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Neurocognitive aging researchers are increasingly focused on the locus coeruleus, a neuromodulatory brainstem structure that degrades with age. With this rapid growth, the field will benefit from consensus regarding which magnetic resonance imaging (MRI) metrics of locus coeruleus structure are most sensitive to age and cognition. To address this need, the current study acquired magnetization transfer- and diffusion-weighted MRI images in younger and older adults who also completed a free recall memory task. Results revealed significantly larger differences between younger and older adults for maximum than average magnetization transfer-weighted contrast (MTC), axial than mean or radial single-tensor diffusivity (DTI), and free than restricted multi-compartment diffusion (NODDI) metrics in the locus coeruleus; with maximum MTC being the best predictor of age group. Age effects for all imaging modalities interacted with sex, with larger age group differences in males than females for MTC and NODDI metrics. Age group differences also varied across locus coeruleus subdivision for DTI and NODDI metrics, and across locus coeruleus hemispheres for MTC. Within older adults, however, there were no significant effects of age on MTC or DTI metrics, only an interaction between age and sex for free diffusion. Finally, independent of age and sex, higher restricted diffusion in the locus coeruleus was significantly related to better (lower) recall variability, but not mean recall. Whereas MTC has been widely used in the literature, our comparison between the average and maximum MTC metrics, inclusion of DTI and NODDI metrics, and breakdowns by locus coeruleus subdivision and hemisphere make important and novel contributions to our understanding of the aging of locus coeruleus structure.

Different exogenous electric fields (EF) can guide cell migration, disrupt proliferation, and program cell development. Studies have shown that many of these processes were initiated at the cell membrane, but the mechanism has been unclear, especially for conventionally non-excitable cells. In this study, we focus on the electrostatic aspects of EF coupling with the cell membrane by eliminating Faradaic processes using dielectric-coated microelectrodes. Our data unveil a distinctive biphasic response of the ERK signaling pathway of epithelial cells (MCF10A) to alternate current (AC) EF. The ERK signal exhibits both inhibition and activation phases, with the former triggered by a lower threshold of AC EF, featuring a swifter peaking time and briefer refractory periods than the later-occurring activation phase, induced at a higher threshold. Interestingly, the biphasic ERK responses are sensitive to the waveform and timing of EF stimulation pulses, depicting the characteristics of electrostatic and dissipative interactions. Blocker tests and correlated changes of active Ras on the cell membrane with ERK signals indicated that both EGFR and Ras were involved in the rich ERK dynamics induced by EF. We propose that the frequency-dependent dielectric relaxation process could be an important mechanism to couple EF energy to the cell membrane region and modulate membrane protein-initiated signaling pathways, which can be further explored to precisely control cell behavior and fate with high temporal and spatial resolution.

Abstract Depression is the second leading-cause of disability in China. Although studies have shown that more than 80% of patients with advanced schistosomiasis (AS) suffer from anxiety and depression, these study groups are all hospitalized patients with AS and do not represent the extent of the disease in the whole group. To our knowledge, there are no studies assessing the severity of depression in patients with other forms of schistosomiasis japonicum. Therefore, it is necessary to evaluate the occurrence and potential risk factors of depression in the schistosomiasis endemic population. This cross-sectional study was conducted in Jiangxi Province, where schistosomiasis is relatively common in China, as the investigation site. The Patient Health Questionnaire-9 (PHQ-9) scale was selected to assess the depressive symptoms in the study population. At the same time, basic personal information of the research subjects and relevant socio-economics and schistosomiasis endemic area indicators were collected. The survey results show that AS has the highest incidence of depression (34.35%), while non-advanced schistosomiasis (N-AS) and control group (CG) have 22.35% and 22.24% respectively; the incidence of depression in AS is significantly higher than in N-AS and CG, while there is no statistical significance in the comparison between N-AS and CG; the incidence of mild depressive symptoms accounts for 61.08%-75.54% of the total incidence of depression in different groups; multivariate analysis shows that the occurrence of moderate/severe depressive symptoms in the AS group was significantly related to above 60 years old, male, the combination of other serious diseases, personal financial difficulties, and marshland and lake endemic areas. In the N-AS group, the occurrence of moderate/severe depressive symptoms was significantly related to the combination of other serious diseases, personal financial difficulties, significant correlation between marshland and lake endemic areas and the level of control of schistosomiasis epidemics. In conclusion, depression is still relatively common among patients with schistosomiasis patients, especially those with AS. It is recommended that the government and relevant departments consider mental health care when developing prevention and control work in schistosomiasis-endemic areas, in order to effectively protect the physical and mental health of schistosomiasis patients and residents in endemic areas.

