Single-cell transcriptome profiling reveals neutrophil heterogeneity in homeostasis and infection.

The full neutrophil heterogeneity and differentiation landscape remains incompletely characterized. Here, we profiled >25,000 differentiating and mature mouse neutrophils using single-cell RNA sequencing to provide a comprehensive transcriptional landscape of neutrophil maturation, function and fate decision in their steady state and during bacterial infection. Eight neutrophil populations were defined by distinct molecular signatures. The three mature peripheral blood neutrophil subsets arise from distinct maturing bone marrow neutrophil subsets. Driven by both known and uncharacterized transcription factors, neutrophils gradually acquire microbicidal capability as they traverse the transcriptional landscape, representing an evolved mechanism for fine-tuned regulation of an effective but balanced neutrophil response. Bacterial infection reprograms the genetic architecture of neutrophil populations, alters dynamic transitions between subpopulations and primes neutrophils for augmented functionality without affecting overall heterogeneity. In summary, these data establish a reference model and general framework for studying neutrophil-related disease mechanisms, biomarkers and therapeutic targets at single-cell resolution.

Synergistic effects of the KDM4C inhibitor SD70 and the menin inhibitor MI-503 against MLL::AF9-driven acute myeloid leukaemia.

MLL-rearranged (MLL-r) leukaemia is observed in approximately 10% of acute myeloid leukaemia (AML) and is associated with a relatively poor prognosis, highlighting the need for new treatment regimens. MLL fusion proteins produced by MLL rearrangements recruit KDM4C to mediate epigenetic reprogramming, which is required for the maintenance of MLL-r leukaemia. In this study, we used a combinatorial drug screen to selectively identify synergistic treatment partners for the KDM4C inhibitor SD70. The results showed that the drug combination of SD70 and MI-503, a potent menin-MLL inhibitor, induced synergistically enhanced apoptosis in MLL::AF9 leukaemia cells without affecting normal CD34+ cells. In vivo treatment with SD70 and MI-503 significantly prolonged survival in AML xenograft models. Differential gene expression analysis by RNA-seq following combined pharmacological inhibition of SD70 and MI-503 revealed changes in numerous genes, with MYC target genes being the most significantly downregulated. Taken together, these data provide preclinical evidence that the combination of SD70 and MI-503 is a potential dual-targeted therapy for MLL::AF9 AML.

Twist family BHLH transcription factor 1 is required for the maintenance of leukemia stem cell in MLL-AF9+ acute myeloid leukemia.

Leukemia stem cells (LSC) are a rare population capable of limitless self-renewal and are responsible for the initiation, maintenance, and relapse of leukemia. Elucidation of the mechanisms underlying the regulation of LSC function could provide novel treatment strategies. Here, we show that TWIST1 is extremely highly expressed in the LSC of MLL-AF9+ acute myeloid leukemia (AML), and its upregulation is positively regulated by KDM4C in a H3K9me3 demethylation-dependent manner. We further demonstrate that TWIST1 is essential for the viability, dormancy, and self-renewal capacities of LSC, and that it promotes the initiation and maintenance of MLL-AF9-mediated AML. In addition, TWIST1 directly interacts and collaborates with HOXA9 in inducing AML in mice. Mechanistically, TWIST1 exerts its oncogenic function by activating the WNT5a/RAC1 axis. Collectively, our study uncovers a critical role of TWIST1 in LSC function and provides new mechanistic insights into the pathogenesis of MLL-AF9+ AML.

Overburden of rare ALMS1 deleterious variants in Chinese early-onset type 2 diabetes with severe insulin resistance.

