Advances in biosensors for major depressive disorder diagnostic biomarkers.

Depression is one of the most common mental disorders and is mainly characterized by low mood or lack of interest and pleasure. It can be accompanied by varying degrees of cognitive and behavioral changes and may lead to suicide risk in severe cases. Due to the subjectivity of diagnostic methods and the complexity of patients' conditions, the diagnosis of major depressive disorder (MDD) has always been a difficult problem in psychiatry. With the discovery of more diagnostic biomarkers associated with MDD in recent years, especially emerging non-coding RNAs (ncRNAs), it is possible to quantify the condition of patients with mental illness based on biomarker levels. Point-of-care biosensors have emerged due to their advantages of convenient sampling, rapid detection, miniaturization, and portability. After summarizing the pathogenesis of MDD, representative biomarkers, including proteins, hormones, and RNAs, are discussed. Furthermore, we analyzed recent advances in biosensors for detecting various types of biomarkers of MDD, highlighting representative electrochemical sensors. Future trends in terms of new biomarkers, new sample processing methods, and new detection modalities are expected to provide a complete reference for psychiatrists and biomedical engineers.

Construction and validation of a novel tumor morphology immune inflammatory nutritional score (TIIN score) for intrahepatic cholangiocarcinoma: a multicenter study.

BACKGROUND: Tumor morphology, immune function, inflammatory levels, and nutritional status play critical roles in the progression of intrahepatic cholangiocarcinoma (ICC). This multicenter study aimed to investigate the association between markers related to tumor morphology, immune function, inflammatory levels, and nutritional status with the prognosis of ICC patients. Additionally, a novel tumor morphology immune inflammatory nutritional score (TIIN score), integrating these factors was constructed. METHODS: A retrospective analysis was performed on 418 patients who underwent radical surgical resection and had postoperative pathological confirmation of ICC between January 2016 and January 2020 at three medical centers. The cohort was divided into a training set (n = 272) and a validation set (n = 146). The prognostic significance of 16 relevant markers was assessed, and the TIIN score was derived using LASSO regression. Subsequently, the TIIN-nomogram models for OS and RFS were developed based on the TIIN score and the results of multivariate analysis. The predictive performance of the TIIN-nomogram models was evaluated using ROC survival curves, calibration curves, and clinical decision curve analysis (DCA). RESULTS: The TIIN score, derived from albumin-to-alkaline phosphatase ratio (AAPR), albumin-globulin ratio (AGR), monocyte-to-lymphocyte ratio (MLR), and tumor burden score (TBS), effectively categorized patients into high-risk and low-risk groups using the optimal cutoff value. Compared to individual metrics, the TIIN score demonstrated superior predictive value for both OS and RFS. Furthermore, the TIIN score exhibited strong associations with clinical indicators including obstructive jaundice, CEA, CA19-9, Child-pugh grade, perineural invasion, and 8th edition AJCC N stage. Univariate and multivariate analysis confirmed the TIIN score as an independent risk factor for postoperative OS and RFS in ICC patients (p < 0.05). Notably, the TIIN-nomogram models for OS and RFS, constructed based on the multivariate analysis and incorporating the TIIN score, demonstrated excellent predictive ability for postoperative survival in ICC patients. CONCLUSION: The development and validation of the TIIN score, a comprehensive composite index incorporating tumor morphology, immune function, inflammatory level, and nutritional status, significantly contribute to the prognostic assessment of ICC patients. Furthermore, the successful application of the TIIN-nomogram prediction model underscores its potential as a valuable tool in guiding individualized treatment strategies for ICC patients. These findings emphasize the importance of personalized approaches in improving the clinical management and outcomes of ICC.

Identification of mine water source based on TPE-LightGBM.

