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Abstract Background Long non-coding RNAs (LncRNAs) have been implicated as critical regulators of cancer tumorigenesis and progression. However, their functions and molecular mechanisms in colorectal cancer (CRC) still remain to be further elucidated. Methods LINC00460 was identified by differential analysis between human CRC and normal tissues and verified by in situ hybridization (ISH) and qRT-PCR. We investigated the biological functions of LINC00460 in CRC by in vitro and in vivo experiments. We predicted the mechanism and downstream functional molecules of LINC00460 by bioinformatics analysis, and confirmed them by dual luciferase reporter gene assay, RNA immunoprecipitation (RIP), RNA pull-down, etc. Results LINC00460 was found to be significantly overexpressed in CRC and associated with poor prognosis. Overexpression of LINC00460 promoted CRC cell immune escape and remodeled a suppressive tumor immune microenvironment, thereby promoting CRC proliferation and metastasis. Mechanistic studies showed that LINC00460 served as a molecular sponge for miR-186-3p, and then promoted the expressions of MYC, CD47 and PD-L1 to facilitate CRC cell immune escape. We also demonstrated that MYC upregulated LINC00460 expression at the transcriptional level and formed a positive feedback loop. Conclusions The LINC00460/miR-186-3p/MYC feedback loop promotes CRC cell immune escape and subsequently facilitates CRC proliferation and metastasis. Our findings provide novel insight into LINC00460 as a CRC immune regulator, and provide a potential therapeutic target for CRC patients.

A detrimental feedback loop between hypoxia and oxidative stress consistently drives macrophage polarization toward a pro-inflammatory M1 phenotype, thus persistently aggravating rheumatoid arthritis (RA) progression. Herein, an enzyme-catalyzed nanoplatform with synergistic hypoxia-relieving and reactive oxygen species (ROS)-scavenging properties was developed using bovine serum albumin-bilirubin-platinum nanoparticles (BSA-BR-Pt NPs). Bilirubin was employed to eliminate ROS, while platinum exhibited a synergistic effect in scavenging ROS and simultaneously generated oxygen. In mice RA model, BSA-BR-Pt NPs treatment exhibited superior effects, resulting in significant improvements in joint inflammation, cartilage damage, and bone erosion, compared to methotrexate, the most widely used antirheumatic drug. Mechanistically, RNA-sequencing data and experimental results elucidated that BSA-BR-Pt NPs induced a re-polarization of hypoxic M1 macrophages to M2 macrophages via switching glycolysis to oxidative phosphorylation through the inhibition of HIF-1α pathway. Collectively, this research for the first time elaborated the underlying mechanism of enzyme-catalyzed nanoplatform in orchestrating macrophage polarization, and identified a novel therapeutic strategy for RA and other inflammatory disorders.

Abstract Background The triglyceride-glucose (TyG) index is associated with the development and prognosis of coronary artery disease (CAD). However, the impact of the TyG index on CAD severity across different glucose metabolism states exhibits significant disparities in previous research. Methods This cross-sectional study comprised 10,433 participants from a prospective cohort. Participants were categorized into four groups based on glucose metabolism state: normal glucose regulation (NGR), prediabetes (pre-DM), diabetes mellitus (DM) without insulin prescribed (Rx), and DM with insulin Rx. The TyG index was determined by the following formula: Ln [TG (mg/dL) × FPG (mg/dL) / 2], where TG is triglycerides and FPG is fasting plasm glucose. Statistical methods such as binary logistic regression, interaction analysis, restricted cubic spline (RCS), and receiver operating characteristic (ROC) were employed to analyze the relationship between the TyG index and CAD severity across the entire population and glucose metabolism subgroups. Mediation analysis was conducted to examine the mediating effects of glycated hemoglobin (HbA1c) on these relationships. Sensitivity analysis was performed to ensure the robustness of the findings. Results Multivariable logistic regression analysis revealed a significant positive association between the TyG index and multi-vessel CAD in the entire population (OR: 1.34; 95% CI: 1.22–1.47 per 1-unit increment). Subgroup analysis demonstrated consistent positive associations in the NGR, pre-DM, and DM non-insulin Rx groups, with the highest OR observed in the NGR group (OR: 1.67; 95% CI: 1.3–2.14 per 1-unit increment). No correlation was found in the DM with insulin Rx subgroup. RCS analyses indicated the distinct dose-response relationships across different glucose metabolism subgroups. Including the TyG index in the established model slightly improved the predictive accuracy, particularly in the NGR group. Mediation analyses showed varying mediating effects of HbA1c among different glucose metabolism subgroups. Sensitivity analysis confirmed the robustness of the aforementioned relationships in the new-onset CAD population and in individuals not using antilipidemic medications. Conclusions The TyG index positively associated with CAD severity across all glucose metabolism states, except for individuals receiving insulin treatment. Moreover, it might serve as a supplementary noninvasive predictor of CAD severity in addition to established factors, especially in NGR patients. Graphical abstract

Abstract Background Mounting evidence supports a significant correlation between the stress hyperglycemia ratio (SHR) and both short- and long-term prognoses in patients with acute coronary syndrome (ACS). Nevertheless, research examining the association between the SHR and the complexity of coronary artery disease (CAD) is scarce. Therefore, this study aimed to explore the association between the SHR and CAD complexity, as assessed by the SYNTAX score, in patients with ACS. Methods A total of 4715 patients diagnosed with ACS were enrolled and divided into five groups according to the quintiles of the SHR. CAD complexity was assessed using the SYNTAX score and categorized as low (≤ 22) or mid/high (> 22) levels. Logistic regression was utilized to examine the association between the SHR and CAD severity (mid-/high SYNTAX score). Restricted cubic spline (RCS) curves were generated to assess the association between the SHR and CAD severity. Subgroup analyses were conducted to stratify outcomes based on age, sex, diabetes mellitus (DM) status, and clinical presentation. Results Among the total ACS population, 503 (10.7%) patients had mid/high SYNTAX scores. Logistic regression analysis revealed that the SHR was an independent risk factor for mid/high SYNTAX scores in a U-shaped pattern. After adjusting for confounding variables, Q1 and Q5 demonstrated elevated odds ratios (ORs) relative to the reference category Q3, with ORs of 1.61 (95% CI: 1.19 ∼ 2.19) and 1.68 (95% CI: 1.24 ∼ 2.29), respectively. Moreover, the ORs for Q2 (1.02, 95% CI: 0.73 ∼ 1.42) and Q4 (1.18, 95% CI: 0.85 ∼ 1.63) resembled that of Q3. Compared with the merged Q2-4 group, the ORs were 1.52 (95% CI: 1.21 ∼ 1.92) for Q1 group and 1.58 (95% CI: 1.25 ∼ 2) for the Q5 group. Subgroup analysis revealed that the U-shaped association between the SHR and mid/high SYNTAX score was attenuated in DM patients (P for interaction = 0.045). Conclusions There were U-shaped associations between the SHR and CAD complexity in ACS patients, with an SHR ranging from 0.68 to 0.875 indicating a relatively lower OR for mid/high SYNTAX scores. Further studies are necessary to both evaluate the predictive value of the SHR in ACS patients and explore the underlying mechanisms of the observed U-shaped associations.

Abstract Machine learning algorithms are frequently used to clinical risk prediction. Our study was designed to predict risk factors of prolonged intra-aortic balloon pump (IABP) use in patients with coronary artery bypass grafting (CABG) through developing machine learning-based models. Patients who received perioperative IABP therapy were divided into two groups based on their length of IABP implantation longer than the 75th percentile for the whole cohort: normal (≤ 10 days) and prolonged (> 10 days) groups. Seven machine learning-based models were created and evaluated, and then the Shapley Additive exPlanations (SHAP) method was employed to further illustrate the influence of the features on model. In our study, a total of 143 patients were included, comprising 56 cases (38.16%) in the prolonged group. The logistic regression model was considered the final prediction model according to its most excellent performance. Furthermore, feature important analysis identified left ventricular end-systolic or diastolic diameter, preoperative IABP use, diabetes, and cardiac troponin T as the top five risk variables for prolonged IABP implantation in patients. The SHAP analysis further explained the features attributed to the model. Machine learning models were successfully developed and used to predict risk variables of prolonged IABP implantation in patients with CABG. This may help early identification for prolonged IABP use and initiate clinical interventions.

