Defective ZnIn2S4 Nanosheets for Visible-Light and Sacrificial-Agent-Free H2O2 Photosynthesis via O2/H2O Redox.

H2O2 photosynthesis has attracted great interest in harvesting and converting solar energy to chemical energy. Nevertheless, the high-efficiency process of H2O2 photosynthesis is driven by the low H2O2 productivity due to the recombination of photogenerated electron-hole pairs, especially in the absence of a sacrificial agent. In this work, we demonstrate that ultrathin ZnIn2S4 nanosheets with S vacancies (Sv-ZIS) can serve as highly efficient catalysts for H2O2 photosynthesis via O2/H2O redox. Mechanism studies confirm that Sv in ZIS can extend the lifetimes of photogenerated carriers and suppress their recombination, which triggers the O2 reduction and H2O oxidation to H2O2 through radical initiation. Theoretical calculations suggest that the formation of Sv can strongly change the coordination structure of ZIS, modulating the adsorption abilities to intermediates and avoiding the overoxidation of H2O to O2 during O2/H2O redox, synergistically promoting 2e- O2 reduction and 2e- H2O oxidation for ultrahigh H2O2 productivity. The optimal catalyst displays a H2O2 productivity of 1706.4 µmol g-1 h-1 under visible-light irradiation without a sacrificial agent, which is ∼29 times higher than that of pristine ZIS (59.4 µmol g-1 h-1) and even much higher than those of reported photocatalysts. Impressively, the apparent quantum efficiency is up to 9.9% at 420 nm, and the solar-to-chemical conversion efficiency reaches ∼0.81%, significantly higher than the value for natural synthetic plants (∼0.10%). This work provides a facile strategy to separate the photogenerated electron-hole pairs of ZIS for H2O2 photosynthesis, which may promote fundamental research on solar energy harvest and conversion.

Response to Comment on "Dying in the Sun: Direct evidence for elevated UV-B radiation at the end-Permian mass extinction".

Seddon and Zimmermann have raised questions about the evidence for increased UV-B flux across the end-Permian mass extinction (EPME) that was presented in our recent study, specifically regarding the measurement of UV-B-absorbing compound (UAC) levels in fossil pollen. We respond to these points, arguing that the comparison of FTIR spectra of >250 million-year-old Permian fossil pollen with ~700-year-old subfossil pollen is not valid and that negligible nonrandom interference derived from water vapor fluctuations during data generation cannot coincidentally produce a substantial UAC peak during the EPME. Furthermore, we refute the suggestion that the measured aromatic peak at 1600 cm-1 could have been influenced by diagenetic products from other organic constituents of pollen. The most productive route forward will be to generate sporomorph geochemical data from additional Permian-Triassic boundary sections to test the results put forward in our study.

Postoperative C-Reactive Protein Predicts Postoperative Delirium in Colorectal Cancer Following Surgery.

Background: Postoperative delirium (POD) is a common complication in operative patients. Neuroinflammation has been reported to be a potential mechanism associated with the development of POD. Identifying available inflammatory markers such as C-reactive protein (CRP) would aid clinicians in early detection of POD. Previous studies have demonstrated that CRP may be a promising predictive marker for POD. Thus, this study aimed to explore the association between CRP and POD among those elderly colorectal cancer (CRC) patients. Methods: 643 patients with CRC were included in this study. CRP levels were measured before operation and on postoperative day 1. The univariate and multivariate regression analyses were used to identify risk factors for POD. Results: Of 643 patients with CRC, 112 cases (17.4%) had POD. CRC patients with POD showed older age, higher CRP level on postoperative day 1, and higher percentage of smoking, diabetes mellitus, and chronic obstructive pulmonary disease (COPD) than CRC patients without POD. Preoperative CRP level was not associated with the POD. Univariate and multivariate regression analyses showed that older age (> 70 years), diabetes mellitus, COPD, and higher CRP level on postoperative day 1 (> 48 mg/L) were risk factors for POD in CRC patients. Conclusion: Postoperative CRP level is an independent indicator for POD among CRC patients, suggesting the predictive role of postoperative CRP levels for POD in elderly CRC patients undergoing surgery.

Glycyrrhizic acid alleviates liver fibrosis in vitro and in vivo via activating CUGBP1-mediated IFN-γ/STAT1/Smad7 pathway.