Mine water inrush is a serious threat to mine safety production. It is very important to identify water inrush source types quickly to prevent and control water damage. In this study, the aqueous chemical components Na+ + K+, Ca2+, Mg2+, Cl-, SO42- and HCO3- of different aquifers in Pingdingshan coalfield were selected as the characteristic values, and the Surface water, Quaternary pore water, Carboniferous limestone karst water, Permian sandstone water, and Cambrian limestone karst water were used as the labels. An intelligent water source discrimination model is proposed by combining data mining, classification models, and reinforcement learning. As outlier data in the samples may interfere with the model recognition ability, the data distribution range was analyzed using box plots, and 20 groups of abnormal samples were excluded. The processed water chemistry data were divided into 80% learning samples and 20% test samples, and the learning samples were fed into a light gradient boosting machine (LightGBM) for training. The tree-structured parson estimator (TPE) obtains the optimal values of the main parameters of LightGBM in a very short time. Substituting the hyperparameters back into the model yields a 13.9% improvement in the accuracy of the model, proving the effectiveness of the TPE algorithm. To further validate the performance of the model, TPE-LightGBM is compared and analyzed with a Random Search-Multi Layer Perceptron Machine (RS-MLP) and Genetic Algorithm-Extreme Gradient Boosting Tree (GA-SVM). The accuracy of TPE-LightGBM, RS-MLP, and GA-SVM is 0.931, 0.759, 0.724 in that order, and the generalization error RMSE is 0.415, 1.05, and 1.313 in that order. The results show that TPE-LightGBM is more advantageous in water source identification and is more resistant to overfitting. By calculating and comparing the information gain of each variable, the contribution of Ca2+ is the highest, so it is necessary to pay attention to the change in Ca2+ concentration. TPE-LightGBM's high accuracy and generalization ability have a good prospect for the identification of sudden water source types.

Exercise-Induced Reduction of IGF1R Sumoylation Attenuates Neuroinflammation in APP/PS1 Transgenic Mice.

INTRODUCTION: Alzheimer's Disease (AD), a progressive neurodegenerative disorder, is marked by cognitive deterioration and heightened neuroinflammation. The influence of Insulin-like Growth Factor 1 Receptor (IGF1R) and its post-translational modifications, especially sumoylation, is crucial in understanding the progression of AD and exploring novel therapeutic avenues. OBJECTIVES: This study investigates the impact of exercise on the sumoylation of IGF1R and its role in ameliorating AD symptoms in APP/PS1 mice, with a specific focus on neuroinflammation and innovative therapeutic strategies. METHODS: APP/PS1 mice were subjected to a regimen of moderate-intensity exercise. The investigation encompassed assessments of cognitive functions, alterations in hippocampal protein expressions, neuroinflammatory markers, and the effects of exercise on IGF1R and SUMO1 nuclear translocation. Additionally, the study evaluated the efficacy of KPT-330, a nuclear export inhibitor, as an alternative to exercise. RESULTS: Exercise notably enhanced cognitive functions in AD mice, possibly through modulations in hippocampal proteins, including Bcl-2 and BACE1. A decrease in neuroinflammatory markers such as IL-1ß, IL-6, and TNF-α was observed, indicative of reduced neuroinflammation. Exercise modulated the nuclear translocation of SUMO1 and IGF1R in the hippocampus, thereby facilitating neuronal regeneration. Mutant IGF1R (MT IGF1R), lacking SUMO1 modification sites, showed reduced SUMOylation, leading to diminished expression of pro-inflammatory cytokines and apoptosis. KPT-330 impeded the formation of the IGF1R/RanBP2/SUMO1 complex, thereby limiting IGF1R nuclear translocation, inflammation, and neuronal apoptosis, while enhancing cognitive functions and neuron proliferation. CONCLUSION: Moderate-intensity exercise effectively mitigates AD symptoms in mice, primarily by diminishing neuroinflammation, through the reduction of IGF1R Sumoylation. KPT-330, as a potential alternative to physical exercise, enhances the neuroprotective role of IGF1R by inhibiting SUMOylation through targeting XPO1, presenting a promising therapeutic strategy for AD.

Coptisine inhibits neointimal hyperplasia through attenuating Pak1/Pak2 signaling in vascular smooth muscle cells without retardation of re-endothelialization.