AIMS: Alström syndrome (AS) is a rare recessive disorder characterised by diabetes, obesity, insulin resistance (IR), and visual and hearing impairments. Mutations in the ALMS1 gene have been identified as the causative agents of AS. This study aimed to explore the relationship between rare ALMS1 variants and clinical features in Chinese patients with early-onset type 2 diabetes (age at diagnosis ≤40 years; EOD). MATERIALS AND METHODS: ALMS1 gene sequencing was performed in 611 Chinese individuals with EOD, 36 with postprandial hyperinsulinemia, and 47 with pre-diabetes and fasting IR. In-silico prediction algorithm and the American College of Medical Genetics Guidelines (ACMG) were used to evaluate the deleteriousness and pathogenicity of the variants. RESULTS: Sixty-two rare ALMS1 variants (frequency <0.005) were identified in 82 patients with EOD. Nineteen variants were predicted to be deleterious (pD). Patients with EOD carrying pD variants had higher fasting C-peptide, postprandial C-peptide, and HOMA2-IR levels than those without variants. The frequency of ALMS1 pD variants in the subgroup with more insulin-resistant EOD was higher than that in other EOD subgroups. Two patients with EOD, obesity, and IR who carried one heterozygous pathogenic/likely pathogenic rare variant of ALMS1 according to ACMG were identified. Moreover, rare heterozygous pD variants of ALMS1 were found in participants from cohorts of postprandial hyperinsulinemia as well as in pre-diabetes with fasting IR. CONCLUSIONS: ALMS1 rare pD variants are enriched in the populations with significant IR, which is a major hallmark of diabetes pathogenesis. Accordingly, our exploratory study provides insights and hypotheses for further studies of gene function.

Prevalence and risk factors of fatigue and its association with quality of life among patients with chronic pancreatitis: A cross-sectional study.

BACKGROUND: Fatigue is a debilitating symptom found in various chronic diseases and is associated with more severe symptoms and worse quality of life (QoL). However, this symptom has not been adequately addressed in chronic pancreatitis (CP), and there have been no studies on fatigue in patients with CP. METHODS: This cross-sectional study was conducted at the Changhai Hospital in Shanghai, China. Data on the patients' sociodemographic, disease, and therapeutic characteristics were collected. Fatigue was assessed using the Multidimensional Fatigue Inventory-20. QoL was assessed utilizing the European Organization for the Research and Treatment of Cancer of QoL questionnaire (EORTC-QLQ-C30). Sleep quality, anxiety and depression, and pain was assessed using Pittsburgh Sleep Quality Index, the Hospital Anxiety and Depression Scale, and the Brief Pain Inventory, respectively. RESULTS: The prevalence of fatigue among Chinese patients with CP was 35.51 % (87/245). Multivariate analysis showed that steatorrhea (OR = 2.638, 95 % CI: 1.117-6.234), history of smoking (OR = 4.627, 95 % CI: 1.202-17.802), history of endoscopic treatment (OR = 0.419, 95 % CI: 0.185-0.950), depression (OR = 5.924, 95 % CI: 2.462-14.255), and sleep disorder (OR = 6.184, 95 % CI: 2.543-15.034) were influencing factors for the presence of fatigue. The scores for global health and all functional dimensions in the EORTC-QLQ-C30 significantly decreased, whereas the scores for all symptom dimensions significantly increased in patients with fatigue. CONCLUSIONS: This study indicated that Fatigue is a common symptom and has a negative impact on the QoL of patients with CP. Steatorrhea, smoking history, endoscopic treatment, depression, and sleep disorders were associated with fatigue.

Diversity of MrTolls and their regulation of antimicrobial peptides expression during Enterobacter cloacae infection in Macrobrachium rosenbergii.

Toll/Toll-like receptor (TLR) is an important pattern recognition receptor that plays an important role in the immunity of animals. Six Toll genes were identified in Macrobrachium rosenbergii, namely, MrToll, MrToll1, MrToll2, MrToll3, MrToll4, and MrToll5. SMART analysis showed that all six Tolls have a transmembrane domain, a TIR domain, and different number of LRR domains. The phylogenetic tree showed that six Tolls were located in six different branches. Among these six Tolls, only MrToll4 contains the QHR motif, which is similar to insect Toll9. MrToll4 belongs to V-type/scc Toll with only one LRRCT domain. MrToll1 and MrToll5 are classical P-type/mcc Toll with two LRRCT domains and an LRRNT. MrTolls were distributed in the hemocytes, heart, hepatopancreas, gills, stomach, and intestine. During the infection of Enterobacter cloacae, the expression level of MrToll and MrToll1-4 was upregulated in the intestine of M. rosenbergii. RNA interference experiments showed that the expression of most antimicrobial peptide (AMP) genes was negatively regulated by MrTolls during E. cloacae infection. On the contrary, crustin (Cru) 3 and Cru4 were inhibited after the knockdown of MrToll, and Cru1 and Cru4 were significantly downregulated with the knockdown of MrToll4 during E. cloacae challenge. These results suggest that MrTolls may be involved in the regulation of AMP expression in the intestine during E. cloacae infection.

