Association of HBeAg decline rate from mid-pregnancy to delivery with HBeAg seroconversion after delivery in hepatitis B virus-infected mothers.

There is still controversy about whether to continue antiviral therapy (AVT) after delivery, especially for pregnant women in the immune tolerance (IT) phase. In this study, a retrospective cohort study was conducted to explore the relationship between hepatitis B e antigen (HBeAg) decline rate (%) from mid-pregnancy to delivery and HBeAg seroconversion postpartum among patients using nucleos(t)ide analogs (NAs) to prevent mother-to-child transmission (MTCT), with the goal of identifying the ideal candidates for postpartum AVT continuation. This retrospective cohort study included 151 postpartum women. Univariate and multivariable logistic regression analyses were conducted to assess the association between the HBeAg decline rate (%) from mid-pregnancy to delivery and HBeAg seroconversion postpartum. Receiver operating characteristic (ROC) analysis was utilized to evaluate the predictive capacity of the HBeAg decline rate (%) and determine the optimal cut-off point. The univariate analysis revealed a significant association between the HBeAg decline rate (%) and HBeAg seroconversion postpartum (OR 1.068, 95% CI: 1.034-1.103, p < .001). In the multivariate regression analysis, adjusting for age, hepatitis B surface antigen (HBsAg) titre (log10 IU/mL) at mid-pregnancy, HBeAg titre (log10 S/CO) at mid-pregnancy, and hepatitis B virus (HBV) DNA load decline rate (%) from mid-pregnancy to delivery, the HBeAg decline rate(%) remained significantly associated with HBeAg seroconversion postpartum (OR 1.050, 95% CI: 1.015-1.093, p = .009). Then HBeAg decline rate (%) was treated as a categorical variable (tertiles) for sensitivity analysis. In the three distinct models, taking Tertile1 as a reference, women in Tertile3 still had a 4.201-fold (OR 4.201, 95% CI: 1.382-12.773, p = .011) higher risk of developing HBeAg seroconversion (p for trend <.05) after adjusting above covariates. The area under the curve (AUC) was 0.723 (95% CI: 0.627-0.819). The optimal cut-off value was 5.43%, with a sensitivity of 0.561, specificity of 0.791, and Youden's index of 0.352.A higher HBeAg decline rate (%) from mid-pregnancy to delivery independently correlated with an increased risk of HBeAg seroconversion postpartum. This decline rate can serve as a valuable clinical indicator for predicting HBeAg seroconversion.

Humoral responses after primary and booster SARS-CoV-2 inactivated vaccination in patients with chronic hepatitis B virus infection: A longitudinal observational study.

Given the pandemic of severe acute respiratory syndrome coronavirus 2 Omicron variants, booster vaccination (BV) using inactivated virus vaccines (the third dose) has been implemented in China. However, the immune responses after BV, especially those against Omicron, in patients with chronic hepatitis B virus (HBV) infection (CHB) are unclear. In this prospective longitudinal study, 114 patients with CHB and 68 healthy controls (HCs) were recruited after receiving inactivated vaccination. The anti-receptor-binding domain (RBD) immunoglobulin G (IgG), neutralizing antibodies (NAbs), neutralization against Omicron (BA2.12.1, BA.4/5), and specific B/T cells were evaluated. In patients, anti-RBD IgG was elevated significantly after BV; the titers were as high as those in HCs. Similar results were obtained for the NAbs. However, compared with that against wild type (WT), the neutralization against Omicron was compromised after BV. The frequency of RBD+ atypical memory B cells increased, but spike-specific cluster of differentiation 4+ /8+ T cells remained unchanged after BV. Moreover, no serious adverse events or HBV reactivation were observed after BV. These results suggest that BV significantly enhanced antibody responses against WT; however, it resulted in compromised antibody responses against Omicron in patients with CHB. Hence, new all-in-one vaccines and optimal vaccination strategies should be studied promptly.

Application of nematicide avermectin enriched antibiotic-resistant bacteria and antibiotic resistance genes in farmland soil.

