Evaluation of imaging indicators in differentiating idiopathic normal pressure hydrocephalus from Alzheimer's disease.

BACKGROUND: There are currently many imaging indicators for idiopathic normal pressure hydrocephalus (iNPH). However, their diagnostic performance has not been well compared, especially in differentiating iNPH from Alzheimer's disease (AD). This study aimed to evaluate the diagnostic performance of these imaging indicators in differentiating iNPH from AD. METHODS: We retrospectively collected patients with iNPH from the West China Hospital between June 2016 and December 2023. Age-sex-matched patients with AD and healthy controls (HCs) are included as controls (ChiCTR2300070078, March 2023). Twelve imaging indicators were evaluated on MRI, including disproportionately enlarged subarachnoid space hydrocephalus (DESH), Evans' index (EI), callosal angle, z-EI, temporal horn, dilated Sylvian fissure, focal sulcal dilation, tight high convexity, deep white matter hyperintensities, periventricular hyperintensities, DESH scale, and Simplified Radscale. We analyzed the receiver operating characteristic curves and calculated the sensitivity, specificity, negative predictive value (NPV), positive predictive value (PPV), and accuracy. RESULTS: A total of 46 patients with iNPH (mean age: 73.1 ± 6.5; 35 males), 46 patients with AD (mean age: 73.0 ± 6.6; 35 males), and 46 HCs (mean age: 73.0 ± 5.9; 35 males) were included. The largest area under the receiver operating characteristic curve (AUC) was found in EI (0.93; 95 % CI: 0.89-0.98) and z-EI (0.93; 95 % CI: 0.87-0.98). DESH scale ≥ 6 had the highest specificity (93 %, 43/46). CONCLUSION: EI and z-EI had the best diagnostic performance in differentiating iNPH from AD. The DESH scale could assist in diagnosing iNPH due to its high specificity.

Shenling Baizhu powder alleviates non-alcoholic fatty liver disease by modulating autophagy and energy metabolism in high-fat diet-induced rats.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) has emerged as a burgeoning health problem worldwide, but no specific drug has been approved for its treatment. Shenling Baizhu powder (SL) is extensively used to treat NAFLD in Chinese clinical practice. However, the therapeutic components and pharmacological mechanisms of SL against NAFLD have not been thoroughly investigated. PURPOSE: This study aimed to investigate the pharmacological impact and molecular mechanism of SL on NAFLD. METHODS: First, we established an animal model of NAFLD by high-fat diet (HFD) feeding, and evaluated the therapeutic efficacy of SL on NAFLD by physiological, biochemical, pathological, and body composition analysis. Next, the effect of SL on autophagic flow in NAFLD rats was evaluated by ultrastructure, immunofluorescence staining, and western blotting. Moreover, an integrated strategy of targeted energy metabolomics and network pharmacology was performed to characterize autophagy-related genes and explore the synergistic effects of SL active compounds. UPLC-MS/MS, molecular docking combined with in vivo and in vitro experiments were conducted to verify the key compounds and genes. Finally, a network was established among SL-herb-compound-genes-energy metabolites-NAFLD, which explains the complicated regulating mechanism of SL on NAFLD. RESULTS: We discovered that SL decreased hepatic lipid accumulation, hepatic steatosis, and insulin resistance, and improved systemic metabolic disorders and pathological abnormalities. Subsequently, an integrated strategy of targeted energy metabolomics and network pharmacology identified quercetin, ellagic acid, kaempferol, formononetin, stigmasterol, isorhamnetin and luteolin as key compounds; catalase (CAT), AKT serine/threonine kinase 1 (AKT), nitric oxide synthase 3 (eNOS), NAD(P)H quinone dehydrogenase 1 (NQO1), heme oxygenase 1 (HO-1) and hypoxia-inducible factor 1 subunit alpha (HIF-1α) were identified as key genes; while nicotinamide adenine dinucleotide phosphate (NADP) and succinate emerged as key energy metabolites. Mechanistically, we revealed that SL may exert its anti-NAFLD effect by inducing autophagy activation and forming a comprehensive regulatory network involving key compounds, key genes, and key energy metabolites, ultimately alleviating oxidative stress, endoplasmic reticulum stress, and mitochondrial dysfunction. CONCLUSION: Our study demonstrated the therapeutic effect of SL in NAFLD models, and establishes a basis for the development of potential products from SL plant materials for the treatment of NAFLD.

