Pulsatilla decoction alleviates DSS-induced UC by activating FXR-ASBT pathways to ameliorate disordered bile acids homeostasis.

Ethnopharmacological relevance: Pulsatilla decoction (PD) is a classical prescription for the treatment of ulcerative colitis. Previous studies have demonstrated that the therapeutic efficacy of PD is closely associated with the activation of Farnesoid X receptor (FXR). The activity of FXR is regulated by apical sodium-dependent bile acid transporter (ASBT), and the FXR-ASBT cascade reaction, centered around bile acid receptor FXR, plays a pivotal role in maintaining bile acid metabolic homeostasis to prevent the occurrence and progression of ulcerative colitis (UC). Aim of the study: To elucidate the underlying mechanism by which PD exerts its proteactive effects against Dextran Sulfate Sodium Salt (DSS)-induced ulcerative colitis, focusing on the modulation of FXR and ASBT. Materials and methods: To establish a model of acute ulcerative colitis, BALB/C mice were administered 3.5% DSS in their drinking water for consecutive 7 days. The disease activity index (DAI) was employed to evaluate the clinical symptoms exhibited by each group of mice. Goblet cell expression in colon tissue was assessed using glycogen schiff periodic acid-Schiff (PAS) and alcian blue staining techniques. Inflammatory cytokine expression in serum and colonic tissues was examined through enzyme-linked immunosorbent assay (ELISA). A PCR Array chip was utilized to screen 88 differential genes associated with the FXR-ASBT pathway in UC treatment with PD. Western blotting (WB) analysis was performed to detect protein expression levels of differentially expressed genes in mouse colon tissue. Results: The PD treatment effectively reduced the Disease Activity Index (DAI) score and mitigated colon histopathological damage, while also restoring weight and colon length. Furthermore, it significantly alleviated the severity of ulcerative colitis (UC), regulated inflammation, modulated goblet cell numbers, and restored bile acid balance. Additionally, a PCR Array analysis identified 21 differentially expressed genes involved in the FXR-ASBT pathway. Western blot results demonstrated significant restoration of FXR, GPBAR1, CYP7A1, and FGF15 protein expression levels following PD treatment; moreover, there was an observed tendency towards increased expression levels of ABCB11 and RXRα. Conclusion: The therapeutic efficacy of PD in UC mice is notable, potentially attributed to its modulation of bile acid homeostasis, enhancement of gut barrier function, and attenuation of intestinal inflammation.

Serum extracellular vesicle-derived miR-21-5p and miR-26a-5p as non-invasive diagnostic potential biomarkers for gastric cancer: A preliminary study.

PURPOSE: Gastric cancer is the most common malignancy worldwide and is the third leading cause of cancer-related deaths, urgently requiring an early and non-invasive diagnosis. Circulating extracellular vesicles may emerge as promising biomarkers for the rapid diagnosis in a non-invasive manner. METHODS: Using high-throughput small RNA sequencing, we profiled the small RNA population of serum-derived extracellular vesicles from healthy controls and gastric cancer patients. Differentially expressed microRNAs (miRNAs) were randomly selected and validated by reverse transcription-quantitative real-time polymerase chain reaction. Receiver operating characteristic curves were employed to assess the predictive value of miRNAs for gastric cancer. RESULTS: In this study, 193 differentially expressed miRNAs were identified, of which 152 were upregulated and 41 were significantly downregulated. Among the differently expressed miRNA, the expression levels of miR-21-5p, miR-26a-5p, and miR-27a-3p were significantly elevated in serum-derived extracellular vesicles of gastric cancer patients. The miR-21-5p and miR-27a-3p were closely correlated with the tumor size. Moreover, the expression levels of serum miR-21-5p and miR-26a-5p were significantly decreased in gastric cancer patients after surgery. CONCLUSIONS: The present study discovered the potential of serum miR-21-5p and miR-26a-5p as promising candidates for the diagnostic and prognostic markers of gastric cancer.

[Effects of long-term positioning tillage on13C assimilate distribution and grain yield formation in wheat]. / 长期定位耕作模式对小麦13CåŒåŒ–ç‰©åˆ†é å’Œç±½ç²’äº§é‡å½¢æˆçš„å½±å“.