The extensive use of antibiotics in medicine and agriculture has resulted in the accumulation of antibiotic-resistant microorganisms and antibiotic resistance genes (ARGs) in environments, which threaten human health and contaminate environment. Nematicide avermectin is widely applied to control root-knot nematodes. The effect of five-years application of avermectin on rhizosphere microbiome and resistome of sick tobacco plants in farmland were investigated in present study. The environmental risks of avermectin was assessed adequately. Metagenomic method was used to analyze antibiotic-resistant bacteria and antibiotic resistance genes in the avermectin-treated soil. The abundance and distribution of antibiotic-resistant bacteria and their antibiotic resistance genes were affected by avermectin application. The antibiotic resistant Proteobacteria occupied the highest percentage (36%) in rhizosphere soil and carried 530 ARGs. Opportunistic human pathogens carrying antibiotic resistance genes were enriched in the avermectin-treated soil. Avermectin application increased the counts of many types of antibiotic resistance genes. The relative abundances of genes adeF, BahA, fusH, ileS, and tlrB in the avermectin-treated soil were significantly greater than in the untreated control soil. Different resistance mechanisms were revealed in the avermectin-treated soil. The efflux of antibiotic (670 ARGs), inactivation of antibiotic (475 ARGs), and alteration of antibiotic target (267 ARGs) were the main resistance mechanisms. Rigid control the avermectin dose and use frequency and other pesticides can decrease soil antibiotic resistance genes and protect agricultural products' safety and public health. Overall, application of nematicide avermectin enriched antibiotic-resistant bacteria and antibiotic resistance genes in farmland soil, which should be on the alert for environment protection.

Associates of Perceived Quality of Life in Chinese Older Adults Living with Cognitive Impairment.

The aim of this study is to examine perceived quality of life in Chinese older adults living with cognitive impairment and explore its associations with caregivers' characteristics. Questionnaires were administered in person to 271 caregiver-care recipient dyads from urban communities in mainland China in 2019. We used the 40-item Alzheimer's Disease-related Quality of Life tool and asked caregiver respondents to indicate care recipients' life conditions. The questionnaire asked caregivers about their sociodemographic characteristics, levels of informal social support, caregiver burden, and depressive symptoms. Caregivers' higher levels of caregiver burden (ß = > -0.19, p < .01) and depressive symptoms (ß = > -0.19, p < .01) amongst caregivers were significantly associated with lower quality of life among care recipients. Informal support from relatives and friends to caregivers did not significantly affect quality of life of care recipients. The results suggested that reducing caregivers' burden and depressive symptoms are essential to promote quality of life of care recipients. Formal support from health professionals, service organizations, and communities are urgently called to promote the wellbeing of Chinese families affected by cognitive impairment.

NIR Light-Mediated Mitochondrial RNA Modification for Cancer RNA Interference Therapeutics.

Mitochondrial RNA (mtRNA) plays a critical role in synthesis of mitochondrial proteins. Interfering mtRNA is a highly effective way to induce cell apoptosis. Herein, we report a near-infrared (NIR) light-mediated mitochondrial RNA modification approach for long-term imaging and effective suppression of tumors. A tumor-targetable NIR fluorescent probe f-CRI consisting of a cyclic RGD peptide, a NIR fluorophore IR780, and a singlet oxygen (1 O2 )-labile furan group for RNA modification was rationally designed and synthesized. This probe was demonstrated to dominantly accumulate in cellular mitochondria and could be covalently conjugated onto mtRNA upon 808 nm irradiation resulting in prolonged retention in tumors. More notably, this covalent modification of mtRNA by f-CRI could perturb the function of mitochondria leading to remarkable tumor suppression. We thus envision that our current approach would offer a potential approach for cancer RNA interference therapeutics.

Alkaline Phosphatase-Controllable and Red Light-Activated RNA Modification Approach for Precise Tumor Suppression.

RNA interference (RNAi) has proved to be a promising modality for disease treatment. However, the promise of conventional RNA therapeutics for clinical application is severely impeded by low delivery efficiency and susceptibility of RNAs to serum RNases. Therefore, developing advanced RNAi technology is an increasing demand for achieving precise medicine. Herein, for the first time, we propose an alkaline phosphatase (ALP)-controllable and red light-activated RNA modification (ALARM) approach for anti-tumor therapeutic application. An ALP-responsive NIR fluorogenic probe f-RCP consisting of a tumor-targeting cyclic RGD peptide, an ALP-activated photosensitizer CyOP, and an 1O2-susceptible furan module for RNA modification was rationally designed and synthesized. Studies have demonstrated that f-RCP can specifically target to liver carcinoma HepG2 cells and spontaneously emit activated NIR/photoacoustic signals upon cleavage by the ALP enzyme, allowing for sensitive detection of ALP-positive tumors. More notably, we surprisingly found that the capability of f-RCP producing singlet oxygen (1O2) under red light irradiation could be simultaneously unlocked, which can ignite the covalent cyclization reaction between furan and nucleobases of intracellular RNA molecules, leading to significant mitochondrial damage and severe apoptosis of tumor cells, in consequence realizing efficient tumor suppression. Most importantly, the potential therapeutic mechanism was first explored on the transcriptomic level. This delicate ALARM strategy may open up new insights into cancer gene therapy.

