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BackgroundLymph node metastasis (LNM) is an important prognostic factor for cervical cancer (CC) and determines the treatment strategy. Hematological indicators have been reported as being useful biomarkers for the prognosis of a variety of cancers. This study aimed to evaluate the feasibility of machine learning models characterized by preoperative hematological indicators to predict the LNM status of CC patients before surgery.MethodsThe clinical data of 236 patients with pathologically confirmed CC were retrospectively analyzed at the Gynecology Oncology Department of the First Affiliated Hospital of Bengbu Medical University from November 2020 to August 2022. The least absolute shrinkage and selection operator (LASSO) was used to select 21 features from 35 hematological indicators and for the construction of 6 machine learning predictive models, including Adaptive Boosting (AdaBoost), Gaussian Naive Bayes (GNB), and Logistic Regression (LR), as well as Random Forest (RF), Support Vector Machines (SVM), and Extreme Gradient Boosting (XGBoost). Evaluation metrics of predictive models included the area under the receiver operating characteristic curve (AUC), accuracy, specificity, sensitivity, and F1-score.ResultsRF has the best overall predictive performance for ten-fold cross-validation in the training set. The specific performance indicators of RF were AUC (0.910, 95% confidence interval [CI]: 0.820–1.000), accuracy (0.831, 95% CI: 0.702–0.960), specificity (0.835, 95% CI: 0.708–0.962), sensitivity (0.831, 95% CI: 0.702–0.960), and F1-score (0.829, 95% CI: 0.696–0.962). RF had the highest AUC in the testing set (AUC = 0.854).ConclusionRF based on preoperative hematological indicators that are easily available in clinical practice showed superior performance in the preoperative prediction of CC LNM. However, investigations on larger external cohorts of patients are required for further validation of our findings.

The uneven spatial and temporal distribution of light resources and water scarcity during the grain-filling stage pose significant challenges for sustainable crop production, particularly in the arid areas of the Loess Plateau in Northwest China. This study aims to investigate the combined effects of drought and shading stress on winter wheat growth and its physio-biochemical and antioxidative responses. Wheat plants were subjected to different drought levels— full irrigation (I100), 75% of full irrigation (I75), 50% of full irrigation (I50), and 25% of full irrigation (I25), and shading treatments — 12, 9, 6, 3 and 0 days (SD12, SD9, SD6, SD3, and CK, respectively) during the grain-filling stage. The effects of drought and shading treatments reduced yield in descending order, with the most significant reductions observed in the SD12 and I25 treatments. These treatments decreased grain yield, spikes per plant, 1000-grain weight, and spikelets per spike by 160.67%, 248.13%, 28.22%, and 179.55%, respectively, compared to the CK. Furthermore, MDA content and antioxidant enzyme activities exhibited an ascending trend with reduced irrigation and longer shading durations. The highest values were recorded in the I75 and SD12 treatments, which increased MDA, SOD, POD, and CAT activities by 65.22, 66.79, 65.07 and 58.38%, respectively, compared to the CK. The Pn, E, Gs, and iCO2 exhibited a decreasing trend (318.14, 521.09, 908.77, and 90.85%) with increasing shading duration and decreasing irrigation amount. Drought and shading treatments damage leaf chlorophyll fluorescence, decreasing yield and related physiological and biochemical attributes.

Background and objectivesUpwards of 50% of acute ischemic stroke (AIS) survivors endure varying degrees of disability, with a recurrence rate of 17.7%. Thus, the prediction of outcomes in AIS may be useful for treatment decisions. This study aimed to determine the applicability of a machine learning approach for forecasting early outcomes in AIS patients.MethodsA total of 659 patients with new-onset AIS admitted to the Department of Neurology of both the First and Second Affiliated Hospitals of Bengbu Medical University from January 2020 to October 2022 included in the study. The patient’ demographic information, medical history, Trial of Org 10,172 in Acute Stroke Treatment (TOAST), National Institute of Health Stroke Scale (NIHSS) and laboratory indicators at 24 h of admission data were collected. The Modified Rankine Scale (mRS) was used to assess the 3-mouth outcome of participants’ prognosis. We constructed nine machine learning models based on 18 parameters and compared their accuracies for outcome variables.ResultsFeature selection through the Least Absolute Shrinkage and Selection Operator cross-validation (Lasso CV) method identified the most critical predictors for early prognosis in AIS patients as white blood cell (WBC), homocysteine (HCY), D-Dimer, baseline NIHSS, fibrinogen degradation product (FDP), and glucose (GLU). Among the nine machine learning models evaluated, the Random Forest model exhibited superior performance in the test set, achieving an Area Under the Curve (AUC) of 0.852, an accuracy rate of 0.818, a sensitivity of 0.654, a specificity of 0.945, and a recall rate of 0.900.ConclusionThese findings indicate that RF models utilizing general clinical and laboratory data from the initial 24 h of admission can effectively predict the early prognosis of AIS patients.

Oysters are notably susceptible to accumulating substantial amounts of cadmium (Cd), leading to food safety concerns, yet the molecular mechanisms are not fully understood. Previous study identified a significant correlation between polymorphisms in the Zip1 and Zip3 of Fujian oyster (Crassostrea angulata) and the levels of Cd accumulation. Zip1 and Zip3, belonging to the Zip family, are primarily responsible for the cellular transport of zinc and other metal ions. To delve deeper into their roles in Cd transport within oysters, this research cloned and analyzed the sequences of Fujian oyster Zip1 and Zip3. The open reading frames for Zip1 and Zip3 were 960 and 978 bp, respectively, encoding proteins of 319 and 325 amino acids. Following Cd exposure, the expression levels of these genes in the mantle, gills, and other tissues initially increased significantly before decreasing, demonstrating a dose-dependent response. The lowest expression levels were observed in the adductor muscle, with Zip1 reaching its highest expression in the mantle and Zip3 in the visceral mass. In vitro RNAi experiments revealed that silencing Zip1 led to a 1.26-fold decrease in new 113Cd accumulation in the mantle, whereas silencing Zip3 resulted in a 1.29-fold increase. Immunohistochemistry showed weak expression of Zip1 and Zip3 proteins in the connective tissue of the mantle. In summary, Zip1 and Zip3 in Fujian oyster can transport Cd as a substrate, and played different roles in the absorption and efflux of Cd.

ObjectiveDiabetic nephropathy (DN) is a major microvascular complication of diabetes and the leading cause of end-stage renal disease. Early detection and prevention of DN are important. Retinol-binding protein 4 (RBP4) has been considered as a single diagnostic marker for the detection of renal impairment. However, the results have been inconsistent. The present meta-analysis aimed to determine the diagnostic potential of RBP4 in patients in type 2 diabetes mellitus (T2DM) with DN.MethodsWe searched PubMed, Web of Science, Embase, Wanfang and CNKI databases from inception until January 2024. The meta-analysis was performed by Stata version 15.0, and sensitivity, specificity, positive and negative likelihood ratios (PLR and NLR), diagnostic odds ratio (DOR) and area under the curve (AUC) were pooled. The Quality Assessment of Diagnostic Accuracy Studies-2 tool was utilized to assess the quality of each included study. In addition, heterogeneity and publication bias were evaluated.ResultsTwenty-nine studies were included in the meta-analysis. The pooled sensitivity and specificity were 0.76 [95% confidence interval (CI), 0.71–0.80] and 0.81 (95% CI, 0.76–0.85), respectively. The results showed a pooled PLR of 4.06 (95% CI, 3.16–5.21), NLR of 0.29 (95% CI, 0.24–0.36) and DOR of 13.76 (95% CI, 9.29–20.37). The area under the summarized receiver operating characteristic curve was given a value of 0.85 (95% CI, 0.82–0.88). No obvious publication bias existed in the Deeks’ funnel plot asymmetry test.ConclusionOur findings suggest that RBP4 has a promising diagnostic value with good sensitivity and specificity for patients with T2DM with DN.

Climate change, characterized by rising atmospheric CO2 levels and temperatures, poses significant challenges to global crop production. Sweet sorghum, a prominent C4 cereal extensively grown in arid areas, emerges as a promising candidate for sustainable bioenergy production. This study investigated the responses of photosynthesis and leaf-scale water use efficiency (WUE) to varying light intensity (I) in sweet sorghum under different temperature and CO2 conditions. Comparative analyses were conducted between the An-I, gs-I, Tr-I, WUEi-I, and WUEinst-I models proposed by Ye et al. and the widely utilized the non-rectangular hyperbolic (NRH) model for fitting light response curves. The Ye's models effectively replicated the light response curves of sweet sorghum, accurately capturing the diminishing intrinsic WUE (WUEi) and instantaneous WUE (WUEinst) trends with increasing I. The fitted maximum values of An, gs, Tr, WUEi, and WUEinst and their saturation light intensities closely matched observations, unlike the NRH model. Despite the NRH model demonstrating high R2 values for An-I, gs-I, and Tr-I modelling, it returned the maximum values significantly deviating from observed values and failed to generate saturation light intensities. It also inadequately represented WUE responses to I, overestimating WUE. Across different leaf temperatures, An, gs, and Tr of sweet sorghum displayed comparable light response patterns. Elevated temperatures increased maximum An, gs, and Tr but consistently declined maximum WUEi and WUEinst. However, WUEinst declined more sharply due to the disproportionate transpiration increase over carbon assimilation. Critically, sweet sorghum An saturated at current atmospheric CO2 levels, with no significant gains under 550 μmol mol−1. Instead, stomatal closure enhanced WUE under elevated CO2 by coordinated gs and Tr reductions rather than improved carbon assimilation. Nonetheless, this response diminished under simultaneously high temperature, suggesting intricate interplay between CO2 and temperature in modulating plant responses. These findings provide valuable insights into photosynthetic dynamics of sweet sorghum, aiding predictions of yield and optimization of cultivation practices. Moreover, our methodology serves as a valuable reference for evaluating leaf photosynthesis and WUE dynamics in diverse plant species.