To provide a theoretical basis and technical support for the high-yield and high-efficiency production of wheat, we examined the effects of different tillage patterns on wheat grain yield of Jimai 22 and the physiological mechanisms in an experiment with three treatments: 14 years in rotary tillage (R), minimal and no tillage (S), and minimal and no tillage with a 2-year subsoiling interval (SS). We assessed the light interception by wheat plant canopy, the distribution of photosynthate transport, and grain yield for the three cultivation modes. The results showed that leaf area index was significantly higher for SS treatment than the other treatments at 14-28 days after anthesis. The interception rate and amount of photosynthetically active radiation in the upper and middle layers of wheat canopy were significantly higher for SS treatment than R and S treatments at 21 days after anthesis. The contribution rate of grain assimilation and the distribution proportion of 13C assimilated in grain, and the maximum and average filling rates, were the highest under SS treatment. The 1000-kernel weight for SS treatment increased by 8.7% and 9.6%, and the grain yield increased by 14.2% and 19.4% compared with R and S treatments, respectively. SS treatment significantly improved light energy utilization by wheat canopy, promoted the accumulation and transport of dry matter, increased the grain-filling rate, increased grain weight, which together contributed to the highest grain yield. Therefore, SS was the optimal tillage pattern under the conditions of this experiment.

[Effects of N, P, and K application rates on distribution of 13C assimilates, starch accumulation in grains and fertilizer utilization of wheat]. / 氮磷钾施用量对小麦旗叶13CåŒåŒ–ç‰©åˆ†é ã€ç±½ç²’æ·€ç²‰ç§¯ç´¯å’Œè‚¥æ–™åˆ©ç”¨çš„å½±å“.

Clarifying the appropriate application rates of N, P, and K fertilizers and the physiological mechanisms of wheat under water-saving recharge irrigation in the North China Plain would provide a theoretical basis for formulating reasonable fertilization plans for high-yield and high-efficiency wheat production. We established four treatments with different amounts of nitrogen (N), phosphorus (P2O5), and potassium (K2O) application: 0, 0, and 0 kg·hm-2 (F0), 180, 75, and 60 kg·hm-2 (F1), 225, 120, and 105 kg·hm-2 (F2), and 270, 165, and 150 kg·hm-2 (F3). During the jointing and anthesis stages of wheat, the relative water content of each treatment in the 0-40 cm soil layer was replenished to 70%, to investigate the differences in wheat flag leaf photosynthetic characteristics, distribution of 13C assimilates, grain starch accumulation, and fertilizer utilization. The results showed that the relative chlorophyll content of flag leaves, photosynthetic and chlorophyll fluorescence parameters, 13C assimilate allocation in each organ, enzyme activities involved in starch synthesis, and starch accumulation in the F1 treatment were significantly higher than that in F0 treatment, which was an important physiological basis for the 20.9% increase in grain yield. The above parameters and yield in the F2 and F3 treatments showed no significant increase compared to F1 treatment, while fertilizer productivity and agronomic efficiency of N, P, and K decreased by 17.5%-58.4% and 12.7%-50.7%, respectively. Therefore, F1 could promote flag leaf photosynthetic assimilate production and grain starch accumulation under water-saving supplementary irrigation conditions, resulting in higher grain yield and fertilizer utilization efficiency.

[Effects of phosphorus application rate on distribution of 13C assimilates and spike formation in different til-lers of wheat with supplementary irrigation]. / 补灌条件下施磷量对小麦不同茎蘖13CåŒåŒ–ç‰©åˆ†é åŠå ¶æˆç©—çš„å½±å“.

To clarify the appropriate rate of phosphorus application and physiological mechanism for promoting wheat tillering and efficient utilization of phosphorus fertilizer with supplementary irrigation, we used 'Jimai 22' wheat variety as the test material, to set up three phosphorus application treatments, including low (90 kg P2O5·hm-2, P1), medium (135 kg P2O5·hm-2, P2), and high (180 kg P2O5·hm-2, P3) application rates, with no phosphorus application as the control (P0). We increased the relative soil water content of each treatment at join-ting stage and anthesis stage to 70%, and measured the area of tiller node, the content of endogenous hormones, the number of tillers in each tiller position, photosynthetic parameters, the distribution of 13C assimilates in each stem and tiller, as well as the grain yield and partial productivity of phosphate fertilizer. The results showed that compared with P0 and P1 treatments, P2 significantly increased the area of tiller node and the trans-zeatin (tZ), the photosynthetic parameters of the uppermost expanded leaves of the main stem, the total tillers per plant, and the distribution of 13C assimilates in each tiller. The number of ears per plant was increased by 0.51 and 0.36, and grain yield was increased by 40.3% and 13.2%, respectively. In P3 treatment, the number of tillers increased, but the panicles per plant, and the grain yield and phosphate fertilizer partial productivity decreased. Our results suggested that the moderate phosphorus treatment (135 kg·hm-2) under supplementary irrigation was suitable for high yield and high efficiency of wheat.

The protective role of phlorizin against lipopolysaccharide-induced acute orchitis in mice associated with changes in gut microbiota composition.