MAPK p38/Ulk1 pathway inhibits autophagy and induces IL-1ß expression in hepatic stellate cells.

In the past, hepatic stellate cells (HSCs) were considered to be noninflammatory cells and to contribute to liver fibrosis by producing extracellular matrix. Recently, it was found that HSCs can also secrete cytokines and chemokines and therefore participate in hepatic inflammation. Autophagy participates in many immune response processes in immune cells. It is unclear whether autophagy is involved in inflammatory cytokine induction in HSCs. MAPK p38, Ulk1 phosphorylation, and the Ulk1-Atg13 complex were analyzed in HSC-T6 cells after LPS treatment. The relationship between autophagy inhibition and inflammation was investigated in primary rat HSCs. We discovered that LPS inhibited autophagy through MAPK p38. The activation of MAPK p38 induced Ulk1 phosphorylation, which disrupted the Ulk1-Atg13 complex and therefore inhibited autophagy. Furthermore, in primary rat HSCs, we demonstrated that autophagy inhibition regulated IL-1ß induction, which depended on the MAPK p38/Ulk1 pathway. Our results reveal a continuous signaling pathway, MAPK p38-Ulk1 phosphorylation-Ulk1-Atg13 disruption, which inhibits autophagy and induces IL-1ß expression in HSCs.NEW & NOTEWORTHY LPS inhibits autophagy in a concentration- and dose-dependent manner in HSC-T6 cells. MAPK p38 induces phosphorylation of Ulk1, which disrupts the Ulk1-Atg13 complex and is therefore required for the inhibition of autophagy by LPS. LPS induces IL-1ß expression via the MAPK p38/Ulk1 pathway in HSCs.

In Vivo Quantitative Assessment of a Radiation Dose Based on Ratiometric Photoacoustic Imaging of Tumor Apoptosis.

Accurately assessing the radiation level of tumors and surrounding tissues is of great significance for the optimization of clinical therapeutic interventions as well as minimizing the radiation-induced side effects. Therefore, the development of noninvasive and sensitive biological dosimeters is vital to achieve quantitative detection of a radiation dose in a living system. Herein, as a proof of concept, we report a tumor-targeted and caspase-3-activatable NIR fluorogenic probe AcDEVD-Cy-RGD consisting of a hemicyanine fluorophore as a signal reporter, a caspase-3 specific Asp-Glu-Val-Asp (DEVD) peptide, and a cyclic Arg-Gly-Asp peptide (cRGD) for tumor targeting. Upon cleavage with activated caspase-3, this probe not only displays the lighted-up NIR fluorescence, but also ratiometric photoacoustic (PA710/PA680) signals concurrently in a caspase-3 concentration-dependent manner, allowing for sensitive and quantitative detection of caspase-3 activity through both fluorescence and PA imaging, which provides the possibility for real-time monitoring of tumor cell apoptosis in a living system. More notably, we utilized this probe to successfully realize the direct visualization of tumor response to chemo- or radiotherapy and, for the first time, achieve the accurate estimation of radiation doses imparted to the tumors. We thus believe that our current strategy would offer an attractive and valuable means for the precise assessment of locally delivered radiation doses in various clinical settings.

Frequent alanine aminotransferase flares and promising antiviral therapy efficacy during the preschool age: An opportunity to achieve HBsAg loss in children with mother-to-child transmitted hepatitis B.

