Tryptophan supplements in high-carbohydrate diets by improving insulin response and glucose transport through PI3K-AKT-GLUT2 pathways in blunt snout bream (Megalobrama amblycephala).

The aim of this experiment was to elucidate the metabolic ramifications of tryptophan supplementation in the context of high-carbohydrate diet-feeding, which is important for improving feeding strategies in aquaculture in order to improve fish carbohydrate metabolism. Juvenile blunt snout bream with an initial mean body mass of 55.0±0.5 g were allocated to consume one of three experimental diets: CN, a normal diet with carbohydrate content of 30% (w/w); HC, a diet with high carbohydrate content of 43% (w/w); and HL, a high-carbohydrate diet to which 0.8% L-tryptophan (L-trp) had been added. These diets were fed for 8 weeks, and the effects of the carbohydrate and tryptophan contents of the diets were assessed. Histological analysis using Hematoxylin and Eosin (H&E) and Oil Red O staining revealed that high-carbohydrate intake was associated with abnormal hepatocyte morphology and excessive liver lipid accumulation, which were notably ameliorated by tryptophan supplementation. A significant increase in plasma glucose, glucagon, AGEs (advanced glycation end products), triglycerides, total cholesterol, and a significant decrease in insulin and hepatic glycogen after a high-carbohydrate diet in terms of plasma indices, compared to the control group. Almost all of them were restored to the normal level in the HL group. The present study might preliminarily suggest that tryptophan supplementation ameliorates the imbalance in glucose metabolism of this species induced by a high-carbohydrate diet. Transcriptomics showed that glucose metabolism under high carbohydrate was mainly regulated by the PI3K-AKT signaling pathway. The mRNA expression and protein levels of GLUT2 also varied with this pathway, which would suggest that sustained activation of this pathway with the addition of tryptophan accelerates glucose transport and insulin secretion under high-carbohydrate diet. Subsequent GTT and ITT experiments have also demonstrated that tryptophan improves glucose tolerance and insulin tolerance in blunt snout bream on a high-carbohydrate diet. In conclusion, these findings elucidate the positive regulatory effect of tryptophan on the PI3K-AKT-GLUT2 pathway under a high carbohydrate diet and provide a theoretical basis for the subsequent rational application of high carbohydrate diets in the future.

Allele-Specific Editing of a Dominant SCN8A Epilepsy Variant Protects against Seizures and Lethality in a Murine Model.

OBJECTIVE: Developmental and epileptic encephalopathies (DEEs) can result from dominant, gain of function variants of neuronal ion channels. More than 450 de novo missense variants of the sodium channel gene SCN8A have been identified in individuals with DEE. METHODS: We studied a mouse model carrying the patient Scn8a variant p.Asn1768Asp. An AAV-PHP.eB virus carrying an allele-specific single guide RNA (sgRNA) was administered by intracerebroventricular injection. Cas9 was provided by an inherited transgene. RESULTS: Allele-specific disruption of the reading frame of the pathogenic transcript generated out-of-frame indels in 1/4 to 1/3 of transcripts throughout the brain. This editing efficiency was sufficient to rescue lethality and seizures. Neuronal hyperexcitability was reduced in cells expressing the virus. INTERPRETATION: The data demonstrate efficient allele-specific editing of a dominant missense variant and support the feasibility of allele-specific therapy for DEE epilepsy. ANN NEUROL 2024.

Characterizing and identifying of miRNAs involved in berberine modulating glucose metabolism of Megalobrama amblycephala.