Objective: Orchitis is a common reproductive disease of male animals, which has serious implications to human and animal reproduction. Additionally, phlorizin (PHN), a common polyphenol in apples and strawberries, has a variety of biological activities, including antioxidant, anti-inflammatory, anti-diabetic, and anti-aging activities. We aimed to determine the protective effects and potential mechanisms of PHN in lipopolysaccharide (LPS)-induced acute orchitis in mice. Method: After 21 days of PHN pretreatment, mice were injected with LPS to induce testicular inflammation, and then the changes of testicular tissue structure, expression of inflammatory factors, testosterone level, expression of testosterone-related genes, adhesion gene and protein expression were detected, and the structural changes in the intestinal flora after PHN treatment were further detected by 16SRNA. Result: Our results demonstrated that PHN treatment reduced LPS-induced testicular injury and body and testicular weight losses. The mRNA expression levels of pro-inflammatory cytokines-related genes and antioxidant enzyme activity were also decreased and elevated, respectively, by PHN administration; however, PHN treatment also reduced the LPS-induced decrease in testosterone levels in the testes. Additionally, further studies found that PHN increased the expression of marker proteins zonula occludens-1 (ZO-1) and occludin associated with the blood testosterone barrier compared with that in LPS treatment groups. To further examine the potential mechanisms of the protective effect of PHN on LPS-induced testicular injury, we compared the differences of gut microbiota compositions between the 100 mg/kg PHN treatment group and the control group using 16SRNA. Metagenomic analyses indicated that the abundances of Bacteroidetes, Muribaculaceae, Lactobacillaceae, uncultured bacterium f Muribaculaceae, and Lactobacillus in the PHN treatment group improved, while potential microbes that can induce intestinal diseases, including Verrucomicrobia, Epsilonbacteraeota, Akkermansiaceae, and Akkermansia decreased in the PHN treatment group. Conclusion: Our results indicate that PHN pretreatment might alleviate orchitis by altering the composition of gut microflora, which may provide a reference for reducing the occurrence of acute orchitis in male animals.

Cu(II)-based complex loaded with drug paclitaxel hydrogels against thyroid cancer and optimizing novel derivatives.

This study introduces a novel approach for synthesizing a Cu(II)-based coordination polymer (CP), {[Cu(L)(4,4´-OBA)]·H2O}n (1), using a mixed ligand method. The CP was successfully prepared by reacting Cu(NO3)2·3H2O with the ligand 3,6-bis(benzimidazol-1-yl)pyridazine in the presence of 4,4´-H2OBA, demonstrating an innovative synthesis strategy. Furthermore, a novel hydrogel composed of hyaluronic acid (HA) and carboxymethyl chitosan (CMCS) with a porous structure was developed for drug delivery purposes. This hydrogel facilitates the encapsulation of CP1, and enables the loading of paclitaxel onto the composite to form HA/CMCS-CP1@paclitaxel. In vitro cell experiments demonstrated the promising modulation of thyroid cancer biomarker genes S100A6 and ARID1A by HA/CMCS-CP1@paclitaxel. Finally, reinforcement learning simulations were employed to optimize novel metal-organic frameworks, underscoring the innovative contributions of this study.

Identifying modifiable factors and their joint effect on brain health: an exposome-wide association study.

Considerable uncertainty remains regarding the associations of multiple factors with brain health. We aimed to conduct an exposome-wide association study on neurodegenerative disease and neuropsychiatry disorders using data of participants from the UK Biobank. Multivariable Cox regression models with the least absolute shrinkage and selection operator technique as well as principal component analyses were used to evaluate the exposures in relation to common disorders of central nervous system (CNS). Restricted cubic splines were conducted to explore potential nonlinear correlations. Then, weighted standardized scores were generated based on the coefficients to calculate the joint effects of risk factors. We also estimated the potential impact of eliminating the unfavorable profiles of risk domains on CNS disorders using population attributable fraction (PAF). Finally, sensitivity analyses were performed to reduce the risk of reverse causality. The current study discovered the significantly associated exposures fell into six primary exposome categories. The joint effects of identified risk factors demonstrated higher risks for common disorders of CNS (HR = 1.278 ~ 3.743, p < 2e-16). The PAF varied by exposome categories, with lifestyle and medical history contributing to majority of disease cases. In total, we estimated that up to 3.7 ~ 64.1% of disease cases could be prevented.This study yielded modifiable variables of different categories and assessed their joint effects on common disorders of CNS. Targeting the identified exposures might help formulate effective strategies for maintaining brain health.

Research on the mechanism of Guanyu Zhixie Granule in intervening gastric ulcers in rats based on network pharmacology and multi-omics.

