Prediction model of no-response before the first transarterial chemoembolization for hepatocellular carcinoma: TACF score.

Previous clinic models for patients with hepatocellular carcinoma (HCC) receiving transarterial chemoembolization (TACE) mainly focused on the overall survival, whereas a simple-to-use tool for predicting the response to the first TACE and the management of risk classification before TACE are lacking. Our aim was to develop a scoring system calculated manually for these patients. A total of 437 patients with hepatocellular carcinoma (HCC) who underwent TACE treatment were carefully selected for analysis. They were then randomly divided into two groups: a training group comprising 350 patients and a validation group comprising 77 patients. Furthermore, 45 HCC patients who had recently undergone TACE treatment been included in the study to validate the model's efficacy and applicability. The factors selected for the predictive model were comprehensively based on the results of the LASSO, univariate and multivariate logistic regression analyses. The discrimination, calibration ability and clinic utility of models were evaluated in both the training and validation groups. A prediction model incorporated 3 objective imaging characteristics and 2 indicators of liver function. The model showed good discrimination, with AUROCs of 0.735, 0.706 and 0.884 and in the training group and validation groups, and good calibration. The model classified the patients into three groups based on the calculated score, including low risk, median risk and high-risk groups, with rates of no response to TACE of 26.3%, 40.2% and 76.8%, respectively. We derived and validated a model for predicting the response of patients with HCC before receiving the first TACE that had adequate performance and utility. This model may be a useful and layered management tool for patients with HCC undergoing TACE.

Effects of oxycodone hydrochloride sustained-release tablets and morphine hydrochloride sustained-release tablets on peripheral blood T cell levels in advanced lung squamous cell carcinoma with moderate to severe cancer pain.

Objective: To investigate the effects of morphine hydrochloride sustained-release tablets and oxycodone hydrochloride sustained-release tablets on T-cell levels in advanced lung squamous cell carcinoma(LUSC) with moderate to severe cancer pain. Methods: A retrospective study was used, ninety-eight patients who were admitted to The First Affiliated Hospital of Hebei North University for treatment of advanced LUSC with moderate to severe cancer pain between January 2021 and December 2021 were randomized into two groups(n=49 each) using the sealed envelope system. The reference group was treated with morphine hydrochloride sustained-release tablets, while the experimental group received oxycodone hydrochloride sustained-release tablets to compare pain relief rates(PRRs), levels of T cells, pain intensity, et al. Blood samples were collected for lymphocyte levels by flow cytometry. Results: The experimental group had significantly higher level than the reference group(P<0.05). Before administration, the two groups did not differ greatly in levels of T-cell subsets or pain scores on the visual analog scale(P>0.05, respectively). At 15 days of administration, the Treg level in the experimental group was higher than in the reference group; T helper 17 and 22 cells were reduced in both groups, and the decrease was more pronounced in the experimental group. At seven and 15 days of administration, the experimental group had a VAS score significantly lower than the reference group(P<0.05). The total adverse reaction rate was significantly lower in the experimental group as compared with the reference group(P<0.05). Conclusions: Oxycodone hydrochloride sustained-release tablets demonstrate desirable efficacy and safety in advanced LUSC with moderate to severe cancer pain by modulating T-cells in the body and improving the PRR.

Fabrication of Luteolin Loaded Zein-Caseinate Nanoparticles and its Bioavailability Enhancement in Rats.

Luteolin loaded zein nanoparticles (Lut-ZNP) were prepared by using sodium caseinate as an electrostatic stabilizer. The formulation of the nanoparticles was optimized. Lut-ZNP were spray-dried, and the physicochemical properties were characterized by SEM, XRD, FT-IR and DSC. Then, the bioavailability of luteolin in rats was determined. Under the formulation of luteolin, zein and sodium caseinate with mass ratio of 1:5:15, the particle size, ζ-potential, encapsulation efficiency and loading efficiency of Lut-ZNP were 171.8 nm, -49.05 mV, 85.85% and 3.15%, respectively. Luteolin existed in the nanoparticles with amorphous form. Lut-ZNP exhibited good redispersibility in water after drying. Compared with free luteolin, the solubility, stability and release of luteolin in Lut-ZNP were greatly improved. Besides, the fecal excretion of luteolin in rats was significantly reduced after oral administration of Lut-ZNP. In addition to native luteolin, its metabolites including sulfate, glucuronidate and methylated glucuronidate were found in rat plasma. Lut-ZNP significantly increased the plasma concentrations of luteolin and its metabolites, and the bioavailability of luteolin was enhanced by 2.92 times.

