Nanoscale covalent organic frameworks for enhanced photocatalytic hydrogen production.

Nanosizing confers unique functions in materials such as graphene and quantum dots. Here, we present two nanoscale-covalent organic frameworks (nano-COFs) that exhibit exceptionally high activity for photocatalytic hydrogen production that results from their size and morphology. Compared to bulk analogues, the downsizing of COFs crystals using surfactants provides greatly improved water dispersibility and light-harvesting properties. One of these nano-COFs shows a hydrogen evolution rate of 392.0 mmol g-1 h-1 (33.3 µmol h-1), which is one of the highest mass-normalized rates reported for a COF or any other organic photocatalysts. A reverse concentration-dependent photocatalytic phenomenon is observed, whereby a higher photocatalytic activity is found at a lower catalyst concentration. These materials also show a molecule-like excitonic nature, as studied by photoluminescence and transient absorption spectroscopy, which is again a function of their nanoscale dimensions. This charts a new path to highly efficient organic photocatalysts for solar fuel production.

Nutrient responses of vascular plants to N2-fixing tree Alnus hirsuta encroachment in a boreal peatland.

The N2-fixing trees Alnus spp. have been widely encroaching into boreal peatlands, but the nutrient responses of native vascular plants remain unclear. Here, we compared nutrient concentrations and isotope signal of six common plants (Betula fruticosa, Salix rosmarinifolia, Vaccinium uliginosum, Rhododendron tomentosum, Chamaedaphne calyculata, and Eriophorum vaginatum) between Alnus hirsuta island and open peatland and assessed plant nutrient responses to A. hirsuta encroachment in boreal peatlands. Alnus hirsuta encroachment increased nitrogen (N) concentration of leaf, branch, and stem. Despite no significant interspecific difference in branch and stem, the increment magnitude of leaf N concentration varied among species, with greatest magnitude for R. tomentosum (55.1% ± 40.7%) and lowest for E. vaginatum (9.80% ± 4.40%) and B. fruticosa (18.4% ± 10.7%). Except for E. vaginatum, the significant increase in δ15N occurred for all organs of shrubs, with interspecific differences in change of leaf δ15N. According to the mass balance equation involving leaf δ15N, R. tomentosum and E. vaginatum, respectively, obtained highest (40.5% ± 19.8%) and lowest proportions (-14.0% ± 30.5%) of N from A. hirsuta. Moreover, the increment magnitudes of leaf N concentration showed a positive linear relationship with the proportion of N from A. hirsuta. In addition, A. hirsuta encroachment reduced leaf phosphorus (P) concentration of deciduous shrubs (i.e., B. fruticosa, S. rosmarinifolia, and V. uliginosum), thus increasing N:P ratio. These findings indicate that Alnus encroachment improves native plant N status and selectively intensifies P limitation of native deciduous shrubs, and highlight that the N acquisition from the symbiotic N2-fixing system regulates plant N responses in boreal peatlands.

An NMR study on the keto-enol tautomerism of 1,3-dicarbonyl drug precursors.

The effective implementation of drug precursor legislation has driven the innovation and design of new alternative substances. The application of 1,3-dicarbonyl precursors as alternative precursors for the synthesis of 1-phenyl-2-propanone (P2P) and 3,4-methylenedioxyphenyl-2-propanone (MDP2P) has created new challenges to legal control. Their 1,3-dicarbonyl structure allows the precursors to exist as an equilibrium mixture of the tautomeric diketo and keto-enolic forms during the nuclear magnetic resonance (NMR) analysis. In this study, the keto-enol tautomerism of four 1,3-dicarbonyl drug pre-precursors, α-phenylacetoacetamide (APAA), methyl α-phenylacetoacetate (MAPA), ethyl α-phenylacetoacetate (EAPA), and methyl 2-(benzo[d][1,3]dioxol-5-yl)-3-oxobutanoate (MAMDPA) were investigated through NMR. One-dimensional (1D) and 2D NMR were combined to assign signals for the diketo and keto-enolic tautomers. Results showed that the keto-enol tautomerism was solvent-dependent but was also influenced by the substituent present in the molecule. Further, the analysis results indicated that majority of substances existed mainly in the diketo form. The enol-keto equilibrium constant (Keq) was stable in dimethyl sulfoxide-d6 and chloroform-d, while unstable for some compounds in acetone-d6 and deuterated methanol. The presence of impurities in the seized sample may disrupt the equilibrium between keto-enol tautomers in 1,3-dicarbonyl precursors. After the optimization of several key quantitative parameters, a quantitative NMR method for the quantification of 1,3-dicarbonyl drug precursors were also developed to facilitate their quantitative analysis. This is the first study to investigate the keto-enol tautomerism and quantification of 1,3-dicarbonyl drug precursors by NMR, providing a new approach for structure analysis and quantification of new precursor analogues.

