Procalcitonin/Albumin Ratio Predicts the Outcome After Severe Traumatic Brain Injury: A Propensity Score-Matched Analysis.

BACKGROUND: The procalcitonin/albumin ratio (PAR), a novel inflammation-based index, has been reported to predict the prognosis following cardiopulmonary bypass surgery and bacterial infection. However, whether PAR can predict the outcome of patients with severe traumatic brain injury (STBI) has not been fully elucidated. This study aimed to investigate the relationship between serum PAR levels and prognosis at 6 months after STBI. METHODS: We retrospectively enrolled 129 patients diagnosed with STBI and collected relevant clinical and laboratory data. Logistic regression analysis was used to estimate the association of PAR with the prognosis of STBI. The receiver operating characteristics curve was performed to examine the predictive use of PAR for prognosis. Propensity score matching (PSM) analysis was also performed to improve the reliability of the results. The primary outcome measures were expressed as a score on the modified Rankin Scale at 6 months. RESULTS: The unfavorable prognosis group had advanced age, lower Glasgow Coma Scale score, higher rate of cerebral hernia and intracranial infection, higher neutrophil/lymphocyte ratio (NLR) and C-reactive protein/albumin ratio (CAR), elevated PAR, and higher rate of pneumonia. Multivariate analysis showed that PAR (before PSM: odds ratio 3.473, 95% confidence interval 2.983-4.043, P < 0.001; after PSM: odds ratio 5.358, 95% confidence interval 3.689-6.491, P < 0.001) was independently associated with unfavorable outcome. The area under the curve of the PAR for predicting an unfavorable outcome was higher than that of the CAR and NLR. CONCLUSIONS: The PAR might be a novel independent risk factor of the outcome after STBI. Moreover, PAR was a better biomarker in predicting the outcome of patients with STBI than CAR and NLR.

The Importance of Fatty Acid Precision Nutrition: Effects of Dietary Fatty Acid Composition on Growth, Hepatic Metabolite, and Intestinal Microbiota in Marine Teleost Trachinotus ovatus.

Our recent study demonstrated that diet with blend oil (named BO1) as lipid, which is designed on the base of essential fatty acid requirement of Trachinotus ovatus, achieved good performance. Here, to confirm its effect and investigate the mechanism, three isonitrogenous (45%) and isolipidic (13%) diets (D1-D3) only differing in dietary lipids, which were, respectively, fish oil (FO), BO1, and blend oil 2 (BO2) consisting of FO and soybean oil at 2 : 3, were formulated and used to feed the T. ovatus juveniles (average initial weight: 7.65 g) for 9 weeks. The results showed that the weight gain rate of fish fed D2 was higher than that of fish fed D3 (P < 0.05) and had no significant difference from that of fish fed D1 (P > 0.05). Correspondingly, compared with the D3 group, fish of the D2 group exhibited better oxidative stress parameters such as lower serum malondialdehyde content and inflammatory indexes in the liver such as the lower expression level of genes encoding four interleukin proteins and tumor necrosis factor α, as well as higher hepatic immune-related metabolites such as valine, gamma-aminobutyric acid, pyrrole-2-carboxylic acid, tyramine, l-targinine, p-synephrine, and butyric acid (P < 0.05). Furthermore, the intestinal probiotic (Bacillus) proportion was significantly higher, while the pathogenic bacteria (Mycoplasma) proportion was significantly lower in the D2 group than that in the D3 group (P < 0.05). The main differential fatty acids of diet D2 were close to those of D1, while the levels of linoleic acid and n-6 PUFA, as well as the ratio of DHA/EPA of D3, were higher than those of D1 and D2. These results indicated that the better performance of D2 such as enhancing growth, reducing oxidative stress, and improving immune responses and intestinal microbial communities in T. ovatus may be mainly due to the good fatty acid composition of BO1, which indicated the importance of fatty acid precision nutrition.

Association between vascular risk factors and idiopathic normal pressure hydrocephalus: a Mendelian randomization study.

