Moreover, this research offers an exhaustive evaluation of techno-economic markers for each scenario, systematically ranked using the proposed AHP methodology..

AimsSubclinical left ventricular (LV) dysfunction may occur in T2DM patients at the early asymptomatic stage, and LV reserve function is a sensitive index to detect subtle LV dysfunction. The purpose of our study is (1) to assess the LV reserve function using treadmill exercise stress echocardiography (ESE) in asymptomatic type 2 diabetes mellitus (T2DM) patients; (2) to explore the link of serum biological parameters and LV reserve function.MethodsThis study included 84 patients with asymptomatic T2DM from September 2021 to July 2022 and 41 sex- and age-matched healthy controls during the corresponding period. All subjects completed treadmill ESE, LV systolic function-related parameters such as global longitudinal strain (GLS) and systolic strain rate (SRs), as well as diastolic function-related parameters such as E wave (E), early diastolic velocity (e′), E/e′ ratio, early diastolic SR (SRe), and late diastolic SR (SRa) were compared at rest and immediately after exercise. The difference between LV functional parameters after treadmill exercise and its corresponding resting value was used to compute LV reserve function. In addition, the associations of LV reserve function and serum biological parameters were analyzed.ResultsPatients with T2DM did not significantly vary from the controls in terms of alterations in LV diastolic reserve measures, the changes of LVGLS and SRs (ΔGLS: 2.19 ± 2.72% vs. 4.13 ± 2.79%, P

Abstract Energy storage technology is the key to achieving a carbon emission policy. The purpose of the paper is to improve the overall performance of the combined cooling, heating and power-ground source heat pump (CCHP-GSHP) system by the battery. A new operation strategy (the two-point operation) is proposed by controlling the power generation unit work. The power generation unit has two operation modes of non-operation and rated efficiency operation by the storage electricity battery. The new operation strategy is compared with the traditional CCHP-GSHP that without a battery. The optimization goals include the primary energy saving ratio, the reduction ratio of carbon dioxide emissions, and the annual total cost saving ratio. The independent GSHP system is used as a reference system. Multipopulation genetic algorithms are selected to achieve the problem of optimization. A hotel building is selected for a case study. The optimal configuration of the coupling system is computed following the electric load strategy. Finally, the results show that the CCHP-GSHP system has a better performance under the new operation strategy compared with the traditional CCHP-GSHP (the primary energy saving ratio increases by 5.5%; the annual carbon dioxide emission reduction ratio increases by 1%; the annual total cost reduction ratio increases by 5.1%). This paper provides reference and suggestions for the integration and operation strategy of CCHP-GSHP in the future.

This paper describes MixGAN-TTS, an efficient and stable non-autoregressive speech synthesis based on diffusion model. The MixGAN-TTS uses a linguistic encoder based on soft phoneme-level alignment and hard word-level alignment approach which explicitly extracts word-level semantic information, and introduces pitch and energy predictors to optimally predict the rhythmic information of the audio. Specifically, we use the GAN to replace the Gaussian function to model the denoising distribution, aiming to enlarge the denoising steps size and reduce the number of denoising steps to accelerate the sampling speed of diffusion model. Diffusion model using GAN can significantly reduce the denoising steps, and to some extent solve the problem of not being able to apply in real-time. The mel-spectrogram is converted into the final audio by the HiFi-GAN vocoder. Experimental results show that the MixGAN-TTS outperforms the other models compared in terms of audio quality and mel-spectrogram modeling capability for 4 denoising steps. The ablation studies demonstrate that the structure of MixGAN-TTS is effective.

Abstract Background Nephrotic syndrome (NS) in children is widely believed to be associated with severe changes in the immune system. Based on lymphocyte subset analysis, we examined the pathogenesis of immune deficiencies in children with NS with varying steroid sensitivity. Methods Our study utilized flow cytometry to retrospectively analyze the ratios of lymphocyte subsets in 204 children with nephrotic syndrome and 19 healthy children. Results Compared with healthy children, the ratio of CD4 + /CD8 + in onset and remission was decreased in SRNS group (p

Development of an efficient technique for accurate and sensitive dibutyl phthalate (DBP) determination is crucial for food safety and environment protection. An ultrasensitive molecularly imprinted polymers (MIP) voltammetric sensor was herein engineered for the specific determination of DBP using poly-l-lysine/poly(3,4-ethylenedioxythiophene)/porous graphene nanocomposite (PLL/PEDOT−PG) and poly(o-phenylenediamine)-imprinted film as a label-free and sensing platform. Fabrication of PEDOT−PG nanocomposites was achieved through a simple liquid–liquid interfacial polymerization. Subsequently, poly-l-lysine (PLL) functionalization was employed to enhance the dispersibility and stability of the prepared PEDOT−PG, as well as promote its adhesion on the sensor surface. In the presence of DBP, the imprinted poly(o-phenylenediamine) film was formed on the surface of PLL/PEDOT−PG. Investigation of the physical properties and electrochemical behavior of the MIP/PLL/PEDOT−PG indicates that the incorporation of PG into PEDOT, with PLL uniformly wrapping its surface, significantly enhanced conductivity, carrier mobility, stability, and provided a larger surface area for specific recognition sites. Under optimal experimental conditions, the electrochemical response exhibited a linear relationship with a logarithm of DBP concentration within the range of 1 fM to 5 µM, with the detection limit as low as 0.88 fM. The method demonstrated exceptional stability and repeatability and has been successfully applied to quantify DBP in plastic packaging materials.

Background: An inactivated poliomyelitis vaccine made from Sabin strains (sIPVs) has widely been used in China since 2015. However, the quantitative data on the instant and persistent inhibition effects of maternal poliovirus antibodies on the immune response to sIPV priming and booster vaccination have not been available yet. Objective: In this study, we aim to explore and quantify the instant and persistent inhibition effect of maternal poliovirus antibodies on the immune response elicited by sIPV primary and booster vaccination. Methods: The immunogenicity data consisting of the days 0 and 30 after the prime and booster vaccination of the sIPV in a phase IV trial were pooled for a quantitative analysis of the inhibition effect of maternal poliovirus antibody. The geometric mean ratio (GMR) was calculated using linear regression models, representing that every 2-fold higher maternal poliovirus antibody titer may result in a (1-GMR) lower postimmunization antibody titer. Results: The GMRs for poliovirus types 1, 2, and 3 were 0.79 (0.77–0.82), 0.85 (0.81–0.89), and 0.87 (0.83–0.91) at 30 days after the priming series, 0.86 (0.83–0.89), 0.81 (0.76–0.85), and 0.86 (0.80–0.93) at one year after the priming series, and 0.96 (0.94–0.99), 0.89 (0.86–0.93), and 0.98 (0.93–1.03) at 30 days after the booster dose. The inhibition effect continued to exist until the booster dose 1 year later, and such a persistent inhibition effect was almost attenuated for poliovirus types 1 and 3, and partly reduced for type 2 at 30 days after the booster dose. Conclusion: A wider interval between the four sIPV doses might be a consideration for reducing the effect of maternal antibodies and subsequently eliciting and maintaining higher antibody levels to protect against poliovirus transmission and infection at the final stage of polio eradication in the global world. This study’s clinical trial registry number is NCT04224519.