Prevalence of mild cognitive impairment and modifiable risk factors: A cross-sectional study in rural older adults with diabetes.

To determine the prevalence and modifiable risk factors for MCI in older adults with T2DM in rural China. This cross-sectional study encompassed 96 villages, employing a cluster sampling approach to recruit eligible older adults with T2DM as study participants. Logistic regression analysis was utilized to identify modifiable risk factors associated with MCI. Average marginal effects were calculated. The discriminatory performance of these risk factors in identifying MCI was evaluated by plotting the receiver operating curve and calculating the value of the area under the curve. A total of 898 older adults with T2DM in our study. The overall prevalence of MCI was 50.22 %. Independent associations with MCI were found in poor self-management ability of diabetes (OR = 0.808, 95 % CI: 0.808, 0.766), depressive symptoms (OR = 3.500, 95 % CI: 1.933, 6.337), moderate (OR = 0.936, 95 % CI: 0.017, 0.075) and high (OR = 0.939, 95 % CI: 0.016, 0.100) levels of physical activity, poorer oral health (OR = 2.660, 95 % CI: 2.226, 3.179), and lower grip strength (OR = 0.913, 95 % CI: 0.870, 0.958). The AUC was 0.967 (95 % CI 0.508-0.470). The prevalence of MCI was high among older adults with T2DM in rural areas of China. The self-management ability of diabetes, depressive symptoms, physical activity, oral health and grip strength were modifiable risk factors of MCI. Targeted interventions should be developed and implemented to address these modifiable risk factors, aiming to enhance cognitive function and mitigate the incidence of MCI in older adults with T2DM.

Analysis of Bending Deformation and Stress of 6063-T5 Aluminum Alloy Multi-Cavity Tube Filled with Liquid.

The production of aluminum alloy multi-lumen tubes primarily involves hot bending formation, a process where controlling thermal deformation quality is difficult. Specifically, the inner cavity wall of the tube is prone to bending instability defects under the bending stress field. To address these challenges in the bending deformation of aluminum alloy multi-lumen tubes, a multi-lumen liquid-filled bypass forming method is proposed in this paper. This study focuses on the 6063-T5 aluminum alloy double-lumen tube as the research object. The liquid-filled bending deformation behavior of the aluminum alloy double-lumen tube was investigated, and the deformation theory of the aluminum alloy double-lumen tube was studied. Through experimental and numerical simulation methods, the influence of support internal pressure, bending radius, and tube wall thickness on the liquid-filled bending deformation behavior of the double-lumen tube was examined. The results indicate that when the value of internal pressure was 7.5 MPa, the straightening of the outer wall was improved by 2.51%, the thinning rate of wall thickness was minimized, and the internal concave defect was effectively suppressed. The liquid-filled bending method provides a promising new approach for the integrated bending and forming of multi-lumen tubes.

Global distribution and drivers of relative contributions among soil nitrogen sources to terrestrial plants.

Soil extractable nitrate, ammonium, and organic nitrogen (N) are essential N sources supporting primary productivity and regulating species composition of terrestrial plants. However, it remains unclear how plants utilize these N sources and how surface-earth environments regulate plant N utilization. Here, we establish a framework to analyze observational data of natural N isotopes in plants and soils globally, we quantify fractional contributions of soil nitrate (fNO3-), ammonium (fNH4+), and organic N (fEON) to plant-used N in soils. We find that mean annual temperature (MAT), not mean annual precipitation or atmospheric N deposition, regulates global variations of fNO3-, fNH4+, and fEON. The fNO3- increases with MAT, reaching 46% at 28.5 °C. The fNH4+ also increases with MAT, achieving a maximum of 46% at 14.4 °C, showing a decline as temperatures further increase. Meanwhile, the fEON gradually decreases with MAT, stabilizing at about 20% when the MAT exceeds 15 °C. These results clarify global plant N-use patterns and reveal temperature rather than human N loading as a key regulator, which should be considered in evaluating influences of global changes on terrestrial ecosystems.

