The Chinese longsnout catfish genome provides novel insights into the feeding preference and corresponding metabolic strategy of carnivores.

Fish show variation in feeding habits to adapt to complex environments. However, the genetic basis of feeding preference and the corresponding metabolic strategies that differentiate feeding habits remain elusive. Here, by comparing the whole genome of a typical carnivorous fish (Leiocassis longirostris Günther) with that of herbivorous fish, we identify 250 genes through both positive selection and rapid evolution, including taste receptor taste receptor type 1 member 3 (tas1r3) and trypsin We demonstrate that tas1r3 is required for carnivore preference in tas1r3-deficient zebrafish and in a diet-shifted grass carp model. We confirm that trypsin correlates with the metabolic strategies of fish with distinct feeding habits. Furthermore, marked alterations in trypsin activity and metabolic profiles are accompanied by a transition of feeding preference in tas1r3-deficient zebrafish and diet-shifted grass carp. Our results reveal a conserved adaptation between feeding preference and corresponding metabolic strategies in fish, and provide novel insights into the adaptation of feeding habits over the evolution course.

SARS-CoV-2-specific T-cell responses are induced in people living with human immunodeficiency virus after booster vaccination.

BACKGROUND: T-cell-mediated immunity is crucial for the effective clearance of viral infection, but the T-cell-mediated immune responses that are induced by booster doses of inactivated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines in people living with human immunodeficiency virus (PLWH) remain unclear. METHODS: Forty-five PLWH who had received antiretroviral therapy (ART) for more than two years and 29 healthy controls (HCs) at Beijing Youan Hospital were enrolled to assess the dynamic changes in T-cell responses between the day before the third vaccine dose (week 0) and 4 or 12 weeks (week 4 or week 12) after receiving the third dose of inactivated SARS-CoV-2 vaccine. Flow cytometry, enzyme-linked immunospot (ELISpot), and multiplex cytokines profiling were used to assess T-cell responses at the three timepoints in this study. RESULTS: The results of the ELISpot and activation-induced marker (AIM) assays showed that SARS-CoV-2-specific T-cell responses were increased in both PLWH and HCs after the third dose of the inactivated SARS-CoV-2 vaccine, and a similar magnitude of immune response was induced against the Omicron (B.1.1.529) variant compared to the wild-type strain. In detail, spike-specific T-cell responses (measured by the ELISpot assay for interferon γ [IFN-γ] release) in both PLWH and HCs significantly increased in week 4, and the spike-specific T-cell responses in HCs were significantly stronger than those in PLWH 4 weeks after the third vaccination. In the AIM assay, spike-specific CD4+ T-cell responses peaked in both PLWH and HCs in week 12. Additionally, significantly higher spike-specific CD8+ T-cell responses were induced in PLWH than in HCs in week 12. In PLWH, the release of the cytokines interleukin-2 (IL-2), tumour necrosis factor-alpha (TNF-α), and IL-22 by peripheral blood mononuclear cells (PBMCs) that were stimulated with spike peptides increased in week 12. In addition, the levels of IL-4 and IL-5 were higher in PLWH than in HCs in week 12. Interestingly, the magnitude of SARS-CoV-2-specific T-cell responses in PLWH was negatively associated with the extent of CD8+ T-cell activation and exhaustion. In addition, positive correlations were observed between the magnitude of spike-specific T-cell responses (determined by measuring IFN-γ release by ELISpot) and the amounts of IL-4, IL-5, IL-2 and IL-17F. CONCLUSIONS: Our findings suggested that SARS-CoV-2-specific T-cell responses could be enhanced by the booster dose of inactivated COVID-19 vaccines and further illustrate the importance of additional vaccination for PLWH.

Supplementation of Mangiferin to a High-Starch Diet Alleviates Hepatic Injury and Lipid Accumulation Potentially through Modulating Cholesterol Metabolism in Channel Catfish (Ictalurus punctatus).

