Novel l-Cysteine Incomplete Degradation Method for Preparation of Procyanidin B2-3'-O-Gallate and Exploration of its in Vitro Anti-inflammatory Activity and in Vivo Tissue Distribution.

In this study, an effective method for preparation of bioactive galloylated procyanidin B2-3'-O-gallate (B2-3'-G) was first developed by incomplete depolymerization of grape seed polymeric procyanidins (PPCs) using l-cysteine (Cys) in the presence of citric acid. The structure-activity relationship of B2-3'-G was further evaluated in vitro through establishing lipopolysaccharide (LPS)-induced inflammation in RAW264.7 cells. The results suggested that the better protective effects of B2-3'-G against inflammation were attributed to its polymerization degree and the introduction of the galloyl group, compared to its four corresponding structural units. In vivo experiments demonstrated that the B2-3'-G prototype was distributed in plasma, small intestine, liver, lung, and brain. Remarkably, B2-3'-G was able to penetrate the blood-brain barrier and appeared to play an important role in improving brain health. Furthermore, a total of 18 metabolites were identified in tissues. Potential metabolic pathways, including reduction, methylation, hydration, desaturation, glucuronide conjugation, and sulfation, were suggested.

Genome-Wide Meta-Analysis Identifies 11 Susceptibility Variants of Vitiligo in the Chinese Han Population.

Vitiligo is an autoimmune disease involving loss of melanocytes. Although several genetic studies have confirmed that genetic factors play an important role, its pathogenesis remains incompletely characterized. In this study, a genome-wide meta-analysis was conducted to search for more susceptibility variants of vitiligo. Tang et al performed a GWAS for cohort I (1117 vitiligo cases and 1701 healthy controls) previously, and we conducted a GWAS for cohort II (3323 vitiligo cases and 7186 healthy controls) in this study, with the results subjected to a genome-wide meta-analysis and linkage disequilibrium analysis. We identify, to our knowledge, 11 previously unreported susceptibility variants, of which 6 variants are located in the intronic regions, and the remaining 5 variants are located within intergenic regions between genes. In addition, the results of polygenic risk score show that the best evaluated effect for target data is among significant SNVs of the base data. The susceptibility genes of vitiligo are mainly enriched in the immune-related functions and pathways. The susceptibility variants expand the role of genetic factors associated with vitiligo. The bioinformatics analysis for risk genes provides further insight into the pathogenesis of vitiligo.

Promoting OH- Adsorption and Diffusion Enables Ultrahigh Capacity and Rate Capability of Nickel Sulfide Cathode for Aqueous Alkaline Zn-Based Batteries.

Aqueous alkaline Zn-based batteries (AAZBs) possess great promise for large-scale applications thanks to their higher discharging plateau and unique reaction mechanism. However, the capacity and rate capability of Ni-based cathodes are still unsatisfactory due to their insufficient OH- adsorption and diffusion ability. Herein, heterostructured Ni3 S2 /Ni(OH)2 nanosheets with outstanding electrochemical performance are synthesized via a facile chemical etching strategy. The heterostructured Ni3 S2 /Ni(OH)2 nanosheet cathode shows significantly increased capacity and rate capability due to its boosted OH- adsorption and diffusion ability compared to Ni3 S2 . Consequently, the assembled Zn//Ni3 S2 /Ni(OH)2 cell can deliver an ultrahigh capacity of 2.26 mAh cm-2 , an excellent rate performance (0.91 mAh cm-2 at 100 mA cm-2 ) and a satisfying cycling stability (1.01 mAh cm-2 at 20 mA cm-2 after 500 cycles). Moreover, a prominent energy density of 3.86 mWh cm-2 is obtained, which exceeds the majority of recently reported AAZBs. This work is expected to provide a new modification direction for developing high-performance nickel sulfide cathode for AAZBs.

Relationship between bilirubin and systemic lupus erythematosus: A systematic review and meta-analysis.