Luteolin-Loaded Nanoparticles for the Treatment of Melanoma.

Background and Purpose: Luteolin (LUT), a flavonoid found in various plants, has been reported to have potential therapeutic effects in melanoma. However, poor water solubility and low bioactivity have severely restricted the clinical application of LUT. Based on the high reactive oxygen species (ROS) levels in melanoma cells, we developed nanoparticles encapsulating LUT with the ROS-responsive material poly(propylene sulfide)-poly(ethylene glycol) (PPS-PEG) to enhance the water solubility of LUT, accelerate the release of LUT in melanoma cells, and further enhance its anti-melanoma effect, providing a viable solution for the application of LUT nano-delivery systems in melanoma therapy. Methods: In this study, LUT-loaded nanoparticles were prepared with PPS-PEG and named as LUT-PPS-NPs. Dynamic light scattering (DLS) and transmission electron microscopy (TEM) were applied to determine the size and morphology of LUT-PPS-NPs. In vitro studies were carried out to determine the uptake and mechanism of LUT-PPS-NPs by SK-MEL-28 melanoma cells. According to the CCK-8 assay, the cytotoxic effects of LUT-PPS-NPs on human skin fibroblasts (HSF) and SK-MEL-28 cells were assessed. Apoptosis assays, cell migration and invasion assays, and proliferation inhibition assays with low and normal density plating were also applied to test the in vitro anti-melanoma effect. Additionally, melanoma models were established utilizing BALB/c nude mice and initially evaluated the growth inhibitory impact following intratumoral injection of LUT-PPS-NPs. Results: The size of LUT-PPS-NPs was 169.77 ± 7.33 nm with high drug loading (15.05 ± 0.07%). In vitro, cellular assays confirmed that LUT-PPS-NPs were efficiently internalized by SK-MEL-28 cells and showed low cytotoxicity against HSF. Moreover, LUT released from LUT-PPS-NPs significantly inhibited tumor cell proliferation, migration and invasion. Animal experiments showed that LUT-PPS-NPs inhibited tumor growth more than 2-fold compared with the LUT group. Conclusion: In conclusion, the LUT-PPS-NPs developed in our study enhanced the anti-melanoma effect of LUT.

Dynamic differentiation of F4/80+ tumor-associated macrophage and its role in tumor vascularization in a syngeneic mouse model of colorectal liver metastasis.

Tumor-associated macrophages (TAMs) are highly heterogeneous and play vital roles in tumor progression. Here we adopted a C57BL/6 mouse model imitating the late-stage colorectal liver metastasis (CRLM) by Mc38 colorectal cancer cell injection via the portal vein. With serial sections of CRLM biopsies, we defined 7-9 days post-injection as the critical period for tumor neovascularization, which was initiated from the innate liver vessels via vessel cooption and extended by vascular mimicry and thereof growth of CD34+cells. In samples with increasing-sized liver metastases, the infiltrated Ly6C+ CD11b+ F4/80- monocytes steadily gained the expression of F4/80, a Kupffer cell marker, before transformed into Ly6C- CD11bint F4/80+ cells, which, the same phenotype was also adapted by Ly6C- CD11b- F4/80+ Kupffer cells. F4/80+ TAMs showed proximity to neovascularization and tumor vessels, functionally angiogenic in vivo; and greatly promoted the activation of a few key angiogenic markers such as VEGFA, Ki67, etc. in endothelial cells in vitro. Depletion of macrophages or diversion of macrophage polarization during neovascularization impeded tumor growth and vascularization and resulted in greatly reduced F4/80+ TAMs, yet increased CD11b+ cells due to inhibition of TAM differentiation. In summary, our results showed dynamic and spatial-temporal F4/80+ TAM transformation within the tumor microenvironment and strengthened its role as perivascular and angiogenic TAMs in CRLM.