Starch is a common source of carbohydrates in aqua feed. High-starch diet can cause hepatic injury and lipid accumulation in fish. Mangiferin (MGF) can regulate lipid metabolism and protect the liver, but there is limited research on its effects in fish. In the present study, we investigated whether MGF could ameliorate high-starch-induced hepatic damage and lipid accumulation in channel catfish. The channel catfish (Ictalurus punctatus) were fed one of four experimental diets for eight weeks: a control diet (NCD), a high-starch diet (HCD), an HCD supplemented with 100 mg/kg MGF (100 MGF), and an HCD supplemented with 500 mg/kg MGF (500 MGF). The results demonstrated that the weight gain rate (WGR) (p = 0.031), specific growth rate (SGR) (p = 0.039), and feed conversion efficiency (FCE) (p = 0.040) of the 500 MGF group were significantly higher than those of the NCD group. MGF supplementation alleviated liver damage and improved antioxidant capacity (T-AOC) compared to those of the HCD group (p = 0.000). In addition, dietary MGF significantly reduced plasma glucose (GLU) (p = 0.000), triglyceride (TG) (p= 0.001), and low-density lipoprotein cholesterol (LDL) (p = 0.000) levels. It is noteworthy that MGF significantly reduced the plasma total cholesterol (TC) levels (p = 0.000) and liver TC levels (p = 0.005) of channel catfish. Dietary MGF improves cholesterol homeostasis by decreasing the expression of genes that are involved in cholesterol synthesis and transport (hmgcr, sqle, srebf2, sp1, and ldlr) and increasing the expression of genes that are involved in cholesterol catabolism (cyp7a1). Among them, the largest fold decrease in squalene epoxidase (sqle) expression levels was observed in the 100 MGF or 500 MGF groups compared with the HCD group, with a significant decrease of 3.64-fold or 2.20-fold (p = 0.008). And the 100 MGF or 500 MGF group had significantly decreased (by 1.67-fold or 1.94-fold) Sqle protein levels compared to those of the HCD group (p = 0.000). In primary channel catfish hepatocytes, MGF significantly down-regulated the expression of sqle (p = 0.030) and reduced cholesterol levels (p = 0.000). In NCTC 1469 cells, MGF significantly down-regulated the expression of sqle (p = 0.000) and reduced cholesterol levels (p = 0.024). In conclusion, MGF effectively inhibits sqle expression and reduces cholesterol accumulation. The current study shows how MGF supplementation regulates the metabolism and accumulation of cholesterol in channel catfish, providing a theoretical basis for the use of MGF as a dietary supplement in aquaculture.

Effects of Dietary Inosine 5'-Monophosphate Supplementation on the Growth Performance and Salinity and Oxidative Stress Resistance of Gibel Carp (Carassius auratus gibelio).

An 88-day feeding trial was conducted to evaluate the effects of dietary inosine 5'-monophosphate (5'-IMP) on the growth performance and salinity and oxidative stress resistance in the juvenile gibel carp CAS III (Carassius auratus gibelio; initial body weight: 7.48 g). Four isonitrogenous and isoenergetic diets containing exogenous 5'-IMP were formulated. P1, P2, P3 and P4 were diets containing 5'-IMP at four concentrations (0, 1, 2 and 4 g kg-1). The four diets were randomly allotted to triplicate tanks in a recirculating system. After the feeding trial, six fish per tank were netted randomly and placed into 12‱ saline water to test their response to salinity stress. The results indicated that the feed conversion rate was enhanced by dietary supplementation with 5'-IMP. The appetite, plasma neuropeptide Y level and feeding rate of the P3 group were lower than those in the control treatment group. Dietary supplementation with 5'-IMP improved the osmoregulatory adaptation of gibel carp under acute salinity stress. Six hours after the salinity stress treatment, in the dietary 5'-IMP treatment group, the plasma cortisol and K+ concentrations were lower and the Na+/K+-ATPase activity was greater than that in the control group. Dietary supplementation with 5'-IMP promoted the expression of the glucocorticoid receptors NKA-α1b and NKCC and retarded the expression of Hsp70 in P4-treated gill filaments and kidneys. Dietary supplementation with 5'-IMP resulted in a stable oxidative-stress-resistant phenotype characterized by increased levels of cellular antioxidants, including SOD, catalase, glutathione peroxidase, glutathione reductase and MPO. The above results of the current study demonstrate that supplementation of 5'-IMP can promote feed utilization and have positive influences on the salinity and oxidative stress resistance of gibel carp.

Characterization of an aspartate aminotransferase encoded by YPO0623 with frequent nonsense mutations in Yersinia pestis.