BackgroundThe occurrence of lymph node metastasis (LNM) is one of the critical factors in determining the staging, treatment and prognosis of cervical cancer (CC). Heart rate variability (HRV) is associated with LNM in patients with CC. The purpose of this study was to validate the feasibility of machine learning (ML) models constructed with preoperative HRV as a feature of CC patients in predicting CC LNM.MethodsA total of 292 patients with pathologically confirmed CC admitted to the Department of Gynecological Oncology of the First Affiliated Hospital of Bengbu Medical University from November 2020 to September 2023 were included in the study. The patient’ preoperative 5-min electrocardiogram data were collected, and HRV time-domain, frequency-domain and non-linear analyses were subsequently performed, and six ML models were constructed based on 32 parameters. Model performance was assessed using the area under the receiver operating characteristic curve (AUC), accuracy, sensitivity, and specificity.ResultsAmong the 6 ML models, the random forest (RF) model showed the best predictive performance, as specified by the following metrics on the test set: AUC (0.852), accuracy (0.744), sensitivity (0.783), and specificity (0.785).ConclusionThe RF model built with preoperative HRV parameters showed superior performance in CC LNM prediction, but multicenter studies with larger datasets are needed to validate our findings, and the physiopathological mechanisms between HRV and CC LNM need to be further explored.

BackgroundLaparoscopic total mesorectal excision (LaTME) is standard surgical methods for rectal cancer, and LaTME operation is a challenging procedure. This study is intended to use machine learning to develop and validate prediction models for surgical difficulty of LaTME in patients with rectal cancer and compare these models’ performance.MethodsWe retrospectively collected the preoperative clinical and MRI pelvimetry parameter of rectal cancer patients who underwent laparoscopic total mesorectal resection from 2017 to 2022. The difficulty of LaTME was defined according to the scoring criteria reported by Escal. Patients were randomly divided into training group (80%) and test group (20%). We selected independent influencing features using the least absolute shrinkage and selection operator (LASSO) and multivariate logistic regression method. Adopt synthetic minority oversampling technique (SMOTE) to alleviate the class imbalance problem. Six machine learning model were developed: light gradient boosting machine (LGBM); categorical boosting (CatBoost); extreme gradient boost (XGBoost), logistic regression (LR); random forests (RF); multilayer perceptron (MLP). The area under receiver operating characteristic curve (AUROC), accuracy, sensitivity, specificity and F1 score were used to evaluate the performance of the model. The Shapley Additive Explanations (SHAP) analysis provided interpretation for the best machine learning model. Further decision curve analysis (DCA) was used to evaluate the clinical manifestations of the model.ResultsA total of 626 patients were included. LASSO regression analysis shows that tumor height, prognostic nutrition index (PNI), pelvic inlet, pelvic outlet, sacrococcygeal distance, mesorectal fat area and angle 5 (the angle between the apex of the sacral angle and the lower edge of the pubic bone) are the predictor variables of the machine learning model. In addition, the correlation heatmap shows that there is no significant correlation between these seven variables. When predicting the difficulty of LaTME surgery, the XGBoost model performed best among the six machine learning models (AUROC=0.855). Based on the decision curve analysis (DCA) results, the XGBoost model is also superior, and feature importance analysis shows that tumor height is the most important variable among the seven factors.ConclusionsThis study developed an XGBoost model to predict the difficulty of LaTME surgery. This model can help clinicians quickly and accurately predict the difficulty of surgery and adopt individualized surgical methods.

IntroductionMany challenges remain for long-term survival of renal allografts. Once-daily sirolimus (SRL) combined with low-dose extended-release tacrolimus (LER-TAC) may improve medication adherence and reduce the potential nephrotoxicity of calcineurin inhibitors (CNI) compared with standard immunosuppression regimens, thus potentially improving long-term graft survival.MethodsThis retrospective, observational, single-center, propensity score matching (PSM) study compared conversion to SRL combined with low-dose ER-TAC and mycophenolic acid (MPA) combined with standard-dose TAC in kidney transplant recipients. After PSM, there were 56 patients in each group. Efficacy, safety, and medication adherence were evaluated over 12 months.ResultsThere was no significant difference between the two groups in terms of graft and recipient survival and incidence of biopsy-proven acute rejection (p = 1.000), and none of the recipients developed dnDSA after conversion. The mean eGFR improved in SRL + LER-TAC group after conversion compared to before conversion (51.12 ± 20.1 ml/min/1.73 m2 vs. 56.97 ± 19.23 ml/min/1.73 m2, p

ObjectiveDisruption in the delicate symphony of genes, microRNA (miRNA), or protein expression can result in the dysregulation of the immune system, leading to the devastating consequences such as lupus nephritis (LN). The capacity of exosomes to transport miRNAs between cells and modify the phenotype of recipient cells implies their involvement in persistent kidney inflammation. This study unveils identifying two previously undiscovered exosomal miRNAs in the serum of LN patients, offering potential solutions to the current challenges in LN diagnosis and management.MethodsInitially, we used a reagent-based kit to isolate serum exosomes from patients with Systemic lupus erythematosus (SLE) and used Trizol method for total RNA extraction. Subsequently, we employed small RNA sequencing to screen for differential expression profiles of exosomal small RNAs. The RT-qPCR method was used to individually validate samples in both the screening and validation cohorts, enabling the identification of candidate small RNAs; specific to LN. We assessed the diagnostic potency using receiver operating characteristic (ROC) curve, and explored the biological roles of miRNAs using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses.ResultsCompared to SLE patients without LN, SLE patients accompanied by LN exhibited significantly spiked levels of exosomal hsa-miR-4796-5p and hsa-miR-7974. The duo of miRNAs, hsa-miR-4796-5p and hsa-miR-7974, exhibited promising potential as biomarkers for diagnosing LN, with an AUC exceeding 0.8. Correlation analysis revealed a strong positive association between these miRNAs and proteinuria, as well as the SLE Disease Activity Index (SLEDAI) score. Moreover, the levels of two miRNAs in LN patients were significantly elevated in comparison to other autoimmune nephritis conditions, such as immunoglobulin A nephropathy (IgAN) and diabetic nephropathy (DN). Furthermore, the bioinformatics analysis indicated that this miRNAs duo can play a pivotal role in the regulation of immune processes by modulating signal pathways, such as the mTOR and PI3K-Akt signaling pathway.ConclusionThis study provides a new ground that serum exosomal miRNAs can effectively identify and predict LN in SLE patients.

IntroductionLow-grade glioma (LGG) is a prevalent malignant tumor in the intracranial region. Despite the advancements in treatment methods for this malignancy over the past decade, significant challenges still persist in the form of drug resistance and tumor recurrence. The Notch signaling pathway plays essential roles in many physiological processes as well as in cancer development. However, the significance of the pathway and family genes in LGG are poorly understood. MethodsWe conducted gene expression profiling analysis using the TCGA dataset to investigate the gene set associated with the Notch signaling pathway. we have proposed a metric called "NotchScore" that quantifies the strength of the Notch signaling pathway and enables us to assess its significance in predicting prognosis and immune response in LGG. We downregulated JAG1 in low-grade gliomas to assess its influence on the proliferation and migration of these tumors. Ultimately, we determined the impact of the transcription factor VDR on the transcription of PDL1 through chip-seq data analysis.ResultsOur findings indicate that tumors with a higher NotchScore, exhibit poorer prognosis, potentially due to their ability to evade the anti-tumor effects of immune cells by expressing immune checkpoints. Among the genes involved in the Notch signaling pathway, JAG1 has emerged as the most representative in terms of capturing the characteristics of both NotchScore and Notch pathways. The experimental results demonstrate that silencing JAG1 yielded a significant decrease in tumor cell proliferation in LGG cell lines. Our study revealed mechanisms by which tumors evade the immune system through the modulation of PDL1 transcription levels via the PI3K-Akt signaling pathway. Additionally, JAG1 potentially influences PDL1 in LGG by regulating the PI3K-Akt signaling pathway and the expression of the transcription factor VDR.DiscussionThese findings contribute to our understanding of immune evasion by tumors in LGG. The insights gained from this research may have implications for the development of therapeutic interventions for LGG.