Association between copy number variation of SERPINA3-1 gene and growth traits in Chinese cattle.

Serpin peptidase inhibitor, clade A (alpha-1 antiproteinase, antitrypsin), member 3 (SERPINA3) belongs to the serine protease inhibitor family A subtype, and contains 8 genes from SERPINA3-1 to SERPINA3-8. Although the regulatory effects of these 8 genes have been revealed one by one in recent years, the related effects of SERPINA3-1 gene on cattle growth is still unclear. This study used quantitative Real time PCR (qPCR) to detect the type of copy number variation (CNV) of SERPINA3-1 gene in a total of 542 Chinese cattle, and expression of SERPINA3-1 gene in different tissues of Qinchuan cattles (adult) on mRNA level. Then association analysis was conducted between the detection results and cattle growth traits. The results showed that the Duplication type in SERPINA3-1 gene performed better on the growth traits and the CNV was significantly correlated with multiple growth traits (p < 0.05). In addition, SERPINA3-1 gene has different expression conditions in different tissues, results showed that SERPINA3-1 gene has a low expression in muscle. In conclusion, we speculate that the SERPINA3-1 gene can be used as a molecular marker and the result of this study could be a basic material for candidate functional genes for beef cattle growth and development.

In order to detect the gene expression diversification of the SERPINA3-1 gene, blood samples were collected from five Chinese cattle breeds, we detected related signal and made an associated analyze with cattle growth traits. We determined the copy number variation distribution of the SERPINA3-1 gene in cattle populations and found that the SERPINA3-1 gene has a certain promoting effect on the growth and development of Chinese cattle. For example, Pinan cattle with Duplication type copy number have a better performance on growth traits. This study has enriched the candidate genes of Chinese cattle molecular breeding and provided basic data for Chinese cattle breeding.

Network pharmacology analysis of the mechanism of Huisheng oral liquid in the treatment of lung cancer.

Background: To study the active ingredient and possible mechanism of Huisheng oral liquid in the treatment of lung cancer by network pharmacology. Methods: The active ingredient and drug targets of Huisheng oral liquid were screened using the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) and Traditional Chinese Medicine Integrated Database (TCMID), and lung cancer targets were screened using the Gene Expression Omnibus (GEO) database. The drug targets of the effective components of Huisheng oral liquid were matched with disease targets and the obtained intersecting targets were imported into the Search Tool for the Retrieval of Interaction Gene/Proteins (STRING) database to construct a protein-protein interaction (PPI) network. R software and the Kyoto Encyclopedia of Genes and Genomes (KEGG) database were used for Gene Ontology (GO) and KEGG enrichment analyses, and Cytoscape software was used to construct a Huisheng oral liquid component target-lung cancer target network. The function and pathway of the therapeutic target of Huisheng oral liquid for lung cancer were analyzed. Results: A total of 1,376 differentially expressed genes (DEGs) of lung cancer were obtained, and 185 potential effective components of Huisheng oral liquid in the treatment of lung cancer were obtained, including quercetin, luteolin, kaempferol, and baicalein. There were 36 intersecting targets between Huisheng oral liquid and lung cancer, and the key targets for lung cancer treatment were CDKN1A, CCNB1, MDM2, CDK1, ErbB2, E2F1, EGFR, etc. Huisheng oral liquid mainly regulates the p53 signaling pathway. Conclusions: The mechanism of Huisheng oral liquid in the treatment of lung cancer is mainly reflected in regulating tumor cell apoptosis, inhibiting angiogenesis, and improving immunity.

Effects and dose-response relationships of exercise intervention on weight loss in overweight and obese children: a meta-regression and system review.