BACKGROUND AND AIMS: Vascular injury-induced endothelium-denudation and profound vascular smooth muscle cells (VSMCs) proliferation and dis-regulated apoptosis lead to post-angioplasty restenosis. Coptisine (CTS), an isoquinoline alkaloid, has multiple beneficial effects on the cardiovascular system. Recent studies identified it selectively inhibits VSMCs proliferation. However, its effects on neointimal hyperplasia, re-endothelialization, and the underlying mechanisms are still unclear. METHODS: Cell viability was assayed by 3-[4,5-dimethylthiazole-2-yl]-2,5-diphenyltetrazolium bromide (MTT) and cell counting kit-8 (CCK-8). Cell proliferation and apoptosis were measured by flow cytometry and immunofluorescence of Ki67 and TUNEL. Quantitative phosphoproteomics (QPP) was employed to screen CTS-responsive phosphor-sites in the key regulators of cell proliferation and apoptosis. Neointimal hyperplasia was induced by balloon injury of rat left carotid artery (LCA). Adenoviral gene transfer was conducted in both cultured cells and LCA. Re-endothelialization was evaluated by Evan's blue staining of LCA. RESULTS: 1) CTS had strong anti-proliferative and pro-apoptotic effects in cultured rat VSMCs, with the EC50 4∼10-folds lower than that in endothelial cells (ECs). 2) Rats administered with CTS, either locally to LCA's periadventitial space or orally, demonstrated a potently inhibited balloon injury-induced neointimal hyperplasia, but had no delaying effect on re-endothelialization. 3) The QPP results revealed that the phosphorylation levels of Pak1S144/S203, Pak2S20/S197, Erk1T202/Y204, Erk2T185/Y187, and BadS136 were significantly decreased in VSMCs by CTS. 4) Adenoviral expression of phosphomimetic mutants Pak1D144/D203/Pak2D20/D197 enhanced Pak1/2 activities, stimulated the downstream pErk1T202/Y204/pErk2T185/Y187/pErk3S189/pBadS136, attenuated CTS-mediated inhibition of VSMCs proliferation and promotion of apoptosis in vitro, and potentiated neointimal hyperplasia in vivo. 5) Adenoviral expression of phosphoresistant mutants Pak1A144/A203/Pak2A20/A197 inactivated Pak1/2 and totally simulated the inhibitory effects of CTS on platelet-derived growth factor (PDGF)-stimulated VSMCs proliferation and PDGF-inhibited apoptosis in vitro and neointimal hyperplasia in vivo. 6) LCA injury significantly enhanced the endogenous phosphorylation levels of all but pBadS136. CTS markedly attenuated all the enhanced levels. CONCLUSIONS: These results indicate that CTS is a promising medicine for prevention of post-angioplasty restenosis without adverse impact on re-endothelialization. CTS-directed suppression of pPak1S144/S203/pPak2S20/S197 and the subsequent effects on downstream pErk1T202/Y204/pErk2T185/Y187/pErk3S189 and pBadS136 underline its mechanisms of inhibition of VSMCs proliferation and stimulation of apoptosis. Therefore, the phosphor-sites of Pak1S144/S203/Pak2S20/S197 constitute a potential drug-screening target for fighting neointimal hyperplasia restenosis.

Exploring the relation of active surveillance schedules and prostate cancer mortality.

BACKGROUND: Active surveillance (AS), where treatment is deferred until cancer progression is detected by a biopsy, is acknowledged as a way to reduce overtreatment in prostate cancer. However, a consensus on the frequency of taking biopsies while in AS is lacking. In former studies to optimize biopsy schedules, the delay in progression detection was taken as an evaluation indicator and believed to be associated with the long-term outcome, prostate cancer mortality. Nevertheless, this relation was never investigated in empirical data. Here, we use simulated data from a microsimulation model to fill this knowledge gap. METHODS: In this study, the established MIcrosimulation SCreening Analysis model was extended with functionality to simulate the AS procedures. The biopsy sensitivity in the model was calibrated on the Canary Prostate Cancer Active Surveillance Study (PASS) data, and four (tri-yearly, bi-yearly, PASS, and yearly) AS programs were simulated. The relation between detection delay and prostate cancer mortality was investigated by Cox models. RESULTS: The biopsy sensitivity of progression detection was found to be 50%. The Cox models show a positive relation between a longer detection delay and a higher risk of prostate cancer death. A 2-year delay resulted in a prostate cancer death risk of 2.46%-2.69% 5 years after progression detection and a 10-year risk of 5.75%-5.91%. A 4-year delay led to an approximately 8% greater 5-year risk and an approximately 25% greater 10-year risk. CONCLUSION: The detection delay is confirmed as a surrogate for prostate cancer mortality. A cut-off for a "safe" detection delay could not be identified.

Rapid detection of trace nitrobenzene in water via SERS using a portable Raman spectrometer.