AIMS: Systemic lupus erythematosus (SLE) is an autoimmune disease with a high prevalence worldwide. This study aimed to examine the correlation between serum bilirubin levels and SLE. METHODS: The Cochrane library, Embase, PubMed, and China National Knowledge Infrastructure (CNKI) databases were examined and assessed until March 2023. RevMan 5.3 software was utilized for the analysis of clinical trails. RESULTS: Five case-control studies were chosen and incorporated, examining the levels of serum bilirubin in patients with SLE compared to healthy individuals, as well as in active SLE patients versus inactive ones, in different sexes and in SLE patients with or without lupus nephritis (LN). The results of this meta-analysis demonstrated that serum bilirubin in healthy individuals were obviously increased compared to SLE patients (MD = 4.76; 95% CI, 3.15-6.38, p < .00001). Additionally, inactive SLE patients had higher levels of bilirubin than active SLE patients (MD = 3.15; 95% CI, 0.46-5.84, p = .02), and SLE patients without lupus nephritis had higher levels of serum bilirubin than those with lupus nephritis (MD = 4.91;95% CI, 2.87-6.95, p < .00001). Nevertheless, there were no disparities observed among SLE patients of varying sexes (MD = 0.34; 95% CI, -0.01 to 0.69, p = .06). CONCLUSION: The concentration of serum bilirubin may potentially be used as an indicator for estimating the advancement of SLE and reflecting the presence of kidney complications in individuals with SLE. Furthermore, more high quality studies were needed to identify these findings.

Stress aggravates imiquimod-induced psoriasiform inflammation by promoting M1 macrophage polarization.

Psychological stress has long been considered to cause the aggravation and recurrence of psoriasis, but the underlying mechanism remains largely unknown. Here, we used a mouse model of restraint-induced stress and imiquimod (IMQ)-induced psoriasiform inflammation to investigate the crosstalk between stress and the skin immune system and their functions in the pathogenesis of psoriasis. We found that stress aggravated skin inflammation and elevated serum corticosterone (CORT) levels in mice. Stress also increased the number of macrophages and glucocorticoid receptor (GR) expression in IMQ-treated mouse skin. GR agonist CORT upregulated the phosphorylation of STAT1 to promote M1 macrophage polarization in vitro. Additionally, GR deletion in macrophages and pharmacologic inhibition of GR improved skin inflammation and reduced M1 macrophage polarization under stress. Taken together, these results indicate that stress aggravates psoriasiform inflammation by promoting CORT/GR signaling-induced M1 macrophage polarization, suggesting that blocking the GR signaling has great potential as an adjuvant treatment for psoriasis patients with chronic stress.

Risk factors associated with attendance at postpartum blood pressure follow-up visit in discharged patients with hypertensive disorders of pregnancy.

BACKGROUND: This study aims to investigate the risk factors for not returning to postpartum blood pressure (BP) follow-up visit at different time points in postpartum discharged hypertensive disorders of pregnancy (HDP) patients. Likewise, females with HDP in China should have a BP evaluation continuously for at least 42 days postpartum and have BP, urine routine, and lipid and glucose screening for 3 months postpartum. METHODS: This study is a prospective cohort study of postpartum discharged HDP patients. Telephone follow-up was conducted at 6 weeks and 12 weeks postpartum, the maternal demographic characteristics, details of labor and delivery, laboratory test results of patients at admission, and adherence to BP follow-up visits postpartum were collected. While logistic regression analysis was used to analyze the factors associated with not returning to postpartum BP follow-up visit at 6 weeks and 12 weeks after delivery, the receiver operating characteristic (ROC) curve was drawn to evaluate the model's predictive value for predicting not returning to postpartum BP visit at each follow-up time point. RESULTS: In this study, 272 females met the inclusion criteria. 66 (24.26%) and 137 (50.37%) patients did not return for postpartum BP visit at 6 and 12 weeks after delivery. A multivariate logistic regression analysis identified education level of high school or below (OR = 3.71; 95% CI = 2.01-6.85; p = 0.000), maximum diastolic BP during pregnancy (OR = 0.97; 95% CI = 0.94-0.99; p = 0.0230)and delivery gestational age (OR = 1.12; 95% CI = 1.005-1.244; p = 0.040)as independent risk factors in predicting not returning to postpartum BP follow-up visit at 6 weeks postpartum, and education level of high school or below (OR = 3.20; 95% CI = 1.805-5.67; p = 0.000), maximum diastolic BP during pregnancy (OR = 0.95; 95% CI = 0.92-0.97; p = 0.000), delivery gestational age (OR = 1.13; 95% CI = 1.04-1.24; p = 0.006) and parity (OR = 1.63; 95% CI = 1.06-2.51; p = 0.026) as risk factors for not returning to postpartum BP follow-up visit at 12 weeks postpartum. The ROC curve analysis indicated that the logistic regression models had a significant predictive value for identify not returning to BP follow-up visit at 6 and 12 weeks postpartum with the area under the curve (AUC) 0.746 and 0.761, respectively. CONCLUSION: Attendance at postpartum BP follow-up visit declined with time for postpartum HDP patients after discharge. Education at or below high school, maximum diastolic BP during pregnancy and gestational age at delivery were the common risk factors for not returning for BP follow-up visit at 6 and 12 weeks postpartum in postpartum HDP patients.