Alanine aminotransferase (ALT) flare remains one of the determinants of initiating antiviral therapy in children with chronic hepatitis B (CHB). Insufficient data exist regarding children with CHB attributed to mother-to-child transmission. This study aimed to assess the occurrence of spontaneous ALT flares and identify factors affecting therapy-induced hepatitis B surface antigen (HBsAg) loss in the flare cohort. We retrospectively included untreated children with mother-to-child transmitted CHB. The primary outcomes were spontaneous ALT flares and therapy-induced HBsAg loss. Among 83 untreated children, 73.5% (61/83) experienced spontaneous ALT flares during the median follow-up of 14.6 months (range, 0.1-177.1 months), with 54.1% of the first ALT flares and 44.3% of ALT peaks occurring within 6 years of age. Thirty-six of 61 children with ALT flares received antiviral therapy, nine (25.0%) of whom achieved therapy-induced HBsAg loss with a median duration of 19.3 months (range, 6.5-56.2 months). The age of initiation of antiviral therapy was the sole predictor of therapy-induced HBsAg loss (HR = 0.544, 95% CI 0.353-0.838, p = 0.006). The restricted cubic spline showed a negative relationship between the age of initiation of antiviral therapy and HBsAg loss and identified that 6.2 years of age discriminated children with therapy-induced HBsAg loss. Kaplan-Meier estimations suggested a higher probability of HBsAg loss in children who started antiviral therapy before 6.2 years old (p = 0.03). In conclusion, asymptomatic ALT flares were frequent in preschool-aged children with mother-to-child transmitted CHB, and early initiation of antiviral therapy showed promising effects in those children with ALT flares.

Incidence of mother-to-child transmission of hepatitis B in relation to maternal peripartum antiviral prophylaxis: A systematic review and meta-analysis.

INTRODUCTION: Mother-to-child transmission (MTCT) of the hepatitis B virus (HBV) is a serious public health challenge. Estimating HBV MTCT incidence by region under different prophylaxis regimens is critical to understanding the regional disease burden and prioritizing interventions. This study aimed to calculate HBV MTCT incidence under different prophylaxis regimens globally and regionally and identify the HBV DNA threshold for maternal peripartum antiviral prophylaxis. MATERIAL AND METHODS: This review was registered in advance in PROSPERO (CRD 42019120567). We searched PubMed, Embase, China National Knowledge Infrastructure, ClinicalTrials.gov, and Cochrane Library databases for studies on MTCT in pregnant women with chronic HBV infection from their inception until June 13, 2022. MTCT was defined as hepatitis B surface antigen (HBsAg) or HBV DNA seropositivity in infants aged 6-12 months. We calculated the pooled HBV MTCT incidence using the DerSimonian-Laird random-effects model. RESULTS: Among 300 studies, 3402 of 63 293 infants had HBV due to MTCT. Without prophylaxis regimens, the pooled HBV MTCT incidence was 31.3%, ranging from 0.0% (95% confidence interval [CI] 0.0%-6.0%; European Region) to 46.1% (95% CI 29.7%-63.0%; Western Pacific Region). Following the introduction of the hepatitis B vaccine, the HBV MTCT incidence decreased from 82.9% to 15.9% in HBeAg-positive women and from 10.3% to 2.3% in HBeAg-negative women. Maternal peripartum antiviral treatment alongside infant immunoprophylaxis further decreased MTCT incidence to 0.3% (95% CI 0.1%-0.5%). Despite infant immunoprophylaxis, the incidences of MTCT at maternal HBV DNA levels of <2.30, 2.00-3.29, 3.00-4.29, 4.00-5.29, 5.00-6.29, 6.00-7.29 and ≥7.00 log10  IU/ml were 0.0% (95% CI 0.0%-0.0%), 0.0% (95% CI 0.0%-0.0%), 0.0% (95% CI 0.0%-0.5%), 0.6% (95% CI 0.0%-2.6%), 1.0% (95% CI 0.0%-3.1%), 4.3% (95% CI 1.8%-7.5%), and 9.6% (95% CI 7.0%-12.5%), respectively. CONCLUSIONS: HBV MTCT incidence varies across regions. The Western Pacific Region bears the heaviest burden. Peripartum antiviral prophylaxis plus infant immunoprophylaxis is promising for interrupting HBV MTCT. Regarding the HBV DNA threshold for peripartum antiviral prophylaxis, maternal HBV DNA of 4.00 log10  IU/ml or greater seems justified.

A bibliometric analysis study of blood flow restriction using CiteSpace.