FOXO is involved in antimicrobial peptides expression during WSSV infection in Exopalaemon carinicauda.

The forkhead box transcription factor O family protein (FOXO) acts as a transcription factor that regulates biological processes regarding DNA repair, immunity, cell cycle regulation, and other biological processes. In this study, EcFOXO was identified from the ridgetail white prawn, Exopalaemon carinicauda. EcFOXO protein contains multiple low-complexity regions and a forkhead (FH) domain. Phylogenetic tree showed that EcFOXO is clustered with crustacean FOXOs. The amino acid sequences of its FH domain are highly similar to the FH domain of FOXOs from other crustaceans. The expression of EcFOXO is altered after white spot syndrome virus (WSSV) stimulation in hepatopancreas and gills. The relationship between EcFOXO and EcRelish was explored by RNA interference (RNAi). Results showed that EcFOXO and EcRelish could positively regulate each other's expression. The expression levels of various antimicrobial peptides (AMPs) significantly reduced after interfering with EcFOXO or EcRelish. These results suggest a positive regulatory loop between EcFOXO and EcRelish, which participates in the innate immunity of ridgetail white prawn by regulating the expression of AMPs during WSSV infection. This study enriches the knowledge about the regulatory mechanism of FOXO in the innate immunity of crustaceans.

Immune function of a C-type lectin with long tandem repeats and abundant threonine in the ridgetail white prawn Exopalaemon carinicauda.

C-type lectins (CTLs) are an important class of pattern recognition receptors (PRRs) that exhibit structural and functional diversity in invertebrates. Repetitive DNA sequences are ubiquitous in eukaryotic genomes, representing distinct modes of genome evolution and promoting new gene generation. Our study revealed a new CTL that is composed of two long tandem repeats, abundant threonine, and one carbohydrate recognition domain (CRD) in Exopalaemon carinicauda and has been designated EcTR-CTL. The full-length cDNA of EcTR-CTL was 1242 bp long and had an open reading frame (ORF) of 999 bp that encoded a protein of 332 amino acids. The genome structure of EcTR-CTL contains 4 exons and 3 introns. The length of each repeat unit in EcTR-CTL was 198 bp, which is different from the short tandem repeats reported previously in prawns and crayfish. EcTR-CTL was abundantly expressed in the intestine and hemocytes. After Vibrio parahaemolyticus and white spot syndrome virus (WSSV) challenge, the expression level of EcTR-CTL in the intestine was upregulated. Knockdown of EcTR-CTL downregulated the expression of anti-lipopolysaccharide factor, crustin, and lysozyme during Vibrio infection. The recombinant CRD of EcTR-CTL (rCRD) could bind to bacteria, lipopolysaccharides, and peptidoglycans. Additionally, rCRD can directly bind to WSSV. These findings indicate that 1) CTLs with tandem repeats may be ubiquitous in crustaceans, 2) EcTR-CTL may act as a PRR to participate in the innate immune defense against bacteria via nonself-recognition and antimicrobial peptide regulation, and 3) EcTR-CTL may play a positive or negative role in the process of WSSV infection by capturing virions.

Differential expression of sNPF in male and female eyestalk leading to sex dimorphism of AMP expression in Procambarus clarkii intestine.

Antimicrobial peptide (AMP) is an important component of crustaceans' innate immune system. In this study, a short neuropeptide F (sNPF) gene (Pc-sNPF) and a Forkhead box O (FOXO) gene (PcFOXO) from Procambarus clarkii were identified. Analysis findings showed that the expression level of AMP genes differed between male and female P. clarkii. Furthermore, Pc-sNPF and PcFOXO were related to the sex dimorphism of AMP. Knockdown of Pc-sNPF in the eyestalk significantly upregulated the expression of PcFOXO and two anti-lipopolysaccharide factors (PcALF4 and PcALFL) in the intestine of P. clarkii. The expression of PcFOXO in the intestine of female P. clarkii was higher than in that of males. Results from RNA interference revealed that PcFOXO positively regulated the expression of PcALF4 and PcALFL in the intestine of male and female P. clarkii. In summary, our study showed that differences in Pc-sNPF expression in eyestalk of male and female P. clarkii leading to sex dimorphism of AMP expression in the intestine are mediated by the sNPF-FOXO-AMP signal pathway called the eyestalk-intestine axis.

