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Alfalfa (Medicago sativa L.) grassland is prone to degradation following multi-year maintenance. Yet, its mechanism regarding the stoichiometry of carbon (C) and nitrogen (N) across plant-soil system is still unclear. To address this issue, the method of space-for-time sampling was employed to investigate alfalfa grasslands with five planting years (5-, 8-, 10-, 15-, and 20-year periods) in the semiarid Loess Plateau. The results showed that the alfalfa above- and underground biomass decreased steadily decrease after the fifth to eighth years, showing a degradation tendency with the extension of planting duration. The mean weight diameter of aggregate registered an increase with planting years. However, the C and N stocks decreased with planting years in five soil aggregate fractions. Specifically, they were the highest in the fifth year and then started to gradually decrease along the 8th, 10th, 15th, and 20th year. Redundancy and correlation analysis confirmed that the C and N stocks of soil aggregates were closely positively associated with those of plant. Overall, the highest stability of soil physical structure was found during the period from the fifth to eighth year, and, afterward, the stability declined. In conclusion, alfalfa plantation improved soil structure stability but aggravated soil C and N stocks, and biomass and soil aggregate indicators accounted for alfalfa field degradation after a certain year of plantation. [ABSTRACT FROM AUTHOR]

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The McMurdo Dry Valleys (MDVs) of Antarctica are a mosaic of extreme habitats which are dominated by microbial life. The MDVs include glacial melt holes, streams, lakes, and soils, which are interconnected through the transfer of energy and flux of inorganic and organic material via wind and hydrology. For the first time, we provide new data on the viral community structure and function in the MDVs through metagenomics of the planktonic and benthic mat communities of Lakes Bonney and Fryxell. Viral taxonomic diversity was compared across lakes and ecological function was investigated by characterizing auxiliary metabolic genes (AMGs) and predicting viral hosts. Our data suggest that viral communities differed between the lakes and among sites: these differences were connected to microbial host communities. AMGs were associated with the potential augmentation of multiple biogeochemical processes in host, most notably with phosphorus acquisition, organic nitrogen acquisition, sulfur oxidation, and photosynthesis. Viral genome abundances containing AMGs differed between the lakes and microbial mats, indicating site specialization. Using procrustes analysis, we also identified significant coupling between viral and bacterial communities (p = 0.001). Finally, host predictions indicate viral host preference among the assembled viromes. Collectively, our data show that: (i) viruses are uniquely distributed through the McMurdo Dry Valley lakes, (ii) their AMGs can contribute to overcoming host nutrient limitation and, (iii) viral and bacterial MDV communities are tightly coupled. [ABSTRACT FROM AUTHOR]

High entropy materials (HEM) have been attracting much attention as emerging catalysts for electrochemical water splitting. HEM catalysts have unique properties such as an interesting cocktail effect, broad design space, customizable electronic structure, and excellent entropy stabilization effect compared with single-digit catalysts. This paper provides a comprehensive overview of the use of HEM as a catalyst for hydrogen evolution reaction (HER), oxygen evolution reaction (OER), and water splitting. HEM design strategies including phase structure modulation, defect engineering, electrode configuration engineering, and computational aids are discussed to develop HEM catalysts with high performance and stability. In particular, the importance of density functional theory, high-throughput screening techniques, and machine learning for the discovery and design of HEM catalysts is emphasized. Finally, the challenges and imminent difficulties are prospected, and the corresponding strategies to deal with these challenges are put forward to promote the development of HEM catalysts in the field of electrochemical water splitting. [ABSTRACT FROM AUTHOR]

Accurate carbon price forecasts are crucial for policymakers and enterprises to understand the dynamics of carbon price fluctuations, enabling them to formulate informed policies and investment strategies. However, due to the non-linear and non-stationary nature of carbon price, traditional models often struggle to achieve high prediction accuracy. To address this challenge, this study proposes a novel integrated prediction framework designed to enhance forecast accuracy. First, the carbon price series is decomposed into a series of smoother subsequences using fast iterative filtering (FIF). Subsequently, an integrated prediction model, AM-TCN-LSTM, is constructed, incorporating the attention mechanism (AM), temporal convolutional networks (TCN), and long short-term memory (LSTM) neural networks. The attention mechanism adaptively captures complex features from multiple factors, while the TCN-LSTM efficiently extracts temporal features from the sequences. Finally, the results from each subsequence are aggregated to generate the final prediction. Five carbon markets in china: Guangdong, Hubei, Shenzhen, Beijing, and Shanghai were selected to verify the validity of the proposed model. Various comparative models and evaluation metrics were employed to assess performance. The results demonstrate that: (1) the TCN-LSTM model achieves higher prediction accuracy compared to single models. (2) FIF is a more effective decomposition method with superior performance compared to EMD-based methods. (3) The proposed model exhibits the highest predictive capability, with MAE values of 0.0964, 0.1403, 1.9476, 2.0848, and 0.5029 for the five carbon markets, significantly outperforming comparison models. (4) The attention mechanism effectively captures the influence of multiple factors on carbon price, particularly within the short-term components. [ABSTRACT FROM AUTHOR]

Background: Rhabdomyosarcoma of the bladder is an infrequent neoplastic condition characterized by a pronounced malignant situation with challenges in treatment due to the lack of standardized guidelines and large-scale of clinical studies. The patient in this case is tested TP53 mutation that may provide new diagnostic and therapeutic options. Case presentation: Here, we reported a 34-year-old male who received bladder tumor resection, and diagnosed as bladder rhabdomyosarcoma with TP53 mutation after the pathology test. This patient underwent 6 rounds of chemotherapy. However, the pelvic tumor recurred 11 months after the first surgery. So, the patient accepted the pelvic tumor resection. Only 3 months after the surgical intervention, the patient underwent abdominal massive metastasis and ultimately succumbed to the illness six months following the second surgery. The course of the illness was 22 months. Conclusion: Bladder rhabdomyosarcoma is a disease with an extremely poor prognosis. Genetic testing holds significant value in the diagnosis and treatment. Perhaps targeted therapy against TP53 is potential valuable for such rare diseases. [ABSTRACT FROM AUTHOR]

Background: The gut microbiome plays a key role in the formation of livestock and poultry traits via serum metabolites, and empirical evidence has indicated these traits are sex-linked. Methods: We examined 106 chickens (54 male chickens and 52 female chickens) and analyzed cecal content samples and serum samples by 16S rRNA gene sequencing and non-targeted metabolomics, respectively. Results: The cecal microbiome of female chickens was more stable and more complex than that of the male chickens. Lactobacillus and Family XIII UCG-001 were enriched in male chickens, while Eubacterium_nodatum_group, Blautia, unclassified_Anaerovoraceae, Romboutsia, Lachnoclostridium, and norank_ Muribaculaceae were enriched in female chickens. Thirty-seven differential metabolites were identified in positive mode and 13 in negative mode, showing sex differences. Sphingomyelin metabolites possessed the strongest association with cecal microbes, while 11β-hydroxytestosterone showed a negative correlation with Blautia. Conclusion: These results support the role of sexual dimorphism of the cecal microbiome and metabolome and implicate specific gender factors associated with production performance in chickens. [ABSTRACT FROM AUTHOR]

