Assessing the hepatotoxicity of phosphogypsum leachate in zebrafish (Danio rerio).

The improper disposal of large amounts of phosphogypsum generated during the production process of the phosphorus chemical industry (PCI) still exists. The leachate formed by phosphogypsum stockpiles could pose a threat to the ecological environment and human health. Nevertheless, information regarding the harmful effects of phosphogypsum leachate on organisms is still limited. Herein, the physicochemical characteristics of phosphogypsum leachate were analyzed, and its toxicity effect on zebrafish (Danio rerio), particularly in terms of hepatotoxicity and potential mechanisms, were evaluated. The results indicated that P, NH3-N, TN, F-, As, Cd, Cr, Co, Ni, Zn, Mn, and Hg of phosphogypsum leachate exceeded the V class of surface water environmental quality standards (GB 3838-2002) to varying degrees. Acute toxicity test showed that the 96 h LC50 values of phosphogypsum leachate to zebrafish was 2.08 %. Under exposure to phosphogypsum leachate, zebrafish exhibited concentration-dependent liver damage, characterized by vacuolization and infiltration of inflammatory cells. The increased in Malondialdehyde (MDA) content and altered activities of antioxidant enzymes in the liver indicated the induction of oxidative stress and oxidative damage. The expression of apoptosis-related genes (P53, PUMA, Caspase3, Bcl-2, and Bax) were up-regulated at low dosage group and down-regulated at medium and high dosage groups, suggesting the occurrence of hepatocyte apoptosis or necrosis. Additionally, phosphogypsum leachate influenced the composition of the zebrafish gut microbiota by reducing the relative abundance of Bacteroidota, Aeromonas, Flavobacterium, Vibrio, and increasing that of Rhodobacter and Pirellula. Correlation analysis revealed that gut microbiota dysbiosis was associated with phosphogypsum leachate-induced hepatotoxicity. Altogether, exposure to phosphogypsum leachate caused liver damage in zebrafish, likely through oxidative stress and apoptosis, with the intestinal flora also playing a significant role. These findings contribute to understanding the ecological toxicity of phosphogypsum leachate and promote the sustainable development of PCI.

Selenium-SelK-GPX4 axis protects nucleus pulposus cells against mechanical overloading-induced ferroptosis and attenuates senescence of intervertebral disc.

Intervertebral disc degeneration (IVDD) is one of the most prevalent spinal degenerative disorders and imposes places heavy medical and economic burdens on individuals and society. Mechanical overloading applied to the intervertebral disc (IVD) has been widely recognized as an important cause of IVDD. Mechanical overloading-induced chondrocyte ferroptosis was reported, but the potential association between ferroptosis and mechanical overloading remains to be illustrated in nucleus pulposus (NP) cells. In this study, we discovered that excessive mechanical loading induced ferroptosis and endoplasmic reticulum (ER) stress, which were detected by mitochondria and associated markers, by increasing the intracellular free Ca2+ level through the Piezo1 ion channel localized on the plasma membrane and ER membrane in NP cells. Besides, we proposed that intracellular free Ca2+ level elevation and the activation of ER stress are positive feedback processes that promote each other, consistent with the results that the level of ER stress in coccygeal discs of aged Piezo1-CKO mice were significantly lower than that of aged WT mice. Then, we confirmed that selenium supplementation decreased intracellular free Ca2+ level by mitigating ER stress through upregulating Selenoprotein K (SelK) expression. Besides, ferroptosis caused by the impaired production and function of Glutathione peroxidase 4 (GPX4) due to mechanical overloading-induced calcium overload could be improved by selenium supplementation through Se-GPX4 axis and Se-SelK axis in vivo and in vitro, eventually presenting the stabilization of the extracellular matrix (ECM). Our findings reveal the important role of ferroptosis in mechanical overloading-induced IVDD, and selenium supplementation promotes significance to attenuate ferroptosis and thus alleviates IVDD, which might provide insights into potential therapeutic interventions for IVDD.

Effects of fulvic acid on broiler performance, blood biochemistry, and intestinal microflora.