Yersinia pestis, the causative agent of plague, is a genetically monomorphic bacterial pathogen that evolved from Yersinia pseudotuberculosis approximately 7,400 years ago. We observed unusually frequent mutations in Y. pestis YPO0623, mostly resulting in protein translation termination, which implies a strong natural selection. These mutations were found in all phylogenetic lineages of Y. pestis, and there was no apparent pattern in the spatial distribution of the mutant strains. Based on these findings, we aimed to investigate the biological function of YPO0623 and the reasons for its frequent mutation in Y. pestis. Our in vitro and in vivo assays revealed that the deletion of YPO0623 enhanced the growth of Y. pestis in nutrient-rich environments and led to increased tolerance to heat and cold shocks. With RNA-seq analysis, we also discovered that the deletion of YPO0623 resulted in the upregulation of genes associated with the type VI secretion system (T6SS) at 26°C, which probably plays a crucial role in the response of Y. pestis to environment fluctuations. Furthermore, bioinformatic analysis showed that YPO0623 has high homology with a PLP-dependent aspartate aminotransferase in Salmonella enterica, and the enzyme activity assays confirmed its aspartate aminotransferase activity. However, the enzyme activity of YPO0623 was significantly lower than that in other bacteria. These observations provide some insights into the underlying reasons for the high-frequency nonsense mutations in YPO0623, and further investigations are needed to determine the exact mechanism.

Real-Time Hemodynamic Changes in the Prefrontal and Bilateral Temporal Cortices During Intradermal Acupuncture for Major Depressive Disorder: A Prospective, Single-Center, Controlled Trial Protocol.

Background: Major depressive disorder (MDD) is highly prevalent, affecting more than 300 million individuals worldwide, and its occurrence may be related to the abnormality of the prefrontal cortex and bilateral temporal cortex. Acupuncture, rooted in the theories of acupoints and meridians, has demonstrated its efficacy in regulating cortical blood flow (CBF) in the brains of MDD patients. As one form of acupuncture, intradermal acupuncture (IA) can alleviate clinical symptoms such as depressive mood and insomnia in MDD patients. However, it remains unknown whether IA will have a specific effect on the prefrontal cortex and bilateral temporal cortex in MDD patients. Methods: In total, 60 participants will be recruited: 20 healthy control participants and 40 MDD patients. All healthy control participants will be allocated to the control group, whereas the 40 MDD patients will be randomly divided into two groups: the gallbladder meridian acupoint (GBA) group and the non-acupoint (NA) group, at a 1:1 allocation ratio. All groups will undergo a one-time IA intervention while their cortical activity is monitored using functional near-infrared spectroscopy (fNIRS). Total hemoglobin, oxygenated hemoglobin, and deoxygenated hemoglobin of the prefrontal and bilateral temporal cortices will be measured by fNIRS during the test procedure. Discussion: This trial aims to use fNIRS to compare real-time hemodynamic changes in the prefrontal and bilateral temporal cortices of healthy individuals and MDD patients during IA. The primary objective is to investigate whether MDD patients exhibit specific real-time responses to IA stimulation in these brain regions. The findings from this study will provide clinical data and a possible theoretical basis for the assumption that stimulation of IA may treat MDD by modulating the relevant brain regions. Trial Registration: The study protocol has been registered in the clinicaltrials.gov with the code NCT05707299.

Regulatory Functions of PurR in Yersinia pestis: Orchestrating Diverse Biological Activities.

The bacterium Yersinia pestis has developed various strategies to sense and respond to the complex stresses encountered during its transmission and pathogenic processes. PurR is a common transcriptional regulator of purine biosynthesis among microorganisms, and it modulates the transcription level of the pur operon to suppress the production of hypoxanthine nucleotide (IMP). This study aims to understand the functions and regulatory mechanisms of purR in Y. pestis. Firstly, we constructed a purR knockout mutant of Y. pestis strain 201 and compared certain phenotypes of the null mutant (201-ΔpurR) and the wild-type strain (201-WT). The results show that deleting purR has no significant impact on the biofilm formation, growth rate, or viability of Y. pestis under different stress conditions (heat and cold shock, high salinity, and hyperosmotic pressure). Although the cytotoxicity of the purR knockout mutant on HeLa and 293 cells is reduced, the animal-challenging test found no difference of the virulence in mice between 201-ΔpurR and 201-WT. Furthermore, RNA-seq and EMSA analyses demonstrate that PurR binds to the promoter regions of at least 15 genes in Y. pestis strain 201, primarily involved in purine biosynthesis, along with others not previously observed in other bacteria. Additionally, RNA-seq results suggest the presence of 11 potential operons, including a newly identified co-transcriptional T6SS cluster. Thus, aside from its role as a regulator of purine biosynthesis, purR in Y. pestis may have additional regulatory functions.

Weak SARS-CoV-2-specific responses of TIGIT-expressing CD8 + T cells in people living with HIV after a third dose of a SARS-CoV-2 inactivated vaccine.