Abstract Background This study aims to thoroughly study the connection between congenital heart disease (CHD) and neurodevelopmental disorders (NDDs) through observational and Mendelian randomization (MR) designs. Methods This observational study uses data from the National Survey of Children’s Health (2020–2021). Multivariable logistic regression and propensity score matching (PSM) were performed to analyze the association. PSM was used to minimize bias for covariates such as age, race, gender, maternal age, birth weight, concussion or brain injury, preterm birth, cerebral palsy, Down syndrome, and other inherited conditions. In MR analyses, inverse variance-weighted measures, weighted median, and MR-Egger were employed to calculate causal effects. Results A total of 85,314 children aged 0–17 were analyzed in this study. In regression analysis, CHD (p = 0.04), the current heart condition (p = 0.03), and the severity of current heart condition (p

Abstract Establishing appropriate metal-support interactions is imperative for acquiring efficient and corrosion-resistant catalysts for water splitting. Herein, the interaction mechanism between Ru nanoparticles and a series of titanium oxides, including TiO, Ti4O7 and TiO2, designed via facile non-stoichiometric engineering is systematically studied. Ti4O7, with the unique band structure, high conductivity and chemical stability, endows with ingenious metal-support interaction through interfacial Ti–O–Ru units, which stabilizes Ru species during OER and triggers hydrogen spillover to accelerate HER kinetics. As expected, Ru/Ti4O7 displays ultralow overpotentials of 8 mV and 150 mV for HER and OER with a long operation of 500 h at 10 mA cm−2 in acidic media, which is expanded in pH-universal environments. Benefitting from the excellent bifunctional performance, the proton exchange membrane and anion exchange membrane electrolyzer assembled with Ru/Ti4O7 achieves superior performance and robust operation. The work paves the way for efficient energy conversion devices.

Objective: DNA damage response (DDR) deficiency has emerged as a prominent determinant of tumor immunogenicity. This study aimed to construct a DDR-related immune activation (DRIA) signature and evaluate the predictive accuracy of the DRIA signature for response to immune checkpoint inhibitor (ICI) therapy in gastrointestinal (GI) cancer. Methods: A DRIA signature was established based on two previously reported DNA damage immune response assays. Clinical and gene expression data from two published GI cancer cohorts were used to assess and validate the association between the DRIA score and response to ICI therapy. The predictive accuracy of the DRIA score was validated based on one ICI-treated melanoma and three pan-cancer published cohorts. Results: The DRIA signature includes three genes (CXCL10, IDO1, and IFI44L). In the discovery cancer cohort, DRIA-high patients with gastric cancer achieved a higher response rate to ICI therapy than DRIA-low patients (81.8% vs. 8.8%; P < 0.001), and the predictive accuracy of the DRIA score [area under the receiver operating characteristic curve (AUC) = 0.845] was superior to the predictive accuracy of PD-L1 expression, tumor mutational burden, microsatellite instability, and Epstein–Barr virus status. The validation cohort demonstrated that the DRIA score identified responders with microsatellite-stable colorectal and pancreatic adenocarcinoma who received dual PD-1 and CTLA-4 blockade with radiation therapy. Furthermore, the predictive performance of the DRIA score was shown to be robust through an extended validation in melanoma, urothelial cancer, and pan-cancer. Conclusions: The DRIA signature has superior and robust predictive accuracy for the efficacy of ICI therapy in GI cancer and pan-cancer, indicating that the DRIA signature may serve as a powerful biomarker for guiding ICI therapy decisions.

Background Labeled antibodies are excellent imaging agents in oncology to non-invasively visualize cancer-related antigens expression levels. However, tumor tracer uptake (TTU) of specific antibodies in-vivo may be inferior to non-specific IgG in some cases. Objectives To explore factors affecting labeled antibody visualization by PD-L1 specific and non-specific imaging of nude mouse tumors. Methods TTU was observed in RKO model on Cerenkov luminescence (CL) and near-infrared fluorescence (NIRF) imaging of radionuclide 131 I or NIRF dyes labeled Atezolizumab and IgG. A mixture of NIRF dyes labeled Atezolizumab and 131 I-labeled IgG was injected, and TTU was observed in the RKO and HCT8 model by NIRF/CL dual-modality in-situ imaging. TTU were observed by 131 I-labeled Atezolizumab and IgG in-vitro distribution. Results Labeled IgG concentrated more in tumors than Atezolizumab. NIRF/CL imaging in 24 to 168 h showed that TTU gradually decreased over time, which decreased more slowly on CL imaging compared to NIRF imaging. The distribution data in-vitro showed that TTU of 131 I-labeled IgG was higher than that of 131 I-labeled Atezolizumab at any time point. Conclusion Non-specific IgG may not be suitable as a control for Atezolizumab in comparing tumor PD-L1 expression in nude mice via labeled antibody optical imaging under certain circumstances.

Abstract Intestinal fibrosis is one of the major complications of inflammatory bowel disease (IBD) and a pathological process that significantly impacts patient prognosis and treatment selection. Although current imaging assessment and clinical markers are widely used for the diagnosis and stratification of fibrosis, these methods suffer from subjectivity and limitations. In this study, we aim to develop a radiomics diagnostic model based on multi-slice computed tomography (MSCT) and clinical factors. MSCT images and relevant clinical data were collected from 218 IBD patients, and a large number of quantitative image features were extracted. Using these features, we constructed a radiomics model and transformed it into a user-friendly diagnostic nomogram. A nomogram was developed to predict fibrosis in IBD by integrating multiple factors. The nomogram exhibited favorable discriminative ability, with an AUC of 0.865 in the validation sets, surpassing both the logistic regression (LR) model (AUC = 0.821) and the clinical model (AUC = 0.602) in the test set. In the train set, the LR model achieved an AUC of 0.975, while the clinical model had an AUC of 0.735. The nomogram demonstrated superior performance with an AUC of 0.971, suggesting its potential as a valuable tool for predicting fibrosis in IBD and improving clinical decision-making. The radiomics nomogram, incorporating MSCT and clinical factors, demonstrates promise in stratifying fibrosis in IBD. The nomogram outperforms traditional clinical models and offers personalized risk assessment. However, further validation and addressing identified limitations are necessary to enhance its applicability.

Abstract Background About 31 individuals with CLTC variants have been reported worldwide, and all reported individuals have motor and mental retardation. CLTC is known to lead to intellectual developmental disorder, autosomal dominant 56. Few studies are focusing on the prenatal stage of the disease. Method An ultrasound examination was performed to obtain the prenatal phenotype. Whole-exome sequencing was used to find the pathogenic variant. Multiple computational tools predicted the conservation and deleteriousness. Minigene assay and western blot were utilized to investigate the effect on splicing of mRNA and protein expression. Result Here we found a novel de novo variant of CLTC in a fetus. The fetus manifested bilateral choroid plexus cysts of the brain, hyperechogenic kidneys, and ventricular septal defect. A heterozygous variant c.3249 + 1G > C was identified in the fetus. This position was conserved and the variant was predicted to be deleterious. Minigene assay revealed the presence of a truncating transcript with the retention of intron 20. Western blot result showed the c.3249 + 1G > C variant elicited degradation of the protein. Conclusion To the best of our knowledge, our study identified a novel de novo variant of CLTC and provided the earliest clinical characteristic of the CLTC variant at the prenatal stage. The functional experiment suggested the variant caused the altering of the RNA splicing and the protein expression. We extended the mutational spectrum of CLTC and provided guidance on genetic counseling.