To study the effects of mineral fulvic acid (FuA) on broiler performance, slaughter performance, blood biochemistry index, antioxidant function, immune performance, and intestinal microflora, 360 Arbor Acres (AA) broiler chickens with similar body weights were randomly divided into 5 groups with 6 replicates in each group and 12 chickens in each replicate in the current study. Chickens in the control group (C) were fed with the basal diet, and chickens in the test groups (I, II, III, and IV) were fed with the diet supplemented with 0.05%, 0.1%, 0.2%, and 0.3% mineral FuA, respectively. The indicators were measured on the hatching day, d 21 and d 35. From the whole experimental period, FuA supplement significantly increased average body weight (ABW) (P < 0.05), average daily gain (ADG) of broilers (P < 0.05), and thymus weight (P < 0.05) in II and IV groups, but bascially reduced the pH value of thigh meat. FuA supplement significantly improved aspartate aminotransferase (AST) activity in the group III on d 35 (P < 0.05) and the serum levels of IgA and IgG on d 21 and d 35 (P < 0.05), but reduced glutathione peroxidase (GSH-Px) level on d 21 (P < 0.05) and malondialdehyde (MDA) level in serum on d 35 (P < 0.05). FuA supplement significantly affected the abundance of Barnesiella, Lachnospiraceae, Alistipes, Lactobacillus, and Christensenellaceae on genus level. Differences between group III and other groups were significant in the genera microflora composition on d 21 and d 35. Functional analysis showed that the cecum microbiota were mainly enriched in carbohydrate metabolism, amino acid metabolism, and energy metabolism. In conclusion, FuA may potentially have significant positive effects on the growth performance and immune function of AA chickens through the modulation of the gut microbiota, and the 0.1% FuA was the best in broiler diet based on the present study.

Xiaotan Sanjie recipe, a compound Chinese herbal medicine, inhibits gastric cancer metastasis by regulating GnT-V-mediated E-cadherin glycosylation.

OBJECTIVE: Xiaotan Sanjie recipe (XTSJ), a Chinese herbal compound medicine, exerts a significant inhibitory effect on gastric cancer (GC) metastasis. This work investigated the mechanism underlying the XTSJ-mediated inhibition of GC metastasis. METHODS: The effect of XTSJ on GC metastasis and the associated mechanism were investigated in vitro, using GC cell lines, and in vivo, using a GC mouse model, by focusing on the expression of Glc-N-Ac-transferase V (GnT-V; encoded by MGAT5). RESULTS: The migration and invasion ability of GC cells decreased significantly after XTSJ administration, which confirmed the efficacy of XTSJ in treating GC in vitro. XTSJ increased the accumulation of E-cadherin at junctions between GC cells, which was reversed by MGAT5 overexpression. XTSJ administration and MGAT5 knockdown alleviated the structural abnormality of the cell-cell junctions, while MGAT5 overexpression had the opposite effect. MGAT5 knockdown and XTSJ treatment also significantly increased the accumulation of proteins associated with the E-cadherin-mediated adherens junction complex. Furthermore, the expression of MGAT5 was significantly lower in the lungs of BGC-823-MGAT5 + XTSJ mice than in those of BGC-823-MGAT5 + solvent mice, indicating that the ability of gastric tumors to metastasize to the lung was decreased in vivo following XTSJ treatment. CONCLUSION: XTSJ prevented GC metastasis by inhibiting the GnT-V-mediated E-cadherin glycosylation and promoting the E-cadherin accumulation at cell-cell junctions. Please cite this article as: Huang N, He HW, He YY, Gu W, Xu MJ, Liu L. Xiaotan Sanjie recipe, a compound Chinese herbal medicine, inhibits gastric cancer metastasis by regulating GnT-V-mediated E-cadherin glycosylation. J Integr Med. 2023; 21(6): 561-574.

Blooming characteristics and breeding system of an invasive plant Gaura parviflora.

