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Kidney stones pose a significant healthcare burden worldwide. Dyslipidemia is a risk factor for kidney stones, but the relationship between remnant cholesterol (RC) and kidney stone risk is unknown. We aimed to investigate the association between RC and the risk of incident kidney stones. We conducted a nested case-control study based on data from Shanghai Kidney Stone Cohort conducted in Shanghai from December 2018 to February 2023. Propensity score matching was used to select 2550 incident kidney stone cases and 7650 controls from a total of 60,158 adults. Baseline fasting plasma samples were collected to measure RC, which was calculated as total cholesterol minus high-density lipoproteins cholesterol and low-density lipoproteins cholesterol. Multivariable conditional logistic regression and a restricted cubic spline were used to estimate the association between tertiles of RC and kidney stone risk. Subgroup and sensitivity analyses were also performed. The baseline RC of incident kidney stone cases and controls were 0.58 (0.57) and 0.54 (0.55), respectively. Incident kidney stones had much higher baseline RC levels than controls (P < 0.001). Higher baseline RC levels were significantly associated with increased kidney stone risk after adjustment for potential confounders (highest vs. lowest tertile: OR 1.16, 95% CI 1.04–1.30; per 1 mmol/L increase: OR 1.16, 95% CI 1.07–1.26). Restricted cubic spline showed a significant positive and linear dose-response relationship between RC and the risk of developing kidney stones (P-overall = 0.005, P-nonlinear = 0.482). Sensitivity analyses yielded consistent results. Elevated RC levels are associated with a greater risk of incident kidney stones in Chinese adults. [ABSTRACT FROM AUTHOR]

Objective: The prevalence of nonalcoholic fatty liver disease (NAFLD) is increasing, presenting a treatment challenge due to limited options. Endoplasmic reticulum (ER) stress and associated lipid metabolism disorders are main causes of NAFLD, making it important to inhibit ER stress for effective treatment. Fagopyrum dibotrys has hypolipidemic, anti-inflammatory and hepatoprotective properties, showing promise in treating NAFLD. However, its effects on ER stress in NAFLD remain unclear. This study used a high-fat diet (HFD) to establish NAFLD mouse models and supplemented with Fagopyrum dibotrys extract (FDE) to evaluate its therapeutic effect and underlying mechanisms. Results: We showed that FDE supplementation reduced the severity of hepatic steatosis and lowered triglycerides (TG) and total cholesterol (TC) levels in NAFLD mice. At the molecular level, FDE supplementation reduced hepatic lipid deposition by downregulating lipogenic markers (SREBP-1c, SCD1) and upregulating fatty acid oxidase CPT1α expression. Additionally, FDE treatment inhibited the overexpression of ER stress markers (GRP78, CHOP, and P-EIF2α) in NAFLD mice livers, and blocked the activation of the PERK-EIF2α-CHOP pathway, demonstrating its role in maintaining ER homeostasis. Considering that activation of the PERK pathway could exacerbate lipid deposition, our findings suggest that FDE has a protective effect against hepatic steatosis in NAFLD mice by attenuating ER stress, and the potential mechanism is through inhibiting the PERK pathway. [ABSTRACT FROM AUTHOR]

Metallogenic geochronology plays a crucial role in the study of ore genesis and mineralization evolution. Unfortunately, accurately determining the metallogenic age of the non‐sulphide Zn–Pb deposits is difficult. Herein, we employed Rb–Sr dating of smithsonite and Sm–Nd dating of coexisting calcite to explore the mineralization ages of the Huoshaoyun Zn–Pb deposit. The Rb–Sr and Sm–Nd isotopic ratios yield isochron ages of 26.6 ± 1.7 and 27.5 ± 7.6 Ma, respectively. These obtained ages are identified as the metallogenic age of the Huoshaoyun deposit. Moreover, investigations into carbonate‐hosted Zn–Pb deposits in the East Tethys Metallogenic belt suggest they have formed in similar tectonic settings and yielded consistent Cenozoic ages. In sum, our research indicates that carbonate‐hosted Pb–Zn metallogenic ages in the East Tethys Metallogenic belt are principally concentrated in the late Palaeogene, and directly related to the collisional orogeny of the Tibetan Plateau during 40–26 Ma. [ABSTRACT FROM AUTHOR]

Background: Cholangiocarcinoma (CCA) is a highly malignant, rapidly progressing tumor of the bile duct. Owing to its chemoresistance, it always has an extremely poor prognosis. Therefore, detailed elucidation of the mechanisms of chemoresistance and identification of therapeutic targets are still needed. Methods: We analyzed the expression of MBD2 (Methyl-CpG-binding domain 2) in CCA and normal bile duct tissues using the public database and immunohistochemistry (IHC). The roles of MBD2 in CCA cell proliferation, migration, and chemoresistance ability were validated through CCK-8, plate cloning assay, wound healing assays and xenograft mouse model. In addition, we constructed a primary CCA mouse model to further confirm the effect of MBD2. RNA-seq and co-IP-MS were used to identify the mechanisms by how MBD2 leads to chemoresistance. Results: MBD2 was upregulated in CCA. It promoted the proliferation, migration and chemoresistance of CCA cells. Mechanistically, MBD2 directly interacted with WDR5, bound to the promoter of ABCB1, promoted the trimethylation of H3K4 in this region through KMT2A, and activated the expression of ABCB1. Knocking down WDR5 or KMT2A blocked the transcriptional activation of ABCB1 by MBD2. The molecular inhibitor MM-102 targeted the interaction of WDR5 with KMT2A. MM-102 inhibited the expression of ABCB1 in CCA cells and decreased the chemoresistance of CCA to cisplatin. Conclusion: MBD2 promotes the progression and chemoresistance of CCA through interactions with WDR5. MM-102 can effectively block this process and increase the sensitivity of CCA to cisplatin. [ABSTRACT FROM AUTHOR]

Background: Chronic migraine is closely related to the dysregulation of neurochemical substances in the brain, with metabolic imbalance being one of the proposed causes of chronic migraine. This study aims to evaluate the metabolic changes between energy metabolism and excitatory and inhibitory neurotransmitters in key brain regions of mice with chronic migraine-like state and to uncover the dysfunctional pathways of migraine. Methods: A chronic migraine-like state mouse model was established by repeated administration of nitroglycerin (NTG). We used von Frey filaments to assess the mechanical thresholds of the hind paw and periorbital in wild-type and familial hemiplegic migraine type 2 mice. After the experiments, tissue was collected from five brain regions: the somatosensory cortex (SSP), hippocampus, thalamus (TH), hypothalamus, and the spinal trigeminal nucleus caudalis (TNC). Proton magnetic resonance spectroscopy (1H-MRS) was employed to study the changes in brain metabolites associated with migraine, aiming to explore the mechanisms underlying metabolic imbalance in chronic migraine-like state. Results: In NTG-induced chronic migraine-like state model, we observed a significant reduction in energy metabolism during central sensitization, an increase in excitatory neurotransmitters such as glutamate, and a tendency for inhibitory neurotransmitters like GABA to decrease. The TNC and thalamus were the most affected regions. Furthermore, the consistency of N-acetylaspartate levels highlighted the importance of the TNC-TH-SSP pathway in the ascending nociceptive transmission of migraine. Conclusion: Abnormal energy metabolism and neurotransmitter imbalance in the brain region of NTG-induced chronic migraine-like state model are crucial mechanisms contributing to the chronicity of migraine. [ABSTRACT FROM AUTHOR]

Objective This study assesses the status and determinants of treatment delays among patients with rifampicin-resistant tuberculosis (RR-TB) in Guizhou Province, 2016-2022, aiming to inform the development of RR-TB control strategies in the region. Methods Data on RR-TB patients from 2016 to 2022 were extracted from the "Tuberculosis Management Information System," a subsystem of the "China Disease Prevention and Control Information System." The trend in treatment delay rates over time was analyzed using Trend chi-square test, while logistic regression models were used to examine the factors influencing these delays. Results From 2016 to 2022, Guizhou Province reported 513 cases of treatment delays among patients with rifampicin-resistant tuberculosis (RR-TB), resulting in a treatment delay rate of 23.29%. The rate of treatment delays decreased from 2016 to 2019 (Trend chi-square test = 9.099, P = 0.003), reaching its lowest in 2018 at 10.53%. However, from 2020 to 2022, the rate of treatment delays exhibited an upward trend (Trend chi-square test = 5.937, P = 0.015), peaking in 2021 at 31.62%. Multivariable analysis indicated that compared to migrant populations, patients undergoing initial treatment, and those tested with molecular biological drug sensitivity tests, non-migrant patients (OR = 1.496, 95%CI = 1.198 to 1.867), new patients (OR = 1.774, 95%CI = 1.344 to 2.342), patients with relapse (OR = 1.494, 95%CI = 1.110 to 2.011), and those tested using traditional drug sensitivity methods (OR = 2.985, 95%CI = 2.323 to 3.834) were at higher risk for treatment delays. Conclusion From 2016 to 2022, the overall trend of treatment delays in rifampicin-resistant tuberculosis (RR-TB) patients in Guizhou Province showed a decline. However, there was an increasing trend during the COVID-19 pandemic. This suggests a need to enhance the prevention and control of drug-resistant tuberculosis in key areas such as Bijie City. There is also a need to intensify health education for patients with drug resistance, implement patient-centered care systems for those patients, expand the application of molecular biological drug sensitivity testing techniques, and strengthen the referral and admission mechanisms for RR-TB patients. [ABSTRACT FROM AUTHOR]