BACKGROUND AND OBJECTIVE: Patients with idiopathic normal pressure hydrocephalus (iNPH) have a higher prevalence of hypertension and diabetes. However, the causal effects of these vascular risk factors on iNPH remain unclear. This study aimed to explore the causal relationship between vascular risk factors (VRFs) and iNPH. METHODS: We conducted the Mendelian randomization (MR) analysis of iNPH. We included nineteen vascular risk factors related to hypertension, diabetes, lipids, obesity, smoking, alcohol consumption, exercise, sleep, and cardiovascular events as exposure factors. We used the inverse-variance weighted method for causal effect estimation and weighted median, maximum likelihood, and MR Egger regression methods for sensitivity analyses. RESULTS: We found that genetically predicting essential hypertension (OR = 1.608 (1.330-1.944), p = 0.013) and increased sleep duration (OR = 16.395 (5.624-47.799), p = 0.009) were associated with higher odds of iNPH. Type 1 diabetes (OR = 0.869 (0.828-0.913), p = 0.004) was associated with lower odds of iNPH. For the other 16 VRFs, there was no evidence that they were significantly associated with iNPH. Sensitivity analyses showed that essential hypertension and type 1 diabetes were significantly associated with iNPH. CONCLUSION: In our MR study on VRFs and iNPH, we found essential hypertension to be a causal risk factor for iNPH. This suggests that hypertension may be involved in the pathophysiological mechanism of iNPH.

PHB2 binds to ERß to induce the autophagy of porcine ovarian granulosa cells through mTOR phosphorylation.

Autophagy of ovarian granulosa cells is one of the reasons which results in follicular atresia. PHB2 regulates many fundamental biological processes and is pivotal in the mitophagy of cells; nevertheless, the autophagy in the porcine ovary and how PHB2 regulates the follicular cells are unknown. Here we report a protein complex that induces autophagy in porcine granulosa cells (PGCs) through the direct interaction of ERß and PHB2. In this study, we aimed to elucidate the autophagy and the role of PHB2 in porcine ovaries using porcine primary ovarian granulosa cells (PGCs). The results showed that PHB2 induces PGCs autophagy because of the change in related genes and protein expression levels. In addition, the results of Co-IP and the distribution of the combination of PHB2 and ERß showed that this complex is also indicated as an essential role of PHB2 in PGCs autophagy. Based on our results, it can be concluded that PHB2 combined with ERß induces PGCs autophagy by targeting the mTOR pathway. This study pinpoints a novel regulatory mechanism of autophagy and demonstrates the existence of a protein complex that may underlie its roles in autophagy in PGCs.

Lipid Nanoparticle Delivery System for mRNA Encoding B7H3-redirected Bispecific Antibody Displays Potent Antitumor Effects on Malignant Tumors.

The therapeutic use of bispecific T-cell engaging (BiTE) antibodies has shown great potential for treating malignancies. BiTE can simultaneously engage CD3ε on T cells and tumor antigen on cancer cells, thus exerting an effective antitumor effect. Nevertheless, challenges in production, manufacturing, and short serum half-life of BiTE have dampened some of the promise and impeded the pace of BiTE-based therapeutics to combat diseases. Nowadays, in vitro-transcribed mRNA has achieved programmed production, which is more flexible and cost-effective than the traditional method of producing recombinant antibody. Here, the authors have developed a BiTE-based mRNA treatment by encapsulating mRNA encoding B7H3×CD3 BiTE into a novel ionizable lipid nanoparticles (LNPs). The authors have found that LNPs have high transfection efficiency, and the hepatosplenic targeting capability of produce high concentrations of BiTE. Above all, a single intravenous injection of BiTE mRNA-LNPs could achieve high levels of protein expression in vivo and significantly prolonged the half-life of the BiTE, which can elicit robust and durable antitumor efficacy against hematologic malignancies and melanoma. Therefore, their results suggested that the therapeutic strategy based on mRNA expression of B7H3×CD3 BiTE is of potential research value and has promising clinical application prospects.

Advances in objective assessment of ergonomics in endoscopic surgery: a review.