The invasiveness and dissemination of exotic species are strongly influenced by its sexual reproduction characteristics, including blooming characteristics and breeding system. Exploring the association of these sexual reproductive traits with invasiveness would be helpful for revealing the mechanism of its successful invasion. We examined the blooming characteristics and breeding system of Gaura parviflora based on field observations, out-crossing index (OCI) estimation, and hand-pollination experiments. The results showed flowering duration of the G. parviflora population (flowering period) was short (more than 3 months). The life span of single flower (floral longevity) was 40.46 h. Its flower diameter was 3.99 mm. Over seven flowers in bloom per inflorescence and most individuals often bloomed synchronously, which showed a 'mass-flowering pattern'. The changing trend of pollen and stigma vitality was relatively similar, but the duration of stigma vitality was 2 h longer than that of pollen. The stigma and the anthers were close to each other at the initial flowering stage, but the stigma removed from the anthers at the full-blooming stage with the style curving downwards. Many pollinators visited flowers in late full-blooming stage, which were mainly Apis mellifera and Syrphidae spp. Their average visiting frequency was 9.8 times·m-2·h-1. The fruit set in natural pollination after emasculation treatment (insect or wind pollination) was signi-ficantly higher than that in bagged and emasculation treatment, and the treatment of emasculated and bagged with nylon net (excluding insect pollination) could also bear fruits, indicating possible existence of ambophily in G. parviflora. The results of pollen ovule ratio (P/O) mensuration, OCI estimation and hand-pollination experiments showed that its mating system type belonged to additive mixed mating system. So, its characteristics, such as smaller flower size, shorter floral longevity and flowering period, were conducive to allocating more resources to plant growth and seed development, which would help improve its total fitness. The changes of spatial position of male and female organs not only avoided interference between male and female functions, but also created opportunities for stigmas to receive outcross pollen. In addition, the 'mass-flowering pattern' was conducive to attracting pollinators. The pollination mechanism of ambophily was helpful to ensure cross-pollination. The additive mixed mating system could provide double reproductive assurance for this species. These reproductive characteristics were significant for the successful invasion and expansion of G. parviflora.

Recent progress in CRISPR-based bioengineering of microbial cell factories for important nutraceuticals synthesis.

Nutraceuticals are defined as food or food components with therapeutic capabilities that have few side effects and are regarded as a natural therapy for preventing the onset of several life-threatening illnesses. The use of microbial cell factories to produce nutraceuticals is considered to be sustainable and promising for meeting market demand. Among the diverse strategies for optimizing microbial cell factories, the CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats) system has emerged as a valuable tool for gene integration, deletion, activation, and downregulation. With the advent of multiplexed and precise CRISPR strategies, optimized microbial cell factories are revolutionizing the yield of nutraceuticals. This review focuses on the development of highly adaptable CRISPR strategies to optimize the production in microbial cell factories of some important nutraceuticals (belonging to the class of carotenoids, flavonoids, stilbenoids, polysaccharides, and nonprotein amino acids). Further, we highlighted current challenges related to the efficiency of CRISPR strategies and addressed potential future directions to fully harness CRISPR strategies to make nutraceutical synthesis in microbial cell factories an industrially favorable method.

The Effects of In Ovo Feeding of Selenized Glucose on Selenium Concentration and Antioxidant Capacity of Breast Muscle in Neonatal Broilers.

This study aims to investigate the impacts of in ovo feeding (IOF) of selenized glucose (SeGlu) on selenium (Se) level and antioxidant capacity of breast muscle in newborn broilers. After candling on 16 day of incubation, a total of 450 eggs were randomly divided into three treatments. On the 17.5th day of incubation, eggs in a control treatment were injected with 0.1 mL of physiological saline (0.75%), while the 2nd group and 3rd group were supplied with 0.1 mL of physiological saline containing 10 µg Se from SeGlu (SeGlu10 group) and 20 µg Se from SeGlu (SeGlu20 group). The results showed that in ovo injection in both SeGlu10 and SeGlu20 increased the Se level and reduced glutathione concentration (GSH) in pectoral muscle of hatchlings (P < 0.05). Compared with the control group, the SeGlu20-treated chicks significantly enhanced the activity of the superoxide dismutase (SOD) and mRNA expression of NAD(P)H quinone dehydrogenase 1 (NQO1) in breast muscle, while there was upregulation in mRNA expressions of glutathione peroxidase 1 (GPX-1) and thioredoxin reductase 1 (TrxR1) and higher total antioxidant capacity (T-AOC) in SeGlu10 treatment (P < 0.05). However, no significant difference on enzyme activities of glutathione peroxidase (GR), glutathione reductase, thioredoxin reductase, concentration of malondialdehyde, and free radical scavenging ability (FRSA) of superoxide radical (O2-•) and hydroxyl radical (OH•) was observed among the three treatments (P > 0.05). Therefore, IOF of SeGlu enhanced Se deposition in breast muscle of neonatal broilers. In addition, in ovo injection of SeGlu could increase the antioxidant capacity of newborn chicks possibly through upregulating the mRNA expression of GPX1, TrxR1, and NQO1, as well as the SOD activity.