The present study, as one part of a larger project that aimed to investigate the effects of dietary berberine (BBR) on fish growth and glucose regulation, mainly focused on whether miRNAs involve in BBR's modulation of glucose metabolism in fish. Blunt snout bream Megalobrama amblycephala (average weight of 20.36 ± 1.44 g) were exposed to the control diet (NCD, 30% carbohydrate), the high-carbohydrate diet (HCD, 43% carbohydrate) and the berberine diet (HCB, HCD supplemented with 50 mg/kg BBR). After 10 weeks' feeding trial, intraperitoneal injection of glucose was conducted, and then, the plasma and liver were sampled at 0 h, 1 h, 2 h, 6 h, and 12 h. The results showed the plasma glucose levels in all groups rose sharply and peaked at 1 h after glucose injection. Unlike the NCD and HCB groups, the plasma glucose in the HCD group did not decrease after 1 h, while remained high level until at 2 h. The NCD group significantly increased liver glycogen content at times 0-2 h compared to the other two groups and then liver glycogen decreased sharply until at times 6-12 h. To investigate the role of BBR that may cause the changes in plasma glucose and liver glycogen, miRNA high-throughput sequencing was performed on three groups of liver tissues at 2 h time point. Eventually, 20 and 12 differentially expressed miRNAs (DEMs) were obtained in HCD vs NCD and HCB vs HCD, respectively. Through function analyzing, we found that HCD may affect liver metabolism under glucose loading through the NF-κB pathway; and miRNAs regulated by BBR mainly play roles in adipocyte lipolysis, niacin and nicotinamide metabolism, and amino acid transmembrane transport. In the functional exploration of newly discovered novel:Chr12_18892, we found its target gene, adenylate cyclase 3 (adcy3), was widely involved in lipid decomposition, amino acid metabolism, and other pathways. Furthermore, a targeting relationship of novel:Chr12_18892 and adcy3 was confirmed by double luciferase assay. Thus, BBR may promote novel:Chr12_18892 to regulate the expression of adcy3 and participate in glucose metabolism.

New therapeutic target NCF1-directed multi-bioactive conjugate therapies prevent preterm birth and adverse pregnancy outcomes.

Preterm birth (PTB) is a leading cause of neonatal morbidity and mortality worldwide, yet the cellular and molecular mechanisms driving this condition remain undeciphered, thus limiting discovery of new therapies. In-depth analyses of human and mouse tissues associated with PTB, in combination with cellular studies, indicated that aberrantly high-expressed neutrophil cytoplasmic factor (NCF) 1 leads to oxidative distress, recruitment, and pro-inflammatory activation of neutrophils and macrophages, while sequentially overexpressed pro-inflammatory mediators induce contractions of uterine smooth muscle cells (USMCs) as well as apoptosis of USMCs and amniotic epithelial cells, thereby causing PTB. According to these new findings, we rationally engineered an amphiphilic macromolecular conjugate LPA by covalently integrating low-molecular-weight heparin, a reactive oxygen species-responsive/scavenging component, and an anti-inflammatory peptide. This bioengineered macromolecular conjugate can self-assemble into multi-bioactive nanoparticles (LPA NP). In a mouse model of PTB, LPA NP effectively delayed PTB and inhibited adverse pregnancy outcomes, by regulating NCF1-mediated oxidative-inflammatory cascades, i.e., attenuating oxidative stress, inhibiting inflammatory cell activation, reducing local inflammation, and decreasing contraction/apoptosis of myometrial cells. Packaging LPA NP into temperature-responsive, self-healing, and bioadhesive hydrogel further potentiated its in vivo efficacies after intravaginal delivery, by prolonging retention time, sustaining nanotherapy release, and increasing bioavailability in the placenta/uterus. Importantly, both the conjugate/nanotherapy and hydrogel formulations exhibited excellent safety profiles in pregnant mice, with negligible side effects on the mother and offspring.

Cluster analysis-based classification of fatigue in stable maintenance hemodialysis patients: a prospective cohort study.

CLINICAL TRIAL REGISTRATION: This study has been registered (ChiCTR2100045493) 2021/04/03.

Brain age prediction using interpretable multi-feature-based convolutional neural network in mild traumatic brain injury.