BACKGROUND: T-cell immunoreceptor with immunoglobulin and immunoreceptor tyrosine-based inhibition motif domains (TIGIT), an inhibitory receptor expressed on T cells, plays a dysfunctional role in antiviral infection and antitumor activity. However, it is unknown whether TIGIT expression on T cells influences the immunological effects of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) inactivated vaccines. METHODS: Forty-five people living with HIV (PLWH) on antiretroviral therapy (ART) for more than two years and 31 healthy controls (HCs), all received a third dose of a SARS-CoV-2 inactivated vaccine, were enrolled in this study. The amounts, activation, proportion of cell subsets, and magnitude of the SARS-CoV-2-specific immune response of TIGIT + CD4 + and TIGIT + CD8 + T cells were investigated before the third dose but 6 months after the second vaccine dose (0W), 4 weeks (4W) and 12 weeks (12W) after the third dose. RESULTS: Compared to that in HCs, the frequency of TIGIT + CD8 + T cells in the peripheral blood of PLWH increased at 12W after the third dose of the inactivated vaccine, and the immune activation of TIGIT + CD8 + T cells also increased. A decrease in the ratio of both T naïve (T N ) and central memory (T CM ) cells among TIGIT + CD8 + T cells and an increase in the ratio of the effector memory (T EM ) subpopulation were observed at 12W in PLWH. Interestingly, particularly at 12W, a higher proportion of TIGIT + CD8 + T cells expressing CD137 and CD69 simultaneously was observed in HCs than in PLWH based on the activation-induced marker assay. Compared with 0W, SARS-CoV-2-specific TIGIT + CD8 + T-cell responses in PLWH were not enhanced at 12W but were enhanced in HCs. Additionally, at all time points, the SARS-CoV-2-specific responses of TIGIT + CD8 + T cells in PLWH were significantly weaker than those of TIGIT - CD8 + T cells. However, in HCs, the difference in the SARS-CoV-2-specific responses induced between TIGIT + CD8 + T cells and TIGIT - CD8 + T cells was insignificant at 4W and 12W, except at 0W. CONCLUSIONS: TIGIT expression on CD8 + T cells may hinder the T-cell immune response to a booster dose of an inactivated SARS-CoV-2 vaccine, suggesting weakened resistance to SARS-CoV-2 infection, especially in PLWH. Furthermore, TIGIT may be used as a potential target to increase the production of SARS-CoV-2-specific CD8 + T cells, thereby enhancing the effectiveness of vaccination.

Study on Carbohydrate Metabolism in Adult Zebrafish (Danio rerio).

Excessive carbohydrate intake leads to metabolic disorders in fish. However, few literatures have reported the appropriate carbohydrate level for zebrafish, and the metabolic response to dietary carbohydrate remains largely unknown in zebrafish. This study assessed the responses of zebrafish and zebrafish liver cell line (ZFL) to different carbohydrate levels. In vivo results showed that ≥30% dietary dextrin levels significantly increased the plasma glucose content, activated the expression of hepatic glycolysis-related genes, and inhibited the expression of hepatic gluconeogenesis-related genes in zebrafish. Oil red O staining, triglyceride content, and Hematoxylin-Eosin staining results showed that dietary dextrin levels of ≥30% significantly increased lipid accumulation and liver damage, as well as processes related to glycolipid metabolism and inflammation in zebrafish. In ZFL, the transcription factor sterol regulatory element binding protein-1c signal intensity, 4,4-difluoro-1,3,5,7,8-pentamethyl-4-bora-3a,4a-diaza-s-indacene (BODIPY 493/503) signal intensity, and triglyceride content were also significantly increased when incubated in high glucose, along with abnormal glycolipid metabolism and increased inflammation-related genes. In conclusion, we demonstrated that the maximum dietary carbohydrate level in adult zebrafish should be less than 30%. Excess dietary carbohydrates (30%-50%) caused hepatic steatosis and damage to zebrafish, similar to that seen in aquaculture species. Thus, this study assessed responses to different carbohydrate levels in zebrafish and illustrated that zebrafish is an optimal model for investigating glucose metabolism in some aquatic animals.

F6P/G6P-mediated ChREBP activation promotes the insulin resistance-driven hepatic lipid deposition in zebrafish.