Background: Cholangiocarcinoma (CCA) is a highly malignant tumor characterized by a lack of effective targeted therapeutic strategies. The protein UHRF1 plays a pivotal role in the preservation of DNA methylation and works synergistically with DNMT1. Posttranscriptional modifications (PTMs), such as ubiquitination, play indispensable roles in facilitating this process. Nevertheless, the specific PTMs that regulate UHRF1 in CCA remain unidentified. Methods: We confirmed the interaction between STUB1 and UHRF1 through mass spectrometry analysis. Furthermore, we investigated the underlying mechanisms of the STUB1-UHRF1/DNMT1 axis via co-IP experiments, denaturing IP ubiquitination experiments, nuclear‒cytoplasmic separation and immunofluorescence experiments. The downstream PLA2G2A gene, regulated by the STUB1-UHRF1/DNMT1 axis, was identified via RNA-seq. The negative regulatory mechanism of PLA2G2A was explored via bisulfite sequencing PCR (BSP) experiments to assess changes in promoter methylation. The roles of PLA2G2A and STUB1 in the proliferation, invasion, and migration of CCA cells were assessed using the CCK-8 assay, colony formation assay, Transwell assay, wound healing assay and xenograft mouse model. We evaluated the effects of STUB1/UHRF1 on cholangiocarcinoma by utilizing a primary CCA mouse model. Results: This study revealed that STUB1 interacts with UHRF1, resulting in an increase in the K63-linked ubiquitination of UHRF1. Consequently, this facilitates the nuclear translocation of UHRF1 and enhances its binding affinity with DNMT1. The STUB1-UHRF1/DNMT1 axis led to increased DNA methylation of the PLA2G2A promoter, subsequently repressing its expression. Increased STUB1 expression in CCA was inversely correlated with tumor progression and overall survival. Conversely, PLA2G2A functions as a tumor suppressor in CCA by inhibiting cell proliferation, invasion and migration. Conclusions: These findings suggest that the STUB1-mediated ubiquitination of UHRF1 plays a pivotal role in tumor progression by epigenetically silencing PLA2G2A, underscoring the potential of STUB1 as both a prognostic biomarker and therapeutic target for CCA. [ABSTRACT FROM AUTHOR]

Since the 12 major signs of aging were revealed in 2023, people's interpretation of aging will go further, which is of great significance for understanding the occurrence, development, and intervention in the aging process. As one of the 12 major signs of aging, cellular senescence refers to the process in which the proliferation and differentiation ability of cells decrease under stress stimulation or over time, often manifested as changes in cell morphology, cell cycle arrest, and decreased metabolic function. Interferon (IFN), as a secreted ligand for specific cell surface receptors, can trigger the transcription of interferon‐stimulated genes (ISGs) and play an important role in cellular senescence. In addition, IFN serves as an important component of SASP, and the activation of the IFN signaling pathway has been shown to contribute to cell apoptosis and senescence. It is expected to delay cellular senescence by linking IFN with cellular senescence and studying the effects of IFN on cellular senescence and its mechanism. This article provides a review of the research on the relationship between IFN and cellular senescence by consulting relevant literature. [ABSTRACT FROM AUTHOR]

Aerodynamic forces acting on a racing car will impact its handling, stability, and steering characteristics. Oversteering typically occurs in racing cars with a significant front-end downforce. In the process of racing, the car's attitude will change, causing a shift in the distribution of front and rear downforce. This, in turn, will impact the car's handling performance. Therefore, in this study, a set of aerodynamic devices with attitude-adaptive function linked to the suspension is designed to reduce aerodynamic attitude sensitivity. The range of the car's attitude changes, the adjustment ability of the front and rear flaps, and the reasonable matching relationship between different operating conditions and the attack angle of the front and rear flaps are confirmed. In this work, the matching relationship is achieved through the use of multiple groups of linkage mechanisms. The aerodynamic characteristics of the entire car are analyzed and simulated in the lap speed simulation. Results showed that the installation of the device reduces the center of pressure (CoP) movement during braking by 52%, the aerodynamic resistance of the entire racing car during acceleration by 19.5%, and the single lap time by 1.5%, while also inhibiting the generation of aerodynamic torque during roll. [ABSTRACT FROM AUTHOR]

Soliton pulsations are ubiquitous feature of non‐stationary soliton dynamics in mode‐locked lasers and many other physical systems. To overcome difficulties related to a huge amount of necessary computations and low efficiency of traditional numerical methods in modeling the evolution of non‐stationary solitons, a two‐parallel bidirectional long short‐term memory recurrent neural network (TP‐Bi_LSTM RNN) is proposed, with the main objective to predict dynamics of vector‐soliton pulsations (VSPs) in various complex states, whose real‐time dynamics is verified by experiments. For two examples, viz., single‐ and bi‐periodic VSPs, with period‐21 and a combination of period‐3 and period‐43, the prediction results are better than provided by direct simulations – namely, deviations produced by the TP‐Bi_LSTM RNN results are 36% and 18% less than those provided by the simulations, respectively. This means that predicted results provided by the neural network are better than numerical simulations. Moreover, the prediction results for unstable VSP state with period‐9 indicate that the optimization of training sets and the number of training iterations are particularly important for the predictability. Besides, the scheme of coded information storage based on the TP‐Bi_LSTM RNN, instead of actual pulse signals, is realized too. The findings offer new applications of deep learning to ultrafast optics and information storage. [ABSTRACT FROM AUTHOR]

The Ziyoutun Cu‐Au district is located in the Jizhong–Yanbian Metallogenic Belt and possesses excellent prospects. However, the thick regolith and complex tectonic settings present challenges in terms of detecting and decomposition of weak geochemical anomalies. To address this challenge, we initially conducted a comprehensive analysis of 1:10,000‐scale soil geochemical data. This analysis included multivariate statistical techniques, such as correlation analysis, R‐mode cluster analysis, Q–Q plots and factor analysis. Subsequently, we decomposed the geochemical anomalies, identifying weak anomalies using spectrum‐area modeling and local singularity analysis. The results indicate that the assemblage of Au‐Cu‐Bi‐As‐Sb represents the mineralization at Ziyoutun. In comparison to conventional methods, spectrum‐area modeling and local singularity analysis outperform in terms of identification of anomalies. Ultimately, we considered four specific target areas (AP01, AP02, AP03 and AP04) for future exploration, based on geochemical anomalies and favorable geological factors. Within AP01 and AP02, the geochemical anomalies suggest potential mineralization at depth, whereas in AP03 and AP04 the surface anomalies require additional geological investigation. Consequently, we recommend conducting drilling, following more extensive surface fieldwork, at the first two targets and verifying surface anomalies in the last two targets. We anticipate these findings will significantly enhance future exploration in Ziyoutun. [ABSTRACT FROM AUTHOR]

Uniform acidizing has been an urgent challenge in strongly heterogeneous and high-temperature carbonate reservoirs. Nanoparticles have been shown to enhance the viscosity of viscoelastic-surfactant (VES) fracturing fluids, thereby improving the proppant carrying capacity of the fluid. However, there is almost no understanding of the nanoparticles on wormhole propagation and diversion in VES acid at low pH values and high salinity. Here, the rheological and adsorption model of nanoparticles in VES acid are established based on experimental results, and the multi-field and multi-scale coupling model of nanoparticles-VES acid is established by introducing the temperature field and two-scale continuum model. Based on the model, the propagation pattern and diverting performance of the wormholes were analyzed. The effects of permeability contrast, temperature, and adsorption on the propagation pattern and diverting performance are systematically investigated. The results show that the synergistic effect of nanoparticles and adsorption divided the invaded zone of spent acid into high-viscosity and low-viscosity zones, and the propagation capacity of the wormholes in the low-permeability reservoir was increased by 17%. The propagation and diverting process of wormholes can be divided into three stages. In stage II, when the additional resistance increased by spent acid is enough to resist the permeability contrast and the wormholes, more acid starts to flow into the low-permeability reservoir. The higher flow rate in the high-permeability reservoir makes the propagation path more complicated, and more branching wormholes are formed. At a reservoir temperature of 393 K, the nanoparticle-VES acid has the poor diverting ability for reservoirs with permeability contrast greater than ten. When the maximum adsorption capacity is 0.008 mol/kg, the diverting performance of nanoparticle-VES acid and VES acid were close. Reducing the adsorption is a very effective way to enhance the diverting performance. When the adsorption capacity is larger, the influence distance of the high viscosity zone formed by the dominant wormholes is limited, and the number of main wormholes in the reservoir becomes significantly large. This study clarifies the propagation law and diverting characteristics of wormholes using nanoparticle-VES acid, fills the technical gap of nanoparticles in acidizing, and provides guidance and a basis for the stimulation of uniform acidizing in high-temperature carbonate. [ABSTRACT FROM AUTHOR]

