Faslpr gene dosage tunes the extent of lymphoproliferation and T cell differentiation in lupus.

Sle1 and Faslpr are two lupus susceptibility loci that lead to manifestations of systemic lupus erythematosus. To evaluate the dosage effects of Faslpr in determining cellular and serological phenotypes associated with lupus, we developed a new C57BL/6 (B6) congenic lupus strain, B6.Sle1/Sle1.Faslpr/+ (Sle1homo.lprhet) and compared it with B6.Faslpr/lpr (lprhomo), B6.Sle1/Sle1 (Sle1homo), and B6.Sle1/Sle1.Faslpr/lpr (Sle1homo.lprhomo) strains. Whereas Sle1homo.lprhomo mice exhibited profound lymphoproliferation and early mortality, Sle1homo.lprhet mice had a lifespan comparable to B6 mice, with no evidence of splenomegaly or lymphadenopathy. Compared to B6 monogenic lupus strains, Sle1homo.lprhet mice exhibited significantly elevated serum ANA antibodies and increased proteinuria. Additionally, Sle1homo.lprhet T cells had an increased propensity to differentiate into Th1 cells. Gene dose effects of Faslpr were noted in upregulating serum IL-1⍺, IL-2, and IL-27. Taken together, Sle1homo.lprhet strain is a new C57BL/6-based model of lupus, ideal for genetic studies, autoantibody repertoire investigation, and for exploring Th1 effector cell skewing without early-age lymphoproliferative autoimmunity.

A potential role for inflammatory cytokines in a rare late-onset capsular block syndrome: a case report.

BACKGROUND: Late-onset capsule block syndrome (CBS) is a rare complication of cataract phacoemulsification and the implantation of a posterior chamber intraocular lens (PCIOL), which manifests six months to years after surgery. The hallmark of CBS is the formation of an opaque liquid substance between the implanted intraocular lens (IOL) and the posterior capsule. However, its pathogenesis remains unclear. CASE PRESENTATION: A 64-year-old female patient with chronic angle-closure glaucoma (axis length < 21 mm) underwent trabeculectomy surgery combined with phacoemulsification and PCIOL. After a 4-year follow-up, a decline in visual acuity occurred in her right eye due to the location of opaque fluid in the visual axis and distension of the capsular bag. The initial course of action was to release the trapped fluid. Neodymium: yttrium-aluminum-garnet (Nd: YAG) laser capsulotomy could not be employed due to her non-dilating pupil and high extension of the posterior capsule. Subsequently, anterior capsule peeling and anterior segment vitrectomy surgery were performed. The depth of the anterior chamber (ACD), the distance between the face of the retro-IOL and the posterior capsule, the best-corrected visual acuity (BCVA), and the visual quality (VQ) were measured both before and after surgery. Inflammatory cytokine levels in the opaque substances (OS) trapped between the PCIOL and the posterior capsule were assessed using a flow cytometer and compared to normal statistical data in aqueous humor. After surgery, the patient experienced a significant improvement in BCVA and VQ. The distance between the face of the retro-IOL and the posterior capsule was on the verge of disappearing. However, ACD did not differ between pre- and post-operatively. Interleukin-8 (IL-8) and basic fibroblast growth factor (BFGF) concentrations were higher in the OS than in aqueous humor, especially in the former. However, the concentration of vascular cell adhesion molecule (VCAM) in the OS was lower than in aqueous humor. CONCLUSIONS: Anterior segment vitrectomy surgery proved to be a successful treatment for late-onset CBS, presenting a challenging case. In the human lens, inflammatory cytokines originating from the opaque substances may contribute to abnormal metabolism in the sealed area, a consequence of late-onset CBS.

Metabolic adaptation to high-starch diet in largemouth bass (Micropterus salmoides) was associated with the restoration of metabolic functions via inflammation, bile acid synthesis and energy metabolism.