Objective: Guanyu Zhixie Granule (GYZXG) is a traditional Chinese medicine compound with definite efficacy in intervening in gastric ulcers (GUs). However, the effect mechanisms on GU are still unclear. This study aimed to explore its mechanism against GU based on amalgamated strategies. Methods: The comprehensive chemical characterization of the active compounds of GYZXG was conducted using UHPLC-Q/TOF-MS. Based on these results, key targets and action mechanisms were predicted through network pharmacology. GU was then induced in rats using anhydrous ethanol (1 mL/200 g). The intervention effects of GYZXG on GU were evaluated by measuring the inhibition rate of GU, conducting HE staining, and assessing the levels of IL-6, TNF-α, IL-10, IL-4, Pepsin (PP), and epidermal growth factor (EGF). Real-time quantitative PCR (RT-qPCR) was used to verify the mRNA levels of key targets and pathways. Metabolomics, combined with 16S rRNA sequencing, was used to investigate and confirm the action mechanism of GYZXG on GU. The correlation analysis between differential gut microbiota and differential metabolites was conducted using the spearman method. Results: For the first time, the results showed that nine active ingredients and sixteen targets were confirmed to intervene in GU when using GYZXG. Compared with the model group, GYZXG was found to increase the ulcer inhibition rate in the GYZXG-M group (p < 0.05), reduce the levels of IL-6, TNF-α, PP in gastric tissue, and increase the levels of IL-10, IL-4, and EGF. GYZXG could intervene in GU by regulating serum metabolites such as Glycocholic acid, Epinephrine, Ascorbic acid, and Linoleic acid, and by influencing bile secretion, the HIF-1 signaling pathway, and adipocyte catabolism. Additionally, GYZXG could intervene in GU by altering the gut microbiota diversity and modulating the relative abundance of Bacteroidetes, Bacteroides, Verrucomicrobia, Akkermansia, and Ruminococcus. The differential gut microbiota was strongly associated with serum differential metabolites. KEGG enrichment analysis indicated a significant role of the HIF-1 signaling pathway in GYZXG's intervention on GU. The changes in metabolites within metabolic pathways and the alterations in RELA, HIF1A, and EGF mRNA levels in RT-qPCR experiments provide further confirmation of this result. Conclusion: GYZXG can intervene in GU induced by anhydrous ethanol in rats by regulating gut microbiota and metabolic disorders, providing a theoretical basis for its use in GU intervention.

Multimode Ultrasound Model for Predicting the Early Treatment Response of Anti-VEGF Agents Plus Anti-PD-1 Antibody in Patients with Unresectable Hepatocellular Carcinoma.

OBJECTIVE: The purpose of the study described was to establish prediction models to initially screen the beneficiary patients with unresectable hepatocellular carcinoma (HCC) in the treatment of anti-vascular endothelial growth factor (VEGF) agents plus anti-programmed cell death-1 (PD-1) antibody. METHODS: A total of 62 patients were enrolled in this study. All patients underwent ultrasound (US), color ddoppler flowing imaging (CDFI), contrast-enhanced ultrasound (CEUS) and laboratory examinations within 2 wk before the treatment. Tumor response was assessed according to mRECIST criteria. Univariate and multivariate analyses were used to select the independent predictors. US + CDFI, CEUS and FULL models were established. Three models were displayed by nomography. Receiver operating characteristic (ROC) and calibration curves were drawn to evaluate the predictive ability of models. Decision curve analysis (DCA) was used to assess the clinical utility of models. RESULTS: On univariate and multivariate analysis, the US boundary (p = 0.037), halo (p = 0.002) and CDFI (p = 0.024) were included in the US + CDFI model. CEUS boundary (p = 0.001) and washout time (p < 0.001) were included in the CEUS model. The number of lesions (p = 0.104), halo on US (p = 0.014), CDFI (p = 0.057) and washout time on CEUS (p = 0.015) were incorporated into the FULL model. The C indices of the US + CDFI, CEUS and FULL models were 0.918, 0.920 and 0.973. CEUS and FULL models yielded a good net benefit for almost all threshold probabilities. CONCLUSION: Nomograms based on US, CDFI, CEUS and clinical characteristics could help to non-invasively predict the response to treatment with anti-PD-1 antibodies plus anti-VEGF agents.

Effect of Spleen Aminopeptide Oral Lyophilized Powder and Fluticasone/salmeterol Powder Inhaler on Pulmonary Function and Incidence of Adverse Reactions in Children with Cough Variant Asthma.