The aim of this study was to determine the effect of different exercise doses on weight loss in obese/overweight children. PubMed, Embase, SPORTDiscus, and the Cochrane library were searched from inception to November 2020 for randomized controlled trials. Fourty six trials involving 2,599 obese/overweight children were finally included. Different exercise dose interventions had different impacts. Exercise intervention reduce body weight (BW) by 1.46 kg (95% CI, -2.35 to -0.56, p=0.001), body fat percentage (BF%) by 2.24 (95% CI, -2.63 to -1.84, p<0.001) and body mass index (BMI) by 1.09 kg/m2 (95% CI, -1.45 to -0.73, p<0.001). Each MET-h/week was association with 0.147 kg (95% CI, -0.287 to -0.007, p=0.039) decrease in BW, 0.060 (95% CI, -0.118 to -0.002, p=0.042) decrease in BF%, and 0.069 kg/m2 (95% CI, -0.125 to -0.014, p=0.015) decrease in BMI. The findings suggest that there is a positive liner between exercise dose and weight loss, each MET-h/week associated with 0.147 kg, 0.060 and 0.069 kg/m2 decrease in body weight, BF%, BMI, respectively.

Ultrasensitive analysis of mirtazapine and its metabolites enantiomers in body fluids using ultrasound-enhanced and surfactant-assisted dispersive liquid-liquid microextraction followed by polymer-mediated stacking in capillary electrophoresis.

A simple, rapid, and sensitive technique for measuring mirtazapine and its metabolites enantiomers in human fluids, such as urine and serum, was developed by applying ultrasound-enhanced and surfactant-assisted dispersive liquid-liquid microextraction (USA-DLLME) integrated with poly(diallyldimethylammonium chloride) (PDDAC)-mediated stacking in capillary electrophoresis (CE). The parameters that affect extraction and stacking performance, such as the extraction volume, surfactant types, surfactant concentrations, salt additives, extraction time, solution pH, and background electrolytes, were comprehensively studied and optimized to achieve optimal detection performance. Under optimal extraction conditions (injection of 120 µL of C2H2Cl4 into 1 mL of a sample solution containing 0.05 mM Brij-35 at pH 10.0) and separation conditions (0.9% PDDAC, 10 mM phosphate, pH 3.0, and 20 mM dimethyl-ß-cyclodextrin), on-line CE stacking of mirtazapine-related chiral drugs was achieved by the two strategies: (i) neutral DM-ß-CD sweep low concentrations of DL-NaSSA and (ii) DL-NASSA is stacked by the difference in the viscosity between the PDDAC and sample zone. An approximately 2,800-4000-fold improvement in detection sensitivity was revealed for mirtazapine, N-demethylmirtazapine, and 8-hydroxymirtazapine enantiomers. The linear ranges for the quantification of all analyte enantiomers were 1.2-150 nM, with a coefficient of determination higher than 0.99; the relative standard deviations in the migration time and peak areas for six analytes were less than 1.8% and 5.8%, respectively. The proposed system provided the limits of detection (signal-to-noise ratio of 3) of the six analytes as 0.3-0.5 nM. The recovery of the six separated analytes spiked in urine and serum samples was revealed to be 82.7%-109.5% and 91%-112.8%, respectively. This advanced technique with high sensitivity enhancement factors was successfully employed to analyze mirtazapine and its metabolites enantiomers in urine and serum samples with reliability.

Compensatory roles of Protein Related to DAN and Cerberus (PRDC) decrease in pulmonary arterial hypertension.

Bone morphogenetic protein (BMP) signaling is commonly suppressed in patients with pulmonary arterial hypertension (PAH), but the compensatory mechanism of BMP signaling suppression is incompletely elucidated. This study aimed to investigate the role of PRDC, an antagonist of BMPs, in PAH and the underlying mechanism. Human lungs were collected and rat PAH was induced (monocrotaline, 60 mg/kg). BMP cascade and PRDC were detected in lungs and distal pulmonary artery smooth muscle cells (dPASMCs). In vitro cell experiments and in vivo supplementation of PRDC in hypertensive rats were subsequently performed. PRDC and BMP cascade all decreased in human and rat hypertensive lungs. Cell experiments confirmed that BMP2/4 inhibited dPASMCs proliferation by increasing cell cycle inhibitors (p21, p27), prevented dPASMCs migration by down-regulating MMP2/9 and up-regulating TIMP1/2 expression, and promoted dPASMCs apoptosis by up-regulating Bax, caspase3/9 and down-regulating Bcl-2 expression, as well as enhancing caspase3/7 activity, while, PRDC reversed the effects of BMP2/4 on dPASMCs proliferation, migration and apoptosis. In vivo trial found that PRDC supplementation deteriorated rat PAH in terms of pulmonary hemodynamics, vasculopathies and right ventricle hypertrophy. Taken together, compensatory decrease of PRDC in hypertensive lungs theoretically slow down the natural course of PAH, suggesting its therapeutic potential in PAH.