A short-term 2-week (2w) and long-term 8-week (8w) feeding trial was conducted to investigate the effects of low-starch (LS) and high-starch (HS) diets on the growth performance, metabolism and liver health of largemouth bass (Micropterus salmoides). Two isonitrogenous and isolipidic diets containing two levels of starch (LS, 9·06 %; HS, 13·56 %) were fed to largemouth bass. The results indicated that HS diet had no significant effects on specific growth rate during 2w, whereas significantly lowered specific growth rate at 8w. HS diet significantly increased hepatic glycolysis and gluconeogenesis at postprandial 24 h in 2w. The hepatosomatic index, plasma alkaline phosphatase, total bile acid (TBA) levels, and hepatic glycogen, TAG, total cholesterol, TBA, and NEFA contents were significantly increased in the HS group at 2w. Moreover, HS diet up-regulated fatty acid and TAG synthesis-related genes and down-regulated TAG hydrolysis and ß-oxidation-related genes. Therefore, the glucolipid metabolism disorders resulted in metabolic liver disease induced by HS diet at 2w. However, the up-regulation of bile acid synthesis, inflammation and energy metabolism-related genes in 2w indicated that largemouth bass was still in a state of 'self-repair' response. Interestingly, all the metabolic parameters were returned to homoeostasis, with up-regulation of intestinal glucose uptake and transport-related genes, even hepatic histopathological analysis showed no obvious abnormality in the HS group in 8w. In conclusion, HS feed induced short-term acute metabolic disorder, but long-term metabolic adaptation to HS diet was related to repairing metabolism disorders via improving inflammatory responses, bile acid synthesis and energy metabolism. These results strongly indicated that the largemouth bass owned certain adaptability to HS diet.

Yellow mealworm (Tenebrio Molitor) enhances intestinal immunity in largemouth bass (Micropterus salmoides) via the NFκB/survivin signaling pathway.

This study aimed to elucidate the mechanisms of yellow mealworm (Tenebrio Molitor, YM) in intestinal immunity and health. Largemouth bass, as an enteritis modeling animal, were fed 3 diets containing YM at 0% (YM0), 24% (YM24) and 48% (YM48). The YM24 group had reduced levels of proinflammatory cytokines, while the YM48 group experienced a negative impact on intestinal health. Next, the Edwardsiella tarda (E. tarda) challenge test consisted of 4 YM diets, 0% (EYM0), 12% (EYM12), 24% (EYM24), and 36% (EYM36). The EYM0 and EYM12 groups exhibited intestinal damage and immunosuppression by the pathogenic bacteria. However, the above adverse phenotypes were attenuated in the EYM24 and EYM36 groups. Mechanistically, the EYM24 and EYM36 groups enhanced intestinal immunity in largemouth bass via activating NFκBp65 and further upregulating survivin expression to inhibit apoptosis. The results identify a protective mechanism of YM as a novel food or feed source by improving intestinal health.

Comparison of the feasibility and safety between distal transradial access and conventional transradial access in patients with acute chest pain: a single-center cohort study using propensity score matching.

BACKGROUND: Distal transradial access (dTRA) has been suggested to have great advantages over cTRA. However, there is a lack of preliminary data on dTRA in patients undergoing emergency coronary angiography (CAG) or percutaneous coronary intervention (PCI). To explore the feasibility and safety of distal transradial access in patients with acute chest pain. METHODS: A total of 1269 patients complaining of acute chest pain in our emergency department from January 2020 to February 2022 were retrospectively included. The patients who met the inclusion criteria were divided into the conventional transradial access (cTRA) group (n = 238) and the dTRA group (n = 158). Propensity score matching was used to minimize the baseline differences. RESULTS: The cannulation success rate in the dTRA group was significantly lower than that in the cTRA group (87.41% vs. 94.81%, p < 0.05). No significant differences in the puncture time and total procedure time were noted between the two groups (p > 0.05). Compared with the cTRA group, the hemostasis duration was significantly shorter [4(4, 4) h vs. 10(8, 10) h, p < 0.001) and the incidence of minor bleeding (BARC Type I and II) was significantly lower in the dTRA group than that in the cTRA group (0.85% vs. 5.48%, p = 0.045). Asymptomatic radial artery occlusion was observed in six patients (5.83%) in the cTRA group and one patient (1.14%) in the dTRA group (p = 0.126). The subgroup analysis of ST-elevation myocardial infarction (STEMI) showed no significant differences in the puncture time, D-to-B time or total procedure time between the two groups. CONCLUSIONS: The dTRA for emergency CAG or PCI has an acceptable success rate and puncture time, a shorter hemostasis time, and a downward trend in RAO rate compared to the cTRA. The dTRA did not increase the D-to-B time in emergency coronary interventions in STEMI patients. On the contrary, a low incidence of RAO by the dTRA created an opportunity for future coronary interventions in non-culprit vessels in the same access. TRIAL REGISTRATION: Retrospectively registered in Chinese Clinical Trial Registry (registry number: ChiCTR2200061104, date of registration: June 15, 2022).

