Hyperspectral and Fluorescence Imaging Approaches for Nondestructive Detection of Rice Chlorophyll.

Estimating and monitoring chlorophyll content is a critical step in crop spectral image analysis. The quick, non-destructive assessment of chlorophyll content in rice leaves can optimize nitrogen fertilization, benefit the environment and economy, and improve rice production management and quality. In this research, spectral analysis of rice leaves is performed using hyperspectral and fluorescence spectroscopy for the detection of chlorophyll content in rice leaves. This study generated ninety experimental spectral datasets by collecting rice leaf samples from a farm in Sichuan Province, China. By implementing a feature extraction algorithm, this study compresses redundant spectral bands and subsequently constructs machine learning models to reveal latent correlations among the extracted features. The prediction capabilities of six feature extraction methods and four machine learning algorithms in two types of spectral data are examined, and an accurate method of predicting chlorophyll concentration in rice leaves was devised. The IVSO-IVISSA (Iteratively Variable Subset Optimization-Interval Variable Iterative Space Shrinkage Approach) quadratic feature combination approach, based on fluorescence spectrum data, has the best prediction performance among the CNN+LSTM (Convolutional Neural Network Long Short-Term Memory) algorithms, with corresponding RMSE-Train (Root Mean Squared Error), RMSE-Test, and RPD (Ratio of standard deviation of the validation set to standard error of prediction) indexes of 0.26, 0.29, and 2.64, respectively. We demonstrated in this study that hyperspectral and fluorescence spectroscopy, when analyzed with feature extraction and machine learning methods, provide a new avenue for rapid and non-destructive crop health monitoring, which is critical to the advancement of smart and precision agriculture.

Synthesis and biological evaluation of orally active anti-Trypanosoma agents.

In previous studies, we developed anti-trypanosome tubulin inhibitors with promising in vitro selectivity and activity against Human African Trypanosomiasis (HAT). However, for such agents, oral activity is crucial. This study focused on further optimizing these compounds to enhance their ligand efficiency, aiming to reduce bulkiness and hydrophobicity, which should improve solubility and, consequently, oral bioavailability. Using Trypanosoma brucei brucei cells as the parasite model and human normal kidney cells and mouse macrophage cells as the host model, we evaluated 30 new analogs synthesized through combinatorial chemistry. These analogs have fewer aromatic moieties and lower molecular weights than their predecessors. Several new analogs demonstrated IC50s in the low micromolar range, effectively inhibiting trypanosome cell growth without harming mammalian cells at the same concentration. We conducted a detailed structure-activity relationship (SAR) analysis and a docking study to assess the compounds' binding affinity to trypanosome tubulin homolog. The results revealed a correlation between binding energy and anti-Trypanosoma activity. Importantly, compound 7 displayed significant oral activity, effectively inhibiting trypanosome cell proliferation in mice.

Lipoproteins and metabolites in diagnosing and predicting Alzheimer's disease using machine learning.

BACKGROUND: Alzheimer's disease (AD) is a chronic neurodegenerative disorder that poses a substantial economic burden. The Random forest algorithm is effective in predicting AD; however, the key factors influencing AD onset remain unclear. This study aimed to analyze the key lipoprotein and metabolite factors influencing AD onset using machine-learning methods. It provides new insights for researchers and medical personnel to understand AD and provides a reference for the early diagnosis, treatment, and early prevention of AD. METHODS: A total of 603 participants, including controls and patients with AD with complete lipoprotein and metabolite data from the Alzheimer's disease Neuroimaging Initiative (ADNI) database between 2005 and 2016, were enrolled. Random forest, Lasso regression, and CatBoost algorithms were employed to rank and filter 213 lipoprotein and metabolite variables. Variables with consistently high importance rankings from any two methods were incorporated into the models. Finally, the variables selected from the three methods, with the participants' age, sex, and marital status, were used to construct a random forest predictive model. RESULTS: Fourteen lipoprotein and metabolite variables were screened using the three methods, and 17 variables were included in the AD prediction model based on age, sex, and marital status of the participants. The optimal random forest modeling was constructed with "mtry" set to 3 and "ntree" set to 300. The model exhibited an accuracy of 71.01%, a sensitivity of 79.59%, a specificity of 65.28%, and an AUC (95%CI) of 0.724 (0.645-0.804). When Mean Decrease Accuracy and Gini were used to rank the proteins, age, phospholipids to total lipids ratio in intermediate-density lipoproteins (IDL_PL_PCT), and creatinine were among the top five variables. CONCLUSIONS: Age, IDL_PL_PCT, and creatinine levels play crucial roles in AD onset. Regular monitoring of lipoproteins and their metabolites in older individuals is significant for early AD diagnosis and prevention.