[Purpose] To assess the current state-of-the-art and the prevailing trends regarding the global use of blood flow restriction (BFR) in the past 20 years. [Participants and Methods] We retrieved literature relating to BFR from 1999 to 2020 using Web of Science. We conducted a bibliometric analysis of countries/institutions, cited journals, authors/cited authors, cited references, and keywords using CiteSpace. An analysis of counts and centrality was used to examine publication output, countries/institutions, core journals, active authors, foundation references, hot topics, and frontiers. [Results] Seven hundred seventy five references were included and the total number of publications has been continually increasing over the investigated period. Representatives of important academic groups are the Japanese scholars from the University of Tokyo as represented by Takashi Abe. Jeremy Paul Loenneke's article (centrality: 0.15) was the most representative and symbolic reference with the highest centrality. The three topics identified were intervention (intensity resistance exercise, IRE), physiology (ischemia and muscular function) and behavior (adaptation and increase). The four frontier topics were phosphorylation, reduction, low intensity and arterial occlusion. [Conclusion] This study provides an insight into BFR and offers valuable information for BFR researchers to identify new perspectives for potential cooperation with collaborators and their related cooperative institutions.

Freshwater crabs could act as vehicles of spreading avian influenza virus.

Avian influenza virus (AIV) possessed significant risk to various animals and human health. Wild birds, especially waterfowls are considered to be the natural reservoir of AIVs. The ecology of AIV is still far from being fully understood. Freshwater crabs are nonnegligible biotic factor in AIV ecosystem. We analyzed the ability of freshwater crabs accumulate and spread AIV. We found that AIV remain infectious in water only for 36 h but persist in crabs for 48 h. Crabs could accumulate AIV in their gills and gastrointestinal tracts. The AIV titers in crabs were higher than the surrounding contaminated water. Crabs could accumulate AIV from contaminated water, carry the virus and spread to naïve crabs via surrounding water. Our study identified freshwater crab as a novel transmission vehicle in AIV ecosystem.

[Research progress on therapeutic potential of quercetin].

Quercetin is a naturally occurring phytochemical with good bioactivity, which mainly exists in the form of glycoside in vegetables, fruits, tea, and wine and exhibits beneficial health effects. Quercetin is a dietary polyphenol that exerts the protective effects through diet or use as a food supplement. Compared with chemical agents, quercetin is widely available and safe. Quercetin has been extensively studied for its anti-diabetic, anti-hypertensive, anti-Alzheimer's disease, anti-arthritic, anti-influenza virus, anti-microbial infection, anti-aging, autophagy-regulating, and cardiovascular protective effects. Studies on its activities against different can-cer cell lines have also been reported recently. However, the poor water solubility, rapid in vivo metabolism, and short half-life of quercetin have led to its low bioavailability, thus limiting its application in the field of medicine. Quercetin nanoparticles and nanoparticle drug delivery system have been effectively utilized for enhancing its bioavailability. This paper reviewed the therapeutic potential of quercetin from both preclinical and clinical aspects and proposed solutions to improve its bioavailability, so as to provide a reference for the therapeutic application of natural compounds in the field of medicine.

[Research progress on rutin derivatives].

Compounds derived from natural products present satisfactory efficacy in disease prevention and treatment. The use of chemical substances in plants to promote healthhas increasingly attracted people's attention. Rutin, a typical flavonoid, is mainly found in various vegetables, fruits and Chinese herbal medicines. As a natural antioxidant, it features many pharmacological activities, such as anti-inflammation, anti-virus, anti-tumor, and prevention and treatment of cardiovascular and cerebrovascular diseases. However, the low bioavailability and poor water solubility limit its clinical application. In view of this, its structure is optimized and modified to afford rutin derivatives with good solubility, high bioavailability, stable metabolism and small toxic side effects. So far, a large number of rutin ethers, esters, and complexes have been synthesized and undergone activity testing. This paper reviews the structural modification of rutin in recent years, and the obtained derivatives have excellent properties and significant biological activity.

Aggregation of Gold Nanoparticles Triggered by Hydrogen Peroxide-Initiated Chemiluminescence for Activated Tumor Theranostics.