Background: Prior research suggests that autonomic modulation investigated by heart rate variability (HRV) might act as a novel predictive biomarker for cancer prognosis, such as in breast cancer and pancreatic cancer. It is not clear whether there is a correlation between autonomic modulation and prognosis in patients with extensive-stage small cell lung cancer (ES-SCLC). Therefore, the purpose of the study was to examine the association between short-term HRV, deceleration capacity (DC) and acceleration capacity (AC) of heart rate and overall survival in patients with ES-SCLC.Methods: We recruited 40 patients with ES-SCLC, and 39 were included in the final analysis. A 5-min resting electrocardiogram of patients with ES-SCLC was collected using a microelectrocardiogram recorder to analyse short-term HRV, DC and AC. The following HRV parameters were used: standard deviation of the normal-normal intervals (SDNN) and root mean square of successive interval differences (RMSSD). Overall survival of patients with ES-SCLC was defined as time from the date of electrocardiogram measurement to the date of death or the last follow-up. Follow-up was last performed on 07 June 2023. There was a median follow-up time of 42.2 months.Results: Univariate analysis revealed that the HRV parameter SDNN, as well as DC significantly predicted the overall survival of ES-SCLC patients (all p < 0.05). Multivariate analysis showed that the HRV parameters SDNN (hazard ratio = 5.254, 95% CI: 1.817–15.189, p = 0.002), RMSSD (hazard ratio = 3.024, 95% CI: 1.093–8.372, p = 0.033), as well as DC (hazard ratio = 3.909, 95% CI: 1.353–11.293, p = 0.012) were independent prognostic factors in ES-SCLC patients.Conclusion: Decreased HRV parameters (SDNN, RMSSD) and DC are independently associated with shorter overall survival in ES-SCLC patients. Autonomic nervous system function (assessed based on HRV and DC) may be a new biomarker for evaluating the prognosis of patients with ES-SCLC.

BackgroundPrior research suggests that cardiovascular autonomic dysfunction might be an early marker of cardiotoxicity induced by antitumor treatment and act as an early predictor of cardiovascular disease-related morbidity and mortality. The impact of thoracic radiotherapy on the parasympathetic and sympathetic nervous systems, however, remains unclear. Therefore, this study aimed to evaluate the short-term effects of thoracic radiotherapy on the autonomic nervous system, using deceleration capacity (DC), acceleration capacity (AC) of heart rate, and heart rate variability (HRV) as assessment tools.MethodsA 5 min electrocardiogram was collected from 58 thoracic cancer patients before and after thoracic radiotherapy for DC, AC, and HRV analysis. HRV parameters employed included the standard deviation of the normal-normal interval (SDNN), root mean square of successive interval differences (RMSSD), low frequency power (LF), high frequency power (HF), total power (TP), and the LF to HF ratio. Some patients also received systemic therapies alongside radiotherapy; thus, patients were subdivided into a radiotherapy-only group (28 cases) and a combined radiotherapy and systemic therapies group (30 cases) for additional subgroup analysis.ResultsThoracic radiotherapy resulted in a significant reduction in DC (8.5 [5.0, 14.2] vs. 5.3 [3.5, 9.4], p = 0.002) and HRV parameters SDNN (9.9 [7.03, 16.0] vs. 8.2 [6.0, 12.4], p = 0.003), RMSSD (9.9 [6.9, 17.5] vs. 7.7 [4.8, 14.3], p = 0.009), LF (29 [10, 135] vs. 24 [15, 50], p = 0.005), HF (35 [12, 101] vs. 16 [9, 46], p = 0.002), TP (74 [41, 273] vs. 50 [33, 118], p

The aim of this study was to evaluate the effects of replacing fish meal (FM) or soy protein concentrate (SPC) with wheat gluten on growth performance, feed utilization, and nutrient digestibility and retention in Japanese seabass (Lateolabrax japonicus). Seven isonitrogenous (441–456 g kg−1 crude protein) and isocaloric (21.5–22.0 MJ kg−1 gross energy) diets were produced to replace 0%, 33.3%, 66.7% and 100% of FM or SPC with a mixture of wheat gluten, wheat, and taurine (GWT, 77.5% wheat gluten, 20.5% wheat and 2.0% taurine). The gradual replacement of protein in FM with GWT had no significant effects on feed intake, whole-body composition, and the hepatosomatic and viscerosomatic indices, but resulted in a linear decrease in the weight gain rate, feed efficiency, and retention of nitrogen, energy, and essential amino acids (Arg, His, Ile, Leu, Lys, Met, Phe, Thr, and Val). The apparent digestibility of most essential amino acids (Cys, His, Leu, Lys, and Phe) and total amino acids increased linearly. Replacement protein in SPC with GWT had no significant effects on feed intake, growth, the feed conversion ratio, whole-body composition, and the hepatosomatic index, but resulted in a linear decrease in nitrogen, energy, and Met retention; the digestibility of Cys and Met increased linearly. Overall, wheat gluten is a more effective alternative for replacing protein in SPC than FM.

Drought is one of the most significant abiotic stress threatening to crop production worldwide. Soybean is a major legume crop with immense economic significance, but its production is highly dependent on optimum rainfall or abundant irrigation. As the global climate changes, it is more important to find solutions to make plants more resilient to drought. The prime aimed of the study is to investigate the effect of melatonin on drought tolerance in soybean and its potential mechanisms. Soybean seedlings were treated with 20% polyethylene glycol 6000 (PEG 6000) and subjected to osmotic stress (14 days) with or without 100 μM melatonin treatment. Our results revealed that melatonin supplementation significantly mitigated PEG-induced growth retardation and increased water absorption ability. Foliar application of melatonin also increased gas exchange and the chlorophyll fluorescence attributes by the mitigation of the osmotic-induced reduction of the reaction activity of photosystems I and II, net photosynthetic rate (Pn), stomatal conductance (Gs), transpiration rate (Tr), electron transport activity, and photosynthetic efficiency. In addition, PEG-induced elevated production of reactive oxygen species (ROS) and malondialdehyde (MDA) content were significantly reversed by melatonin treatment. Equally important, melatonin boosted the antioxidant activities of soybean plants. Moreover, osmotic stress substantially increased abscisic acid (ABA) accumulation in roots and leaves, while melatonin-received plant leaves accumulated less ABA but roots content higher ABA. Similarly, melatonin significantly suppressed ABA biosynthesis and signaling gene expression in soybean exposed to drought stress. Furthermore, osmotic stress significantly suppressed plasmalemma (GmPIPs) and tonoplast aquaporin (GmTIPs) genes expression, and their transcript abundance was up-regulated by melatonin co-addition. Taken together, our results indicated that melatonin potentially improves drought tolerance of soybean through the regulation of ABA and aquaporin gene expression, increasing photosynthetic efficiency as well as enhancing water uptake efficiency.

Amphibian metamorphosis resembles mammalian postembryonic development, a period around birth when many organs mature into their adult forms and when plasma thyroid hormone (T3) concentration peaks. T3 plays a causative role for amphibian metamorphosis. This and its independence from maternal influence make metamorphosis of amphibians, particularly anurans such as pseudo-tetraploid Xenopus laevis and its highly related diploid species Xenopus tropicalis, an excellent model to investigate how T3 regulates adult organ development. Studies on intestinal remodeling, a process that involves degeneration of larval epithelium via apoptosis and de novo formation of adult stem cells followed by their proliferation and differentiation to form the adult epithelium, have revealed important molecular insights on T3 regulation of cell fate during development. Here, we review some evidence suggesting that T3-induced activation of cell cycle program is important for T3-induced larval epithelial cell death and de novo formation of adult intestinal stem cells.

BackgroundPrevious studies have shown that the predictive value of traditional linear (time domain and frequency domain) heart rate variability (HRV) for the survival of patients with advanced non-small cell lung cancer (NSCLC) is controversial. Nonlinear methods, based on the concept of complexity, have been used to evaluate HRV, providing a new means to reveal the physiological and pathological changes in HRV. This study aimed to assess the association between heartbeat complexity and overall survival in patients with advanced NSCLC.MethodsThis study included 78 patients with advanced NSCLC (mean age: 62.0 ± 9.3 years). A 5-min resting electrocardiogram of advanced NSCLC patients was collected to analyze the following HRV parameters: time domain indicators, i.e., standard deviation of the normal-normal intervals (SDNN) and root mean square of successive interval differences (RMSSD); frequency domain indicators, i.e., total power (TP), low frequency power (LF), high frequency power (HF), and the ratio of LF to HF (LF/HF); nonlinear HRV indicators characterizing heartbeat complexity, i.e., approximate entropy (ApEn), sample entropy (SampEn), and recurrence quantification analysis (RQA) indexes: mean diagonal line length (Lmean), maximal diagonal line length (Lmax), recurrence rate (REC), determinism (DET), and shannon entropy (ShanEn).ResultsUnivariate analysis revealed that the linear frequency domain parameter HF and nonlinear RQA parameters Lmax, REC, and DET were significantly correlated with the survival of advanced NSCLC patients (all p