Visible-light-induced C(sp3)-H bromination of 4-methylthiophene derivatives with HBr/H2O2.

A convenient method to synthesize ethyl 4-(bromomethyl)thiophene-3-carboxylate derivatives has been developed via a visible-light-induced radical process in good yields and with wide functional group tolerance under air conditions and at ambient temperature. The present protocol has the advantages of a high atom economy, easy purification, and environmental friendliness as it employs HBr as the bromine source and the cheap and low-toxic H2O2 as the oxidant. The synthetic utility of this method is demonstrated by a gram scale reaction and its application in the innovative synthesis of the clinical drug relugolix.

Screening of key immune-related gene in Parkinson's disease based on WGCNA and machine learning. / 基于WGCNAå’Œæœºå™¨å­¦ä¹ ç­›é€‰å¸•é‡‘æ£®ç— å ç–«ç›¸å ³å ³é”®åŸºå› .

OBJECTIVES: Abnormal immune system activation and inflammation are crucial in causing Parkinson's disease. However, we still don't fully understand how certain immune-related genes contribute to the disease's development and progression. This study aims to screen key immune-related gene in Parkinson's disease based on weighted gene co-expression network analysis (WGCNA) and machine learning. METHODS: This study downloaded the gene chip data from the Gene Expression Omnibus (GEO) database, and used WGCNA to screen out important gene modules related to Parkinson's disease. Genes from important modules were exported and a Venn diagram of important Parkinson's disease-related genes and immune-related genes was drawn to screen out immune related genes of Parkinson's disease. Gene ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) were used to analyze the the functions of immune-related genes and signaling pathways involved. Immune cell infiltration analysis was performed using the CIBERSORT package of R language. Using bioinformatics method and 3 machine learning methods [least absolute shrinkage and selection operator (LASSO) regression, random forest (RF), and support vector machine (SVM)], the immune-related genes of Parkinson's disease were further screened. A Venn diagram of differentially expressed genes screened using the 4 methods was drawn with the intersection gene being hub nodes (hub) gene. The downstream proteins of the Parkinson's disease hub gene was identified through the STRING database and a protein-protein interaction network diagram was drawn. RESULTS: A total of 218 immune genes related to Parkinson's disease were identified, including 45 upregulated genes and 50 downregulated genes. Enrichment analysis showed that the 218 genes were mainly enriched in immune system response to foreign substances and viral infection pathways. The results of immune infiltration analysis showed that the infiltration percentages of CD4+ T cells, NK cells, CD8+ T cells, and B cells were higher in the samples of Parkinson's disease patients, while resting NK cells and resting CD4+ T cells were significantly infiltrated in the samples of Parkinson's disease patients. ANK1 was screened out as the hub gene. The analysis of the protein-protein interaction network showed that the ANK1 translated and expressed 11 proteins which mainly participated in functions such as signal transduction, iron homeostasis regulation, and immune system activation. CONCLUSIONS: This study identifies the Parkinson's disease immune-related key gene ANK1 via WGCNA and machine learning methods, suggesting its potential as a candidate therapeutic target for Parkinson's disease.

A hydrogel-functionalized silver nanocluster for bacterial-infected wound healing.