Exonuclease III/Cas12a Cascade Amplification Strategy and Smartphone-Based Portable Fluorescence Detector to Repurpose the Commercial AFP Strip for the POCT of Multiple RNAs.

Point of care testing (POCT) of nucleic acid (NA) contributes to the timely disease diagnosis, like bacteria and virus screening in households or resource-constrained areas, but its development has always been stagnant. Herein, we proposed an exonuclease III cascaded with CRISPR/Cas12a (Exo-III/Cas12a) amplification strategy and constructed a smartphone-based portable fluorescence detector (SPFD) to repurpose the commercial alpha-fetoprotein (AFP) strip for the ultrasensitive and hand-held detection of NA samples. In detail, the target-initiated-Exo-III/Cas12a strategy realizes the signal amplification and liberates AFP from magnetic beads through the trans-cleavages of activated Cas12a toward the AFP aptamer. After magnetic separation and migration, the fluorescence signals of the test (FT) and control (FC) lines on the AFP strip were digitally output by the SPFD, and the FT/FC was employed for the quantitative analysis to minimize external disturbances and improve accuracy. We experimentally assessed the universe applicability of the proposed NA-POCT platform toward miRNA-155, 16S rRNA of Staphylococcus aureus, and ORF1a/b RNA of Covid-19 pseudovirus, achieving favorable detection limits of 42 aM, 18 CFU/mL, and 87 copies/µL, respectively. Moreover, its simplicity, universality, and admirable detection performance demonstrate a great potential in the aspect of rapidly transforming the existing POCT devices for multiple new applications at the time of need.

Exosomes repairment for sciatic nerve injury: a cell-free therapy.

Sciatic nerve injury (SNI) is a common type of peripheral nerve injury typically resulting from trauma, such as contusion, sharp force injuries, drug injections, pelvic fractures, or hip dislocations. It leads to both sensory and motor dysfunctions, characterized by pain, numbness, loss of sensation, muscle atrophy, reduced muscle tone, and limb paralysis. These symptoms can significantly diminish a patient's quality of life. Following SNI, Wallerian degeneration occurs, which activates various signaling pathways, inflammatory factors, and epigenetic regulators. Despite the availability of several surgical and nonsurgical treatments, their effectiveness remains suboptimal. Exosomes are extracellular vesicles with diameters ranging from 30 to 150 nm, originating from the endoplasmic reticulum. They play a crucial role in facilitating intercellular communication and have emerged as highly promising vehicles for drug delivery. Increasing evidence supports the significant potential of exosomes in repairing SNI. This review delves into the pathological progression of SNI, techniques for generating exosomes, the molecular mechanisms behind SNI recovery with exosomes, the effectiveness of combining exosomes with other approaches for SNI repair, and the changes and future outlook for utilizing exosomes in SNI recovery.

Regulatory emotional self-efficacy and self-compassion mediate anxiety, depression, body image distress and subjective well-being in women with polycystic ovary syndrome: A cross-sectional study.

AIMS: This study aims to investigate the mediating role of regulatory emotional self-efficacy and self-compassion in the relationship among anxiety, depression, body image distress and subjective well-being among women with polycystic ovary syndrome. DESIGN: A cross-sectional study. METHODS: The study recruited 510 women with polycystic ovary syndrome from a tertiary hospital affiliated with a university in Hunan Province, China. The study employed several tools to collect data, including the Generalized Anxiety Scale, the Patient Health Questionnaire-9, the Body Image States Scale, the Self-Compassion Scale, the Regulatory Emotional Self-Efficacy Scale and the Index of Well-being questionnaire. Data analysis was carried out using descriptive analysis, spearman correlation analysis, ordinary least squares regression and bootstrapping. RESULTS: The study's findings indicate that regulatory emotional self-efficacy and self-compassion both act as mediators in the connection between anxiety, depression, body image distress and subjective well-being among women with polycystic ovary syndrome. CONCLUSION: The study emphasizes the significance of regulatory emotional self-efficacy and self-compassion in promoting well-being among women with polycystic ovary syndrome. It also implies that interventions targeted at enhancing these factors could potentially enhance the subjective well-being of women affected by PCOS. IMPACT: Our study's primary contribution is to underscore the crucial mediating roles of regulatory emotional self-efficacy and self-compassion in the relationship among anxiety, depression, body image distress and subjective well-being. Our study indicates that clinical practitioners should prioritize improving the regulatory emotional self-efficacy and self-compassion of women with polycystic ovary syndrome, reducing their anxiety, depression and body image distress and improving their subjective well-being. REPORTING METHOD: This study was reported according to the Standards for Reporting Qualitative Research (SRQR). PATIENT OR PUBLIC CONTRIBUTION: No patient or public contribution outside of participation in the actual study for purposes of data collection.