[The role of semaphorin 4D in the mechanism of bisphosphonate-related osteonecrosis of the jaw in rats].

PURPOSE: To study the expression level of semaphorin 4D (Sema4D) in bisphosphonate-related osteonecrosis of the jaw (BRONJ) and to explore its possible role in the occurrence of BRONJ. METHODS: BRONJ-like rat model was established by intraperitoneal injection of zoledronic acid assisted with tooth extraction. The maxillary specimens were extracted for imaging and histological examination, and bone marrow mononuclear cells(BMMs) and bone marrow mesenchymal stem cells(BMSCs) of each group were obtained in vitro for co-culture. Trap staining and counting were performed on monocytes after osteoclast induction. RAW264.7 cells were induced by osteoclast orientation under bisphosphonates(BPs) environment, and Sema4D expression was detected. Similarly, MC3T3-E1 cells and BMSCs were induced to osteogenic orientation in vitro, and the expression level of osteogenic and osteoclastic related genes ALP, Runx2, and RANKL was detected under the intervention of BPs, Sema4D and Sema4D antibody. Statistical analysis of the data was performed using GraphPad Prism 8.0 software. RESULTS: BRONJ-like rat model was successfully constructed. Two weeks after tooth extraction, the healing of the tooth extraction wound in the experimental group was significantly limited, and the tooth extraction wound was exposed. H-E staining results showed that regeneration of new bone in the extraction socket of the experimental group was significantly restricted, dead bone was formed, and the healing of the soft tissue was limited. The results of trap staining showed that the number of osteoclasts in the experimental group was significantly less than that in the control group. Micro-CT results showed that bone mineral density and bone volume fraction in the extraction socket of the experimental group were significantly lower than those of the control group. Immunohistochemical results showed that compared with the control group, the expression level of Sema4D in the experimental group was significantly increased. In vitro studies showed that compared with the control group, the osteoclast induction of BMMs in the experimental group was significantly lower than that in the control group. BMSCs in the experimental group significantly reduced the induction of osteoclasts. Osteoclastic induction experiments revealed that bisphosphonates could effectively inhibit the formation of osteoclasts, and the expression of Sema4D was significantly reduced. Osteogenic induction experiment found that Sema4D significantly reduced the expression of Runx2 and RANKL genes in osteoblasts, while the expression of ALP gene decreased and the expression of RANKL up-regulated after adding Sema4D antibody. CONCLUSIONS: BPs can interfere with normal bone healing time by up-regulating the expression of Sema4D in tissues, leading to coupling disorder between osteoclasts and osteoblasts with inhibition of the maturation of osteoclasts, thereby inhibiting the growth of osteoblasts. Differentiation and expression of related osteogenic factors mediate the development of BRONJ.

Adverse skin reactions induced by sintilimab in advanced lung squamous carcinoma: a case report and review of the literature.

Background: Sintilimab is an immune checkpoint inhibitor (ICI). It can induce immune-related Adverse Events (irAEs). Severe adverse skin reactions are rare, but the mortality rate is high. We report the first case of successful treatment of adverse skin reactions using traditional Chinese medicine (TCM). Case Description: Here we present the case of a 67-year-old male with advanced lung squamous carcinoma. After 8 cycles of chemotherapy, the patient's disease progressed and the treatment regimen was adjusted to sintilimab combined with albumin paclitaxel and cisplatin. Thirty-two days after this cycle, the patient reported a sporadic rash with pruritus on the face, front chest, and both upper limbs. The area of rash was 40%, and the adverse reaction was grade 3. The level of interleukin-related indicators was above normal. The patient's skin symptoms disappeared after treatment with hormones, TCM, and other drugs. The patient's adverse skin reaction was due to an immune-related toxicity caused by sintilimab, so treatment with sintilimab was suspended. The albumin-paclitaxel plus cisplatin regimen was continued to treat lung cancer. Conclusions: Although rare, case of fatal adverse reaction caused by sintilimab have been reported. We recommend early monitoring and recognition of symptoms. During management, high-dose hormones combined TCM may be helpful.