Abstract Background Congenital heart defects (CHDs) are the most common birth defects. Assessment of the incidence, distribution, disease spectrum, and genetic deficits of fetal CHDs in China is urgently needed. Methods A national echocardiography screening program for fetal CHDs was implemented in 92 prenatal screening–diagnostic centers in China. Findings A total of 18,171 fetal CHD cases were identified from 2,452,249 pregnancies, resulting in 7·4/1,000 as the national incidence rate of fetal CHD. The incidences of fetal CHD in the six geographical regions, the southern, central, eastern, southwestern, northern, and northwestern, were 7·647 (CI: 7·383–7·915), 7·839 (CI: 7·680–8·000), 7·647 (CI: 7·383–7·915), 7·562 (CI: 7·225–7·907), 5·618 (CI: 5·337–5·906), and 4·716 (CI: 4·341–5·108), respectively, per 1,000 pregnancies. Overall, ventricular septal defect was the most common fetal CHD, accounting for 17.04% of screened pregnancies nationwide, and tetralogy of Fallot, the most common anomaly in the major defect of fetal CHD, was the second most common, accounting for 9.72%. A total of 76.24% cases of fetal CHD were found to be an isolated intracardiac single defect. The remaining 23.76% of cases of fetal CHD had multiple heart defects. Among all extracardiac malformations, the central nervous system (CNS) was the most common tissue with extracardiac anomalies associated with CHD, accounting for 22.89% of fetal CHD cases. Chromosomal karyotyping identified trisomy 18 as the most common chromosomal abnormality in fetal CHD. We also documented that CHD-containing syndromes could be identified with a comprehensive approach integrating prenatal ultrasound, MRI, pathological autopsy, and cytogenetics and molecular genetics. Conclusion Implementation of prenatal echocardiography as a practically feasible platform to screen fetal CHD will reduce the financial and emotional burden of CHD, which may facilitate intrauterine and neonatal intervention of CHD.

To investigate highway vehicle lane-changing behavior, we utilized the publicly available naturalistic driving dataset, HighD, to extract the movement data of vehicles involved in lane changes and their proximate counterparts. We employed univariate and multivariate Cox proportional hazards models alongside random survival forest models to analyze the influence of various factors on lane change duration, assess their statistical significance, and compare the performance of multiple random survival forest models. Our findings indicate that several variables significantly impact lane change duration, including the standard deviation of lane-changing vehicles, lane-changing vehicle speed, distance to the following vehicle in the target lane, lane-changing vehicle length, and distance to the following vehicle in the current lane. Notably, the standard deviation and vehicle length act as protective factors, with increases in these variables correlating with longer lane change durations. Conversely, higher lane-changing vehicle speeds and shorter distances to following vehicles in both the current and target lanes are associated with shorter lane change durations, indicating their role as risk factors. Feature variable selection did not substantially improve the training performance of the random survival forest model based on our findings. However, validation set evaluation showed that careful feature variable selection can enhance model accuracy, leading to improved AUC values. These insights lay the groundwork for advancing research in predicting lane-changing behaviors, understanding lane-changing intentions, and developing pre-emptive safety measures against hazardous lane changes.

In view of the problem that peanut harvesting in hilly areas mainly involves fresh food, and that the peanut-picking purity rate is low and there is high breakage in the peanut-harvesting process, key components such as the picking system of a fresh-peanut-picking crawler combine harvester, the picking tooth, and the concave screen were designed, and ANSYS Workbench 2020 software was used to check the reliability of the picking roller under working conditions in hilly areas. In the process of equipment operation, the picking purity rate and breakage rate were the main evaluation indexes, and the Box–Behnken test method was used to study the speed of the peanut-picking roller, the feeding amount, and the picking gap as the test factors. The results showed that the picking purity rate is 98.95%, with an error margin of 0.98%, compared to the predicted value under the conditions of 342 r/min speed, 0.75 kg/s feeding amount, and 32 mm picking gap. The breakage rate is 4.23% and the error is 0.4% compared with the predicted value, indicating that the optimized model is reliable and predictive. This study provides a theoretical basis for the optimal design of the peanut-picking system of peanut-picking combine harvesters in hilly areas.

ObjectiveThis study evaluated the predictive value of the vasoactive-ventilation-renal (VVR) score in identifying the risk of weaning failure after cardiac surgery and developing a nomogram model to help physicians improve the success rate of weaning from mechanical ventilation in adult patients undergoing postoperative cardiac surgery.MethodsClinical data were retrospectively collected from adult patients who underwent extracorporeal circulation cardiac surgery at the First Affiliated Hospital of Nanjing Medical University between August 2022 and April 2023 and who were subsequently transferred to the Intensive Care Unit (ICU) and treated with vasoactive drugs. Patients were divided into successful and unsuccessful weaning groups based on first-attempt weaning success. Variable selection was regularized using univariate logistic regression and Least absolute shrinkage and selection operator (LASSO) regularization. Multivariate logistic regression was performed to identify predictors and a nomogram was created to predict the risk of weaning failure.ResultsA total of 519 patients were included in the study. After selecting multiple stepwise variables, the VVR score before weaning, the modified Sequential Organ Failure Assessment (mSOFA) score on weaning day, and mechanical ventilation duration before weaning were determined as predictive indicators of weaning failure in adult patients after cardiac surgery. The optimal cut-off values for these indicators were 18.46 points, 4.33 points, and 20.50 h, respectively. The predictive model constructed using these three factors demonstrated good predictive performance.ConclusionsThe VVR score before weaning accurately predicts the probability of weaning failure in adult patients after cardiac surgery. The weaning risk-predictive nomogram model, established based on the VVR score, mSOFA score, and mechanical ventilation duration before weaning, demonstrated robust predictive ability.

Abstract Immune checkpoints play key roles in maintaining self-tolerance. Targeted potentiation of the checkpoint molecule PD-L1 through in situ manipulation offers clinical promise for patients with autoimmune diseases. However, the therapeutic effects of these approaches are often compromised by limited specificity and inadequate expression. Here, we report a two-step dual-anchor coupling strategy for enhanced immobilization of PD-L1 on target endogenous cells by integrating bioorthogonal chemistry and physical insertion of the cell membrane. In both type 1 diabetes and rheumatoid arthritis mouse models, we demonstrate that this approach leads to elevated and sustained conjugation of PD-L1 on target cells, resulting in significant suppression of autoreactive immune cell activation, recruitment of regulatory T cells, and systematic reshaping of the immune environment. Furthermore, it restores glucose homeostasis in type 1 diabetic mice for over 100 days. This specific in situ bioengineering approach potentiates the functions of PD-L1 and represents its translational potential.

Abstract Osteoarthritis (OA), a common joint disorder with articular cartilage degradation as the main pathological change, is the major source of pain and disability worldwide. Despite current treatments, the overall treatment outcome is unsatisfactory. Thus, patients with severe OA often require joint replacement surgery. In recent years, mesenchymal stem cells (MSCs) have emerged as a promising therapeutic option for preclinical and clinical palliation of OA. MSC-derived exosomes (MSC-Exos) carrying bioactive molecules of the parental cells, including non-coding RNAs (ncRNAs) and proteins, have demonstrated a significant impact on the modulation of various physiological behaviors of cells in the joint cavity, making them promising candidates for cell-free therapy for OA. This review provides a comprehensive overview of the biosynthesis and composition of MSC-Exos and their mechanisms of action in OA. We also discussed the potential of MSC-Exos as a therapeutic tool for modulating intercellular communication in OA. Additionally, we explored bioengineering approaches to enhance MSC-Exos’ therapeutic potential, which may help to overcome challenges and achieve clinically meaningful OA therapies.