Developing endogenous photo-activated theranostic platforms to overcome the limitation of low tissue-penetration from external light sources is highly significant for cancer diagnosis and treatment. We report a H2 O2 -initiated chemiluminescence (CL)-triggered nanoparticle aggregation strategy to activate theranostic functions of gold nanoparticles (AuNPs) for effective tumor imaging and therapy. Two types of AuNPs (tAuNP & mAuNP) were designed and fabricated by conjugating 2,5-diphenyltetrazole and methacrylic acid onto the surface of AuNPs, respectively. Luminol was adsorbed onto the mAuNPs to afford self-illuminating mAuNP/Lu NPs that could produce strong CL by reaction with H2 O2 in the tumor microenvironment, which triggers significant aggregation of AuNPs resulting in enhanced accumulation and retention of AuNPs for activated photoacoustic imaging and photothermal therapy of tumors. We thus believe that this approach may offer a promising tool for effective tumor treatment.

Royal Free Hospital-Nutritional Prioritizing Tool improves the prediction of malnutrition risk outcomes in liver cirrhosis patients compared with Nutritional Risk Screening 2002.

The European Society for Clinical Nutrition and Metabolism (ESPEN) guidelines recommend the Royal Free Hospital-Nutritional Prioritizing Tool (RFH-NPT) to identify malnutrition risk in patients with liver disease. However, little is known about the application of the RFH-NPT to screen for the risk of malnutrition in China, where patients primarily suffer from hepatitis virus-related cirrhosis. A total of 155 cirrhosis patients without liver cancer or uncontrolled co-morbid illness were enrolled in this prospective study. We administered the Nutritional Risk Screening 2002 (NRS-2002), RFH-NPT, Malnutrition Universal Screening Tool (MUST) and Liver Disease Undernutrition Screening Tool (LDUST) to the patients within 24 h after admission and performed follow-up observations for 1·5 years. The RFH-NPT and NRS-2002 had higher sensitivities (64·8 and 52·4 %) and specificities (60 and 70 %) than the other tools with regard to screening for malnutrition risk in cirrhotic patients. The prevalence of nutritional risk was higher under the use of the RFH-NPT against the NRS-2002 (63 v. 51 %). The RFH-NPT tended more easily to detect malnutrition risk in patients with advanced Child-Pugh classes (B and C) and lower Model for End-stage Liver Disease scores (<15) compared with NRS-2002. RFH-NPT score was an independent predictive factor for mortality. Patients identified as being at high malnutrition risk with the RFH-NPT had a higher mortality rate than those at low risk; the same result was not obtained with the NRS-2002. Therefore, we suggest that using the RFH-NPT improves the ability of clinicians to predict malnutrition risk in patients with cirrhosis primarily caused by hepatitis virus infection at an earlier stage.

Fabrication of Ag3PO4/TiO2@molecular sieve (MS) ternary composites with remarkably enhanced visible light-responded photocatalytic activity and mechanism insight.

In this study, Ag3PO4/TiO2@molecular sieve (MS) ternary composites were fabricated via in-situ deposition and hydrothermal growth method for photocatalytic degradation of formaldehyde and sodium isobutyl xanthate (SIBX) under visible light irradiation. XRD, PL, UV-vis, UPS, SEM-EDS and XPS techniques were adopted to characterize the composite. The results show that the MS material was indexed as zeolite P and Ag3PO4-TiO2 hybrid structure could improve the absorption of visible light and greatly inhibit the recombination of photogenerated charge carriers by introducing 3 times TiO2. After evaluating the photocatalytic activity and kinetics model, it is found that photocatalytic activity is consistent with the apparent first-order kinetic model. The Ag3PO4/TiO2-3@MS ternary composite under visible light irradiation appears the highest removal rate with 97.9% of formaldehyde and 96.7% of SIBX, respectively. Furthermore, the reusability of the photocatalyst was investigated by successive reuse. After five reuses, the removal rates reached 97.3% and 94.6% within 105 min for formaldehyde and SIBX, respectively. At last, the proposed mechanism of the photocatalytic reaction and the degradation routes of formaldehyde and SIBX were systematically discussed.

[Research progress on antitumor activity of quercetin derivatives].