Neuroendocrine carcinoma of the endometrium: a retrospective analysis of data from a single center.

BACKGROUND: Neuroendocrine carcinoma (NEC) originating from the endometrium is rare, and there is limited knowledge regarding its diagnosis and optimal management. In this study, we present our experience with 11 patients with endometrial NEC, aiming to provide guidance for clinical practice. METHODS: We retrospectively collected the clinical, pathological, and treatment data of 11 patients with endometrial NEC who were treated at the First Affiliated Hospital of Zhengzhou University from January 2011 to July 2023. The clinicopathological characteristics, treatment and prognosis of these patients were analyzed. RESULTS: The median age of the patients was 55.0 (39.0-64.0) years, and the median tumor size was 40.0 (33.0-60.0) mm. Irregular vaginal bleeding was the most common symptom observed in 10 out of 11 patients, while metabolic syndrome occurred in only 2 out of 11 patients. Six out of the 11 patients were diagnosed at an early stage. Among the patients, 6 were diagnosed with endometrial NECs, while the remaining patients had a combination of endometrial NEC and other non-NEC endometrial carcinomas. All patients underwent surgery, except for one who received only chemotherapy due to multiple metastases. After surgery, adjuvant chemotherapy was administered to 5 patients, chemotherapy combined with radiotherapy was given to 3 patients, and 2 patients did not receive any adjuvant therapy. A total of 10 patients completed the follow-up, with a median follow-up time of 51.0 (14.3-81.0) months. Unfortunately, 2 patients died from the disease. CONCLUSION: NECs originating from the endometrium might not be affected by metabolic disorders. Preoperative diagnosis of these tumors was challenging. The primary approach for managing endometrial NEC can be multimodal treatment centered around surgery.

Emerging ferroptosis inhibitors as a novel therapeutic strategy for the treatment of neonatal hypoxic-ischemic encephalopathy.

Neonatal hypoxia-ischemia encephalopathy (NHIE), an oxygen deprivation-mediated brain injury due to birth asphyxia or reduced cerebral blood perfusion, often leads to lifelong sequelae, including seizures, cerebral palsy, and mental retardation. NHIE poses a significant health challenge, as one of the leading causes of neonatal morbidity and mortality globally. Despite this, available therapies are limited. Numerous studies have recently demonstrated that ferroptosis, an iron-dependent non-apoptotic regulated form of cell death characterized by lipid peroxidation (LPO) and iron dyshomeostasis, plays a role in the genesis of NHIE. Moreover, recently discovered compounds have been shown to exert potential therapeutic effects on NHIE by inhibiting ferroptosis. This comprehensive review summarizes the fundamental mechanisms of ferroptosis contributing to NHIE. We focus on various emerging therapeutic compounds exhibiting characteristics of ferroptosis inhibition and delineate their pharmacological benefits for the treatment of NHIE. This review suggests that pharmacological inhibition of ferroptosis may be a potential therapeutic strategy for NHIE.

Antitumor progenitor exhausted CD8+ T cells are sustained by TCR engagement.

The durability of an antitumor immune response is mediated in part by the persistence of progenitor exhausted CD8+ T cells (Tpex). Tpex serve as a resource for replenishing effector T cells and preserve their quantity through self-renewal. However, it is unknown how T cell receptor (TCR) engagement affects the self-renewal capacity of Tpex in settings of continued antigen exposure. Here we use a Lewis lung carcinoma model that elicits either optimal or attenuated TCR signaling in CD8+ T cells to show that formation of Tpex in tumor-draining lymph nodes and their intratumoral persistence is dependent on optimal TCR engagement. Notably, attenuated TCR stimulation accelerates the terminal differentiation of optimally primed Tpex. This TCR-reinforced Tpex development and self-renewal is coupled to proximal positioning to dendritic cells and epigenetic imprinting involving increased chromatin accessibility at Egr2 and Tcf1 target loci. Collectively, this study highlights the critical function of TCR engagement in sustaining Tpex during tumor progression.