Molecular characterization of vascular endothelial growth factor b from spotted sea bass (Lateolabrax maculatus) and its potential roles in decreasing lipid deposition.

Vascular endothelial growth factor B (VEGFB), a member of the VEGF family, exhibits limited angiogenic activity in mammals but plays an unexpected role in targeting lipids to peripheral tissues. However, its role in lipid metabolism in fish is unknown. In this study, the vegfb gene was cloned and characterized from spotted sea bass (Lateolabrax maculatus). It encodes 254 amino acids and possesses the typical characteristics of the Vegfb family, demonstrating high homology with those from other vertebrate species. The vegfb gene exhibits the highest expression levels in the liver, followed by the gills, intestine, and adipose tissues in spotted sea bass. In vivo, high-lipid diets decreased vegfb expression and increased lipid deposition in liver of fish. In vitro, palmitic acid + oleic acid treatment or vegfb knockdown significantly increased TG and TC contents, promoting lipid droplet deposition in hepatocytes. Vegfb overexpression has the opposite effects, inhibiting lipid deposition and downregulating fatty acid transport and adipogenesis genes. In contrast, the vegfb knockdown significantly upregulated the expression levels of c/ebpα, plin2, and dgat1 (P < 0.05). These results demonstrate that Vegfb may play an important role in reducing lipid deposition by regulating fatty acid transport and adipogenesis in the hepatocytes of spotted sea bass.

Improvement in Muscle Fatty Acid Bioavailability and Volatile Flavor in Tilapia by Dietary α-Linolenic Acid Nutrition Strategy.

To investigate the modification of muscle quality of farmed tilapia through dietary fatty acid strategies, two diets were formulated. Diet SO, using soybean oil as the lipid source, and diet BO, using blended soybean and linseed oils, each including 0.58% and 1.35% α-linolenic acid (ALA), respectively, were formulated to feed juvenile tilapia for 10 weeks. The muscular nutrition composition, positional distribution of fatty acid in triglycerides (TAGs) and phospholipids (PLs), volatile flavor, lipid mobilization and oxidation were then analyzed. The results showed that there was no distinct difference between the SO and BO groups in terms of the nutrition composition, including crude protein, crude lipid, TAGs, PLs, and amino acid. Although the fatty acid distribution characteristics in ATGs and PLs showed a similar trend in the two groups, a higher level of n-3 PUFA (polyunsaturated fatty acid) and n-3 LC-PUFA (long-chain polyunsaturated fatty acid) bound to the glycerol backbone of TAGs and PLs was detected in the BO group than the SO group, whereas the opposite was true for n-6 PUFA. Additionally, the muscular volatile aldehyde and alcohol levels were higher in the BO group. Moreover, the expression of enzymatic genes and protein activities related to lipid mobilization (LPL, LPCAT, DGAT) and oxidation (LOX and GPX) was higher in the BO group. The results demonstrate that high-ALA diets may improve the fatty acid bioavailability and volatile flavor of tilapia by improving the lipid mobilization and oxidation, which provides new ideas for the improvement of muscle quality in farmed fish.

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.

Terrestrial Compound Protein Replacing Dietary Fishmeal Improved Digestive Enzyme Activity, Immune Response, Intestinal Microflora Composition, and Protein Metabolism of Golden Pompano (Trachinotus ovatus).

