Paraprobiotic and postbiotic forms of Bacillus siamensis improved growth, immunity, liver and intestinal health in Lateolabrax maculatus fed soybean meal diet.

Live commensal Bacillus siamensis LF4 showed reparative potentials against high SM-induced negative effects, but whether its paraprobiotic (heat-killed B. siamensis, HKBS) and postbiotic (cell-free supernatant, CFS) forms had reparative functions and potential mechanisms are not yet known. In this study, the reparative functions of HKBS and CFS were investigated by establishing an injured model of spotted seabass (Lateolabrax maculatus) treated with dietary high soybean meal (SM). The results showed that HKBS and CFS effectively mitigated growth suppression, immune deficiency, and liver injury induced by dietary high SM. Simultaneously, HKBS and CFS application positively shaped intestinal microbiota by increased the abundance of beneficial bacteria (Fusobacteria, Firmicutes, Bacteroidota, and Cetobacterium) and decreased harmful bacteria (Proteobacteria and Plesiomonasare). Additionally, HKBS and CFS improved SM-induced intestinal injury by restoring intestinal morphology, upregulating the expression of tight junction proteins, anti-inflammatory cytokines, antimicrobial peptides, downregulating the expression of pro-inflammatory cytokines and apoptotic proteins. Furthermore, HKBS and CFS intervention significantly activated TLR2, TLR5 and MyD88 signaling, and eventually inhibited p38 and NF-κB pathways. In conclusion, paraprobiotic (HKBS) and postbiotic (CFS) from B. siamensis LF4 can improve growth, immunity, repair liver and intestinal injury, and shape intestinal microbiota in L. maculatus fed high soybean meal diet, and TLRs/p38 MAPK/NF-κB signal pathways might be involved in those processes. These results will serve as a base for future application of paraprobiotics and postbiotics to prevent and repair SM-induced adverse effects in fish aquaculture.

Pleurotus eryngii root waste and soybean meal co-fermented protein improved the growth, immunity, liver and intestinal health of largemouth bass (Micropterus salmoides).

The present study aimed to evaluate the effect of king oyster mushroom (Pleurotus eryngii) root waste and soybean meal co-fermented protein (CFP) on growth performance, feed utilization, immune status, hepatic and intestinal health of largemouth bass (Micropterus salmoides). Largemouth bass (12.33 ± 0.18 g) were divided into five groups, fed with diets containing 0 %, 5 %, 10 %, 15 % and 20 % CFP respectively for 7 weeks. The growth performance and dietary utilization were slightly improved by the supplementation of CFP. In addition, improved immunoglobulin M (IgM) content and lysozyme activity in treatments confirm the enhancement of immunity in fish by the addition of CFP, especially in fish fed 20 % CFP (P < 0.05). Furthermore, CFP significantly improved liver GSH (glutathione) content in groups D10 and D15 (P < 0.05), and slightly improved total antioxidant capacity (T-AOC), superoxide dismutase (SOD) activity while slightly reduced malondialdehyde (MDA) content. Simultaneously, the upregulation of lipolysis-related genes (PPARα, CPT1 and ACO) expression and downregulation of lipid synthesis-related genes (ACC and DGAT1) expression was recorded in the group D20 compared with the control (P < 0.05), which were consistent with the decreased liver lipid contents, suggests that lipid metabolism was improved by CFP. In terms of intestinal structural integrity, ameliorated intestinal morphology in treatments were consistent with the upregulated Occludin, Claudin-1 and ZO-1 genes expression. The intestinal pro-inflammatory cytokines (TNF-α and IL-8) expression were suppressed while the anti-inflammatory cytokines (IL-10 and TGF-ß) were activated in treatments. The expression of antimicrobial peptides (Hepcidin-1, Piscidin-2 and Piscidin-3) and intestinal immune effectors (IgM and LYZ) were slightly up-regulated in treatments. Additionally, the relative abundance of intestinal beneficial bacteria (Firmicutes) increased while the relative abundance of potential pathogenic bacteria (Fusobacterium and Proteobacteria) decreased, which indicated that the intestinal microbial community was well-reorganized by CFP. In conclusion, dietary CFP improves growth, immunity, hepatic and intestinal health of largemouth bass, these data provided a theoretical basis for the application of this novel functional protein ingredient in fish.