A new nomogram model for the individualized prediction of mild cognitive impairment in elderly patients with type 2 diabetes mellitus.

Background: A high risk of developing mild cognitive impairment (MCI) is faced by elderly patients with type 2 diabetes mellitus (T2DM). In this study, independent risk factors for MCI in elderly patients with T2DM were investigated, and an individualized nomogram model was developed. Methods: In this study, clinical data of elderly patients with T2DM admitted to the endocrine ward of the hospital from November 2021 to March 2023 were collected to evaluate cognitive function using the Montreal Cognitive Assessment scale. To screen the independent risk factors for MCI in elderly patients with T2DM, a logistic multifactorial regression model was employed. In addition, a nomogram to detect MCI was developed based on the findings of logistic multifactorial regression analysis. Furthermore, the accuracy of the prediction model was evaluated using calibration and receiver operating characteristic curves. Finally, decision curve analysis was used to evaluate the clinical utility of the nomogram. Results: In this study, 306 patients were included. Among them, 186 patients were identified as having MCI. The results of multivariate logistic regression analysis demonstrated that educational level, duration of diabetes, depression, glycated hemoglobin, walking speed, and sedentary duration were independently correlated with MCI, and correlation analyses showed which influencing factors were significantly correlated with cognitive function (p <0.05). The nomogram based on these factors had an area under the curve of 0.893 (95%CI:0.856-0.930)(p <0.05), and the sensitivity and specificity were 0.785 and 0.850, respectively. An adequate fit of the nomogram in the predictive value was demonstrated by the calibration plot. Conclusions: The nomogram developed in this study exhibits high accuracy in predicting the occurrence of cognitive dysfunction in elderly patients with T2DM, thereby offering a clinical basis for detecting MCI in patients with T2DM.

Risk factors and prediction model construction for peripherally inserted central catheter-related infections.

Objective: To establish a predictive modeling for the risk of bloodstream infection associated with peripherally inserted central catheter (PICC). Methods: Patients receiving PICC treatment in Shenzhen People's Hospital from June 2020 to December 2020 were retrospectively enrolled and divided into the infection group and the non-infection group according to the presence and absence of PICC-related infections. Then, relevant clinical information of patients was collected and the predictors of PICC-related infection were screened by the least absolute shrinkage and selection operator regression (LASSO) model. Besides, multivariate logistic regression was used to analyze the influencing factors of PICC-related infection, A nomogram was constructed based on the results of the multivariate analysis. Ultimately, a receiver operating characteristic (ROC) curve was plotted to analyze the application value of influencing factors to predict PICC-related infections. Results: A total of 505 patients were included, including 75 patients with PICC-related infections (14.85%). The main pathogen was gram-positive cocci. The predictors screened by LASSO included age >60 years, catheter movement, catheter maintenance cycle, insertion technique, immune function, complications, and body temperature ≥37.2 °C before PICC placement. Multivariate logistic regression analysis showed that independent risk factors of infections related to PICC included age >60 years [odds ratio (OR) = 1.722; 95% confidence interval (CI) = 1.312-3.579; P = 0.006], catheter movement (OR = 1.313; 95% CI = 1.119-3.240; P = 0.014), catheter maintenance cycle >7 days (OR = 2.199; 95% CI = 1.677-4.653; P = 0.000), direct insertion (OR = 1.036; 95% CI = 1.019-2.743; P = 0.000), poor immune function (OR = 2.322; 95% CI = 2.012-4.579; P = 0.000), complications (OR = 1.611; 95% CI = 1.133-3.454; P = 0.019), and body temperature ≥37.2 °C before PICC placement (OR = 1.713; 95% CI = 1.172-3.654; P = 0.012). Besides, the area under the ROC curve was 0.889. Conclusion: PICC-related infections are associated with factors such as age >60 years, catheter movement, catheter maintenance cycle, insertion technique, immune function, complications, and body temperature ≥37.2 °C before PICC placement. Additionally, the LASSO model is moderately predictive for predicting the occurrence of PICC-related infections.

DRANetSplicer: A Splice Site Prediction Model Based on Deep Residual Attention Networks.