Abstract Dysregulation of the gut microbiome has associated with the occurrence and progression of non-alcoholic fatty liver disease (NAFLD). To determine the diagnostic capacity of this association, we compared fecal microbiomes across 104 participants including non-NAFLD controls and NAFLD subtypes patients that were distinguished by magnetic resonance imaging. We measured their blood biochemical parameters, 16 S rRNA-based gut microbiota and fecal short-chain fatty acids (SCFAs). Multi-omic analyses revealed that NAFLD patients exhibited specific changes in gut microbiota and fecal SCFAs as compared to non-NAFLD subjects. Four bacterial genera (Faecalibacterium, Subdoligranulum, Haemophilus, and Roseburia) and two fecal SCFAs profiles (acetic acid, and butyric acid) were closely related to NAFLD phenotypes and could accurately distinguish NAFLD patients from healthy non-NAFLD subjects. Twelve genera belonging to Faecalibacterium, Subdoligranulum, Haemophilus, Intestinibacter, Agathobacter, Lachnospiraceae_UCG-004, Roseburia, Butyricicoccus, Actinomycetales_unclassified, [Eubacterium]_ventriosum_group, Rothia, and Rhodococcus were effective to distinguish NAFLD subtypes. Of them, combination of five genera can distinguish effectively mild NAFLD from non-NAFLD with an area under curve (AUC) of 0.84. Seven genera distinguish moderate NAFLD with an AUC of 0.83. Eight genera distinguish severe NAFLD with an AUC of 0.90. In our study, butyric acid distinguished mild-NAFLD from non-NAFLD with AUC value of 0.83. And acetic acid distinguished moderate-NAFLD and severe-NAFLD from non-NAFLD with AUC value of 0.84 and 0.70. In summary, our study and further analysis showed that gut microbiota and fecal SCFAs maybe a method with convenient detection advantages and invasive manner that are not only a good prediction model for early warning of NAFLD occurrence, but also have a strong ability to distinguish NAFLD subtypes.

Abstract Early, rapid, and accurate diagnostic tests play critical roles not only in the identification/management of individuals infected by SARS-CoV-2, but also in fast and effective public health surveillance, containment, and response. Our aim has been to develop a fast and robust fluorescence in situ hybridization (FISH) detection method for detecting SARS-CoV-2 RNAs by using an HEK 293 T cell culture model. At various times after being transfected with SARS-CoV-2 E and N plasmids, HEK 293 T cells were fixed and then hybridized with ATTO-labeled short DNA probes (about 20 nt). At 4 h, 12 h, and 24 h after transfection, SARS-CoV-2 E and N mRNAs were clearly revealed as solid granular staining inside HEK 293 T cells at all time points. Hybridization time was also reduced to 1 h for faster detection, and the test was completed within 3 h with excellent results. In addition, we have successfully detected 3 mRNAs (E mRNA, N mRNA, and ORF1a (−) RNA) simultaneously inside the buccal cells of COVID-19 patients. Our high-resolution RNA FISH might significantly increase the accuracy and efficiency of SARS-CoV-2 detection, while significantly reducing test time. The method can be conducted on smears containing cells (e.g., from nasopharyngeal, oropharyngeal, or buccal swabs) or smears without cells (e.g., from sputum, saliva, or drinking water/wastewater) for detecting various types of RNA viruses and even DNA viruses at different timepoints of infection.

Derivatives of the potassium-sparing diuretic amiloride are preferentially cytotoxic toward tumor cells relative to normal cells, and have the capacity to target tumor cell populations resistant to currently employed therapeutic agents. However, a major barrier to clinical translation of the amilorides is their modest cytotoxic potency, with estimated IC50 values in the high micromolar range. Here we report the synthesis of ten novel amiloride derivatives and the characterization of their cytotoxic potency toward MCF7 (ER/PR-positive), SKBR3 (HER2-positive) and MDA-MB-231 (triple negative) cell line models of breast cancer. Comparisons of derivative structure with cytotoxic potency toward these cell lines underscore the importance of an intact guanidine group, and uncover a strong link between drug-induced cytotoxicity and drug lipophilicity. We demonstrate that our most potent derivative called LLC1 is preferentially cytotoxic toward mouse mammary tumor over normal epithelial organoids, acts in the single digit micromolar range on breast cancer cell line models representing all major subtypes, acts on cell lines that exhibit both transient and sustained resistance to chemotherapeutic agents, but exhibits limited anti-tumor effects in a mouse model of metastatic breast cancer. Nonetheless, our observations offer a roadmap for the future optimization of amiloride-based compounds with preferential cytotoxicity toward breast tumor cells.