Introduction: Ropeginterferon alfa-2b is a novel mono-pegylated proline-interferon. This clinical study aimed to evaluate its antiviral efficacy of ropeginterferon alfa-2b against SARS-CoV-2 infection. Methods: This is a multicenter, randomized, open-label study. Adult patients with confirmed SARS-CoV-2 infection with initial cycle threshold (Ct) value < 30 and symptom onset within 4 days were enrolled. Eligible patients were randomized in a 2:1 ratio to receive a single 250-µg dose of ropeginterferon alfa-2b subcutaneously plus standard of care (SOC) or to receive SOC alone. The primary endpoint was the proportion of patients with a negative RT-PCR result for SARS-CoV-2 or discharged from the hospital before Day 8. Change in clinical status based on the World Health Organization (WHO) clinical progression scale and pulmonary infiltrations through chest radiograph were also evaluated. Results: A total of 132 patients were enrolled and treated with study medication. Higher percentages of patients who achieved Ct ≥ 30 or were discharged from the hospital were observed on Day 8 and every other time point of assessment, i.e., Days 5, 11, 15, and 22, in the ropeginterferon alfa-2b group compared to the SOC alone group. However, the difference was statistically significant on Day 11 but not on Day 8. The primary endpoint was not met. The ropeginterferon alfa-2b group showed a higher improvement rate in lung infiltration on Day 5 (27.6% vs. 0.0%, p = 0.0087) and a higher improvement rate in WHO clinical progression scores on Day 8 (69.4% vs. 35.3%, p = 0.03) than those in the SOC group. No ropeginterferon alfa-2b-related serious adverse event was observed. Conclusion: Our data show that ropeginterferon alfa-2b with SOC shortened the duration of SARS-CoV-2 shedding compared with SOC alone. In addition, ropeginterferon alfa-2b as an additional therapy could be beneficial by improving lung infiltration. [ABSTRACT FROM AUTHOR]

This study focuses on exploring the indication and importance of selenium (Se) and tellurium (Te) in distinguishing different genetic types of ore deposits. Traditional views suggest that dispersed elements are unable to form independent deposits, but are hosted within deposits of other elements as associated elements. Based on this, the study collected trace elemental data of pyrite, sphalerite, and chalcopyrite in various types of Se-Te bearing deposits. The optimal end-elements for distinguishing different genetic type deposits were recognized by principal component analysis (PCA) and the silhouette coefficient method, and discriminant diagrams were drawn. However, support vector machine (SVM) calculation of the decision boundary shows low accuracy, revealing the limitations in binary discriminant visualization for ore deposit type discrimination. Consequently, two machine learning algorithms, random forest (RF) and SVM, were used to construct ore genetic type classification models on the basis of trace elemental data for the three types of metal sulfides. The results indicate that the RF classification model for pyrite exhibits the best performance, achieving an accuracy of 94.5% and avoiding overfitting errors. In detail, according to the feature importance analysis, Se exhibits higher Shapley Additive Explanations (SHAP) values in volcanogenic massive sulfide (VMS) and epithermal deposits, especially the latter, where Se is the most crucial distinguishing element. By comparison, Te shows a significant contribution to distinguishing Carlin-type deposits. Conversely, in porphyry- and skarn-type deposits, the contributions of Se and Te were relatively lower. In conclusion, the application of machine learning methods provides a novel approach for ore genetic type classification and discrimination research, enabling more accurate identification of ore genetic types and contributing to the exploration and development of mineral resources. [ABSTRACT FROM AUTHOR]

Background: Intrahepatic cholangiocarcinoma (ICCA) is a heterogeneous group of malignant tumors characterized by high recurrence rate and poor prognosis. Heterochromatin Protein 1α (HP1α) is one of the most important nonhistone chromosomal proteins involved in transcriptional silencing via heterochromatin formation and structural maintenance. The effect of HP1α on the progression of ICCA remained unclear. Methods: The effect on the proliferation of ICCA was detected by experiments in two cell lines and two ICCA mouse models. The interaction between HP1α and Histone Deacetylase 1 (HDAC1) was determined using Electrospray Ionization Mass Spectrometry (ESI-MS) and the binding mechanism was studied using immunoprecipitation assays (co-IP). The target gene was screened out by RNA sequencing (RNA-seq). The occupation of DNA binding proteins and histone modifications were predicted by bioinformatic methods and evaluated by Cleavage Under Targets and Tagmentation (CUT & Tag) and Chromatin immunoprecipitation (ChIP). Results: HP1α was upregulated in intrahepatic cholangiocarcinoma (ICCA) tissues and regulated the proliferation of ICCA cells by inhibiting the interferon pathway in a Signal Transducer and Activator of Transcription 1 (STAT1)-dependent manner. Mechanistically, STAT1 is transcriptionally regulated by the HP1α-HDAC1 complex directly and epigenetically via promoter binding and changes in different histone modifications, as validated by high-throughput sequencing. Broad-spectrum HDAC inhibitor (HDACi) activates the interferon pathway and inhibits the proliferation of ICCA cells by downregulating HP1α and targeting the heterodimer. Broad-spectrum HDACi plus interferon preparation regimen was found to improve the antiproliferative effects and delay ICCA development in vivo and in vitro, which took advantage of basal activation as well as direct activation of the interferon pathway. HP1α participates in mediating the cellular resistance to both agents. Conclusions: HP1α-HDAC1 complex influences interferon pathway activation by directly and epigenetically regulating STAT1 in transcriptional level. The broad-spectrum HDACi plus interferon preparation regimen inhibits ICCA development, providing feasible strategies for ICCA treatment. Targeting the HP1α-HDAC1-STAT1 axis is a possible strategy for treating ICCA, especially HP1α-positive cases. [ABSTRACT FROM AUTHOR]

Objective To analyze adverse outcomes and influencing factors of elderly pulmonary tuberculosis patients in Guizhou Province and to provide a scientific basis for effective treatment of elderly pulmonary tuberculosis patients. Methods The medical records information of elderly pulmonary tuberculosis patients aged 65 and above in Guizhou Province from January 1, 2011, to December 31, 2022, was extracted from the Tuberculosis Monitoring Report Management Information System. The time trend of adverse outcomes was analyzed using the chi-square trend test, inter-group comparison was conducted using the chi-square test, and binary logistic regression was employed to analyze influencing factors. Results From 2011 to 2022, 10, 820 elderly patients with pulmonary tuberculosis had adverse outcomes in Guizhou Province, with an adverse outcome rate of 12.91 %. The rate of adverse outcomes increased from 2011 to 2015 (χtrend² = 62.080, P < 0.001), and decreased from 2016 to 2022 (χtrend² = 38.163, P < 0.001). Regarding regional distribution, Bijie City had the highest rate of adverse outcomes, and TongrenCity had the lowest rate (% = 808. 188, P < 0.001). The results of multivariate analysis showed that compared with the patients who were female, ethnic minorities, 65-69 years old, without comorbidities, newly treated, pathogenic negative, and without other tuberculosis, the patients were more likely to develop tuberculosis. Male (OR = 1.323, 95% CI = 1.267-1.380), Han ethnic group (OR = 1.168, 95% CI = 1.117-1.222), 70-74 years old (OR = 1.244,95% CI = 1.181-1.310),75-79 years old (Oft = 1.612, 95% CI = 1) 525-1.704), ≥80 years old (OR = 2.322, 95% CI = 2.178-2.476), comorbidities (OR = 1.261, 95% CI = 1.179-1.348), retreatment (OR = 1.526, 95% CI = 1.423-1.636), positive pathogen (OR = 1.244, 95% CI = 1.181-1.310) and other tuberculosis (OR = 1.245, 95% CI = 1.161-1.336) were risk factors for poor outcomes. Conclusion Since the implementation of the "13th Five-Year Plan" for tuberculosis prevention and treatment, the adverse outcome rate of elderly tuberculosis patients in Guizhou Province has shown a gradual decreasing trend, but the distribution of the adverse outcome rate is uneven, which suggests that we need to continue to maintain a high degree of vigilance and strengthen preventive and control measures. [ABSTRACT FROM AUTHOR]