BACKGROUND: Convolutional neural network (CNN) can capture the structural features changes of brain aging based on MRI, thus predict brain age in healthy individuals accurately. However, most studies use single feature to predict brain age in healthy individuals, ignoring adding information from multiple sources and the changes in brain aging patterns after mild traumatic brain injury (mTBI) were still unclear. METHODS: Here, we leveraged the structural data from a large, heterogeneous dataset (N = 1464) to implement an interpretable 3D combined CNN model for brain-age prediction. In addition, we also built an atlas-based occlusion analysis scheme with a fine-grained human Brainnetome Atlas to reveal the age-sstratified contributed brain regions for brain-age prediction in healthy controls (HCs) and mTBI patients. The correlations between brain predicted age gaps (brain-PAG) following mTBI and individual's cognitive impairment, as well as the level of plasma neurofilament light were also examined. RESULTS: Our model utilized multiple 3D features derived from T1w data as inputs, and reduced the mean absolute error (MAE) of age prediction to 3.08 years and improved Pearson's r to 0.97 on 154 HCs. The strong generalizability of our model was also validated across different centers. Regions contributing the most significantly to brain age prediction were the caudate and thalamus for HCs and patients with mTBI, and the contributive regions were mostly located in the subcortical areas throughout the adult lifespan. The left hemisphere was confirmed to contribute more in brain age prediction throughout the adult lifespan. Our research showed that brain-PAG in mTBI patients was significantly higher than that in HCs in both acute and chronic phases. The increased brain-PAG in mTBI patients was also highly correlated with cognitive impairment and a higher level of plasma neurofilament light, a marker of neurodegeneration. The higher brain-PAG and its correlation with severe cognitive impairment showed a longitudinal and persistent nature in patients with follow-up examinations. CONCLUSION: We proposed an interpretable deep learning framework on a relatively large dataset to accurately predict brain age in both healthy individuals and mTBI patients. The interpretable analysis revealed that the caudate and thalamus became the most contributive role across the adult lifespan in both HCs and patients with mTBI. The left hemisphere contributed significantly to brain age prediction may enlighten us to be concerned about the lateralization of brain abnormality in neurological diseases in the future. The proposed interpretable deep learning framework might also provide hope for testing the performance of related drugs and treatments in the future.

Medication burden in patients with dialysis-dependent CKD: a systematic review.

This systematic review aimed to statistically profile the medication burden and associated influencing factors, and outcomes in patients with dialysis-dependent chronic kidney disease (DD-CKD). Studies of medication burden in patients with DD-CKD in the last 10 years from 1 January 2013 to 31 March 2024 were searched from PubMed, Embase, and Cochrane databases. Newcastle-Ottawa Scale (NOS) or Agency for Healthcare Research and Quality (AHRQ) methodology checklist was used to evaluate quality and bias. Data extraction and combining from multiple groups of number (n), mean, and standard deviation (SD) were performed using R programming language (version4.3.1; R Core Team, Vienna, Austria). A total of 10 studies were included, and the results showed a higher drug burden in patients with DD-CKD. The combined pill burden was 14.57 ± 7.56 per day in hemodialysis (HD) patients and 14.63 ± 6.32 in peritoneal dialysis (PD) patients. The combined number of medications was 9.74 ± 3.37 in HD and 8 ± 3 in PD. Four studies described the various drug classes and their proportions, in general, antihypertensives and phosphate binders were the most commonly used drugs. Five studies mentioned factors associated with medication burden. A total of five studies mentioned medication burden-related outcomes, with one study finding that medication-related burden was associated with increased treatment burden, three studies finding that poor medication adherence was associated with medication burden, and another study finding that medication complexity was not associated with self-reported medication adherence. Limitations: meta-analysis was not possible due to the heterogeneity of studies.

Sn-based film electrodeposited on Ag foil for selective electrochemical CO2 reduction to CO.

Electrochemical CO2 reduction (ECR) to valuable chemicals and fuels using renewable energy is a promising way to reduce carbon emission. Herein, Sn-based films were electrodeposited on Ag foil surfaces (Sn/Ag-y) for selective ECR to CO, where y represented the concentration of SnCl2 in the electrodeposition bath. The Sn/Ag-20 electrode achieved a high CO faradaic efficiency of 96.0% with a current density of 69.3 mA cm-2. The enhanced catalytic performance could be attributed to appropriate superficial properties, large electrochemical active surface areas, low charge transfer resistance, efficient stabilization capacity of the CO2˙- intermediates, and suitable combination with electrolytes.