Prevention of COVID-19 with vaccine requires multiple doses and updated boosters to maintain protection; however currently there are no tests that can measure immunity and guide clinical decisions about timing of booster doses. This study examined the association between the risk of COVID-19 breakthrough infections and receptor binding domain (RBD) antibody levels and receipt of booster of COVID-19 vaccines. A community sample of Los Angeles County adults were surveyed between 2021 and 2022 to determine if they had a self-reported breakthrough infection. Predictors included RBD antibody levels, measured by binding antibody responses to the ancestral strain at baseline and self-reported booster shot during the study period. Of the 859 participants, 182 (21%) reported a breakthrough infection. Irrespective of the level of antibodies, the risk of breakthrough infection was similar, ranging from 19 to 23% (P = 0.78). The risk of breakthrough infections was lower among participants who had a booster shot (P = 0.004). The protective effect of a booster shot did not vary by antibody levels prior to receiving the booster. This study found no association between RBD antibody levels and risk of breakthrough infections, while the receipt of booster was associated with lower risk of breakthrough infections, which was independent of pre-booster antibody levels. Therefore, antibody levels might not be a useful guide for clinical decisions about timing of booster doses.

Tears within the stabilizing muscles of the shoulder, known as the rotator cuff (RC), are the most common cause of shoulder pain-often presenting in older patients and requiring expensive advanced imaging for diagnosis. Despite the high prevalence of RC tears within the elderly population, there is no previously published work examining shoulder kinematics using markerless motion capture in the context of shoulder injury. Here we show that a simple string pulling behavior task, where subjects pull a string using hand-over-hand motions, provides a reliable readout of shoulder mobility across animals and humans. We find that both mice and humans with RC tears exhibit decreased movement amplitude, prolonged movement time, and quantitative changes in waveform shape during string pulling task performance. In rodents, we further note the degradation of low dimensional, temporally coordinated movements after injury. Furthermore, a logistic regression model built on our biomarker ensemble succeeds in classifying human patients as having a RC tear with > 90% accuracy. Our results demonstrate how a combined framework bridging animal models, motion capture, convolutional neural networks, and algorithmic assessment of movement quality enables future research into the development of smartphone-based, at-home diagnostic tests for shoulder injury.

Abstract Nasopharyngeal carcinoma (NPC) presents a significant medical challenge due to its high incidence rate and poor prognosis, which are attributed primarily to tumor metastasis and drug resistance. Sine oculis homeobox homolog 1 (SIX1) has been identified as a crucial target for cancer treatment. However, its role in NPC remains incompletely understood. This study investigated the mechanisms by which the degradation of the SIX1 protein, which is mediated by ubiquitin, affects the malignant characteristics of NPC throughout the cell cycle. Our findings reveal that reduced expression of the itchy E3 ubiquitin ligase E3 (ITCH) in NPC impedes the degradation of the SIX1 protein, leading to enhance oncogenic properties. Knockdown experiments which SIX1 was inhibited demonstrated a decrease in the proliferation, migration, and invasion of NPC cell lines, whereas overexpression of SIX1 yielded the opposite effects. Further experimental validation revealed that SIX1 promotes NPC progression via the cell division cycle 27 (CDC27)/cyclin B1 axis. These findings provide valuable insights into potential therapeutic targets and prognostic indicators for NPC treatment, emphasizing the ITCH/SIX1/CDC27/cyclin B1 axis as a promising target for novel therapies.

Abstract This study analysed the relationship between the structured and unstructured activities of preschoolers and their mental and physical health, and also investigated the predicted changes in mental and physical health by reallocating activity time. This cross-sectional study was carried out with 324 preschoolers. Video recording and SOPARC activity observation system was used for the division of structured and unstructured activities. An accelerometer sensor was used to measure activity intensity. The SDQ psychological questionnaire was adopted to collect data on internalizing difficulties, externalizing difficulties, total difficulties and pro-social behaviours. Physical indices including body shape (height, weight, BMI), and physical fitness (upper and lower limb strength, flexibility, agility, and balance) were collected using Chinese toddler physical fitness measurement tools. Component data and isotemporal reallocation analyses were conducted using R Studio (Version 4.2). A total of 308 preschoolers (160 boys; aged 4.50 ± 0.93 years) were included in the data analysis. The activities composition, adjusted for sex, area, mental level (for mental indicators), or age (for physical indicators), was significantly correlated with various measurement indicators (p