BACKGROUND: Hepatic fibrosis, a common pathological feature of chronic liver injuries, is a serious public health problem and lacks effective therapy. Glycyrrhizic acid (GA) is a bioactive ingredient in the root of traditional Chinese medicine licorice, and exhibits remarkable anti-viral, anti-inflammatory and hepatoprotective actions. PURPOSE: Here we aimed to investigated whether GA provided a therapeutic efficacy in hepatic fibrosis and uncover its molecular mechanisms. STUDY DESIGN AND METHODS: We investigated the anti-fibrosis effects of GA using CCl4-induced mouse mode of liver fibrosis as well as TGF-ß1-activated human LX-2 cells and primary hepatic stellate cells (HSCs). CUGBP1-mediated IFN-γ/STAT1/Smad7 signaling was examined with immunofluorescence staining and western blot analysis. We designed and studied the binding of GA to CUGBP1 using in silico docking, and validated by microscale thermophoresis (MST) assay. RESULTS: GA obviously attenuated CCl4-induced liver histological damage, and reduced serum ALT and AST levels. Meanwhile, GA decreased liver fibrogenesis markers such as α-SMA, collagen α1, HA, COL-III, and LN in the hepatic tissues. Mechanistically, GA remarkably elevated the levels of IFN-γ, p-STAT1, Smad7, and decreased CUGBP1 in vivo and in vitro. Over-expression of CUGBP1 completely abolished the anti-fibrotic effect of GA and regulation on IFN-γ/STAT1/Smad7 pathway in LX-2 cells and primary HSCs, confirming CUGBP1 played a pivotal role in the protection by GA from liver fibrosis. Further molecular docking and MST assay indicated that GA had a good binding affinity with the CUGBP1 protein. The dissociation constant (Kd) of GA and CUGBP1 was 0.293 µM. CONCLUSION: Our study demonstrated for the first time that GA attenuated liver fibrosis and hepatic stellate cell activation by promoting CUGBP1-mediated IFN-γ/STAT1/Smad7 signalling pathways. GA may be a potential candidate compound for preventing or reliving liver fibrosis.

Dying in the Sun: Direct evidence for elevated UV-B radiation at the end-Permian mass extinction.

Land plants can adjust the concentration of protective ultraviolet B (UV-B)-absorbing compounds (UACs) in the outer wall of their reproductive propagules in response to ambient UV-B flux. To infer changes in UV-B radiation flux at Earth's surface during the end-Permian mass extinction, we analyze UAC abundances in ca. 800 pollen grains from an independently dated Permian-Triassic boundary section in Tibet. Our data reveal an excursion in UACs that coincide with a spike in mercury concentration and a negative carbon-isotope excursion in the latest Permian deposits, suggesting a close temporal link between large-scale volcanic eruptions, global carbon and mercury cycle perturbations, and ozone layer disruption. Because enhanced UV-B radiation can exacerbate the environmental deterioration induced by massive magmatism, ozone depletion is considered a compelling ecological driver for the terrestrial mass extinction.

Oleanolic acid regulates the Treg/Th17 imbalance in gastric cancer by targeting IL-6 with miR-98-5p.

BACKGROUND: Gastric cancer (GC) was a type of malignant tumor with a very high fatality rate. Oleanolic acid (OA) was a class of pentacyclic triterpenes which was proved to have anti-cancer activity. While the specific molecular mechanism of OA's role in inhibiting GC was not fully understood. This study aimed to explore how OA played an anti-cancer role in GC. METHODS: Expression of miR-98-5p was examined using qPCR, and expression levels of Treg/Th17-related factors were evaluated using qPCR and western blot. Flow cytometry was conducted to assess the proportion of Treg cells and Th17 cells. Besides, dual luciferase reporter assay was performed to verify that IL-6 was a target of miR-98-5p. RESULTS: Downregulation of miR-98-5p and upregulation of Treg/Th17-related factors were observed in GC tissues. What's more, the Treg/Th17 imbalance was found in PBMCs of GC patients. Overexpression of miR-98-5p promoted balance of Treg/Th17 cells via directly targeting IL-6 to downregulate expression of IL-6. Finally, OA could promote balance of Treg/Th17 cells by upregulating expression of miR-98-5p. DISCUSSION: All our results proved that OA could promote balance of Treg/Th17 cells in GC by targeting IL-6 with miR-98-5p, indicating a potential drug for treatment of GC.