Abstract Design A two-round Delphi survey was conducted to seek opinions from experts about the index system for the evaluation of training courses of clinical nursing staff’s information literacy. Besides, a non-randomized controlled experimental study was adopted to check the application effect of the training courses. Aims This study intended to construct a training course of information literacy for clinical nurses, train nurses in order to improve their information literacy level and provide theoretical reference for the training of information literacy courses for clinical nurses. Methods Two rounds of Delphi study were conducted for the study among 26 clinical medical and nursing experts as well as educational experts from 5 different provinces and cities in China. From July 2022 to October 2022, a total of 84 clinical nurses from two hospitals were selected by the convenience sampling method, of which the nurses in one hospital were the control group and the nurses in the other hospital were the observation group. 42 nurses in the observation group were trained by the constructed information literacy training course. Questionnaire evaluation was used to compare the differences in the level of information literacy of nurses and the training effect between the two groups. Results The results of the Delphi consultation showed that the expert’s judgment coefficient was 0.958, the expert’s familiarity was 0.946, and the expert’s authority coefficient was 0.952. Finally, a training course of information literacy for clinical nurses with 4 course categories and 45 specific course contents was formed. Among them, nursing information awareness included 7 courses, nursing information knowledge 15 courses, nursing information ability 19 courses, and nursing information ethics 4 courses. The results of the empirical study showed that the information literacy level of the nurses in the observation group after the training of the information literacy course was improved, and the scores in nursing information awareness, nursing information knowledge, nursing information ability, and information ethics were significantly higher than those in the control group after training (P

To explore the effects of different irrigation approaches, mulching, and their interaction on greenhouse melon (Cucumis melo L.) production and water use, a field experiment was conducted in Northern China using four treatments: mulching drip irrigation (MDI), mulching furrow irrigation (MFI), drip irrigation (DI), and furrow irrigation (FI; CK). The plant biomass, yield, water consumption, and water use efficiency (WUE) of melons were measured at different growth stages. The results showed that mulching has significant positive impacts on the growth as well as the fruit yield of melons. However, the water use characteristics of the plant were more greatly determined by the various irrigation approaches, and there was a significant interaction between the irrigation approach and mulching for both the total water consumption and WUE of the greenhouse melon. Of these treatments, MDI resulted in the highest yield of 38.49 t/hm2, which was significantly higher than the yields obtained with DI (32.36 t·hm−2) and FI (CK, 30.34 t·hm−2). In addition, the water consumption under MDI was 45.80% lower than FI (CK), which resulted in the promotion of WUE under MDI. The WUE range of the greenhouse melon is as follows: MDI (334.77 kg·mm−1·hm−2) > DI (244.84 kg·mm−1·hm−2) > MFI (189.78 kg·mm−1·hm−2) > FI (CK; 142.94 kg·mm−1·hm−2). The findings of this study indicate that mulching can boost melon yield, and drip irrigation can limit water consumption. This study provides a reference point for policymakers, indicating that drip irrigation with plastic mulching could be a feasible adaptation strategy for increasing greenhouse melon production in Northern China, as well as other agriculture regions that suffer from water shortages.

Tumor cells are characterized by a delicate balance between elevated oxidative stress and enhanced antioxidant capacity. This intricate equilibrium, maintained within a threshold known as redox homeostasis, offers a unique perspective for cancer treatment by modulating reactive oxygen species (ROS) levels beyond cellular tolerability, thereby disrupting this balance. However, currently used chemotherapy drugs require larger doses to increase ROS levels beyond the redox homeostasis threshold, which may cause serious side effects. How to disrupt redox homeostasis in cancer cells more effectively remains a challenge. In this study, we found that sodium selenite and docosahexaenoic acid (DHA), a polyunsaturated fatty acid extracted from marine fish, synergistically induced cytotoxic effects in colorectal cancer (CRC) cells. Physiological doses of DHA simultaneously upregulated oxidation and antioxidant levels within the threshold range without affecting cell viability. However, it rendered the cells more susceptible to reaching the upper limit of the threshold of redox homeostasis, facilitating the elevation of ROS levels beyond the threshold by combining with low doses of sodium selenite, thereby disrupting redox homeostasis and inducing MAPK-mediated paraptosis. This study highlights the synergistic anticancer effects of sodium selenite and DHA, which induce paraptosis by disrupting redox homeostasis in tumor cells. These findings offer a novel strategy for more targeted and less toxic cancer therapies for colorectal cancer treatment.

Most studies on Chinese dormitories are carried out in summer, while few focus on a transition season or winter. This study evaluated the air quality of a student dormitory in a university in the Beijing area by using a questionnaire survey and on-site measurements. The CO2 concentration was used as an indoor air quality evaluation index to characterize the freshness of the air, and different window opening conditions in the dormitory were simulated, with corresponding improvement plans proposed. The results of this study revealed that the air quality and thermal comfort of the student dormitories during a transition season and winter fell short of expectations. According to the survey, students who opened their windows frequently had a better subjective perception of the air quality. However, due to the large temperature difference between day and night, more than 80% of the students felt too cold when opening the windows. For daytime conditions, the area of unilateral ventilation window opening should not be less than 0.39 m2, the area of bilateral ventilation window opening should not be less than 0.13 m2, and the time taken to close the windows and doors should not exceed the maximum ventilation interval. Empirical equations were fitted for nighttime conditions based on the CO2 concentration, number of people in the room, and window opening area, resulting in a reasonable window opening area of 0.349 m2~0.457 m2. In sum, this study assessed the air quality status within typical university dormitories across varying seasons, gaining a clear understanding of how different ventilation strategies and occupant densities influence air freshness and thermal comfort. Based on these insights, a practical and optimized window area recommendation was formulated to enhance the indoor environmental quality in these dormitories.

Abstract Effective reprogramming of chronic wound healing remains challenging due to the limited drug delivery efficacy hindered by physiological barriers, as well as the inappropriate dosing timing in distinct healing stages. Herein, a core-shell structured microneedle array patch with programmed functions (PF-MNs) is designed to dynamically modulate the wound immune microenvironment according to the varied healing phases. Specifically, PF-MNs combat multidrug-resistant bacterial biofilm at the early stage via generating reactive oxygen species (ROS) under laser irradiation. Subsequently, the ROS-sensitive MN shell gradually degrades to expose the MN core component, which neutralizes various inflammatory factors and promotes the phase transition from inflammation to proliferation. In addition, the released verteporfin inhibits scar formation by blocking Engrailed-1 (En1) activation in fibroblasts. Our experiments demonstrate that PF-MNs promote scarless wound repair in mouse models of both acute and chronic wounds, and inhibit the formation of hypertrophic scar in rabbit ear models.

Genetically modified intestinal organoids are being explored as potential surrogates of immortalized cell lines and gene-engineered animals. However, genetic manipulation of intestinal organoids is time-consuming, and the efficiency is far beyond satisfactory. To ensure the yield of the genetically modified organoids, large quantity of starting materials is required, and the procedure usually takes more than 10 days. Two major obstacles that restrict the genetic delivery efficiency are the three-dimensional culture condition and that the genetic delivery is carried out in cell suspensions. In the present study, we introduce a novel highly efficient strategy for building genetically modified intestinal organoids in which genetic delivery was performed in freshly established monolayer primary intestinal epithelial cells under two-dimensional conditions and subsequentially transformed into three-dimensional organoids. The total procedure can be finished within 10 hr while displaying much higher efficiency than the traditional methods. Furthermore, this strategy allowed for the selection of transgenic cells in monolayer conditions before establishing high-purity genetically modified intestinal organoids.