Background: Minimally invasive surgery, in particular endoscopic surgery, has revolutionized the benefits for patients, but poses greater challenges for surgeons in terms of ergonomics. Integrating ergonomic assessments and interventions into the multi-stage endoscopic procedure contributes to the surgeon's musculoskeletal health and the patient's intraoperative safety and postoperative recovery. Objective: The purpose of this study was to overview the objective assessment techniques, tools and assessment settings involved in endoscopic procedures over the past decade and to identify the potential factors that induce differences in high workloads in endoscopic procedures and ultimately to design a framework for ergonomic assessment in endoscopic surgery. Methods: Literature searches were systematically conducted in the OVID, pubmed and web of science database before October 2022, and studies evaluating ergonomics during the process of endoscopic procedures or simulated procedures were both recognized. Results: Our systematic review of 56 studies underscores ergonomic variations in endoscopic surgery. While endoscopic procedures, predominantly laparoscopy, typically incur less physical load than open surgery, extended surgical durations notably elevate ergonomic risks. Surgeon characteristics, such as experience level and gender, significantly influence these risks, with less experienced and female surgeons facing greater challenges. Key assessment tools employed include electromyography for muscle fatigue and motion analysis for postural evaluation. Conclusion: This review aims to provide a comprehensive analysis and framework of objective ergonomic assessments in endoscopic surgery, and suggesting avenues for future research and intervention strategies. By improving the ergonomic conditions for surgeons, we can enhance their overall health, mitigate the risk of WMSDs, and ultimately improve patient outcomes.

IL4I1 in M2-like macrophage promotes glioma progression and is a promising target for immunotherapy.

Background: Glioma is the prevailing malignant intracranial tumor, characterized by an abundance of macrophages. Specifically, the infiltrating macrophages often display the M2 subtype and are known as tumor-associated macrophages (TAMs). They have a critical role in promoting the oncogenic properties of tumor cells. Interleukin-4-induced-1 (IL4I1) functions as an L-phenylalanine oxidase, playing a key part in regulating immune responses and the progression of various tumors. However, there is limited understanding of the IL4I1-mediated cross-talk function between TAMs and glioma cell in the glioma microenvironment. Methods: TCGA, GTEx, and HPA databases were applied to assess the IL4I1 expression, clinical characteristics, and prognostic value of pan-cancer. The link between IL4I1 levels and the prognosis, methylation, and immune checkpoints (ICs) in gliomas were explored through Kaplan-Meier curve, Cox regression, and Spearman correlation analyses. The IL4I1 levels and their distribution were investigated by single-cell analysis and the TIMER 2 database. Additionally, validation of IL4I1 expression was performed by WB, RT-qPCR, IHC, and IF. Co-culture models between glioma cells and M2-like macrophages were used to explore the IL4I1-mediated effects on tumor growth, invasion, and migration of glioma cells. Moreover, the function of IL4I1 on macrophage polarization was evaluated by ELISA, RT-qPCR, WB, and siRNA transfection. Results: Both transcriptome and protein levels of IL4I1 were increased obviously in various tumor types, and correlated with a dismal prognosis. Specifically, IL4I1 was implicated in aggressive progression and a dismal prognosis for patients with glioma. A negative association was noticed between the glioma grade and DNA promoter methylation of IL4I1. Enrichment analyses in glioma patients suggested that IL4I1 was linked to cytokine and immune responses, and was positively correlated with ICs. Single-cell analysis, molecular experiments, and in vitro assays showed that IL4I1 was significantly expressed in TAMs. Importantly, co-culture models proved that IL4I1 significantly promoted the invasion and migration of glioma cells, and induced the polarization of M2-like macrophages. Conclusion: IL4I1 could be a promising immunotherapy target for selective modulation of TAMs and stands as a novel macrophage-related prognostic biomarker in glioma.

Beneficial effects of re-feeding high α-linolenic acid diets on the muscle quality, cold temperature and disease resistance of tilapia.