The preventive effect of seamless nursing care on pressure ulcer and related complications in elderly inpatients.

OBJECTIVE: To study the preventive effect of seamless nursing care on pressure ulcer and related complications in elderly inpatients. METHODS: This study was performed in 132 elderly patients aged over 65 years. According to the random number table, these patients were allocated to the control group (n=66) and the experimental group (n=66). Patients in the control group received routine care, while those in the experimental group received both routine care and seamless nursing care. The number and grade of pressure ulcer during hospitalization, average length of stay, satisfaction in care, and incidence of complications during hospitalization were compared between the two groups. RESULTS: The incidence of pressure ulcer in the experimental group, which consisted of grade 1 pressure ulcer (2 cases) was significantly lower than that in the control group (P=0.001), which consisted of grade 1 pressure ulcer (9 cases) and grade 2 pressure ulcer (5 cases). The incidence of complications (wound infection and muscle aches) in the experimental group was significantly lower than that in the control group (P<0.05). Compared with the control group, the average length of stay in the experimental group was decreased (P<0.001). Satisfaction with care in the experimental group was significantly higher than that in the control group (P<0.01). CONCLUSION: Seamless nursing care contributes to the reduced number of pressure ulcer, reduced incidence of related complications, and improved satisfaction with care.

Ligustrazine alleviates cyclophosphamide-induced hepatotoxicity via the inhibition of Txnip/Trx/NF-κB pathway.

AIMS: Cyclophosphamide (CP) is a common therapeutic drug for cancer, but exposure to CP can cause acute hepatotoxicity. This study aimed to elucidate the protective effects of Ligustrazine (2, 3, 5, 6-tetramethylpyrazine, TMP) on hepatotoxicity induced by CP or its active metabolite 4-hydroperoxycyclophosphamide (4-HC). MAIN METHODS: We presented a comprehensive investigation about the hepatoprotection of TMP on CP-induced mice and 4-HC-treated HSC-LX2 cells. Liver function was detected via enzyme-linked immunosorbent assay (ELISA). Hepatic histopathology analysis was performed via hematoxylin and eosin (H&E) and Masson staining. Survival of hepatocytes was detected by TUNEL assay. Related proteins in the thioredoxin (Trx)-interacting protein (Txnip)/Trx/Nuclear factor-kappa B (NF-κB) pathway were measured by western blotting. KEY FINDINGS: The results indicated that CP or 4-HC could increase the levels of alanine aminotransferase and aspartate aminotransferase, enhance inflammatory factors and oxidative indicators, and suppress the activity of oxidoreductases. Moreover, significant changes in liver histological structure, fibrosis, and cell death were observed through the activation of Txnip/Trx/NF-κB pathway. In contrast, administration of TMP significantly reversed these above changes. Furthermore, TMP intervention participated in the inhibition of NLRP3 inflammasome accompanied with pyroptosis, as well as upregulating Trx expression and downregulating p-NF-κB, while the protective effect of TMP was limited to the involvement of Txnip overexpression. SIGNIFICANCE: TMP treatment could significantly alleviate the hepatotoxicity process as evidenced by improving the structure and function of the liver, inhibiting oxidative stress and inflammation accompanied with pyroptosis, which was positively correlated with the inhibition of Txnip/Trx/NF-κB pathway.

miR-96 regulates liver tumor-initiating cells expansion by targeting TP53INP1 and predicts Sorafenib resistance.

Liver tumor-initiating cells (T-ICs) contribute to tumorigenesis, progression, recurrence and drug resistance of hepatocellular carcinoma (HCC). However, the underlying mechanism for the propagation of liver T-ICs remains unclear. In the present study, our finding shows that miR-96 is upregulated in liver T-ICs. Functional studies revealed that forced miR-96 promotes liver T-ICs self-renewal and tumorigenesis. Conversely, knockdown miR-96 inhibits liver T-ICs self-renewal and tumorigenesis. Mechanistically, miR-96 downregulates TP53INP1 via its mRNA 3'UTR in liver T-ICs. Furthermore, the miR-96 expression determines the responses of hepatoma cells to sorafenib treatment. Analysis of patient cohorts and patient-derived xenografts (PDXs) further demonstrate that the miR-96 may predict sorafenib benefits in HCC patients. Our findings revealed the crucial role of the miR-96 in liver T-ICs expansion and sorafenib response, rendering miR-96 as an optimal target for the prevention and intervention of HCC.