The difference of the retinal structural and microvascular characteristics in patients with MOGAD-ON and AQP4-ON.

BACKGROUND: Antibodies against myelin-oligodendrocyte-glycoprotein (MOG-Abs) associated disease (MOGAD) has been recognized as a disease entity. Optic neuritis (ON) is the most common symptom in MOGAD. To demonstrate the differences in retinal microvascular characteristics between patients with MOGAD-ON and aquaporin-4 antibody (AQP4-Ab) positive ON. METHODS: In a prospective study, optical coherence tomography (OCT) and optical coherence tomography angiography (OCTA) were used to measure retinal and microvascular parameters. RESULTS: Twenty-six MOGAD-ON eyes, 40 AQP4-ON eyes, and 60 control eyes were included in the study. The thickness of RNFL and GCC in MOGAD-ON eyes was significantly lower than that of HC (p < 0.001, respectively), but comparable to AQP4-ON eyes. The vessel density in retina capillary plexus (RCP) was reduced significantly in MOGAD-ON than that in AQP4-ON (p < 0.05, respectively). The visual accuracy was positively correlated with vessel density of superficial RCP in MOG-ON (p = 0.001) and positively correlated with the thickness of the inner retina layer in AQP4-ON (p < 0.001). CONCLUSION: The retinal neuro-axonal damages between MOGAD-ON and AQP4-ON were comparable. Unlike AQP4-ON eyes, microvascular densities were significantly reduced in MOGAD-ON and were positively correlated with the deterioration of visual acuity in MOGAD-ON. TRIAL REGISTRATION: Clinical and Imaging Patterns of Neuroinflammation Diseases in China (CLUE, NCT: 04106830).

The Value of Optical Coherence Tomography Angiography in Pituitary Adenomas.

OBJECTIVE: This study aims to explore the value of retinal vessel density (VD) in diagnosing optic nerve injuries in patients with pituitary adenomas using optical coherence tomography angiography (OCTA). METHODS: In this cross-sectional retrospective study, 100 patients with pituitary adenomas and 71 participants for normal controls, who visited the Beijing Tiantan Hospital from January 2019 to May 2021, were enrolled. The OCTA was used to measure retinal thickness and VD, and the correlation of these parameters with visual field (VF) factors was analyzed. Receiver operating characteristic curves were used to compare the value of the above parameters in diagnosing VF abnormalities in the patients with pituitary adenomas; the differences in retinal VD between 41 patients with pituitary adenomas who had normal retinal thicknesses and 41 patients in the normal control group with no statistical differences in gender and age were compared. RESULTS: The radial peripapillary capillary (RPC) density, superficial retinal capillary plexus (SRCP) density, retinal nerve fiber layer thickness, and ganglion cell layer complex thickness correlated with VF parameters (p < 0.05). The RPC density in the temporal quadrant had the highest capability in diagnosing VF abnormalities, with an area under the curve = 0.821, p < 0.001, with 72.3% sensitivity and 82.7% specificity. The mean RPC density and RPC density in the nasal and temporal quadrants in the 41 patients with pituitary adenomas who had normal retinal thicknesses were reduced compared with the normal control group (49.95% ± 1.86% vs. 51.30% ± 1.87%, p = 0.002; 49.09% ± 3.13% vs. 50.41% ± 3.90%, p = 0.034; 54.33% ± 3.14% vs. 55.89% ± 3.08%, p = 0.020) and other parameters had no statistical differences compared with the normal control group. CONCLUSIONS: The density of the RPC and SRCP may also be sensitive and specific indicators of VF damage in patients with pituitary adenomas. Measuring retinal VD in patients with pituitary adenomas may be a supplement to help identify VF impairments. In addition, abnormal retinal vascular density may indicate VF impairment in patients who are unable to cooperate with VF examinations.