Obesity, abdominal obesity, metabolic obesity phenotypes, and Helicobacter pylori infection: results from NHANES 1999-2000.

BACKGROUND: Recent studies on the association between Helicobacter pylori (H. pylori) infection and obesity have reported conflicting results. Therefore, the purpose of our study was to investigate the association of obesity, abdominal obesity, and metabolic obesity phenotypes with H. pylori infection. METHODS: A cross-sectional study of 1568 participants aged 20 to 85 was conducted using the National Health and Nutrition Examination Survey (NHANES) cycle 1999-2000. Logistic regression models were employed to evaluate the association of general obesity as defined by body mass index (BMI), abdominal obesity as defined by waist circumference (WC) and waist-height ratio (WHtR), and metabolic obesity phenotypes with H. pylori seropositivity. Subgroup analyses stratified by age were conducted to explore age-specific differences in this association. RESULTS: After grouping individuals according to their WHtR, the prevalence rate of WHtR ≥ 0.5 in H. pylori-seropositive participants was significantly higher than that in H. pylori-seronegative participants (79.75 vs. 68.39, P < 0.001). The prevalence of H. pylori seropositivity in non-abdominal obesity and abdominal obesity defined by WHtR was 24.97% and 31.80%, respectively (P < 0.001). In the subgroup analysis, the adjusted association between abdominal obesity, as defined by the WHtR, and H. pylori seropositivity was significant in subjects aged < 50 years (OR = 2.23; 95% CI, 1.24-4.01; P = 0.01) but not in subjects aged ≥ 50 years (OR = 0.84; 95% CI, 0.35-1.99; P = 0.66). Subjects older than 50 years old had an OR (95% CI) for metabolically healthy obesity of 0.04 (0.01-0.35) compared with the control group. H. pylori seropositivity was consistently not associated with obesity as defined by BMI. CONCLUSIONS: Abdominal obesity, as defined by the WHtR, was associated with H. pylori infection in subjects aged ≤ 50 years.

Chronic arsenite exposure induced skeletal muscle atrophy by disrupting angiotensin II-melatonin axis in rats.

Arsenic is a well-known environmental toxicant and emerging evidence suggests that arsenic exposure has potential skeletal muscle toxicity; however, the underlying mechanism has not yet been clarified. The aim of this study was to investigate the correlation among adverse effects of subchronic and chronic environmental arsenic exposure on skeletal muscle as well as specific myokines secretion and angiotensin II (AngII)-melatonin (MT) axis in rats. Four-week-old rats were exposed to arsenite (iAs) in drinking water at environmental relevant concentration of 10 ppm for 3 or 9 months. Results indicated that the gastrocnemius muscle had atrophied and its mass was decreased in rats exposed to arsenite for 9 months, whereas, they had no significant changes in rats exposed to arsenite for 3 months. The levels of serum-specific myokine irisin and gastrocnemius muscle insulin-like growth factor-1 (IGF-1) were increased in 3-month exposure group and decreased in 9-month exposure group, while serum myostatin (MSTN) was increased significantly in 9-month exposure group. In addition, serum AngII level increased both in 3- and 9-month exposure groups, while serum MT level increased in 3-month exposure group and decreased in 9-month exposure group. Importantly, the ratio of AngII to MT level in serum increased gradually with the prolongation of arsenite exposure. It showed a certain correlation between AngII-MT axis and gastrocnemius muscle mass, gastrocnemius muscle level of IGF-1 or serum levels of irisin and MSTN. In conclusion, the disruption of AngII-MT axis balance may be a significant factor for skeletal muscle atrophy induced by chronic environmental arsenic exposure.

α-Mangostin Exhibits a Therapeutic Effect on Spinal Cystic Echinococcosis by Affecting Glutamine Metabolism.