Background: Cough variant asthma is a prevalent condition among children with chronic cough, significantly impacting their health and well-being. Objective: This study aimed to assess the impact of spleen aminopeptide oral lyophilized powder and fluticasone/salmeterol powder inhaler on pulmonary function and the incidence of adverse reactions in children with cough variant asthma. Methods: A total of 60 children with cough variant asthma admitted to the Pediatric Department of Cangzhou Central Hospital between July 2019 and June 2020 were enrolled in the study. Using the random number table method, they were assigned to either the observation group or the control group, with 30 cases in each group. The control group received treatment with fluticasone/salmeterol powder inhalers, while the observation group received a combination of fluticasone/salmeterol powder inhalers and spleen aminopeptide oral lyophilized powder. After 8 weeks of treatment, various clinical parameters, including forced vital capacity, forced expiratory volume per second/forced vital capacity, peak expiratory flow, fractional exhaled nitric oxide (FeNO), interleukin-4 (IL-4), IL-10, eosinophils in induced sputum, and serum CD4+ and CD8+ levels, were compared between the two groups. Results: The observation group exhibited a higher total effective rate of clinical efficacy compared to the control group [90.00% vs. 63.33%; OR (95% CI) 3.00 (1.01-8.92), P = .048)]. After 8 weeks, the observation group demonstrated higher levels of forced vital capacity, forced expiratory volume per second/forced vital capacity, peak expiratory flow [OR (95% CI) 0.48 (0.26-0.88), P = .017; OR (95% CI) 0.29 (0.14-0.57) 2.57 (1.46-4.52) 0.33 (0.16-0.70), P = .000, .001, .003], IL-10 [OR (95% CI) 0.29 (0.14-0.57), P = .000], and lower levels of FeNO [OR (95% CI) 0.48 (0.26-0.88), P = .017], IL-4, and eosinophils [OR (95% CI) 2.57 (1.46-4.52) 0.33 (0.16-0.70), P = .001, .003] compared to the control group (P < .05). Furthermore, the observation group exhibited higher levels of CD4+ and CD4+/CD8+ compared to the control group [OR (95% CI) 0.41 (0.25-0.67) 0.33 (0.20-0.56) 1.73 (1.18-2.55), P = .000, .000, .001]. Computed tomography measurements revealed significantly lower airway wall thickness, basement membrane thickness, and total airway wall area in the observation group compared to the control group [OR (95% CI) 0.18 (0.10-0.33) 0.23 (0.13-0.41) 0.28 (0.15-0.51), P = .000, .000, .000]. The incidence of adverse reactions did not significantly differ between the groups (6.67% vs. 3.33%; P > .05). Conclusion: The combination treatment of spleen aminopeptide oral lyophilized powder and fluticasone/salmeterol powder inhaler effectively improves lung function, FeNO levels, and airway inflammation, while enhancing cellular and humoral immune function in children with cough variant asthma. These findings have significant clinical implications and warrant further promotion and application of this treatment approach.

Artificial Intelligence-Assisted Prescription Determination for Orthokeratology Lens Fitting: From Algorithm to Clinical Practice.

OBJECTIVES: To explore the potential of artificial intelligence (AI) to assist prescription determination for orthokeratology (OK) lenses. METHODS: Artificial intelligence algorithm development followed by a real-world trial. A total of 11,502 OK lenses fitting records collected from seven clinical environments covering major brands. Records were randomly divided in a three-way data split. Cross-validation was used to identify the most accurate algorithm, followed by an evaluation using an independent test data set. An online AI-assisted system was implemented and assessed in a real-world trial involving four junior and three senior clinicians. RESULTS: The primary outcome measure was the algorithm's accuracy (ACC). The ACC of the best performance of algorithms to predict the targeted reduction amplitude, lens diameter, and alignment curve of the prescription was 0.80, 0.82, and 0.83, respectively. With the assistance of the AI system, the number of trials required to determine the final prescription significantly decreased for six of the seven participating clinicians (all P <0.01). This reduction was more significant among junior clinicians compared with consultants (0.76±0.60 vs. 0.32±0.60, P <0.001). Junior clinicians achieved clinical outcomes comparable to their seniors, as 93.96% (140/149) and 94.44% (119/126), respectively, of the eyes fitted achieved unaided visual acuity no worse than 0.8 ( P =0.864). CONCLUSIONS: AI can improve prescription efficiency and reduce discrepancies in clinical outcomes among clinicians with differing levels of experience. Embedment of AI in practice should ultimately help lessen the medical burden and improve service quality for myopia boom emerging worldwide.

Global survey of hgcA-carrying genomes in marine and freshwater sediments: Insights into mercury methylation processes.