Insulin-sensitive lipogenesis dominates the body lipid deposition; however, nonalcoholic fatty liver disease (NAFLD) develops in the insulin-resistant state. The regulation mechanism of insulin resistance-driven NAFLD remains elusive. Using zebrafish model of insulin resistance (ZIR, insrb-/-) and mouse hepatocytes (NCTC 1469), we explored the regulation mechanism of insulin resistance-driven hepatic lipid deposition under the stimulation of carbohydrate diet (CHD). In ZIR model, insulin resistance induced hyperlipidemia and elevated hepatic lipid deposition via elevating the gene/protein expressions of lipogenic enzymes, that was activated by carbohydrate response element binding protein (ChREBP), rather than sterol regulatory element binding proteins 1c (SREBP-1c). The metabolomic analysis in zebrafish and silencing of chrebp in mouse hepatocytes revealed that the increased hepatic frucotose-6-phosphate (F6P) and glucose-6-phosphate (G6P) promoted the ChREBP-mediated lipid deposition. We further identified that F6P alone was sufficient to activate ChREBP-mediated lipid deposition by a SREBP-1c-independent manner. Moreover, we clarified the suppressed hepatic phosphofructokinase/glucose-6-phosphatase functions and the normal glucokinase function preserved by glucose transporter 2 (GLUT2) manipulated the increased F6P/G6P content in ZIR. In conclusion, the present study revealed that insulin resistance promoted hepatic lipid deposition via the F6P/G6P-mediated ChREBP activation. Our findings deciphered the main regulation pathway for the liver lipid deposition in the insulin-resistant state and identified F6P as a new potential regulator for ChREBP.

Adenosine deaminase acting on RNA 1 (ADAR1) as crucial regulators in cardiovascular diseases: structures, pathogenesis, and potential therapeutic approach.

Cardiovascular diseases (CVDs) are a group of diseases that have a major impact on global health and are the leading cause of death. A large number of chemical base modifications in ribonucleic acid (RNA) are associated with cardiovascular diseases. A variety of ribonucleic acid modifications exist in cells, among which adenosine deaminase-dependent modification is one of the most common ribonucleic acid modifications. Adenosine deaminase acting on ribonucleic acid 1 (Adenosine deaminase acting on RNA 1) is a widely expressed double-stranded ribonucleic acid adenosine deaminase that forms inosine (A-to-I) by catalyzing the deamination of adenosine at specific sites of the target ribonucleic acid. In this review, we provide a comprehensive overview of the structure of Adenosine deaminase acting on RNA 1 and summarize the regulatory mechanisms of ADAR1-mediated ribonucleic acid editing in cardiovascular diseases, indicating Adenosine deaminase acting on RNA 1 as a promising therapeutic target in cardiovascular diseases.

Optimizing Treatment for Major Depressive Disorder in Adolescents: The Impact of Intradermal Acupuncture - A Randomized Controlled Trial Protocol.

Background: Major depressive disorder (MDD) exhibits a pronounced occurrence among adolescents, aligning closely with the lifetime prevalence rate of 16.6% observed in adults. It is difficult to treat and prone to recurrence. Acupuncture has shown potential in enhancing treatment effectiveness. Nonetheless, there is a lack of research on the use of intradermal acupuncture (IA) in treating adolescent MDD. Methods: This study is a double-blind, randomized controlled trial. A cohort of 120 participants will be assigned randomly to three distinct groups, namely a Selective Serotonin Reuptake Inhibitors (SSRIs)-only group, a sham intradermal acupuncture combined with SSRIs (SIA) group, and an active intradermal acupuncture combined with SSRIs (AIA) group. Hamilton Depression Rating Scale will serve as the primary outcome, while Patient Health Questionnaire-9, Self-Rating Depression Scale, Pittsburgh Sleep Quality Index, and Short Form 36 Questionnaire will serve as secondary outcomes in assessing the amelioration of depressive symptoms in patients. These data will be analyzed using SPSS26.0 software. Results: We will assess the efficacy and safety of IA for MDD using commonly employed clinical psychiatric scales. Conclusion: The efficacy of IA in treating adolescent MDD may be demonstrated in this study, suggesting its potential for optimizing MDD treatment schemes. Trial Registration: ClinicalTrials.gov Identifier: NCT05832619 (April 27, 2023).

Effects of Different Dietary Selenium Sources on the Meat Quality and Antioxidant Capacity of Yellow Catfish (Pelteobagrus fulvidraco).

To assess the effect of dietary selenium (Se) sources on the meat quality and antioxidant capacity of yellow catfish (Pelteobagrus fulvidraco), sodium selenite (Na2SeO3), Se yeast, and selenium-enriched Spirulina platensis (Se-SP) were supplemented in the control diet at 0.30 mg Se/kg feed to formulate four diets. The experimental period lasted 50 days. The results showed that Se levels in the plasma, liver, muscle, and whole body were significantly increased by dietary Se yeast supplementation (P < 0.05) but showed no change in response to Na2SeO3 (P > 0.05). The three types of Se all increased the firmness and decreased the fracturability of the muscles (P < 0.05), but only Na2SeO3 resulted in higher springiness, flexibility, stringiness, and stickiness (P < 0.05). In addition, the muscle n-3 polyunsaturated fatty acid (PUFA) content was increased by Se yeast (P < 0.05). Regarding antioxidant capacity, dietary Se yeast and Se-SP supplementation improved hepatic glutathione peroxidase activity but decreased hepatic malondialdehyde content (P < 0.05). Given these results, Se yeast was found to be the optimal source of Se for yellow catfish for higher tissue retention, antioxidant capacity, and PUFA levels. Dietary Se is an effective way to regulate the meat quality and antioxidant capacity of yellow catfish.