LTA and PGN from Bacillus siamensis can alleviate soybean meal-induced enteritis and microbiota dysbiosis in Lateolabrax maculatus.

An eight-week feeding trial was designed to assess which component of commensal Bacillus siamensis LF4 can mitigate SBM-induced enteritis and microbiota dysbiosis in spotted seabass (Lateolabrax maculatus) based on TLRs-MAPKs/NF-кB signaling pathways. Fish continuously fed low SBM (containing 16 % SBM) and high SBM (containing 40 % SBM) diets were used as positive (FM group) and negative (SBM group) control, respectively. After feeding high SBM diet for 28 days, fish were supplemented with B. siamensis LF4-derived whole cell wall (CW), cell wall protein (CWP), lipoteichoic acid (LTA) or peptidoglycan (PGN) until 56 days. The results showed that a high inclusion of SBM in the diet caused enteritis, characterized with significantly (P < 0.05) decreased muscular thickness, villus height, villus width, atrophied and loosely arranged microvillus. Moreover, high SBM inclusion induced an up-regulation of pro-inflammatory cytokines and a down-regulation of occludin, E-cadherin, anti-inflammatory cytokines, apoptosis related genes and antimicrobial peptides. However, dietary supplementation with CW, LTA, and PGN of B. siamensis LF4 could effectively alleviate enteritis caused by a high level of dietary SBM. Additionally, CWP and PGN administration increased beneficial Cetobacterium and decreased pathogenic Plesiomonas and Brevinema, while dietary LTA decreased Plesiomonas and Brevinema, suggesting that CWP, LTA and PGN positively modulated intestinal microbiota in spotted seabass. Furthermore, CW, LTA, and PGN application significantly stimulated TLR2, TLR5 and MyD88 expressions, and inhibited the downstream p38 and NF-κB signaling. Taken together, these results suggest that LTA and PGN from B. siamensis LF4 could alleviate soybean meal-induced enteritis and microbiota dysbiosis in L. maculatus, and p38 MAPK/NF-κB pathways might be involved in those processes.

The Degradation of Aqueous Oxytetracycline by an O3/CaO2 System in the Presence of HCO3-: Performance, Mechanism, Degradation Pathways, and Toxicity Evaluation.

This research constructed a novel O3/CaO2/HCO3- system to degrade antibiotic oxytetracycline (OTC) in water. The results indicated that CaO2 and HCO3- addition could promote OTC degradation in an O3 system. There is an optimal dosage of CaO2 (0.05 g/L) and HCO3- (2.25 mmol/L) that promotes OTC degradation. After 30 min of treatment, approximately 91.5% of the OTC molecules were eliminated in the O3/CaO2/HCO3- system. A higher O3 concentration, alkaline condition, and lower OTC concentration were conducive to OTC decomposition. Active substances including ·OH, 1O2, ·O2-, and ·HCO3- play certain roles in OTC degradation. The production of ·OH followed the order: O3/CaO2/HCO3- > O3/CaO2 > O3. Compared to the sole O3 system, TOC and COD were easier to remove in the O3/CaO2/HCO3- system. Based on DFT and LC-MS, active species dominant in the degradation pathways of OTC were proposed. Then, an evaluation of the toxic changes in intermediates during OTC degradation was carried out. The feasibility of O3/CaO2/HCO3- for the treatment of other substances, such as bisphenol A, tetracycline, and actual wastewater, was investigated. Finally, the energy efficiency of the O3/CaO2/HCO3- system was calculated and compared with other mainstream processes of OTC degradation. The O3/CaO2/HCO3- system may be considered as an efficient and economical approach for antibiotic destruction.

High dietary wheat starch negatively regulated growth performance, glucose and lipid metabolisms, liver and intestinal health of juvenile largemouth bass, Micropterus salmoides.