Meta-analysis of cancer risk among end stage renal disease undergoing maintenance dialysis.

Currently, there is no consensus on whether maintenance dialysis increases cancer risk in patients with end-stage renal disease (ESRD). Therefore, this study was to systematically evaluate the risk of cancer among ESRD patients undergoing maintenance dialysis. Related studies on the impact of maintenance dialysis on cancer risk were retrieved from PubMed, Embase, Cochrane Library, and other databases from their respective inceptions to 19 February 2021. ESRD patients receiving maintenance dialysis were classified into cancer including non-melanoma skin cancer (NMSC) and cancer excluding NMSC. Standardized incidence ratio (SIR) with its 95% confidence interval (95% CI) was calculated to assess cancer risk. Fourteen studies were included in the meta-analysis. The risk of cancer in patients undergoing maintenance dialysis (with or without NMSC) was significantly higher than controls both in cancer including NMSC (SIR = 1.38, 95% CI: 1.27-1.49, P < 0.001) and cancer excluding NMSC (SIR = 1.34, 95% CI: 1.23-1.47, P < 0.001). Subgroup results identified the higher risk of cancer incidence in both men and women receiving maintenance dialysis. Meanwhile, elevated excess risks were observed among patients with younger age and shorter follow-up time (P < 0.001). Meanwhile, the combined SIR of bladder, cervix, colorectum, kidney, liver, thyroid, tongue, and other cancers were all increased (P < 0.05). ESRD patients undergoing dialysis has higher risk of cancer.

Valence Engineering Enhancing NH4 + Storage Capacity of Manganese Oxides.

Ammonium ions (NH4 + ), as non-metallic charge carriers, are attracting attention in aqueous batteries due to its low molar mass, element sufficiency, and non-toxicity. However, the host materials for NH4 + storage are still limited. Herein, an oxygen defects-rich manganese oxide (MnO2-x ) for NH4 + storage are reported. The oxygen defects can endow the MnO2-x sample with improved electric conductivity and low interface activation energy. The electrochemical reaction mechanism is also verified by using ex situ X-ray photoelectron spectroscopy (XPS) and fourier transform infrared spectroscopy (FT-IR), demonstrating the insertion and extraction of NH4 + in the MnO2-x by formation/breaking of a hydrogen bond. As a result, MnO2-x delivers a high capacity of 109.9 mAh g-1 at the current density of 0.5 A g-1 and retention of 24 mAh g-1 after 1000 cycles at the current density of 4 A g-1 , outperforming the pristine MnO2 sample.

CircRNA Circ_0000118 Regulates Malignancy of Cervical Cancer Cells by Regulating miR-211-5p/miR-377-3p/AKT2 Axis.

CircRNAs are implicated in the development of several cancers. Nevertheless, the involvement of circ_0000118 in the development of cervical cancer (CC) remains unclear. Circ_0000118 levels in tumor tissues and cells were examined by qRT-PCR. The function of circ_0000118 in regulating the malignancy of CC cells was investigated using functional assays, including CCK-8, colony formation, transwell, and tube formation experiments. The functional interaction between circ_0000118 and microRNAs were validated by dual-luciferase activity assay and RNA precipitation experiments. In vivo mouse model was employed to assess the effect of circ_0000118 in the tumorigenesis of CC cells. Circ_0000118 was overexpressed in CC cells and tissues. Loss-of-function experiments demonstrated that circ_0000118 knockdown impaired the proliferation and tumor sphere formation, as well as the angiogenic potential of CC cells. RNA interaction experiments confirmed that circ_0000118 sponged miR-211-5p and miR-377-3p. AKT2 was found to be a target gene negatively modulated by miR-211-5p and miR-377-3p. AKT2 overexpression rescued the inhibition of circ_0000118 downregulation on CC cells. Our study suggested that circ_0000118 functions as an oncogenic factor in progression of CC by maintaining AKT2 level through targeting miR-211-5p and miR-377-3p as a ceRNA (competitive endogenous RNA), which provides novel therapeutic target in the management of CC.