Abstract Sepsis-associated encephalopathy (SAE) is a frequent and severe complication in septic patients, characterized by diffuse brain dysfunction resulting from systemic inflammation. Accurate prediction of long-term mortality in these patients is critical for improving clinical outcomes and guiding treatment strategies. We conducted a retrospective cohort study using the MIMIC IV database to identify adult patients diagnosed with SAE. Patients were randomly divided into a training set (70%) and a validation set (30%). Least absolute shrinkage and selection operator regression and multivariate logistic regression were employed to identify significant predictors of 1-year mortality, which were then used to develop a prognostic nomogram. The model’s discrimination, calibration, and clinical utility were assessed using the area under the receiver operating characteristic curve (AUC), calibration plots, and decision curve analysis, respectively. A total of 3,882 SAE patients were included in the analysis. The nomogram demonstrated strong predictive performance with AUCs of 0.881 (95% CI: 0.865, 0.896) in the training set and 0.859 (95% CI: 0.830, 0.888) in the validation set. Calibration plots indicated good agreement between predicted and observed 1-year mortality rates. The decision curve analysis showed that the nomogram provided greater net benefit across a range of threshold probabilities compared to traditional scoring systems such as Glasgow Coma Scale and Sequential Organ Failure Assessment. Our study presents a robust and clinically applicable nomogram for predicting 1-year mortality in SAE patients. This tool offers superior predictive performance compared to existing severity scoring systems and has significant potential to enhance clinical decision-making and patient management in critical care settings.

Abstract Migratory cells exist in the heart, such as immune cells, fibroblasts, endothelial cells, etc. During myocardium injury, such as ischemia–reperfusion (MIRI), cells migrate to the site of injury to perform repair functions. However, excessive aggregation of these cells may exacerbate damage to the structure and function of the heart, such as acute myocarditis and myocardial fibrosis. Myocardial injury releases exosomes, which are a type of vesicle with signal transduction function and the miRNA carried by exosomes can control cell migration function. Therefore, regulating this migratory cell population through cardiac-derived exosomal miRNA is crucial for protecting and maintaining cardiac function. Through whole transcriptome RNA sequencing, exosomal miRNA sequencing and single-cell dataset analysis, we (1) determined the potential molecular regulatory role of the lncRNA‒miRNA‒mRNA axis in MIRI, (2) screened four important exosomal miRNAs that could be released by cardiac tissue, and (3) screened seven genes related to cell locomotion that are regulated by four miRNAs, among which Tradd and Ephb6 may be specific for promoting migration of different cells of myocardial tissue in myocardial infarct. We generated a core miRNA‒mRNA network based on the functions of the target genes, which may be not only a target for cardiac repair but also a potential diagnostic marker for interactions between the heart and other tissues or organs. In conclusion, we elucidated the potential mechanism of MIRI in cardiac remodeling from the perspective of cell migration, and inhibition of cellular overmigration based on this network may provide new therapeutic targets for MIRI and to prevent MIRI from developing into other diseases.

Abstract Sponge city stormwater management (SCSM) strategy in China aims for sustainable stormwater handling. While many studies have examined the technical aspects of sponge city green infrastructure (SCGI), few have explored public perspectives. This study sought to understand public perceptions, the perceived value of SCGI’s ecosystem service benefits, and the potential for diverse financial compensation methods in sponge city construction. A survey conducted in five Northeastern Chinese cities, involving 1,534 participants, was analyzed using descriptive statistics and logistic regression. The findings reveal no significant correlation between socio-demographic factors and understanding of stormwater management, indicating the concept’s broad accessibility. Public valuation of ecosystem services showed clear priorities, and factors like homeownership and flood experiences significantly impacted the valuation of specific services. Moreover, the study identified a generally positive public attitude towards investing in SCSM, particularly through stormwater fees, underscoring the viability of diverse funding mechanisms. These insights are pivotal for policymakers and urban planners in formulating sustainable and resilient urban water management strategies.