BackgroundUrinary tract infections (UTI) is a prevalent condition in those with diabetes, and in severe cases, it may escalate to sepsis. Therefore, it is important to analyze the risk variables associated with sepsis in diabetes individuals with UTI.MethodsThis research was a retrospective cross-sectional analysis. From January 2011 to June 2022, a group of individuals with diabetes were identified as having UTI at a tertiary hospital situated in Southeastern China. Patient data, including information on urine culture, was collected retrospectively from a clinical record database. The participants were categorized into the sepsis and non-sepsis groups. The risk variables were derived using both uni-and multiple- variable regression analysis.ResultsThe research included 1919 patients, of whom 1106 cases (57.63%) had positive urine cultures. In total, 445 blood culture samples were tested, identifying 186 positive cases (41.80%). The prevalence of bacteria in urine and blood samples was highest for Escherichia coli and Klebsiella pneumoniae, respectively. Moreover, 268 individuals (13.97%) exhibited sepsis. The regression analysis indicated a positive correlation between sepsis and albumin (ALB)55.84 mg/L and white blood cell count (WBC) >8.485 X 109/L in diabetic cases with UTIs. By integrating the three aforementioned parameters, the area under the receiver operating characteristic curve was 0.809.ConclusionsThe early detection of sepsis in diabetic individuals with UTI may be achieved using a comprehensive analysis of CRP, WBC, and ALB test findings.

BackgroundBrain atrophy is a type of neurological and psychiatric disorder characterized by a decrease in brain tissue volume and weight for various reasons and can have a serious impact on the quality of life of patients. Although there are many studies on brain atrophy, there is a lack of relevant bibliometric studies. Therefore, this study aims to provide a visual analysis of global trends in brain atrophy research over the past 16 years.MethodsCiteSpace and VOSviewer were used to visually analyze publication output, scientific collaborations, cocitations, publishing journals, and keywords to determine the current status and future trends of brain atrophy research. Materials published from 2008 to 2023 were collected from the Web of Science Core Collection (WoSCC) database. This study placed no restrictions on the types of literature and focused on English language publications.ResultsA total of 3,371 publications were included in the analysis. From 2008 to 2023, the number of publications increased annually. In terms of national and academic institutions, universities in the United States and University College London rank first in publication out. Barkhof Frederik and Zivadinov Robert are the most prolific researchers in this field. The publication with the highest cocitation strength is “Deep gray matter volume loss drives disability worsening in multiple sclerosis.” Keyword clustering analysis showed that “Alzheimer’s disease” and “multiple sclerosis” are current popular topics. The analysis of emergent words indicates that “cerebral small vessel disease,” “neurodegeneration,” and “cortex/gray matter volume” may become hot research topics in the coming years.ConclusionThis study analyses papers on brain atrophy from the past 16 years, providing a new perspective for research in this field. In the past 16 years, research on brain atrophy has received increasing attention. The quality of articles in this field is generally high. Extensive national cooperation already exists. The statistical results indicate that a stable core author group in the field of brain atrophy has almost formed.

To understand the current situation and development trend of energy consumption and carbon emissions in the fishery industry, a Long-Range Energy Alternatives Planning System (LEAP)-fishery model for Zhoushan City was constructed, and the trends of energy consumption and carbon emissions in the Zhoushan City fishery industry were analyzed under the business-as-usual scenario, the low-carbon scenario, and the strengthened low-carbon scenario. The results show that under the business-as-usual scenario, the future energy consumption of Zhoushan City’s fisheries in general shows an increasing trend, and the composition of energy consumption in all scenarios is primarily dominated by fossil energy, with diesel and coal predominating. In terms of the structure of end-use energy consumption, fishing vessels and aquaculture consume the most energy, with energy consumption exceeding 30% of total energy consumption in all scenarios. In terms of the emission reduction contribution rate, which the promotion of clean energy generation, the improvement of energy efficiency, and the reduction of aquaculture production play key roles in the low-carbon development of the fishery industry. From an economic perspective, carbon reduction measures such as reduction of aquaculture production and increased efficiency of energy delivery would have significant economic benefits, but these measures have limitations. Finally, suggestions are made to optimize the energy structure, improve the implementation of energy intensity and total energy control, and strengthen public awareness of energy conservation to reduce carbon emissions from the fishery industry, thus making the research in this paper relevant to real-world situations.

AbstractBackground Intravenous immunoglobulin (IVIG) resistance is of prime importance in Kawasaki disease (KD). In this study, we examined the value and mechanism of serum amyloid A (SAA) level in predicting IVIG resistance in patients with KD.Methods SAA levels were measured in 497 consecutive patients with KD before IVIG therapy in the training set. The patients were divided into two groups (IVIG-responsive and IVIG-resistant) according to the American Heart Association (AHA) definition of IVIG resistance. Demographic, echocardiographic, and laboratory data were also retrospectively analyzed and tabulated to predict IVIG resistance. The predictive value of SAA was validated on test sets of prospective data. Cytokine microarrays were analyzed from 4 patients with resistant to IVIG, 4 patients with responsive to IVIG and 4 healthy volunteers.Results During the training set, 409 patients with KD were enrolled, of whom 43 (10.5%) were resistant to initial IVIG treatment and 47 (11.49%) had coronary artery lesions (CALs). Serum levels of SAA were higher in the IVIG resistant group compared to the IVIG responsive group, (380.00 [204.40–547.25] vs 230.85 [105.40–490.00] mg/L; p = .008). The values of total bilirubin, C-reactive protein, neutrophils, alanine aminotransferase, aspartate aminotransferase, interleukin-6(IL-6), and procalcitonin were significantly higher in the IVIG-resistant group than in the IVIG-responsive group (p

[Objective] The ecological environmental changes of Zhoushan Island from 2000 to 2020 were dynamically monitored and evaluated in order o provide a scientific reference for the evaluation of the ecological quality of similar island areas. [Methods] Remote sensing images of Zhoushan Island in 2000, 2005, 2010, 2015, and 2020 were selected on the Google Earth Engine (GEE) platform. Wetness, greenness, heat, and dryness were extracted for coupling, and the remote sensing environmental index (RSEI) was obtained. The principal component analysis method was then used to evaluate changes in the quality of the ecological environment of Zhoushan Island. [Results] ① The mean values of RSEI on Zhoushan Island at the five time points were 0.631 2, 0.637 5, 0.611 6, 0.550 3, and 0.502 4, respectively, with a total decrease of 20.41% over the study period. ② The ecological quality of Zhoushan Island exhibited a downward trend over time, with the area of the island having excellent and good ecological quality decreasing by 24.39%, and the area with poor and poorer quality increasing by 19.82%. ③ During the study period, human development activities on Zhoushan Island have increased significantly, land use types have changed, and climate change and human activities have combined to degrade the ecological environment of Zhoushan Island. [Conclusion] RSEI was effectively used to monitor and evaluate the ecological environmental quality of the island. The ecological environmental quality of Zhoushan Island was relatively stable during the early part of the study period, but there was an obvious decline in environmental quality during the later part of the study period, with a total decrease of about 20.41% during the study period.

Sika deer are known to prefer oak leaves, which are rich in tannins and toxic to most mammals; however, the genetic mechanisms underlying their unique ability to adapt to living in the jungle are still unclear. In identifying the mechanism responsible for the tolerance of a highly toxic diet, we have made a major advancement by explaining the genome of sika deer. We generated the first high-quality, chromosome-level genome assembly of sika deer and measured the correlation between tannin intake and RNA expression in 15 tissues through 180 experiments. Comparative genome analyses showed that the UGT and CYP gene families are functionally involved in the adaptation of sika deer to high-tannin food, especially the expansion of the UGT family 2 subfamily B of UGT genes. The first chromosome-level assembly and genetic characterization of the tolerance to a highly toxic diet suggest that the sika deer genome may serve as an essential resource for understanding evolutionary events and tannin adaptation. Our study provides a paradigm of comparative expressive genomics that can be applied to the study of unique biological features in non-model animals.