FoxO1 in Micropterus salmoides: Molecular characterization and its roles in glucose metabolism by glucose or insulin-glucose loading.

Forkhead box O1 (FoxO1), a nuclear transcription factor, plays an important role in insulin-mediated glucose metabolism. In this study, FoxO1 gene from largemouth bass (Micropterus salmoides) was cloned and characterized, and its effects on hepatic glucose metabolism regulated by insulin-AKT pathway were investigated in response to glucose or insulin-glucose injection. The full-length cDNA of FoxO1 consisted of 2541 bp and encoded 680 amino acids. Sequence alignments and phylogenetic analysis revealed that FoxO1 exhibited a high degree of conservation among teleost, retaining one forkhead domain, one transactivation domain, and three phosphorylation sites. FoxO1 mRNA was expressed in a wide range of tissues, and high in the brain and liver. Glucose loading resulted in persistent hyperglycemia, and plasma insulin levels remained unchanged except at 1 h. After the insulin-glucose injection, insulin levels were significantly elevated and glucose levels recovered to the basal value after 6 h, which indicated insufficient insulin secretion caused persistent hyperglycemia in this species. Compared with the glucose injection group, transcript levels and enzyme activities of hepatic glycolysis-related genes (GK and PK) were significantly activated, and gluconeogenesis-related genes (PEPCK and G6Pase) were significantly depressed at 3 h after the insulin-glucose injection. Besides, phosphorylation of AKT-FoxO1 pathway was significantly activated. Therefore, insulin improved glucose metabolism by activating the AKT-FoxO1 phosphorylation  to decrease hyperglycemia stress after the meal, which indicated insufficient insulin secretion was the reason for glucose intolerance in largemouth bass. Meanwhile, conserved S267 and S329 phosphorylation sites of FoxO1 were confirmed to be regulated by AKT and mediated the glucose metabolism. In conclusion, activation of insulin-AKT-FoxO1 pathway improved glucose tolerance through mediating glucose metabolism in largemouth bass.

Female northern grass lizards judge mates by body shape to reinforce local adaptation.

BACKGROUND: Identifying the factors that contribute to divergence among populations in mate preferences is important for understanding of the manner in which premating reproductive isolation might arise and how this isolation may in turn contribute to the evolutionary process of population divergence. Here, we offered female northern grass lizards (Takydromus septentrionalis) a choice of males between their own population and another four populations to test whether the preferences that females display in the mating trials correlate with phenotypic adaptation to local environments, or to the neutral genetic distance measured by divergence of mitochondrial DNA sequence loci. RESULTS: Females showed a strong preference for native over foreign males. Females that mated with native versus foreign males did not differ from each other in mating latency, or copulation duration. From results of the structural equation modelling we knew that: 1) geographical distance directly contributed to genetic differentiation and environmental dissimilarity; 2) genetic differentiation and environmental dissimilarity indirectly contributed to female mate preference, largely through their effects on morphological divergence; and 3) females judged mates by body shape (appearance) and discriminated more strongly against morphologically less familiar allopatric males. CONCLUSIONS: Local adaptation rather than neutral genetic distance influences female mate preference in T. septentrionalis. The tendency to avoid mating with foreign males may indicate that, in T. septentrionalis, local adaptations are more valuable than genetic novelties. Our results highlight the importance of comprehensive studies integrating ecological, molecular and behavioral approaches to understand population divergence in female mate preferences as the consequence of local adaptations.

Hexokinase2 controls angiogenesis in melanoma by promoting aerobic glycolysis and activating the p38-MAPK signaling.