Compacting Electric Double Layer Enables Carbon Electrode with Ultrahigh Zn Ion Storage Capability.

Carbon-based cathodes for aqueous zinc ion hybrid supercapacitors (ZHSCs) typically undergo low Zn ion storage capability due to their electric double layer capacitance (EDLC) energy storage mechanism that is restricted by specific surface area and thickness of electric double layer (EDL). Here, we report a universal surface charge modulation strategy to effectively enhance the capacitance of carbon materials by decreasing the thickness of EDL. Amino groups with lone pair electrons were chosen to increase the surface charge density and enhanced the interaction between carbon electrode and Zn ions, thus effectively compacting the EDL. Consequently, amino functionalized porous carbon based ZHSCs can deliver an ultrahigh capacity of 255.2 mAh g-1 along with excellent cycling stability (95.5 % capacity retention after 50 000 cycles) in 1 M ZnCl2 electrolyte. This study demonstrates the feasibility of EDL modified carbon as Zn2+ storage cathode and great prospect for constructing high performance ZHSCs.

Defect Engineering Triggers Exceptional Sonodynamic Activity of Manganese Oxide Nanoparticles for Cancer Therapy.

Sonodynamic therapy (SDT) has received increasing interest in cancer treatment, but its clinical application is still constrained by the low activity of sonosensitizers and their unclear mechanism. Herein, a kind of oxygen-deficient manganese oxide (MnOx) nanoparticles with greatly enhanced sonodynamic activity and good biocompatibility is developed as an advanced sonosensitizer. The introduced oxygen defects can remarkably enhance the electrical conductivity of manganese oxide (MnO) nanoparticles and serve as charge trapping sites to prohibit the electron-hole pair recombination upon ultrasound (US) irradiation. Such distinct merits promote the generation of reactive oxygen species (ROS), making MnOx as a decent sonosensitizer for SDT, and thus endowing MnOx with higher ROS production under US irradiation. As a demonstration, the MnOx nanoparticles decorated by 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-2000] (MnOx-DSPE-PEG), a biocompatible coverage to enhance the dispersion ability, achieve a superior tumor killing efficiency of 96%, substantially higher than the MnO-DSPE-PEG counterpart (9%). Our experimental results also reveal that MnOx-DSPE-PEG nanoparticles induce the death of tumor cells by targeting polyunsaturated fatty acids in their membrane with US-triggered ROS. Furthermore, the as-designed sonosensitizers exhibit negligible toxicity toward the treated mice.

Unshared Pair Electrons of Zincophilic Lewis Base Enable Long-life Zn Anodes under "Three High" Conditions.

The hydrogen evolution and dendrite issues are the notorious culprits of the limited lifespan and Coulombic efficiency (CE) of Zn anodes, particularly at harsh test conditions. Herein, considering the Lewis acidic feature of Zn2+ , abundant unshared pair electrons of zincophilic Lewis bases are proposed as decent electrolyte additives to stabilize Zn anodes at "Three High" conditions (high depth of discharge, high areal capacity and high current). The unshared pair electrons can remove H2 O from Zn2+ solvated sheaths and confine the activity of H2 O by breaking its hydrogen bonding network. The combination of these factors effectively restricts H2 O-involved side reactions and enables dendrite-free Zn deposition, even at harsh conditions. The effectiveness of this strategy is fully proved by a series of Lewis base molecules. Noticeably, the Zn||Zn cell with an area of 20 cm2 , using DMF-containing electrolyte can be stably cycled over 1000 h at 60 % DOD, with a 100 % CE.

Calcium/calmodulin-dependent protein kinase IV promotes imiquimod-induced psoriatic inflammation via macrophages and keratinocytes in mice.