To investigate the effects of re-feeding high α-linolenic acid (ALA) diets on the muscle quality, cold temperature and disease resistance of the tilapia with nutritional history of soybean oil diets, three experimental diets with linoleic aicd (LA)/ALA ratios at 9 (D1, taking soybean oil as lipid sources), 3 and 1 (D2 and D3, taking soybean and linseed oils as lipid sources) were prepared to re-feed juveniles for 10 weeks, and the growth performance, muscle quality were analyzed. After the re-feeding trial, the fish were fasted for 8 weeks at cold temperature (15°C-20 °C) and then subjected to the Aeromonas hydrophila challenge, and the cold temperature and disease resistance of the fish were evaluated. It was shown that a comparable growth performance was detected among the three dietary groups, while, the high feed efficiency and low viscerosomatic and hepatosomatic index were detected in the D2 and D3 groups compared with the D1 group. In addition, the docosahexaenoic acid (DHA) and n-3 polyunsaturated fatty acid (PUFA) levels of the muscle increased in a parallel pattern with the dietary ALA levels, and the muscular tenderness, adhesiveness, and chewiness were modified substantially in fish fed the diets D2 and D3. After 8-week fasting at cold temperature, the low serum total antioxidant capacity (T-AOC) and malondialdehyde (MDA) levels, and high serum lysozyme (LZM) and C3 levels were observed in the D2 and D3 groups compared with the D1 group. It was also shown that high eicosapentaenoic acid (EPA), DHA, and n-3 PUFA levels were observed in the intestine, liver, and spleen of fish from D2 and D3 groups. Correspondingly, in the fish of the D2 and D3 groups, the mRNA levels of lzm in the liver, intestine, and spleen, and c3 in the intestine and spleen were increased, while the mRNA levels of il-1ß, ifn-γ, and tnf-α in the intestine, and ifn-γ, tnf-α in the liver, as well as spleen il-1ß, were decreased. Furthermore, the survival at day 15 post-challenge of A. hydrophila in the D2 and D3 groups were higher than those of the D1 group. The results demonstrated that re-feeding high ALA diets were beneficial to the muscle quality, cold temperature and disease resistance in the tilapia, and provide a basis for selecting the dietary lipid sources of tilapia pre-winter feed.

Enzymatic Synthesis of Diacylglycerol-Enriched Oil by Two-Step Vacuum-Mediated Conversion of Fatty Acid Ethyl Ester and Fatty Acid From Soy Sauce By-Product Oil as Lipid-Lowering Functional Oil.

Soy sauce by-product oil (SSBO), a by-product of the soy sauce production process, is the lack of utilization due to an abundance of free fatty acid (FFA) and fatty acid ethyl ester (EE). The utilization of low-cost SSBO to produce value-added diacylglycerol (DAG)-enriched oil and its applications are promising for the sustainability of the oil industry. The objective of this study was to utilize SSBO containing a high content of EE and FFA as raw material to synthesize DAG-enriched oil and to evaluate its nutritional properties in fish. Based on different behaviors between the glycerolysis of EE and the esterification of FFA in one-pot enzymatic catalysis, a two-step vacuum-mediated conversion was developed for the maximum conversions of EE and FFA to DAG. After optimization, the maximum DAG yield (66.76%) and EE and FFA conversions (96 and 93%, respectively) were obtained under the following optimized conditions: lipase loading 3%, temperature 38°C, substrate molar ratio (glycerol/FFA and EE) 21:40, a vacuum combination of 566 mmHg within the initial 10 h and 47 mmHg from the 10th to 14th hour. Further nutritional study in fish suggested that the consumption of DAG-enriched oil was safe and served as a functional oil to lower lipid levels in serum and liver, decrease lipid accumulation and increase protein content in body and muscle tissues, and change fatty acid composition in muscle tissues. Overall, these findings were vital for the effective utilization of SSBO resources and the development of future applications for DAG-enriched oil as lipid-lowering functional oil in food.

Activin A attenuates apoptosis of granulosa cells in atretic follicles through ERß-induced autophagy.

It is well known that approximately 99% of ovarian follicles in mammals suffer from a degenerative process known as atresia, which is a huge waste of genetic resource in female animals. Studies have shown that activin A (ACT-A) is located in ovarian granulosa cells and has different effects in granulosa cell depending on species. Although granulosa cells play a critical role during follicular atresia, the mechanism of action of ACT-A in bovine ovarian granulosa cells (BGC) is poorly understood. In this study, we first determined the apoptosis of BGCs isolated from growth follicles and atretic follicles respectively. Then, BGC isolated from atretic follicles were used as a model to elucidate the role of ACT-A in cattle ovary. The results showed that apoptosis occurred in both growing follicles and atretic follicles, and the percentage of apoptotic cells in atretic follicles was higher than that in growing follicles. The current results indicated that ACT-A can attenuate apoptosis of BGC by maintaining the function of BGC in atretic follicles. Increased ERß induced by ACT-A promoted BGC autophagy but had no effect on apoptosis. In summary, this study suggests that ACT-A attenuates BGC apoptosis in atretic follicles by ERß-mediated autophagy signalling.

Insulin activates LC-PUFA biosynthesis of hepatocytes by regulating the PI3K/Akt/mTOR/Srebp1 pathway in teleost Siganus canaliculatus.