In the context of global food crisis, applying the phytohormone-brassinosteroids (BRs) in combination with the fungicide-pyraclostrobin (Pyr) was beneficial for plant quality and productivity in several field trials. However, in addition to the benefits of disease control due to the innate fungicidal activity of Pyr, it remains to be understood whether the coapplication of BL+ Pyr exerts additional growth-promoting effects. For this purpose, the effects of BL treatment, Pyr treatment, and BL+ Pyr treatment in Arabidopsis thaliana were compared. The results showed that the yield increased at a rate of 25.6% in the BL+Pyr group and 9.7% in the BL group, but no significant change was observed in the Pyr group. Furthermore, the BL+Pyr treatment increased the fresh weight of both the leaves and the inflorescences. In contrast, the Pyr and BL treatments only increased the fresh weight of leaves and inflorescences, respectively. Additionally, the BL + Pyr treatment increased the Pn, Gs, Tr, Vc, max, Jmax, VTPU, ETR, Fv’/Fm’, ΦPSII, Rd, AYE and Rubisco enzyme activity by 26%, 38%, 40%, 16%, 19%, 15%, 9%, 10%, 17%, 179%, 18% and 32%, respectively. While, these paraments did not change significantly by the BL or Pyr treatments. Treatment with BL + Pyr and Pyr, rather than BL, improved the chlorophyll a and chlorophyll b contents by upregulating genes related to chlorophyll biosynthesis and downregulating genes related to chlorophyll degradation. Additionally, according to transcriptomic and metabolomic analysis, the BL+ Pyr treatment outperformed the individual BL or Pyr treatments in activating the transcription of genes involved in photosynthesis and increasing sugar accumulation. Our results first validated that the combined usage of BL and Pyr exerted striking synergistic effects on enhancing plant biomass and yield by increasing photosynthetic efficiency. These results might provide new understanding for the agricultural effects by the co-application of BL and Pyr, and it might stimulate the efforts to develop new environment-friendly replacement for Pyr to minimize the ecotoxicology of Pyr.

In order to study the current situation of the anxiety of college students in the post-pandemic era and the effect of physical exercise on anxiety, this study explores the influence of social support and proactive personality as mediating variables on the anxiety of college students from the perspective of physical exercise. Firstly, anxiety symptoms and anxious emotions are defined. Secondly, a questionnaire survey is conducted for a well-known university in a certain city, and different questionnaire scales are developed from the physical exercise, anxiety, social support, and proactive personality assessment of college students. Finally, the results of the survey are statistically analyzed to explore the relieving effect of physical exercise on anxiety. The results reveal that there is a significant gender difference in the level of physical exercise, and the amount of physical exercise of the male students is generally higher than that of female students. In addition, the intensity, time, and frequency of exercise of male students are more than that of female students, but there is no obvious difference between them and whether they were only children. Physical exercise habits, social support, proactive personality traits, and anxiety of college students have a significant correlation. Through the analysis of the chain mediation effect, Ind2 (0.0140) is the largest coefficient among the three paths, indicating that the path of influencing social support through physical exercise habits, followed by affecting proactive personality traits, and then impacting anxiety has the strongest explanatory force. According to the results, strategies to relieve the anxiety of college students are given. This study can provide a reference for the research on the methods to alleviate their anxiety under the influence of the epidemic.

Background: Previous studies have shown that heart rate variability (HRV) analysis is a sensitive indicator of chemotherapy-induced cardiotoxicity. However, most studies to date have observed long-term effects using long-term analyses. The main purpose of this study was to evaluate the acute effect of chemotherapy on the cardiac autonomic nervous system (ANS) in patients with cervical cancer (CC) by examining short-term HRV.Methods: Fifty patients with CC admitted to the Department of Gynecology and Oncology of the First Affiliated Hospital of Bengbu Medical College were enrolled in the study. Based on their chemotherapy regimens, the patients were divided into a DC group (docetaxel + carboplatin) and a TC group (paclitaxel + carboplatin). A 5-min resting electrocardiogram (ECG) was collected before and the day after chemotherapy: the time domain (standard deviation of normal-to-normal intervals (SDNN) and root mean square of successive differences (RMSSD)) and frequency domain (low-frequency power (LF), high-frequency power (HF), and (LF/HF)) parameters were analyzed, and the differences before and after chemotherapy were compared.Results: The results showed that SDNN, RMSSD and HF were significantly higher in the DC and TC groups after chemotherapy than before (p < 0.05, Cohen’s d > 0.5). In addition, LF was significantly higher after TC than before chemotherapy (p < 0.05, Cohen’s d > 0.3), and LF/HF was significantly lower after DC than before chemotherapy (p < 0.05, Cohen’s d > 0.5).Conclusion: Chemotherapy combining taxane and carboplatin can increase the HRV of CC patients in the short term, and HRV may be a sensitive tool for the early detection of chemotherapy-induced cardiac ANS perturbations.

ObjectiveThis study aimed to examine the associations among mental health related eHealth literacy (eHL), mental health-seeking attitude, and wellbeing among Chinese young electronic media users during the COVID-19 pandemic.MethodsA web-based cross-sectional survey was conducted in Guangzhou, China. The modified eHealth literacy Scale, Mental Help-Seeking Attitudes Scale, and Short Warwick-Edinburgh Mental Wellbeing Scale were used. Structural equation modeling (SEM) examined the associations between them and was adjusted by several controlled variables.ResultsTotally, 1,008 participants completed the questionnaire and provided valid responses. The eHL showed a statistically significant and direct effect on mental wellbeing in this sample. The higher the level of eHL, the better wellbeing of the participants. The mental health-seeking attitude is also positively correlated with mental wellbeing, indicating that the more positive attitude toward seeking mental health services, the better the wellbeing participants reported. The higher level of eHL is significantly associated with a more positive attitude toward seeking mental health services.ConclusionTraining to improve eHL may optimize young electronic media users' mental health outcomes. Development and use of a mental health specific eHL instrument in future studies should be encouraged.

IntroductionAutoantibodies against inflammatory cytokines may be used for the prevention of atherosclerosis. Preclinical studies consider colony-stimulating factor 2 (CSF2) as an essential cytokine with a causal relationship to atherosclerosis and cancer. We examined the serum anti-CSF2 antibody levels in patients with atherosclerosis or solid cancer.MethodsWe measured the serum anti-CSF2 antibody levels via amplified luminescent proximity homogeneous assay-linked immunosorbent assay based on the recognition of recombinant glutathione S-transferase-fused CSF2 protein or a CSF2-derived peptide as the antigen.ResultsThe serum anti-CSF2 antibody (s-CSF2-Ab) levels were significantly higher in patients with acute ischemic stroke (AIS), acute myocardial infarction (AMI), diabetes mellitus (DM), and chronic kidney disease (CKD) compared with healthy donors (HDs). In addition, the s-CSF2-Ab levels were associated with intima-media thickness and hypertension. The analyzes of samples obtained from a Japan Public Health Center-based prospective study suggested the utility of s-CSF2-Ab as a risk factor for AIS. Furthermore, the s-CSF2-Ab levels were higher in patients with esophageal, colorectal, gastric, and lung cancer than in HDs but not in those with mammary cancer. In addition, the s-CSF2-Ab levels were associated with unfavorable postoperative prognosis in colorectal cancer (CRC). In CRC, the s-CSF2-Ab levels were more closely associated with poor prognosis in patients with p53-Ab-negative CRC despite the lack of significant association of the anti-p53 antibody (p53-Ab) levels with the overall survival.ConclusionS-CSF2-Ab was useful for the diagnosis of atherosclerosis-related AIS, AMI, DM, and CKD and could discriminate poor prognosis, especially in p53-Ab-negative CRC.

The study investigated the effects of compound fibers composed of psyllium husk powder (PHP, 0.3%) and methylcellulose (MC, 0, 0.3, 0.6, 0.9, and 1.2%) on the storage stability, rheology, and microstructure of sodium caseinate emulsions. Results showed that the emulsion stability was enhanced with the increased concentrations of MC, especially at the concentration of 1.2%. The oil droplet size in the emulsions was decreased as the concentrations of compound fibers increased, which was further confirmed by the optical microscope analysis. The rheological measurements and cryo-scanning electron microscopy results indicated that compound fibers improved the viscosity of the emulsions, and formed a strong three-dimensional network structure. The results of confocal laser scanning microscope and surface protein concentration measurements showed that compound fibers were evenly distributed into the oil droplet surface. The above results demonstrate that compound fibers are an effective thickener and emulsifier in enhancing the stability properties of oil-in-water (O/W) emulsions stabilized by sodium caseinate.

β-glucan is widely used in aquaculture due to its immunostimulatory effects, but the specific effect and potential regulatory mechanism on largemouth bass (Micropterus salmoides) are still unclear. Here, we evaluated the effects of β-glucan on growth, resistance to Aeromonas schubertii, intestinal health, and transcriptome of largemouth bass to reveal the potential regulators, metabolic pathways, and altered differential microbiota. Four experimental diets were designed with β-glucan supplementation levels of 0 (control), 100 (LA-100), 200 (MA-200), and 300 (HA-300) mg kg-1, and each diet was fed to largemouth bass (79.30 ± 0.50 g) in triplicate for 70 days, followed by a 3-day challenge experiment. Results showed that different β-glucan supplementations had no significant effects on growth performance and whole-body composition. Fish fed a diet with 300 mg kg-1 β-glucan significantly increased the activity of lysozyme than those fed diets with 0 and 100 mg kg-1 β-glucan. In addition, the survival rate of largemouth bass in β-glucan supplementation groups was significantly higher than the control group at 12- and 24-h challenge by Aeromonas schubertii. Transcriptome analysis showed that a total of 1,245 genes were differentially expressed [|log2(fold change)| ≥1, q-value ≤0.05], including 109 immune-related differentially expressed genes (DEGs). Further analysis revealed that significantly upregulated and downregulated DEGs associated with immunity were mapped into 12 and 24 pathways, respectively. Results of intestinal microflora indicated that fish fed a diet with 300 mg kg-1 β-glucan had higher bacterial richness and diversity as evaluated by Sobs, Chao, Ace, and Simpson indices, but no significant differences were found in the comparison groups. Furthermore, 300 mg kg-1 β-glucan significantly increased the relative abundance of Mycoplasma and decreased Proteobacteria (mainly Escherichia-Shigella and Escherichia coli) and Bacillus anthracis in largemouth bass intestinal microflora. The findings of this study provided new insights that will be valuable in future studies to elucidate the mechanism of immunity enhancement by β-glucan.