Largemouth bass (Micropterus salmoides) were fed with three diets containing 6%, 12%, and 18% wheat starch for 70 days to examine their impacts on growth performance, glucose and lipid metabolisms, and liver and intestinal health. The results suggested that the 18% starch group inhibited the growth, and improved the hepatic glycogen content compared with the 6% and 12% starch groups (P < 0.05). High starch significantly improved the activities of glycolysis-related enzymes, hexokinase (HK), glucokinase (GK), phosphofructokinase (PFK), and pyruvate kinase (PK) (P < 0.05); promoted the mRNA expression of glycolysis-related phosphofructokinase (pfk); decreased the activities of gluconeogenesis-related enzymes, pyruvate carboxylase (PC), and phosphoenolpyruvate carboxykinase (PEPCK); and reduced the mRNA expression of gluconeogenesis-related fructose-1,6-bisphosphatase-1(fbp1) (P < 0.05). High starch reduced the hepatic mRNA expressions of bile acid metabolism-related cholesterol hydroxylase (cyp7a1) and small heterodimer partner (shp) (P < 0.05), increased the activity of hepatic fatty acid synthase (FAS) (P < 0.05), and reduced the hepatic mRNA expressions of lipid metabolism-related peroxisome proliferator-activated receptor α (ppar-α) and carnitine palmitoyltransferase 1α (cpt-1α) (P < 0.05). High starch promoted inflammation; significantly reduced the mRNA expressions of anti-inflammatory cytokines transforming growth factor-ß1 (tgf-ß1), interleukin-10 (il-10), and interleukin-11ß (il-11ß); and increased the mRNA expressions of pro-inflammatory cytokine tumor necrosis factor-α (tnf-α), interleukin-1ß (il-1ß), and interleukin-8 (il-8) in the liver and intestinal tract (P < 0.05). Additionally, high starch negatively influenced the intestinal microbiota, with the reduced relative abundance of Trichotes and Actinobacteria and the increased relative abundance of Firmicutes and Proteobacteria. In conclusion, low dietary wheat starch level (6%) was more profitable to the growth and health of M. salmoides, while high dietary starch level (12% and 18%) could regulate the glucose and lipid metabolisms, impair the liver and intestinal health, and thus decrease the growth performance of M. salmoides.

[Abnormalities in signal transduction of Purkinje cells in spinocerebellar ataxias: a review].

Spinocerebellar ataxias (SCAs) are a group of autosomal dominant neurodegenerative diseases that have been currently identified with numerous subtypes exhibiting genetic heterogeneity and clinical variability. Purkinje neuronal degeneration and cerebellar atrophy are common pathological features among most SCA subtypes. The physiological functions of Purkinje cells are regulated by multiple factors, and their dysfunction in signal transduction may lead to abnormal cerebellar motor control. This review summarizes the abnormalities in voltage-gated ionic channels, intracellular calcium signaling, and glutamate signaling transduction of Purkinje cells in SCAs, aiming to provide a theoretical basis for further understanding the common pathogenesis of SCAs and developing specific treatments.

Urolithin A exerts antiobesity effects through enhancing adipose tissue thermogenesis in mice.

Obesity leads to multiple health problems, including diabetes, fatty liver, and even cancer. Here, we report that urolithin A (UA), a gut-microflora-derived metabolite of pomegranate ellagitannins (ETs), prevents diet-induced obesity and metabolic dysfunctions in mice without causing adverse effects. UA treatment increases energy expenditure (EE) by enhancing thermogenesis in brown adipose tissue (BAT) and inducing browning of white adipose tissue (WAT). Mechanistically, UA-mediated increased thermogenesis is caused by an elevation of triiodothyronine (T3) levels in BAT and inguinal fat depots. This is also confirmed in UA-treated white and brown adipocytes. Consistent with this mechanism, UA loses its beneficial effects on activation of BAT, browning of white fat, body weight control, and glucose homeostasis when thyroid hormone (TH) production is blocked by its inhibitor, propylthiouracil (PTU). Conversely, administration of exogenous tetraiodothyronine (T4) to PTU-treated mice restores UA-induced activation of BAT and browning of white fat and its preventive role on high-fat diet (HFD)-induced weight gain. Together, these results suggest that UA is a potent antiobesity agent with potential for human clinical applications.