The ever-growing challenges of traditional antibiotic therapy and chronic wound healing have created a hot topic for the development and application of new antimicrobial agents. Silver nanoclusters (Ag NCs) with ultrasmall sizes (<2 nm) and antibacterial effects are promising candidates for next-generation antibiotics, particularly against multi-drug resistant strains. However, the biosafety in the clinical application of Ag NCs remains suboptimal despite some existing studies of Ag NCs for biomedical applications. Considering this, an ultrasmall Ag NC with excellent water solubility was synthesized by a two-phase ligand-exchange method, which exhibits broad-spectrum antibacterial performance. The minimum inhibitory concentrations of Ag NCs against MRSA, S. aureus, P. aeruginosa and E. coli were evaluated as 50, 80, 5 and 5 µg mL-1, respectively. Furthermore, a carbomer hydrogel was prepared to be incorporated into the Ag NCs for achieving excellent biocompatibility and biosafety. In vitro experiments demonstrate that the Ag NC-gel exhibits good antibacterial properties with lower cytotoxicity. Finally, in vivo experiments suggest that this ultrasmall Ag NC functionalized with the hydrogel can serve as an effective and safe antimicrobial agent to aid in wound healing.

Insulin-like growth factor binding protein-3 (igfbp-3) and igfbp-5 in yellowtail kingfish (Seriola lalandi): molecular characterization and expression levels under different nutritional status and stocking density.

Insulin-like growth factor-binding proteins (IGFBPs) play important roles in regulating growth and development by binding to IGF, where IGFBP-3 and IGFBP-5 are the main binding carriers of IGF in the circulation system. In the present study, the gene sequences of igfbp-3, igfbp-5a, and igfbp-5b were cloned from the liver of yellowtail kingfish (Seriola lalandi). The ORF sequences of igfbp-3, igfbp-5a, and igfbp-5b were 888, 801, and 804 bp in length, which encoded 295, 266, and 267 amino acids, respectively. The above three genes were widely expressed in yellowtail kingfish tissues, with igfbp-3 being the most highly expressed in the heart, brain, and gonads, while igfbp-5a and igfbp-5b were both most highly expressed in the liver and kidney. The expression levels of igfbp-3, igfbp-5a, and igfbp-5b were detected throughout the embryonic and larval stages, suggesting their roles in early development and growth regulation of yellowtail kingfish. Besides, igfbp-3 and igfbp-5a were significantly up-regulated in the liver under food deprivation and high-density rearing conditions, which was exactly opposite to the growth performance of yellowtail kingfish, implying that they may serve as biomarkers of adverse culture conditions. Overall, the above results initially identified the molecular characteristics of igfbp-3/-5a/-5b in yellowtail kingfish and implied that they might play important roles in the growth and development, providing a basis for further research on underlying regulatory mechanisms.

Preparation of porous polylactic acid nanofibers and application in non-electret high-efficiency filtration composites.

Air pollution caused by fine particulate matter (PM0.3) has drawn increasing attention as an overwhelming threat to public health. Electret treatment is commonly used to improve the filtration performance of commercial fibrous filter materials by enhancing the electrostatic adsorption effect, but it is greatly affected by environmental factors (especially humidity). Moreover, filter materials are generally non-degradable and non-recyclable, causing serious environmental pollution. Herein, a strategy to manufacture fully degradable polylactic acid (PLA) filtration composites based on porous PLA nanofibers prepared by electrospinning was investigated in this study. Porous, bead-on-string and conventional PLA nanofibers could be obtained by adjusting spinning condition parameters. The porous PLA nanofibers exhibited 9.8 times greater specific surface area (24.01 m2 g-1) and 18 times more cumulative pore volume (0.108 cm3 g-1) than conventional PLA nanofibers. More importantly, fibrous filtration composites based on porous PLA nanofibers possessed a high PM0.3 filtration efficiency (99.9989%), low pressure drop (90.35 Pa) and high air permeability (72.4 Pa-1) at an air flow rate of 32 L min-1 without electret treatment. The fibrous filtration composites based on conventional or bead-on-string PLA nanofibers also exhibited excellent filtration performance (>99.99%), but the associated high pressure drop and low air permeability limited their application.