BACKGROUND: WEE1 is a critical kinase in the DNA damage response pathway and has been shown to be effective in treating serous uterine cancer. However, its role in gliomas, specifically low-grade glioma (LGG), remains unclear. The impact of DNA methylation on WEE1 expression and its correlation with the immune landscape in gliomas also need further investigation. METHODS: This study used data from The Cancer Genome Atlas (TCGA), Chinese Glioma Genome Atlas (CGGA), and Gene Expression Omnibus (GEO) and utilized various bioinformatics tools to analyze gene expression, survival, gene correlation, immune score, immune infiltration, genomic alterations, tumor mutation burden, microsatellite instability, clinical characteristics of glioma patients, WEE1 DNA methylation, prognostic analysis, single-cell gene expression distribution in glioma tissue samples, and immunotherapy response prediction based on WEE1 expression. RESULTS: WEE1 was upregulated in LGG and glioblastoma (GBM), but it had a more significant prognostic impact in LGG compared to other cancers. High WEE1 expression was associated with poorer prognosis in LGG, particularly when combined with wild-type IDH. The WEE1 inhibitor MK-1775 effectively inhibited the proliferation and migration of LGG cell lines, which were more sensitive to WEE1 inhibition. DNA methylation negatively regulated WEE1, and high DNA hypermethylation of WEE1 was associated with better prognosis in LGG than in GBM. Combining WEE1 inhibition and DNA methyltransferase inhibition showed a synergistic effect. Additionally, downregulation of WEE1 had favorable predictive value in immunotherapy response. Co-expression network analysis identified key genes involved in WEE1-mediated regulation of immune landscape, differentiation, and metastasis in LGG. CONCLUSION: Our study shows that WEE1 is a promising indicator for targeted therapy and prognosis evaluation. Notably, significant differences were observed in the role of WEE1 between LGG and GBM. Further investigation into WEE1 inhibition, either in combination with DNA methyltransferase inhibition or immunotherapy, is warranted in the context of LGG. [ABSTRACT FROM AUTHOR]

Objective: Recent research suggests a potential link between the gut microbiome (GM) and epilepsy. We undertook a Mendelian randomization (MR) study to determine the possible causal influence of GM on epilepsy and its various subtypes, and explore whether cytokines act as mediators. Methods: We utilized Genome-Wide Association Study (GWAS) summary statistics to examine the causal relationships between GM, cytokines, and four epilepsy subtypes. Furthermore, we assessed whether cytokines mediate the relationship between GM and epilepsy. Significant GMs were further investigated using transcriptomic MR analysis with genes mapped from the FUMA GWAS. Sensitivity analyses and reverse MR were conducted for validation, and false discovery rate (FDR) correction was applied for multiple comparisons. Results: We pinpointed causal relationships between 30 GMs and various epilepsy subtypes. Notably, the Family Veillonellaceae (OR:1.03, 95%CI:1.02-1.05, p = 0.0003) consistently showed a strong positive association with child absence epilepsy, and this causal association endured even after FDR correction (p-FDR < 0.05). Seven cytokines were significantly associated with epilepsy and its subtypes. A mediating role for cytokines has not been demonstrated. Sensitivity tests validated the primary MR analysis outcomes. Additionally, no reverse causality was detected between significant GMs and epilepsy. Of the mapped genes of notable GMs, genes like BLK, FDFT1, DOK2, FAM167A, ZSCAN9, RNGTT, RBM47, DNAJC21, SUMF1, TCF20, GLO1, TMTC1, VAV2, and RNF14 exhibited a profound correlation with the risk factors of epilepsy subtypes. Conclusion: Our research validates the causal role of GMs and cytokines in various epilepsy subtypes, and there has been no evidence that cytokines play a mediating role between GM and epilepsy. This could provide fresh perspectives for the prevention and treatment of epilepsy. [ABSTRACT FROM AUTHOR]

Recycling strategies for mixed plastics and textile blends currently aim for recycling only one of the components. Here, we demonstrate a water coupling strategy to co-hydrolyze polyester/cotton textile blends into polymer monomers and platform chemicals in gamma-valerolactone. The blends display a proclivity for achieving an augmented 5-hydroxymethylfurfural yield relative to the degradation of cotton alone. Controlled experiments and preliminary mechanistic studies underscore that the primary driver behind this heightened conversion rate lies in the internal water circulation. The swelling and dissolving effect of gamma-valerolactone on polyester enables a fast hydrolysis of polyester at much lower concentration of acid than the one in the traditional hydrolysis methods, effectively mitigating the excessive degradation of cotton-derived product and undesirable product formation. In addition, the system is also applicable to different kinds of blends and PET mixed plastics. This strategy develops an attractive path for managing end-of-life textiles in a sustainable and efficient way. [ABSTRACT FROM AUTHOR]

Introduction: Sleep insufficiency has been linked to an increased risk of high blood pressure and cardiovascular diseases. Emerging studies have demonstrated that impaired baroreflex sensitivity (BRS) is involved in the adverse cardiovascular effects caused by sleep deprivation, however, the underlying mechanisms remain unknown. Therefore, the present study aims to clarify the role of abnormal renin-angiotensin system in the nucleus tractus solitarii (NTS) in impaired BRS induced by sleep deprivation. Methods: Rats were randomly divided into two groups: normal sleep (Ctrl) and chronic sleep deprivation (CSD) group. Rats were sleep deprived by an automated sleep deprivation system. The blood pressure, heart rate, BRS, the number of c-Fos positive cells and the expression of angiotensin (Ang) II subtype I receptors (AT1R) in the NTS of rats were assessed. Results: Compared to Ctrl group, CSD group exhibited a higher blood pressure, heart rate, and reduced BRS. Moreover, the number of c-Fos positive cells and local field potential in the NTS in CSD group were increased compared with the Ctrl group. It was shown that the expression of the AT1R and the content of Ang II and the ratio of Ang II to Ang-(1-7) were increased in the NTS of rats in CSD group compared to Ctrl group. In addition, microinjection of losartan into the NTS significantly improved the impaired BRS caused by sleep deprivation. Discussion: In conclusion, these data suggest that the elevated AT1R expression in the NTS mediates the reduced BRS induced by chronic sleep deprivation. [ABSTRACT FROM AUTHOR]

Objectives: Multi-Criteria Decision Analysis (MCDA) has gained increasing attention in supporting drug risk-benefit assessment, pricing and reimbursement, as well as optimization of clinical interventions. The objective of this study was to systematically collect and categorize evaluation criteria and techniques of weighting and scoring of MCDA for drug value assessment. Methods: A systematic review of the literature was conducted across seven databases to identify articles utilizing the MCDA frameworks for the evaluation of drug value. Evaluation criteria mentioned in the included studies were extracted and assigned to 5 dimensions including clinical, economic, innovative, societal and humanistic value. A descriptive statistical analysis was performed on the identified drug value evaluation criteria, as well as the weighting and scoring techniques employed. The more a criterion or technique were mentioned in articles, the more important we consider it. Results: Out of the 82 articles included, 111 unique criteria were identified to evaluate the value of drug. Among the 56 unique criteria (448 times) used to measure clinical value, the most frequently mentioned were "comparative safety/tolerability" (58 times), "comparative effectiveness/efficacy" (56 times), "comparative patient-perceived health/patient reported outcomes" (37 times), "disease severity" (34 times), and "unmet needs" (25 times). Regarding economic value measurement, out of the 20 unique criteria (124 times), the most frequently utilized criteria were "cost of intervention" (17 times), "comparative other medical costs" (16 times), and "comparative non-medical costs" (18 times). Out of the 10 criteria (18 times) for assessing innovative value, "a novel pharmacological mechanism" was the most frequently mentioned criterion (5 times). Among the 22 criteria (73 times) used to measure societal value, "system capacity and appropriate use of intervention" was the most frequently cited criterion (14 times). Out of the 3 criteria (15 times) utilized to measure humanistic value, "political/historical/cultural context" was the most frequently mentioned criterion (9 times). Furthermore, 11 scoring and 11 weighting techniques were found from various MCDA frameworks. "Swing weighting" and "a direct rating scale" were the most frequently used techniques in included articles. Conclusion: This study comprehensively presented the current evaluation dimensions, criteria, and techniques for scoring and weighting in drug-oriented MCDA articles. By highlighting the frequently cited evaluation criteria and techniques for scoring and weighting, this analysis will provide a foundation to reasonably select appropriate evaluation criteria and technique in constructing the MCDA framework that aligns with research objectives. [ABSTRACT FROM AUTHOR]