Neonatal necrotizing enterocolitis (NEC), the most significant causes of neonatal mortality, is a disease of acute intestinal inflammation. At present, it is not clear exactly how the disease is caused, but it has been suggested that this disorder is a result of a complex interaction among prematurity, enteral feeding and inappropriate pro-inflammation response and bacterial infection of the intestine. A microRNA (miRNA) is a class of endogenous non-coding single-stranded RNA that is about 23 nucleotides long engaging in the regulation of the gene expression. Recently, numerous studies have determined that abnormal miRNA expression plays important roles in various diseases, including NEC. Here, we summarized the role of miRNAs in NEC. We introduce the biosynthetic and function of miRNAs and then describe the possible mechanisms of miRNAs in the initiation and development of NEC, including their influence on the intestinal epithelial barrier's function and regulation of the inflammatory process. Finally, this review aids in a comprehensive understanding of the current miRNA to accurately predict the diagnosis of NEC and provide ideas to find potential therapeutic targets of miRNA for NEC. In conclusion, our aims are to highlight the close relationship between miRNAs and NEC and to summarize the practical value of developing diagnostic biomarkers and potential therapeutic targets of NEC.

Background: It has previously been shown that the time-domain characteristic of heart rate variability (HRV) is an independent prognostic factor for lung cancer patients with brain metastasis (LCBM). However, it is unclear whether the nonlinear dynamic features contained in HRV are associated with prognosis in patients with LCBM. Recurrence quantification analysis (RQA) is a common nonlinear method used to characterize the complexity of heartbeat interval time series. This study was aimed to explore the association between HRV RQA parameters and prognosis in LCBM patients.Methods: Fifty-six LCBM patients from the Department of Radiation Oncology, the First Affiliated Hospital of Bengbu Medical College, were enrolled in this study. Five-minute ECG data were collected by a mini-ECG recorder before the first brain radiotherapy, and then heartbeat interval time series were extracted for RQA. The main parameters included the mean diagonal line length (Lmean), maximal diagonal line length (Lmax), percent of recurrence (REC), determinism (DET) and Shannon entropy (ShanEn). Patients were followed up (the average follow-up time was 19.2 months, a total of 37 patients died), and the relationships between the RQA parameters and survival of LCBM patients were evaluated by survival analysis.Results: The univariate analysis showed that an Lmax of >376 beats portended worse survival in LCBM patients. Multivariate Cox regression analysis revealed that the Lmax was still an independent prognostic factor for patients with LCBM after adjusting for confounders such as the Karnofsky performance status (KPS) (HR = 0.318, 95% CI: 0.151–0.669, p = 0.003).Conclusion: Reduced heartbeat complexity indicates a shorter survival time in patients with LCBM. As a non-invasive biomarker, RQA has the potential for application in evaluating the prognosis of LCBM patients.

We report findings in a 34-year-old female patient who presented with fulminant myocarditis 8 days after receiving the first dose of the ZF2001 RBD-subunit vaccine against coronavirus disease 2019 (COVID-19). Autopsy showed severe interstitial myocarditis, including multiple patchy infiltrations of lymphocytes and monocytes in the myocardium of the left and right ventricular walls associated with myocyte degeneration and necrosis. This report highlights the details of clinical presentations and autopsy findings of myocarditis after ZF2001 (RBD-subunit vaccine) vaccination. The correlation between vaccination and death due to myocarditis is discussed.

AimTo investigate the value of pretreatment blood biomarkers combined with magnetic resonance imaging (MRI) in predicting the efficacy of neoadjuvant chemoradiotherapy (NCRT) in patients with locally advanced rectal cancer (LARC).MethodsThis study involved patients with LARC who received NCRT and subsequently underwent total mesenteric excision from June 2015 to June 2021 at the First Affiliated Hospital of Soochow University. Patients with incomplete courses of neoadjuvant therapy, comorbidities with other malignancies or diseases that affect the study outcome, and those who underwent unplanned surgery were ultimately excluded. Laboratory data such as albumin, CEA, various blood cell levels, and MRI related data such as tumor regression grade assessed by magnetic resonance imaging (mrTRG) were collected from the included patients one week prior to NCRT. MrTRG is a common clinical imaging metric used to assess the degree of tumor regression in rectal cancer, primarily based on morphological assessment of residual tumor. Furthermore, pretreatment blood biomarkers such as neutrophil to lymphocyte ratio (NLR), lymphocyte to monocyte ratio (LMR), albumin to fibrinogen ratio (AFR), and prealbumin to fibrinogen ratio (PFR) were assessed. The independent variables for pathologic complete response (pCR) to NCRT were determined by univariate and multivariate logistic regression analyses. Receiver operating characteristic (ROC) curve analysis was used to examine the performance of MRI with or without pretreatment blood biomarkers in predicting pCR using DeLong’s method. A nomogram was created and confirmed internally.ResultsFifty-nine individuals with LARC satisfied the inclusion criteria, among which 23 showed pCR after NCRT. Logistic regression analysis demonstrated that pretreatment CEA (≤ 3 µg/L, OR = 0.151, P = 0.039), NLR (OR = 4.205, P = 0.027), LMR (OR = 0.447, P = 0.034), and PFR (OR = 0.940, P = 0.013) were independent predictors of pCR to NCRT. The AUCs of mrTRG alone and mrTRG plus the above four pretreatment blood biomarkers were 0.721 (P =0.0003) and 0.913 (P

Intimal hyperplasia (IH) is a prominent pathological event that occurs during in-stent restenosis and atherosclerosis. Ferroptosis, characterized by iron-dependent and lipid peroxidation, has become the recent focus of studies on the occurrence and progress of cardiovascular diseases. However, there are few studies on ferroptosis and IH. Therefore, we aimed to identify and validate ferroptosis-related markers in IH to explore new possibilities for IH diagnosis and treatment. The IH microarray dataset (GSE182291) was downloaded from the Gene Expression Omnibus (GEO) database and ferroptosis-related genes (FRGs) were obtained from the FerrDb databases. The differentially expressed genes (DEGs) were analyzed using the GEO2R. Overlapping was performed to identify the ferroptosis-related DEGs among the DEGs and FRGs. Then, clustering, Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment, and protein–protein interaction (PPI) analyses were performed. Subsequently, the hub genes were identified using Cytoscape and hub gene–transcription factors and hub gene–microRNA networks were constructed. Finally, real-time qPCR (RT-qPCR) and immunohistochemistry (IHC) were used to verify the mRNA and protein levels of the hub FRGs in IH. Thirty-four FRGs showing significantly different expression were identified from a total of 1,197 DEGs 2 days after ligation; 31 FRGs were selected from a total of 1,556 DEGs 14 days after ligation. The GO and KEGG analyses revealed that these 34 ferroptosis-related DEGs identified 2 days after ligation were mainly enriched in the basolateral plasma membrane, ferroptosis, lipid and atherosclerosis, and IL-17 signaling pathways. The 31 ferroptosis-related DEGs in endometrial hyperplasia identified 14 days after ligation were mainly enriched in response to oxidative stress, ferroptosis, tumor necrosis factor signaling pathway, and lipid and atherosclerosis. Five hub FRGs (Il1b, Ptgs2, Cybb, Cd44, and Tfrc) were identified using PPI networks; four hub FRGs (Il1b, Ptgs2, Cybb, and Cd44) were validated to be upregulated 2 and 14 days after ligation using RT-qPCR and show significantly different expression 14 days after ligation via IHC. Our findings verify the expression of hub DEGs related to ferroptosis in IH and elucidate the potential relationship between ferroptosis and IH, providing more evidence about the vital role of ferroptosis in IH.