Commensal Bacillus siamensis LF4 induces antimicrobial peptides expression via TLRs and NLRs signaling pathways in intestinal epithelial cells of Lateolabrax maculatus.

Antimicrobial peptides (AMPs) play an important role in modulating intestinal microbiota, and our previous study showed that autochthonous Baccilus siamensis LF4 could shape the intestinal microbiota of spotted seabass (Lateolabrax maculatus). In the present study, a spotted seabass intestinal epithelial cells (IECs) model was used to investigate whether autochthonous B. siamensis LF4 could modulate the expression of AMPs in IECs. And then, the IECs were treated with active, heat-inactivated LF4 and its supernatant to illustrate their AMPs inducing effects and the possible signal transduction mechanisms. The results showed that after 3 h of incubation with 108 CFU/mL B. siamensis LF4, lactate dehydrogenase (LDH), glutamic oxaloacetic transaminase (GOT), glutamic propylic transaminase (GPT) activities in supernatant decreased significantly and obtained minimum values, while supernatant alkaline phosphatase (AKP) activity, ß-defensin protein level and IECs Na+/K+-ATPase activity, AMPs (ß-defensin, hepcidin-1, NK-lysin, piscidin-5) genes expression increased significantly and obtained maximum values (P < 0.05). Further study demonstrated that the active, heat-inactivated LF4 and its supernatant treatments could effectively decrease the LDH, GOT, and GPT activities in IECs supernatant, increase AKP activity and ß-defensin (except LF4 supernatant treatment) protein level in IECs supernatant and Na+/K+-ATPase and AMPs genes expression in IECs. Treatment with active and heat-inactivated B. siamensis LF4 resulted in significantly up-regulated the expressions of TLR1, TLR2, TLR3, TLR5, NOD1, NOD2, TIRAP, MyD88, IRAK1, IRAK4, TRAF6, TAB1, TAB2, ERK, JNK, p38, AP-1, IKKα, IKKß and NF-κB genes. Treatment with B. siamensis LF4 supernatant also resulted in up-regulated these genes, but not the genes (ERK, JNK, p38, and AP-1) in MAPKs pathway. In summary, active, heat-inactivated and supernatant of B. siamensis LF4 can efficiently induce AMPs expression through activating the TLRs/NLRs-MyD88-dependent signaling, active and heat-inactivated LF4 activated both the downstream MAPKs and NF-κB pathways, while LF4 supernatant only activated NF-κB pathway.

Probiotic components of Bacillus siamensis LF4 mitigated ß-conglycinin caused cell injury via modulating TLR2/MAPKs/NF-κB signaling in Lateolabrax maculatus.

ß-conglycinin is a recognized factor in leading to intestinal inflammation and limiting application of soybean meal in aquaculture. Our previous study reported that heat-killed B. siamensis LF4 could effectively mitigate inflammatory response and apoptosis caused by ß-conglycinin in spotted seabass (Lateolabrax maculatus) enterocytes, but the mechanisms involved are not fully understood. In the present study, therefore, whole cell wall (CW), peptidoglycan (PG) and lipoteichoic acid (LTA) and cell-free supernatant (CFS) have been collected from B. siamensis LF4 and their mitigative function on ß-conglycinin-induced adverse impacts and mechanisms underlying were evaluated. The results showed that ß-conglycinin-induced cell injury, characterized with significantly decreased cell viability and increased activities of lactate dehydrogenase, glutamic oxaloacetic transaminase, glutamic propylic transaminase (P < 0.05), were reversed by subsequent heat-killed B. siamensis LF4 and its CW, LTA, PG and CFS treatment. Enterocytes co-cultured with heat-killed B. siamensis LF4 and its CW, LTA, PG and CFS (especially PG) significantly increased expressions of anti-inflammatory genes (IL-2, IL-4, IL-10 and TGF-ß1), tight junction proteins (ZO-1, occludin and claudin-b) and antimicrobial peptides (ß-defensin, hepcidin-1, NK-lysin and piscidin-5), and decreased expressions of pro-inflammatory genes (IL-1ß, IL-8 and TNF-α) and apoptosis-related genes (caspase 3, caspase 8 and caspase 9) (P < 0.05), indicating their excellent mitigation effects on ß-conglycinin-induced cell damages. In addition, heat-killed B. siamensis LF4 and its CW, LTA, PG and CFS significantly increased TLR2 mRNA level (especially in PG treatment), and decreased MAPKs (JNK, ERK, p38 and AP-1) and NF-κB related genes expressions. In conclusion, heat-killed B. siamensis LF4 and its CW, LTA, PG and CFS could modulating TLR2/MAPKs/NF-κB signaling and alleviating ß-conglycinin-induced enterocytes injury in spotted seabass (L. maculatus), and PG presented the best potential.