The precise identification of splice sites is essential for unraveling the structure and function of genes, constituting a pivotal step in the gene annotation process. In this study, we developed a novel deep learning model, DRANetSplicer, that integrates residual learning and attention mechanisms for enhanced accuracy in capturing the intricate features of splice sites. We constructed multiple datasets using the most recent versions of genomic data from three different organisms, Oryza sativa japonica, Arabidopsis thaliana and Homo sapiens. This approach allows us to train models with a richer set of high-quality data. DRANetSplicer outperformed benchmark methods on donor and acceptor splice site datasets, achieving an average accuracy of (96.57%, 95.82%) across the three organisms. Comparative analyses with benchmark methods, including SpliceFinder, Splice2Deep, Deep Splicer, EnsembleSplice, and DNABERT, revealed DRANetSplicer's superior predictive performance, resulting in at least a (4.2%, 11.6%) relative reduction in average error rate. We utilized the DRANetSplicer model trained on O. sativa japonica data to predict splice sites in A. thaliana, achieving accuracies for donor and acceptor sites of (94.89%, 94.25%). These results indicate that DRANetSplicer possesses excellent cross-organism predictive capabilities, with its performance in cross-organism predictions even surpassing that of benchmark methods in non-cross-organism predictions. Cross-organism validation showcased DRANetSplicer's excellence in predicting splice sites across similar organisms, supporting its applicability in gene annotation for understudied organisms. We employed multiple methods to visualize the decision-making process of the model. The visualization results indicate that DRANetSplicer can learn and interpret well-known biological features, further validating its overall performance. Our study systematically examined and confirmed the predictive ability of DRANetSplicer from various levels and perspectives, indicating that its practical application in gene annotation is justified.

RyR2 Stabilizer Attenuates Cardiac Hypertrophy by Downregulating TNF-α/NF-κB/NLRP3 Signaling Pathway through Inhibiting Calcineurin.

The effect of Ryanodine receptor2 (RyR2) and its stabilizer on cardiac hypertrophy is not well known. C57/BL6 mice underwent transverse aortic contraction (TAC) or sham surgery were administered dantrolene, the RyR2 stabilizer, or control drug. Dantrolene significantly alleviated TAC-induced cardiac hypertrophy in mice, and RNA sequencing was performed implying calcineurin/NFAT3 and TNF-α/NF-κB/NLRP3 as critical signaling pathways. Further expression analysis and Western blot with heart tissue as well as neonatal rat cardiomyocyte (NRCM) model confirmed dantrolene decreases the activation of calcineurin/NFAT3 signaling pathway and TNF-α/NF-κB/NLRP3 signaling pathway, which was similar to FK506 and might be attenuated by calcineurin overexpression. The present study shows for the first time that RyR2 stabilizer dantrolene attenuates cardiac hypertrophy by inhibiting the calcineurin, therefore downregulating the TNF-α/NF-κB/NLRP3 pathway.

Targeting novel regulated cell death：Ferroptosis, pyroptosis, and autophagy in sepsis-associated encephalopathy.

Sepsis-associated encephalopathy (SAE), a common neurological complication of sepsis, is a heterogenous complex clinical syndrome caused by the dysfunctional response of a host to infection. This dysfunctional response leads to excess mortality and morbidity worldwide. Despite clinical relevance with high incidence, there is a lack of understanding for its both its acute/chronic pathogenesis and therapeutic management. A better understanding of the molecular mechanisms behind SAE may provide tools to better enhance therapeutic efficacy. Mounting evidence indicates that some types of non-apoptotic regulated cell death (RCD), such as ferroptosis, pyroptosis, and autophagy, contribute to SAE. Targeting these types of RCD may provide meaningful targets for future treatments against SAE. This review summarizes the core mechanism by which non-apoptotic RCD leads to the pathogenesis of SAE. We focus on the emerging types of therapeutic compounds that can inhibit RCD and delineate their beneficial pharmacological effects against SAE. Within this review we suggest that pharmacological inhibition of non-apoptotic RCD may serve as a potential therapeutic strategy against SAE.

Polystyrene microplastics induce anxiety via HRAS derived PERK-NF-κB pathway.