PurposeTo investigate the expression and possible role of Sirtuin1 or Silent mating–type information regulation 2 homolog-1 (SIRT1) in post-necrotizing enterocolitis stricture.Materials and MethodsThe expression characteristics of SIRT1 and TGF-β1 in post-necrotizing enterocolitis stricture were detected by immunohistochemistry. The siRNA-SIRT1 was used to inhibit the expression of SIRT1 in intestinal epithelial cells-6 (IEC-6), and qRT-PCR, WB, and ELISA were utilized to detect the changes of Transforming growth factor-β1 (TGF-β1), nuclear factor (NF)-κB, tumor necrosis factor-α (TNF-α), tight junction protein-1 (ZO-1), and vascular endothelial growth factor (VEGF) expressions. The IEC-6 cell proliferation and migration ability were tested via CCK8 kit and Transwell test. The expression of E-cadherin and Vimentin in cells was detected by immunofluorescence.ResultsThe CRP, IL-6, IL-10, and IFN-γ in the serum of Necrotizing enterocolitis (NEC) intestinal stenosis patients were significantly higher than the reference values. The SIRT1 protein was under-expressed and the TGF-β1 protein was overexpressed in NEC intestinal stenosis tissue. And the expression of SIRT1 was negatively correlated with TGF-β1. At the time of diagnosis of NEC, the expression of SIRT1 decreased in children with respiratory distress syndrome and CRP level increased. After inhibiting the expression of SIRT1 in IEC6 cells, the expression levels of TGF-β1, Smad3, and NF-κB were decreased, and the expression of ZO-1 was also decreased. The proliferation and migration ability of IEC6 cells was decreased significantly, and the expression of E-cadherin and Vimentin proteins in IEC6 cells did not change significantly.ConclusionPromotion of intestinal fibrosis by inflammation may be the mechanism of post-necrotizing enterocolitis stricture. SIRT1 may be a protective protein of NEC. The probable mechanism is that SIRT1 can regulate intestinal fibrosis and can protect the intestinal mucosal barrier function to participate in the process of post-necrotizing enterocolitis stricture.

The purpose of this study was to analyze the injury characteristics of patients and therapeutic strategies for patients injured in the last three big earthquakes in China, so as to provide a reference for the improvement of emergency plans for earthquakes. The analysis was based on the data provided by the Mianyang Central Hospital (MCH) from May 12th, 2008 to September 26th, 2017. Microsoft EXCEL software was used for data input, and SPSS was used for statistical analysis. A total of 1,390 earthquake-related patients were hospitalized in MCH. Most patients were admitted to the hospital within the first 2 weeks after the earthquake. The main causes for seismic injuries involved hit/strike by objects or building collapse /burying. Extremity fractures accounted for most injuries, especially 3 days after an earthquake. But soft tissue injuries cannot be neglected. Most earthquake patients were mainly treated by means of surgery and the majority were related to orthopedics. We found that different areas, population, and religions needed a tailored approach to the rescue effort. Therefore, the earthquake magnitude scale has a significant influence on mechanisms, types and severity of the injury of patients injured in earthquakes, as well as their timely transfer, management, and prognosis. Traumatic injuries are very common and thereby various surgical procedures especially orthopedic and neurosurgery are the domain of treatment modalities. Disaster preparedness and combined surgical team effort need to be focused on to reduce both mortality and morbidity.

ObjectivesA huge population, especially the elderly, suffers from otogenic vertigo. However, the multi-modal vestibular network changes, secondary to periphery vestibular dysfunction, have not been fully elucidated. We aim to identify potential microstate electroencephalography (EEG) signatures for otogenic vertigo in this study.Materials and MethodsPatients with recurrent otogenic vertigo and age-matched healthy adults were recruited. We performed 256-channel EEG recording of all participants at resting state. Neuropsychological questionnaires and vestibular function tests were taken as a measurement of patients’ symptoms and severity. We clustered microstates into four classes (A, B, C, and D) and identified their dynamic and syntax alterations of them. These features were further fed into a support vector machine (SVM) classifier to identify microstate signatures for vertigo.ResultsWe compared 40 patients to 45 healthy adults, finding an increase in the duration of Microstate A, and both the occurrence and time coverage of Microstate D. The coverage and occurrence of Microstate C decreased significantly, and the probabilities of non-random transitions between Microstate A and D, as well as Microstate B and C, also changed. To distinguish the patients, the SVM classifier, which is built based on these features, got a balanced accuracy of 0.79 with a sensitivity of 0.78 and a specificity of 0.8.ConclusionThere are several temporal dynamic alterations of EEG microstates in patients with otogenic vertigo, especially in Microstate D, reflecting the underlying process of visual-vestibular reorganization and attention redistribution. This neurophysiological signature of microstates could be used to identify patients with vertigo in the future.

BackgroundEvidence suggests that the risk of recurrence and death in patients with early cervical cancer (ECC) undergoing minimally invasive surgery is significantly higher than that in patients undergoing open surgery. However, the mechanisms underlying such a difference remain unclear. Heart rate variability (HRV) represents autonomic nerve activity, which is related to tumorgenesis and can be used as a prognostic indicator for various cancers. The main purpose of this study was to explore the difference in the effects of laparoscopic and open surgery on HRV in ECC patients.MethodsA total of 68 ECC (FIGO IA1 with lymphovascular space invasion -IIA2) patients undergoing radical hysterectomy for the first time (84% open group vs. 16% laparoscopic group) were included. A single-lead micro-ECG recorder was used to collect 5 min electrocardiograms 1 day before the operation and 3 days after the operation, and then HRV time domain and frequency domain indices were analyzed, including mean heart rate (MeanHR), maximum heart rate (MaxHR), minimum heart rate (MinHR), the standard deviation of all normal-to-normal intervals (SDNN), the root mean square of successive interval differences (RMSSD), very low-frequency power (VLF), low-frequency power (LF), high-frequency power (HF), total power (TP), and the ratio of LF to HF (LF/HF).ResultsHeart rate (i.e., MeanHR, MaxHR, and MinHR) were significantly higher, and HRV (i.e., SDNN, RMSSD, LF, HF, and TP) were significantly lower after the operation than before the operation in both the laparoscopic and open groups (P < 0.05). The postoperative reduction in RMSSD and HF was significantly higher in the laparoscopic group than in the open group (P < 0.05).ConclusionsThese data suggest that radical hysterectomy can lead to increased heart rate and decreased HRV in patients with ECC, which can negatively affect cardiac autonomic regulation. Compared with open surgery, laparoscopic surgery has a greater negative impact on the HRV of ECC patients.

Background: The effectiveness of apatinib and cabozantinib for the treatment of radioactive iodine–refractory differentiated thyroid cancer (RAIR-DTC) has been demonstrated recently. We aimed to evaluate the cost-effectiveness of these treatments from the Chinese healthcare system perspective.Methods: Two partitioned survival models over a 10-year horizon were built to compare the cost and effectiveness of apatinib vs. placebo and cabozantinib vs. placebo based on the clinical data from the phase 3 randomized REALITY and COSMIC-311 trials. Costs and utility data were obtained from the literature and institutional database. The incremental cost-effectiveness ratio (ICER) was calculated. One-way and probabilistic sensitivity analysis was performed to test the robustness of the conclusion.Results: Apatinib yielded an additional quality-adjusted life-year (QALY) of 0.74 at an additional cost of Chinese Renminbi ¥44,077. The ICER was ¥93,460 (US dollar $13545)/QALY and it was below the current willingness-to-pay (WTP) threshold of ¥217341/QALY. Cabozantinib was associated with an additional QALY of 0.79 at an extra cost of ¥3,55,614 when compared with placebo, and the ICER was ¥4,52,325 ($65,554)/QALY, which was above the WTP threshold. The conclusion were robust under one-way and probabilistic sensitivity analysis. The price of cabozantinib has to drop to ¥5.87/mg (39% of the current price) for it has a 50% likelihood of being cost-effective.Conclusion: Apatinib is cost-effective for RAIR-DTC when compared with placebo from the perspective of Chinese healthcare system. However, based on the current evidence, cabozantinib might not be cost-effective and a reduction of price is warranted.

Ischemia-reperfusion injury (IRI) is a common complication associated with liver surgery, and macrophages play an important role in hepatic IRI. Liraglutide, a glucagon-like peptide-1 (GLP-1) analog primarily used to treat type 2 diabetes and obesity, regulates intracellular calcium homeostasis and protects the cardiomyocytes from injury; however, its role in hepatic IRI is not yet fully understood. This study aimed to investigate whether liraglutide can protect the liver from IRI and determine the possible underlying mechanisms. Our results showed that liraglutide pretreatment significantly alleviated the liver damage caused by ischemia-reperfusion (I/R), as evidenced by H&E staining, serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels, and TUNEL staining. Furthermore, the levels of inflammatory cytokines elicited by I/R were distinctly suppressed by liraglutide pretreatment, accompanied by significant reduction in TNF-α, IL-1β, and IL-6 levels. Furthermore, pretreatment with liraglutide markedly inhibited macrophage type I (M1) polarization during hepatic IRI, as revealed by the significant reduction in CD68+ levels in Kupffer cells (KCs) detected via flow cytometry. However, the protective effects of liraglutide on hepatic IRI were partly diminished in GLP-1 receptor-knockout (GLP-1R-/-) mice. Furthermore, in an in vitro study, we assessed the role of liraglutide in macrophage polarization by examining the expression profiles of M1 in bone marrow-derived macrophages (BMDMs) from GLP-1R-/- and C57BL/6J mice. Consistent with the results of the in vivo study, liraglutide treatment attenuated the LPS-induced M1 polarization and reduced the expression of M1 markers. However, the inhibitory effect of liraglutide on LPS-induced M1 polarization was largely abolished in BMDMs from GLP-1R-/- mice. Collectively, our study indicates that liraglutide can ameliorate hepatic IRI by inhibiting macrophage polarization towards an inflammatory phenotype via GLP-1R. Its protective effect against liver IRI suggests that liraglutide may serve as a potential drug for the clinical treatment of liver IRI.