Commensal Bacillus siamensis LF4 ameliorates ß-conglycinin induced inflammation in intestinal epithelial cells of Lateolabrax maculatus.

ß-conglycinin and glycinin, two major heat-stable anti-nutritional factors in soybean meal (SM), have been suggested as the key inducers of intestinal inflammation in aquatic animals. In the present study, a spotted seabass intestinal epithelial cells (IECs) were used to compare the inflammation-inducing effects of ß-conglycinin and glycinin. The results showed that IECs co-cultured with 1.0 mg/mL ß-conglycinin for 12 h or 1.5 mg/mL glycinin for 24 h significantly decreased the cell viability (P < 0.05), and overstimulated inflammation and apoptosis response by significantly down-regulating anti-inflammatory genes (IL-2, IL-4, IL-10 and TGF-ß1) expressions and significantly up-regulated pro-inflammatory genes (IL-1ß, IL-8 and TNF-α) and apoptosis genes (caspase 3, caspase 8 and caspase 9) expressions (P < 0.05). Subsequently, a ß-conglycinin based inflammation IECs model was established and used for demonstrating whether commensal probiotic B. siamensis LF4 can ameliorate the adverse effects of ß-conglycinin. The results showed ß-conglycinin-induced cell viability damage was completely repaired by treated with 109 cells/mL heat-killed B. siamensis LF4 for ≥12 h. At the same time, IECs co-cultured with 109 cells/mL heat-killed B. siamensis LF4 for 24 h significantly ameliorated ß-conglycinin-induced inflammation and apoptosis by up-regulating anti-inflammatory genes (IL-2, IL-4, IL-10 and TGF-ß1) expressions and down-regulated pro-inflammatory genes (IL-1ß, IL-8 and TNF-α) and apoptosis genes (caspase 3, caspase 8 and caspase 9) expressions (P < 0.05). In summary, both ß-conglycinin and glycinin can lead to inflammation and apoptosis in spotted seabass IECs, and ß-conglycinin is more effective; commensal B. siamensis LF4 can efficiently ameliorate ß-conglycinin induced inflammation and apoptosis in IECs.

Kinetics and mechanism study of dyes degradation in electric field-promoting catalytic wet air oxidation process.

Wet air oxidation (WAO) is a clean and eco-friendly technology for dyes removal, but the high operating temperature and pressure limit its practical application. In the present work, an electric field-promoting (EF-promoting) catalytic WAO process is developed to degrade dyes under room condition. The oxidation kinetics of four different types of dyes and their degradation pathways are studied. A kinetic model is constructed by including the exogenous electric field into the Langmuir-Hinshelwood-Hougen-Watson (LHHW) mechanism framework, and quantitative structure-activity relationship (QSAR) analysis is conducted to correlate the kinetic parameters to the physicochemical properties of the dyes. A negative linear relationship is found between the adsorption equilibrium constants of the dyes and their first ionization energies, and their surface reaction rate constants are positively linearly associated to Esum (ELUMO + EHOMO). The degradation pathways of the different dyes are proposed according to the degradation intermediates and the activities of the atoms within the dye molecules. The heteroatoms N and S, and the atom C connecting the aromatic rings are identified as the susceptible sites upon the electrophilic attack of O2. Bond cleavage at these sites gives rise to aromatic fragments which are eventually mineralized via carboxyl acids. The results of this work is helpful for guiding the design and operation of the EF-promoting catalytic WAO process into the treatment of various dye wastewaters.