The effective on intradermal acupuncture based on changes in biological specificity of acupoints for major depressive disorder: study protocol of a prospective, multicenter, randomized, controlled trial.

Background: Antidepressants still have some side effects in treating major depressive disorder (MDD), and acupuncture therapy is a complementary therapy of research interest for MDD. Acupoints are sensitive sites for disease response and stimulation points for acupuncture treatment. Prior studies suggest that the biological specificity of acupoints is altered in physiological and pathological situations. Therefore, we hypothesize that the biological specificity of acupoints is associated with the diagnosis of MDD and that stimulating acupoints with significant biological specificity can achieve a better therapeutic effect than clinical common acupoints. This study aims to investigate the efficacy and safety of intradermal acupuncture (IA) treatment for MDD based on changes in the biological specificity of acupoints. Methods: The first part of the study will enroll 30 MDD patients and 30 healthy control (HC) participants to assess pain sensitivity and thermal specificity of MDD-related acupoints using a pressure pain threshold gauge (PTG) and infrared thermography (IRT). The potentially superior acupoints for treating MDD will be selected based on the results of PTG and IRT tests and referred to as pressure pain threshold strong response acupoints (PSA) and temperature strong response acupoints (TSA).The second part of the study will enroll 120 eligible MDD patients randomly assigned to waiting list (WL) group, clinical common acupoint (CCA) group, TSA group, and PSA group in a 1:1:1:1 ratio. The change in the Patient Health Questionnaire-9 Items (PHQ-9), the MOS item short-form health survey (SF-36), pressure pain threshold, temperature of acupoints, and adverse effects will be observed. The outcomes of PHQ-9 and SF-36 measures will be assessed before intervention, at 3 and 6 weeks after intervention, and at a 4-week follow-up. The biological specificity of acupoint measures will be assessed before intervention and at 6 weeks after intervention. All adverse effects will be assessed. Discussion: This study will evaluate the therapeutic effect and safety of IA for MDD based on changes in the biological specificity of acupoints. It will investigate whether there is a correlation between the biological specificity of MDD-related acupoints and the diagnosis of MDD and whether stimulating strong response acupoints is superior to clinical common acupoints in the treatment of MDD. The study's results may provide insights into the biological mechanisms of acupuncture and its potential as a complementary therapy for MDD. Clinical Trial Registration: ClinicalTrials.gov, identifier: NCT05524519.

Sequential Activations of ChREBP and SREBP1 Signals Regulate the High-Carbohydrate Diet-Induced Hepatic Lipid Deposition in Gibel Carp (Carassius gibelio).

The present study investigated the sequential regulation signals of high-carbohydrate diet (HCD)-induced hepatic lipid deposition in gibel carp (Carassius gibelio). Two isonitrogenous and isolipidic diets, containing 25% (normal carbohydrate diet, NCD) and 45% (HCD) corn starch, were formulated to feed gibel carp (14.82 ± 0.04 g) for 8 weeks. The experimental fish were sampled at 2nd, 4th, 6th, and 8th week. In HCD group, the hyperlipidemia and significant hepatic lipid deposition (oil red O area and triglyceride content) was found at 4th, 6th, and 8th week, while the significant hyperglycemia was found at 2nd, 4th, and 8th week, compared to NCD group (P < 0.05). HCD induced hepatic lipid deposition via increased hepatic lipogenesis (acc, fasn, and acly) but not decreased hepatic lipolysis (hsl and cpt1a). When compared with NCD group, HCD significantly elevated the hepatic sterol regulatory element binding proteins 1 (SREBP1) signals (positive hepatocytes and fluorescence intensity) at 4th, 6th, and 8th week (P < 0.05). The hepatic SREBP1 signals increased from 2nd to 6th week, but decreased at 8th week due to substantiated insulin resistance (plasma insulin levels, plasma glucose levels, and P-AKTSer473 levels) in HCD group. Importantly, the hepatic carbohydrate response element binding protein (ChREBP) signals (positive hepatocytes, fluorescence intensity, and expression levels) were all significantly elevated by HCD-induced glucose-6-phosphate (G6P) accumulation at 2nd, 4th, 6th, and 8th week (P < 0.05). Compared to 2nd and 4th week, the hepatic ChREBP signals and G6P contents was significantly increased by HCD at 6th and 8th week (P < 0.05). The HCD-induced G6P accumulation was caused by the significantly increased expression of hepatic gck, pklr, and glut2 (P < 0.05) but not 6pfk at 4th, 6th, and 8th week, compared to NCD group. These results suggested that the HCD-induced hepatic lipid deposition was mainly promoted by SREBP1 in earlier stage and by ChREBP in later stage for gibel carp. This study revealed the sequential regulation pathways of the conversion from feed carbohydrate to body lipid in fish.