Effects of Hibernation on Colonic Epithelial Tissue and Gut Microbiota in Wild Chipmunks (Tamias sibiricus).

The gut microbiota plays a crucial role in the host's metabolic processes. Many studies have shown significant changes in the gut microbiota of mammals during hibernation to adapt to the changes in the external environment, but there is limited research on the colonic epithelial tissue and gut microbiota of the wild chipmunks during hibernation. This study analyzed the diversity, composition, and function of the gut microbiota of the wild chipmunk during hibernation using 16S rRNA gene high-throughput sequencing technology, and further conducted histological analysis of the colon. Histological analysis of the colon showed an increase in goblet cells in the hibernation group, which was an adaptive change to long-term fasting during hibernation. The dominant gut microbial phyla were Bacteroidetes, Firmicutes, and Proteobacteria, and the relative abundance of them changed significantly. The analysis of gut microbiota structural differences indicated that the relative abundance of Helicobacter typhlonius and Mucispirillum schaedleri increased significantly, while unclassified Prevotella-9, unclassified Prevotellaceae-UCG-001, unclassified Prevotellaceae-UCG-003 and other species of Prevotella decreased significantly at the species level. Alpha diversity analysis showed that hibernation increased the diversity and richness of the gut microbiota. Beta diversity analysis revealed significant differences in gut microbiota diversity between the hibernation group and the control group. PICRUSt2 functional prediction analysis of the gut microbiota showed that 15 pathways, such as lipid metabolism, xenobiotics biodegradation and metabolism, amino acid metabolism, environmental adaptation, and neurodegenerative diseases, were significantly enriched in the hibernation group, while 12 pathways, including carbohydrate metabolism, replication and repair, translation, and transcription, were significantly enriched in the control group. It can be seen that during hibernation, the gut microbiota of the wild chipmunk changes towards taxa that are beneficial for reducing carbohydrate consumption, increasing fat consumption, and adapting more strongly to environmental changes in order to better provide energy for the body and ensure normal life activities during hibernation.

Analysis of critical states based on acoustic emission signals during progressive failure of wood.

The analysis of critical states during fracture of wood materials is crucial for wood building safety monitoring, wood processing, etc. In this paper, beech and camphor pine are selected as the research objects, and the acoustic emission signals during the fracture process of the specimens are analyzed by three-point bending load experiments. On the one hand, the critical state interval of a complex acoustic emission signal system is determined by selecting characteristic parameters in the natural time domain. On the other hand, an improved method of b_value analysis in the natural time domain is proposed based on the characteristics of the acoustic emission signal. The K-value, which represents the beginning of the critical state of a complex acoustic emission signal system, is further defined by the improved method of b_value in the natural time domain. For beech, the analysis of critical state time based on characteristic parameters can predict the "collapse" time 8.01 s in advance, while for camphor pines, 3.74 s in advance. K-value can be analyzed at least 3 s in advance of the system "crash" time for beech and 4 s in advance of the system "crash" time for camphor pine. The results show that compared with traditional time-domain acoustic emission signal analysis, natural time-domain acoustic emission signal analysis can discover more available feature information to characterize the state of the signal. Both the characteristic parameters and Natural_Time_b_value analysis in the natural time domain can effectively characterize the time when the complex acoustic emission signal system enters the critical state. Critical state analysis can provide new ideas for wood health monitoring and complex signal processing, etc.

[Applicability of H2FPEF and HFA-PEFF Scores in Chinese Patients Suffering From Heart Failure With Preserved Ejection Fraction and Heart Failure With Preserved Ejection Fraction Complicated With Atrial Fibrillation].