Mercury (Hg) methylation is a microbially mediated process that produces methylmercury (MeHg), a bioaccumulative neurotoxin. A highly conserved gene pair, hgcAB, is required for Hg methylation, which provides a basis for identifying Hg methylators and evaluating their genomic composition. In this study, we conducted a large-scale omics analysis in which 281 metagenomic freshwater and marine sediment samples from 46 geographic locations across the globe were queried. Specific objectives were to examine the prevalence of Hg methylators, to identify horizontal gene transfer (HGT) events involving hgcAB within Hg methylator communities, and to identify associations between hgcAB and microbial biochemical functions/genes. Hg methylators from the phyla Desulfobacterota and Bacteroidota were dominant in both freshwater and marine sediments while Firmicutes and methanogens belonging to Euryarchaeota were identified only in freshwater sediments. Novel Hg methylators were found in the Phycisphaerae and Planctomycetia classes within the phylum Planctomycetota, including potential hgcA-carrying anammox metagenome-assembled genomes (MAGs) from Candidatus Brocadiia. HGT of hgcA and hgcB were identified in both freshwater and marine methylator communities. Spearman's correlation analysis of methylator genomes suggested that in addition to sulfide, thiosulfate, sulfite, and ammonia may be important parameters for Hg methylation processes in sediments. Overall, our results indicated that the biochemical drivers of Hg methylation vary between marine and freshwater sites, lending insight into the influence of environmental perturbances, such as a changing climate, on Hg methylation processes.

High-valent metal-oxo species transformation and regulation by co-existing chloride: Reaction pathways and impacts on the generation of chlorinated by-products.

High-valent metal-oxo species (HMOS) have been extensively recognized in advanced oxidation processes (AOPs) owing to their high selectivity and high chemical utilization efficiency. However, the interactions between HMOS and halide ions in sewage wastewater are complicated, leading to ongoing debates on the intrinsic reactive species and impacts on remediation. Herein, we prepared three typical HMOS, including Fe(IV), Mn(V)-nitrilotriacetic acid complex (Mn(V)NTA) and Co(IV) through peroxymonosulfate (PMS) activation and comparatively studied their interactions with Cl- to reveal different reactive chlorine species (RCS) and the effects of HMOS types on RCS generation pathways. Our results show that the presence of Cl- alters the cleavage behavior of the peroxide OO bond in PMS and prohibits the generation of Fe(IV), spontaneously promoting SO4•- production and its subsequent transformation to secondary radicals like Cl• and Cl2•-. The generation and oxidation capacity of Mn(V)NTA was scarcely influenced by Cl-, while Cl- would substantially consume Co(IV) and promote HOCl generation through an oxygen-transfer reaction, evidenced by density functional theory (DFT) and deuterium oxide solvent exchange experiment. The two-electron-transfer standard redox potentials of Fe(IV), Mn(V)NTA and Co(IV) were calculated as 2.43, 2.55 and 2.85 V, respectively. Due to the different reactive species and pathways in the presence of Cl-, the amounts of chlorinated by-products followed the order of Co(II)/PMS > Fe(II)/PMS > Mn(II)NTA/PMS. Thus, this work renovates the knowledge of halide chemistry in HMOS-based systems and sheds light on the impact on the treatment of salinity-containing wastewater.

Electroacupuncture improves low-grade duodenal inflammation in FD rats by reshaping intestinal flora through the NF-κB p65/NLRP3 pyroptosis pathway.

Electroacupuncture (EA) is an effective alternative for the treatment of functional dyspepsia (FD). It reduces low-grade duodenal inflammation and improves the symptoms of FD by downregulating the expression of NF-κB p65 and NLRP3, but its mechanism needs to be elucidated. To examine the regulatory effect of electroacupuncture (EA) on intestinal flora and NF-κB p65/NLRP3 pyroptosis pathway in FD rats. The FD rat model was established via multi-factor stress intervention for two weeks. The rats were randomly divided into the NC group, model group, NF-kB inhibitor group (NF-κB inhibitor BAY 11-7082 was administered), EA group, and EA + NF-kB inhibitor group. After 14 days of treatment, the rats were sacrificed, and the protein and mRNA levels of NF-κB p65, IκB, and NLRP3 in the duodenum were evaluated by Western blotting assays and real-time fluorescent quantitative PCR. The Illumina MiSeq sequencing platform was used to analyze the V4 region of the 16S rRNA gene of intestinal flora and predict functional genes. The concentration of short-chain fatty acids (SCFAs) in feces was assessed by metabolomics. EA can decrease low-grade duodenal inflammation and promote gastrointestinal motility in FD rats. This effect is mediated by inhibition of the NF-κB p65/NLRP3 pyroptosis pathway, an increase in the alpha and beta diversity of gut microbiota in the duodenum, an increase in the abundance of beneficial bacteria at the phylum and genus levels, and an increase in the content of SCFAs. The protective effect of EA against FD might involve multiple hierarchy and pathways. EA may remodel intestinal flora by inhibiting the NF-κB p65/NLRP3 pyroptosis pathway, thereby improving low-grade duodenal inflammation in FD rats.

Comparative Transcriptomics Uncovers Upstream Factors Regulating BnFAD3 Expression and Affecting Linolenic Acid Biosynthesis in Yellow-Seeded Rapeseed (Brassica napus L.).