Background: Acute kidney injury (AKI) frequently occurs after aortic surgery and has a significant impact on patient outcomes. Early detection or prediction of AKI is crucial for timely interventions. This study aims to develop and validate a novel model for predicting AKI following aortic surgery. Methods: We enrolled 156 patients who underwent on-pump aortic surgery in our hospital from February 2023 to April 2023. Postoperative levels of eight cytokines related to macrophage polarization analyzed using a multiplex cytokine assay. All-subset regression was used to select the optimal cytokines to predict AKI. A logistic regression model incorporating the selected cytokines was used for internal validation in combination with a bootstrapping technique. The model’s ability to discriminate between cases of AKI and non-AKI was assessed using receiver operating characteristic (ROC) curve analysis. Results: Of the 156 patients, 109 (69.87%) developed postoperative AKI. Interferon-gamma (IFN-γ) and interleukin-4 (IL-4) were identified as candidate AKI predictors. The cytokine-based model including IFN-γ and IL-4 demonstrated excellent discrimination (C-statistic: 0.90) and good calibration (Brier score: 0.11). A clinical nomogram was generated, and decision curve analysis revealed that the cytokine-based model outperformed the clinical factor-based model in terms of net benefit. Moreover, both IFN-γ and IL-4 emerged as independent risk factors for AKI. Patients in the second and third tertiles of IFN-γ and IL-4 concentrations had a significantly higher risk of severe AKI, a higher likelihood of requiring renal replacement therapy, or experiencing in-hospital death. These patients also had extended durations of mechanical ventilation and intensive care unit stays, compared with those in the first tertile (all p for group trend

BackgroundRobust immune cell gene expression signatures are central to the analysis of single cell studies. Nearly all known sets of immune cell signatures have been derived by making use of only single gene expression datasets. Utilizing the power of multiple integrated datasets could lead to high-quality immune cell signatures which could be used as superior inputs to machine learning-based cell type classification approaches.ResultsWe established a novel workflow for the discovery of immune cell type signatures based primarily on gene-versus-gene expression similarity. It leverages multiple datasets, here seven single cell expression datasets from six different cancer types and resulted in eleven immune cell type-specific gene expression signatures. We used these to train random forest classifiers for immune cell type assignment for single-cell RNA-seq datasets. We obtained similar or better prediction results compared to commonly used methods for cell type assignment in independent benchmarking datasets. Our gene signature set yields higher prediction scores than other published immune cell type gene sets in random forest-based cell type classification. We further demonstrate how our approach helps to avoid bias in downstream statistical analyses by re-analysis of a published IFN stimulation experiment.Discussion and conclusionWe demonstrated the quality of our immune cell signatures and their strong performance in a random forest-based cell typing approach. We argue that classifying cells based on our comparably slim sets of genes accompanied by a random forest-based approach not only matches or outperforms widely used published approaches. It also facilitates unbiased downstream statistical analyses of differential gene expression between cell types for significantly more genes compared to previous cell classification algorithms.

Abstract Background Programmed cell death 1 ligand 1(PD-L1) is overexpressed in many tumors. The radionuclide-labeled anti-PD-L1 monoclonal antibody can be used for imaging and therapy of PD-L1 overexpressing cancer. Here, we described 131I-labeled Atezolizumab (131I-Atezolizumab, targeting PD-L1) as a therapeutic agent for colorectal cancer with PD-L1 overexpression. Methods 131I-Atezolizumab was prepared by the Iodogen method. The expression levels of PD-L1 in different human colorectal cells were determined by flow cytometry, western blot and cell binding assay. The immunoreactivity of 131I-Atezolizumab to PD-L1 high-expressing cells was determined by immunoreactive fraction. The killing abilities of different concentrations of 131I-Atezolizumab on cells with high and low expression of PD-L1 were detected by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) method. Cerenkov luminescence imaging (CLI) and radioimmunotherapy (RIT) of 131I-Atezolizumab were performed on two human colorectal cancer models. The distribution and tumor targeting of 131I-Atezolizumab were evaluated by imaging. Tumor volume and survival time were used as indicators to evaluate the anti-tumor effect of 131I-Atezolizumab. Results The expression level of PD-L1 in vitro determined by the cell binding assay was related to the data of flow cytometry and western blot. 131I-Atezolizumab can specifically bind to PD-L1 high-expressing cells in vitro to reflect the expression level of PD-L1. Immunoreactive fraction of PD-L1 high-expressing RKO cells with 131I-Atezolizumab was 52.2%. The killing ability of 131I-Atezolizumab on PD-L1 high-expressing cells was higher than that of low-expressing cells. CLI proved that the specific uptake level of tumors depends on the expression level of PD-L1. Effect of 131I-Atezolizumab RIT showed an activity-dependent tumor suppressor effect on RKO tumor-bearing mice with high PD-L1 expression. 131I-Atezolizumab (37 MBq) can improve the median survival time of mice (34 days), compared to untreated mice (27 days) (P = 0.027). Although a single activity(37 MBq) of 131I-Atezolizumab also inhibited the tumors of HCT8 tumor-bearing mice with low PD-L1 expression (P

Rational regulation of electrochemical reconfiguration and exploration of activity origin are important for electrocatalysis. Here, a novel CoC2O4@MXene tubular catalyst is rationally designed to achieve rapid complete reconfiguration engineering during the hydrogen evolution reaction process.

Abstract Purpose In recent years, time in range (TIR), defined as a percentage within a target time range, has attracted much attention. This study was aimed to investigate the short-term effects of Time in Rang on diabetic patients undergoing toe amputation in a more specific and complete manner. Methods A retrospective analysis on patients with diabetic foot ulcer (DFU) treated by toe amputation or foot amputation at the First Affiliated Hospital of Wenzhou Medical University between January 2015 and December 2019 were evaluated. A 1:1 match was conducted between the TIR

Accurately analyzing the water system’s status in a region is crucial for mitigating water resource constraints on the development of island areas. This study centers on Zhoushan, an archipelago city, and employs the water footprint theory (WFT) and the logarithmic mean Divisia index (LMDI) model to scrutinize the evolution of water footprints from 2010 to 2020. It also dissects the impacts of economic, technological, and population factors on these changes. The findings are as follows: From 2010 to 2020, Zhoushan’s total water footprint has remained relatively stable, but its structure is imbalanced, indicating an unhealthy development. The agricultural water footprint dominates, though its proportion has steadily declined from 64% to 28%, while the imported water footprint has significantly increased from 2% to 29%. The skewed distribution of internal and external water consumption contributes to this imbalance, with internal water use accounting for a staggering 86.43%. The ecological security of water resources appears bleak, with average water scarcity and pressure indices reaching 0.42 and 0.41, respectively, indicating an overloaded state of water resources. Despite a 144.50% growth in water footprint efficiency from 2010 to 2020, the average water resource sustainability index merely stands at 0.531, and its sustainability remains precarious. The LMDI model results unveil that technological factors are the primary negative driving factors, contributing to 47.06% of the changes in Zhoushan’s water resource utilization. Conversely, economic and population factors play positive roles, contributing 42.29% and 10.65%, respectively. Therefore, in the course of development, there should be a focus on promoting water-saving tec-nologies, and continuously enhancing the efficiency of water resource utilization. Simultaneously, attention should be given to the development of the tertiary sector and the water resource pressure resulting from the mobile population, aiming to achieve sustainable water resource utilization and further ensure the ecological security of Zhoushan City.