Spinal cystic echinococcosis, a severely neglected, rare disease, is characterized by high morbidity, disability, and mortality in prevalent regions. Due to the high-risk nature of surgical treatment and the ineffectiveness of conventional drugs, there is an unmet need for novel safe and effective drugs for the treatment of this disease. In this study, we examined the therapeutic effects of α-mangostin for spinal cystic echinococcosis, and explored its potential pharmacological mechanism. The repurposed drug exhibited a potent in vitro protoscolicidal effect and significantly inhibited the evolution of larval encystation. Moreover, it demonstrated a remarkable anti-spinal cystic echinococcosis effect in gerbil models. Mechanistically, we found that α-mangostin intervention led to intracellular depolarization of mitochondrial membrane potential and reactive oxygen species generation. In addition, we observed elevated expression of autophagic proteins, aggregation of autophagic lysosomes, activated autophagic flux, and disrupted larval microstructure in protoscoleces. Further metabolite profiling showed that glutamine was imperative for autophagic activation and anti-echinococcal effects mediated by α-mangostin. These results suggest that α-mangostin is a potentially valuable therapeutic option against spinal cystic echinococcosis through its effect on glutamine metabolism.

Phosphorylation of androgen receptor by mTORC1 promotes liver steatosis and tumorigenesis.

BACKGROUND AND AIMS: Androgen receptor (AR) has been reported to play an important role in the development and progression of man's prostate cancer. Hepatocellular carcinoma (HCC) is also male-dominant, but the role of AR in HCC remains poorly understood. Mechanistic target of rapamycin complex 1 (mTORC1) also has been reported to be highly activated in HCC. In this study, we aimed to explore the role of AR phosphorylation and its relationship with mTORC1 in hepatocarcinogenesis. APPROACH AND RESULTS: In vitro experiment, we observed that mTORC1 interacts with hepatic AR and phosphorylates it at S96 in response to nutrient and mitogenic stimuli in HCC cells. S96 phosphorylation promotes the stability, nuclear localization, and transcriptional activity of AR, which enhances de novo lipogenesis and proliferation in hepatocytes and induces liver steatosis and hepatocarcinogenesis in mice independently and cooperatively with androgen. Furthermore, high ARS96 phosphorylation is observed in human liver steatotic and HCC tissues and is associated with overall survival and disease-free survival, which has been proven as an independent survival predictor for patients with HCC. CONCLUSIONS: AR S96 phosphorylation by mTORC1 drives liver steatosis and HCC development and progression independently and cooperatively with androgen, which not only explains why HCC is man-biased but also provides a target molecule for prevention and treatment of HCC and a potential survival predictor in patients with HCC.

TWIST1 preserves hematopoietic stem cell function via the CACNA1B/Ca2+/mitochondria axis.

Mitochondria of hematopoietic stem cells (HSCs) play crucial roles in regulating cell fate and preserving HSC functionality and survival. However, the mechanism underlying HSC regulation remains poorly understood. Here, we identify transcription factor TWIST1 as a novel regulator of HSC maintenance through modulation of mitochondrial function. We demonstrate that Twist1 deletion results in significantly decreased lymphoid-biased HSC frequency, markedly reduced HSC dormancy and self-renewal capacity, and skewed myeloid differentiation in steady-state hematopoiesis. Twist1-deficient HSCs are more compromised in tolerance of irradiation- and 5-fluorouracil-induced stresses and exhibit typical phenotypes of senescence. Mechanistically, Twist1 deletion induces transactivation of voltage-gated calcium channel (VGCC) Cacna1b, which exhausts lymphoid-biased HSCs, impairs genotoxic hematopoietic recovery, and enhances mitochondrial calcium levels, metabolic activity, and reactive oxygen species production. Suppression of VGCC by a calcium channel blocker largely rescues the phenotypic and functional defects in Twist1-deleted HSCs under both steady-state and stress conditions. Collectively, our data, for the first time, characterize TWIST1 as a critical regulator of HSC function acting through the CACNA1B/Ca2+/mitochondria axis and highlight the importance of Ca2+ in HSC maintenance. These observations provide new insights into the mechanisms for the control of HSC fate.

GADD45g acts as a novel tumor suppressor, and its activation suggests new combination regimens for the treatment of AML.