Exposure to environmentally hazardous substances is recognized as a significant risk factor for neurological associated disorders. Among these substances, polystyrene microplastics (PS-MPs), widely utilized in various consumer products, have been reported to exhibit neurotoxicity. However, the potential association of PS-MPs with abnormal anxiety behaviors, along with the underlying molecular mechanisms and key proteins involved, remains insufficiently explored. Here, we delineated the potential mechanisms of PS-MPs-induced anxiety through proteomics and molecular investigations. We characterized the PS-MPs, observed their accumulation in the brain, leading to anxiety-like behavior in mice, which is correlated with microglia activation and pro-inflammatory response. Consistent with these findings, our studies on BV2 microglia cells showed that PS-MPs activated NF-κB-mediated inflammation resulting in the upregulation of pro-inflammatory cytokines such as TNFα and IL-1ß. Of particular significance, HRAS was identified as a key factor in the PS-MPs induced pro-inflammatory response through whole proteomics analysis, and knockdown of H-ras effectively inhibited PS-MPs induced PERK-NF-κB activation and associated pro-inflammatory response in microglia cells. Collectively, our findings highlight that PS-MPs induce anxiety of mice via the activation of the HRAS-derived PERK-NF-κB pathway in microlglia. Our results contribute valuable insights into the molecular mechanisms of PS-MPs-induced anxiety, and may offer implications for addressing neurotoxicity and prevention the adverse effects of environmentally hazardous substances, including microplastics.

A MgAl-LDH-CuS nanosheet-based thermo-responsive composite hydrogel with nir-responsive angiogenesis inhibitor releasing capability for multimode starvation therapy.

The rapid proliferation of tumors is highly dependent on the nutrition supply of blood vessels. Cutting off the nutrient supply to tumors is an effective strategy for cancer treatment, known as starvation therapy. Although various hydrogel-based biomaterials have been developed for starvation therapy through glucose consumption or intravascular embolization, the limitations of single-mode starvation therapy hinder their therapeutic effects. Herein, we propose a dual-function nutrition deprivation strategy that can block the nutrients delivery through extravascular gelation shrinkage and inhibit neovascularization through angiogenesis inhibitors based on a novel NIR-responsive nanocomposite hydrogel. CuS nanodots-modified MgAl-LDH nanosheets loaded with angiogenesis inhibitor (sorafenib, SOR) are incorporated into the poly(n-isopropylacrylamide) (PNIPAAm) hydrogel by radical polymerization to obtain the composite hydrogel (SOR@LDH-CuS/P). The SOR@LDH-CuS/P hydrogel can deliver hydrophobic SOR with a NIR-responsive release behavior, which could decrease the tumor vascular density and accelerate cancer cells apoptosis. Moreover, the SOR@LDH-CuS/P hydrogel exhibits higher (3.5 times) compressive strength than that of the PNIPAAm, which could squeeze blood vessels through extravascular gelation shrinkage. In vitro and in vivo assays demonstrate that the interruption of nutrient supply by gelation shrinkage and the prevention of angiogenesis by SOR is a promising strategy to inhibit tumor growth for multimode starvation therapy.

Discrimination of opium from Afghanistan and Myanmar by infrared spectroscopy coupled with machine learning methods.

Afghanistan and Myanmar are two overwhelming opium production places. In this study, rapid and efficient methods for distinguishing opium from Afghanistan and Myanmar were developed using infrared spectroscopy (IR) coupled with multiple machine learning (ML) methods for the first time. A total of 146 authentic opium samples were analyzed by mid-IR (MIR) and near-IR (NIR), within them 116 were used for model training and 30 were used for model validation. Six ML methods, including partial least squares discriminant analysis (PLS-DA), orthogonal PLS-DA (OPLS-DA), k-nearest neighbour (KNN), support vector machine (SVM), random forest (RF), and artificial neural networks (ANNs) were constructed and compared to get the best classification effect. For MIR data, the average of precision, recall and f1-score for all classification models were 1.0. For NIR data, the average of precision, recall and f1-score for different classification models ranged from 0.90 to 0.94. The comparison results of six ML models for MIR and NIR data showed that MIR was more suitable for opium geography classification. Compared with traditional chromatography and mass spectrometry profiling methods, the advantages of MIR are simple, rapid, cost-effective, and environmentally friendly. The developed IR chemical profiling methodology may find wide application in classification of opium from Afghanistan and Myanmar, and also to differentiate them from opium originating from other opium producing countries. This study presented new insights into the application of IR and ML to rapid drug profiling analysis.