In situ identification of TATP and DADP particles collected with transparent tape by Raman spectroscopy and imaging.

Triacetone triperoxide (TATP) and its byproduct diacetone diperoxide (DADP) are commonly used home-made high explosives in bombing cases and terrorist attacks. However, these two peroxide explosives are unstable and prone to thermal decomposition, leading to challenges in sample collection and preparation in bombing cases. Therefore, there is an urgent need to develop an in situ identification method for TATP and DADP. Compared to the solvent-based swabbing methods commonly used for trace explosive collection, the tape lifting method can collect explosive particles and other potential evidence without damaging fingerprints or DNA. This study aims to develop a tape lifting method to collect trace explosive particles in bombing cases and an in situ method to identify TATP and DADP particles on the sticky side of transparent tape directly using laser confocal Raman spectroscopy. One type of fingerprint tape and two types of office tape were used to collect peroxide explosive particles followed by particle fixation on glass slides. Laser confocal Raman spectroscopy was applied to directly identify target particles, without peeling the attached tape off the glass slide. A solid-state laser emitting at 473 nm was suitable for Raman and imaging analysis of TATP and DADP. To mimic the real situation, the synthetic TATP and DADP were passed through a 100-mesh sieve, respectively. Fifty µg of each explosive powder was weighed, mixed and spread on a wooden table with dust in an area of 10 × 10 cm2. Subsequently, the samples were collected with the fingerprint tape. A targeted area of the tape with suspicious particles was imaged for analysis. Based on the difference between the characteristic Raman bands of TATP and DADP, the band ranges of 530-550 cm-1 and 750-770 cm-1 were selected, respectively, for obtaining the distribution information. The combination of Raman technology and the tape lifting method shows great potential for in situ identification of forensic samples by providing chemical and spatial information.

Polysaccharide from wild morels alters the spatial structure of gut microbiota and the production of short-chain fatty acids in mice.

Polysaccharides from morels possess many characteristics beneficial to health, such as anti-tumor and immunomodulatory activities. The gut microbiota plays a critical role in the modulation of immune function. However, the impact of morel polysaccharides on the gut microbiota has not yet been explored. In this study, a high-throughput pyrosequencing technique was used to investigate the effects of MP, a new heteropolysaccharide extracted from wild morels, on the diversity and composition of microbiota along the intestine in mice, as well as the production of short-chain fatty acids (SCFAs). The results showed that MP treatment increased the number of operational taxonomic unit (OTUs) and diversity along the intestine, especially in the small intestine. MP treatment induced a significant decrease in the number of Firmicutes and a significant increase in the number of Bacteroidetes in the small intestine microbiota. It was also observed that the relative abundance of SCFA-producing bacteria, especially Lachnospiraceae, was increased in both the cecum and colon of MP-treated mice. Moreover, MP promoted the production of SCFAs in mice. These results provide a foundation for further understanding the health benefits conferred by morel polysaccharides.

High-dose omega-3 polyunsaturated fatty acid supplementation might be more superior than low-dose for major depressive disorder in early therapy period: a network meta-analysis.