In this study, we used endostatin (ES)-induced apoptosis of endothelial cells to study the role of Hexokinase2 (HK2) in the control of angiogenesis in melanoma. Real-time polymerase chain reaction and Western blot analysis were performed to explore the effect of HK2, lactate, and ES on the levels of caspase-9/3, ATP, and p38/MAPK activation. ES increased the levels of caspase-9/3 while decreasing the level of ATP, whereas ES + HK2 and lactate both restored the normal levels of caspase-9/3 and ATP. In addition, cells transfected with HK2 short hairpin RNA1 (HK2shRNA1) and HK2shRNA2 showed an evident decrease in the levels of caspase-9/3 along with an obvious increase in the level of ATP. Knockdown of HK2 also increased O2 consumption while decreasing the extracellular level of lactate and the phosphorylation of p38-mitogen-activated protein kinase (MAPK). On the other hand, the lactate treatment elevated the phosphorylation of p38-MAPK under time- and concentration-dependent manner. In the study, we clarified the role of HK2 in the control of apoptosis of ECs, which plays an important role in the angiogenesis of melanoma by promoting aerobic glycolysis and activating the p38-MAPK signaling.

3,4-Methylenedioxymethamphetamine causes cytotoxicity on 661W cells through inducing macrophage polarization.

The abuse of 3,4-methylenedioxymethamphetamine (MDMA), a psychedelic drug, can lead to a variety of disorders in neural system, including the death of retinal neural cells. MDMA at lower doses does not cause obvious cytotoxicity to photoreceptor cells, indicating potential indirect mechanisms which have not yet been elucidated. This study investigated the effect of MDMA at nontoxic concentration on macrophage activation state and its resultant toxicity to photoreceptor cells. Using a co-culture system, cytotoxicity was caused by MDMA on 661W cells after co-culturing with RAW264.7 macrophage. Results showed that MDMA induced the macrophages to M1 polarization, releasing more pro-inflammatory cytokines, upregulating the M1-related gene and protein expression. The phenotype, secretion pattern, and cytotoxicity of the macrophages treated by MDMA are comparable to those of the ones stimulated by IFNγ and LPS. Our study demonstrated that MDMA promoted macrophage polarization to M1 and induced inflammatory response, providing the scientific rationale for the photoreceptor cell damage caused by the MDMA abuse.

MiR-503 promotes the migration and invasion of colorectal cancer cells by regulating PDCD4.

PURPOSE: MicroRNAs are expressed abnormally in colorectal cancer (CRC) and could participate in its development. In this study we aimed to explore the molecular mechanisms of miR-503 in the genesis of CRC. METHODS: The relative expression of miR-503 and programmed cell death 4 (PDCD4) tumor suppressor in CRC tissues and cell lines were detected by qRT-PCR and Western blot. Cell migration and cell invasion were assessed by transwell assay. Moreover, the confirmation of the direct target of miR-503 in CRC was performed by luciferase reporter assay. RESULTS: The expression of miR-503 was increased remarkably in CRC, while PDCD4 decreased. Moreover, PDCD4 was verified as a specific target of miR-503 in CRC and it could reverse the effect of miR-503 on CRC cells. Furthermore, the abnormal expression of miR-503 played an important role in regulating of the development of CRC cells. In addition, PDCD4 protein expression and miR-503 mRNA expression were negatively correlated in CRC tissues. CONCLUSION: The inhibitory effect of miR-503 in CRC was realized by the upregulation of PDCD4, suggesting that miR-503/PDCD4 axis might play a critical role in CRC and could possibly be a therapeutic target.

Effect of 25-hydroxyvitamin D3 on rotavirus replication and gene expressions of RIG-I signalling molecule in porcine rotavirus-infected IPEC-J2 cells.