Abstract Sulfate dry-wet cycle erosion significantly affects the mechanical properties of concrete. Investigating the uniaxial compressive stress-strain relationship under these conditions is essential for developing accurate constitutive models. This study analyzes the uniaxial stress-strain curves of concrete subjected to dry-wet cycles in 5% and 15% sulfate solutions. The results show that the initial compaction phase in the stress-strain relationship is particularly pronounced under increasing sulfate concentrations and cycle counts. The concrete experiences an extended compaction phase, which accounts for up to 35.71% of the total strain process. This finding challenge traditional constitutive models, which struggle to accurately describe this phase. To address this issue, the study develops a nonlinear stress-strain model for concrete, incorporating the initial damage caused by sulfate dry-wet cycle erosion, based on Weibull statistical damage mechanics principles. The research indicates that the effects of sulfate concentration and cycle count are predominantly reflected in the pronounced nonlinearity of the skeleton strain function’s opening size (a) and shape characteristics (b), modeled using a fourth-degree polynomial. The model demonstrates an excellent fit to experimental data with an R 2 value of 0.99989, showing that the proposed nonlinear stress-strain relationship effectively captures the uniaxial mechanical behavior of concrete under sulfate dry-wet cycle erosion and provides a robust framework for developing constitutive models in such environments.

Abstract N6-methyladenosine (m6A) is the most prevalent modification found in eukaryotic RNA and played a significant role in various cancers. However, the mechanism by which m6A modification influences cervical cancer (CC) tumorigenesis remains unclear. Therefore, we aim to elucidate the role and mechanism of METTL3 in CC progression. In the present study, we observed a significant upregulation of METTL3 in CC tissues and cell lines. Knockdown of METTL3 resulted in reduced growth, migration, and invasion of CC cells, as well as affected apoptosis, while overexpression of METTL3 reversed these effects. Through a combined analysis of meRIP-seq and Ribo-seq data following METTL3 knockdown, NEK2 was identified as a key target of METTL3 in CC cells. Correlation analysis, MeRIP-qPCR, and luciferase reporter assay suggested that METTL3 regulates NEK2 expression through m6A modification. NEK2 synergized with METTL3 to mediate the malignant phenotype of CC cells. The METTL3-NEK2 axis promoted CC progression by activating the Wnt/β-catenin pathway and inhibiting the apoptosis pathway. In conclusion, METTL3 facilitated the malignant progression of CC and contributed to the formation of the METTL3-NEK2 regulatory axis in an m6A-dependent manner, which represented a potential target for CC therapy.

Abstract This research was intended to compare the clinical efficacy of hepatic arterial infusion chemotherapy (HAIC) in conjunction with lenvatinib and PD1 inhibitors to first-line systemic chemotherapy for advanced intrahepatic cholangiocarcinoma(ICC). The research enrolled advanced ICC patients who underwent HAIC plus lenvatinib and PD1 inhibitor(n = 51) or first-line systemic chemotherapy(cisplatin + gemcitabine, n = 39) between July 2020 to January 2023 in Zhongshan People’s Hospital.Their clinical outcomes were assessed through measurement of parameters encompassing objective response rate (ORR), disease control rate (DCR), median overall survival (mOS), median progression-free survival (mPFS), median duration of response (mDOR), and treatment-related adverse events (TRAEs). In accordance with the RECIST1.1, the ORR in the HAIC + L + P and SC groups was 43.1% and 20.5%, while the DCR was 90.2% and 69.2%, respectively (P = 0.04 and = 0.02, respectively). The change in the maximum diameter of intrahepatic target lesions in patients before and after treatment and the diameter of intrahepatic tumors in the HAIC + L + P group were sharply smaller versus the SC group ( P

Abstract The leafminer Liriomyza trifolii causes severe economic damage on ornamental and horticultural crops in China. Rapid cold hardening (RCH) is a phenomenon where cold tolerance in insects can be significantly enhanced after a short-term acclimation to low temperatures. In this study, the regulation of transcription in response to cold hardening was investigated in L. trifolii adults, and fatty acids and cryoprotectant levels were measured. The composition of fatty acids changed after RCH treatment, and glucose and trehalose levels showed significant accumulation after acclimation, thus indicating that changes in fatty acids and cryoprotectants contribute to RCH in L. trifolii. RNA-seq was used to analyze transcriptional regulation after a 4 h hardening period and showed that differentially expressed genes clustered in multiple metabolic pathways, which indicates the importance of transcriptional regulation in RCH. This study expands our knowledge of biochemical and transcriptional changes in L. trifolii during cold hardening and provides a basis for further investigations aimed at understanding thermal adaptation in insects.