Insulin is well known an important metabolic regulator in glucose and lipid metabolism. It has been proved to activate long-chain (≥ C20) polyunsaturated fatty acids (LC-PUFA) biosynthesis in mammals, but little is known about such a role in fish. To explore the effects and molecular mechanisms of insulin in fish LC-PUFA biosynthesis, we treated the rabbitfish S. canaliculatus hepatocyte line (SCHL) cells with 65 nM insulin for 12 h, and the results showed that the mRNA levels of genes encoding the key enzymes and transcription factor involved in rabbitfish LC-PUFA biosynthesis such as Δ6Δ5 fads2, elovl5 and srebp1, as well as those of PI3K pathway genes including pdk1, akt2 and mtor increased significantly. Moreover, SCHL cells treated with different PI3K/Akt pathway inhibitors (LY294002, Wortmannin, AKTi-1/2) alone or combined with insulin decreased the mRNA levels of PI3K/Akt/mTOR downstream signaling genes, including Δ6Δ5 fads2, Δ4 fads2, elovl5, elovl4 and srebp1. While PI3K/Akt agonists (740 Y-P, IGF-1, SC-79) had the opposite results. The results of fatty acid composition analysis of hepatocytes showed that insulin stimulation increased the Δ6Δ5 Fads2-dependent PUFA desaturation indexes, while Elovl5-dependent PUFA elongation indexes had upward trends, and consequently LC-PUFA contents increased. Taken together, these results indicated that insulin activated LC-PUFA biosynthesis probably through PI3K/Akt/mTOR/Srebp1 pathway in S. canaliculatus hepatocytes.

Effects of dietary leucine and valine levels on growth performance, glycolipid metabolism and immune response in Tilapia GIFT Oreochromis niloticus.

An 8-week feeding trial was performed to evaluate the effects of dietary leucine (Leu) and valine (Val) levels on growth performance, glycolipid metabolism and immune response in Oreochromis niloticus. Fish (15.23 ± 0.05 g) were randomly fed four diets containing two Leu levels (1.2% and 2.3%) and two Val levels (0.7% and 1.4%) as a 2 × 2 experimental design (LL-LV, LL-HV, HL-LV and HL-HV). Compared with LL-LV group, the growth parameters (final weight, daily growth coefficient (DGC) and growth rate per metabolic body weight (GRMBW)), feed conversion rate (FCR), the activities of intestinal amylase, lipase, creatine kinase (CK) and Na+, K+-ATPase, liver NAD+/NADH ratio, as well as the expression of SIRT1, GK, PK, FBPase, PPARα, CPT IA, ACO and IL10 all increased significantly in the HL-LV group; however, in the high Val group, final weight, DGC, GRMBW, intestinal enzyme activities, as well as the expression of PEPCK, SREBP1, FAS, IL8 and IL10 of the HL-HV group were significantly lower than those of the LL-HV group, while the opposite was true for the remaining indicators. Significant interactions between dietary Leu and Val were observed in final weight, DGC, GRMBW, plasma IL1ß and IL6 levels, intestinal amylase and CK activities, liver NAD+/NADH ratio, as well as the expression of SIRT1, PK, PEPCK, FBPase, SREBP1, FAS, PPARα, CPT IA, ACO, NF-κB1, IL1ß, IL6 and IL10. The highest values of growth parameters, intestinal enzyme activities and expression of SIRT1, FBPase, PPARα, CPT IA and ACO were observed in the HL-LV group, while the opposite was true for the expression of SREBP1, FAS, PPARα, NF-κB1, IL1ß and IL6. Overall, our findings indicated that dietary Leu and Val can effect interactively, and fish fed with diets containing 2.3% Leu with 0.7% Val had the best growth performance and hepatic health status of O. niloticus.

Controlling nutritional status score and prognostic nutrition index predict the outcome after severe traumatic brain injury.