The study evaluated whether a 25-hydroxyvitamin D3 (25D3) supplementation decreases the replication of rotavirus by the retinoic acid-inducible gene I (RIG-I) signalling pathway in a porcine small intestinal epithelial cell line (IPEC-J2). The results show that IPEC-J2 cells express high baseline levels of 1α-hydroxylase (CYP27B1), which converts inactive 25D3 to the active 1,25-dihydroxyvitamin D3 (1,25D3). Porcine rotavirus (PRV) infection alone resulted in a significant increase in CYP27B1 mRNA, which augmented the production of active vitamin D. Physiological concentrations of 25D3 were found to decrease PRV replication in IPEC-J2 cells. RIG-I plays an important role in the recognition of double-stranded RNA virus by host cells. Upon recognition, RIG-I triggers a series of signalling molecules such as interferon-ß (IFN-ß) promoter stimulator 1 (IPS-1) leading to the expression of type I interferons (IFN-ß). Active 25D3 that was generated by PRV-infected IPEC-J2 cells led to an increased expression of toll-like receptors 3 (TLR3), RIG-I, IPS-1, IFN-ß and IFN-stimulated genes 15 (ISG15) with important innate immune functions. Inhibiting CYP27B1 also failed to increase RIG-I, IPS-1, IFN-ß and ISG15 mRNA expression. These observations suggest that 25D3 can directly inhibit PRV in IPEC-J2 cells, which requires this active form of vitamin D. The anti-rotavirus effect of 25D3 is mediated at least in part by RIG-I signalling pathways in IPEC-J2 cells.

Dietary vitamin D supplementation attenuates immune responses of pigs challenged with rotavirus potentially through the retinoic acid-inducible gene I signalling pathway.

In the present study, twenty-four Duroc × Landrance × Yorkshire (initial body weight (BW) of 21·82 (sem 2·06) kg) cross-bred pigs were used to determine whether dietary vitamin D supplementation could confer protection against viral infections through the retinoic acid-inducible gene I (RIG-I) signalling pathway in pigs. Experimental treatments were arranged in a 2 × 2 factorial manner with the main effects of immune challenge (control v. porcine rotavirus (PRV) challenge) and dietary concentrations of vitamin D (200 and 5000 IU; where 1 IU of vitamin D is defined as the biological activity of 0.025 mg of cholecalciferol). The pigs were fed a diet containing 200 or 5000 IU vitamin D in the first week of the study period. On day 8, the pigs were orally dosed with 4 ml of Dulbecco's modified Eagle's medium/Ham's F-12 medium containing PRV or essential medium (control). Serum samples were collected on day 8 (pre-challenge), and 6 d after the PRV challenge, the pigs were killed to evaluate intestinal morphology and tissue gene expression following the last blood collection. Pigs challenged with PRV had decreased BW gain (P< 0·01), feed intake (P< 0·01), villus height (P< 0·01), faecal consistency (P< 0·05), and serum 1,25-dihydroxyvitamin D concentration (P< 0·01) and increased (P< 0·01) serum IL-2, IL-6 and interferon (IFN)-ß concentrations. Vitamin D supplementation mitigated these effects. The mRNA expression of RIG-I (P< 0·01), IFN-ß promoter stimulator 1 (P< 0·01), IFN-ß (P< 0·01) and interferon-stimulated gene 15 (ISG 15 ) (P< 0·01) was up-regulated by the PRV challenge and vitamin D supplementation in the intestine. In conclusion, vitamin D supplementation could activate the RIG-I signalling pathway and thus alleviate the negative effects caused by PRV challenge.

Gut microbiota-bile acid crosstalk and metabolic fatty liver in spotted seabass (Lateolabrax maculatus): The role of a cholesterol, taurine and glycine supplement.