Objective To analyze the diagnostic values of H2FPEF and HFA-PEFF scores for heart failure with preserved ejection fraction (HFpEF) and HFpEF complicated with atrial fibrillation (HFpEF-AF) in Chinese patients and explore the related factors. Methods A cross-sectional study was conducted.A total of 835 consecutive HFpEF patients treated in the Department of Geriatric Cardiology,the First Hospital of Lanzhou University from 2009 to 2020 were selected and assigned to a HFpEF-AF group (n=267) and a HFpEF group (n=568) according to the presence of AF or not.HFA-PEFF and H2FPEF scores were used for retrospective diagnosis and the diagnostic consistency of the two scores was assessed.One hundred and thirty-six healthy volunteers with age and sex matching the patients during the same period were selected as healthy controls.The receiver operating characteristic (ROC) curves were established for H2FPEF and HFA-PEFF scores in diagnosing HFpEF-AF and HFpEF,on the basis of which the diagnostic performance of the two scores was evaluated. Results There was no difference in the HFA-PEFF score between the two groups (P=0.070).However,the HFpEF-AF group had higher mean H2FPEF score and higher proportion of patients with the score no less than 6 than the HFpEF group (P<0.001).According to the ROC curves,HFA-PEFF and H2FPEF scores demonstrated high performance in diagnosing all HFpEF patients,with the area under the curve (AUC) of 0.892 and 0.922 and the optimal cut-offs of 4 and 4,respectively.The HFA-PEFF score showed similar performance in diagnosing HFpEF and HFpEF-AF,with the AUC of 0.899 and 0.911,respectively.The H2FPEF score had higher performance in diagnosing HFpEF-AF (AUC of approximately 1.000) and low performance in diagnosing HFpEF (AUC of 0.885). Conclusions The HFA-PEFF score is applicable in the diagnosis of both HFpEF and HFpEF-AF.The H2FPEF score may underestimate HFpEF in Chinese patients,and its applicability in the Chinese patients with HFpEF alone remains to be investigated.

Phytochemical analysis and anticancer effect of Camellia oleifera bud ethanol extract in non-small cell lung cancer A549 cells.

Camellia oleifera is a medicine food homology plant widely cultivated in the Yangtze River Basin and southern China due to its camellia oil. Camellia oleifera bud and fruit exist simultaneously, and its bud is largely discarded as waste. However, C. oleifera bud has been used in traditional Chinese medicine to treat a variety of ailments. Thus, the purpose of this study was to identify the chemical components of C. oleifera bud ethanol extract (EE) and first evaluate its anticancer effects in non-small cell lung cancer A549 cells. Based on UHPLC-Q-Orbitrap-MS analysis, seventy components were identified. For anticancer activity, C. oleifera bud EE had remarkable cytotoxic effect on non-small cell lung cancer A549 (IC50: 57.53 ± 1.54 µg/mL) and NCI-H1299 (IC50: 131.67 ± 4.32 µg/mL) cells, while showed lower cytotoxicity on non-cancerous MRC-5 (IC50 > 320 µg/mL) and L929 (IC50: 179.84 ± 1.08 µg/mL) cells. It dramatically inhibited the proliferation of A549 cells by inducing cell cycle arrest at the G1 phase. Additionally, it induced apoptosis in A549 cells through a mitochondria-mediated pathway, which decreased mitochondrial membrane potential, upregulated Bax, activated caspase 9 and caspase 3, and resulted in PARP cleavage. Wound healing and transwell invasion assays demonstrated that C. oleifera bud EE inhibited the migration and invasion of A549 cells in a dose-dependent manner. The above findings indicated that C. oleifera bud EE revealed notable anticancer effects by inhibiting proliferation, inducing apoptosis, and suppressing migration and invasion of A549 cells. Hence, C. oleifera bud ethanol extract could serve as a new source of natural anticancer drugs.

Rh(III)-Catalyzed Diastereo- and Enantioselective Regiodivergent (Hetero)Arylamidation of (Homo)Allylic Sulfides.

A rhodium-catalyzed 3-component conjunctive diastereo- and regioselective arylamidation of (homo)allylic sulfides, organon boronic acids, and dioxazolones is reported. These reactions deliver the 1,2-insertion and 2,1-insertion arylamidation products, respectively, for allylic sulfides and homoallylic sulfides. The enantioselective arylamidation of terminal and internal allylic sulfides is achieved, furnishing various 1,3-N,S compounds featuring one or two contiguous stereocenters in high yields and with high diastereo- and enantioselectivities. Mechanistic studies suggest a change in the turnover-limiting and selectivity-determining steps induced by the native and easily removable sulfide group.