OBJECTIVES: Immune-nutritional status is correlated with a clinical outcome in critical illness. Recently, controlling nutritional status (CONUT) score and prognostic nutrition index (PNI) has been reported to predict prognosis following cancer and other diseases. The aim of this study was to explore the relationship between the CONUT score and PNI and 6-month outcome in patients with severe traumatic brain injury (STBI). METHODS: We retrospectively analyzed the clinical data of 78 patients with STBI, including the CONUT score and PNI. Patients were divided into high CONUT group and low CONUT group. Patients were also divided into high PNI and low PNI group respectively. The 6-month outcome was evaluated by the modified Rankin scale (mRS). The unfavorable outcome was defined as mRS score ≥3. RESULTS: The unfavorable outcome group had lower Glasgow coma scale (GCS) scores, serum albumin, total cholesterol, PNI, and higher CONUT scores (P < 0.05). Both CONUT scores and PNI were strongly correlated with mRS (r = 0.429, P < 0.05; r = -0.590, P < 0.05, respectively). After adjustment for confounding factors, the odds ratios of CONUT scores and PNI for predicting unfavorable outcome were 10.478 (95% CI: 2.793-39.301) and -0.039 (95% CI: 0.008-0.204), respectively. The area under the curve (AUC) of CONUT scores for predicting unfavorable outcome was 0.777 (95% CI: 0.674-0.880, P < 0.01), which was similar to PNI (0.764, 95% CI: 0.657-0.87, P < 0.01). CONCLUSION: Both CONUT scores and PNI might be novel independent predictors of the poor outcome in STBI.

Interactions between dietary carbohydrate and thiamine: implications on the growth performance and intestinal mitochondrial biogenesis and function of Megalobrama amblycephala.

A12-week experiment was conducted to evaluate the influences of thiamine ongrowth performance, and intestinal mitochondrial biogenesis and function of Megalobramaamblycephala fed a high-carbohydrate (HC) diet. Fish (24·73 (sem 0·45) g) were randomly assigned to one of four diets: two carbohydrate (CHO) levels (30 and 45 %) and two thiamine levels (0 and 1·5 mg/kg). HC diets significantly decreased DGC, GRMBW, FIMBW, intestinal activities of amylase, lipase, Na+, K+-ATPase, CK, complexes I, III and IV, intestinal ML, number of mitochondrial per field, ΔΨm, the P-AMPK: T-AMPK ratio, PGC-1ß protein expression as well as the transcriptions of AMPKα1, AMPKα2, PGC-1ß, mitochondrial transcription factor A, Opa-1, ND-1 and COX-1 and 2, while the opposite was true for ATP, AMP and reactive oxygen species, and the transcriptions of dynamin-related protein-1, fission-1 and mitochondrial fission factor. Dietarythiamine concentrations significantly increased DGC, GRMBW, intestinal activities of amylase, Na+, K+-ATPase, CK, complexes I and IV, intestinal ML, number of mitochondrial per field, ΔΨm, the P-AMPK:T-AMPK ratio, PGC-1ß protein expression as well as the transcriptions of AMPKα1, AMPKα2, PGC-1ß, Opa-1, ND-1, COX-1 and 2, SGLT-1 and GLUT-2. Furthermore, a significant interaction between dietary CHO and thiamine was observed in DGC, GRMBW, intestinal activities of amylase, CK, complexes I and IV, ΔΨm, the AMP:ATP ratio, the P-AMPK:T-AMPK ratio, PGC-1ß protein expression as well as the transcriptions of AMPKα1, AMPKα2, PGC-1ß, Opa-1, COX-1 and 2, SGLT-1 and GLUT-2. Overall, thiamine supplementation improved growth performance, and intestinal mitochondrial biogenesis and function of M. amblycephala fed HC diets.

Systemic immune-inflammation index predicts the outcome after aneurysmal subarachnoid hemorrhage.

Systemic inflammatory response is closely related to the pathogenesis and prognosis in critical patients. Recently, systemic immune-inflammation index (SII), an indicator of systemic inflammatory response, was proved to predict the outcome in cancerous and non-cancerous diseases. The aim of this study is to investigate the association between SII on admission and 6-month outcome in patients with aneurysmal subarachnoid hemorrhage (aSAH). The clinical data and prognosis of 76 patients with aSAH were analyzed. The 6-month outcome was assessed by the modified Rankin scale(mRS). The unfavorable outcome was defined as mRS score ≥ 3. In addition, multivariate analysis was conducted to investigate factors independently associated with the favorable outcome. Receiver operating characteristic (ROC) curve analysis was undertaken to identify the best cut-off value of SII for the discriminate between favorable and unfavorable outcome in these patients. Thirty-six patients (47.4%) in our study had an unfavorable outcome (mRS ≥ 3) at 6 months, and twenty-four (66.7%) of them were in the high-SII group. A significantly higher SII on admission was observed in patients with unfavorable functional outcome at 6 months. Binary logistic regression analysis showed that there was an independent association between SII on admission and 6-month clinical outcome (adjusted OR = 4.499, 95%CI: 1.242-16.295, P < 0.05). The AUC of the SII for predicting unfavorable outcome was 0.692 (95% CI: 0.571-0.814, P < 0.05). Systemic immune-inflammation index (SII) could be a novel independent prognostic factor for aSAH patients at the early stage of the disease.