Activation of peroxymonosulfate by biochar-supported Fe3O4 derived from oily sludge to enhance the oxidative degradation of tetracycline hydrochloride.

Carbon materials used for catalysis in advanced oxidation processes tend to be obtained from cheap and readily available raw materials. We constructed a carbon material, OSC@Fe3O4, by loading Fe3O4 onto the pyrolyzed hazardous waste oily sludge. OSC@Fe3O4 was then used to activate peroxymonosulfate (PMS) for the removal of tetracycline hydrochloride (TTCH) from water. At 298 K, 0.2 g⋅L-1 of catalyst and 0.3 g⋅L-1 of PMS, the reaction rate constant of the OSC@I-2/PMS system reached 0.079 min-1, with a TTCH removal efficiency of 92.6%. The degradation efficiency of TTCH remained at 81% after five cycles. The specific surface area and pore volume of OSC@I-2 were 263.9 m2⋅g-1 and 0.42 cm3⋅g-1, respectively, which improved the porous structure of the carbon material and provided more active points, thus improving the catalytic performance. N and S were doped into the oily sludge carbon due to the presence of N- and S-containing compounds in the raw oily sludge. N and S doping led to more electron-rich sites with higher negative charges in OSC@I-2 and gave the oily sludge carbon a higher affinity to PMS, thereby promoting its ability to activate PMS. Sulfate radicals (SO4•‾) played a dominant role in the degradation of TTCH, with demethylation and the breaking of double bonds being a possible degradation pathway. A biotoxicity test showed that the microbial toxicity of the degradation intermediates was significantly reduced. This work provides a strategy for the application of PMS-based catalysts derived from waste carbon resources.

Irinotecan plus temozolomide in relapsed Ewing sarcoma: an integrated analysis of retrospective studies.

BACKGROUND: The prognosis of patients with relapsed Ewing sarcoma is poor. In this study, we aimed to pooled-analyze the efficacy and safety of the combination of irinotecan and temozolomide in treating patients with relapsed Ewing sarcoma. METHODS: PubMed, Cochrane CENTRAL, Web of Science, and EMBASE were systematically searched on September 27, 2021. The primary outcomes were rates of objective response and disease control, and the secondary outcomes were toxicities. RESULTS: Six retrospective studies with 184 patients were enrolled in the analysis. The median age ranged from 14 to 21. The integrated rates were 44% (95% confidence interval [CI] 31-58) for objective response and 66% (55-77) for disease control. Grade 3-4 neutropenia, thrombocytopenia, and diarrhea occurred in 8% (3-16), 7% (3-11), and 8% (5-10) of chemotherapeutic cycles, respectively. 18% (7-32) and 6% (2-11) of patients suffered grade 3-4 neutropenia and thrombocytopenia after irinotecan plus temozolomide treatment. CONCLUSION: Irinotecan plus temozolomide combination chemotherapy showed antitumor activity and an acceptable safety profile in patients with relapsed Ewing sarcoma. More future prospective studies are needed to confirm the retrospective results.

The efficacy and safety of cemiplimab in locally advanced or metastatic cutaneous squamous cell carcinoma: A comparative analysis of retrospective studies versus prospective studies.

Cemiplimab has been widely recommended by international guidelines to treat patients with locally advanced or metastatic cutaneous squamous cell carcinoma (CSCC). In this study, we conducted a comparative analysis to integrate the efficacy and safety data in the published prospective and retrospective studies for better understanding the application of cemiplimab. The online databases (PubMed, Cochrane CENTRAL, Web of Science, and EMBASE) were searched to find out eligible studies from inception to November 4, 2021. The "R" software and the "meta" package were used to synthesize the objective response rates (ORRs), disease control rates (DCRs), and the incidences of treatment-related adverse events (TRAEs). Overall, three retrospective studies with 398 patients and three prospective studies with 219 patients were enrolled. The pooled ORR and DCR were 53% (95% confidence interval [CI] 46-59) and 70% (95% CI 57-82) for retrospective studies versus 45% (95% CI 39-52) and 68% (95% CI 56-79) for prospective studies. In regard of toxicities, prospective studies reported much higher incidences of any grade (99% vs. 47%) and grade 3-4 TRAEs (43% vs. 15%) against retrospective studies. The most reported TRAE was fatigue, followed by diarrhea and pruritus. In addition, nine treatment-related deaths (four in retrospective studies vs. five in prospective studies) were documented. In both retrospective and prospective clinical practices, cemiplimab could be an effective regimen for locally advanced or metastatic CSCC patients, but toxicities during the treatment deserve further attention.