Genome-wide characterization of cytochrome P450 genes reveals the potential roles in fruit ripening and response to cold stress in tomato.

Plant cytochrome P450 (CYP) superfamily, the largest enzyme metabolism family, has been identified in many species and plays a vital role in plant development and stress response via secondary metabolite biosynthesis. A comprehensive identification and functional investigation of CYPs in tomato plants would contribute to deeper understanding of their biological significance. In this study, 268 tomato CYP genes were identified and found to be unevenly located on 12 chromosomes. Based on the phylogenetic analysis, these 268 SlCYPs were classed into two distinct clades (A-type and non-A-type) and nine clans, including 48 families. Moreover, 67 tandem and 22 WGD (whole genome duplication)/segmental duplication events were detected, of which 12 SlCYP genes experienced both WGD/segmental and tandem duplication events, indicating that tandem duplication plays a major role in the expansion of the SlCYP family. Besides, 48 pairs containing 41 SlCYP and 44 AtCYP genes were orthologous, while 216 orthologous pairs were obtained between tomato and potato. The expression level of all SlCYP genes in tomato tissues at different development stages was analyzed, and most expressed SlCYPs showed a tissue-specific pattern. Meanwhile, 143 differentially expressed SlCYPs were identified under cold stress. Furthermore, the RT-qPCR results indicated that SlCYPs may be involved in fruit ripening and cold tolerance in tomato seedlings. These findings provide valuable insights into the evolutionary relationships and functional characteristics of SlCYPs, which can be utilized for further investigation of fruit metabolic pathways and cold tolerance in tomato.

Metabolic profiling of lumateperone in vitro and in vivo by UPLC-Q Exactive Orbitrap HRMS, and its pharmacokinetic study in rat plasma by LC-MS/MS.

Lumateperone is a novel agent approved by FDA for treatment of schizophrenia in adults. To elucidate the species differences in the of biotransformation of lumateperone and its pharmacokinetic (PK) characteristics in rats, the metabolite identification of lumateperone was carried out in rat, dog and human liver microsomes, and rat plasma after oral administration using UPLC-Q Exactive Orbitrap high-resolution mass spectrometry HRMS. Furtherly, the PK characteristics of lumateperone and its N-demethylated metabolite (M3) in rat plasma were investigated using a validated LC-MS/MS method following intravenous and oral administration. Fourteen phase I metabolites were found in liver microsomes and ten of them were observed in rat plasma. N-demethylation, carbonylation, dehydrogenation, and piperazine ring cleavage were main metabolic pathway of lumateperone. No unique metabolites were formed in human liver microsomes. After rapid absorption in rats, lumateperone was quickly metabolized and eliminated with bioavailability of less than 5%. The exposure level of M3 was about 1.5-fold higher than that of lumateperone in rat plasma. Lumatperone underwent extensive metabolism and was absorbed rapidly in rats. Metabolite M3 had equivalent or slightly higher exposure levels than lumateperone. This study provides essential PK information to facilitate further pharmacodynamic researches of lumateperone.

Parkinson's disease with anxiety: clinical characteristics and their correlation with oxidative stress, inflammation, and pathological proteins.