Molecular characterization of thioredoxin-interacting protein (TXNIP) from Megalobrama amblycephala and its potential roles in high glucose-induced inflammatory response.

This study aimed to characterize the full-length cDNA of thioredoxin-interacting protein (TXNIP) from Megalobrama amblycephala, and investigate its roles in high glucose (HC)-induced inflammatory response. The cDNA obtained covered 2706-bp with an open reading frame of 1203-bp encoding 400 amino acids, compared to Cyprinus carpio, it showed 89.96% homology. The highest expression of txnip was observed in head kidney followed by spleen and liver. After a 12-week feeding trial, high-carbohydrate diet remarkably increased txnip expression in liver and white muscle. Glucose administration resulted in a remarkably increased liver txnip expression, which peaked at 1 h. Thereafter, the expression decreased remarkably to the basal value at 12 h. However, insulin injection resulted in a significant decrease in txnip expression with minimum values attained at 2 h. Subsequently, it gradually increased to the normal values. Moreover, in the in-vitro study, over-expression of txnip along with remarkably increased il-1ß and il-6 expression in hepatocytes, and its knockdown led to remarkably reduced il-1ß expression. Furthermore, metformin treatment remarkably increased the cell viability and trx expression of hepatocytes under high glucose, while the opposite was true for ROS levels, LDH activity, the ALT/AST ratio, Txnip protein content and the transcriptions of txnip, tnfα and il-1ß.

Sp1 is Involved in Vertebrate LC-PUFA Biosynthesis by Upregulating the Expression of Liver Desaturase and Elongase Genes.

The rabbitfish Siganus canaliculatus was the first marine teleost demonstrated to have the ability for the biosynthesis of long-chain (≥C20) polyunsaturated fatty acids (LC-PUFA) from C18 PUFA precursors, and all the catalytic enzymes including two fatty acyl desaturase 2 (Δ4 Fads2 and Δ6/Δ5 Fads2) and two elongases (Elovl4 and Elovl5) have been identified, providing a good model for studying the regulatory mechanisms of LC-PUFA biosynthesis in fish. Stimulatory protein 1 (Sp1) has been speculated to be a vital transcription factor in determining the promoter activity of Fads-like genes in fish, however its regulatory effects on gene expression and LC-PUFA biosynthesis have not been demonstrated. Bioinformatic analysis predicted potential Sp1 binding sites in the promoters of the rabbitfish Δ6/Δ5 fads2 and elovl5, but not in Δ4 fads2 promoter. Here we cloned full-length cDNA of the rabbitfish sp1 gene, which encoded a putative protein of 701 amino acids, and was expressed in all tissues studied with highest levels in gill and eyes. The dual luciferase reporter assay in HepG2 line cells demonstrated the importance of the Sp1 binding site for the promoter activities of both Δ6/Δ5 fads2 and elovl5. Moreover, the electrophoretic mobility shift assay confirmed the direct interaction of Sp1 with the two promoters. Insertion of the Sp1 binding site of Δ6/Δ5 fads2 promoter into the corresponding region of the Δ4 fads2 promoter significantly increased activity of the latter. In the Siganus canaliculatus hepatocyte line (SCHL) cells, mRNA levels of Δ6/Δ5 fads2 and elovl5 were positively correlated with the expression of sp1 when sp1 was overexpressed or knocked-down by RNAi or antagonist (mithramycin) treatment. Moreover, overexpression of sp1 also led to a higher conversion of 18:2n-6 to 18:3n-6, 18:2n-6 to 20:2n-6, and 18:3n-3 to 20:3n-3, which related to the functions of Δ6/Δ5 Fads2 and Elovl5, respectively. These results indicated that Sp1 is involved in the transcriptional regulation of LC-PUFA biosynthesis by directly targeting Δ6/Δ5 fads2 and elovl5 in rabbitfish, which is the first report of Sp1 involvement in the regulation of LC-PUFA biosynthesis in vertebrates.