CaMK4 has an important function in autoimmune diseases, and the contribution of CaMK4 in psoriasis remains obscure. Here, we show that CaMK4 expression is significantly increased in psoriatic lesional skin from psoriasis patients compared to healthy human skin as well as inflamed skin from an imiquimod (IMQ)-induced mouse model of psoriasis compared to healthy mouse skin. Camk4-deficient (Camk4-/-) mice treated with IMQ exhibit reduced severity of psoriasis compared to wild-type (WT) mice. There are more macrophages and fewer IL-17A+γδ TCR+ cells in the skin of IMQ-treated Camk4-/- mice compared to IMQ-treated WT mice. CaMK4 inhibits IL-10 production by macrophages, thus allowing excessive psoriatic inflammation. Deletion of Camk4 in macrophages alleviates IMQ-induced psoriatic inflammation in mice. In keratinocytes, CaMK4 inhibits apoptosis as well as promotes cell proliferation and the expression of pro-inflammatory genes such as S100A8 and CAMP. Taken together, these data indicate that CaMK4 regulates IMQ-induced psoriasis by sustaining inflammation and provides a potential target for psoriasis treatment.

Methods for Rational Design of Advanced Zn-Based Batteries.

Rechargeable aqueous zinc-based batteries (AZBs) have received massive attention as promising contenders for the future large-scale energy storage due to their low cost, inherent safety, and abundant resources. However, the insufficient energy density and poor stability have become the key to hinder their further application. As is well known, the energy densities (E, Wh kg-1 ) of AZBs are determined by the specific capacity (mAh g-1 ) and output voltage (V). Given the fixed redox potential and capacity of the Zn metal anode, the energy density of AZBs is mainly determined by the cathode material, and the rich material systems of the cathode provide more possibilities to this field. Meanwhile, the methods to improve the stability and performance of the Zn anodes have gained more and more attention due to the severe Zn dendrite growth that can pierce the separator and lead to short-circuiting of the cell. Therefore, in this review, we comprehensively summarize the rational design methods in optimizing the cathode, anode, and device architecture, and classic examples of each catalogue are discussed in details as well. Last, the issues and outlook for further development of high performance AZBs are also presented.

Human Leukocyte Antigen Fine-Mapping and Correlation Analysis of Han and Minority Leprosy Patients in Southern China.

Backround: Leprosy is very prevalent in many populations around the world, which is well known that both alleles for human leukocyte antigen (HLA) as well as single nucleotide polymorphisms (SNPs) in the HLA region are common in leprosy patients. Previous studies have identified leprosy-associated susceptibility genes that explain only part of disease risk and heritability. In view of the complicated characteristics of the major histocompatibility complex (MHC) region, this study aimed to explore the development and variation of HLA in leprosy and its possible mechanism. Methods: Previous genome-wide association data were extracted from Han and minority populations in southern China for HLA fine-mapping studies. Insertion and deletion (INDEL), SNP, and copy number variation (CNV) imputation were determined by using the Thousand People Database (1KGP Phase 3 Dataset) as a reference panel. The HAN-MHC database was used to input the HLA classical alleles and amino acids in the MHC region, and further step-regression analysis was performed to analyze independent variation signals associated with leprosy. Results: The most significant locus rs75324027 (the same locus as rs602875 in the HLA-DR region) [p = 7.49E-09, OR= 0.62, 95%,CI: 0.52-0.73] in the intergene region between HLA-DQA1 and HLA-DRB1 was related with leprosy in M-S(Han leprosy patients in south China)disease. In M-SM (Leprosy patients of ethnic minorities in south China)disease, one of the most significant loci of the HLA-DQB1 gene was 6-32626438-A-T (p = 4.49E-08, OR = 0.36, 95%,CI: 0.25-0.52). Therefore, rs75324027 is a locus in M-S disease, and 6-32626438-a-T may be a new locus in M-SM disease. The interaction between 6 and 32626438-A-T and RS75324027 was analyzed, and A significant interaction relationship was found. In the optimal model, the accuracy of prediction was 0.5974, cross-validation Consistency:10, p = 0.0107. Conclusion: In conclusion, this study is the first to assess the association between HLA and leprosy susceptibility in Han and other minority populations in southern China using the Thousand Population database and the Han MHC database. In addition, our analysis validated the previously reported locus rs602875 in the HLA-DR region and for the first time identified an unreported independent locus in leprosy among ethnic minorities in southern China.