Background: Previous studies suggests that gut microbiomes are associated with the formation and progression of aneurysms. However, the causal association between them remains unclear. Methods: A two-sample Mendelian randomization was conducted to investigate whether gut microbiomes have a causal effect on the risk of intracerebral aneurysm (IA), thoracic aortic aneurysm (TAA) and abdominal aortic aneurysm (AAA), and aortic aneurysm (AA). Single nucleotide polymorphisms (SNPs) smaller than the locus-wide significance level (1 × 10-5) were selected as instrumental variables. We used inverse-variance weighted (IVW) test as the primary method for the evaluation of causal association. MR-Egger, weighted median, weighted mode, and MR Pleiotropy Residual Sum and Outlier (MR-PRESSO) methods were conducted for sensitive analysis. The p-value was adjusted by the false discovery rate (FDR) which adjust the results of multiple comparisons, a p < 0.05 and q < 0.1 was considered a significant causal association. Additionally, a p < 0.05 and q > 0.1 was considered a suggestive causal effect. Additionally, reverse MR was also performed to exclude the possibility of reverse causality. Results: The phylum Firmicutes (OR = 0.62; 95% CI, 0.48-0.81), class Lentisphaeria (OR = 0.75; 95% CI, 0.62-0.89), and order Victivallales (OR = 0.75; 95% CI, 0.62-0.89) have a causal protective effect on the risk of AAA. Additionally, class Verrucomicrobia, class Deltaproteobacteria, order Verrucomicrobiale, family Verrucomicrobiacea, genus Eubacterium rectale group, genus Akkermansia, and genus Clostridium innocuum group were negatively associated with the risk of different types of aneurysms, whereas class Negativicutes, order Selenomonadales, and genus Roseburia had positive causal association with different types of aneurysms (p < 0.05; q > 0.1). Further sensitivity analysis validated the robustness of our MR results, and no reverse causality was found with these gut microbiomes (p > 0.05). Conclusion: Our MR analysis confirmed the causal association of specific gut microbiomes with AAA, and these microbiomes were considered as protective factors. Our result may provide novel insights and theoretical basis for the prevention of aneurysms through regulation of gut microbiomes. [ABSTRACT FROM AUTHOR]

Surfactants are widely used in the fracturing fluid to enhance the imbibition and thus the oil recovery rate. However, current numerical models cannot capture the physics behind capillary imbibition during the wettability alteration by surfactants. Although the interacting capillary bundle (ICB) model shows potential in characterizing imbibition rates in different pores during wettability alteration, the existing ICB models neglect the influence of wettability and viscosity ratio on the imbibition behavior, making it difficult to accurately describe the oilewater imbibition behavior within the porous media. In this work, a new ICB mathematical model is established by introducing pressure balance without assuming the position of the leading front to comprehensively describe the imbibition behavior in a porous medium under different conditions, including gaseliquid spontaneous imbibition and oilewater imbibition. When the pore size distribution of a tight rock is known, this new model can predict the changes of water saturation during the displacement process in the tight rock, and also determine the imbibition rate in pores of different sizes. The water saturation profiles obtained from the new model are validated against the waterflooding simulation results from the CMG, while the imbibition rates calculated by the model are validated against the experimental observations of gaseliquid spontaneous imbibition. The good match above indicates the newly proposed model can show the water saturation profile at a macroscopic scale while capture the underlying physics of the multiphase flow in a porous medium at a microscopic scale. Simulation results obtained from this model indicate that both wettability and viscosity ratio can affect the sequence of fluid imbibition into pores of different sizes during the multiphase flow, where less-viscous wetting fluid is preferentially imbibed into larger pores while more-viscous wetting fluid tends to be imbibed into smaller pores. Furthermore, this model provides an avenue to calculate the imbibition rate in pores of different sizes during wettability alteration and capture the non-Darcy effect in micro- and nano-scale pores. [ABSTRACT FROM AUTHOR]

Background: Currently, disease-modifying therapies (DMTs) for progressive multiple sclerosis (PMS) are widely used in clinical practice. At the same time, there are a variety of drug options for DMTs, but the effect of the drugs that can better relieve symptoms and improve the prognosis are still inconclusive. Objectives: This systematic review aimed to evaluate the efficacy and safety of DMTs for PMS and to identify the best among these drugs. Methods: MEDLINE, EMBASE, the Cochrane Library, and clinicaltrials.gov were systematically searched to identify relevant studies published before 30 January, 2023. We assessed the certainty of the evidence using the confidence in the network meta-analysis (CINeMA) framework. We estimated the summary risk ratio (RR) for dichotomous outcomes and mean differences (MD) for continuous outcomes with 95% credible intervals (CrIs). Results: We included 18 randomized controlled trials (RCTs) involving 9,234 patients in the study. DMT can effectively control the disease progression of MS. Among them, mitoxantrone, siponimod, and ocrelizumab are superior to other drug options in delaying disease progression (high certainty). Mitoxantrone was the best (with high certainty) for mitigating deterioration (progression of disability). Ocrelizumab performed best on the pre- and post-treatment Timed 25-Foot Walk test (T25FW; low certainty), as did all other agents (RR range: 1.12–1.05). In the 9-Hole Peg Test (9HPT), natalizumab performed the best (high certainty), as did all other agents (RR range: 1.59–1.09). In terms of imaging, IFN-beta-1b performed better on the new T2 hypointense lesion on contrast, before and after treatment (high certainty), while siponimod performed best on the change from baseline in the total volume of lesions on T2-weighted image contrast before and after treatment (high certainty), and sWASO had the highest area under the curve (SUCRA) value (100%). In terms of adverse events (AEs), rituximab (RR 1.01), and laquinimod (RR 1.02) were more effective than the placebo (high certainty). In terms of serious adverse events (SAEs), natalizumab (RR 1.09), and ocrelizumab (RR 1.07) were safer than placebo (high certainty). Conclusion: DMTs can effectively control disease progression and reduce disease deterioration during the treatment of PMS. [ABSTRACT FROM AUTHOR]

Clustered regularly interspaced short palindromic repeats (CRISPR)-associated protein 9 (CRISPR-Cas9) system has been widely applied in cultivated crops, but limited in their wild relatives. Nicotiana alata is a typical wild species of genus Nicotiana that is globally distributed as a horticultural plant and well-studied as a self-incompatibility model. It also has valuable genes for disease resistance and ornamental traits. However, it lacks an efficient genetic transformation and genome editing system, which hampers its gene function and breeding research. In this study, we developed an optimized hypocotyl-mediated transformation method for CRISPR-Cas9 delivery. The genetic transformation efficiency was significantly improved from approximately 1% to over 80%. We also applied the CRISPR-Cas9 system to target the phytoene desaturase (NalaPDS) gene in N. alata and obtained edited plants with PDS mutations with over 50% editing efficiency. To generate self-compatible N. alata lines, a polycistronic tRNA-gRNA (PTG) strategy was used to target exonic regions of allelic S-RNase genes and generate targeted knockouts simultaneously. We demonstrated that our system is feasible, stable, and high-efficiency for N. alata genome editing. Our study provides a powerful tool for basic research and genetic improvement of N. alata and an example for other wild tobacco species. [ABSTRACT FROM AUTHOR]