Attenuated glucose uptake promotes catabolic metabolism through activated AMPK signaling and impaired insulin signaling in zebrafish.

Glucose metabolism in fish remains a controversial area of research as many fish species are traditionally considered glucose-intolerant. Although energy homeostasis remodeling has been observed in fish with inhibited fatty acid ß-oxidation (FAO), the effects and mechanism of the remodeling caused by blocked glucose uptake remain poorly understood. In this study, we blocked glucose uptake by knocking out glut2 in zebrafish. Intriguingly, the complete lethality, found in Glut2-null mice, was not observed in glut2-/- zebrafish. Approxiamately 30% of glut2-/- fish survived to adulthood and could reproduce. The maternal zygotic mutant glut2 (MZglut2) fish exhibited growth retardation, decreased blood and tissue glucose levels, and low locomotion activity. The decreased pancreatic ß-cell numbers and insulin expression, as well as liver insulin receptor a (insra), fatty acid synthesis (chrebp, srebf1, fasn, fads2, and scd), triglyceride synthesis (dgat1a), and muscle mechanistic target of rapamycin kinase (mtor) of MZglut2 zebrafish, suggest impaired insulin-dependent anabolic metabolism. Upregulated expression of lipolysis (atgl and lpl) and FAO genes (cpt1aa and cpt1ab) in the liver and proteolysis genes (bckdk, glud1b, and murf1a) in muscle were observed in the MZglut2 zebrafish, as well as elevated levels of P-AMPK proteins in both the liver and muscle, indicating enhanced catabolic metabolism associated with AMPK signaling. In addition, decreased amino acids and elevated carnitines of the MZglut2 zebrafish supported the decreased protein and lipid content of the whole fish. In summary, we found that blocked glucose uptake impaired insulin signaling-mediated anabolism via ß-cell loss, while AMPK signaling-mediated catabolism was enhanced. These findings reveal the mechanism of energy homeostasis remodeling caused by blocked glucose uptake, which may be a potential strategy for adapting to low glucose levels.

The efficacy and cerebral mechanism of intradermal acupuncture for major depressive disorder: a study protocol for a randomized controlled trial.

Background: Major depressive disorder (MDD) has emerged as the fifth leading cause of years lived with disability, with a high prevalent, affecting nearly 4% of the global population. While available evidence suggests that intradermal acupuncture may enhance the effectiveness of antidepressants, whether its efficacy is a specific therapeutic effect or a placebo effect has not been reported. Moreover, the cerebral mechanism of intradermal acupuncture as a superficial acupuncture (usually subcutaneous needling to a depth of 1-2 mm) for MDD remains unclear. Methods: A total of 120 participants with MDD will be enrolled and randomized to the waiting list group, sham intradermal acupuncture group and active intradermal acupuncture group. All 3 groups will receive a 6-week intervention and a 4-week follow-up. The primary outcome will be measured by the Hamilton Depression Rating Scale-17 and the secondary outcome measures will be the Self-Rating depression scale and Pittsburgh sleep quality index. Assessments will be conducted at baseline, 3 weeks, 6 weeks, and during the follow-up period. In addition, 20 eligible participants in each group will be randomly selected to undergo head magnetic resonance imaging before and after the intervention to explore the effects of intradermal acupuncture on brain activity in MDD patients. Discussion: If the intradermal acupuncture is beneficial, it is promising to be included in the routine treatment of MDD. Clinical Trial Registration: Clinicaltrials.gov, NCT05720637.

Dietary yeast glycoprotein supplementation improves the growth performance, intestinal health and disease resistance of largemouth bass (Micropterus salmoides) fed low-fishmeal diets.