Retraction: Inhibition of ClC-5 suppresses proliferation and induces apoptosis in cholangiocarcinoma cells through the Wnt/ß-catenin signaling pathway.

[Retraction to: BMB Rep. 2022 June 30; 55(6): 299-304.] Retraction: "Inhibition of ClC-5 suppresses proliferation and induces apoptosis in cholangiocarcinoma cells through the Wnt/ß-catenin signaling pathway," by Zhe Shi, Liyuan Zhou, Yan Zhou, Xiaoyan Jia, Xiangjun Yu, Xiaohong An and Yanzhen Han, BMB Rep. 2022; 55(6) 299-304: The above article, published online on 30 June 2022 in BMB Reports https://doi.org/10.5483/ BMBRep.2022.55.6.044), has been retracted by agreement between the authors and the journal's Editor in Chief. The authors unable to replicate certain results presented in the article and have therefore made the difficult decision to withdraw it. Editorial Board, BMB Reports.

APOE ε4 allele status modulates the spatial patterns of progressive atrophy in the temporal lobes after mild traumatic brain injury.

INTRODUCTION: We evaluated how the apolipoprotein E (APOE) ε4 allele modulated the spatial patterns of longitudinal atrophy in the Alzheimer's disease-vulnerable brain areas of patients with mild traumatic brain injury (mTBI) from the acute to chronic phase post injury. METHODS: Fifty-nine adult patients with acute mTBI and 48 healthy controls with APOE ε4 allele testing underwent T1-weighted magnetic resonance imaging and neuropsychological assessments with 6 to 12 months of follow-up. Progressive brain volume loss was compared voxel-wise in the temporal lobes. RESULTS: Patients with the APOE ε4 allele presented significant longitudinal atrophy in the left superior and middle temporal gyri, where the progressive gray matter volume loss predicted longitudinal impairment in language fluency, whereas mTBI APOE ε4 allele noncarriers showed mainly significant longitudinal atrophy in the medial temporal lobes, without significant neuropsychological relevance. DISCUSSION: The atrophy progression observed in mTBI patients with the APOE ε4 allele may increase the possibility of developing a specific phenotype of Alzheimer's disease with language dysfunction. Highlights: The apolipoprotein E (APOE) ε4 allele and mild traumatic brain injury (mTBI) are risk factors for Alzheimer's disease (AD) progression.It is unclear how the interaction of mTBI with the APOE ε4 allele impacts the progressive atrophy topography in AD-vulnerable brain regions.In this study, patients with the APOE ε4 allele showed progressive atrophy patterns similar to the early stage of logopenic variant of primary progressive aphasia (lvPPA) phenotype of AD. APOE ε4 allele carriers with mTBI history may be at the risk of developing a given AD phenotype with language dysfunction.

1,2,3-Thiadiazole as a Modifiable and Scalable Directing Group for ortho-C-H Functionalization.

In the last few decades, directed C-H bond functionalization has had enormous applicability in academia and industry. The development of a novel, readily accessible, and scalable directing group with modifiable ability is highly desirable in C-H functionalization. Herein, we report the 1,2,3-thiadiazole as a modifiable directing group for C-H amidation and alkynylation with dioxazolones, p-toluenesulfonyl azide, and bromoalkynes in high yield. The densely functionalized 1,2,3-thiadiazole products are modified into thioamide, multisubstituted furan, γ-thiapyrone, thiazole, and various alkynyl sulfides through simple and one-step reactions. The competition experiments reveal that the directing ability of 1,2,3-thiadiazole is slightly weaker than pyridine and bidentate amide but stronger than the widely used carboxylate.

Serum biomarkers and disease progression in CT-negative mild traumatic brain injury.