Based on the existing permanent load equilibrium method, influence matrix method and adaptive control method, a distributed algorithm and control method for the cable forces of hybrid laminated girder cable-stayed bridges is proposed. The method uses the permanent load equilibrium approach to initially determine the permanent load cable forces, then adjusts it based on the influence matrix of the main girder displacement, and finally combines the calculation of finite element software to determine the cable forces that satisfy the internal force requirements of each member of the hybrid laminated girder cable-stayed bridge under the joint action of permanent load and live load. Through adjusting the cable force of an actual bridge, it can be found that this method is highly efficient in calculation, and the efficiency and accuracy of control of the cable forces are high, ensuring that the cable forces and alignment of the bridge structure after completion are in line with the design expectations. [ABSTRACT FROM AUTHOR]

For hydrogen fuel cell vehicles, energy management strategies (EMS) are vital for balancing fuel cell and battery power, limiting fuel cell power, maintaining state of charge (SOC) fluctuation range and mitigating degradation. Reinforcement learning-based EMS, especially using deep Q-network (DQN) and deep deterministic policy gradient (DDPG), have demonstrated potential for enhancing the fuel economy of hybrid electric vehicles (HEV) and fuel cell electric vehicles (FCEV). This research proposes mutation protection DQN (MPD)-based EMS to improve hydrogen fuel economy and reduce fuel cell degradation under driving cycles with plenty of mutations. By quantifying mutation, exploring its relationship with driving conditions and integrating a mutation protection module with DQN, MPD-based EMS achieves approximately 11% and 6% better fuel economy compared to the other two learning-based EMS. Additionally, it also reduces fuel cell degradation by approximately 21% and 13%. • Quantifying the mutation of driving conditions through variance. • Utilizing information entropy to process mutations. • Introducing a dynamic mutation threshold value. • Designing mutation protection module and integrating it into the DQN. [ABSTRACT FROM AUTHOR]

To investigate the protective effect of dihydromyricetin (DHM) against exercise-induced muscle damage (EIMD) in mice and its potential mechanism. Adult male C57BL/6J mice were randomly divided into control group (CG), exercise group (EG), and exercise + 100 mg/kg weight •d DHM (DHM) group. The intervention lasted for four weeks, during which the animals in the EG and DHM groups were subjected to exercise training for 1 h per day. The day after the training, a 90-min treadmill exercise (slope: 0 and speed: 18 m/min) was conducted in both EG and DHM groups. Samples of blood and gastrocnemius muscles were harvested from the three groups 24 h after the exercise, followed by the measurement of serum creatine kinase (CK) and lactate dehydrogenase (LDH) activities, total superoxide dismutase (T-SOD) activity, malondialdehyde (MDA), and skeletal muscle mitochondrial enzyme complex I and II activities. Histological changes in the skeletal muscle were observed by transmission electron microscopy, and the protein expressions of mitochondrial function-related pathways were detected by Western blotting. Skeletal muscle morphological changes and mitochondrial damage were alleviated in the DHM group compared to those in the EG. The activities of EIMD markers CK and LDH and the level of lipid peroxidation were notably repressed and the serum T-SOD activity was enhanced after DHM intervention. Western blotting demonstrated that the expressions of sirtuin type 3 (SIRT3), estrogen-related receptor alpha, and peroxisome proliferator-activated receptor-gamma coactivator-1 alpha in the skeletal muscle of mice increased after the DHM intervention. DHM can relieve EIMD in mice, possibly by promoting the recovery of the mitochondrial structure and function in the skeletal muscle of mice after high-intensity exercise via the activation of the SIRT3 signaling pathway. [ABSTRACT FROM AUTHOR]

To optimize the hydrogen consumption, lifespan of the fuel cell (FC), and durability of the lithium-ion battery in fuel cell electric vehicles (FCEVs), energy management strategies (EMSs) have been developed and implemented in the vehicle control units (VCUs) by engineers. Recently, with the rapid development of artificial intelligence, reinforcement learning (RL)-based EMS have shown great promise among various strategies. However, RL-based EMS tends to exhibit relatively poorer performance when faced with novel environments owing to the requirement for learning. This study proposes an enhanced EMS, Scalable Learning in Novel Environment (SLNE)-based EMS. This EMS performs well in unknown and dynamic environments by integrating a memory library (ML) composed of the Dirichlet process (DRP) clustering algorithm combined with the Chinese restaurant process (CRP) using the expectation-maximization (EM) algorithm for updates and the deep Q-network (DQN). Simulation and comparison are conducted under two novel driving cycles to evaluate the performance of the dynamic programming (DP)-based EMS, rule-based EMS, DQN-based EMS, and SLNE-based EMS. By comparing reward, power, and degradation, the results indicate that the proposed SLNE-based EMS demonstrates excellent convergence and adaptability when facing a novel and dynamic environment. Additionally, the proposed SLNE-based EMS achieves approximately 5% improvement in fuel economy, approximately 4.5% reduction in fuel cell degradation rate, and improved durability of the lithium-ion battery, compared with DQN-based EMS. [Display omitted] • The scalable learning in novel environment-based EMS is proposed for an FCEV. • The SLNE-based EMS performs well from the start when facing novel driving cycles. • The SLNE-based EMS demonstrates a higher reward ceiling and lower fluctuations. • Considering the fuel cell degradation, proposed EMS can better enhance the lifespan. • The fuel consumption of the SLNE-based EMS is 5% lower than that of the DQN-based EMS. [ABSTRACT FROM AUTHOR]

Sertoli cells are an important type of somatic cell in the testis that are in direct contact with spermatogonia in vivo and play an important role in the process of spermatogenesis. Chlorogenic acid (CGA) plays a pivotal role in the regulation of the mammalian cell heat stress response. For example, CGA treatment protects porcine oocytes from heat stress-induced apoptosis and prevents reduced embryo quality. However, the role of CGA treatment in protecting porcine testicular Sertoli cells against heat-induced damage has rarely been studied. This study aimed to identify the protective effects of CGA on oxidative stress and apoptosis in Sertoli cells under heat stress. The present results demonstrated that the addition of CGA significantly inhibited the accumulation of reactive oxygen species (ROS) and apoptosis in Sertoli cells induced by heat stress and decreased the expression of CASP3 protein and the BAX/BCL-2 protein ratio. CGA pretreatment also prevented the heat stress-induced reductions in the mitochondrial membrane potential, PCNA protein expression, and SOD and CAT activities. Moreover, CGA treatment reversed S phase cell cycle arrest and increased the HSP70 protein expression levels. Overall, these results suggest that oxidative damage participates in the inhibition of the proliferation of Sertoli cells and the increase in their apoptosis induced by heat stress, and the protective effects of CGA treatment on Sertoli cells under heat stress provide a theoretical basis for preventing heat stress injury in animals. • CGA ameliorated heat stress-induced intracellular ROS accumulation in porcine testicular Sertoli cells. • CGA inhibited heat stress-induced apoptosis in porcine testicular Sertoli cells. • CGA ameliorated heat stress-induced cell cycle arrest and mitochondrial dysfunction in porcine testicular Sertoli cells. [ABSTRACT FROM AUTHOR]

Photocatalytic water splitting for hydrogen production is a promising solution to converse solar energy to green fuel. A high-performance photocatalyst system always requires fast surface reaction rate and efficient charge separation. Herein, a novel strategy that photo-assisted silanizing-hydrolyzing method is used to trigger in situ surface hydroxylation selectively on Si atoms of micro-sized 6H-SiC particles. Due to this functionalization, the results show that the silanizing-hydrolyzing process occurs at the Si sites while the C is passivated, leading the Si atoms with electron deficiency property by XPS characterization. It also drives the SiC surface from native hydrophobicity to hydrophilicity, which is benefit to proton absorption and desorption of generated H 2 by FT-IR and contact angle (CA) result. Furthermore, the photo-electron-chemical characterization demonstrate the charge migration and separation of SiC are promoted. The DFT calculation further indicates these surface properties changes are mainly attribute to the surface electron polarization through the hydroxylation, inducing the Si-O spatial charge separation. More importantly, the positive Si atoms exhibit an appropriate proton absorption energy, resulting in easily H 2 desorption from SiC surface. The hydrogen evolution is significantly enhanced by 33 times compared to pristine SiC without any cocatalysts introduced. Our method provides an efficient route to design an environmental-friendly photocatalytic material SiC and construct highly efficient solar energy conversion systems, which can simultaneously facilitate carrier generation, transportation and surface reduction reaction rate. • A photo-assisted silanizing-hydrolyzing method is used to hydroxylate SiC surface. • The hydroxylation is selectively on Si atoms while C atoms are passivation. • The SiC surface changes from native hydrophobicity to easily hydrophilicity. • Surface electron polarization and proton activation on SiC surface are achieved. • The appropriate H+ absorption energy leads an easy desorption of generated H 2. [ABSTRACT FROM AUTHOR]