Nitrobenzene is currently the most widely used explosive substance, and is known for its high toxicity and mutagenicity. It can cause severe environmental and water pollution, posing a risk to public health. Among various explosives analysis methods, surface-enhanced Raman spectroscopy (SERS) has the advantages of fast analysis speed, low detection cost, and easy operation, and has become one of the most promising analytical detection methods. Here, we present a portable and reliable sol-based SERS method for the detection of trace amounts of 2,4,6-trinitrotoluene (TNT) in different water bodies. The Meisenheimer complex formed by nitrobenzene and hydrazine hydrate can assemble on unmodified Au nanoparticles in a sol via Au-N bonds, enabling rapid detection of TNT in seawater, lake water, and tap water using a portable Raman spectrometer. Experimental results show that this SERS method can complete the detection within a few minutes and the detection sensitivity can reach 0.01 mg L-1, which is far lower than China's national standard of no more than 0.5 mg L-1. Furthermore, this method was also successfully applied to detect trace 2,4-dinitrotoluene (2,4-DNT) and picric acid (2,4,6-trinitrophenol) in water, demonstrating its strong applicability for on-site detection of nitrobenzene explosives.

Predictive value of HTS grade in patients with intrahepatic cholangiocarcinoma undergoing radical resection: a multicenter study from China.

BACKGROUND: Intrahepatic cholangiocarcinoma (ICC) is a highly malignant tumor with a poor prognosis. This study aimed to investigate whether Hemoglobin, Albumin, Lymphocytes, and Platelets (HALP) score and Tumor Burden Score (TBS) serves as independent influencing factors following radical resection in patients with ICC. Furthermore, we sought to evaluate the predictive capacity of the combined HALP and TBS grade, referred to as HTS grade, and to develop a prognostic prediction model. METHODS: Clinical data for ICC patients who underwent radical resection were retrospectively analyzed. Univariate and multivariate Cox regression analyses were first used to find influencing factors of prognosis for ICC. Receiver operating characteristic (ROC) curves were then used to find the optimal cut-off values for HALP score and TBS and to compare the predictive ability of HALP, TBS, and HTS grade using the area under these curves (AUC). Nomogram prediction models were constructed and validated based on the results of the multivariate analysis. RESULTS: Among 423 patients, 234 (55.3%) were male and 202 (47.8) were aged ≥ 60 years. The cut-off value of HALP was found to be 37.1 and for TBS to be 6.3. Our univariate results showed that HALP, TBS, and HTS grade were prognostic factors of ICC patients (all P < 0.05), and ROC results showed that HTS had the best predictive value. The Kaplan-Meier curve showed that the prognosis of ICC patients was worse with increasing HTS grade. Additionally, multivariate regression analysis showed that HTS grade, carbohydrate antigen 19-9 (CA19-9), tumor differentiation, and vascular invasion were independent influencing factors for Overall survival (OS) and that HTS grade, CA19-9, CEA, vascular invasion and lymph node invasion were independent influencing factors for recurrence-free survival (RFS) (all P < 0.05). In the first, second, and third years of the training group, the AUCs for OS were 0.867, 0.902, and 0.881, and the AUCs for RFS were 0.849, 0.841, and 0.899, respectively. In the first, second, and third years of the validation group, the AUCs for OS were 0.727, 0.771, and 0.763, and the AUCs for RFS were 0.733, 0.746, and 0.801, respectively. Through the examination of calibration curves and using decision curve analysis (DCA), nomograms based on HTS grade showed excellent predictive performance. CONCLUSIONS: Our nomograms based on HTS grade had excellent predictive effects and may thus be able to help clinicians provide individualized clinical decision for ICC patients.

Construction and validation of a novel prognostic model for intrahepatic cholangiocarcinoma based on a combined scoring system of systemic immune-inflammation index and albumin-bilirubin: a multicenter study.