It is recommended that pregnant women be physically active to promote maternal and child health. This study aimed to explore the prevalence of physical inactivity and its modifiable predictors in the three trimesters in Chinese pregnant women. Four hundred forty-four pregnant women completed the Pregnant Physical Activity Questionnaire in the first, second, and third trimesters. The prevalence of physical inactivity reached its highest (66.2%) in the first trimester and lowest (19.4%) in the second trimester. Pregnant women with inadequate physical activity knowledge and low self-efficacy were at higher risk for physical inactivity. Monitoring physical inactivity could be incorporated into antenatal care and start from the first trimester. Prenatal care professionals should take action to increase pregnant women's physical activity self-efficacy and knowledge to enhance their physical activity. [ABSTRACT FROM AUTHOR]

The effects of strain rate on the yielding strength and maximum temperature at shear bands in a typical Zr41.2Ti13.8Ni10Cu12.5Be22.5 (Vit 1) bulk metallic glass are investigated under tension and compression over a wide range of strain rates at ambient temperature. Using the modified cooperative shear model incorporating the notable internal thermal effect at high strain rates, the transition of the strain rate effect of yielding strength from the sudden decrease to the subsequent slow change with increasing the strain rate is quantitatively characterized. The fracture surface temperature evolution under different shear band evolution times is captured by a hierarchical multi-scale model of heat conduction. Dynamic strain rates shorten the shear band evolution time, leading to an increase in the maximum temperature at shear bands compared to quasi-static loadings. [ABSTRACT FROM AUTHOR]

Introduction: Wheat is a food crop with a large global cultivation area, and the content and quality of wheat glutenin accumulation are important indicators of the quality of wheat flour. Methods: To elucidate the gene expression regulation and metabolic characteristics related to the gluten content during wheat grain formation, transcriptomic and metabolomic analyses were performed for the high gluten content of the Xinchun 26 cultivar and the low proteins content of the Xinchun 34 cultivar at three periods (7 d, 14 d and 21 d) after flowering. Results: Transcriptomic analysis revealed that 5573 unique differentially expressed genes (DEGs) were divided into two categories according to their expression patterns during the three periods. The metabolites detected were mainly divided into 12 classes. Lipid and lipid-like molecule levels and phenylpropanoid and polyketide levels were the highest, and the difference analysis revealed a total of 10 differentially regulated metabolites (DRMs) over the three periods. Joint analysis revealed that the DEGs and DRMs were significantly enriched in starch and sucrose metabolism; the citrate cycle; carbon fixation in photosynthetic organisms; and alanine, aspartate and glutamate metabolism pathways. The genes and contents of the sucrose and gluten synthesis pathways were analysed, and the correlation between gluten content and its related genes was calculated. Based on weighted correlation network analysis (WGCNA), by constructing a coexpression network, a total of 5 specificmodules and 8 candidate genes that were strongly correlated with the three developmental stages of wheat grain were identified. Discussion: This study provides new insights into the role of glutenin content in wheat grain formation and reveals potential regulatory pathways and candidate genes involved in this developmental process. [ABSTRACT FROM AUTHOR]

Glioma represents the most common primary cancer of the central nervous system in adults. Glycosylation is a prevalent post-translational modification that occurs in eukaryotic cells, leading to a wide array of modifications on proteins. We obtained the clinical information, bulk RNA-seq data, and single-cell RNA sequencing (scRNA-seq) from The Cancer Genome Atlas (TCGA), Chinese Glioma Genome Atlas (CGGA), Gene Expression Omnibus (GEO), and Repository of Molecular Brain Neoplasia Data (Rembrandt) databases. RNA sequencing data for normal brain tissues were accessed from the Genotype- Tissue Expression (GTEx) database. Then, the glycosylation genes that were differentially expressed were identified and further subjected to variable selection using a least absolute shrinkage and selection operator (LASSO)- regularized Cox model. We further conducted enrichment analysis, qPCR, nomogram, and single-cell transcriptome to detect the glycosylation signature. Drug sensitivity analysis was also conducted. A five-gene glycosylation signature (CHPF2, PYGL, GALNT13, EXT2, and COLGALT2) classified patients into low- or high-risk groups. Survival analysis, qPCR, ROC curves, and stratified analysis revealed worse outcomes in the high-risk group. Furthermore, GSEA and immune infiltration analysis indicated that the glycosylation signature has the potential to predict the immune response in glioma. In addition, four drugs (crizotinib, lapatinib, nilotinib, and topotecan) showed different responses between the two risk groups. Glioma cells had been classified into seven lines based on single-cell expression profiles. The five-gene glycosylation signature can accurately predict the prognosis of glioma and may offer additional guidance for immunotherapy. [ABSTRACT FROM AUTHOR]

Background: As a novel antidepressant drug, zuranolone has been initially applied in treating depression. This study investigated the efficacy and safety of its administration in patients with depression. Methods: The Embase, PubMed, and Cochrane library databases were searched for available studies up to 1 Nov 2023. The primary outcome was the change on day 15 depression severity scores compared to baseline. Secondary outcomes included remission and response rates on day 15. Safety outcomes included incidence of treatment-emergent adverse events (TEAEs) and individual AEs. Trial sequential analysis (TSA) was used to evaluate the ideal samplesize. Results: Six studies with 1884 patients were included. Zuranolone offered significantly greater changes in day 15 depression severity scores (mean difference = 2.43, 95% confidence interval [CI]: 1.36 to 3.49, p < 0.00001) compared to placebo; this was also observed at other time points. Differences in response (relative risk [RR] = 1.33, 95% CI: 1.15 to 1.54, p < 0.0001) and remission (RR = 1.46, 95% CI: 1.15 to 1.85, p = 0.002) rates were also statistically significant. For safety outcomes, zuranolone group showed more incidence of TEAE than the placebo group (RR: 1.15, 95% CI: 1.06 to 1.25, p = 0.0005, I2 = 0%). As for individual AEs, significant differences were observed in dizziness (RR = 2.17, 95% CI: 1.22 to 3.86, p = 0.008) and somnolence (RR = 2.43, 95% CI: 1.35 to 4.37, p = 0.003. No significant difference was observed in other AEs. The result of TSA indicated that the cumulative curve crossed the conventional (Z = 1.96) boundary but not reach TSA boundary (RIS = 1910). Conclusion: Our findings suggest that zuranolone has a rapid short-term antidepressant effect during administration. Although more TEAEs were observed in zuranolone, most of them were slight and temporary. However, studies with larger sample sizes and longer follow-up are needed. [ABSTRACT FROM AUTHOR]

Background: The infusion of phenylephrine to prevent spinal-induced hypotension (SIH) in cesarean delivery may decrease the rostral spread of a spinal local anesthetic. We hypothesized that infusion of norepinephrine may decrease the rostral spread of spinal anesthesia, similar to that caused by phenylephrine. The aim of this study was to compare the block height of spinal anesthesia in the presence or absence of norepinephrine infusion administered to prevent SIH during cesarean delivery. Methods: Eighty patients were enrolled and allocated into groups receiving a norepinephrine infusion (group N) or saline infusion (group C). After intrathecal injection of hyperbaric bupivacaine 10 mg, the block height for cold and pinprick sensation was checked 10 and 20 min after the injection. The demographic characteristics, spinal anesthesia, side effects, and neonatal outcomes were also recorded. Results: The block height for cold and pinprick sensation was similar between the two groups, although the incidence of hypotension was significantly lower (p < 0.00) in group N than in group C. Systolic blood pressure was also more stable in group N than in group C, with the incidence of interventions being significantly lower in group N. There was no significant difference in patient satisfaction between the two groups. Conclusion: Evidence from this study suggested that prophylactic norepinephrine infusion does not reduce the rostral spread of spinal anesthesia in pregnancy. We suggest that it is not necessary to increase the dose of an intrathecal local anesthetic for cesarean delivery when prophylactic norepinephrine is administered. [ABSTRACT FROM AUTHOR]