BACKGROUND: The application of n-3 Polyunsaturated Fatty Acids (n-3 PUFAs) supplementation for major depressive disorder (MDD) has been widely discussed in recent years, but its efficacy and application are still controversial. This network meta-analysis was conducted to compare the efficacy of different dosages of n-3 PUFAs on MDD patients in the early period of treatment. METHODS: Randomized controlled trials (RCTs) exploring the efficacy of n-3 PUFA supplementation for patients with MDD were retrieved from the databases of Pubmed, Embase and the Cochrane Library. RCTs comparing the efficacy of n-3 PUFA for adult (≥18 years) MDD patients without comorbidity were eligible for our study. The score of depressive symptoms in early therapy period of the treatment (≤9 weeks) was extracted. Standardized mean deviations (SMDs) of all the sores from the eligible RCTs were synthesized in a pairwise meta-analysis in frequentist framework and a random-effects network meta-analysis in Bayesian framework for the overall and subgroups (high- and low-dose) efficacy of n-3 PUFAs. RESULTS: A total of 910 MDD patients in 10 trials with 3 adjuvant therapy strategies (high-dose n-3 PUFAs, low-dose n-3 PUFAs and placebo) were included. Results of pairwise meta-analysis showed that n-3 PUFAs were superior to placebo (SMD: 1.243 ± 0.596; 95% CI: 0.060 ~ 2.414). Results of the network meta-analysis showed that both the high (SMD: 0.908 ± 0.331; 95% CI: 0.262 ~ 1.581) and the low-dose (SMD: 0.601 ± 0.286; 95% CI: 0.034 ~ 1.18) n-3 PUFAs were superior to placebo, and the efficacy of high-dose n-3 PUFAs is superior to that of low-dose. CONCLUSIONS: High-dose n-3 PUFAs supplementation might be more superior than low-dose in the early therapy period for MDD. More head-to-head clinical trials need to be carried out to provide more direct comparison and enhance the evidence of the efficacy of n-3PUFAs for MDD.

Effects of polysaccharides from wild morels on immune response and gut microbiota composition in non-treated and cyclophosphamide-treated mice.

Polysaccharides isolated from mushrooms have been identified as potential prebiotics that could impact gut microbiota. In this study, a water-soluble polysaccharide (MP) extracted from wild morels was evaluated for its effects on the gut microbiota of non-treated and cyclophosphamide (CP)-treated mice. The results showed that MP restored the spleen weight and increased the counts of white blood cells and lymphocytes in the peripheral blood and spleen of the CP-treated mice. Mice treated with MP exhibited increased levels of short-chain fatty acid (SCFA)-producing bacteria, especially Lachnospiraceae, compared to normal mice, and increased levels of Bacteroidetes and SCFA-producing bacteria, especially Ruminococcaceae, compared to the CP-treated mice. Moreover, MP treatment increased the production of valeric acid and decreased the production of acetic acid in the non-treated mice and increased the production of acetic acid, propionic acid, butyric acid, and valeric acid in the CP-treated mice. These results show that MP is potentially good for health.

Association Between the Polymorphism of Aldehyde Dehydrogenase 2 Gene and Cerebral Infarction in a Hakka Population in Southern China.

Genetic factors play an important role in determining the susceptibility to ischemic stroke. Herein, we examined the association of an aldehyde dehydrogenase 2 (ALDH2) gene polymorphism with cerebral infarction. Patients with cerebral infarction (n = 963) and healthy controls (n = 921) were included. Genotyping was performed using gene chip platform analysis, and Sanger sequencing was used to confirm ALDH2 genotypes. The risk prediction of ALDH2 polymorphisms for cerebral infarction was examined under three genetic modes of inheritance. For males, ALDH2*2/*2 genotype was a significant risk factor for cerebral infarction in the co-dominant model (age-, smoking-, and drinking-adjusted OR 1.514, 95% CI 1.005-2.282, p = 0.047) and the recessive model (age-, smoking-, and drinking-adjusted OR 1.601, 95% CI 1.078-2.379, p = 0.020). However, for females, ALDH2*2/*2 genotype was a protective factor for cerebral infarction in the co-dominant model (age-, smoking-, and drinking-adjusted OR 0.450 95% CI 0.215-0.941, p = 0.034) and the recessive model (age-, smoking-, and drinking-adjusted OR 0.440, 95% CI 0.214-0.903, p = 0.025). Further, logistic regression analysis revealed that age, smoking, hypertension, hyperlipidemia, and hypercholesterolemia were significant risks for the presence of cerebral infarction. In conclusion, these findings support an association of ALDH2 gene polymorphisms with ischemic stroke in a Chinese Hakka population. In particular, homozygote ALDH2*2/*2 may be a risk factor for cerebral infarction in males, but contribute to reduced risk for cerebral infarction in females.