Acute myeloid leukemia (AML) is an aggressive hematopoietic malignancy for which there is an unmet need for novel treatment strategies. Here, we characterize the growth arrest and DNA damage-inducible gene gamma (GADD45g) as a novel tumor suppressor in AML. We show that GADD45g is preferentially silenced in AML, especially in AML with FMS-like tyrosine kinase 3-internal tandem duplication (FLT3-ITD) mutations and mixed-lineage leukemia (MLL)-rearrangements, and reduced expression of GADD45g is correlated with poor prognosis in patients with AML. Upregulation of GADD45g impairs homologous recombination DNA repair, leading to DNA damage accumulation, and dramatically induces apoptosis, differentiation, and growth arrest and increases sensitivity of AML cells to chemotherapeutic drugs, without affecting normal cells. In addition, GADD45g is epigenetically silenced by histone deacetylation in AML, and its expression is further downregulated by oncogenes FLT3-ITD and MLL-AF9 in patients carrying these genetic abnormalities. Combination of the histone deacetylase 1/2 inhibitor romidepsin with the FLT3 tyrosine kinase inhibitor AC220 or the bromodomain inhibitor JQ1 exerts synergistic antileukemic effects on FLT3-ITD+ and MLL-AF9+ AML, respectively, by dually activating GADD45g. These findings uncover hitherto unreported evidence for the selective antileukemic role of GADD45g and provide novel strategies for the treatment of FLT3-ITD+ and MLL-AF9+ AML.

Three STAT isoforms formed by selective splicing are involved in the regulation of anti-lipopolysaccharide factor expression in Macrobrachium nipponense during WSSV infection.

White spot syndrome virus (WSSV), a double-stranded DNA virus, is harmful in aquaculture. The signal transducer and activator of transcription (STAT) has been shown to play a role during host infection with the virus, but the exact mechanism by which it acts is unclear. In this study, three STAT isoforms (MnSTAT1, MnSTAT2, and MnSTAT3) were identified in Macrobrachium nipponense. The full-length sequence of MnSTAT1 was 3336 bp, with 2259 bp open reading frame (ORF), encoding a 852 amino acids protein. The full-length sequence of MnSTAT2 was 2538 bp, and the ORF was 2391 bp, encoding 796 amino acids. The full-length sequence of MnSTAT3 sequence was 2618 bp, and the ORF was 2340 bp, encoding 779 amino acids. MnSTAT1-3 is produced by alternative last exon. MnSTAT1-3 all contain a STAT_int, a STAT_alpha, a STAT_bind, and a SH2 structure. MnSTAT1-3 are widely expressed in various tissues tested. The expression levels of MnSTAT1-3 in the intestine of M. nipponense were upregulated at multiple time points following WSSV stimulation. The expression of seven anti-lipopolysaccharide factors (ALFs) was significantly reduced with the knockdown of MnSTATs during WSSV infection. Results showed that MnSTATs regulated the expression of intestinal ALFs and was involved in the innate immunity against WSSV of M. nipponense.

mARC dependent NO synthesis activates CanA-Relish-AMPs signal pathway in Eriocheir sinensis during nitrite stress.

As a signal molecule, nitric oxide (NO) can induce the production of antimicrobial peptides (AMPs) in invertebrate innate immunity and is produced through NO synthase (NOS) oxidation or nitrite reduction. Although the role of NOS-derived NO has been extensively studied, studies on nitrite-dependent NO are relatively scarce. In this study, we identified a mitochondrial amidoxime reducing component (mARC), a kind of nitrite reductase, in Eriocheir sinensis. Under nitrite stress, the expression level of EsmARC in the intestine of E. sinensis increased, and the production of NO increased. Furthermore, EsmARC knockdown resulted in a remarkable decrease in NO concentration. These findings indicate that nitrite stress induces the expression of mARC, which promotes the production of NO in E. sinensis. In addition, the expression levels of AMPs in the intestine were upregulated under nitrite stress. Moreover, EsmARC knockdown resulted in the downregulated expression of AMPs. EsmARC plays a positive role in the synthesis of AMPs under nitrite stress. Calcineurin subunit A (CanA) is a serine/threonine protein phosphatase involved in the process by which NO regulates the expression of AMPs. EsCanA knockdown significantly inhibited the transcription of EsRelish and the expression of AMPs under nitrite stress, and EsRelish silencing resulted in the downregulated expression levels of AMPs under nitrite stress. These results indicate that nitrite stress activates the CanA-Relish-AMP pathway in E. sinensis. In summary, mARC-dependent NO synthesis activates the CanA-Relish-AMP signal pathway in E. sinensis during nitrite stress. This research provides novel insights into the relationship between nitrite stress and NO-dependent immune signal activation in crustaceans.

Expression levels of serine proteases, their homologs, and prophenoloxidase in the Eriocheir sinensis with hepatopancreatic necrosis syndrome (HPNS) and their expression regulation by Runt.