Background: The degree of inflammation and immune status is widely recognized to be associated with intrahepatic cholangiocarcinoma (ICC) and is closely linked to poor postoperative survival. The purpose of this study was to evaluate whether the systemic immune-inflammatory index (SII) and the albumin bilirubin (ALBI) grade together exhibit better predictive strength compared to SII and ALBI separately in patients with ICC undergoing curative surgical resection. Methods: A retrospective analysis was performed on a cohort of 374 patients with histologically confirmed ICC who underwent curative surgical resection from January 2016 to January 2020 at three medical centers. The cohort was divided into a training set comprising 258 patients and a validation set consisting of 116 patients. Subsequently, the prognostic predictive abilities of three indicators, namely SII, ALBI, and SII+ALBI grade, were evaluated. Independent risk factors were identified through univariate and multivariate analyses. The identified independent risk factors were then utilized to construct a nomogram prediction model, and the predictive strength of the nomogram prediction model was assessed through Receiver Operating Characteristic (ROC) survival curves and calibration curves. Results: Univariate analysis of the training set, consisting of 258 eligible patients with ICC, revealed that SII, ALBI, and SII+ALBI grade were significant prognostic factors for overall survival (OS) and recurrence-free survival (RFS) (p < 0.05). Multivariate analysis revealed the independent significance of SII+ALBI grade as a risk factor for postoperative OS and RFS (p < 0.05). Furthermore, we conducted an analysis of the correlation between SII, ALBI, SII+ALBI grade, and clinical features, indicating that SII+ALBI grade exhibited stronger associations with clinical and pathological characteristics compared to SII and ALBI. We constructed a predictive model for postoperative survival in ICC based on SII+ALBI grade, as determined by the results of multivariate analysis. Evaluation of the model's predictive strength was performed through ROC survival curves and calibration curves in the training set and validation set, revealing favorable predictive performance. Conclusion: The SII+ALBI grade, a novel classification based on inflammatory and immune status, serves as a reliable prognostic indicator for postoperative OS and RFS in patients with ICC.

RIG-I promotes immune evasion of colon cancer by modulating PD-L1 ubiquitination.

Colon cancer is one of the most prevalent cancers and exhibits high mortality worldwide. Despite the certain success in the immunotherapy of many tumor types, the limited response of colon cancer to immunotherapy remains a difficult problem. Retinoic acid-inducible gene-I (RIG-I) is a crucial component in innate antiviral immunity, but its role in antitumor immunity remains unclear. Here, in this report, we found that silencing RIG-I decreased resistance to tumor cells killed by T cells and attenuated colon tumor growth in immunocompetent mice. Meanwhile, overexpressing RIG-I promoted tumor progression, and high expression of RIG-I sensitized cells to anti-programmed cell death protein-1 (PD-1) therapy in vivo. Interestingly, we found that RIG-I influenced programmed cell death ligand 1 (PD-L1) expression to promote colon cancer immune evasion without relying on type I interferon stimulation. Mechanistically, RIG-I could compete with Speckle Type POZ protein (SPOP) to bind PD-L1, leading to attenuation of the polyubiquitination and proteasomal degradation of PD-L1. Collectively, our work reveals new insights into the contribution of RIG-I to driving immune evasion by maintaining the stability of PD-L1 through post-translational modification and provides a promising biomarker of the efficacy of immunotherapy in colon cancer.

RIG-I promotes cell proliferation in esophageal squamous cell carcinoma by facilitating p21 degradation.

Retinoic acid-inducible gene-I (RIG-I) is considered a key sensor for host recognition of RNA virus infections. Recent studies have shown that RIG-I also regulates carcinogenesis. However, the role of RIG-I in esophageal squamous cell carcinoma (ESCC) remains unclear. We investigated the RIG-I expression in ESCC cells using a public database, immunohistochemistry, and Western blotting. We evaluated the proliferative activity of ESCC cells using CCK-8, colony formation, and EdU staining assays. Further, we determined the ESCC cell-cycle changes using flow cytometry and the ubiquitination of p21 in the cells using cycloheximide chase and ubiquitination assays. Finally, we verified the in vivo effects of RIG-I on ESCC cells by constructing xenograft models. RIG-I was highly expressed in ESCC cells and significantly promoted their proliferation and cell-cycle. Moreover, RIG-I knockdown inhibited xenograft growth in nude mice. Furthermore, RIG-I accelerated the cell-cycle by promoting the ubiquitination and degradation of p21. Overall, this study revealed that the increased expression of RIG-I due to ESCC accelerated the progression of esophageal cancer by promoting the ubiquitination and degradation of p21, which is related to the prognosis of ESCC. Thus, RIG-I may be a novel therapeutic target for ESCC treatment.

Retrospective study: risk assessment model for osteoporosis-a detailed exploration involving 4,552 Shanghai dwellers.