BackgroundThe aim of this prospective study was to evaluate the association between heart rate variability (HRV) and overall survival of lung cancer patients with brain metastases (LCBM).MethodsFifty-six LCBM patients were enrolled in this study. Five-minute electrocardiograms were collected before the time to first brain radiotherapy. HRV was analyzed quantitatively by using the time domain parameters, i.e., the standard deviation of all normal-normal intervals (SDNN) and the root mean square of successive differences (RMSSD). Survival time for LCBM patients was defined as from the date of HRV testing to the date of death or the last follow-up.ResultsIn the univariate analysis, SDNN ≤ 13 ms (P = 0.003) and RMSSD ≤ 4.8 ms (P = 0.014) significantly predicted poor survival. Multivariate analysis confirmed that RMSSD ≤ 4.8 ms (P = 0.013, hazard ratio = 3.457, 95% confidence interval = 1.303–9.171) was also an independent negative prognostic factor after adjusting for mean heart rate, Karnofsky performance status, and number of brain metastases in LCBM patients.ConclusionDecreased RMSSD is independently associated with shorter survival time in LCBM patients. HRV might be a novel predictive biomarker for LCBM prognosis.

Here we demonstrate a facile method by which to deliver complex spatiotemporal stimulation to neural networks in fast patterns, to trigger interesting forms of circuit-level plasticity in cortical areas. We present a complete platform by which patterns of electricity can be arbitrarily defined and distributed across a brain circuit, either simultaneously, asynchronously, or in complex patterns that can be easily designed and orchestrated with precise timing. Interfacing with acute slices of mouse cortex, we show that our system can be used to activate neurons at many locations and drive synaptic transmission in distributed patterns, and that this elicits new forms of plasticity that may not be observable via traditional methods, including interesting measurements of associational and sequence plasticity. Finally, we introduce an automated “network assay” for imaging activation and plasticity across a circuit. Spatiotemporal stimulation opens the door for high-throughput explorations of plasticity at the circuit level, and may provide a basis for new types of adaptive neural prosthetics.

ObjectiveThe psychological condition of healthcare workers since the COVID-19 pandemic has attracted the attention of many studies. However, few have reported on psychosocial problems of primary healthcare workers in the COVID-19 pandemic. This study aimed to examine the mediating roles of social support and resilience in COVID-19-related work stress and symptoms of anxiety and depression.MethodsA total of 840 primary healthcare workers in 17 community health centers in Guangzhou, China, were recruited from May to July 2021. Data on demographic characteristics, COVID-19-related work stress, social support, resilience, anxiety and depression were collected. A structural equation model was used for mediation analysis.ResultsMore than half of participants reported mild or more severe (at least borderline abnormal) symptoms of anxiety (68.1%) and depression (55.6%). Social support and resilience mediate the association between COVID-19-related work stress and symptoms of anxiety and depression, respectively. Furthermore, the association between work stress and symptoms of anxiety and depression was also mediated by an accumulation of social support and resilience. The indirect effect of COVID-19-related work stress on anxiety and depression through resilience was much greater than other indirect effects.ConclusionAnxiety and depression were prevalent among primary healthcare workers. This study highlights the psychological impact of the COVID-19-related psychosocial work environment on primary healthcare workers. There is an urgent need to improve working conditions for primary healthcare workers in the COVID-19 and to implement intervention strategies aimed at increasing individual resilience alongside the establishment of external supportive work environments.

Avian influenza viruses can be efficiently transmitted through mucous membranes, and conventional vaccines are not effective in protecting against mucosal infection by influenza viruses. To induce multiple immune responses in an organism, we constructed a recombinant Lactobacillus plantarum expressing the influenza virus antigen HA1 with the adjuvant dendritic cell-targeting peptide (DCpep). The recombinant L. plantarum strains NC8Δ-pWCF-HA1 and NC8Δ-pWCF-HA1-DCpep were used to immunize mice via oral administration, and the humoral, cellular and mucosal immune responses were evaluated. In addition, the serum levels of specific antibodies and hemagglutination inhibition (HI) levels were also measured. Our results showed that recombinant L. plantarum activated dendritic cells in Peyer’s patches (PPs), increased the numbers of CD4+IFN-γ+ and CD8+IFN-γ+ cells in the spleen and mesenteric lymph nodes (MLNs), and affected the ability of CD4+ and CD8+ cells to proliferate in the spleen and MLNs. Additionally, recombinant L. plantarum increased the number of B220+IgA+ cells in PPs and the level of IgA in the lungs and different intestinal segments. In addition, specific IgG, IgG1 and IgG2a antibodies were induced at high levels in the mice serum, specific IgA antibodies were induced at high levels in the mice feces, and HI potency was significantly increased. Thus, the recombinant L. plantarum strains NC8Δ-pWCF-HA1 and NC8Δ-pWCF-HA1-DCpep have potential as vaccine candidates for avian influenza virus.

Hypertension is one of the major causes of public health problems. Multiple factors affecting gastrointestinal tract function are involved in hypertension. Emerging studies have manifested that gut intervention may play significant roles in regulating blood pressure but the underlying mechanisms are complex and not fully clear. Here, we report a case of 66 years old male who had a long history of hypertension and received Miles surgery for rectal carcinoma. The blood pressure of this patient was returned to normal levels after the operation. The possible reasons could be the modulation of sympathetic tone and the gut microbiota-brain axis. This report provides evidence about the relevance between hypertension and gut intervention particularly in the colorectal sites and gives hints for investigating the possible mechanisms of hypertension and the novel strategy for blood pressure control.

Blood inflammatory biomarkers, including the neutrophil-to-lymphocyte ratio (NLR), the lymphocyte-to-monocyte ratio (LMR), and the platelet-to-lymphocyte ratio (PLR), play a significant role in determining the prognosis of patients with cervical cancer (CC). Currently, no methods are available to predict these indexes pre-operatively. Cardiac autonomic function is determined based on the heart rate variability (HRV), which is also associated with a progressive inflammatory response and cancer. Thus, the main aim of this study was to evaluate the feasibility of using pre-operative HRV parameters in CC patients to predict post-operative blood inflammation biomarkers as a means of determining prognosis. Between 2020 and 2021, 56 patients who were diagnosed with CC and then underwent hysterectomy surgery at the Department of Gynecologic Oncology, First Affiliated Hospital, Bengbu Medical College were enrolled in this study. Five-minute electrocardiogram data were collected 1 day before the operation for analysis of HRV parameters, including frequency domain parameters (LF, HF, and LF/HF) and Poincaré plot parameters (SD1, SD2, and SD2/SD1). Venous blood was collected 2 days post-operatively and inflammatory biomarkers were evaluated, with the NLR, LMR, and PLR determined. Pre-operative SD2 was significantly associated with post-operative PLR, with each 1-unit increase in SD2 decreasing the PLR value by 2.4 ± 0.9 (P < 0.05). Besides, LF/HF was significantly correlated with NLR, with each 1-unit increase in LF/HF increasing the NLR value by 1.1 ± 0.5 (P < 0.05). This association was independent of patient age and body mass index. These results suggest that the pre-operative autonomic nervous system plays a role in the regulation of post-operative cancer inflammation and that pre-operative HRV parameters can potentially predict post-operative inflammation and facilitate clinical treatment decisions.

ObjectiveDysregulation of transfer RNA (tRNA)-derived small noncoding RNA (tsRNA) signatures in human serum has been found in various diseases. Here, we determine whether the signatures of tsRNAs in serum can serve as biomarkers for diagnosis or prognosis of systemic lupus erythematosus (SLE).MethodsInitially, small RNA sequencing was employed for the screening serum tsRNAs obtained from SLE patients, followed by validation with TaqMan probe-based quantitative reverse transcription-PCR (RT-PCR) assay. Receiver operating characteristic (ROC) curve analysis was used to assess the diagnostic efficacy. The biological functions of tsRNAs were identified by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) assay.ResultsWe first analyzed tsRNA signatures in SLE serum and identified that tRF-His-GTG-1 was significantly upregulated in SLE serum. The combination of tRF-His-GTG-1 and anti-dsDNA could serve as biomarkers for diagnosing SLE with a high area under the curve (AUC) of 0.95 (95% CI = 0.92–0.99), sensitivity (83.72%), and specificity (94.19%). Importantly, the noninvasive serum tRF-His-GTG-1 could also be used to distinguish SLE with LN or SLE without LN with AUC of 0.81 (95% CI, 0.73–0.88) and performance (sensitivity 66.27%, specificity 96.15%). Moreover, the serum tsRNA is mainly secreted via exosome and can directly target signaling molecules that play crucial roles in regulating the immune system.ConclusionIn this study, it has been demonstrated for the first time that serum tsRNAs can be employed as noninvasive biomarkers for the efficient diagnosis and prediction of nephritis in SLE.