OBJECTIVE: This study was performed to explore the differences in the clinical characteristics and oxidative stress indicators, inflammatory factors, and pathological proteins in serum between Parkinson's disease (PD) with anxiety (PD-A) and with no anxiety (PD-NA) patients, and further correlations among clinical characteristics and above variables were analyzed in PD-A and PD-NA groups. METHODS: A total of 121 patients with PD were enrolled in this study and assessed by the Hamilton Anxiety Scale (14 items) (HAMA-14). These patients were divided into PD-A and PD-NA groups according to a cut-off point of 7 of HAMA-14. Demographic variables were collected, and clinical symptoms were assessed by multiple rating scales. The levels of free radicals, inflammatory factors, and pathological proteins in serum were measured by chemical colorimetric method and enzyme-linked immunosorbent assay (ELISA). The differences of above variables were compared between PD-A and PD-NA groups, and the correlations of clinical symptoms with the abovevariables were analyzed in PD-A and PD-NA groups. RESULTS: The frequency of PD-A was 62.81%. PD-A group exhibited significantly impaired motor dysfunction and multiple non-motor symptoms, including fatigue, sleep behavior disorder, restless leg syndrome and autonomic dysfunction, and dramatically compromised activities of daily living compard with PD-NA group. PD-A group displayed prominently increasedlevels of hydroxyl radical (·OH) and tumor necrosis factor (TNF)-α, and a decreased nitric oxide (NO) level in serum compared with PD-NA group (P<0.001, P = 0.001, P= 0.027, respectively). ·OH, NO, and TNF-α were identified as the risk factors of PD-A (OR = 1.005, P = 0.036; OR = 0.956, P = 0.017; OR = 1.039, P = 0.033, respectively). In PD patients, HAMA-14 score was significantly and positively correlated with the levels of ·OH and TNF-α in serum (P<0.001, P = 0.002, respectively). In PD-A group, ·OH level was significantly and negatively correlated with Aß1-42 level, while TNF-α level was significantly and positively correlated with P-tau (S396) level in serum. CONCLUSIONS: The frequency of PD-A is high. PD-A patients present more severe motor dysfunction and multiple non-motor symptoms, and poorer activities of daily living. The increased levels of ·OH and TNF-α levels and the decreased NO level in serum are all associated with more severe anxiety in PD patients.Findings from this study may provide in-depth insights into the clinical characteristics, underlying mechanisms of PD-A, and potential correlations among anxiety, oxidative stress, inflammation, and cognitive decline in PD patients.

Complanatuside A ameliorates 2,4,6-trinitrobenzene sulfonic acid-induced colitis in mice by regulating the Th17/Treg balance via the JAK2/STAT3 signaling pathway.

Immunity imbalance of T helper 17 (Th17)/regulatory T (Treg) cells is involved in the pathogenesis of Crohn's disease (CD). Complanatuside A (CA), a flavonol glycoside, exerts anti-inflammatory activities and our study aimed to identify its effect on TNBS-induced colitis and the possible mechanisms. We found that CA alleviated the symptoms of colitis in TNBS mice, as demonstrated by prevented weight loss and colon length shortening, as well as decreased disease activity index scores, inflammatory scores, and levels of proinflammatory factors. Flow cytometry analysis showed that CA markedly reduced the percentage of Th17 cells while increasing the percentage of Treg cells in TNBS mice. Under Th17 cell polarizing conditions, CA inhibited the differentiation of Th17 cells while the Treg cell differentiation was elevated under Treg cell polarizing conditions. Furthermore, it was observed that JAK2 interacted with CA through six hydrogen bonds via molecular docking. The phosphorylation of JAK2/STAT3 was reduced by CA, which might be correlated with the protective effect of CA on colitis. In conclusion, CA reduced the imbalance of Th17/Treg cells by inhibiting the JAK2/STAT3 signaling pathway in TNBS-induced colitis, which may provide novel strategies for CD treatment.

Gustatory Receptor 206 Participates in the Foraging Behavior of Larvae of Polyphagous Pest Spodoptera litura.

Insect gustatory receptors (GRs) aid in the precise identification of deterrent or stimulant compounds associated with food, mating, and egg-laying. Thus, they are promising targets for developing efficient insecticides. Here, 61 GRs in the chemosensory organs of Spodoptera litura larvae and adults were identified. Among them, SlitGR206 exhibited larval labium (LL)-specific expression characteristics. To explore the role of SlitGR206, a bacterial expression system was established to produce high-quality double-stranded RNA (dsRNA) and suppress SlitGR206 expression in LL. Subsequent behavioral assessments revealed that SlitGR206 silencing influenced larval feeding preferences and absorption. Moreover, it was found to reduce the ability of larvae to forage the five crucial host odorants. These findings demonstrate that SlitGR206 likely plays an indirect regulatory role in host recognition, consequently affecting foraging behavior. This provides a crucial foundation for the analysis of functional diversity among insect GRs and the precise development of nucleic acid pesticides in the future.