Aqueous two-phase extraction (ATPE) has been extensively utilized for the extraction and separation of tiny-molecule substances as a new system (system with short-chain ethanol and inorganic salts). In this study, an innovative method of extracting anthocyanins from mulberry was developed, employing microwave-assisted extraction with ethanol/ammonium sulfate as a biphasic extractant. Response surface methodology (RSM) was utilized to optimize anthocyanin extraction conditions: 39% ethanol (w/w), 13% ammonium sulfate (w/w), and liquid-to-solid ratio of 45:1, microwave duration 3 min, microwave temperature 32 °C, and microwave power 480 Watt (W). High-performance liquid chromatography (HPLC) analysis demonstrated no significant differences in the structure of mulberry anthocyanins before and after MAATPE treatment, furthermore. The extraction behavior of MAATPE was due to hydrogen bonding, according to Fourier transform infrared spectroscopy (FT-IR). Scanning electron microscopy analysis found that MAATPE damaged the cell structure via a microwave enhancement effect, which was more favorable to anthocyanin dissolution than standard extraction methods. The DPPH free radical scavenging rate of mulberry extracts at 0.5 mg/mL was higher than that of vitamin C (96.4 ± 0.76%), and the ABTS free radical scavenging rate (82.52 ± 2.13%) was close to that of vitamin C, indicating that MAATPE-derived mulberry extracts have good antioxidant activity. [ABSTRACT FROM AUTHOR]

[Display omitted] Increased mitochondrial damage plays a critical role in many neurodegeneration-related diseases such as Parkinson's disease (PD) and Down syndrome (DS). Thus, enhancement of mitochondrial degradation by small molecule compounds may provide promising new strategies to tackle these diseases. Here, we explored the strategy to induce clearance of mitochondria by targeting them to the autophagy machinery by autophagy-tethering compounds (ATTECs). We provided the proof-of-concept evidence demonstrating that the bifunctional compound (mT1) binding to both the outer mitochondrial membrane protein TSPO and the autophagosome protein LC3B simultaneously may enhance the engulfment of damaged mitochondria by autophagosomes and subsequent autophagic degradation of them. In addition, preliminary experiments suggest that mT1 attenuated disease-relevant phenotypes in both a PD cellular model and a DS organoid model. Taken together, we demonstrate the possibility of degrading mitochondria by bifunctional ATTECs, which confirms the capability of degrading organelles by ATTECs and provides potential new strategies in the intervention of mitochondria-related disorders. [ABSTRACT FROM AUTHOR]

Background: Cholangiocarcinoma (CCA) refers to a collection of malignant tumors that develop from the biliary epithelium. Extensive clinical evidence and epidemiological observations indicate a concerning increase in both the incidence and mortality rates of CCA. Surgical resection is currently the sole available cure for CCA. However, it is unfortunate that only a fraction of patients has access to surgery at the time of diagnosis. Moreover, there is a high incidence of cancer recurrence after resection, and systemic treatments have limited efficacy. Therefore, the identification of novel biomarkers for CCA-targeted molecular therapy remains a crucial task in oncology research. Results: Our study demonstrated that low expression of RSPO3 was associated with poorer survival rates in patients with CCA. We found that the RSPO3 promoter DNA was hypermethylated in CCA, which was correlated with the low expression of RSPO3. The expression of RSPO3 was influenced by the balance between the DNA methyltransferase DNMT3a and the DNA demethylase TET1 in CCA. In vitro and in vivo experiments showed that targeting RSPO3 promoter DNA methylation using dCas9DNMT3a promoted tumorigenicity of CCA, while targeted RSPO3 promoter DNA demethylation using dCas9TET1CD inhibited CCA tumorigenicity. Additionally, in our primary CCA model, knockdown of Rspo3 promoted CCA progression, whereas overexpression of Rspo3 inhibited CCA progression. Conclusions: Our findings suggest that increased methylation and decreased expression of RSPO3 may indicate a poor prognosis in CCA. Restoring RSPO3 expression by targeting promoter DNA demethylation could offer insights for precise treatment of CCA. [ABSTRACT FROM AUTHOR]

Objectives: To investigate whether machine learning, which is widely used in disease prediction and diagnosis based on demographic data and serological markers, can predict herpes occurrence in patients with systemic lupus erythematosus (SLE). Methods: A total of 286 SLE patients were included in this study, including 200 SLE patients without herpes and 86 SLE patients with herpes. SLE patients were randomly divided into a training group and a test group, and 18 demographic characteristics and serological indicators were compared between the two groups. Results: We selected basophil, monocyte, white blood cell, age, immunoglobulin E, SLE Disease Activity Index, complement 4, neutrophil, and immunoglobulin G as the basic features of modeling. A random forest model had the best performance, but logistic and decision tree analyses had better clinical decision‐making benefits. Random forest had a good consistency between feature importance judgment and feature selection. The 10‐fold cross‐validation showed the optimization of five model parameters. Conclusion: The random forest model may be an excellently performing model, which may help clinicians to identify SLE patients whose disease is complicated by herpes early. [ABSTRACT FROM AUTHOR]

Flat band has attracted more and more interest in recent years, motivated by its discovery in twisted bilayer graphene (TBG). In this work, we report our study of the impurity effect on this flat band system, which is an important issue for real materials. Employing the Lanczos recursive method, we solve the local density of states (LDOS) around a potential impurity. We find for large impurity size, a series of bound states are formed inside the impurity, and the flat band peak in LDOS is suppressed near the impurity boundary and shifted by the impurity potential deep inside the impurity. As the impurity size becomes smaller, the effect on the flat band becomes weaker, as anticipated from the large scale of the underlying Wannier function. This property distinguishes with the usual flat band systems with small localized Wannier orbitals, and indicates the flat band in TBG is more stable against small-size impurities. [ABSTRACT FROM AUTHOR]

Optical chaos has attracted widespread attention owing to its complex dynamic behaviors. However, the time delay signature (TDS) caused by the external cavity mode reduces the complexity of optical chaos. We propose and numerically demonstrate the critical dispersion of chirped fiber Bragg grating (CFBG) for eliminating the TDS of laser chaos in this work. The critical dispersion, as a function of relaxation frequency and bandwidth of the optical spectrum, is found through extensive dynamics simulations. It is shown that the TDS can be eliminated when the dispersion of CFBG is above this critical dispersion. In addition, the influence of dispersive feedback light and output light from a laser is investigated. These results provide important quantitative guidance for designing chaotic semiconductor lasers without TDS. [ABSTRACT FROM AUTHOR]

Objective: Clinical evaluation of systemic lupus erythematosus (SLE) disease activity is limited and inconsistent, and high disease activity significantly, seriously impacts on SLE patients. This study aims to generate a machine learning model to identify SLE patients with high disease activity. Method: A total of 1014 SLE patients with low disease activity and 453 SLE patients with high disease activity were included. A total of 94 clinical, laboratory data and 17 meteorological indicators were collected. After data preprocessing, we use mutual information and multisurf to evaluate and select the importance of features. The selected features are used for machine learning modeling. Performance of the model is evaluated and verified by a series of binary classification indicators. Results: We screened out hematuria, proteinuria, pyuria, low complement, precipitation, sunlight and other features for model construction by integrated feature selection. After hyperparameter optimization, the LGB has the best performance (ROC: AUC = 0.930; PRC: AUC = 0.911, APS = 0.913; balance accuracy: 0.856), and the worst is the naive bayes (ROC: AUC = 0.849; PRC: AUC = 0.719, APS = 0.714; balance accuracy: 0.705). Finally, the selection of features has good consistency in the composite feature importance bar plot. Conclusion: We identify SLE patients with high disease activity by a simple machine learning pipeline, especially the LGB model based on the characteristics of proteinuria, hematuria, pyuria and other feathers screened out by collective feature selection. [ABSTRACT FROM AUTHOR]

This document is a correction notice for an article titled "STUB1-mediated K63-linked ubiquitination of UHRF1 promotes the progression of cholangiocarcinoma by maintaining DNA hypermethylation of PLA2G2A" published in the Journal of Experimental & Clinical Cancer Research. The authors discovered errors in the Supplementary Materials of the original article, specifically in Figure S1-S3 and their corresponding legends. The errors have been corrected and updated, but they do not impact the overall findings or conclusions of the article. The correction notice provides a link to the corrected electronic supplementary material. The publisher, Springer Nature, remains neutral regarding jurisdictional claims and institutional affiliations. [Extracted from the article]