Optimization of the vancomycin administration regimen by clinical pharmacists based on a population pharmacokinetics model: a prospective interventional study.

In vancomycin treatment, the rates of correct blood sampling and initial trough concentrations within the target range are very low. Studies of interventions by clinical pharmacists based on population pharmacokinetics (PPK) models are limited. This study aimed to evaluate the intervention effect of clinical pharmacist-mediated optimization of the vancomycin administration regimen based on a PPK model. Retrospectively enrolled patients constituted the control group, and prospectively enrolled patients constituted the intervention group. The vancomycin administration regimen, trough concentration, pharmacokinetic parameters, and clinical outcomes of the two groups were compared. The control and intervention groups comprised 236 and 138 patients, respectively. Compared with those in the control group, the therapeutic drug monitoring (TDM) and correct TDM sampling time rates in the intervention group were significantly higher (76.92% vs. 43.59%; 63.9% vs. 39.0%, both p < 0.001). The rates of an initial trough concentration within 10-20 mg/L and an adjusted regimen were also significantly higher in the intervention group (55.80% vs. 30.51%, 71.95% vs. 39.18%, both p < 0.001). The rate of an area under the curve (AUC) within 400-650 mg·h/L was higher in the intervention group than in the control group (52.7% vs. 36.6%, p < 0.001). The eradication rates of Gram-positive bacteria were 91.4% in the intervention group and 81.3% in the control group (p = 0.049). Eight patients developed acute kidney injury (AKI) in the control group; however, no AKI occurred in the intervention group (p = 0.029). Intervention by clinical pharmacists can increase the rate of correct sampling time. Using the PPK model combined with Bayesian estimation, clinical pharmacists can greatly increase the trough concentration and AUCs within the target range, especially for adjusted regimens. Higher PK/PD target rates resulted in better Gram-positive bacterial eradication and reduced renal toxicity of vancomycin.

Imputation of the major histocompatibility complex region identifies major independent variants associated with bullous pemphigoid and dermatomyositis in Han Chinese.

As autoimmune skin diseases, both bullous pemphigoid (BP) and dermatomyositis (DM) show significant associations with the major histocompatibility complex (MHC) region. In fact, the coexistence of BP and DM has been previously reported. Therefore, we hypothesized that there may be a potential genetic correlation between BP and DM. Based on data for 312 BP patients, 128 DM patients, and 6793 healthy control subjects, in the MHC region, we imputed single-nucleotide polymorphisms (SNP), insertions and deletions (INDEL), and copy number variations (CNV) using the 1KGP phase 3 dataset and amino acids (AA) and SNP using a Han-MHC reference database. An association study revealed the most significant SNP associated with BP, namely, rs580921 (p = 1.06E-08, odds ratio [OR] = 1.61, 95% confidence interval [CI] = 1.37-1.90), which is located in the C6orf10 gene, and the most significant classic human leukocyte antigen (HLA) allele associated with DM, namely, HLA-DPB1*1701 (p = 6.56E-10, OR = 3.61, 95% CI = 2.40-5.42). Further stepwise regression analyses with rs580921 identified a threonine at position 163 of the HLA-B gene as a new independent disease-associated AA, and HLA-DPB1*1701 indicated that no loci were significant. Three-dimensional ribbon models revealed that the HLA-B AA position 163 (p = 3.93E-07, OR = 1.64, 95% CI = 1.35-1.98) located in the α2 domain of the HLA-B molecule was involved in the process of specific antigen presentation. The calculations showed that there was no significant genetic correlation between BP and DM. Our study identified three significant loci in the MHC region, proving that the HLA region was significantly correlated with BP and DM separately. Our research highlights the key role of the MHC region in disease susceptibility.

Impact of Different Oak Chips' Aging on the Volatile Compounds and Sensory Characteristics of Vitis amurensis Wines.