Twelve New Genomic Loci Associated With Bone Mineral Density.

Aiming to identify more genomic loci associated with bone mineral density (BMD), we conducted a joint association analysis of 2 genome-wide association study (GWAS) by the integrative association method multi-trait analysis of GWAS (MTAG). The first one is the single GWAS of estimated heel BMD (eBMD) in the UK biobank (UKB) cohort (N = 426,824), and the second one is the GWAS meta-analysis of total body BMD (TB-BMD) in 66,628 participants from 30 studies. Approximate conditional association analysis was performed in the identified novel loci to identify secondary association signal. Statistical fine-mapping was conducted to prioritize plausible credible risk variants (CRVs). Candidate genes were prioritized based on the analyses of cis- expression quantitative trait locus (cis-eQTL) and cis-protein QTL (cis-pQTL) information as well as the functional category of the SNP. By integrating the information carried in over 490,000 participants, this largest joint analysis of BMD GWAS identified 12 novel genomic loci at the genome-wide significance level (GWS, p = 5.0 × 10-8), nine of which were for eBMD and four were for TB-BMD, explaining an additional 0.11 and 0.23% heritability for the two traits, respectively. These loci include 1p33 (lead SNP rs10493130, peBMD = 3.19 × 10-8), 5q13.2 (rs4703589, peBMD = 4.78 × 10-8), 5q31.3 (rs9324887, pTB-BMD = 1.36 × 10-9), 6p21.32 (rs6905837, peBMD = 3.32 × 10-8), 6q14.1 (rs10806234, peBMD = 2.63 × 10-8), 7q21.11 (rs10806234, pTB-BMD = 3.37 × 10-8), 8q24.12 (rs11995866, peBMD = 6.72 × 10-9), 12p13.31 (rs1639122, peBMD = 4.43 × 10-8), 12p12.1 (rs58489179, peBMD = 4.74 × 10-8), 12q24.23 (rs75499226, peBMD = 1.44 × 10-8), 19q13.31 (rs7255083, pTB-BMD = 2.18 × 10-8) and 22q11.23 (rs13056137, pTB-BMD = 2.54 × 10-8). All lead SNPs in these 12 loci are nominally significant in both original studies as well as consistent in effect direction between them, providing solid evidence of replication. Approximate conditional analysis identified one secondary signal in 5q13.2 (rs11738874, pconditional = 5.06 × 10-9). Statistical fine-mapping analysis prioritized 269 CRVs. A total of 65 candidate genes were prioritized, including those with known biological function to bone development (such as FGF1, COL11A2 and DEPTOR). Our findings provide novel insights into a better understanding of the genetic mechanism underlying bone development as well as candidate genes for future functional investigation.

Two novel pleiotropic loci associated with osteoporosis and abdominal obesity.

Aiming to uncover a shared genetic basis of abdominal obesity and osteoporosis, we performed a bivariate GWAS meta-analysis of femoral neck BMD (FNK-BMD) and trunk fat mass adjusted by trunk lean mass (TFMadj) in 11,496 subjects from 6 samples, followed by in silico replication in the large-scale UK Biobank (UKB) cohort. A series of functional investigations were conducted on the identified variants. Bivariate GWAS meta-analysis identified two novel pleiotropic loci 12q15 (lead SNP rs73134637, p = 3.45 × 10-7) and 10p14 (lead SNP rs2892347, p = 2.63 × 10-7) that were suggestively associated and that were replicated in the analyses of related traits in the UKB sample (osteoporosis p = 0.06 and 0.02, BMI p = 0.03 and 4.61 × 10-3, N up to 499,520). Cis-eQTL analysis demonstrated that allele C at rs73134637 was positively associated with IFNG expression in whole blood (N = 369, p = 0.04), and allele A at rs11254759 (10p14, p = 9.49 × 10-7) was negatively associated with PRKCQ expression in visceral adipose tissue (N = 313, p = 0.04) and in lymphocytes (N = 117, p = 0.03). As a proof-of-principle experiment, the function of rs11254759, which is 235 kb 5'-upstream from PRKCQ gene, was investigated by the dual-luciferase reporter assay, which clearly showed that the haplotype carrying rs11254759 regulated PRKCQ expression by upregulating PRKCQ promoter activity (p = 4.60 × 10-7) in an allelic specific manner. Mouse model analysis showed that heterozygous PRKCQ deficient mice presented decreased fat mass compared to wild-type control mice (p = 3.30 × 10-3). Mendelian randomization analysis demonstrated that both FNK-BMD and TFMadj were causally associated with fracture risk (p = 1.26 × 10-23 and 1.18 × 10-11). Our findings may provide useful insights into the genetic association between osteoporosis and abdominal obesity.