Abstract Background Pectus excavatum is the most common congenital chest wall defect. Thoracolumbar spinal stenosis and kyphoscoliosis was seen in patients with pectus excavatum. It can be caused by ossification of the ligamentum flavum, which is rare in patients with pectus excavatum. Case presentation We reported a 26-year-old woman presented bilateral lower extremities weakness and numbness for two months, progressive worsening. She was diagnosed as thoracolumbar spinal stenosis with ossification of the ligamentum flavum, thoracolumbar kyphoscoliosis associated with pectus excavatum. The posterior instrumentation, decompression with laminectomy, and de-kyposis procedure with multilevel ponte osteotomy were performed. Her postoperative course was uneventful and followed up regularly. Good neurologic symptoms improvement and spinal alignment were achieved. Conclusions Pectus excavatum, kyphoscoliosis associated with thoracolumbar spinal stenosis is rare, and thus her treatment options are very challengeable. Extensive laminectomy decompression and de-kyphosis procedures can achieve good improvement of neurologic impingement and spinal alignment.

Abstract Structural anomalies of the central nervous system (CNS) are one of the most common fetal anomalies found during prenatal imaging. However, the genomic architecture of prenatal imaging phenotypes has not yet been systematically studied in a large cohort. Patients diagnosed with fetal CNS anomalies were identified from medical records and images. Fetal samples were subjected to low-pass and deep whole-genome sequencing (WGS) for aneuploid, copy number variation (CNV), single-nucleotide variant (SNV, including insertions/deletions (indels)), and small CNV identification. The clinical significance of variants was interpreted based on a candidate gene list constructed from ultrasound phenotypes. In total, 162 fetuses with 11 common CNS anomalies were enrolled in this study. Primary diagnosis was achieved in 62 cases, with an overall diagnostic rate of 38.3%. Causative variants included 18 aneuploids, 17 CNVs, three small CNVs, and 24 SNVs. Among the 24 SNVs, 15 were novel mutations not reported previously. Furthermore, 29 key genes of diagnostic variants and critical genes of pathogenic CNVs were identified, including five recurrent genes: i.e., TUBA1A, KAT6B, CC2D2A, PDHA1, and NF1. Diagnostic variants were present in 34 (70.8%) out of 48 fetuses with both CNS and non-CNS malformations, and in 28 (24.6%) out of 114 fetuses with CNS anomalies only. Hypoplasia of the cerebellum (including the cerebellar vermis) and holoprosencephaly had the highest primary diagnosis yields (>70%), while only four (11.8%) out of 34 neural tube defects achieved genetic diagnosis. Compared with the control group, rare singleton loss-of-function variants (SLoFVs) were significantly accumulated in the patient cohort.

Recently, the morbidity and mortality of pancreatic cancer have been increasing year by year. Because of its deep anatomical location and because most presented patients often suffer from abdominal pain or jaundice, it is difficult to diagnose pancreatic cancer at an early stage, leading to late clinical stage and poor prognosis. integrated positron emission tomography/magnetic resonance imaging (PET/MRI) fusion imaging not only has the characteristics of high resolution and multi-parameter imaging of MRI, but also combines the high sensitivity and the semi-quantitative characteristics of PET. In addition, the continuous development of novel MRI imaging and PET imaging biomarkers provide a unique and precise research direction for future pancreatic cancer research. This review summarizes the value of PET/MRI in the diagnosis, staging, efficacy monitoring, and prognosis evaluation of pancreatic cancer, and prognosis for developing emerging imaging agents and artificial intelligence radiomics in pancreatic cancer.

Objective Escherichia coli (E. coli) is the most common opportunistic clinical micro-organism with high drug resistance. This study aimed to analyse the resistance pattern of E. coli according to patient age and clinical sample type.Design and setting This retrospective observational study was conducted in a tertiary hospital in southeastern China.Participants E. coli strains were isolated from blood, urine and sputum of infected inpatients. The patients were divided into four age groups: children (0–14 years old, including neonatal and non-neonatal groups), youths (15–40 years old), middle-aged (41–60 years old) and old (>60 years old).Results A total of 7165 E. coli strains were collected from all samples. Compared with urine and blood isolates, more sputum isolates were resistant against 12 tested antibiotics. Furthermore, urine isolates were more resistant to levofloxacin than sputum and blood isolates. Although the patients’ age was not associated with resistance rates of E. coli strains isolated from blood, a larger proportion of urine-derived strains from youths were resistant to sulfamethoxazole-trimethoprim and piperacillin-tazobactam than those from old people. The sputum strains from the elderly were more resistant to most of the tested antibiotics compared with sputum strains isolated from children.Conclusions The resistance profile of E. coli is different among age groups and specimen sources and should be considered during E. coli infection treatment.

Abstract Background Short-rib thoracic dysplasia 3 with or without polydactyly (SRTD3, OMIM: 613091) is an autosomal recessive disorder. SRTD3 presents clinically with a narrow thorax, short ribs, shortened tubular bones, and acetabular roof abnormalities. Clinical signs of SRTD3 vary among individuals. Pathogenic variants of DYNC2H1 (OMIM: 603297) have been reported to cause SRTD3. Methods We performed a detailed clinical prenatal sonographic characterization of a foetus with SRTD3. Trio whole-exome sequencing was used to identify causative variants in the family. The identified variants in the families were validated by Sanger sequencing and mass spectrometry. Multiple computational tools were used to predict the harmfulness of the two variants. A minigene splicing assay was carried out to evaluate the impact of the splice-site variant. Results We evaluated prenatal sonographic images of the foetus with SRTD3, including abnormal rib curvature, narrow thorax, bilateral hypoplastic lungs, bilateral polydactyly, syndactyly, and foetal visceral situs inversus with mirror-image dextrocardia. We revealed novel compound variants of DYNC2H1 (NM_001377.3:c.11483T > G (p.Ile3828Arg) and c.2106 + 3A > T). Various statistical methods predicted that the variants would cause harmful effects on genes or gene products. The minigene assay findings suggested that c.2106 + 3A > T caused the skipping over exon 14, producing an exon 14 loss in the protein. Conclusion This study identified a foetus with SRTD3 with situs inversus totalis with mirror-image dextrocardia in a Chinese family, revealing two novel compound heterozygous dynein cytoplasmic 2 heavy chain 1 (DYNC2H1) variants, expanding the phenotypic spectrum of SRTD3. The minigene study of c.2106 + 3A > T was predicted to cause an inframe exclusion of exon 14, which was predicted to have important molecular functions. Our findings strongly supported the use of WES in prenatal diagnosis and helped to understand the correlation of genotype and phenotypes of DYNC2H1. The specific sonographic findings and the molecular diagnosis helped add experience to further our expertise in prenatal counselling for SRTD3.

Developing hydrolytic nanozymes remains challenging. Here the authors present a rational methodology to design hydrolytic nanozyme by developing a data-informed strategy to screen and identify potential scaffold and active sites of hydrolase-like nanozyme.

Abstract Background Birth defects are responsible for approximately 7% of neonatal deaths worldwide by World Health Organization in 2004. Many methods have been utilized for examining the congenital anomalies in fetuses. This study aims to investigate the efficiency of simultaneous CNV-seq and whole-exome sequencing (WES) in the diagnosis of fetal anomaly based on a large Chinese cohort. Methods In this cohort study, 1800 pregnant women with singleton fetus in Hubei Province were recruited from 2018 to 2020 for prenatal ultrasonic screening. Those with fetal structural anomalies were transferred to the Maternal and Child Health Hospital of Hubei Province through a referral network in Hubei, China. After multidisciplinary consultation and decision on fetal outcome, products of conception (POC) samples were obtained. Simultaneous CNV-seq and WES was conducted to identify the fetal anomalies that can compress initial DNA and turnaround time of reports. Results In total, 959 couples were finally eligible for the enrollment. A total of 227 trios were identified with a causative alteration (CNV or variant), among which 191 (84.14%) were de novo. Double diagnosis of pathogenic CNVs and variants have been identified in 10 fetuses. The diagnostic yield of multisystem anomalies was significantly higher than single system anomalies (32.28% vs. 22.36%, P = 0.0183). The diagnostic rate of fetuses with consistent intra- and extra-uterine phenotypes (172/684) was significantly higher than the rate of these with inconsistent phenotypes (17/116, P = 0.0130). Conclusions Simultaneous CNV-seq and WES analysis contributed to fetal anomaly diagnosis and played a vital role in elucidating complex anomalies with compound causes.