A pooled analysis of adding olanzapine to guideline-recommended antiemetic therapy for breast cancer patients treated with an anthracycline and cyclophosphamide in prospective and retrospective studies.

PURPOSE: As an antipsychotic agent that targets multiple neurotransmitter receptors, olanzapine has been added to antiemetic therapies. For better understanding the application of olanzapine in antiemetic strategies for breast cancer patients who suffered anthracycline plus cyclophosphamide-induced nausea and vomiting, we comprehensively reviewed the antiemetic researches related to olanzapine and pooled-analyzed the results to confirm the efficacy and safety of olanzapine in breast cancer. METHODS: PubMed, Web of Science, EMBASE, and Cochrane CENTRAL databases were searched from inception through Sep 15, 2021. Both prospective and retrospective studies were eligible. The primary outcomes were complete response (defined as no vomiting and no use of rescue medications) and no nausea rate, and the secondary outcome was treatment-related adverse events. RESULTS: Four studies with 466 breast cancer patients were identified in the pooled analysis. In the acute period (0-24 h), the olanzapine group had significantly higher rates of complete response (71.3% vs 48.1%, odds ratio [OR]: 2.66, 95% confidence interval [CI] 1.39-5.11, p = 0.003) and no nausea (70.0% vs 43.0%, OR: 3.55, 95% CI 1.76-7.18, p = 0.04) than the placebo group, while in the delayed period, the olanzapine group was also superior to the placebo group in terms of the complete response (82.5% vs 63.3%, OR: 3.81, 95% CI 1.58-9.15, p = 0.003) and no nausea (66.3% vs 51.9%, OR: 2.08, 95% CI 1.03-4.21, p = 0.04) rates. During the overall period in prospective studies, the proportions of complete response (50.0% vs 34.2%, OR: 1.93, p = 0.04) and no nausea (51.3% vs 25.3%, OR: 3.40, p = 0.0006) in the olanzapine group were higher than those in the placebo group. CONCLUSION: Highly emetogenic chemotherapy breast patients could benefit from olanzapine-contained antiemetic therapy. Furthermore, since the cost is low, olanzapine is worth further clinical application and promotion.

RIG-I modulates Src-mediated AKT activation to restrain leukemic stemness.

Retinoic acid (RA)-inducible gene I (RIG-I) is highly upregulated and functionally implicated in the RA-induced maturation of acute myeloid leukemia (AML) blasts. However, the underlying mechanism and the biological relevance of RIG-I expression to the maintenance of leukemogenic potential are poorly understood. Here, we show that RIG-I, without priming by foreign RNA, inhibits the Src-facilitated activation of AKT-mTOR in AML cells. Moreover, in a group of primary human AML blasts, RIG-I reduction renders the Src family kinases hyperactive in promoting AKT activation. Mechanistically, a PxxP motif in RIG-I, upon the N-terminal CARDs' association with the Src SH1 domain, competes with the AKT PxxP motif for recognizing the Src SH3 domain. In accordance, mutating PxxP motif prevents Rig-I from inhibiting AKT activation, cytokine-stimulated myeloid progenitor proliferation, and in vivo repopulating capacity of leukemia cells. Collectively, our data suggest an antileukemia activity of RIG-I via competitively inhibiting Src/AKT association.

Recycling respirator masks to a high-value product: From COVID-19 prevention to highly efficient battery separator.