Background: Osteoporosis, a prevalent orthopedic issue, significantly influences patients' quality of life and results in considerable financial burden. The objective of this study was to develop and validate a clinical prediction model for osteoporosis risk, utilizing computer algorithms and demographic data. Method: In this research, a total of 4,552 residents from Shanghai were retrospectively included. LASSO regression analysis was executed on the sample's basic characteristics, and logistic regression was employed for analyzing clinical characteristics and building a predictive model. The model's diagnostic capacity for predicting osteoporosis risk was assessed using R software and computer algorithms. Results: The predictive nomogram model for bone loss risk, derived from the LASSO analysis, comprised factors including BMI, TC, TG, HDL, Gender, Age, Education, Income, Sleep, Alcohol Consumption, and Diabetes. The nomogram prediction model demonstrated impressive discriminative capability, with a C-index of 0.908 (training set), 0.908 (validation set), and 0.910 (entire cohort). The area under the ROC curve (AUC) of the model was 0.909 (training set), 0.903 (validation set), and applicable to the entire cohort. The decision curve analysis further corroborated that the model could efficiently predict the risk of bone loss in patients. Conclusion: The nomogram, based on essential demographic and health factors (Body Mass Index, Total Cholesterol, Triglycerides, High-Density Lipoprotein, Gender, Age, Education, Income, Sleep, Alcohol Consumption, and Diabetes), offered accurate predictions for the risk of bone loss within the studied population.

Novel signaling axis of FHOD1-RNF213-Col1α/Col3α in the pathogenesis of hypertension-induced tunica media thickening.

Hypertension-induced tunica media thickening (TMT) is the most important fundamental for the subsequent complications like stroke and cardiovascular diseases. Pathogenically, TMT originates from both vascular smooth muscle cells (VSMCs) hypertrophy due to synthesizing more amount of intracellular contractile proteins and excess secretion of extracellular matrix. However, what key molecules are involved in the pathogenesis of TMT is unknown. We hypothesize that formin homology 2 domain-containing protein 1 (FHOD1), an amply expressed mediator for assembly of thin actin filament in VSMCs, is a key regulator for the pathogenesis of TMT. In this study, we found that FHOD1 expression and its phosphorylation/activation were both upregulated in the arteries of three kinds of hypertensive rats. Ang-II induced actin filament formation and hypertrophy through activation and upregulation of FHOD1 in VSMCs. Active FHOD1-mediated actin filament assembly and secretions of collagen-1α/collagen-3α played crucial roles in Ang-II-induced VSMCs hypertrophy in vitro and hypertensive TMT in vivo. Proteomics demonstrated that activated FL-FHOD1 or its C-terminal diaphanous-autoregulatory domain significantly upregulated RNF213 (ring finger protein 213), a 591-kDa cytosolic E3 ubiquitin ligase with its loss-of-functional mutations being a susceptibility gene for Moyamoya disease which has prominent tunica media thinning in both intracranial and systemic arteries. Mechanistically, activated FHOD1 upregulated its downstream effector RNF213 independently of its classical pathway of decreasing G-actin/F-actin ratio, transcription, and translation, but dependently on its C-terminus-mediated stabilization of RNF213 protein. FHOD1-RNF213 signaling dramatically promoted collagen-1α/collagen-3α syntheses in VSMCs. Our results discovered a novel signaling axis of FHOD1-RNF213-collagen-1α/collagen-3α and its key role in the pathogenesis of hypertensive TMT.

Dynamics in Liver Stiffness Measurements Predict Outcomes in Advanced Chronic Liver Disease.

BACKGROUND & AIMS: Liver stiffness measurements (LSMs) provide an opportunity to monitor liver disease progression and regression noninvasively. We aimed to determine the prognostic relevance of LSM dynamics over time for liver-related events and death in patients with chronic liver disease. METHODS: Patients with chronic liver disease undergoing 2 or more reliable LSMs at least 180 days apart were included in this retrospective cohort study and stratified at baseline (BL) as nonadvanced chronic liver disease (non-ACLD, BL-LSM < 10 kPa), compensated ACLD (cACLD; BL-LSM ≥ 10 kPa), and decompensated ACLD. Data on all consecutive LSMs and clinical outcomes were collected. RESULTS: There were 2508 patients with 8561 reliable LSMs (3 per patient; interquartile range, 2-4) included: 1647 (65.7%) with non-ACLD, 757 (30.2%) with cACLD, and 104 (4.1%) with decompensated ACLD. Seven non-ACLD patients (0.4%) and 83 patients with cACLD (10.9%) developed hepatic decompensation (median follow-up, 71 months). A 20% increase in LSM at any time was associated with an approximately 50% increased risk of hepatic decompensation (hazard ratio, 1.58; 95% CI, 1.41-1.79; P < .001) and liver-related death (hazard ratio, 1.45; 95% CI, 1.28-1.68; P < .001) in patients with cACLD. LSM dynamics yielded a high accuracy to predict hepatic decompensation in the following 12 months (area under the receiver operating characteristics curve = 0.933). The performance of LSM dynamics was numerically better than dynamics in Fibrosis-4 score (0.873), Model for End-Stage Liver Disease (0.835), and single time-point LSM (BL-LSM: 0.846; second LSM: 0.880). Any LSM decrease to <20 kPa identified patients with cACLD with a substantially lower risk of hepatic decompensation (hazard ratio, 0.13; 95% CI, 0.07-0.24). If reliable, LSM also confers prognostic information in decompensated ACLD. CONCLUSIONS: Repeating LSM enables an individual and updated risk assessment for decompensation and liver-related mortality in ACLD.