In this work, different oak chips were used to age Vitis amurensis wine, and the effects on sensory properties were observed. Twenty-one different oak chips were added to a one-year-old wine made by a traditional technique. The wine was aged for 6 months before analysis by CIELab for color parameters, GC-MS for volatile compounds, and electronic tongue and a tasting panel for sensory properties. The results showed that the addition of any tested oak chip could significantly strengthen the wine's red color. Among 61 volatile compounds, alcohols presented the highest concentrations (873 to 1401 mg/L), followed by esters (568 to 1039 mg/L) and organic acids (157 to 435 mg/L), while aldehydes and volatile phenols occurred at low concentrations. Different oak species with different toasting levels could affect, to varying degrees, the concentrations of esters, alcohols, and volatile phenols, but to a lesser extent those of aldehydes. Sensory analysis by a tasting panel indicated that non- and moderately roasted oak chips gave the wines higher scores than those with heavy toasting levels. The major mouthfeel descriptors determined by electronic tongue were in good agreement with those from the tasting panel.

Ultrathin-FeOOH-Coated MnO2 Sonosensitizers with Boosted Reactive Oxygen Species Yield and Remodeled Tumor Microenvironment for Efficient Cancer Therapy.

Sonodynamic therapy (SDT) typically suffers from compromised anticancer efficacy owing to the low reactive oxygen species (ROS) yield and complicated tumor microenvironment (TME) which can consume ROS and support the occurrence and development of tumors. Herein, ultrathin-FeOOH-coated MnO2 nanospheres (denoted as MO@FHO) as sonosensitizers which can not only facilitate ultrasound (US)-triggered ROS but also tune the TME by hypoxia alleviation, H2 O2 consumption as well as glutathione (GSH) depletion are designed. The FeOOH coating will boost the production yield of singlet oxygen (1 O2 ) and hydroxyl radicals (• OH) by inhibiting the recombination of US-initiated electron-hole pairs and Fenton-like reaction, respectively. Additionally, the catalase-like and GSH peroxidase-like activities of MO@FHO nanospheres enable them to break the TME equilibrium via hypoxia alleviation and GSH depletion. The combination of high ROS yield and fundamental destruction of TME equilibrium results in satisfactory antitumor outcomes, as demonstrated by the high tumor suppression efficacy of MO@FHO on MDA-MB-231-tumor-bearing mice. No obvious toxicity is detected to normal tissues at therapeutic doses in vivo. The capability to modulate the ROS production and TME simultaneously can afford new probability for the development of advanced sonosensitizers for synergistic comprehensive cancer therapy.

The Impact of a Multifaceted Pharmacist-Led Antimicrobial Stewardship Program on Antibiotic Use: Evidence From a Quasi-Experimental Study in the Department of Vascular and Interventional Radiology in a Chinese Tertiary Hospital.

Objective: The objective of the study was to assess the impact of multifaceted clinical pharmacist-led antimicrobial stewardship (AMS) program on the rational use of antibiotics for patients who receive vascular and interventional radiology therapies. Methods: A quasi-experimental retrospective intervention design with a comparison group was applied to the practice of antibiotic use in the department of vascular and interventional radiology in a Chinese tertiary hospital. We used difference-in-differences (DID) analysis to compare outcomes before and after the AMS intervention between the intervention group and control group, to determine whether intervention would lead to changes in irrationality of antibiotic prescribing, antibiotic utilization, cost of antibiotics, and length of hospital stay. Results: The DID results showed that the intervention group was associated with a reduction in the average consumption of antibiotics (p = 0.017) and cost of antibiotics (p = 0.006) and cost per defined daily dose (DDD) (p = 0.000). There were no significant differences in the mean change of total costs and length of stay between the two groups (p > 0.05). The average inappropriate score of perioperative antimicrobial prophylaxis in the intervention group declined by 0.23, while it decreased by 0.02 in the control group [0.21 (95% CI, -0.271 to -0.143); p = 0.000]. The average inappropriate score of non-surgical antimicrobial prophylaxis in the intervention group declined by 0.14, while it increased by 0.02 in the control group [0.16 (95% CI, -0.288 to -0.035); p = 0.010]. The average inappropriate score of the therapeutic use of antibiotics in the intervention group declined by 0.07, while it decreased by 0.01 in the control group [0.06 (95% CI, -0.115 to -0.022); p = 0.003]. Conclusions: This study provides evidence that implementation of AMS interventions was associated with a marked reduction of antibiotic use, cost of antibiotics, and irrationality of antibiotic prescribing in China.