COVID-19 is a pandemic that has caused serious disruption in almost every day-to-day life around the world, and wearing a mask is essential for human safety from this virus. However, masks are non-recyclable materials, and the accumulation of masks used every day causes serious environmental issues. In this study, we investigate the recycling of mask materials for addressing the environmental problems and transforming as a high value-added material through chemical modification of masks. The recycled mask is applied as a separator for aqueous rechargeable batteries, and shows outstanding safety and electrochemical performance than the existing separator. This approach will lead to an advanced energy technology considering nature after overcoming COVID-19.

Photocatalytic reduction of Cr(VI) via surface modified g-C3N4 by acid-base regulation.

Cr(VI) is a class of highly toxic heavy metals. In this study, alkali-modified g-C3N4 (cOH-CN) and acid-modified g-C3N4 (cH-CN) materials were successfully synthesized, and their photocatalytic activities for Cr(VI) reduction under visible light irradiation were tested. Owing to defect structures by cH-CN and -OH group introduction by cOH-CN, the modified materials exhibited a larger surface area, more abundant pore structures, a wider visible light absorption range, higher energy gap values, and a stronger capacity for electron-hole pair separation. As a result, satisfactory Cr(VI) reduction performance was gained by these two photocatalysts. Almost all Cr(VI) was converted to Cr(III) after 60 min of treatment in the presence of these two catalysts, while it was only 30% for the pristine g-C3N4 materials. Relatively higher dosages of cH-CN and cOH-CN and acidic conditions both improved Cr(VI) reduction in the cH-CN and cOH-CN photocatalytic systems. Cr(VI) reduction was mainly initiated by free electrons in the photocatalytic system of the modified materials. Finally, Cr(VI) in the photocatalytic system was almost completely converted to Cr(III). Furthermore, the stability and recycling of the cH-CN and cOH-CN catalysts were evaluated.

Mitochondrial aconitase controls adipogenesis through mediation of cellular ATP production.

Mitochondrial aconitase (Aco2) catalyzes the conversion of citrate to isocitrate in the TCA cycle, which produces NADH and FADH2, driving synthesis of ATP through OXPHOS. In this study, to explore the relationship between adipogenesis and mitochondrial energy metabolism, we hypothesize that Aco2 may play a key role in the lipid synthesis. Here, we show that overexpression of Aco2 in 3T3-L1 cells significantly increased lipogenesis and adipogenesis, accompanied by elevated mitochondrial biogenesis and ATP production. However, when ATP is depleted by rotenone, an inhibitor of the respiratory chain, the promotive role of Aco2 in adipogenesis is abolished. In contrast to Aco2 overexpression, deficiency of Aco2 markedly reduced lipogenesis and adipogenesis, along with the decreased mitochondrial biogenesis and ATP production. Supplementation of isocitrate efficiently rescued the inhibitory effect of Aco2 deficiency. Similarly, the restorative effect of isocitrate was abolished in the presence of rotenone. Together, these results show that Aco2 sustains normal adipogenesis through mediating ATP production, revealing a potential mechanistic link between TCA cycle enzyme and lipid synthesis. Our work suggest that regulation of adipose tissue mitochondria function may be a potential way for combating abnormal adipogenesis related diseases such as obesity and lipodystrophy.

Multilevel resistive random access memory achieved by MoO3/Hf/MoO3stack and its application in tunable high-pass filter.

In this work, the multilevel resistive random access memories (RRAMs) have been achieved by using the structure of Pt/MoO3/Hf/MoO3/Pt with four stable resistance states. The devices show good retention property of each state (>104s) and large memory window (>104). The simulation and experimental study reveal that the resistive switching mechanism is ascribed to combination of the conductive filament in the stack of MoO3/Hf next to the top electrode and redox reaction at the interface of Hf/MoO3next to bottom electrode. The fitting results of current-voltage characteristics under low sweep voltage indicate that the conduction of HRSs is dominated by the Poole-Frenkel emission and that of LRS is governed by the Ohmic conduction. Based on the RRAM, the tunable high-pass filter (HPF) with configurable filtering characteristics has been realized. The gain-frequency characteristics of the programmable HPF show that the filter has high resolution and wide programming range, demonstrating the viability of the multilevel RRAMs for future spiking neural network and shrinking the programmable filters with low power consumption.