Multi-parameter surface plasmon resonance instrument for multiple nucleic acid quantitative detection.

Multiplex nucleic acid assays can simultaneously detect the characteristics of different target nucleic acids in complex mixtures and are used in disease diagnosis, environmental monitoring, and food safety. However, traditional nucleic acid amplification assays have limitations such as complicated operation, long detection time, unstable fluorescent labeling, and mutual interference of multiplex nucleic acids. We developed a real-time, rapid, and label-free surface plasmon resonance (SPR) instrument for multiplex nucleic acid detection. The multiparametric optical system based on total internal reflection solves the multiplex detection problem by cooperating with linear light source, prism, photodetector, and mechanical transmission system. An adaptive threshold consistency correction algorithm is proposed to solve the problem of inconsistent responsiveness of different detection channels and the inability of quantitative comparison. The instrument achieves label-free and amplification-free rapid detection of these biomarkers for miRNA-21 and miRNA-141, which are widely expressed in breast cancer and prostate cancer. The multiplex nucleic acid detection takes 30 min and the biosensor has good repeatability and specificity. The instrument has a limit of detection (LODs) of 50 nM for target oligonucleotides, and the smallest absolute amount of sample that can be detected is about 4 pmol. It provides a simple and efficient point-of-care testing (POCT) detection platform for small molecules such as DNA and miRNA.

To infer the probability of cervical ossification of the posterior longitudinal ligament and explore its impact on cervical surgery.

The ossification of the posterior longitudinal ligament (OPLL) in the cervical spine is commonly observed in degenerative changes of the cervical spine. Early detection of cervical OPLL and prevention of postoperative complications are of utmost importance. We gathered data from 775 patients who underwent cervical spine surgery at the First Affiliated Hospital of Guangxi Medical University, collecting a total of 84 variables. Among these patients, 144 had cervical OPLL, while 631 did not. They were randomly divided into a training cohort and a validation cohort. Multiple machine learning (ML) methods were employed to screen the variables and ultimately develop a diagnostic model. Subsequently, we compared the postoperative outcomes of patients with positive and negative cervical OPLL. Initially, we compared the advantages and disadvantages of various ML methods. Seven variables, namely Age, Gender, OPLL, AST, UA, BMI, and CHD, exhibited significant differences and were used to construct a diagnostic nomogram model. The area under the curve (AUC) values of this model in the training and validation groups were 0.76 and 0.728, respectively. Our findings revealed that 69.2% of patients who underwent cervical OPLL surgery eventually required elective anterior surgery, in contrast to 86.8% of patients who did not have cervical OPLL. Patients with cervical OPLL had significantly longer operation times and higher postoperative drainage volumes compared to those without cervical OPLL. Interestingly, preoperative cervical OPLL patients demonstrated significant increases in mean UA, age, and BMI. Furthermore, 27.1% of patients with cervical anterior longitudinal ligament ossification (OALL) also exhibited cervical OPLL, whereas this occurrence was only observed in 6.9% of patients without cervical OALL. We developed a diagnostic model for cervical OPLL using the ML method. Our findings indicate that patients with cervical OPLL are more likely to undergo posterior cervical surgery, and they exhibit elevated UA levels, higher BMI, and increased age. The prevalence of cervical anterior longitudinal ligament ossification was also significantly higher among patients with cervical OPLL.

lncRNA MIR503HG Targets miR-191-5p/PLCD1 Axis and Negatively Modulates Apoptosis, Extracellular Matrix Disruption, and Inflammation in Abdominal Aortic Aneurysm.