Abstract Background Granulosa cells (GCs) in cumulus oophorus highly express follicle stimulating hormone receptor (FSHR), which is the most important mediator of both estradiol synthesis and oocyte maturation. Obese women have elevated free fatty acids (FFAs) levels in their follicular fluids and decreased FSHR expression in GCs, which is related to an altered protein kinase B/glycogen synthase kinase 3β (Akt/GSK3β) signaling pathway. Such FFA increases accompany 3-fold rises in pseudokinase 3 (TRIB3) expression and reduce the Akt phosphorylation status in both the human liver and in insulinoma cell lines. Therefore, in a high FFA environment, we determined if TRIB3 mediates regulation of FSHR via the Akt/GSK3β signaling pathway in human GCs. Methods GCs from women undergoing in vitro fertilization were collected and designated as high and low FFAs cohorts based on their follicular fluid FFA content. GCs with low FFA levels and a human granulosa-like tumor (KGN) cell line were exposed to palmitic acid (PA), which is a dominate FFA follicular fluid constituent. The effects were assessed of this substitution on the Akt/GSK3β signaling pathway activity as well as the expressions of TRIB3 and FSHR at both the gene and protein levels by qPCR, Western blot and immunofluorescence staining analyses. Meanwhile, the individual effects of TRIB3 knockdown in KGN cells and p-AKT inhibitors were compared to determine the mechanisms of FFA-induced FSHR downregulation. Results The average FSH dose consuming per oocyte (FSH dose/oocyte) was elevated and Top embryo quality ratio was decreased in women with high levels of FFAs in their follicular fluid. In these women, the GC TRIB3 and ATF4 protein expression levels were upregulated which was accompanied by FSHR downregulation. Such upregulation was confirmed based on corresponding increases in their gene expression levels. On the other hand, the levels of p-Akt decreased while p-GSK3β increased in the GCs. Moreover, TRIB3 knockdown reversed declines in FSHR expression and estradiol (E2) production in KGN cells treated with PA, which also resulted in increased p-Akt levels and declines in the p-GSK3β level. In contrast, treatment of TRIB3-knockdown cells with an inhibitor of p-Akt (Ser473) resulted in rises in the levels of both p-GSK3β as well as FSHR expression whereas E2 synthesis fell. Conclusions During exposure to a high FFA content, TRIB3 can reduce FSHR expression through stimulation of the Akt/GSK3β pathway in human GCs. This response may contribute to inducing oocyte maturation.

Abstract Background Congenital scoliosis caused by failure of multiply vertebral segmentation with concave fused rib or unsegmented bar combined with contralateralhemivertebra is usually rigid and produces enormous asymmetric growth. Fusionless techniques have less advantage and come with some complications. Paucity of data was reported for children with complex congenital scoliosis using two-staged osteotomy surgery. Methods From 2006 to 2016, 11 patients less than 10 years old undergoing two staged osteotomy surgery for complex rigid congenital scoliosis were retrospectively reviewed. The analysis included age at initial surgery, second surgery and at the latest follow-up, and complications. Changes in coronal major curve, thoracic kyphosis, lumbar lodorsis, apex vertebra translation, T1-T12 length, T1-S1 length, trunk shift, and SVAwere included in radiological evaluation. Results In all, the mean follow-up was 72.5 ± 23.8 (42 to 112) months. The mean flexibility of the spine was 17.4 and 17.8 % before two surgeries. The mean age at the initial surgery was 6.6 ± 2.6 (2.5–10) years. The mean fusion level was 4.6 ± 1.3 (2 to 6) segments. The mean scoliosis improved from 67.4° to 23.7° after initial surgery and was 17.4° at the latest follow-up. The average increase of T1-S1 length was 0.92 cm per year. No patients had neurological complications. Conclusions Two-staged osteotomy surgery including hemivertebrae resection or Y-shaped osteotomy can achieve good radiological and clinical outcomes without severe complications. This procedure can be an option of treatment for complex congenital scoliosis.

Hollyhock (Alcea rosea (Linn). Cavan) is an herbaceous flowering plant with significant applications in urban greening, soil remediation, and traditional medicine. However, its genetic diversity and molecular characteristics at the population level have not been explored yet. Here, the phenotypic and genetic diversity of 162 hollyhock accessions from China revealed extensive variation among 11 traits and strong correlations between several quantitative traits. Whole-genome re-sequencing of 32 randomly chosen accessions identified 10,468,760 core single-nucleotide polymorphisms (SNPs) distributed evenly across the genome, except for on chromosome 21, and the average nucleotide diversity (π) was calculated to be 0.00397. Principal component analysis showed that these 32 accessions could be divided into four subpopulations, which was in agreement with the population structure analysis, and the subpopulations were strongly correlated with geographic location. A neighbor-joining dendrogram displayed similar clusters, except for accessions HuB25 and HLJ28, which formed two separate clusters. Our findings illuminate the genetic diversity in hollyhock and provide valuable information for hollyhock breeding.

Prostate cancer (PCa) induced death is the predominant cause of cancer-related death among men in 48 countries. After radical treatment, biochemical recurrence has become an important factor for prognosis. The early detection and diagnosis of recurrent lesions are very helpful in guiding treatment and improving the prognosis. PET/CT is a promising method for early detection of lesions in patients with biochemical recurrence of prostate cancer. This article reviews the progress of the research on PET/CT in the PCa biochemical recurrence and aims to introduce new technologies and provide more direction for future research.

Abstract Background Two ipsilateral hemivertebrae is less common and presents severe growth imbalance caused by the vertebral anomalies. However, there is a paucity of reports regarding to two ipsilateral thoracolumbar hemivertebrae. The purpose of present study is to evaluate the long-term outcomes of the posterior surgical correction of thoraco-lumbar spine deformity caused by two ipsilateral hemivertebrae. Methods From 2006 to 2014, a total of 14 consecutive pediatric patients with congenital thoraco-lumbar hemivertebrae were treated by posterior excision of hemivertebrae with short segment fusion. The following parameters were measured: coronal major curvature, cranial and caudal compensatory curvature, segmental kyphosis, lumbar lordosis, trunk shift, apical vertebra translation and sagittal vertical axis. These results were compared and evaluated in preoperatively, immediately postoperatively and at the final follow-up. All patients had a minimum of 5 years follow-up. Results The mean age at surgery was 11.1 ± 4.8 years (2yos to 17yos). The mean follow-up period was 80.2 ± 19.4 months (60mons to 117mons). There was a mean improvement of 74.2% in the coronal major curve from a mean angle of 64.1° before surgery to 15.8° at the final follow-up. The cranial and caudal curves improved of 69.8 and 69.0% from 25.6° to 7.7°, 26.9 to 8.2, respectively. The mean thoraco-lumbar kyphosis was 59.9° before and 13.6° after surgery, 20.8° at the final follow-up. Alignment in the coronal and sagittal plane was either maintained or improved within normal values in all patients. Conclusions Good correction and spinal balance can be achieved by posterior-only hemivertebrectomy in patients with thoracolumbar kyphocsoliosis caused by two ipsilateral hemivertebra. The complication of neurological injury is low but a technically demanding procedure. More attention should be paid in residual curve progression after surgery.