Terrestrial compound protein (Cpro) can be potentially used to replace fishmeal (FM) in the marine carnivorous teleost, golden pompano (Trachinotus ovatus). Four isonitrogenous (45%) and isolipidic (12%) diets named FM30, AP80, PP80, and CP80 were formulated. FM30 (control) contained 30% FM and 25% basic protein, while AP80, PP80, and CP80 only contained 6% FM, where 80% FM and 25% basic protein of control diet were completely replaced by animal protein, plant protein, and Cpro, respectively. After golden pompano juveniles (initial weight: 10.32 ± 0.09 g) were, respectively, fed the four diets in floating sea cages for 10 weeks, the growth performance, intestinal digestive enzyme activity, and immune responses, protein metabolism indices of the CP80 group were similar to or better than those of the FM30 group (P > 0.05), and significantly better than those of the AP80 and PP80 groups. Specifically, the weight gain (WG), feed conversion ratio (FCR), activity of alanine transaminase (ALT), growth hormone (GH), and insulin-like growth factor-1 (IGF-1) contents of serum, mRNA level of interleukin-10 (il-10), zonula occludens-2 (zo-2), claudin-3, claudin-12, and eukaryotic translation initiation factor 4G (eif4g) were significantly higher, and the activity of α-amylase (AMS), lipase (LPS) in the foregut and midgut, interleukin-8 (il-8) expression in the intestine was significantly lower than that in the CP80 group, compared with those in AP80 and PP80 groups (P < 0.05). Moreover, the intestinal microflora composition of golden pompano fed with the CP80 diet was improved. Specifically, at the phylum level, the relative abundance of harmful bacterial strains cyanobacteria and TM7 of CP80 group was similar to those of FM30 group (P > 0.05), but was significantly lower than those of AP80 and PP80 groups (P < 0.05). At the genus level, the beneficial bacterial strains Agrobacterium and Blantia of CP80 group were also similar to those of FM30 group (P < 0.05), which were significantly higher than those of AP80 and PP80 groups, but the beneficial bacterial strains Bifidobacterium and Devosia of CP80 group were significantly higher than that in the other groups (P < 0.05). Besides, in diet CP80, the contents of amino acids and anti-nutritional factor, as well as the in vitro digestion rate were comparable to those of FM30, and the anti-nutritional factor content was between AP80 and PP80; total essential amino acids (EAAs) and methionine contents were higher than those in AP80, the glycine content was higher than that in PP80. Taken together, these results indicated that the CP80 diet had better amino acid composition and relatively low content of anti-nutritional factors, as well as high-digestion rate, and thus leads to the fish fed CP80 displaying improved effects in digestive enzyme activity, immune response, protein metabolism, and intestinal microbiota composition, which may be the important reasons to explain why that 80% of FM can be replaced by Cpro in the diet of golden pompano.

Progress on the roles of zinc in sperm cryopreservation.

One of the effective methods for the long-term preservation of mammalian genetic resources is the cryopreservation of semen. However, a number of parameters, including diluents, the rate of freezing and thawing, cryoprotectants, etc., can easily alter the survival of frozen-thawed sperm. Numerous studies have documented the addition of a variety of zinc compounds, to the diluents used to cryopreserve sperm. The primary objective of this review is to briefly describe that adding zinc to diluents as an antioxidant significantly enhances frozen-thawed sperm quality. Second, a summary of the present understanding of zinc's molecular mechanism on semen cryopreservation is provided. Thirdly, this study addresses that nanoparticles of zinc can offer suggestions for raising cryopreservation effectiveness.

HDAC3 inhibitor (BRD3308) modulates microglial pyroptosis and neuroinflammation through PPARγ/NLRP3/GSDMD to improve neurological function after intraventricular hemorrhage in mice.