Blood proteins are emerging as potential biomarkers for mild traumatic brain injury (mTBI). Molecular pathology of mTBI underscores the critical roles of neuronal injury, neuroinflammation, and vascular health in disease progression. However, the temporal profile of blood biomarkers associated with the aforementioned molecular pathology after CT-negative mTBI, their diagnostic and prognostic potential, and their utility in monitoring white matter integrity and progressive brain atrophy remain unclear. Thus, we investigated serum biomarkers and neuroimaging in a longitudinal cohort, including 103 CT-negative mTBI patients and 66 matched healthy controls (HCs). Angiogenic biomarker vascular endothelial growth factor (VEGF) exhibited the highest area under the curve of 0.88 in identifying patients from HCs. Inflammatory biomarker interleukin-1ß and neuronal cell body injury biomarker ubiquitin carboxyl-terminal hydrolase L1 were elevated in acute-stage patients and associated with deterioration of cognitive function from acute-stage to 6-12 mo post-injury period. Notably, axonal injury biomarker neurofilament light (NfL) was elevated in acute-stage patients, with higher levels associated with impaired white matter integrity in acute-stage and progressive gray and white matter atrophy from 3- to 6-12 mo post-injury period. Collectively, our findings emphasized the potential clinical value of serum biomarkers, particularly NfL and VEGF, in diagnosing mTBI and monitoring disease progression.

Aquafeed fermentation improves dietary nutritional quality and benefits feeding behavior, meat flavor, and intestinal microbiota of Chinese mitten crab (Eriocheir sinensis).

Normally, proper fermentation can be an efficient and widely used method to improve feed quality in animal rearing; however, the studies on crustaceans, especially Eriocheir sinensis, remain limited. This study aimed to investigate whether feed fermentation could meliorate dietary nutritional value and benefit E. sinensis rearing. First, non-fermented feed (NFD) and fermented feed (FD) were produced and assessed, respectively. Then, the "Y" maze feed choice behavior test (180 times; 30 times, 6 rounds) was conducted to assess the attractiveness of these 2 feeds for crabs. Finally, a total of 80 crabs (44.10 ± 0.80 g) were randomly assigned into 2 groups with 4 replicates, and fed the experimental diets for 8 weeks to evaluate the effects of each feed on growth, antioxidant capacity, meat flavor, and intestinal microbiota. In this study, FD showed higher levels of crude protein (P < 0.01), soluble protein (P < 0.01), amino acids (P < 0.05), lactic acid (P < 0.001), and lower levels of crude fiber (P < 0.05) and antinutritional factors (agglutinin, trypsin inhibitor, glycinin, and ß-conglycinin) (P < 0.001) than NFD. Additionally, FD was more attractive to crabs than NFD (P < 0.01) and it stimulated the appetite of crabs more than NFD (P < 0.05). The growth performance, feed efficiency, and digestive enzyme activity of FD-fed crabs were significantly higher than those of NFD-fed crabs (P < 0.05). The electronic sensory measurements and free amino acid profiles revealed that the FD diet had positive impacts on the meat flavor of crabs, particularly in "sweet" and "umami" tastes. Moreover, the antioxidant capacity of FD-fed crabs was significantly higher than that of NFD-fed crabs (P < 0.05). Fermented feed also affected the diversity and composition of intestinal microflora. The functional prediction of microbial communities showed that crabs fed FD had a better microecological environment in the intestine. In conclusion, the fermentation of aquafeed could be an effective approach to enhance feed quality and therefore benefit E. sinensis rearing.

Canagliflozin alters the gut, oral, and ocular surface microbiota of patients with type 2 diabetes mellitus.