The Correlation Between Fall Prevention Knowledge and Behavior in Stroke Outpatients.

BACKGROUND: Stroke outpatients have a high risk of falling. However, fall prevention measures in the community are insufficient to effectively reduce the fall rate among outpatients with stroke. We aimed to determine the correlation between fall prevention knowledge and behavior among outpatients with stroke and provide new strategies for community fall prevention. METHODS: We recruited 124 patients with stroke who were followed up in the outpatient department of a tertiary hospital in Zhuhai, China. Patients were assessed using a general information questionnaire, a fall prevention knowledge questionnaire for patients with stroke, and the Stroke Fall Prevention Behavior Scale. IBM SPSS 22.0 software was used for statistical analysis. RESULTS: The median fall prevention knowledge was 82.76 (68.97, 93.10) points, out of 100. The mean (SD) score for fall prevention behavior was 2.90 (0.52; range, 1-4) points. Fall prevention knowledge scores were positively related to those fall prevention behavior (Spearman r = 0.454, P < .01). CONCLUSION: Levels of fall prevention knowledge among outpatients with stroke were adequate, and this population had medium to high levels of fall prevention behavior. Better knowledge was accompanied with better prevention of falls. However, whether enriching the knowledge could lead to improvement of fall prevention is still undetermined.

Association of genetic variations in IL-6/IL-6R pathway genes with gastric cancer risk in a Chinese population.

Interleukin-6 (IL-6) and its receptor (IL-6R) were regarded to be responsible for the occurrence of gastric cancer for their regulation roles in the inflammation. The genetic variations in these two genes (IL-6: rs6949149, rs1800796, rs10499563 and IL-6R: rs2228145) have been suggested to be associated with gastric cancer risk. However, the published results were inconsistent among subjects of different ethnicity. To evaluate such an association in Chinese population, we carried out this case-control study based on 473 patients with gastric cancer and 474 healthy controls, whose genotypes were detected by the Sequenom MassARRAY platform, and Helicobacter pylori infection was assessed by immunogold testing kit. This study showed that rs1800796 CG genotype was associated with decreased risk of gastric cancer (adjusted OR=0.75, 95% CI: 0.57-0.99, p=0.043). The stratified analysis revealed that, in the Helicobacter pylori negative infection subgroup, rs2228145 AC (adjusted OR=0.64, 95% CI: 0.42-0.97) and AC/CC (adjusted OR=0.66, 95% CI: 0.45-0.99) genotypes were associated with decreased risk of gastric cancer, respectively. In contrast, in the Helicobacter pylori positive infection subgroup, rs10499563 TC (adjusted OR=0.64, 95% CI: 0.43-0.95), CC (adjusted OR=0.35, 95% CI: 0.14-0.90), TC/CC (adjusted OR=0.59, 95% CI: 0.40-0.87) genotype were associated with decreased gastric cancer risk, respectively. Moreover, in the male subgroup, rs1800796 CG (adjusted OR=0.61, 95% CI: 0.44-0.84) and CG/GG (adjusted OR=0.67, 95% CI: 0.49-0.91) genotype were associated with decreased risk of gastric cancer, respectively. In short, this study suggested that IL-6R rs2228145 and IL-6 rs10499563 genotype were associated with decreased risk of gastric cancer for the individuals with negative and positive Helicobacter pylori infection.