The occurrence of hepatopancreatic necrosis syndrome (HPNS) has seriously affected the sustainable development of Chinese mitten crab (Eriocheir sinensis) farming industry. Limited studies have focused on the immune responses in crabs with HPNS. Serine proteases (SPs) and SP homologs (SPHs) play important roles in the innate immunity of crustaceans. This study investigated the effects of HPNS on the expression levels of genes related to prophenoloxidase (proPO) activation system, and the relationship between Runt transcription factor and the transcriptions of these genes. Eight SPs and five SPHs (SPH1-4, Mas) were identified from E. sinensis. SPs contain a catalytic triad of "HDS", while SPHs lack a catalytic residue. SPs and SPHs all contain a conservative Tryp_SPc domain. Evolutionary analysis showed that EsSPs, EsSPHs, EsPO, and EsRunt were clustered with SPs, SPHs, POs, and Runts of other arthropods, respectively. In crabs with HPNS, the expression levels of six SPs (1, 3, 4, 6, 7, and 8), five SPHs, and PO were significantly upregulated in the hepatopancreas. The knockdown of EsRunt could evidently decrease the expression levels of four SPs (3, 4, 5 and 8), five SPHs (SPH1-4, Mas), and PO. Therefore, the occurrence of HPNS activates the proPO system. Furthermore, the expression levels of partial genes related to proPO system were regulated by Runt. The activation of innate immune system may be a strategy for crabs with HPNS to improve immunity and fight diseases. Our study provides a new understanding of the relationship between HPNS and innate immunity.

Metal-organic framework derived CdSe wrapped with rGO for enhanced lithium storage performance.

Considering the advantages of MOF-based, CdSe-based, and rGO-based materials, CdSe nanoparticles encapsulated with rGO (CdSe@rGO) were synthesized by a metal-organic framework derived method. CdSe nanoparticles encapsulated with rGO can effectively tolerate volume expansion and improve electrical conductivity, leading to excellent cycling stability (396 mAh g-1at 0.3 A g-1after 200 cycles, 311 mAh g-1at 0.5 A g-1after 500 cycles), and rate performance (562 mAh g-1at 0.1 A g-1and 122.2 mAh g-1at 4 A g-1) for lithium-ion storage. This strategy for preparing metal selenides protected by carbon layers can be extended to the design of other high-performance materials.

Effects of ginseng consumption on the biomarkers of oxidative stress: A systematic review and meta-analysis.

Oxidative stress (OS) is a key factor involved in the initiation and development of chronic diseases. Despite its widespread acceptance as an antioxidant, the effects of ginseng on OS in human clinical trials have not been comprehensively analyzed. Therefore, this study aimed to synthesize the results of previous randomized clinical trials (RCTs) examining the impact of ginseng consumption on OS indicators. PubMed, Web of Science, Scopus, and Cochrane databases were searched for articles on the effects of ginseng consumption on oxidative stress markers up to March 20, 2023. Standardized mean difference (SMD) and 95% confidence intervals (CIs) were used to assess effect sizes. Twelve RCTs with 15 effect sizes revealed that the effects of ginseng lowered serum malondialdehyde (MDA) levels (SMD = 0.45, 95% CI: -0.87, -0.08; p = 0.03) and significantly increased the serum total antioxidant capacity (TAC) (SMD = 0.23, 95% CI: 0.01, 0.45; p = 0.04), oxidative dismutase (SOD) (SMD = 0.39, 95% CI: 0.21, 0.57; p < 0.0001), glutathione (GSH) (SMD = 0.36; 95% CI: 0.11, 0.61; p = 0.005), and glutathione reductase (GR) (SMD = 0.56; 95% CI: 0.31, 0.81; p < 0.0001) levels compared to the effects of placebo. However, the effects on serum glutathione peroxidase (GPx) and catalase (CAT) were not significant. Moreover, subgroup analysis based on intervention duration showed that ginseng consumption increased GPx (SMD = 0.91, 95% CI: 0.05, 1.78; p = 0.039) and CAT (SMD = 0.74, 95% CI: 0.27, 1.21; p = 0.002) levels after more than 4 weeks of intervention. According to the results of this meta-analysis, ginseng supplementation dramatically reduced MDA levels and increased TAC, SOD, GSH, and GR levels. Our results open up a new line of defense against oxidative stress-induced diseases.