Background: Modifications in the gut microbiota may be a crucial factor in the efficacy of canagliflozin (Cana) in managing patients with type 2 diabetes mellitus (T2DM). However, the interplay between oral and ocular surface microbiota and this treatment remains poorly explored. Aim: This study aimed to assess alterations in the gut, oral, and ocular surface microbiota pre- and post-Cana treatment in patients with T2DM. Methods: In this 30-day, controlled before-and-after study, 21 treatment-naïve patients with T2DM received sole treatment with Cana (100 mg/day), and were matched with 10 healthy controls based on gender and age. Using 16S rRNA sequencing, changes in the gut, oral, and ocular surface microbiota pre- and post-Cana treatment were assessed and compared with those of healthy controls. Concurrently, diabetes-related clinical parameters were recorded over the study period. The trial was registered in the Chinese Clinical Trial Registry (ChiCTR200034878). Results: A noticeable shift was observed in the gut, oral, and ocular surface microbiota pre- and post-Cana treatment. The post-Cana treatment gut microbiota was more similar to that of the healthy controls. Network correlation analysis revealed that modifications in the gut, oral, and ocular surface microbiota were related to changes in clinical parameters, especially for the ocular surface microbiota. Clinical parameters: A significant decrease in fasting plasma glucose (8.22 ± 2.19 vs 6.87 ± 1.09 mmol/L), glycated serum protein [291.00 (264.00, 353.00) vs 275.00 (251.00, 342.50) µmol/L], hemoglobin A1c (7.39 ± 1.18 vs 7.12 ± 1.33%), body mass index (25.32 ± 2.99 vs 24.83 ± 2.95 kg/m2), systolic blood pressure (129.05 ± 17.51 vs 123.43 ± 14.82 mmHg), and urinary creatinine [158.40 (74.75, 219.15) vs 79.70 (56.25, 138.10) µmmol/kg] levels was noted after 30-day Cana monotherapy (P < 0.05). Gut microbiome: Treatment with Cana resulted in an increase in the relative abundance of short-chain fatty acid (SCFA)-producing bacteria, particularly Lachnospiraceae UCG 004, Bacteroides, and Lachnospiraceae NK4A136 group. Oral microbiota: After Cana treatment, a significant increase of Prevotella and Veillonella, both of which are known to be closely associated with SCFAs, was observed. Ocular surface microbiota: Post-Cana administration, the ocular surface microbiota exhibited the most distinct changes in structure and composition. Remarkably, the majority of the increased ocular surface microbiota could produce SCFAs within the gut microbiota. Conclusion: Cana effectively improved the dysregulated glucose metabolism in patients with T2DM. This improvement can potentially be attributed to the restoration of balance among the gut, oral, and ocular surface microbial communities. Clinical trial registration: https://www.chictr.org.cn/showproj.html?proj=56487, identifier ChiCTR2000034878.

Cd/Cd(OH)2 Nanosheets Enhancing the Electrocatalytic Activity of CO2 Reduction to CO.

Electric-driven conversion of carbon dioxide (CO2 ) to carbon monoxide (CO) under mild reaction conditions offers a promising approach to mitigate the greenhouse effect and the energy crisis. Surface engineering is believed to be one of the prospective methods for enhancing the electrocatalytic activity of CO2 reduction. Herein, hydroxyl (OH) groups were successfully introduced to cadmium nanosheets to form cadmium and cadmium hydroxide nanocomposites (i. e. Cd/Cd(OH)2 nanosheets) via a facile two-step method. The as-prepared Cd/Cd(OH)2 /CP (CP indicates carbon paper) electrode displays excellent electrocatalytic activity for CO2 reduction to produce CO. The Faradaic efficiency of CO reaches 98.3 % and the current density achieves 23.8 mA cm-2 at -2.0 V vs. Ag/Ag+ in a CO2 -saturated 30 wt% 1-butyl-3-methylimidazole hexafluorophosphate ([Bmim]PF6 )-65 wt% acetonitrile (CH3 CN)-5 wt% water (H2 O) electrolyte. And the CO partial current density can reach up to 71.6 mA cm-2 with the CO Faradaic efficiency of more than 85 % at -2.3 V vs. Ag/Ag+ , which stands out against Cd/CP, Cd(OH)2 /CP, and Cd/CdO/CP electrodes. The excellent electrocatalytic performance of the Cd/Cd(OH)2 /CP electrode can be attributed to its unique structural properties, suitable OH groups, perfect interaction with electrolyte, abundant active sites and fast electron transfer rate.