BackgroundThe effectiveness of Sacituzumab Govitecan (SG) for metastatic triple-negative breast cancer (mTNBC) has been demonstrated. We aimed to evaluate its cost-effectiveness on mTNBC from the Chinese and United States (US) perspective.MethodsA partitioned survival model was developed to compare the cost and effectiveness of SG versus single-agent chemotherapy based on clinical data from the ASCENT phase 3 randomized trial. Cost and utility data were obtained from the literature. The incremental cost-effectiveness ratio (ICER) was measured, and one-way and probabilistic sensitivity analyses (PSA) were performed to observe model stability. A Markov model was constructed to validate the results.ResultsIn China, SG yielded an additional 0.35 quality-adjusted life-year (QALY) at an additional cost of Chinese Renminbi ¥2257842. The ICER was ¥6375856 ($924037)/QALY. In the US, SG yielded the same additional QALY at an extra cost of $175393 and the ICER was $494479/QALY. Similar results were obtained from the Markov model. One-way sensitivity analyses showed that SG price had the greatest impact on the ICER. PSA showed the probability of SG to be cost-effective when compared with chemotherapy was zero at the current willing-to-pay threshold of ¥217341/QALY and $150000/QALY in China and the US, respectively. The probability of cost-effectiveness of SG would approximate 50% if its price was reduced to ¥10.44/mg in China and $3.65/mg in the US.ConclusionSG is unlikely to be a cost-effective treatment of mTNBC at the current price both in China and the US.

Cardiac autonomic modulation, assessed by heart rate variability (HRV), is associated with tumor pathogenesis and development as well as invasion and metastasis. This study aimed to examine this association in breast cancer (BC) patients. A total of 133 patients (average age 49.2years) with BC or benign breast tumors were divided into three groups: benign group, early-stage group, and advanced-stage group. About 5-min resting ECG was collected for the analysis of linear and nonlinear HRV parameters. Multiple logistic regression models were performed to test the independent contribution of HRV to breast tumor stage. The advanced-stage group had significantly reduced HRV compared to the benign and early-stage groups. In particular, for each 1-SD increase in SD2, SD of normal-to-normal intervals, very-low frequency, total power, and low frequency, the odds of having advanced staging decreased by 69.3, 64.3, 58.3, 53.3, and 65.9%, respectively. These associations were independent of age, body mass index, mean heart rate (HR), and respiratory rate (RR). These findings suggest an association between HRV and breast tumor stage, and HRV parameters may help construct an effective early diagnostic and clinical prognostic model.

Although embryonic stem cells or induced pluripotent stem cells are able to differentiate into inner ear hair cells (HCs), they have drawbacks limiting their clinical application, including a potential risk of tumourigenicity. Direct reprogramming of fibroblasts to inner ear HCs could offer an alternative solution to this problem. Here, we present a stepwise guidance protocol to induce mouse embryonic fibroblasts to differentiate into inner ear HC-like cells (HCLs) via mesenchymal-to-epithelial transition and then acquisition of otic sensory epithelial cell traits by overexpression of three key transcription factors. These induced HCLs express multiple HC-specific proteins, display protrusions reminiscent of ciliary bundle structures, respond to voltage stimulation, form functional mechanotransduction channels, and exhibit a transcriptional profile of HC signature. Together, our work provides a new method to produce functional HCLs in vitro, which may have important implications for studies of HC development, drug discovery, and cell replacement therapy for hearing loss.

Objective: Diabetic nephropathy (DN) is a major microvascular complication of diabetes and the leading cause of end-stage renal disease. Early detection and prevention of DN are important. Retinol-binding protein 4 (RBP4) has been considered as a single diagnostic marker for the detection of renal impairment. However, the results have been inconsistent. The present meta-analysis aimed to determine the diagnostic potential of RBP4 in patients in type 2 diabetes mellitus (T2DM) with DN. Methods: We searched PubMed, Web of Science, Embase, Wanfang and CNKI databases from inception until January 2024. The meta-analysis was performed by Stata version 15.0, and sensitivity, specificity, positive and negative likelihood ratios (PLR and NLR), diagnostic odds ratio (DOR) and area under the curve (AUC) were pooled. The Quality Assessment of Diagnostic Accuracy Studies-2 tool was utilized to assess the quality of each included study. In addition, heterogeneity and publication bias were evaluated. Results: Twenty-nine studies were included in the meta-analysis. The pooled sensitivity and specificity were 0.76 [95% confidence interval (CI), 0.71-0.80] and 0.81 (95% CI, 0.76-0.85), respectively. The results showed a pooled PLR of 4.06 (95% CI, 3.16-5.21), NLR of 0.29 (95% CI, 0.24-0.36) and DOR of 13.76 (95% CI, 9.29-20.37). The area under the summarized receiver operating characteristic curve was given a value of 0.85 (95% CI, 0.82-0.88). No obvious publication bias existed in the Deeks' funnel plot asymmetry test. Conclusion: Our findings suggest that RBP4 has a promising diagnostic value with good sensitivity and specificity for patients with T2DM with DN. [ABSTRACT FROM AUTHOR]

Climate change, characterized by rising atmospheric CO2 levels and temperatures, poses significant challenges to global crop production. Sweet sorghum, a prominent C4 cereal extensively grown in arid areas, emerges as a promising candidate for sustainable bioenergy production. This study investigated the responses of photosynthesis and leaf-scale water use efficiency (WUE) to varying light intensity (I) in sweet sorghum under different temperature and CO2 conditions. Comparative analyses were conducted between the An-I, gs-I, Tr-I, WUEi-I, and WUEinst-I models proposed by Ye et al. and the widely utilized the non-rectangular hyperbolic (NRH) model for fitting light response curves. The Ye's models effectively replicated the light response curves of sweet sorghum, accurately capturing the diminishing intrinsic WUE (WUEi) and instantaneous WUE (WUEinst) trends with increasing I. The fitted maximum values of An, gs, Tr, WUEi, and WUEinst and their saturation light intensities closely matched observations, unlike the NRH model. Despite the NRH model demonstrating high R2 values for An-I, gs-I, and Tr-I modelling, it returned the maximum values significantly deviating from observed values and failed to generate saturation light intensities. It also inadequately represented WUE responses to I, overestimating WUE. Across different leaf temperatures, An, gs, and Tr of sweet sorghum displayed comparable light response patterns. Elevated temperatures increased maximum An, gs, and Tr but consistently declined maximum WUEi and WUEinst. However, WUEinst declined more sharply due to the disproportionate transpiration increase over carbon assimilation. Critically, sweet sorghum An saturated at current atmospheric CO2 levels, with no significant gains under 550 mmol mol-1. Instead, stomatal closure enhanced WUE under elevated CO2 by coordinated gs and Tr reductions rather than improved carbon assimilation. Nonetheless, this response diminished under simultaneously high temperature, suggesting intricate interplay between CO2 and temperature in modulating plant responses. These findings provide valuable insights into photosynthetic dynamics of sweet sorghum, aiding predictions of yield and optimization of cultivation practices. Moreover, our methodology serves as a valuable reference for evaluating leaf photosynthesis and WUE dynamics in diverse plant species. [ABSTRACT FROM AUTHOR]

Placenta-specific protein 9 (PLAC9) is a putative secretory protein that was initially identified in the placenta and is involved in cell proliferation and motility. Bioinformatics analyses revealed that PLAC9 is repressed in lung cancers (LCs), especially lung adenocarcinomas, compared to that in the paired adjacent normal tissues, indicating that PLAC9 might be involved in the pathogenesis of pulmonary diseases. To investigate the potential role of PLAC9 in the abnormal reprogramming of airway epithelial cells (AECs), a key cause of pulmonary diseases, we constructed a stable PLAC9-overexpressing human bronchial epithelial cell line (16HBE-GFP-Plac9). We utilized the proteomic approach isobaric tag for relative and absolute quantification (iTRAQ) to analyze the effect of PLAC9 on cellular protein composition. Gene ontology (GO) and pathway analyses revealed that GO terms and pathways associated with cell proliferation, cell cycle progression, and cell motility and migration were significantly enriched among the proteins regulated by PLAC9. Our in vitro results showed that PLAC9 overexpression reduced cell proliferation, altered cell cycle progression, and increased cell motility, including migration and invasion. Our findings suggest that PLAC9 inhibits cell proliferation through S phase arrest by altering the expression levels of cyclin/cyclin-dependent kinases (CDKs) and promotes cell motility, likely via the concerted actions of cyclins, E-cadherin, and vimentin. Since these mechanisms may underlie PLAC9-mediated abnormal human bronchial pathogenesis, our study provides a basis for the development of molecular targeted treatments for LCs.

Menopause and associated renal complications are linked to systemic redox stress, and the causal factors remain unclear. As the role of Hypericum perforatum L. (HPL) in menopause-induced kidney disease therapy is still ambiguous, we aim to explore the effects of HPL on systemic redox stress under ovariectomy (OVX)-induced kidney dysfunction conditions. Here, using combined proteomic and metabolomic approaches, we constructed a multi-scaled “HPL-disease-gene-metabolite” network to generate a therapeutic “big picture” that indicated an important link between glutathione redox stress and kidney impairment. HPL exhibited the potential to maintain cellular redox homeostasis by inhibiting gamma-glutamyltransferase 1 (Ggt1) overexpression, along with promoting the efflux of accumulated toxic amino acids and their metabolites. Moreover, HPL restored alanyl-aminopeptidase (Anpep) expression and metabolite shifts, promoting antioxidative metabolite processing, and recovery. These findings provide a comprehensive description of OVX-induced glutathione redox stress at multiple levels and support HPL therapy as an effective modulator in renal tissues to locally influence the glutathione metabolism pathway and subsequent redox homeostasis.