Effects of high moisture ear corn on production performance, milk fatty acid composition, serum antioxidant status, and immunity in primiparous dairy cows.

Objective: This study evaluated the effects of high moisture ear corn (HMEC) on production performance, milk fatty acid composition, serum antioxidant status, and immunity in primiparous dairy cows. Methods: A total of 45 healthy primiparous Holstein cows (36.50±4.30 kg of milk/day, 201±9.00 lactating days in milk) were sorted into 3 groups: control group (CG, n = 15), 50% HMEC (replacing 50% steam-flaked corn with HMEC, n = 15), and 100% HMEC (replacing steam-flaked corn with HMEC, n = 15) on an equal dry matter (DM) basis. The study consisted of adaptation period of 14 days, followed by a formal period of 60 days. Feed intake and milk yield were recorded daily. Milk and blood samples were collected on 1, 30, and 60 d of the experimental period. Results: The 50% HMEC group and 100% HMEC group significantly increased (p<0.05) milk yield and dry matter intake (DMI) in dairy cows compared to the control group (CG). The 100% HMEC group showed an increase (p<0.05) in 4% fat-corrected milk (4% FCM). Both the 50% HMEC group and 100% HMEC group exhibited significant decreases (p<0.05) in the content of C10:0, C12:0, and C14:0 fatty acids, along with a significant increase (p<0.05) in cis-9C18:1 content. The saturated fatty acid (SFA) content was significantly lower (p<0.05) in the 50% HMEC and 100% HMEC groups than that of CG. Conversely, the monounsaturated fatty acid (MUFA) content was higher (p<0.05) in the 50% HMEC and 100% HMEC groups than that in CG. Notably, the 100% HMEC group significantly increased (p<0.05) the serum superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) content, while also decreasing the serum malondialdehyde (MDA) content (p<0.05). Moreover, the 100% HMEC group significantly increased (p<0.05) the content of immunoglobulin G (IgG) and immunoglobulin M (IgM). Conclusion: High moisture ear corn could improve production performance and milk fatty acid levels and enhance immunity and antioxidant capacity in dairy cows. These results lay the foundation for the wider application of HMEC in ruminant animal diets.

APLN promotes the proliferation, migration, and glycolysis of cervical cancer through the PI3K/AKT/mTOR pathway.

Apelin (APLN) is an endogenous ligand of the G protein-coupled receptor APJ (APLNR). APLN has been implicated in the development of multiple tumours. Herein, we determined the effect of APLN on the biological behaviour and underlying mechanisms of cervical cancer. The expression and survival curves of APLN were determined using Gene Expression Profiling Interactive Analysis. The cellular functions of APLN were detected using CCK-8, clone formation, EdU, Transwell assays, flow cytometry, and seahorse metabolic analysis. The underlying mechanisms were elucidated using gene set enrichment analysis and Western blotting. APLN was upregulated in the samples of patients with cervical cancer and is associated with poor prognosis. APLN knockdown decreased the proliferation, migration, and glycolysis of cervical cancer cells. The opposite results were observed when APLN was overexpressed. Mechanistically, we determined that APLN was critical for activating the PI3K/AKT/mTOR pathway via APLNR. APLN receptor inhibitor ML221 reversed the effect of APLN overexpression on cervical cancer cells. Treatment with LY294002, the PI3K inhibitor, drastically reversed the oncological behaviour of APLN-overexpressing C-33A cells. APLN promoted the proliferation, migration, and glycolysis of cervical cancer cells via the PI3K/AKT/mTOR pathway.

Chain-mediating effects of kinesiophobia and self-efficacy on pain catastrophizing and physical activity in haemophilia patients.