Supplementing cholamine to diet lowers laying rate by promoting liver fat deposition and altering intestinal microflora in laying hens.

The effects of cholamine, a raw material for synthesis of some active lipids, are unknown in poultry. To address this, 180 52-wk-old Hyline laying hens were randomly divided into 3 groups (20 replicates per group with three hens per replicate). The control group and the treatment groups (treatment 1 and 2) were fed basal diet and the diet supplemented with 500 or 1,000 mg of cholamine per kilogram of the diet for 35 d, respectively. The data showed that supplementary cholamine significantly lowered egg production, daily feed intake, serum high-density lipoprotein cholesterol level, liver index, and the percentages of C15:0 and C20:0 in fatty acid composition of liver, significantly elevated hepatic triglyceride content, the ratio of villus height to crypt depth (P < 0.05), and the percentage of C18:2n-6 and the ratio of n-6 to n-3 polyunsaturated fatty acids in liver fat (P < 0.10). Moreover, supplementary cholamine altered the relative abundance of some intestinal bacteria with a decrease in the alpha biodiversity (P < 0.10). Additionally, transcriptome analysis on the livers of the treatment vs. the control groups identified 1,151 up- and 914 down-regulated differentially expressed genes (DEGs), and pathway analysis revealed that the suppressed Notch signaling pathway and the enhanced Oxidative phosphorylation pathway were enriched with DEGs. Particularly, fat absorption, transport and oxidative phosphorylation-related DEGs (e.g., FABP1, APOA4, and PCK1) were significantly induced, but fatty acid synthesis, and lipid package and secretion-related DEGs (e.g., FASN, SCD, and MTTP) were not. In conclusion, supplementary cholamine may lower egg production by promoting hepatic lipid deposition and reducing abundances of beneficial intestinal bacteria and microfloral biodiversity in laying hens.

Integrative pharmacogenomics revealed three subtypes with different immune landscapes and specific therapeutic responses in lung adenocarcinoma.

Background: Pharmacogenomics is crucial for individualized drug therapy and plays an increasingly vital role in precision medicine decision-making. However, pharmacogenomics-based molecular subtypes and their potential clinical significance remain primarily unexplored in lung adenocarcinoma (LUAD). Methods: A total of 2065 samples were recruited from eight independent cohorts. Pharmacogenomics data were generated from the profiling of relative inhibition simultaneously in mixtures (PRISM) and the genomics of drug sensitivity in cancer (GDSC) databases. Multiple bioinformatics approaches were performed to identify pharmacogenomics-based subtypes and find subtype-specific properties. Results: Three reproducible molecular subtypes were found, which were independent prognostic factors and highly associated with stage, survival status, and accepted molecular subtypes. Pharmacogenomics-based subtypes had distinct molecular characteristics: S-Ⅰ was inflammatory, proliferative, and immune-evasion; S-Ⅱ was proliferative and genetics-driven; S-III was metabolic and methylation-driven. Finally, our study provided subtype-guided personalized treatment strategies: Immune checkpoint blockers (ICBs), doxorubicin, tipifarnib, AZ628, and AZD6244 were for S-Ⅰ; Cisplatin, camptothecin, roscovitine, and A.443654 were for S-Ⅱ; Docetaxel, paclitaxel, vinorelbine, and BIBW2992 were for S-III. Conclusion: We provided a novel molecular classification strategy and revealed three pharmacogenomics-based subtypes for LUAD patients, which uncovered potential subtype-related and patient-specific therapeutic strategies.