Neuroinflammation plays a vital role in intraventricular hemorrhage (IVH). Excessive neuroinflammation after IVH can activate the inflammasome in the cell and accelerate the occurrence of pyroptosis in cells, produce more inflammatory mediators, increase cell death, and lead to neurological deficits. Previous studies have reported that BRD3308 (BRD), an inhibitor of histone deacetylation by histone deacetylase 3 (HDAC3), suppresses inflammation-induced apoptosis and exhibits anti-inflammatory properties. However, it is unclear how BRD reduces the occurrence of the inflammatory cascade. In this study, we stereotactically punctured the ventricles of male C57BL/6J mice and injected autologous blood via the tail vein to simulate ventricular hemorrhage. Magnetic resonance imaging was used to detect ventricular hemorrhage and enlargement. Our findings demonstrated that BRD treatment significantly improved neurobehavioral performance and decreased neuronal loss, microglial activation, and pyroptosis in the hippocampus after IVH. At the molecular level, this treatment upregulated the expression of peroxisome proliferator-activated receptor γ (PPARγ) and inhibited NLRP3-mediated pyroptosis and inflammatory cytokines. Therefore, we concluded that BRD reduced pyroptosis and neuroinflammation and improve nerve function in part by activating the PPARγ/NLRP3/GSDMD signaling pathway. Our findings suggest a potential preventive role for BRD in IVH.

A comparative study on the tolerance of tilapia (Oreochromis niloticus) to high carbohydrate and high lipid diets.

A 12-wk trial was conducted to compare the tolerance of tilapia to high carbohydrate and high lipid diets. Three isonitrogenous and isoenergetic diets, whose carbohydrate and lipid levels were the following: 35.0% and 8% (control), 44.2% and 4% (D1, high carbohydrate), and 25.8% and 12% (D2, high lipid), respectively. Three hundred tilapias (27 ± 0.11 g) were fed the diets for 10 wk (4 replicates per group); 72 fish from the D1 group were continually fed the D1 (D1D1) and 72 fish from the D2 were continually fed the D2 (D2D2) diet for 2 wk (3 replicates each group) to evaluate the tilapia's capacity to tolerate high carbohydrate and high lipid diets, respectively. Another 36 fish from D1 group were continually fed D2 (D1D2) for comparison with D1D1 and D2D2 groups. In phase 1, hepatosomatic index, liver triglycerides (TG), glucose tolerance (GT) and crude protein in the whole body in D1 group were higher than those in D2 group (P < 0.05). During phase 2, D1D1 group had lower feed intake and weight gain, as well as lower serum total protein and albumin than that of D2D2 group (P < 0.05), while its liver glycogen was significantly higher than that in D1D2 and D2D2 groups (P < 0.05). Moreover, serum glucose and GT were higher in D1D1 and D1D2 groups than those in D2D2 group (P < 0.05). By contrast, D2D2 group had significantly higher intraperitoneal fat, subcutaneous adipose tissue (SCAT) and liver TG than those in D1D1 group (P < 0.05). The mRNA expression of brain npy, hepatic nrf2, gst1 and hepatic transcriptomic data showed that immune-related genes (gama, mrc2, mhc2 and cd163), were downregulated in D1D1 group compared to D2D2 and D1D2 groups. Taken together: 1) tilapia have higher tolerance to a high lipid diet than high carbohydrate diet; 2) despite retention of glucose tolerance, the continuous feeding of D1 diet impaired tilapia's appetite, weight gain rate and host immune response; 3) specific distribution of fat in intraperitoneal regions, SCAT and liver may be a risk-avoidance strategy in tilapia in response to a continuous D2 diet.

Dietary Fishmeal Can Be Partially Replaced with Non-Grain Compound Proteins through Evaluating the Growth, Biochemical Indexes, and Muscle Quality in Marine Teleost Trachinotus ovatus.