BACKGROUND: There is a lack of research on the relationship between pain catastrophizing, kinesiophobia, and physical activity (PA) in people with haemophilia (PWH), and the underlying mechanisms connecting these variables remain unclear. AIM: The study's aim was to clarify the roles of kinesiophobia and self-efficacy in the relationship between pain catastrophizing and PA in PWH. METHODS: This cross-sectional study included adult PWH at the Haemophilia Centre of a Tertiary hospital in Beijing, China. The following questionnaires were used to collect data: the general information, the International Physical Activity Short Questionnaire, the Pain Catastrophizing Scale, the Tampa Scale of Kinesiophobia Scale, and the Exercise Self-Efficacy Scale. RESULTS: The study included a total of 187 PWH, including 154 having haemophilia A and 33 having haemophilia B. The median interquartile range of PA was 594 (198, 1554) MET-min/wk. There were significant differences in PA of patients based on age stage, treatment modality, highest pain score within the last seven days, and presence of haemophilic arthropathy (p < .05). It was showed that pain catastrophizing could directly predict PA (p < .001), accounting for 38.13% of the total effect. Pain catastrophizing also had indirect effects on PA through the mediating factors of kinesiophobia or self-efficacy, and through the chain-mediating effect of kinesiophobia and self-efficacy, accounting for 38.40%, 17.07%, and 6.40%, respectively. CONCLUSION: The study discovered that PWH have limited PA due to pain catastrophizing. This not only directly affects their activity but also indirectly influences it through kinesiophobia and self-efficacy.

Dual growth factor methacrylic alginate microgels combined with chitosan-based conduits facilitate peripheral nerve repair.

Treating severe peripheral nerve injuries is difficult. Nerve repair with conduit small gap tubulization is a treatment option but still needs to be improved. This study aimed to assess the use of microgels containing growth factors, along with chitosan-based conduits, for repairing nerves. Using the water-oil emulsion technique, microgels of methacrylic alginate (AlgMA) that contained vascular endothelial growth factor (VEGF) and brain-derived neurotrophic factor (BDNF) were prepared. The effects on rat Schwann cells (RSC96) and human umbilical vein endothelial cells (HUVECs) were evaluated. Chitosan-based conduits were fabricated and used in conjunction with microgels containing two growth factors to treat complete neurotmesis in rats. The results showed that the utilization of dual growth factor microgels improved the migration and decreased the apoptosis of RSC96 cells while promoting the growth and formation of tubes in HUVECs. The utilization of dual growth factor microgels and chitosan-based conduits resulted in notable advancements in the regeneration and myelination of nerve fibers, recovery of neurons, alleviation of muscle atrophy and recovery of neuromotor function and nerve conduction. In conclusion, the use of dual growth factor AlgMA microgels in combination with chitosan-based conduits has the potential to significantly improve the effectiveness of nerve repair.

Dabrafenib mitigates the neuroinflammation caused by ferroptosis in experimental autoimmune encephalomyelitis by up regulating Axl receptor.

Multiple sclerosis is an autoimmune disease that causes inflammatory damage to the central nervous system. At present, the pathogenesis of the disease is unknown. There is a lack of few effective therapy medications available. Therefore, it is necessary to further explore the pathogenesis of this illness and develop potential therapeutic drugs. Dabrafenib is potential therapeutic medicine for nervous system disease. In this study, we preliminarily studied the possible mechanism of dabrafenib in the treatment of multiple sclerosis from the perspective of ferroptosis. First, we observed that dabrafenib significantly improved symptoms of gait abnormalities, limb weakness or paralysis, and down-regulated levels of spinal cord inflammation in an experimental autoimmune encephalitis (EAE) model. Meanwhile, we also observed that dabrafenib could inhibit the proteins of ferroptosis in spinal cord tissue of EAE mice by Western blot. The results of immunohistochemical analysis showed that the effect of dabrafenib on ferroptosis mainly occurred in microglia. Second, dabrafenib was demonstrated to be able to inhibit the S phase of the cell cycle, reduce ROS levels, and reinstate mitochondrial activity in the LPS-induced BV2 inflammatory cell model. Futhermore, we found that dabrafenib inhibits P-JAK2 and P-STAT3 activation by acting Axl receptor, which in turn prevents neurogenic inflammation in microglia. The co-stimulated BV2 cell model with LPS and Erastin also verified these findings. Ultimately, the Axl knockout mice used to construct the EAE model allowed for the confirmation that dabrafenib prevented ferroptosis in microglia by up-regulating Axl receptor, which reduced the inflammatory demyelination associated with EAE. In summary, our research demonstrates the advantages of dabrafenib in multiple sclerosis treatment, which can prevent ferroptosis in microglia in multiple sclerosis through up-regulating Axl receptor, thus halting the progression of multiple sclerosis.