The active ingredients extracted from yeast are important for regulating animal health. The aim of the current research was to explore the impacts of dietary yeast glycoprotein (YG) on the growth performance, intestinal morphology, antioxidant capacity, immunity and disease resistance of largemouth bass (Micropterus salmoides). A total of 375 juvenile fish (6.00 ± 0.03 g) were allocated into 15 fiberglass tanks. Triplicate tanks were assigned to each diet. The dietary YG inclusion was as follows: the first group was given a high fishmeal diet (40% fishmeal, 0% YG) (FM) and the second group was given a low fishmeal diet (30% fishmeal and 15% soybean meal, 0% YG) (LFM). The fish in the third, fourth and fifth groups were fed the LFM diet supplemented with 0.5% (LFM+YG0.5), 1.0% (LFM+YG1.0) and 2.0% (LFM+YG2.0) YG, respectively. After a 60- day feeding trial, a challenge test using A. hydrophila was carried out. The results showed that the final body weight (FBW) and weight gain rate (WGR) in the LFM+YG2.0 group were significantly higher than those in the LFM group and were no significantly different from those in the FM group. This may be partially related to the activation of the target of rapamycin (TOR) signaling pathway. Dietary YG supplementation enhanced intestinal physical barriers by upregulating the intestinal tight junction protein related genes (claudin1, occludin and zo2) and improving the structural integrity of the gut, which may be partially associated with AMPK signaling pathway. Moreover, dietary YG increased the antioxidant capacity in the gut, upregulated intestinal anti-inflammatory factors (il-10, il1-1ß and tgf-ß) and downregulated proinflammatory factors (il-1ß and il-8), which may be partially related to the Nrf2/Keap1 signaling pathways. The results of the challenge test indicated that dietary supplementation with 0.5 or 1.0% YG can increase the disease tolerance of largemouth bass against A. hydrophila. In conclusion, the present results indicated that dietary supplementation with YG promotes the growth performance, intestinal immunity, physical barriers and antioxidant capacity of largemouth bass. In addition, 1.0% of dietary YG is recommended for largemouth bass based on the present results.

Resveratrol alleviates lipopolysaccharide-induced liver injury by inducing SIRT1/P62-mediated mitophagy in gibel carp (Carassius gibelio).

Introduction: Resveratrol (RES) is a polyphenol organic compound with antioxidant and anti-inflammatory properties. This study aimed to determine whether and how RES can alleviate liver injury in lipopolysaccharide (LPS)-induced gibel carp. Methods: Gibel carp were fed a diet with or without RES and were cultured for 8 weeks, followed by LPS injection. Results and discussion: The results suggested that RES attenuated the resulting oxidative stress and inflammation by activating the Nrf2/Keap1 pathway and inhibiting the NF-κB pathway, as confirmed by changes in oxidative stress, inflammation-related gene expression, and antioxidant enzyme activity. Furthermore, RES cleared damaged mitochondria and enhanced mitochondrial biogenesis to mitigate reactive oxygen species (ROS) accumulation by upregulating the SIRT1/PGC-1α and PINK1/Parkin pathways and reducing p62 expression. Overall, RES alleviated LPS-induced oxidative stress and inflammation in gibel carp through mitochondria-related mechanisms.

Compared to Fishmeal, Dietary Soybean Meal Improves the Reproductive Performance of Female Yellow Catfish (Pelteobagrus fulvidraco) Broodstock.

To investigate the effects of different dietary protein sources on the reproductive performance of female broodstock, yellow catfish (Pelteobagrus fulvidraco) were fed with three experimental diets using fishmeal (FM), soybean meal (SBM), and rapeseed meal (RSM) as main protein sources, respectively. Females (initial weight: 64.56 ± 0.45 g) were distributed into 9 net cages for feeding trial. Results indicated that 30% dietary SBM improved the reproductive performance for higher gonadosomatic index (GSI), relative fecundity, total egg production, egg diameter, and hatching rate. In addition, SBM and RSM diets resulted in higher estradiol (E2), vitellogenin (VTG), luteinizing hormones (LH), and lower follicle-stimulating hormone (FSH) and testosterone (T) in plasma (P < 0.05) of female broodstock. Dietary SBM and RSM also resulted in lower mesenteric fat index (MFI), plasma total cholesterol (TC), plasma total bilirubin (T-Bil) contents, and gonadal cortisol concentrations, while dietary SBM downregulated the transcription levels of steroidogenesis-related proteins by negative feedback (P < 0.05). The results demonstrated that dietary SBM and RSM could promote sex steroid hormone and VTG biosynthesis and showed hypocholesterolemic effects. Besides, 30% dietary SBM inclusion could improve the reproductive performance of female yellow catfish broodstock.