With the increasing temperature and pressure in the cylinder of the diesel engine, the in-cylinder environment gradually exceeded the thermodynamic critical point of hydrocarbon fuel. Compared with subcritical spray, the phase transformation mechanism of supercritical spray is essentially changed. In this paper, the n-heptane fuel sprays in three conditions case 1 (T1 = 400 K P1 = 2 MPa), case 2 (T2 = 600 K P2 = 2 MPa), and case 3 (T3 = 800 K P3 = 6 MPa) were obtained by high-speed digital schlieren method on the test platform of a constant volume combustion bomb. The spray liquid phase, liquid–gas mixed layer, and mixture were divided, and the variation rules of the spray cone angle, the liquid phase length, maximum interface thickness, and liquid– gas mixed layer area were discussed. The results showed that the higher the ambient temperature and pressure, the more severe the fragmentation of the spray. Compared with the subcritical condition, the spray penetration distance in the supercritical condition tended to be flat faster. Compared with 400 K, 2 MPa condition, the spray cone angle was about 33° and 50% larger at 800 K, 6 MPa condition. The liquid core area at 800 K, 6 MPa condition was 60 cm², reduced by 75% compared with 400 K, 2 MPa condition, resulting in better spray diffusion and mixing with atmospheric gas. The sensitivity analysis of ambient temperature and pressure on spray characteristic parameters shows that temperature has a greater impact on the interface mixing layer area (VIP = 1.23), and pressure has a greater on penetration distance and spray penetration rate (VIP = 1.23). When the environmental conditions exceed the thermodynamic critical point, the area of the liquid–gas mixed layer increases due to the transformation of spray from evaporation to diffusion and the phenomenon of interfacial layer enrichment. In summary, the supercritical condition promotes the mixing of spray and environment and has a positive effect on spray diffusion and atomization. [ABSTRACT FROM AUTHOR]

In order to explore the relationship between local autonomous cultural and creative industries and economic and cultural upgrading, this paper uses a questionnaire survey to conduct practical investigation and analysis, and discusses the relationship between the following aspects. Local self-government, The results show that local autonomous cultural creativity can promote economic growth and improve cultural level, and there is a certain correlation between economic growth and cultural upgrading, but the correlation is poor, indicating that the impact of economic growth on cultural upgrading is indirect, and cultural upgrading and economic growth are the main factors for the development of local autonomous cultural and creative industries. Local autonomy is the main influencing factor of economic growth and cultural upgrading, and it is also a combination factor for the development of cultural and creative industries. Therefore, strengthening local autonomy, promoting economic growth, and cultural upgrading can promote the development of cultural and creative industries. [ABSTRACT FROM AUTHOR]

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In this study, a gravity unloading method based on electrostatic adsorption is proposed to address the issue of large flexibility in membrane phased-array antennas. Through considering the gravity distribution of the antenna and the edge effect of the electrode system, the unloading efficiency and system robustness are improved using a grouping strategy and size optimization. The deformation equilibrium equation under both gravity and electrostatic fields is established, and the voltage optimization model of the electrode system is also formulated with the goal of complete compensation for gravity deformation. The advantages and effectiveness of the proposed method are demonstrated by comparing simulation and unloading experiment results with those obtained using the suspension method. Both results indicate that the electrostatic unloading method can achieve the same unloading effect as the suspension method. Moreover, without introducing in-plane deformations during unloading, this method enhances accuracy and provides valuable insights for optimizing the assembly and testing processes. [ABSTRACT FROM AUTHOR]

Background: Endovascular thrombectomy (EVT) is an important treatment for patients with acute ischemic stroke (AIS). A number of studies have suggested that anesthesia type (conscious sedation vs. general anesthesia) during intra-arterial treatment for acute ischemic stroke has implications for patient outcomes. Methods: PubMed, EMBASE, Cochrane Library and clinicaltrials.gov were searched for randomized controlled trials (RCTs) that were performed to evaluate general anesthesia (GA) and conscious sedation (CS) up to May 30, 2023. Review Manager 5.3 software was used to assess the data. The risk ratio (RR) and mean difference (MD) were analyzed and calculated with a fixed effect model. Results: We pooled 930 patients from seven RCTs. We conducted a meta-analysis comparing the outcomes of GA and CS in the included trials. The rate of functional independence in the GA group was higher than that in the CS group (RR: 1.17, 95% CI: 1.00-1.35; P = 0.04; I² = 16%). The GA group had a higher successful recanalization rate than the CS group (RR: 1.15, 95% CI: 1.08-1.22; P < 0.0001; I² = 26%). The GA group had a higher pneumonia rate than the CS group (RR: 1.69, 95% CI: 1.22-2.34; P = 0.002; I² = 26%). In addition, there was no significant difference between GA and CS with respect to the National Institutes of Health Stroke Scale (NIHSS) score at 24 h (P = 0.62), Modified Rankin Scale (mRS) score at 90 days (P = 0.25), intracerebral hemorrhage (P = 0.54), and mortality at 3 months (P = 0.61). Conclusion: GA demonstrated superiority over CS in achieving successful recanalization and functional independence at 3 months when performing EVT in AIS patients. However, it was also associated with a higher risk of pneumonia. Further studies, particularly those with long-term follow-ups, are necessary to identify precise strategies for selecting the appropriate anesthetic modality in EVT patients. Systematic review registration: INPLASY202370116. [ABSTRACT FROM AUTHOR]

Background: A series of clinical trials support the effectiveness of monoclonal antibodies for generalized myasthenia gravis (MG) compared to the placebo, but the priority among drugs remains unclear. Therefore, we conduct a frequentist network meta-analysis (NMA) to compare the relative effects of different drugs for generalized MG. Methods: PubMed, Embase, Cochrane Library, and clinicaltrials.gov were systematically searched for eligible studies up to 1 June 2023. The primary outcome was efficacy (Myasthenia Gravis Activities of Daily Living [MG-ADL] score and Quantitative Myasthenia Gravis [QMG] score) and safety (adverse events [AEs]). Mean difference (MD) and risk ratio (RR) with their 95% credible intervals (95%CrIs) were used to show the effect size of continuous and categorical variables, respectively. The quality of evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. Results: Thirteen studies involving 1167 individuals were identified for NMA. For efficacy outcomes, belimumab, efgartigimod, mezagitamab 600mg, and nipocalimab 60mg/kg were inferior to rozanolixzumab 7mg/kg (MD ranged from 2 to 3.69) and rozanolixzumab 10mg/kg (MD ranged from 2.04 to 3.72) in MG-ADL score, and rozanolixzumab had the highest rank probability (83%) according to the subjective surface under the curve ranking area (SUCRA). For QMG score, batoclimab 340mg (MD ranged from 4.32 to 8.52) and batoclimab 680mg (MD ranged from 4.11 to 9.31) were more effective than placebo and other monoclonal antibodies except for rozanolixzumab, with the highest SUCRA value (93% and 97% respectively). For safety outcomes, belimumab achieved the highest SUCRA value (89.8%) with significant statistical difference compared to rozanolixzumab 7mg/kg (RR 0.08, 95%CrI 0.01 to 0.94) and rozanolixzumab 10mg/kg (RR 0.08, 95%CrI 0.01 to 0.86). Conclusion: While all monoclonal antibodies were superior to the placebo, rozanolixzumab and batoclimab might be the most effective for generalized MG. However, rozanolixzumab was associated with higher incidence of AEs. Given the limitations inherent in indirect comparisons, further head-to-head and extensive observational studies are necessary to confirm our findings. [ABSTRACT FROM AUTHOR]