α-Linolenic acid (ALA) is an important nutrient component in rapeseed oil, and rapeseed breeders want to either restrain or enhance the function of fatty acid desaturases (FADs) in the ALA biosynthesis pathway. To determine the reason for the upregulation of rapeseed BnFAD genes in two high-ALA accessions, R8Q10 and YH25005, we compared their transcriptome profiles in the seed at 24 days after pollination (DAP) with those of two low-ALA lines, A28 and SW. The expression levels of twenty-eight important genes in the seed samples at 20, 27, and 34 DAP were also investigated using an RT-qPCR. The expression levels of genes involved in flavonoid and proanthocyanidin synthesis, including BnCHS, BnCHI, BnDFR, BnFLS1, BnLDOX, BnBAN, BnTT10, and BnTT12 and genes encoding the transcription factors BnTT1, BnTT2, BnTT8, and BnTT16 were lower in R8Q10 and YH25005 than in A28 and SW. The expression levels of genes encoding master transcription factors in embryo development, such as BnLEC1, BnABI3, BnFUS3, BnL1L, BnAREB3, and BnbZIP67, were elevated significantly in the two high-ALA accessions. Combined with previous results in the Arabidopsis and rapeseed literature, we speculated that the yellow-seededness genes could elevate the activity of BnLEC1, BnABI3, BnFUS3, and BnbZIP67, etc., by reducing the expression levels of several transparent testa homologs, resulting in BnFAD3 and BnFAD7 upregulation and the acceleration of ALA synthesis. Yellow-seededness is a favorable factor to promote ALA synthesis in the two high-ALA accessions with the yellow-seeded trait. These findings provide initial insights into the transcriptomic differences between high-/low-ALA germplasms and a theoretic basis for seed quality breeding.

[Inhibition of Autophagy Augments the Anticancer Activity of KPT-330 in Mantle Cell Lymphoma Cells].

OBJECTIVE: To investigate the influence of novel CRM1 inhibitor KPT-330 on the autophagy of mantle cell lymphoma (MCL) cells, and effect of KPT-330 on the prolifiration of MCL cells in the presence or absence of autophagy inhibitor. METHODS: CCK-8 assay was used to detect the effect of KPT-330 on MCL cell lines Z-138， Jeko-1， Granta-519， Rec-1. The effect of KPT-330 on autophagy features were determined by detecting acidic vesicular organelles (AVO) by MDC staining under fluorescence microscope and detecting protein expression of LC3B-II assessed by Western blot. Further combined application of lysosomal inhibitor Chloroquine (CQ) was used to observe its effect on the increase of LC3B-Ⅱ caused by KPT-330. CalcuSyn 2.0 software was used to detected the Combination index (CI) of KPT-330 combined with CQ. RESULTS: The proliferation of MCL cell lines （Z-138, Jeko-1, Grant-519, Rec-1） could be inhibited by KPT-330 in a dose-dependent manner (r =0.930, 0.946, 0.691, 0.968 respectively). The number of acidic vesicular organelles (AVO) and the expression of LC3B-II were increased in KPT-330 treated Jeko-1 and Granta-519 cells in a dose-dependent manner (r Jeko-1=0.993, r Granta-519=0.971). LC3B-II protein amounts still increased upon KPT-330 treatment with the existence of lysosomal inhibitor CQ in Jeko-1 and Granta-519 cells, which was higher than CQ or KPT-330 single drug group. The combination of KPT-330 and CQ produced the synergistic effects on cells proliferation inhibition with CalcuSyn 2.0 analysis. CONCLUSION: KPT-330 can inhibit MCL cell proliferation and induce autophagy. KPT-330 combined with autophagy inhibitor CQ could produce synergistic anti MCL effects, providing experimental basis for clinical combination therapy.

Does the Dose of Standard Adjuvant Chemotherapy Affect the Triple-negative Breast Cancer Benefit from Extended Capecitabine Metronomic Therapy? An Exploratory Analysis of the SYSUCC-001 Trial.