[Research advances of chemical constituents and analytical methods of Citri Reticulatae Pericarpium Viride and Citri Reticulatae Pericarpium].

Citri Reticulatae Pericarpium Viride(CRPV) and Citri Reticulatae Pericarpium(CRP) are two commonly used Chinese medicinal materials. They have the same origin while are harvested in different seasons and have different clinical effects. They contain similar chemical components, like flavonoids, terpenes, volatile oils, and alkaloids. Although it has been demonstrated that differential components exist between them, there is still a lack of systematic comparison. Many studies have reported the chemical composition and quality evaluation of CRPV and CRP, including the characterization of flavonoids, alkaloids, and volatile oils via thin-layer chromatography, high-performance liquid chromatography, gas chromatography, infrared spectroscopy, and ultraviolet spectroscopy. A few studies have explored the differences between CRPV and CRP. In this paper, we systematically summarized the reported chemical composition, analytical methods, and quality evaluation of CRPV and CRP in recent ten years, aiming to facilitate the research on the pharmacodynamic material basis, quality evaluation, and standard improvement of CRPV and CRP.

Shengmai San for Treatment of Cardiotoxicity from Anthracyclines: A Systematic Review and Meta-Analysis.

OBJECTIVE: To systematically evaluate the efficacy of Shengmai San in patients with cardiotoxicity of anthracyclines. METHODS: Randomized controlled trials (RCTs) were identified by searching China National Knowledge Infrastructure (CNKI), Wanfang Database, Chinese Biomedical Literature Database (CBM), PubMed, Cochrane Library, and Embase Databases from the inceptions until December 2020. The Cochrane Handbook was used to evaluate the risk of bias in the included studies. Data analysis was conducted using RevMan 5.3 software. RESULTS: Totally 19 RCTs with 2,331 participants were included in this review. Results showed that in improving arrhythmia (13 RCTs, n=1,877, RR=0.37, 95%CI 0.25 to 0.52, P<0.00001), the treatment group was superior to the control group. In terms of reducing left ventricular end-diastolic diameter (LVEDD, 2 RCTs, n=128, MD=-0.79, 95%CI -0.93 to -0.65, P<0.00001) and left ventricular end systolic diameter (LVESD, 2 RCTs, n=128, MD=-0.58, 95%CI -0.82 to -0.35, P<0.00001), the treatment group was also better than the control group. In reducing myocardial enzymes such as creatine kinase (CK) [(3 RCTs, n=256, SMD=-0.80, 95%CI -1.16 to -0.44, P<0.0001), (2 RCTs, n=126, SMD=-0.62, 95%CI -0.98 to -0.26, P=0.0007)], the treatment group was superior to the control group. CONCLUSION: Shengmai San has a positive effect on the treatment of cardiotoxicity from anthracyclines. However, in the future, it is still necessary to conduct high-quality RCTs to verify its efficacy.

Theophylline Extracted from Fu Brick Tea Affects the Metabolism of Preadipocytes and Body Fat in Mice as a Pancreatic Lipase Inhibitor.

The dramatic increase in obesity is putting people under increasing pressure. Lipase inhibitors, as a kind of effective anti-obesity drug, have attracted more and more researchers' attention in recent years because of their advantages of acting on the intestinal tract and having no side effects on the central nervous system. In this study, lipase inhibitor Fu Brick Theophylline (FBT) was screened based on enzyme molecular dynamics, and the inhibition mechanism of lipase inhibitors on obesity was analyzed and discussed at the cellular level and animal model level. We found that FBT had high inhibition effects of lipase with an IC50 of 1.02~0.03 µg/mL. Firstly, the laboratory used 3T3-L1 proadipocytes as models, flow cytometry was used to detect the effects of FBT on the cycle, apoptosis and intracellular ROS activity of proadipocytes. To study the contents of triglyceride, total cholesterol, related metabolites and related gene and protein expression in adipocytes. The results showed that FBT could reduce ROS production and inflammatory factor mRNA expression during cell differentiation. Secondly, by establishing the animal model of high-fat feed ob nutritional obese mice, the morphological observation and gene expression analysis of body weight, fat rate, adipocyte and hepatocyte metabolism of FBT obese mice were further discussed. It was proven that FBT can effectively reduce the degree of fatty liver, prevent liver fibrosis and fat accumulation, and improve the damage of mitochondrial membrane structure. This study provides a theoretical basis for the screening and clinical treatment of lipase inhibitors.