The First Complete Genome Sequence of a Novel Tetrastichus brontispae RNA Virus-1 (TbRV-1).

The complete sequence of a novel RNA virus isolated from Tetrastichus brontispae (TbRV-1) was determined to be 12,239 nucleotides in length with five non-overlapping, linearly arranged coding sequences (CDS), potentially encoding nucleoproteins, hypothetical proteins, matrix proteins, glycoproteins, and RNA-dependent RNA polymerases. Sequence analysis indicated that the RNA-dependent RNA polymerase of TbRV-1 shares a 65% nucleotide and 67% amino acid sequence identity with Hubei dimarhabdovirus 2, suggesting that TbRV-1 is a member of the dimarhabdovirus supergroup. This corresponded to the result of the phylogenetic analysis. The affiliation of TbRV-1 with members of the family Rhabdoviridae was further validated by similar transcription termination motifs (GGAACUUUUUUU) to the Drosophila sigmavirus. The prevalence of TbRV-1 in all tissues suggested that the virus was constitutive of, and not specific to, any wasp tissue. To our knowledge, this is the first report on the complete genome sequence of a dimarhabdovirus in parasitoids.

Combination of label-free quantitative proteomics and transcriptomics reveals intraspecific venom variation between the two strains of Tetrastichus brontispae, a parasitoid of two invasive beetles.

The venom apparatus is a conserved organ in parasitoids that shows adaptations correlated with life-style diversification. Combining transcriptomics and label-free quantitative proteomics, here we explored the venom apparatus components of the endoparasitoid Tetrastichus brontispae (Eulophidae), and provide a comparison of the venom apparatus proteomes between its two closely related strains, T. brontispae-Octodonta nipae (Tb-On) and T. brontispae-Brontispa longissima (Tb-Bl). Tb-Bl targets the B. longissima pupa as its habitual host. However, Tb-On is an experimental derivative of Tb-Bl, which has been exposed to the O. nipae pupa as host consecutively for over 40 generation. Results showed that approximately 1505 venom proteins were identified in the T. brontispae venom apparatus. The extracts contained novel venom proteins, such as 4-coumarate-CoA ligase 4. A comparative venom proteome analysis revealed that significant quantitative and qualitative differences in venom composition exist between the two strains; although the most abundant venom proteins were shared between them. The differentially produced proteins were mainly enriched in fatty acid biosynthesis and melanotic encapsulation response. Six of these enriched proteins presented increased levels in Tb-On, and this result was validated by parallel reaction monitoring (PRM) analysis. Overall, our data reveal that venom composition can evolve quickly and respond to host selection.

Dexmedetomidine Attenuates Acute Lung Injury Induced by Heatstroke and Improve Outcome.

INTRODUCTION: Dexmedetomidine (DEX) has been demonstrated to inhibit inflammatory response and protect against multiorgan injury in various scenarios. The objectives of the present study were to ascertain whether DEX is able to attenuate acute lung injury (ALI) under heatstroke (HS), and to explore the underlying mechanism. METHODS: Male C57BL/6 mice were exposed to ambient temperature of 39.5 ±â€Š0.2°C until core temperature reach 43°C. DEX or 0.9% saline was injected i.p. immediately. At the end of the experiment, bronchoalveolar lavage fluid (BALF) and lung tissue were harvested. RESULTS: HS induce ALI and pulmonary dysfunction, while DEX treatment could significantly inhibit lung injury and improve respiratory dysfunction under HS. The overall effect was beneficial and improved the 72 h cumulative survival rate of mice with HS. Furthermore, HS significantly elevated the levels of cytokines in BALF, as well as increased the activity of toll-like receptor 4 (TLR4)/MyD88/nuclear factor-κB (NFκB) signaling pathway in lung tissue, while DEX treatment could inhibit such effects. Finally, DEX could upregulate the expression of caveolin 1 downregulated by HS, which may contribute to the inhibition of TLR4/MyD88/NFκB signaling pathway. DISCUSSION: In conclusion, the present results indicated that DEX may protect against lung inflammatory response and injury under HS via TLR4/MyD88/NFκB signaling pathway, and caveolin-1 may participate in the effects.