Abstract Accurate classification of rail transit stations is crucial for successful Transit-Oriented Development (TOD) and sustainable urban growth. This paper introduces a novel classification model integrating traditional methodologies with advanced machine learning algorithms. By employing mathematical models, clustering methods, and neural network techniques, the model enhances the precision of station classification, allowing for a refined evaluation of station attributes. A comprehensive case study on the Chengdu rail transit network validates the model’s efficacy, highlighting its value in optimizing TOD strategies and guiding decision-making processes for urban planners and policymakers. The study employs several regression models trained on existing data to generate accurate ridership forecasts, and data clustering using mathematical algorithms reveals distinct categories of stations. Evaluation metrics confirm the rationality and accuracy of the results. Additionally, a neural network achieving high accuracy on labeled data enhances the model’s predictive capabilities for unlabeled instances. The research demonstrates high accuracy, with the Mean Squared Error (MSE) for regression models (Multiple Linear Regression (MLR), Deep-Learning Neural Network (DNN), and K-Nearest Neighbor (KNN)) remaining below 0.012, while the neural networks used for station classification achieve 100% accuracy across seven time intervals and 98.15% accuracy for the eighth, ensuring reliable ridership forecasts and classification outcomes. Accuracy in rail transit station classification is critical, as it not only strengthens the model’s predictive capabilities but also ensures more reliable data-driven decisions for transit planning and development, allowing for more precise ridership forecasts and evidence-based strategies for optimizing TOD. This classification model provides stakeholders with valuable insights into the dynamics and features of rail transit stations, supporting sustainable urban development planning.

Abstract The basal dislocations play a key role in the deformation of hexagonal Mg alloys. However, its core structure and mechanical behavior have thus far not yet been understood adequately, largely owing to the fact that the basal dislocation, often decorated with segregated solute atmosphere and dissociated into two partials, cannot be modeled accurately. Significant discrepancies exist between theoretically calculated and experimentally observed structures for these dissociated dislocations. Here we present a comprehensive theoretical scheme to model them in the Mg alloys with alloying elements of Y, Zn, Al and Li, respectively. Firstly, solute–dislocation interactions were computed by appropriate first-principles calculations. Secondly, the statistic solute concentration at a dislocation is estimated by a Fermi–Dirac distribution. Finally, all these effects on dislocations are integrated into an improved two-dimensional Peierls–Nabarro model to predict their core structures and mechanical behaviors in Mg alloys. It is shown that although Zn, Al and Li atoms have little effect on basal dislocations, Y atoms can largely increase their dissociated width. Furthermore, when it moves from its ground state configuration, the dissociated dislocation can further be widened, such that its dissociated widths in a Mg–0.8Y (at%) alloy at 300 K can reach 12–36 nm, in rather good agreement with the experimentally observed values of 20–30 nm. Besides, the Peierls and yield stresses of Mg alloys shall increase with increasing added solute concentration, while they are decreased drastically with increasing the temperature from 300 to 800 K, but with the Mg-Y alloy as somewhat exception, which is again consistent with experimental observations.

Abstract Fructose injection is occasionally used to dilute ademetionine 1,4-butanedisulfonate injection for patients who cannot receive glucose or sodium chloride injections in clinical settings. Since our PIVAS staff reported that discoloration occurred after ademetionine 1,4-butanedisulfonate dissolved with fructose injection, this study aims to investigate the stability of ademetionine 1,4-butanedisulfonate in fructose and glucose solutions. Ademetionine 1,4-butanedisulfonate was purchased and diluted with fructose or glucose injection for compatibility testing. The solutions were maintained under various conditions for different periods of time, after which the concentration of ademetionine 1,4-butanedisulfonate and other impurities was analyzed. The chemical structures of unknown impurities were further investigated by liquid chromatography-tandem mass spectrometry. The analytical method was validated and was deemed to be suitable for the analyses in this study. Compatibility tests indicated that ademetionine 1,4-butanedisulfonate is sensitive to temperature, illumination, and pH. When diluted with fructose or glucose, the concentration of ademetionine 1,4-butanedisulfonate decreased over time. The contents of impurities increased accordingly. Additionally, an unknown impurity was identified, speculated to be a hydroxyl oxidation product of ademetionine based on the LC-MS/MS results. Both fructose and glucose injections can be used as diluents for ademetionine 1,4-butanedisulfonate, and the resulting mixture remains stable for up to 8 h after preparation.