Machine learning-based integration develops an immune-derived lncRNA signature for improving outcomes in colorectal cancer.

Long noncoding RNAs (lncRNAs) are recently implicated in modifying immunology in colorectal cancer (CRC). Nevertheless, the clinical significance of immune-related lncRNAs remains largely unexplored. In this study, we develope a machine learning-based integrative procedure for constructing a consensus immune-related lncRNA signature (IRLS). IRLS is an independent risk factor for overall survival and displays stable and powerful performance, but only demonstrates limited predictive value for relapse-free survival. Additionally, IRLS possesses distinctly superior accuracy than traditional clinical variables, molecular features, and 109 published signatures. Besides, the high-risk group is sensitive to fluorouracil-based adjuvant chemotherapy, while the low-risk group benefits more from bevacizumab. Notably, the low-risk group displays abundant lymphocyte infiltration, high expression of CD8A and PD-L1, and a response to pembrolizumab. Taken together, IRLS could serve as a robust and promising tool to improve clinical outcomes for individual CRC patients.

Yindan Jiedu granules exhibit anti-inflammatory effect in patients with novel Coronavirus disease (COVID-19) by suppressing the NF-κB signaling pathway.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is a pandemic that has caused a high number of deaths worldwide. Inflammatory factors may play important roles in COVID-19 progression. Yindan Jiedu granules (YDJDG) can inhibit the progression of COVID-19, but the associated mechanism is unclear. PURPOSE: To evaluate the therapeutic effects of YDJDG on COVID-19 and explore its underlying mechanism. METHODS: We recruited 262 participants and randomly assigned 97 patients each to the YDJDG and control groups using one-to-one propensity score matching (PSM). Clinical effects were observed and serum inflammatory and immune indicators were measured. The target network model of YDJDG was established by predicting and determining the targets of identified compounds. The main constituents of the YDJDG extracts were identified and evaluated using high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) and molecular docking. Besides, the anti-inflammatory effects of YDJDG and its specific biological mechanism of action were studied. RESULTS: After PSM, the results showed that compared with the control group, the YDJDG group had a shorter time of dissipation of acute pulmonary exudative lesions (p < 0.0001), shorter time to negative conversion of viral nucleic acid (p < 0.01), more rapid decrease in serum amyloid A level and erythrocyte sedimentation rate (p < 0.0001), and a higher rate of increase in CD4+T cell count (p = 0.0155). By overlapping the genes of YDJDG and COVID-19, 213 co-targeted genes were identified. Metascape enrichment analysis showed that 25 genes were significantly enriched in the NF-κB pathway, which were mainly targets of luteolin, quercetin, and kaempferol as confirmed by MS analysis. Molecular docking revealed that the ligands of three compounds had strong interaction with NF-κB p65 and IκBα. In vivo, YDJDG significantly protected animals from lipopolysaccharide (LPS)-induced acute lung injury (ALI), decreasing the lung wet/dry weight ratio, ALI score, and lung histological damage. In LPS-treated RAW264.7 cells, YDJDG suppressed nuclear translocation of NF-κB p65. In vivo and in vitro, YDJDG exerted anti-inflammatory effects by inhibiting the production of inflammatory cytokines (IL-6, IL-1ß, and TNF-α). These effects were accompanied by the inhibition of NF-ĸB activation and IκBα phosphorylation. CONCLUSION: YDJDG may shorten the COVID-19 course and delay its progression by suppressing inflammation via targeting the NF-κB pathway.

Radiologic Response Combined with Dermatologic Toxicities is the Most Robust Predictor of Survival Benefits in Patients with Inoperable Hepatocellular Carcinoma After Transarterial Chemoembolization Plus Sorafenib Therapy.