Cloning, functional characterization and nutritional regulation of Δ6 fatty acyl desaturase in the herbivorous euryhaline teleost Scatophagus argus.

Marine fish are generally unable or have low ability for the biosynthesis of long-chain polyunsaturated fatty acids (LC-PUFA) from C18 PUFA precursors, with some notable exceptions including the herbivorous marine teleost Siganus canaliculatus in which such a capability was recently demonstrated. To determine whether this is a unique feature of S. canaliculatus or whether it is common to the herbivorous marine teleosts, LC-PUFA biosynthetic pathways were investigated in the herbivorous euryhaline Scatophagus argus. A putative desaturase gene was cloned and functionally characterized, and tissue expression and nutritional regulation were investigated. The full-length cDNA was 1972 bp, containing a 1338 bp open-reading frame encoding a polypeptide of 445 amino acids, which possessed all the characteristic features of fatty acyl desaturase (Fad). Functional characterization by heterologous expression in yeast showed the protein product of the cDNA efficiently converted 18:3n-3 and 18:2n-6 to 18:4n-3 and 18:3n-6, respectively, indicating Δ6 desaturation activity. Quantitative real-time PCR showed that highest Δ6 fad mRNA expression was detected in liver followed by brain, with lower expression in other tissues including intestine, eye, muscle, adipose, heart kidney and gill, and lowest expression in stomach and spleen. The expression of Δ6 fad was significantly affected by dietary lipid and, especially, fatty acid composition, with highest expression of mRNA in liver of fish fed a diet with a ratio of 18:3n-3/18:2n-6 of 1.72:1. The results indicated that S. argus may have a different LC-PUFA biosynthetic system from S. canaliculatus despite possessing similar habitats and feeding habits suggesting that LC-PUFA biosynthesis may not be common to all marine herbivorous teleosts.

SNPs of hemocyanin C-terminal fragment in shrimp Litopenaeus vannamei.

In this study, we identified a variable region in the C-terminus of hemocyanin from the shrimp Litopenaeus vannamei (2288-2503bp, HcSC) by sequence alignments. A total of 13 SNPs were identified by PCR-SSCP and HcSC clone sequencing. The SSCP patterns of HcSC could be modulated in Vibro parahaemolyticus-treated shrimps. A novel SSCP band with four SNP sites was identified in V. parahaemolyticus-resistant shrimps. More importantly, three of these four SNPs introduced variations in amino acid sequence and possibly secondary structure of the HcSC polypeptide and resulted in a higher agglutinative activity against seven pathogenic bacteria. These results suggest that the C-terminus of shrimp L. vannamei hemocyanin possesses SNPs, which may be related to shrimp resistance to different pathogens.

Cloning and characterisation of the SpToll gene from green mud crab, Scylla paramamosain.

Toll/Toll-like receptors (TLRs), one of the most important pattern recognition receptors (PRRs), play a crucial role in innate immune responses in both invertebrates and vertebrates. In this study, we cloned and characterised a Toll gene from Scylla paramamosain (SpToll). Bioinformatic analysis predicted that SpToll contained one open reading frame of 3018bp and encoded a single-pass transmembrane domain protein of 1005 amino acids. Further, SpToll could be clustered into one branch along with other arthropod Tolls in a phylogenetic tree. SpToll transcripts could be detected by RT-PCR from all tissues examined including the heart, gill, hepatopancreas, stomach, intestine, muscle, eyestalk and hemocytes. Infection by Vibrio parahemolyticus up-regulated SpToll mRNA expression in hemocytes after 48h. The profile of single nucleotide polymorphisms (SNPs) in the leucine-rich repeats (LRRs) domain of SpToll in three healthy crabs was then evaluated. Two hundred and twenty SNPs with a frequency of about 1.0-4.0% were identified in hemocyte DNA/cDNA. Surprisingly, the adenine to guanine transition at position 1372 (c.1372A>G) had a frequency of about 50%. Finally, the results showed that challenge with V. parahemolyticus stimulated the appearance of two sets of SNPs in crabs. More importantly, the c.1372A>G mutation could contribute to a low mortality after V. parahemolyticus infection and introduce variation of charge and secondary structure into the SpToll polypeptide. In summary, these studies suggested a novel Toll homologue in crab and identified a SNP with potential pathogen-resistant activities. The result will be important for the investigation of crab immune defense mechanisms.