Purpose: Results from studies of extended capecitabine after the standard adjuvant chemotherapy in early stage triple-negative breast cancer (TNBC) were inconsistent, and only low-dose capecitabine from the SYSUCC-001 trial improved disease-free survival (DFS). Adjustment of the conventional adjuvant chemotherapy doses affect the prognosis and may affect the efficacy of subsequent treatments. This study investigated whether the survival benefit of the SYSUCC-001 trial was affected by dose adjustment of the standard adjuvant chemotherapy or not. Patients and Methods: We reviewed the adjuvant chemotherapy regimens before the extended capecitabine in the SYSUCC-001 trial. Patients were classified into "consistent" (standard acceptable dose) and "inconsistent" (doses lower than acceptable dose) dose based on the minimum acceptable dose range in the landmark clinical trials. Cox proportional hazards model was used to investigate the impact of dose on the survival outcomes. Results: All 434 patients in SYSUCC-001 trial were enrolled in this study. Most of patients administered the anthracycline-taxane regimen accounted for 88.94%. Among patients in the "inconsistent" dose, 60.8% and 47% received lower doses of anthracycline and taxane separately. In the observation group, the "inconsistent" dose of anthracycline and taxane did not affect DFS compared with the "consistent" dose. Moreover, in the capecitabine group, the "inconsistent" anthracycline dose did not affect DFS compared with the "consistent" dose. However, patients with "consistent" taxane doses benefited significantly from extended capecitabine (P=0.014). The sufficient dose of adjuvant taxane had a positive effect of extended capecitabine (hazard ratio [HR] 2.04; 95% confidence interval [CI] 1.02 to 4.06). Conclusion: This study found the dose reduction of adjuvant taxane might negatively impact the efficacy of capecitabine. Therefore, the reduction of anthracycline dose over paclitaxel should be given priority during conventional adjuvant chemotherapy, if patients need dose reduction and plan for extended capecitabine.

Mice harboring the T316N variant in the GABAAR γ2 subunit exhibit sleep-related hypermotor epilepsy phenotypes and hypersynchronization in the thalamocortical pathway.

OBJECTIVE: Sleep-related hypermotor epilepsy (SHE) is a focal epilepsy syndrome characterized by seizures that predominantly occur during sleep. The pathogenesis of these seizures remains unclear. We previously detected rare variants in GABRG2, which encodes the γ2 subunit of γ-aminobutyric acid type A receptor (GABAAR), in patients with SHE and demonstrated that these variants impaired GABAAR function in vitro. However, the mechanisms by which GABRG2 variants contribute to seizure attacks during sleep remain unclear. METHODS: In this study, we designed a knock-in (KI) mouse expressing the mouse Gabrg2 T316N variant, corresponding to human GABRG2 T317N variant, using CRISPR/Cas9. Continuous video-electroencephalogram monitoring and in vivo multichannel electrophysiological recordings were performed to explore seizure susceptibility to pentylenetetrazol (PTZ), alterations in the sleep-wake cycle, spontaneous seizure patterns, and synchronized activity in the motor thalamic nuclei (MoTN) and secondary motor cortex (M2). Circadian variations in the expression of total, membrane-bound, and synaptic GABAAR subunits were also investigated. RESULTS: No obvious changes in gross morphology were detected in Gabrg2T316N/+ mice compared to their wild-type (Gabrg2+/+) littermates. Gabrg2T316N/+ mice share key phenotypes with patients, including sleep fragmentation and spontaneous seizures during sleep. Gabrg2T316N/+ mice showed increased susceptibility to PTZ-induced seizures and higher mortality after seizures. Synchronization of the local field potentials between the MoTN and M2 was abnormally enhanced in Gabrg2T316N/+ mice during light phase, when sleep dominates, accompanied by increased local activities in the MoTN and M2. Interestingly, in Gabrg2+/+ mice, GABAAR γ2 subunits showed a circadian increase on the neuronal membrane and synaptosomes in the transition from dark phase to light phase, which was absent in Gabrg2T316N/+ mice. CONCLUSION: We generated a new SHE mouse model and provided in vivo evidence that rare variants of GABRG2 contribute to seizure attacks during sleep in SHE.

[Cerebral oxygen metabolism and brain electrical activity of healthy full-term neonates in high-altitude areas: a multicenter clinical research protocol]. / é«˜æµ·æ‹”åœ°åŒºå¥åº·è¶³æœˆæ–°ç”Ÿå„¿è„‘æ°§ä»£è°¢åŠè„‘ç”µæ´»åŠ¨å·®å¼‚çš„å¤šä¸­å¿ƒä¸´åºŠç ”ç©¶æ–¹æ¡ˆ.

Further evidence is needed to explore the impact of high-altitude environments on the neurologic function of neonates. Non-invasive techniques such as cerebral near-infrared spectroscopy and amplitude-integrated electroencephalography can provide data on cerebral oxygenation and brain electrical activity. This study will conduct multiple cerebral near-infrared spectroscopy and amplitude-integrated electroencephalography monitoring sessions at various time points within the first 3 days postpartum for healthy full-term neonates at different altitudes. The obtained data on cerebral oxygenation and brain electrical activity will be compared between different altitudes, and corresponding reference ranges will be established. The study involves 6 participating centers in the Chinese High Altitude Neonatal Medicine Alliance, with altitude gradients divided into 4 categories: 800 m, 1 900 m, 2 400 m, and 3 500 m, with an anticipated sample size of 170 neonates per altitude gradient. This multicenter prospective cohort study aims to provide evidence supporting the impact of high-altitude environments on early brain function and metabolism in neonates.