Hyperbaric oxygen therapy in acute ischemic stroke: a review.

Stroke, also known as cerebrovascular disease, is a common and serious neurological disease, which is also the fourth leading cause of death in the United States so far. Hyperbaric medicine, as an emerging interdisciplinary subject, has been applied in the treatment of cerebral vascular diseases since the 1960s. Now it is widely used to treat a variety of clinical disorders, especially hypoxia-induced disorders. However, owing to the complex mechanisms of hyperbaric oxygen (HBO) treatment, the therapeutic time window and the undefined dose as well as some common clinical side effects (such as middle ear barotrauma), the widespread promotion and application of HBO was hindered, slowing down the hyperbaric medicine development. In August 2013, the US Food and Drug Administration declared artery occlusion as one of the 13 specific indications for HBO therapy. This provides opportunities, to some extent, for the further development of hyperbaric medicine. Currently, the mechanisms of HBO therapy for ischemic stroke are still not very clear. This review focuses on the potential mechanisms of HBO therapy in acute ischemic stroke as well as the time window.

Interleukin-23A is associated with tumor growth in Helicobacter-pylori-related human gastric cancer.

BACKGROUND: Interleukin (IL)-23 is one of the newly identified inflammatory cytokines, and inflammation is also known to be related to the development of gastric cancer (GC). The role of IL-23 in gastric cancer, however, is largely unknown. In the present study, we investigated the expression and possible role of IL-23A in human GC. METHODS: The expression of IL-23A and IL-17A in human GC tissues was determined by immunohistochemistry, and the relationship between IL-23A expression and clinical characteristics of GC was investigated. The serum concentration of IL-23A and IL-17A was also tested by ELISA. The source and role of IL-23A in GC were studied in vitro by Flowcytometry, MTS (Owen's reagent) assay and Western blot. RESULTS: IL-23A, IL-23 receptor (IL-23R) and IL-17A were all overexpressed in human GC tissues, and the level of IL-23A was well correlated with IL-17A in GC tissues as well as in patient's serum. Macrophages and GC cells were the main source of IL-23A secretion upon stimulation of H. pylori lysate. Furthermore, we found that IL-23A promoted proliferation of GC cell lines via IL-17A/IL-17 receptor antagonist (IL-17RA) /nuclear factor-κB (NF-κB) signaling. CONCLUSIONS: The high expression of IL-23A is associated with GC. IL-23A can promoted GC cells growth by inducing the secretion of IL-17A in tumor microenvironment. Our results suggest that the serum concentration of IL-23A is a good biomarker of poor clinical prognosis in GC patients.

IL1 receptor antagonist gene IL1-RN variable number of tandem repeats polymorphism and cancer risk: a literature review and meta-analysis.

IL1 receptor antagonist (IL1RA) and IL1beta (IL1ß), members of the pro-inflammatory cytokine interleukin-1 (IL1) family, play a potential role against infection and in the pathogenesis of cancers. The variable number of tandem repeats (VNTR) polymorphism in the second intron of the IL1 receptor antagonist gene (IL1-RN) and a polymorphism in exon 5 of IL1B (IL1B+3954C>T, rs1143634) have been suggested in predisposition to cancer risk. However, studies have shown inconsistent results. To validate any association, a meta-analysis was performed with 14,854 cases and 19,337 controls from 71 published case-control studies for IL1-RN VNTR and 33 eligible studies contained 7,847 cases and 8917 controls for IL1B +3954. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated from comparisons to assess the strength of the association. There was significant association between the IL1-RN VNTR polymorphism and the risk of cancer for any overall comparison. Furthermore, cancer type stratification analysis revealed that there were significantly increased risks of gastric cancer, bladder cancer and other cancer groups. Infection status analysis indicated that the H. pylori or HBV/HCV infection and IL1-RN VNTR genotypes were independent factors for developing gastric or hepatocellular cancers. In addition, a borderline significant association was observed between IL1B+3954 polymorphism and the increased cancer risk. Although some modest bias could not be eliminated, this meta-analysis suggested that the IL1-RN VNTR polymorphisms may contribute to genetic susceptibility to gastric cancer. More studies are needed to further evaluate the role of the IL1B+3954 polymorphism in the etiology of cancer.