In the context of human food shortages, the incorporation of non-grain feedstuff in fish feed deserves more research attention. Here, the feasibility and appropriate ratio of non-grain compound protein (NGCP, containing bovine bone meal, dephenolized cottonseed protein, and blood cell meal) for dietary fishmeal (FM) replacement were explored in golden pompano (Trachinotus ovatus). Four isonitrogenous (45%) and isolipidic (12%) diets (Control, 25NGP, 50NGP, and 75NGP) were prepared. Control contained 24% FM, whereas the FM content of 25NGP, 50NGP, and 75NGP was 18%, 12%, and 6%, respectively, representing a 25%, 50%, and 75% replacement of FM in Control by NGCP. Juvenile golden pompano (initial weight: 9.71 ± 0.04 g) were fed the four diets for 65 days in sea cages. There was no significant difference between the 25NGP and Control groups in terms of weight gain, weight gain rate, and specific growth rate; contents of crude protein, crude lipid, moisture, and ash in muscle and whole fish; muscle textural properties including hardness, chewiness, gumminess, tenderness, springiness, and cohesiveness; and serum biochemical indexes including total protein, albumin, blood urea nitrogen, HDL cholesterol, total cholesterol, and triglycerides. However, the golden pompano in 50NGP and 75NGP experienced nutritional stress, and thus some indicators were negatively affected. In addition, compared to the Control group, the expression levels of genes related to protein metabolism (mtor, s6k1, and 4e-bp1) and lipid metabolism (pparγ, fas, srebp1, and acc1) of the 25NGP group showed no significant difference, but the 4e-bp1 and pparγ of the 75NGP group were significantly upregulated and downregulated, respectively (p < 0.05), which may explain the decline in fish growth performance and muscle quality after 75% FM was replaced by NGCP. The results suggest that at least 25% FM of Control can be replaced by NGCP, achieving a dietary FM content of as low as 18%; however, the replacement of more than 50% of the dietary FM negatively affects the growth and muscle quality of golden pompano.

TUG-891 inhibits neuronal endoplasmic reticulum stress and pyroptosis activation and protects neurons in a mouse model of intraventricular hemorrhage.

Pyroptosis plays an important role in hemorrhagic stroke. Excessive endoplasmic reticulum stress can cause endoplasmic reticulum dysfunction and cellular pyroptosis by regulating the nucleotide-binding oligomerization domain and leucine-rich repeat pyrin domain-containing protein 3 (NLRP3) pathway. However, the relationship between pyroptosis and endoplasmic reticulum stress after intraventricular hemorrhage is unclear. In this study, we established a mouse model of intraventricular hemorrhage and found pyroptosis and endoplasmic reticulum stress in brain tissue. Intraperitoneal injection of the selective GPR120 agonist TUG-891 inhibited endoplasmic reticulum stress, pyroptosis, and inflammation and protected neurons. The neuroprotective effect of TUG-891 appears related to inhibition of endoplasmic reticulum stress and pyroptosis activation.

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.

Integrated printed BDNF-stimulated HUCMSCs-derived exosomes/collagen/chitosan biological scaffolds with 3D printing technology promoted the remodelling of neural networks after traumatic brain injury.

The restoration of nerve dysfunction after traumatic brain injury (TBI) faces huge challenges due to the limited self-regenerative abilities of nerve tissues. In situ inductive recovery can be achieved utilizing biological scaffolds combined with endogenous human umbilical cord mesenchymal stem cells (HUCMSCs)-derived exosomes (MExos). In this study, brain-derived neurotrophic factor-stimulated HUCMSCs-derived exosomes (BMExos) were composited with collagen/chitosan by 3D printing technology. 3D-printed collagen/chitosan/BMExos (3D-CC-BMExos) scaffolds have excellent mechanical properties and biocompatibility. Subsequently, in vivo experiments showed that 3D-CC-BMExos therapy could improve the recovery of neuromotor function and cognitive function in a TBI model in rats. Consistent with the behavioural recovery, the results of histomorphological tests showed that 3D-CC-BMExos therapy could facilitate the remodelling of neural networks, such as improving the regeneration of nerve fibres, synaptic connections and myelin sheaths, in lesions after TBI.

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.

Sodium oxamate reduces lactate production to improve the glucose homeostasis of Micropterus salmoides fed high-carbohydrate diets.