Background: This meta-analysis evaluates the efficacy and safety of amyloid-ß (Aβ) targeted therapies for delaying cognitive deterioration in Alzheimer's disease (AD). Methods: PubMed, EMBASE, the Cochrane Library, and ClinicalTrials.gov were systematically searched to identify relevant studies published before January 18, 2023. Results: We pooled 33,689 participants from 42 studies. The meta-analysis showed no difference between anti-Aβ drugs and placebo in the Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog), and anti-Aβ drugs were associated with a high risk of adverse events [ADAS-Cog: MDs= -0.08 (-0.32 to 0.15), p = 0.4785; AEs: RR= 1.07 (1.02 to 1.11), p = 0.0014]. Monoclonal antibodies outperformed the placebo in delaying cognitive deterioration as measured by ADAS-Cog, Clinical Dementia Rating-Sum of Boxes (CDR-SB), Mini-Mental State Examination (MMSE) and Alzheimer's Disease Cooperative Study-Activities of Daily Living (ADCS-ADL), without increasing the risk of adverse events [ADASCog: MDs= -0.55 (-0.89 to 0.21), p = 0.001; CDR-SB: MDs= -0.19 (-0.29 to -0.10), p < 0.0001; MMSE: MDs= 0.19 (0.00 to 0.39), p = 0.05; ADCS-ADL: MDs= 1.26 (0.84 to 1.68), p < 0.00001]. Intravenous immunoglobulin and γ-secretase modulators (GSM) increased cognitive decline in CDR-SB [MDs= 0.45 (0.17 to 0.74), p = 0.002], but had acceptable safety profiles in AD patients. γ-secretase inhibitors (GSI) increased cognitive decline in ADAS-Cog, and also in MMSE and ADCS-ADL. BACE-1 inhibitors aggravated cognitive deterioration in the outcome of the Neuropsychiatric Inventory (NPI). GSI and BACE-1 inhibitors caused safety concerns. No evidence indicates active Aβ immunotherapy, MPAC, or tramiprosate have effects on cognitive function and tramiprosate is associated with serious adverse events. Conclusion: Current evidence does not show that anti-Aβ drugs have an effect on cognitive performance in AD patients. However, monoclonal antibodies can delay cognitive decline in AD. Development of other types of anti-Aβ drugs should be cautious. [ABSTRACT FROM AUTHOR]

Ensuring mitochondrial quality is essential for maintaining neuronal homeostasis, and mitochondrial transport plays a vital role in mitochondrial quality control. In this review, we first provide an overview of neuronal mitochondrial transport, followed by a detailed description of the various motors and adaptors associated with the anterograde and retrograde transport of mitochondria. Subsequently, we review the modest evidence involving mitochondrial transport mechanisms that has surfaced in acute neurological disorders, including traumatic brain injury, spinal cord injury, spontaneous intracerebral hemorrhage, and ischemic stroke. An in-depth study of this area will help deepen our understanding of the mechanisms underlying the development of various acute neurological disorders and ultimately improve therapeutic options. [ABSTRACT FROM AUTHOR]

The BAHD acyltransferase family is a class of proteins in plants that can acylate a variety of primary and specialized secondary metabolites. The typically acylated products have greatly improved stability, lipid solubility, and bioavailability and thus show significant differences in their physicochemical properties and pharmacological activities. Here, we review the protein structure, catalytic mechanism, and phylogenetic reconstruction of plant BAHD acyltransferases to describe their family characteristics, acylation reactions, and the processes of potential functional differentiation. Moreover, the potential applications of the BAHD family in human activities are discussed from the perspectives of improving the quality of economic plants, enhancing the efficacy of medicinal plants, improving plant biomass for use in biofuel, and promoting stress resistance of land plants. This review provides a reference for the research and production of plant BAHD acyltransferases. [ABSTRACT FROM AUTHOR]

The lack of irrigation water in agricultural soils poses a significant constraint on global crop production. In-depth investigation into microRNAs (miRNAs) has been widely used to achieve a comprehensive understanding of plant defense mechanisms. However, there is limited knowledge on the association of miRNAs with drought tolerance in cigar tobacco. In this study, a hydroponic experiment was carried out to identify changes in plant physiological characteristics, miRNA expression and metabolite profile under drought stress, and examine the mitigating effects of selenium (Se) application. The shoot dry weight of drought-stressed plants was approximately half (50.3%) of that in non-stressed (control) conditions. However, plants supplied with Se attained 38.8% greater shoot dry weight as compared to plants with no Se supply under drought stress. Thirteen miRNAs were identified to be associated with drought tolerance. These included 7 known (such as nta-miR156b and nta-miR166a) and 6 novel miRNAs (such as novel-nta-miR156-5p and novel-nta-miR209-5p) with the target genes of squamosa promoter-binding-like protein 4 (SPL4), serine/threonine protein phosphatase 2A (PPP2A), cation/calcium exchanger 4-like (CCX4), extensin-1 -like (EXT1) and reduced wall acetylation 2 (RWA2). Further investigation revealed that the expression levels of Ext1 and RWA2 were significantly decreased under drought stress but increased with Se addition. Moreover, key metabolites such as catechin and N-acetylneuraminic acid were identified, which may play a role in the regulation of drought tolerance. The integrated analysis of miRNA sequencing and metabolome highlighted the significance of the novel-nta)miR97-5p- LRR-RLK- catechin pathway in regulating drought tolerance. Our findings provide valuable insights into the molecular mechanisms underlying drought tolerance and Se-induced stress alleviation in cigar tobacco. [ABSTRACT FROM AUTHOR]

Previous studies have revealed cellular heterogeneity in intervertebral discs (IVDs). However, the cellular and molecular alteration patterns of cell populations during degenerative progression remain to be fully elucidated. To illustrate the cellular and molecular alteration of cell populations in intervertebral disc degeneration (IDD), we perform single cell RNA sequencing on cells from four anatomic sites of healthy and degenerative goat IVDs. EGLN3+ StressCs, TGFBR3+ HomCs and GPRC5A+ RegCs exhibit the characteristics associated with resistance to stress, maintaining homeostasis and repairing, respectively. The frequencies and signatures of these cell clusters fluctuate with IDD. Notably, the chondrogenic differentiation programme of PROCR+ progenitor cells is altered by IDD, while notochord cells turn to stemness exhaustion. In addition, we characterise CAV1+ endothelial cells that communicate with chondrocytes through multiple signalling pathways in degenerative IVDs. Our comprehensive analysis identifies the variability of key cell clusters and critical regulatory networks responding to IDD, which will facilitate in-depth investigation of therapeutic strategies for IDD. [ABSTRACT FROM AUTHOR]