The prevalent practice of substituting fishmeal with plant protein frequently leads to disturbances in bile acid metabolism, subsequently increasing the incidence of metabolic liver diseases. Bile acid nutrients such as cholesterol, taurine and glycine have been shown to enhance bile acid synthesis and confer beneficial effects on growth. Therefore, this study aimed to investigate the effects of cholesterol-taurine-glycine (Ch-Tau-Gly) supplement on bile acid metabolism and liver health in spotted seabass (Lateolabrax maculatus) fed a plant-based diet. Two isonitrogenous and isolipidic diets were formulated: (1) plant protein-based diet (PP); (2) PP supplemented 0.5% cholesterol, 0.5% taurine and 1.3% glycine (CTG). Each experimental diet was randomly fed to quadruplicate groups of 30 feed-trained spotted seabass in each tank. The results revealed that supplementing plant-based diet with Ch-Tau-Gly supplement led to an increase in carcass ratio (meat yield) in spotted seabass (P < 0.05), indirectly contributing positively to their growth. The dietary supplement effectively suppressed endogenous cholesterol synthesis in the liver, promoted the expression of bile acid synthesis enzyme synthesis, and simultaneously the expression of intestinal fxr and its downstream genes, including hnf4α and shp (P < 0.05). The reduction in Lactobacillus_salivarius and bile salt hydrolase (BSH) were observed in CTG group with concurrently increased conjugated chenodeoxycholic acid (CDCA) bile acids (P < 0.05), suggesting the enhancement of the hydrophilicity of the bile acid pool. In CTG group, fatty liver was alleviated with a corresponding increase in lipid metabolism, characterized by a downregulation of genes associated with lipogenesis and lipid droplet deposition, along with an upregulation of genes related to lipolysis. Our study underscored the ability of Ch-Tau-Gly supplement to influence the gut microbiota, leading to an increase in the levels of conjugated CDCA (P < 0.05) in the bile acid pool of spotted seabass. The interplay between the gut microbiota and bile acids might constitute a crucial pathway in the promotion of liver health. These findings offer a promising solution, suggesting that Ch-Tau-Gly supplement have the potential to promote the growth of aquatic species and livestock fed on plant-based diets while addressing issues related to metabolic fatty liver.

The application of protease in aquaculture: Prospects for enhancing the aquafeed industry.

Low-fishmeal and protein-saving diets are two prominent nutritional strategies utilized to address challenges related to the scarcity and sustainability of protein sources in aquaculture. However, these diets have been associated with adverse effects on the growth performance, feed utilization, and disease resistance of aquatic animals. To mitigate these challenges, exogenous protease has been applied to enhance the quality of diets with lower protein contents or fishmeal alternatives, thereby improving the bioavailability of nutritional ingredients. Additionally, protease preparations were also used to enzymatically hydrolyze fishmeal alternatives, thus enhancing their nutritional utilization. The present review aims to consolidate recent research progress on the use of protease in aquaculture and conclude the benefits and limitations of its application, thereby providing a comprehensive understanding of the subject and identifying opportunities for future research.

Drug Repurposing: Research Progress of Niclosamide and Its Derivatives on Antibacterial Activity.

The development of antibiotic resistance complicates the treatment of infectious diseases and is a global public health threat. However, drug repurposing can address this resistance issue and reduce research and development costs. Niclosamide is a salicylanilide compound approved by the Food and Drug Administration (FDA), and it has been used clinically for treating parasitic infections for many years. Recent studies have shown that niclosamide can inhibit bacterial and fungus activity by affecting the quorum sensing system, biofilm formation, cell membrane potential, and other mechanisms. Here, we discuss recent advances in the antimicrobial applications of niclosamide and its derivatives to provide new perspectives in treating infectious diseases.

Growth, Antioxidant Capacity, and Liver Health in Largemouth Bass (Micropterus salmoides) Fed Multi-Strain Yeast-Based Paraprobiotic: A Lab-to-Pilot Scale Evaluation.