PURPOSE: The survival benefits of patients with inoperable hepatocellular carcinoma (HCC) who undergo transarterial chemoembolization (TACE) and receive sorafenib therapy remain controversial. We aimed to identify clinical predictors in patients with inoperable HCC undergoing TACE and receiving sorafenib. METHODS: Between January 2014 and December 2017, 148 consecutive patients with inoperable HCC who were treated with TACE plus sorafenib were retrospectively analyzed. Critical clinical factors associated with overall survival (OS) were identified by Cox regression model analysis. Kaplan-Meier methods were used to calculate the survival times, which were compared with the log-rank test. RESULTS: Macrovascular invasion (MVI), radiologic response and sorafenib-related dermatologic toxicities were identified as independent factors associated with OS. MVI is a known prognostic factor before treatment. The median OS of patients with either radiologic response or dermatologic toxicities was significantly improved compared with that of patients without it (both 23.0 vs. 7.0 months, P < 0.001). The median OS of patients with a combination of radiologic response and dermatologic toxicities was significantly longer than that of patients with either radiologic response or dermatologic toxicities, as well as no response (25.0 vs. 14.0 vs. 6.0 months, respectively, P < 0.001), and the predictive value was confirmed across patients with different baseline characteristics in terms of MVI, α-fetoprotein level, performance status and liver function. CONCLUSION: The combination of radiologic response and sorafenib-related dermatologic toxicities is the most robust predictor of survival benefits for HCC patients after TACE plus sorafenib therapy. LEVEL OF EVIDENCE: Level 3.

A green rust-coated expanded perlite particle electrode-based adsorption coupling with the three-dimensional electrokinetics that enhances hexavalent chromium removal.

A green rust-coated expanded perlite (GR-coated Exp-p) microelectrode was synthesized and incorporated into a column-mode three-dimensional electrokinetic (3D-EK) platform to effectively pursue a continuous Cr(VI) removal from the aqueous solution. Brucite-like layers of GR were decorated onto the Exp-p material. The molar ratio of Fe(II) to Fe(III) played a most vital role among the three synthesis factors in influencing the performance of the particle electrode. For the equilibrium adsorption experiments, the target maximum adsorption capacity of 122 mg/g was predicted by a target optimizer and desirability function at the conditions following the pH of 4.7, the initial concentration of 172.4 mg/L, the dosage of 0.28 g/L, and the temperature of 28.96 °C, respectively. SO42-, Cl-, and NO3- fiercely competed with Cr(VI) anions in the acidic conditions for the locally positive sites. A low concentration and a slow flow were favored in the column-mode 3D-EK platform. The pseudo-first-order and Langmuir models were suitable for describing the kinetics and isotherms of the adsorption process, respectively. Cr(VI) anions were electrostatically attracted to the silanol groups and GR surface of the adsorbent, subsequently reduced in both heterogeneity and homogeneity, and finally immobilized by coordinating with silanediol groups and silanetriol groups.

Dietary Selenized Glucose Increases Selenium Concentration and Antioxidant Capacity of the Liver, Oviduct, and Spleen in Laying Hens.

Selenized glucose (SeGlu) is a new type of organic selenium (Se) that is synthesized through the selenide reaction of glucose with sodium hydrogen selenide. This study aimed to clarify the influence of dietary SeGlu on the Se level and antioxidant capacity of the liver, oviduct, and spleen in laying hens. A total of 360, 60-week-old, Hy-Line Brown laying hens were randomly assigned to three treatment groups: a basal diet alone (control group, without adding exogenous Se) or the basal diet supplemented with 0.3 mg/kg of Se from sodium selenite (SS) or 5 mg/kg of Se from SeGlu. Diets with SeGlu increased Se levels in the liver, oviduct, and spleen of laying hens (P < 0.001). Compared with the control and SS groups, diet supplemented with SeGlu enhanced glutathione peroxidase (GSH-Px) activity and total antioxidant capacity (T-AOC) in the spleen and oviduct as well as the scavenging ability of 2, 2-diphenyl-1-picrylhydrazyl free radical (DPPH•) in the oviduct (P < 0.05). Compared with the control group, SeGlu treatment resulted in an increase (P < 0.05) in GSH-Px activity, T-AOC, and scavenging abilities of hydroxyl radical and DPPH• in the liver of hens. In addition, dietary SeGlu and SS decreased the hydrogen peroxide level in the oviduct in comparison to the control group (P < 0.05). Therefore, dietary SeGlu increased Se concentration and antioxidant ability in the liver, oviduct, and spleen of laying hens. Moreover, SeGlu may be used as a potential source of Se additive in laying hen production.