Accurate and stable carbon price forecasts serve as a reference for assessing the stability of the carbon market and play a vital role in enhancing investment and operational decisions. However, realizing this goal is still a significant challenge, and researchers usually ignore multi-step-ahead and interval forecasting due to the non-linear and non-stationary characteristics of carbon price series and its complex fluctuation features. In this study, a novel hybrid model for accurately predicting carbon prices is proposed. The proposed model combines multi-step-ahead and interval carbon price forecasting based on the Hampel identifier (HI), time-varying filtering-based empirical mode decomposition (TVFEMD), and transformer model. First, HI identifies and corrects outliers in carbon price. Second, TVFEMD decomposes carbon price into several intrinsic mode functions (imfs) to reduce the non-linear and non-stationarity of carbon price to obtain more regular features in series. Next, these imfs are reconstructed by sample entropy (SE). Subsequently, the orthogonal array tuning method is used to optimize the transformer model's hyperparameters to obtain the optimal model structure. Finally, after hyperparameter optimization and quantile loss function, the transformer is used to perform multi-step-ahead and interval forecasting on each part of the reconstruction, and the final prediction result is obtained by summing them up. Five pilot carbon trading markets in China were selected as experimental objects to verify the proposed model's prediction performance. Various benchmark models and evaluation indicators were selected for comparison and analysis. Experimental results show that the proposed HI-TVFEMD-transformer hybrid model achieves an average MAE of 0.6546, 1.3992, 1.6287, and 2.2601 for one-step, three-step, five-step, and ten-step-ahead forecasting, respectively, which significantly outperforms other models. Furthermore, interval forecasts almost always have a PICI above 0.95 at a confidence interval of 0.1, thereby indicating the effectiveness of the hybrid model in describing the uncertainty in the forecasts. Therefore, the proposed hybrid model is a reliable carbon price forecasting tool that can provide a dependable reference for policymakers and investors. [ABSTRACT FROM AUTHOR]

Sepsis presents as a severe infectious disease frequently documented in clinical settings. Characterized by its systemic inflammatory response syndrome, sepsis has the potential to trigger multi-organ dysfunction and can escalate to becoming life-threatening. A common fallout from sepsis is acute lung injury (ALI), which often progresses to acute respiratory distress syndrome (ARDS). Macrophages, due to their significant role in the immune system, are receiving increased attention in clinical studies. Macrophage polarization is a process that hinges on an intricate regulatory network influenced by a myriad of signaling molecules, transcription factors, epigenetic modifications, and metabolic reprogramming. In this review, our primary focus is on the classically activated macrophages (M1-like) and alternatively activated macrophages (M2-like) as the two paramount phenotypes instrumental in sepsis' host immune response. An imbalance between M1-like and M2-like macrophages can precipitate the onset and exacerbate the progression of sepsis. This review provides a comprehensive understanding of the interplay between macrophage polarization and sepsisinduced acute lung injury (SALI) and elaborates on the intervention strategy that centers around the crucial process of macrophage polarization. [ABSTRACT FROM AUTHOR]

Introduction: The detection of smoking behavior is an emerging field faced with challenges in identifying small, frequently occluded objects like cigarette butts using existing deep learning technologies. Such challenges have led to unsatisfactory detection accuracy and poor model robustness. Methods: To overcome these issues, this paper introduces a novel smoking detection algorithm, YOLOv8-MNC, which builds on the YOLOv8 network and includes a specialized layer for small target detection. The YOLOv8-MNC algorithm employs three key strategies: (1) It utilizes NWD Loss to mitigate the effects of minor deviations in object positions on IoU, thereby enhancing training accuracy; (2) It incorporates the Multi-head Self-Attention Mechanism (MHSA) to bolster the network's global feature learning capacity; and (3) It implements the lightweight general up-sampling operator CARAFE, in place of conventional nearest-neighbor interpolation up-sampling modules, minimizing feature information loss during the up-sampling process. Results: Experimental results from a customized smoking behavior dataset demonstrate significant improvement in detection accuracy. The YOLOv8-MNC model achieved a detection accuracy of 85.887%, signifying a remarkable increase of 5.7% in the mean Average Precision (mAP@0.5) when compared to the previous algorithm. Discussion: The YOLOv8-MNC algorithm represents a valuable step forward in resolving existing problems in smoking behavior detection. Its enhanced performance in both detection accuracy and robustness indicates potential applicability in related fields, thus illustrating a meaningful advancement in the sphere of smoking behavior detection. Future efforts will focus on refining this technique and exploring its application in broader contexts. [ABSTRACT FROM AUTHOR]

Objective: In recent years, several studies have used computed tomography perfusion (CTP) to assess whether mechanical thrombectomy can be performed in patients with large-vessel occlusion (LVO) stroke in an extended time window. However, it has the disadvantage of being time-consuming and expensive. This study aimed to compare the impact of the CTP group with the non-CTP group [non-contrast CT (NCCT) ± CT angiography (CTA)] on the prognosis of this patient population. Methods: A search of PubMed, EMBASE, and the Cochrane Library databases was conducted to collect randomized controlled trials (RCTs) comparing the two strategies. Outcome indicators and factors influencing prognosis were summarized by standardized mean differences, ratios, and relative risks with 95% confidence intervals using a random-effects model. Results: A total of two RCTs were included in the combined analysis. There were no significant differences in the main outcome indicators (modified Rankin Scale score at 90 days, successful postoperative reperfusion rate) or the incidence of adverse events (90-day mortality and symptomatic intracranial hemorrhage) between the NCCT ± CTA and CTP groups. The time from the last puncture appeared to be significantly shorter in the NCCT ± CTA group than in the CTP group (SMD: -0.14; 95% CI: -0.24, -0.04). Among them, age (OR: 0.96; 95% CI: 0.94, 0.98), ASPECTS (OR: 1.18; 95% CI: 1.12, 1.24), NIHSS score (OR: 0.90; 95% CI: 0.89, 0.91), and diabetes (OR: 0.69; 95% CI: 0.54, 0.88) were associated with a 90-day independent functional outcome. Conclusion: These findings suggest that the choice of NCCT ± CTA (without CTP) for the assessment of mechanical thrombectomy within 6-24 h after LVO in the anterior circulation is not significantly different from CTP; instead, the choice of NCCT ± CTA significantly reduces the time from onset to arterial puncture. [ABSTRACT FROM AUTHOR]

Background: Immunoglobulin A nephropathy (IgAN) is one of the leading causes of end-stage kidney disease (ESKD). Many studies have shown the significance of pathological manifestations in predicting the outcome of patients with IgAN, especially T-score of Oxford classification. Evaluating prognosis may be hampered in patients without renal biopsy. Methods: A baseline dataset of 690 patients with IgAN and an independent follow-up dataset of 1,168 patients were used as training and testing sets to develop the pathology T-score prediction (Tpre) model based on the stacking algorithm, respectively. The 5-year ESKD prediction models using clinical variables (base model), clinical variables and real pathological T-score (base model plus Tbio), and clinical variables and Tpre (base model plus Tpre) were developed separately in 1,168 patients with regular follow-up to evaluate whether Tpre could assist in predicting ESKD. In addition, an external validation set consisting of 355 patients was used to evaluate the performance of the 5-year ESKD prediction model using Tpre. Results: The features selected by AUCRF for the Tpre model included age, systolic arterial pressure, diastolic arterial pressure, proteinuria, eGFR, serum IgA, and uric acid. The AUC of the Tpre was 0.82 (95% CI: 0.80–0.85) in an independent testing set. For the 5-year ESKD prediction model, the AUC of the base model was 0.86 (95% CI: 0.75–0.97). When the Tbio was added to the base model, there was an increase in AUC [from 0.86 (95% CI: 0.75–0.97) to 0.92 (95% CI: 0.85–0.98); P = 0.03]. There was no difference in AUC between the base model plus Tpre and the base model plus Tbio [0.90 (95% CI: 0.82–0.99) vs. 0.92 (95% CI: 0.85–0.98), P = 0.52]. The AUC of the 5-year ESKD prediction model using Tpre was 0.93 (95% CI: 0.87–0.99) in the external validation set. Conclusion: A pathology T-score prediction (Tpre) model using routine clinical characteristics was constructed, which could predict the pathological severity and assist clinicians to predict the prognosis of IgAN patients lacking kidney pathology scores. [ABSTRACT FROM AUTHOR]