Intra‐tumor bacteria promote tumor growth and inactivate cancer‐chemotherapeutics, causing poor treatment prognoses. Combined administration of cancer‐chemotherapeutics and antibiotics may disturb the oral and intestinal microflora in critically‐ill patients. To establish intra‐tumor co‐delivery of cancer‐chemotherapeutics and antibiotics, gemcitabine and ciprofloxacin are loaded in so‐called "self‐targeting", highly blood‐compatible, synthetic DCPA‐H2O liposomes equipped with complexed water for pH‐responsiveness. Liposomal pH‐responsiveness can be maintained by in‐shell loading of gemcitabine and in‐core loading of ciprofloxacin. These dual‐loaded liposomes are stealthily transported in the blood circulation to accumulate in the acidic environment of an infected tumor. Upon tumor self‐targeting, liposomes are fused with tumor cells and infecting bacteria and are disassembled to simultaneously release gemcitabine and ciprofloxacin. Treatment of mice with these self‐targeting liposomes yields significantly higher responses of Escherichia coli infected tumors with respect to both infection and tumor volume than gemcitabine and ciprofloxacin co‐delivered from non‐self‐targeting liposomes or free gemcitabine with or without ciprofloxacin in solution. [ABSTRACT FROM AUTHOR]

Integrating the advantages of both inorganic ceramic and organic polymer solid‐state electrolytes, small‐molecule solid‐state electrolytes represented by LiI‐3‐hydroxypropionitrile (LiI‐HPN) inorganic–organic hybrid systems possess good interfacial compatibility and high modulus. However, their lack of intrinsic Li+ conduction ability hinders potential application in lithium metal batteries until now, despite containing LiI phase composition. Herein, inspired by evolution tendency of ionic conduction behaviors together with first‐principles molecular dynamics simulations, we propose a stepped‐amorphization strategy to break the Li+ conduction bottleneck of LiI‐HPN. It involves three progressive steps of composition (LiI‐content increasing), time (long‐time standing), and temperature (high‐temperature melting) regulations, to essentially construct a small‐molecule‐based composite solid‐state electrolyte with intensified amorphous degree, which realizes efficient conversion from an I− to Li+ conductor and improved conductivity. As a proof, the stepped‐optimized LiI‐HPN is successfully operated in lithium metal batteries cooperated with Li4Ti5O12 cathode to deliver considerable compatibility and stability over 250 cycles. This work not only clarifies the ionic conduction mechanisms of LiI‐HPN inorganic–organic hybrid systems, but also provides a reasonable strategy to broaden the application scenarios of highly compatible small‐molecule solid‐state electrolytes. [ABSTRACT FROM AUTHOR]

The travel source–sink phenomenon is a typical urban traffic anomaly that reflects the imbalanced dissipation and aggregation of human mobility activities. It is useful for pertinently balancing urban facilities and optimizing urban structures to accurately sense the spatiotemporal ranges of travel source–sinks, such as for public transportation station optimization, sharing resource configurations, or stampede precautions among moving crowds. Unlike remote sensing using visual features, it is challenging to sense imbalanced and arbitrarily shaped source–sink areas using human mobility trajectories. This paper proposes a density-based adaptive clustering method to identify the spatiotemporal ranges of travel source–sink patterns. Firstly, a spatiotemporal field is utilized to construct a stable neighborhood of origin and destination points. Then, binary spatiotemporal statistical hypothesis tests are proposed to identify the source and sink core points. Finally, a density-based expansion strategy is employed to detect the spatial areas and temporal durations of sources and sinks. The experiments conducted using bicycle trajectory data in Shanghai show that the proposed method can accurately extract significantly imbalanced dissipation and aggregation events. The travel source–sink patterns detected by the proposed method have practical reference, meaning that they can provide useful insights into the redistribution of bike-sharing and station resources. [ABSTRACT FROM AUTHOR]

Integrating the advantages of both inorganic ceramic and organic polymer solid‐state electrolytes, small‐molecule solid‐state electrolytes represented by LiI‐3‐hydroxypropionitrile (LiI‐HPN) inorganic–organic hybrid systems possess good interfacial compatibility and high modulus. However, their lack of intrinsic Li+ conduction ability hinders potential application in lithium metal batteries until now, despite containing LiI phase composition. Herein, inspired by evolution tendency of ionic conduction behaviors together with first‐principles molecular dynamics simulations, we propose a stepped‐amorphization strategy to break the Li+ conduction bottleneck of LiI‐HPN. It involves three progressive steps of composition (LiI‐content increasing), time (long‐time standing), and temperature (high‐temperature melting) regulations, to essentially construct a small‐molecule‐based composite solid‐state electrolyte with intensified amorphous degree, which realizes efficient conversion from an I− to Li+ conductor and improved conductivity. As a proof, the stepped‐optimized LiI‐HPN is successfully operated in lithium metal batteries cooperated with Li4Ti5O12 cathode to deliver considerable compatibility and stability over 250 cycles. This work not only clarifies the ionic conduction mechanisms of LiI‐HPN inorganic–organic hybrid systems, but also provides a reasonable strategy to broaden the application scenarios of highly compatible small‐molecule solid‐state electrolytes. [ABSTRACT FROM AUTHOR]

Purpose: This study aims to investigate the applicability of lower lid margin thickness (LLMT) measurements in adults with and without meibomian gland dysfunction (MGD) by optical coherence tomography (OCT) and keratograph. Methods: This is a cross-sectional, observational study. A hundred and eight volunteers aged 20 to 79, including 68 MGD patients and 40 normal subjects, were recruited. Using OCT and keratograph to measure the LLMT from the posterior lash line to anterior edge or outer edge of the tear meniscus was separately performed two times by the same person. Results: The mean age of normal and MGD subjects was 50.5 ± 14.2 years and 55.8 ± 15.5 years, respectively. The LLMT with OCT and keratograph in MGD patients was significantly greater than that in normal subjects (1.06 ± 0.27 and 1.03 ± 0.25 mm vs. 0.90 ± 0.20 and 0.86 ± 0.16 mm, respectively). In both normal and MGD subjects, the tear meniscus height and LLMT with OCT were both greater than that with keratograph (P < 0.05), and intraclass correlation coefficient (ICC) demonstrated a good agreement in the LLMT measurements between two devices (ICC = 0.83 and 0.79, respectively). Additionally, the LLMT in MGD patients was appeared to be positively correlated with meiboscore (rs = 0.37, P = 0.002). Conclusions: The OCT and keratograph were two reliable tools in the LLMT measurements, which may have potential applications for diagnosis and evaluation of MGD. Furthermore, we found that the LLMT measured by OCT was greater than that measured by keratograph. [ABSTRACT FROM AUTHOR]

Wind speed is the dominant meteorological factor affecting wind turbine power generation. Existing wind speed fluctuation division algorithms only focus on the wind speed changing process, but strong uncertainty exists in the wind speed–power conversion, which has been demonstrated as a multi-power transfer relationship under wind speed fluctuation. Therefore, a wind speed power transfer fluctuation partitioning (PTFP) algorithm is proposed, which fully considers the wind speed variation and power transfer characteristics to refine the modeling of wind power forecasting. The power transfer characteristics are investigated according to the wind speed–power conversion error of a wind farm. The measured wind speeds from three sources and fuzziness under different fluctuation trends are discussed based on the scatter distribution and probabilistic wind speed power curve. The model errors under different changing trends are quantitatively analyzed. Subsequently, the operation data of two wind farms in China are divided using the PTFP algorithm. The modeling error is reduced compared to that without considering the power transfer characteristics and the rationality of the proposed algorithm is demonstrated. The PTFP algorithm is also applied to wind power forecasting to verify its applicability. The results demonstrate that the proposed model can improve prediction accuracy on all time scales. [ABSTRACT FROM AUTHOR]