Cupping Therapy for Diseases: An Overview of Scientific Evidence from 2009 to 2019.

Cupping therapy has been accepted worldwide, and many studies have been conducted to reveal its curative effects and mechanisms. To comprehensively evaluate the effect of cupping therapy, database including China Network Knowledge Infrastructure (CNKI), Chinese Scientific Journal Database VIP, Wan Fang Database, Chinese Biomedicine (CBM), PubMed and Web of Science were searched from 2009-2019. We summarized all the meta-analyses, randomized controlled trials, clinical trials and the mechanisms studies of cupping therapy in the previous 10 years, hoping to provide a reference for the clinical applications and studies.

The second harmonic neurons in auditory midbrain of Hipposideros pratti are more tolerant to background white noise.

Although acoustic communication is inevitably influenced by noise, behaviorally relevant sounds are perceived reliably. The noise-tolerant and -invariant responses of auditory neurons are thought to be the underlying mechanism. So, it is reasonable to speculate that neurons with best frequency tuned to behaviorally relevant sounds will play important role in noise-tolerant perception. Echolocating bats live in groups and emit multiple harmonic signals and analyze the returning echoes to extract information about the target features, making them prone to deal with noise in their natural habitat. The echolocation signal of Hipposideros pratti usually contains 3-4 harmonics (H1H4), the second harmonic has the highest amplitude and is thought to play an essential role during echolocation behavior. Therefore, it is reasonable to propose that neurons tuned to the H2, named the H2 neurons, can be more noise-tolerant to background noise. Taking advantage of bat's stereotypical echolocation signal and single-cell recording, our present study showed that the minimal threshold increases (12.2 dB) of H2 neurons in the auditory midbrain were comparable to increase in bat's call intensity (14.2 dB) observed in 70 dB SPL white noise condition, indicating that the H2 neurons could work as background noise monitor. The H2 neurons had higher minimal thresholds and sharper frequency tuning, which enabled them to be more tolerant to background noise. Furthermore, the H2 neurons had consistent best amplitude spikes and sharper intensity tuning in background white noise condition than in silence. Taken together, these results suggest that the H2 neurons might account for noise-tolerant perception of behaviorally relevant sounds.

The enhancement of the perception of saltiness by Sichuan pepper oleoresin in a NaCl model solution.

Health concerns related to the intake of salt have necessitated the investigation into NaCl reduction by examining the cross-modal interaction between the perception of saltiness and pungency elicited by Sichuan pepper oleoresin (Spo). The category scale and the generalized Labeled Magnitude Scale (gLMS) were used to determine the degree to which Spo enhanced the perception of saltiness in the NaCl model solution. Sixty-eight participants were divided into the hyposensitive, semi-sensitive, and hypersensitive groups according to individual exponent. The power functions of saltiness under different pungency carriers were obtained. The level of enhancement varied between the different sensitivity groups and pungency carriers. In the hypersensitive group, the low and strong pungency carriers effectively enhanced the perception of saltiness at low to moderate, and moderate to strong NaCl solutions, respectively. In the semi-sensitive group, low and moderate pungency carriers induced additive effect in the perception of saltiness at full and moderately strong NaCl solutions, respectively. However, the additive effect was inadequate in the hypo-sensitive group. Therefore, the low pungency solution was more feasible for enhancing in the perception of saltiness, while the maximum NaCl reduction percentages corresponded to the hypersensitive and semi-sensitive groups at 38.61% and 39.06%, respectively. This research not only provided insight into the effect of pungency on the perception of saltiness as it related to individual sensitivity, but also presented valuable information regarding flavor when developing food with reduced salt content.