A multi-strain yeast-based paraprobiotic (MsYbP) comprising inactive cells and polysaccharides (ß-glucan, mannan oligosaccharides, and oligosaccharides) derived from Saccharomyces cerevisiae and Cyberlindnera jadinii could ensure optimal growth and health in farmed fish. This study assessed the impact of an MsYbP on the growth, immune responses, antioxidant capacities, and liver health of largemouth bass (Micropterus salmoides) through lab-scale (65 days) and pilot-scale (15 weeks) experiments. Two groups of fish were monitored: one fed a control diet without the MsYbP and another fed 0.08% and 0.1% MsYbP in the lab-scale and pilot-scale studies, respectively (referred to as YANG). In the lab-scale study, four replicates were conducted, with 20 fish per replicate (average initial body weight = 31.0 ± 0.8 g), while the pilot-scale study involved three replicates with approximately 1500 fish per replicate (average initial body weight = 80.0 ± 2.2 g). The results indicate that the MsYbP-fed fish exhibited a significant increase in growth in both studies (p < 0.05). Additionally, the dietary MsYbP led to a noteworthy reduction in the liver function parameters (p < 0.05), such as alanine aminotransferase (ALT), aspartate aminotransferase (AST) and alkaline phosphatase (AKP), and hepatic nuclear density, indicating improved liver health. Furthermore, the dietary MsYbP elevated the antioxidative capacity of the fish by reducing their malondialdehyde levels and increasing their levels and gene expressions related to antioxidative markers, such as total antioxidant ca-pacity (T-AOC), total superoxide dismutase (T-SOD), glutathione peroxidase (GSH-Px), catalase (CAT), nuclear factor erythroid 2-related factor 2 (nrf2) and kelch-1ike ech-associated protein (keap1) in both studies (p < 0.05). In terms of hepatic immune responses, the lab-scale study showed an increase in inflammation-related gene expressions, such as interleukin-1ß (il-1ß) and transforming growth factor ß1 (tgf-ß1), while the pilot-scale study significantly suppressed the expressions of genes related to inflammatory responses, such as tumor necrosis factor α (tnfα) and interleukin-10 (il-10) (p < 0.05). In summary, our findings underscore the role of dietary multi-strain yeast-based paraprobiotics in enhancing the growth and liver health of largemouth bass, potentially through increased antioxidative capacity and the modulation of immune responses, emphasizing the significance of employing yeast-based paraprobiotics in commercial conditions.

Toxic Epidermal Necrolysis Observed in a Patient With the HLA-B*1502 Treated With Levofloxacin.

PURPOSE: To determine the relationship between HLA-B gene mutations and levofloxacin-induced toxic epidermal necrolysis (TEN). METHODS: A 71-year-old Chinese woman developed TEN after oral administration of solifenacin (5 mg) and levofloxacin (0.5 g) for cystitis. HLA-B*5801 and HLA-B*1502 alleles were detected using real-time PCR. FINDINGS: After supportive therapy (antiallergic treatments, plasma exchange, etc) and withdrawal of the culprit medication levofloxacin, the patient was discharged with re-epithelialization of the exfoliated skin. The patient was HLA-B*1502 allele positive and HLA-B*5801 allele negative. IMPLICATIONS: This is the first report of levofloxacin-induced TEN suspected to be caused by mutations in the HLA-B*1502 allele.

A missense GDF5 variant causes brachydactyly type A1 and multiple-synostoses syndrome 2.

Objective: This study aimed to identify the molecular defects and clinical manifestations in a Chinese family with brachydactyly (BD) type A1 (BDA1) and multiple-synostoses syndrome 2 (SYNS2). Methods: A Chinese family with BDA1 and SYNS2 was enrolled in this study. Whole-exome sequencing was used to analyze the gene variants in the proband. The sequences of the candidate pathogenic variant in GDF5 was validated via Sanger sequencing. I-TASSER and PyMOL were used to analyze the functional domains of the corresponding mutant proteins. Results: The family was found to have an autosomal-dominantly inherited combination of BDA1 and SYNS2 caused by the S475N variant in the GDF5 gene. The variant was located within the functional region, and the mutated residue was found to be highly conserved among species. Via bioinformatic analyses, we predicted this variant to be deleterious, which perturb the protein function. The substitution of the negatively charged amino acid S475 with the neutral N475 was predicted to disrupt the formation of salt bridges with Y487 and impair the structure, stability, and function of the protein, consequently, the abnormalities in cartilage and bone development ensue. Conclusions: A single genetic variant (S475N) which disrupt the formation of salt bridges with Y487, in the interface of the antagonist- and receptor-binding sites of GDF5 concurrently causes two pathological mechanisms. This is the first report of this variant, identified in a Chinese family with BDA1 and SYNS2.