Abstract This study aimed to investigate whether the plant DNA damage levels and DNA damage response (DDR) are regulated during Agrobacterium infection and potentially manipulated by Agrobacterium to facilitate T-DNA integration. We investigated the plant genomic response to Agrobacterium infection by measuring gamma H2AX levels, which reflect the levels of double-strand DNA breaks (DSBs), and by characterizing transcription of three major DNA repair marker genes NAC82, KU70, and AGO2. These experiments revealed that, globally, Agrobacterium infection did not result in a major increase in DSB content in the host genome. The transcription of the DNA damage repair genes, on the other hand, was elevated upon the wild-type Agrobacterium infection. This transcriptional outcome was largely negated by a mutation in the bacterial virB5 gene which encodes the virulence (Vir) protein B5, a minor component of Agrobacterium pilus necessary for the translocation of Vir effector proteins into the host cell, suggesting that the transcriptional activation of the cellular DNA damage repair machinery requires the transport into the host cell of the Agrobacterium effectors, i.e., the VirD2, VirD5, VirE2, VirE3, and VirF proteins. Most likely, a combination of several of these Vir effectors is required to activate the host DNA repair as their individual loss- or gain-of-function mutants did not significantly affect this process.

Abstract Urethral reconstruction presents a challenging issue in urology, primarily due to the limited availability of alternative materials for repair. The advancement of bioengineering technology has brought new hope to researchers, with a focus on the selection of appropriate biological scaffolds and seed cells. In order to find an ideal alternative material, we used platelet-rich fibrin as the bioscaffold and urothelial cells as the seed cells, meanwhile, we intended to investigate the effect of platelet-rich fibrin on the biological properties of urothelial cells. We transformed and characterised induced pluripotent stem cells into urothelial cells and prepared platelet-rich fibrin. Platelet-rich fibrin was cultured in a complex with urothelial cells to observe the effect of platelet-rich fibrin on the proliferation and migration ability of urothelial cells. The results showed that the induced pluripotent stem cells were successfully transformed into urothelial cells, platelet-rich fibrin was regularly arranged in cords, with platelets and other structures distributed between them, and the proliferation and migration of urothelial cells were significantly increased. These results suggested that platelet-rich fibrin is biocompatible with urothelial cells and it promotes the proliferation and migration of urothelial cells, which lays a good foundation for its use as an alternative material for urethral repair.

Abstract Metastatic colorectal cancer continues to have a high fatality rate, with approximately only 14% of patients surviving more than 5 years. To improve the survival rate of these patients, the development of new therapeutic drugs is a priority. In this study, we investigated the effects of Oroxylin A on the metastasis of human colorectal cancer cells and its potential molecular mechanism. This study utilised CCK8 assay, transwell assay, flow cytometry, western blot analysis, molecular docking, HE staining, immunofluorescence staining, and xenograft models. The proliferation, migration, and invasion of colon cancer cells were effectively suppressed by Oroxylin A in a dose-dependent manner. Oroxylin A has the potential to inhibit the process of epithelial‒mesenchymal transition (EMT) by upregulating the expression of E-cadherin, a marker associated with epithelial cells, while downregulating the levels of N-cadherin, Snail, vimentin, and slug, which are markers associated with mesenchymal cells. In addition, 200 mg/kg of Oroxylin A inhibited the growth of colorectal tumours. Molecular docking technology revealed that Oroxylin A can bind to TGFβ and inhibit the activation of the TGFβ-smad signalling pathway. The overexpression of TGFβ weakened the inhibitory effect of Oroxylin A on the proliferation, migration, and invasion of human colorectal cancer cells, as well as the promoting effect on apoptosis. Oroxylin A inhibited the activation of the TGF-smad signalling pathway and the EMT process, thereby suppressing the migration and invasion of human colorectal cancer cells.