Research trends and hotspots of ferroptosis in neurodegenerative diseases from 2013 to 2023: A bibliometrics study.

Background: With the aging population, the incidence of neurodegenerative diseases increases yearly, seriously impacting human health. Various journals have published studies on the pathogenesis of ferroptosis in neurodegenerative diseases. However, bibliometric analysis in this field is still lacking. The study aims to visually analyze global research trends in this field over the past decade. Methods: The articles and reviews regarding ferroptosis in neurodegenerative diseases were retrieved from the Web of Science on September 1, 2023. Citespace [version 6.2. R4 (64-bit)] and VOSviewer (version 1.6.18) were used to conduct the bibliometric and knowledge-map analysis. Results: In total, 370 studies were included in the paper and ranked by their citation frequency. Many articles on ferroptosis in neurodegenerative diseases have been published in the past decade. The country, institution, author, and journal with the highest publications were China, Guangzhou Medical University, Maher, Pamela, and Free Radical Biology And Medicine, respectively. The analysis of keyword co-occurrence indicated that research frontiers were molecular mechanisms of ferroptosis in neurodegenerative diseases, especially a few key pathways that triggered ferroptosis in these diseases, including lipid peroxidation signaling, iron metabolism, and GSH/GPX4 signaling. In addition, ferroptosis inhibitors such as liproxstatins and ferrostatins had protective effects in animal models of neurodegenerative diseases. Therefore, future attention should also be focused on therapeutic drugs that target ferroptosis. Conclusion: This study comprehensively analyzed the publications on ferroptosis in neurodegenerative diseases from a bibliometric perspective. Research on this topic is currently expanding at a rapid pace, and the China holds a leading position in this field by its scientific achievements and productivity. Moreover, the research frontiers were molecular mechanisms of ferroptosis in neurodegenerative diseases and developing targeted therapeutic drugs. In summary, our results showed an all-sided overview of the knowledge atlas and a valuable reference for the future research in this field.

Groundwater hydrochemistry, source identification and health assessment based on self-organizing map in an intensive mining area in Shanxi, China.

The Changzhi Basin in Shanxi is renowned for its extensive mining activities. It's crucial to comprehend the spatial distribution and geochemical factors influencing its water quality to uphold water security and safeguard the ecosystem. However, the complexity inherent in hydrogeochemical data presents challenges for linear data analysis methods. This study utilizes a combined approach of self-organizing maps (SOM) and K-means clustering to investigate the hydrogeochemical sources of shallow groundwater in the Changzhi Basin and the associated human health risks. The results showed that the groundwater chemical characteristics were categorized into 48 neurons grouped into six clusters (C1-C6) representing different groundwater types with different contamination characteristics. C1, C3, and C5 represent uncontaminated or minimally contaminated groundwater (Ca-HCO3 type), while C2 signifies mixed-contaminated groundwater (HCO3-Ca type, Mixed Cl-Mg-Ca type, and CaSO4 type). C4 samples exhibit impacts from agricultural activities (Mixed Cl-Mg-Ca), and C6 reflects high Ca and NO3- groundwater. Anthropogenic activities, especially agriculture, have resulted in elevated NO3- levels in shallow groundwater. Notably, heightened non-carcinogenic risks linked to NO3-, Pb, F-, and Mn exposure through drinking water, particularly impacting children, warrant significant attention. This research contributes valuable insights into sustainable groundwater resource development, pollution mitigation strategies, and effective ecosystem protection within intensive mining regions like the Changzhi Basin. It serves as a vital reference for similar areas worldwide, offering guidance for groundwater management, pollution prevention, and control.