Background: Parkinson's disease (PD) is a neurodegenerative disorder defined by progressive motor and non-motor symptoms. Currently, the pro-cognitive effects of transcranial direct current stimulation (tDCS) and repetitive transcranial magnetic stimulation (rTMS) are well-supported in previous literatures. However, controversy surrounding the optimal therapeutic target for motor symptom improvement remains. Objective: This network meta-analysis (NMA) was conducted to comprehensively evaluate the optimal strategy to use rTMS and tDCS to improve motor symptoms in PD. Methods: We searched PubMed, Embase, and Cochrane electronic databases for eligible randomized controlled studies (RCTs). The primary outcome was the changes of Unified Parkinson's Disease Rating Scale (UPDRS) part III score, the secondary outcomes were Time Up and Go Test (TUGT) time, and Freezing of Gait Questionnaire (FOGQ) score. The safety outcome was indicated by device-related adverse events (AEs). Result: We enrolled 28 studies that investigated various strategies, including high-frequency rTMS (HFrTMS), low-frequency rTMS (LFrTMS), anodal tDCS (AtDCS), AtDCS_ cathode tDCS (CtDCS), HFrTMS_LFrTMS, and Sham control groups. Both HFrTMS (short-term: mean difference (MD) −5.21, 95% credible interval (CrI) −9.26 to −1.23, long-term: MD −4.74, 95% CrI −6.45 to −3.05), and LFrTMS (long-term: MD −4.83, 95% CrI −6.42 to −3.26) were effective in improving UPDRS-III score compared with Sham stimulation. For TUGT time, HFrTMS (short-term: MD −2.04, 95% CrI −3.26 to −0.8, long-term: MD −2.66, 95% CrI −3.55 to −1.77), and AtDCS (short-term: MD −0.8, 95% CrI −1.26 to −0.34, long-term: MD −0.69, 95% CrI −1.31 to −0.08) produced a significant difference compared to Sham stimulation. However, no statistical difference was found in FOGQ score among the various groups. According to the surface under curve ranking area, HFrTMS ranked first in short-term UPDRS-III score (0.77), short-term (0.82), and long-term (0.84) TUGT time, and short-term FOGQ score (0.73). With respect to the safety outcomes, all strategies indicated few and self-limiting AEs. Conclusion: HFrTMS may be the optimal non-invasive brain stimulation (NIBS) intervention to improve motor function in patients with PD while NIBS has generally been well tolerated. However, further studies focusing on the clinical outcomes resulting from the different combined schedules of tDCS and rTMS are required. [ABSTRACT FROM AUTHOR]

Background: Chronic subdural hematoma (CSDH) is a neurosurgical condition with high prevalence. Many surgical approaches are recommended for treating CSDH, but there needs to be a consensus on the optimal technique. This network meta-analysis (NMA) compared the efficacy and safety of different surgical treatments for CSDH. Methods: Electronic databases, including PubMed, Embase, and the Cochrane Library, were searched for relevant studies up to February 2023. An NMA was performed to compare the outcomes of patients with CSDH treated by singlehole or double-hole craniotomy (SBHC and DBHC, respectively), twist-drill craniotomy (TDC), mini-craniotomy, and craniotomy. The NMA protocol was registered at INPLASY (registration no. 202320114). Results: The NMA included 38 studies with 7,337 patients. For efficacy outcomes, DBHC showed the highest surface under the cumulative ranking area (SUCRA) values for recurrence (96.3%) and reoperation (87.4%) rates. DBHC differed significantly from mini-craniotomy in recurrence rate (odds ratio [OR] = 0.58, 95% confidence interval [CI]: 0.35, 0.97) and from SBHC (OR = 0.48, 95% CI: 0.25, 0.91) and TDC (OR = 0.40, 95% CI: 0.20, 0.82) in reoperation rate. For operative time, TDC was superior to SBHC (mean difference [MD] = -2.32, 95% CI: -3.78 to -0.86), DBHC (MD = -3.61, 95% CI: -5.55, -1.67), and mini-craniotomy (MD = -3.39, 95% CI: -5.70, -1.08). Patients treated by TDC had a shorter hospital stay than those treated by SBHC (MD = -0.82, 95% CI: -1.51, -0.12). For safety outcomes, there were no significant differences between groups in mortality and complication rates; however, mini-craniotomy (79.8%) and TDC (78.1%) had the highest SUCRAs. Conclusion: DBHC may be the most effective surgical treatment for CSDH based on the low recurrence and reoperation rates, although all examined techniques were relatively safe. [ABSTRACT FROM AUTHOR]

Background: Several clinical trials have shown that intra-arterial thrombolysis using alteplase during mechanical thrombectomy (MT) has a better outcome than MT alone in ischemic stroke management. We performed the current metaanalysis to estimate the efficacy and safety of MT with intra-arterial alteplase therapy. Methods: The MEDLINE, Embase, Cochrane Library, and ClinicalTrials.gov databases were searched up to Mar. 2022 to identify the clinical trials that compared MT alone versus MT with intra-arterial alteplase therapy. STATA 16.0 was used for statistical analysis. The odds ratios (ORs) and 95% confidence intervals (95%CIs) were calculated with a random effect model. Results: Seven studies involving 1,083 participants were included. The primary outcomes were better functional outcomes, defined as a modified Rankin Scale (mRS) score between 0 and 2 at 90 days, and successful recanalization, defined as a modified thrombolysis in cerebral infarction (mTICI) score = 2b. Compared to MT alone, MT with intra-arterial alteplase did not lead to higher mTICI scores (OR 1.58, 95%CI 0.94 to 2.67, p = 0.085, I2 = 16.8%) but did lead to better mRS (OR 1.37, 95%CI 1.01 to 1.86, p = 0.044). There was no increase in mortality or bleeding events in the overall or subgroup analyses. Conclusion: MT with intra-arterial alteplase did not improve the recanalization rate but provided better functional outcomes. The intervention did not increase adverse effects in any subgroup at the same time. [ABSTRACT FROM AUTHOR]

Drug resistance in tumours has seriously hindered the therapeutic effect. Tumour drug resistance is divided into primary resistance and acquired resistance, and the recent study has found that a significant proportion of cancer cells can acquire stable drug resistance from scratch. This group of cells first enters the drug tolerance state (DT state) under drug pressure, and gradually acquires stable drug resistance through adaptive mutations in this state. Although the specific mechanisms underlying the formation of drug tolerant cells (DTCs) remain unclear, various proteins and signalling pathways have been identified as being involved in the formation of DTCs. In the current review, we summarize the characteristics, molecular mechanisms and therapeutic strategies of DTCs in detail. [ABSTRACT FROM AUTHOR]

Candida albicans (C. albicans) is an opportunistic pathogenic fungus that often causes mucosal and systemic infections. Several pattern recognition receptors (PRRs), such as Toll-like receptors (TLRs) and C-type lectin receptors (CLRs), have been implicated in the host recognition of C. albicans. These PRRs recognize the pathogen-associated molecular patterns (PAMPs) of C. albicans to activate innate immune cells, thereby rapidly inducing various inflammatory responses by activating intracellular signaling cascades. Herbal medicine and its active components deserve priority development due to their low toxicity and high antibacterial, antiviral and antifungal activities. This review discussed the activities of herbal compounds against C. albicans and their related mechanisms, especially their regulatory role on innate immune cells such as neutrophils, macrophages, and dendritic cells (DCs) implicated in C. albicans infections. Our work aims to find new therapeutic drugs and targets to prevent and treat diseases caused by C. albicans infection with the mechanisms by which this fungus interacts with the innate immune response. [ABSTRACT FROM AUTHOR]