As the most prevalent subtype of aortic aneurysm, abdominal aortic aneurysm (AAA) features the apoptosis, extracellular matrix (ECM) disruption, and inflammation response of vascular smooth muscle cells (VSMCs). Noncoding RNAs (ncRNAs) are crucial factors in AAA progression, while the investigations have not been fully explained. miR-191-5p upregulation is found in aortic aneurysm. However, its role in AAA has not been addressed. This research purposed to excavate the possible and associated molecular axis of miR-191-5p in AAA. In our study, miR-191-5p level was detected to be high in the tissues from AAA patients in comparison with the control group. After miR-191-5p expression was enhanced, cell viability was repressed, cell apoptosis was boosted, and ECM disruption and the inflammation response were fortified. Furthermore, the relationship among MIR503HG, miR-191-5p, and phospholipase C delta 1 (PLCD1) in VSMCs was disclosed via mechanism assays. Decreased MIR503HG lacked the inhibition on miR-191-5p targeting PLCD1, resulting in downregulation of PLCD1, which facilitated the progression of AAA. Thus, targeting MIR503HG/miR-191-5p/PLCD1 pathway will provide an additional method for the cure of AAA patients.

Spatial effects of the agricultural ecosystem services based on environmental kuznets curve in Mengyin county, China.

Worldwide most agroecosystems effort to increase production and yields and leads to damages of a series of non-provisioning ecosystem services (ESs). To fill in the knowledge gaps pertaining to the understanding of complex relationship between agricultural harvests and other ESs, therefore this study aims to estimate the existence of Environmental Kuznets Curve (EKC) for agricultural ESs by incorporating the spatial factors. Based on the test of the spatial autocorrelation of agricultural ESs, the estimation results of spatial model are compared with general regression to explain the spatial effect of agricultural ESs. The results show that (1) contrary to expectation, the curve of the nonlinear relationship between agricultural ESs and annual household income is an inverted U-shape, and not an upright U-shape; (2) compared to non-spatial model, the turning point of the inverted U-shaped curve for agricultural ESs under the direct effect would happen earlier and happen later under the indirect effect; (3) years of formal education, vegetation coverage of field margin and cultivated land area have significantly impact on local agricultural ESs, and local perennial crops has significantly impact on agricultural ESs of neighboring villages. Results of this study have a promising application prospect to promote sustainable development of agriculture.

Personalized intrahepatic cholangiocarcinoma prognosis prediction using radiomics: Application and development trend.

Radiomics was proposed by Lambin et al. in 2012 and since then there has been an explosion of related research. There has been significant interest in developing high-throughput methods that can automatically extract a large number of quantitative image features from medical images for better diagnostic or predictive performance. There have also been numerous radiomics investigations on intrahepatic cholangiocarcinoma in recent years, but no pertinent review materials are readily available. This work discusses the modeling analysis of radiomics for the prediction of lymph node metastasis, microvascular invasion, and early recurrence of intrahepatic cholangiocarcinoma, as well as the use of deep learning. This paper briefly reviews the current status of radiomics research to provide a reference for future studies.

NAT10 mediated mRNA acetylation modification patterns associated with colon cancer progression and microsatellite status.

N4-acetylcytidine (ac4C) is one type of RNA modification found in eukaryotes. RNA acetylation modifications are gradually expanding in oncology. However, the role of RNA acetylation modifications in colorectal cancer and its association with colorectal cancer microsatellite status remain unclear. Using public databases and in vitro experiments, we verified the expression and biological function of NAT10, as the key RNA acetylation modification enzyme, in colorectal cancer. The results showed that NAT10 was highly expressed in colorectal cancer, and significantly promoted colorectal cancer cell proliferation. NAT10 was also involved in several aspects of cell homoeostasis such as ion transport, calcium-dependent phospholipid binding, and RNA stability. NAT10 expression positively correlated with immune infiltration in colorectal cancer. We further constructed a risk regression model for mRNA acetylation in colorectal cancer using acetylation-related differential genes. We found that tumour immune infiltration, microsatellite instability (MSI) proportion, tumour immune mutation burden, and patient response to immunotherapy were positively correlated with risk scores. For the first time, our study showed that the level of mRNA acetylation modification level is elevated in colorectal cancer and positively correlates with immune infiltration and microsatellite status of patients. Based on our findings, NAT10 may be a new target for colorectal cancer treatment.