Agmatinase (AGMAT) is an enzyme that hydrolyzes agmatine to putrescine and urea. In this study, we explored the functions of AGMAT in colorectal cancer (CRC). By performing gain-of-function and loss-of-function experiments, we investigated the roles of AGMAT in proliferation, cell cycle progression, and apoptosis of CRC cells. We also established a colitis-associated colorectal cancer model by challenging mice with azoxymethane (AOM) and dextran sodium sulfate (DSS), and we subsequently silenced AGMAT expression in mice by adeno-associated virus 9 (AAV9)-mediated delivery of short hairpin RNA (shRNA). In vitro experiments showed that overexpression of AGMAT accelerated the proliferation and inhibited the apoptosis of CRC cells, and AGMAT knockdown exhibited the opposite effects. Interestingly, the oncogenic transcription factor, c-Myc, could bind to the AGMAT promoter and transcriptionally increase AGMAT expression in CRC cells. Additionally, c-Myc and AGMAT were upregulated in the colon of AOM/DSS-treated mice, and AGMAT silencing significantly mitigated colitis in AOM/DSS-treated mice, as evidenced by the increased colon length, attenuated crypt damage, and reduced levels of inflammatory indicators (myeloperoxidase, interleukin-6, tumor necrosis factor-α, inducible nitric oxide synthase, and phosphorylated p65) in colon tissues. Notably, AGMAT silencing decreased both the number and size of tumors, reduced expression of proliferating cell nuclear antigen, and inhibited phosphorylation of protein kinase B (AKT) and extracellular signal-regulated kinase in the colon of AOM/DSS-treated mice. Overall, we determined that AGMAT facilitates tumor progression in CRC. Our findings will be helpful in the search for potential therapeutic targets for CRC. [ABSTRACT FROM AUTHOR]

Objective: Diagnosis of lupus nephritis (LN) is a complex process, which usually requires renal biopsy. We aim to establish a machine learning pipeline to help diagnosis of LN. Methods: A cohort of 681 systemic lupus erythematosus (SLE) patients without LN and 786 SLE patients with LN was established, and a total of 95 clinical, laboratory data and 17 meteorological indicators were collected. After tenfold cross-validation, the patients were divided into training set and test set. The features selected by collective feature selection method of mutual information (MI) and multisurf were used to construct the models of logistic regression, decision tree, random forest, naive Bayes, support vector machine (SVM), light gradient boosting (LGB), extreme gradient boosting (XGB), and artificial neural network (ANN), the models were compared and verified in post-analysis. Results: Collective feature selection method screens out antistreptolysin (ASO), retinol binding protein (RBP), lupus anticoagulant 1 (LA1), LA2, proteinuria and other features, and the hyperparameter optimized XGB (ROC: AUC = 0.995; PRC: AUC = 1.000, APS = 1.000; balance accuracy: 0.990) has the best performance, followed by LGB (ROC: AUC = 0.992; PRC: AUC = 0.997, APS = 0.977; balance accuracy: 0.957). The worst performance is naive Bayes model (ROC: AUC = 0.799; PRC: AUC = 0.822, APS = 0.823; balance accuracy: 0.693). In the composite feature importance bar plots, ASO, RF, Up/Ucr, and other features play important roles in LN. Conclusion: We developed and validated a new and simple machine learning pathway for diagnosis of LN, especially the XGB model based on ASO, LA1, LA2, proteinuria, and other features screened out by collective feature selection. [ABSTRACT FROM AUTHOR]

Background: Primary pelvis and spine osteosarcoma (PSOS) is a specific type of osteosarcoma that is difficult to treat and has a poor prognosis. In recent years, the research on osteosarcoma has been increasing, but there have been few studies on PSOS; in particular, there have been a lack of analyses with a large sample size. This study aimed to construct and validate a model to predict the overall survival (OS) of PSOS patients, as currently there are no tools available for assessing their prognosis. Methods: Data including demographic information, clinical characteristics, and follow-up information on patients with PSOS were collected from the Surveillance, Epidemiology, and End Results (SEER) database, as well as from the Spine Tumor Center of Changzheng Hospital. Variable selection was achieved through a backward procedure based on the Akaike Information Criterion (AIC). Prognostic factors were identified by univariate and multivariate Cox analysis. A nomogram was further constructed for the estimation of 1-, 3-, and 5-year OS. Calibration plots, the concordance index (C-index), and the receiver operating characteristic (ROC) were used to evaluate the prediction model. Results: In total, 83 PSOS patients and 90 PSOS patients were separately collected from the SEER database and Changzheng Hospital. In the SEER cohort, liver metastasis, lung metastasis, and chemotherapy were recognized as independent prognostic factors for OS (p < 0.05) and were incorporated to construct the initial nomogram. However, the initial nomogram showed poor predictive accuracy in internal and external validation. Then, we shifted our focus to the Changzheng data. Lung metastasis involving segments, Eastern Cooperative Oncology Group (ECOG) performance score, alkaline phosphatase (ALP) level, and en bloc resection were ultimately identified as independent prognostic factors for OS (p < 0.05) and were further incorporated to construct the current nomogram, of which the bias-corrected C-index was 0.834 (0.824–0.856). The areas under the ROC curves (AUCs) of the current nomogram regarding 1-, 3-, and 5-year OS probabilities were 0.93, 0.96, and 0.92, respectively. Conclusion: We have developed a predictive model with satisfactory performance and clinical practicability, enabling effective prediction of the OS of PSOS patients and aiding clinicians in decision-making. [ABSTRACT FROM AUTHOR]

In the present study, gelatin-based films incorporating squid pen chitosan obtained by high hydrostatic pressure (HHP chitosan) at varying proportions were prepared and their properties were compared with films containing untreated chitosan. The resulting films were characterized by analyzing the physical, morphological, mechanical and barrier properties. The addition of different ratios of HHP chitosan to the gelatin-based film yielded significant improvements in mechanical and moisture barrier properties. The reason for this might be that HHP chitosan contributed to a regular and dense microstructure of the composite films due to forming a three-dimensional network structure in gelatin-based films with enhanced intermolecular interactions. The FTIR spectra showed no new chemical bond formed by incorporating HHP chitosan into gelatin-based film. The SEM micrographs showed that the gelatin-based film fabricated with three types of chitosan had a homogeneous surface morphology, indicating good compatibility of the materials. Compared to the gelatin-based films containing untreated chitosan, films containing HHP chitosan significantly delayed oxidative deterioration in oil during storage. Therefore, the chitosan obtained by HHP treatment could have a potential application in edible gelatin-based films as packaging materials. [ABSTRACT FROM AUTHOR]

Rational design of wide electrochemical window (ECW) electrolytes to pair with high‐voltage cathodes is an emerging trend to push the energy density limits of current rechargeable batteries. Traditional single‐electronic/gas‐phase approximation‐based methods (e.g., highest occupied molecular orbital/lowest unoccupied molecular orbital) are increasingly recognized to have large deviations from experiments when predicting ECWs of electrolytes involving complex solvent interactions. Specifically, by examining available experimental ECWs of 68 electrolyte solvents extracted from ≈140 000 literature sources, which are conventionally divided into five functional‐group categories (covering commonly used carbonate‐based ethylene carbonate (EC)/propylene carbonate (PC) and ether‐based tetrahydrofuran), it is found that mean‐absolute‐errors (MAE) of traditional methods reach up to 3.25 V. Herein, a thermodynamic cycle‐based ECW prediction approach is proposed including two long‐term overlooked reorganization‐energy and solvation‐energy corrections, each of which can be quantified by two geometric descriptors (λ and ΔGsol), reducing MAE below 0.68 V. Following this, a database containing ECWs for 308 electrolyte solvents, obtained by traversing single functional‐group substitutions, is established. Furthermore, two omitted solvents with ECWs over 6.00 V and excellent structural stabilities (bond‐length change < 0.10 Å during redox process) are retrieved by stepwise screening of structural/electronic parallel properties. This study demonstrates the benefits of improving ECW prediction accuracy and accumulating descriptors to accelerate rapid screening of superior battery electrolytes. [ABSTRACT FROM AUTHOR]

Pairing Li-free transition-metal-based cathodes (MX) with Li-metal anodes is an emerging trend to overcome the energy-density limitation of current rechargeable Li-ion technology. However, the development of practical Li-free MX cathodes is plagued by the existing notion of low voltage due to the long-term overlooked voltage-tuning/phase-stability competition. Here, we propose a p-type alloying strategy involving three voltage/phase-evolution stages, of which each of the varying trends are quantitated by two improved ligand-field descriptors to balance the above contradiction. Following this, an intercalation-type 2H-V1.75Cr0.25S4 cathode tuned from layered MX2 family is successfully designed, which possesses an energy density of 554.3 Wh kg−1 at the electrode level accompanied by interfacial compatibility with sulfide solid-state electrolyte. The proposal of this class of materials is expected to break free from scarce or high-cost transition-metal (e.g. Co and Ni) reliance in current commercial cathodes. Our experiments further confirm the voltage and energy-density gains of 2H-V1.75Cr0.25S4. This strategy is not limited to specific Li-free cathodes and offers a solution to achieve high voltage and phase stability simultaneously. [ABSTRACT FROM AUTHOR]

In this letter, A wideband filtering phase shifter is proposed based on vertically installed planar (VIP) circuit structures, where the VIP circuit is used to realize a tight coupling. The even‐odd mode analysis is adopted to analyze the whole structure. Then, a 45° filtering phase shifter is designed to verify the validity of the design methodology. The simulated and measured results demonstrate that the proposed phase shifter has low insertion losses (<0.5 dB) and excellent return losses (<−15 dB). The 3°‐phase shift bandwidth is more than 64.31%. [ABSTRACT FROM AUTHOR]