The study was performed to evaluate the effects of the reduced lactate production by sodium oxamate (SO) on growth performance, lactate and glucose and lipid metabolism, and glucose tolerance of Micropterus salmoides fed high-carbohydrate (CHO) diets. In in vitro study, primary hepatocytes were incubated for 48 h in a control medium (5.5 mM glucose), a high-glucose medium (25 mM glucose, HG), or a SO-containing high-glucose medium (25 mM glucose + 50 mM SO, HG-SO). Results indicated lactate and triglyceride (TG) levels, and lactate dehydrogenase a (LDH-a) expression in the HG-SO group were remarkably lower than those of the HG group. In in vivo study, M. salmoides (5.23 ± 0.03 g) were fed four diets containing a control diet (10% CHO, C) and three SO contents [0 (HC), 100 (HC-SO1), and 200 (HC-SO2) mg·kg-1, respectively] of high-CHO diets (20% CHO) for 11 wk. High-CHO diets significantly reduced weight gain rate (WGR), specific growth rate (SGR), p-AMPK-to-t-AMPK ratio, and expression of insulin receptor substrate 1 (IRS1), insulin-like growth factor I (IGF-I), insulin-like growth factor I receptor (IGF-IR), fructose-1,6-biphosphatase (FBPase), peroxisome proliferator-activated receptor α (PPARα), and carnitine palmitoyl transferase 1α (CPT1α) compared with the C group, whereas the opposite was true for plasma levels of glucose, TG, lactate, tissue glycogen, and lipid contents, and expression of LDH-a, monocarboxylate transporter 1 and 4 (MCT1 and MCT4), insulin, glucokinase (GK), pyruvate dehydrogenase E1 subunit (PDH), sterol-regulatory element-binding protein 1 (SREBP1), fatty acid synthase (FAS). The HC-SO2 diets remarkably increased WGR, SGR, p-AMPK-to-t-AMPK ratio, and expression of IRS1, IGF-I, IGF-IR, GK, PDHα, PDHß, FAS, acetyl-CoA carboxylase 1 (ACC1), PPARα, and CPT1α compared with the HC group. Besides, HC-SO2 diets also enhanced glucose tolerance of fish after a glucose loading. Overall, the reduced lactate production by SO benefits growth performance and glucose homeostasis of high-CHO-fed M. salmoides through the enhancement of glycolysis, lipogenesis, and fatty acid ß-oxidation coupled with the suppression of glycogenesis and gluconeogenesis.

GPR120-ERK1-Srebp1c signaling pathway regulates long-chain polyunsaturated fatty acids biosynthesis in marine teleost Siganus canaliculatus.

The rabbitfish Siganus canaliculatus is the first marine teleost reported to possess long-chain polyunsaturated fatty acids (LC-PUFA) biosynthetic ability; its regulatory mechanisms have been investigated at the transcriptional and posttranscriptional levels, but little is known about its regulation at the cellular signaling level. The present study investigated the regulatory role of the G-protein-coupled receptor 120 (GPR120) signaling pathway in LC-PUFA biosynthesis in rabbitfish. S. canaliculatus hepatocyte line (SCHL) cells treated with GRP120 agonists (TUG891 and GW9508) showed significantly lower docosahexaenoic acid (DHA) content and mRNA levels of the key genes involved in LC-PUFA biosynthesis, encoding Δ6/Δ5 Fads2, Elovl5, and transcriptional factor Srebp1c. Transcriptome analysis of the treated SCHL cells showed significantly lower mRNA levels of genes encoding extracellular signal-regulated kinase 1 (ERK1), AMP-activated protein kinase (AMPKα2), target of rapamycin (TORC2) and Srebp1c, suggesting that these proteins are potentially involved in the GRP120 signaling pathway. Moreover, treatment of SCHL cells with signaling chemicals of ERK1, AMPKα2, TORC2, and Srebp1c confirmed the involvement of the ERK1-Srebp1c signaling pathway in the regulation of LC-PUFA biosynthesis. The mRNA levels of Srebp1c, Δ6/Δ5 fads2 and elovl5 were significantly lower in cells treated with PUFAs (linoleic acid, α-linolenic acid, arachidonic acid, eicosapentaenoic acid, DHA) but higher in those treated with ERK1 inhibitors (U0126 and CI-1040). CI-1040-treated cells showed significantly higher DHA content, but the other treatment groups (except PD98059) showed significantly lower DHA content. These results indicate that the GPR120-ERK1-Srebp1c signaling pathway regulates rabbitfish LC-PUFA biosynthesis, representing a novel regulatory mechanism in vertebrates.

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.

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.

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.