Abstract Chronic heart failure (CHF) can induce chronic kidney disease (CKD), called type 2 cardio-renal syndrome (CRS2). The mechanism is not completely clear, and there is a lack of early warning biomarkers of CKD in the context of CHF. Two CKD, one CHF-PBMC and four CHF-cardiac tissue expression profile datasets were obtained from GEO database. Differential expression analysis and WGCNA were used to detect CKD key genes and CHF-related secreted proteins. Protein–protein interaction (PPI), functional enrichment, and cMAP analysis reveal potential mechanisms and drugs of CHF-related CKD. Five machine learning algorithms were used to screen candidate biomarkers, construct a diagnostic nomogram for CKD and validate it in two external cohorts. Clinical serum samples were collected in our hospital to evaluate the correlation and diagnostic value of biomarkers and CKD. 225 CKD key genes and 316 CHF-related secreted proteins were identified. Four key subgroups, including 204 genes, were identified as CRS2-related pathogenic genes by PPI analysis. Enrichment analysis revealed that the identified subgroups exhibited significant enrichment in cytokine action, immune responses, and inflammatory processes. The cMAP analysis highlighted metiradone as a drug with greater potential for therapeutic intervention for CRS2. Utilizing five machine learning algorithms, three hub genes (CD48, COL3A1, LOXL1) were pinpointed as potential biomarkers for CKD, and a nomogram model was constructed. Receiver operating characteristic analysis demonstrated that the nomogram’s area under the curve (AUC) exceeded 0.80 in both the CKD combined dataset and two external cohorts. In addition, the three biomarkers were significantly correlated with the glomerular filtration rate, and the AUC of the model predicting disease progression was 0.944. Furthermore, analysis of immune cell infiltration indicated a correlation between the three biomarkers and the infiltration fraction of macrophages, neutrophils, and other immune cells in CKD. Our clinical cohort validated the expression patterns of three biomarkers in serum, and the diagnostic model achieved an AUC of 0.876. CHF has the potential to facilitate the progression of CKD via the release of cardiac and PBMC secreted proteins. Furthermore, CD48, COL3A1, and LOXL1 have been identified as potential biomarkers for the detection of CKD.

Abstract To evaluate the prognosis and influencing factors of retinal vein occlusion (RVO) in patients with concomitant carotid artery disease receiving anti-vascular endothelial growth factor (VEGF) treatment. Patients diagnosed with RVO and receiving anti-VEGF treatment were included. Eye and clinical data were collected. The patients were divided into a group with concomitant carotid artery disease (Group A) and a group without concomitant carotid artery disease (Group B). The risk factors affecting the visual prognosis of RVO patients with concomitant carotid artery disease were analyzed. Among 177 eligible patients with RVO, 101 had concomitant carotid artery disease (Group A), while 76 did not (Group B). Group A had a significantly lower treatment effectiveness rate than Group B (P

Abstract To endow the prey with intelligent movement behavior and improve the performance of Golden Jackal Optimization (GJO), a Q-learning Improved Gold Jackal Optimization (QIGJO) algorithm is proposed. This paper introduces five update mechanisms and proposes double-population Q-learning collaborative mechanism to select appropriate update mechanisms to improve GJO performance. Additionally, a new convergence factor is incorporated to enhance convergence capability of GJO. QIGJO demonstrates excellent performance across 23 benchmark functions, CEC2022, and three classical engineering design problems, indicating high convergence accuracy and significantly enhanced global exploration capability. The reliability optimization model of the hydraulic system for concrete pump trucks was established based on a Continuous-time Multi-dimensional T-S dynamic Fault Tree (CM-TSdFT), considering the two-dimensional factors of operating time and number of impacts. Utilizing QIGJO to optimize this model yielded excellent results, providing valuable methodological support for reliability optimization of hydraulic systems.

Abstract Prior research show that relative deprivation can decrease individuals’ psychological well-being. However, the underlying mechanism between relative deprivation and psychological well-being remains unclear. To explore the mediating effects of self-efficacy and self-control on the relationship between relative deprivation and psychological well-being. 426 undergraduate students submitted the online survey that assessed their psychological well-being, relative deprivation, self-efficacy and self-control. Students experienced high levels of psychological well-being, moderate to high levels of relative deprivation and moderate levels of self-efficacy and self-control. Parallel mediators of self-efficacy and self-control on the relationship between relative deprivation and psychological well-being were significant (each p

Abstract This study examined the association between visual impairment, visual impairment corrected by wearing eyeglasses, academic performance, and mental health among junior high school students in rural China. Visual acuity assessments were conducted on 19,425 junior high school students by trained medical and research professionals to determine the presence of visual impairment. All sample students were surveyed with a questionnaire that asked about individual and family characteristics, eyeglasses ownership, and educational aspirations and included a standardized math test. Students then completed an official Chinese simplified version of the Strengths and Difficulties Questionnaire (SDQ) to assess their mental health multidimensionally. Among our sample, 37.2% of them suffered from visual impairment, but only 43.4% of the visually impaired students wore proper eyeglasses. Approximately 9.3% of students were categorized as high risk for mental health problems based on their SDQ score. A significant positive association existed between impaired vision and poorer mental health, and eyeglasses usage was associated with better mental health among visually impaired students. For students with better academic performance, eyeglasses usage associated with better mental health. Eyeglasses usage shows a positive association with higher education aspiration both for students with better and worse academic performance. The significant positive relationship between eyeglasses usage and mental health may guide future interventions and policies designed to improve student mental health by supplying them with eyeglasses.