The study was performed to identify bioactive constituents from the inner bark of Betula schmidtii. Seven compounds were isolated through silica gel and Sephadex LH‐20 column chromatography, and identified to be betulin (1), betulinic acid (2), β‐sitosterol (3), lupeol (4), kojic acid (5), 1,7‐bis‐(ρ‐hydroxyphenyl)‐(3,4‐dihydroxy)‐hepan‐5‐one (6), and platyphyllenone (7) using EI‐MS, 1D‐, and 2D‐NMR data. Compounds 5, 6, and 7 show antioxidant effect with IC50 values of 18.23 ± 1.08, 29.37 ± 1.42, and 40.14 ± 1.75 μM in DPPH free radical scavenging activity. Compounds 4 and 5 show an antioxidant effect with IC50 values of 28.21 ± 1.80 and 37.74 ± 1.02 μM in DCHF‐DA intracellular ROS generations. Compounds 5, 6, and 7 also exhibited mushroom tyrosinase inhibitory activity with IC50 values of 17.42 ± 1.08, 47.17 ± 1.92, and 26.64 ± 1.40 μM. Compound 1 showed cell viability of 24.50 ± 6.30 and 45.60 ± 3.10% at 10 and 25 μM, while compound 6 showed 11.20 ± 1.40% at 25 μM in glutamate‐induced damaged mouse neuronal cells. [ABSTRACT FROM AUTHOR]

One nucleotide substitution in codon 30 of HLA‐DRB4*01:03:01:01 results in a novel allele, HLA‐DRB4*01:179. [ABSTRACT FROM AUTHOR]

Achieving deep blue thermally activated delayed fluorescent (TADF) materials with narrow emission still remains a challenge. Herein, two deep blue TADF emitters DCBTRZ and PPCTRZ were designed and synthesized by directly using host materials, 1,4-di(carbazol-9-yl)benzene (DCB) and 2-[4-(9H-carbazol-9-yl)phenyl]-1-phenyl-1H-phenanthro[9,10-d]imidazole (PPC) as donors, and 2,4,6-triphenyl-1,3,5-triazine (TRZ) as an acceptor. The two emitters have typical TADF properties. Both of them can emit deep blue fluorescence with a very narrow full-width at half-maximum (FWHM) of 42 nm in toluene. The photoluminescence quantum yields (PLQYs) of DCBTRZ and PPCTRZ are 39.6% and 38.2% in doped films, respectively. Devices based on DCBTRZ and PPCTRZ achieve deep blue emission (440 and 442 nm) with maximum external quantum efficiencies (EQEmax) of 6.68% and 6.55%, respectively. Meanwhile, they exhibit very high color purity. The CIEy and FWHM of devices employing DCBTRZ and PPCTRZ are 0.059/0.063 and 56/54 nm, respectively, meeting the standard of NTSC for deep-blue emitters, which indicates excellent application prospects in displays. The results suggest that this strategy for developing deep blue TADF materials with narrow emission and CIEy < 0.06 directly employing host materials as donors is feasible and effective. [ABSTRACT FROM AUTHOR]

Meteorites record processes that occurred before and during the formation of the Solar System in the form of nucleosynthetic anomalies: isotopic compositions that differ from the Solar System patterns. Nucleosynthetic anomalies are rarely seen in volatile elements such as potassium at bulk meteorite scale. We measured potassium isotope ratios in 32 meteorites and identified nucleosynthetic anomalies in the isotope potassium-40. The anomalies are larger and more variable in carbonaceous chondrite (CC) meteorites than in noncarbonaceous (NC) meteorites, indicating that CCs inherited more material produced in supernova nucleosynthesis. The potassium-40 anomaly of Earth is close to that of the NCs, implying that EarthÕs potassium was mostly delivered by NCs. [ABSTRACT FROM AUTHOR]

Introduction: Surveys are common research tools, and questionnaires revisions are a common occurrence in longitudinal studies. Revisions can, at times, introduce systematic shifts in measures of interest. We formulate that questionnaire revision are a stochastic process with transition matrices. Thus, revision shifts can be reduced by first estimating these transition matrices, which can be utilized in estimation of interested measures. Materials and method: An ideal survey response model is defined by mapping between the true value of a participant's response to an interval in the grouped data type scale. A population completed surveys multiple times, as modeled with multiple stochastic process. This included stochastic processes related to true values and intervals. While multiple factors contribute to changes in survey responses, here, we explored the method that can mitigate the effects of questionnaire revision. We proposed the Version Alignment Method (VAM), a data preprocessing tool, which can separate the transitions according to revisions from all transitions via solving an optimization problem and using the revision-related transitions to remove the revision effect. To verify VAM, we used simulation data to study the estimation error and a real life MJ dataset containing large amounts of long-term questionnaire responses with several questionnaire revisions to study its feasibility. Result: We compared the difference of the annual average between consecutive years. Without adjustment, the difference is 0.593 when the revision occurred, while VAM brought it down to 0.115, where difference between years without revision was in the 0.005, 0.125 range. Furthermore, our method rendered the responses to the same set of intervals, thus comparing the relative frequency of items before and after revisions became possible. The average estimation error in L infinity was 0.0044 which occupied the 95% CI which was constructed by bootstrap analysis. Conclusion: Questionnaire revisions can induce different response bias and information loss, thus causing inconsistencies in the estimated measures. Conventional methods can only partly remedy this issue. Our proposal, VAM, can estimate the aggregate difference of all revision-related systematic errors and can reduce the differences, thus reducing inconsistencies in the final estimations of longitudinal studies. [ABSTRACT FROM AUTHOR]

Background: Cyclophilin (CYP) belongs to the immunophilin family and has peptidyl-prolyl cis-trans isomerase (PPIase) activity, which catalyzes the cis-trans isomerization process of proline residues. CYPs widely exist in eukaryotes and prokaryotes, and contain a conserved cyclophilin-like domain (CLD). Plant cyclophilins are widely involved in a range of biological processes including stress response, metabolic regulation, and growth and development. Result: In this study, 30 cyclophilin genes on 15 chromosomes were identified from the 'Golden Delicious' apple (M. domestica) genome. Phylogenetic analysis showed that the cyclophilin family genes can be divided into three clades in Malus. Collinear analysis showed that ten gene pairs were the result of segmental duplication. Analysis of gene and protein structure further supported the phylogenetic tree and collinearity analysis. The expression of MdCYPs in different organs was higher in leaves, flowers, and fruits. Ten and eight CYPs responded to drought and salt stress, respectively. MdCYP16, a nuclear-localized MD CYP, was screened from the intersection of the two expression profiling datasets and was highly sensitive to drought and salt stress. GUS staining of transgenic Arabidopsis indicated that MdCYP16 may be involved in the regulation of abiotic stress. Conclusion: This study systematically analyzed members of the apple cyclophilin family and confirmed the involvement of MdCYP16 as a nuclear-localized MD cyclophilin that acts in response to salt and drought stress in apple. Our work identifies members of the apple cyclophilin gene family, and provides an important theoretical basis for in-depth study of cyclophilin function. Additionally, the analysis provides candidate genes that may be involved in stress response in apple. [ABSTRACT FROM AUTHOR]

Exposure of infectious biofilms to dispersants induces high bacterial concentrations in blood that may cause sepsis. Preventing sepsis requires simultaneous biofilm dispersal and bacterial killing. Here, self-targeting DCPA(2-(4-((1,5-bis(octadecenoyl)1,5-dioxopentan-2-yl)carbamoyl)pyridin-1-ium-1-yl)acetate) liposomes with complexed water were self-assembled with ciprofloxacin loaded in-membrane and PEGylated as a lipid-membrane component, together with bromelain loaded in-core. Inside biofilms, DCPA-H 2 O and PEGylated ciprofloxacin became protonated, disturbing the balance in the lipid-membrane to cause liposome-burst and simultaneous release of bromelain and ciprofloxacin. Simultaneous release of bromelain and ciprofloxacin enhanced bacterial killing in Staphylococcus aureus biofilms as compared with free bromelain and/or ciprofloxacin. After tail-vein injection in mice, liposomes accumulated inside intra-abdominal staphylococcal biofilms. Subsequent liposome-burst and simultaneous release of bromelain and ciprofloxacin yielded degradation of the biofilm matrix by bromelain and higher bacterial killing without inducing septic symptoms as obtained by injection of free bromelain and ciprofloxacin. This shows the advantage of simultaneous release from liposomes of bromelain and ciprofloxacin inside a biofilm. [Display omitted] [ABSTRACT FROM AUTHOR]