Quercetin is a kind of typical flavonoid, mainly found in various vegetables, fruits and Chinese herbs that are consumed daily, with the functions of anti-oxidation, anti-tumor, prevention and treatment of cardiovascular and cerebrovascular diseases. Quercetin is a natural compound with defined anti-tumor activity. Due to its low bioavailability and poor water solubility, quercetin has limitations in clinical application. The quercetin derivatives with good solubility, high bioavailability, metabolic stability, and low toxicity have been obtained through modification of quercetin structure. In recent years, a large number of quercetin ethers, esters, complexes, C-4 carbonyloxy substituted derivatives, A,B-ring modified compounds and other derivatives have been synthesized and tested for in vitro anticancer activity. The quercetin derivatives with anti-tumor activity synthesized in the last 5 years were reviewed in this paper.

Effects of Non-invasive Brain Stimulation on Headache Intensity and Frequency of Headache Attacks in Patients With Migraine: A Systematic Review and Meta-Analysis.

BACKGROUND: Non-invasive brain stimulation (NIBS) techniques such as repetitive transcranial magnetic stimulation (rTMS), as well as transcranial direct current stimulation (tDCS) electrically stimulate the brain and modify brain activity to suppress pain. This method is emerging as a potential clinical intervention against migraine. OBJECTIVE: To quantitatively review the efficacy of rTMS and tDCS in randomized controlled trials (RCTs) in modifying headache intensity and frequency of headache attacks in patients suffering from migraine. METHODS: We searched 5 databases: PubMed, EMBASE, Web of Science, Cochrane Library, and Scopus for articles from January 2000 to September 2018. Any RCT regarding the efficacy on rTMS and tDCS on patients with migraine, was considered to be included. A random effects meta-analysis was performed to pool effect sizes of outcomes related to headache intensity or frequency of headache attacks. The methodological quality of the included RCTs was assessed using the Physiotherapy Evidence Database scale. RESULTS: Nine RCTs with 276 participants in total (experimental group [EG] = 149; control group [CG] = 127) were included in this review. Five included articles used rTMS (EG = 81; CG = 80), and 4 used tDCS (EG = 68; CG = 47). Meta-analysis of excitatory primary motor cortex (M1) stimulation showed significant effects on reducing headache intensity in patients with migraine (Hedges' g = -0.94; 95% CI, -1.28 to -0.59; P < .001, I2  = 18.39%) with a large effect size. Meta-analysis of excitatory M1 stimulation showed significant effects on reducing frequency of headache attacks in patients with migraine, with a large effect size (Hedges' g = -0.88; 95% CI, -1.38 to -0.38; P = .001, I2  = 57.15%). Excitatory dorsolateral prefrontal cortex stimulation showed a significant effect on the headache intensity in patients with migraine (Hedges' g = -1.14; 95% CI, -2.21 to -0.07; P = .04, I2  = 61.86%) with a large effect size. However, reductions of frequency of headache attacks was not significant. LIMITATIONS: Potential differential effects of rTMS and tDCS, various sham methods, and potential overlapping headache disorders among included subjects may affect the estimation of effect sizes. CONCLUSION: Excitatory NIBS of the M1 is likely to reduce headache intensity and the frequency of headache attacks in patients with migraine.

Removal of chemical oxygen demand (COD) and heavy metals by catalytic ozonation-microbial fuel cell and Acidithiobacillus ferrooxidans leaching in flotation wastewater (FW).

A catalytic ozonation-microbial fuel cell and Acidithiobacillus ferrooxidans leaching process was used in treating flotation wastewater to remove chemical oxygen demand (COD) and heavy metals in this study. The results indicated that when adding 1 g/L of manganese/modified activated carbon catalyst and 1.5 g/min ozone flow, the COD could be degraded from 2,043.67 mg/L to 711.4 mg/L. After that, the COD could continue decreasing down to 72.56 mg/L through an air-cathode single chamber microbial fuel cell (SCMFCs), coated with 0.4 mg/cm2 platinum catalyst, after 15 days. Meanwhile, the maximum voltages and the ultimate power density of the SCMFCs reached 378.96 mV and 7,608.35 mW/m2, respectively. For filter residue, when 1.2 g/L Fe3+, 10% (m/v) filter residue, and 10% Acidithiobacillus ferrooxidans were added, the copper leaching rate could reach 92.69% after 7 days if the pH values were adjusted to 1.9. Furthermore, the other heavy metals were also decreased to a level lower than the pollution control standard (Chinese standard GB3838-2002). The leaching parameters in terms of pH, redox potential, and cyclic voltammetry showed that the addition of an appropriate concentration of Fe3+ to the leaching systems was beneficial to copper dissolution.