Assessment of the combined vulnerability to droughts and heatwaves in Shandong Province in summer from 2000 to 2018.

Droughts and heat waves exhibit synergistic effects and are among the world's most costly disasters. To explore the spatiotemporal differences and formation mechanisms of the combined vulnerability to droughts and heat waves in Shandong Province over the past 20 years, a vulnerability scoping diagram (VSD) model with three dimensions-exposure, sensitivity, and adaptability-was constructed to assess and compare the combined vulnerability to high-temperature and drought events, considering economic and social conditions. The results showed that (1) over the past 20 years, heat waves and droughts have increased in Shandong Province. The number of high-temperature events significantly increased in the west and decreased along the eastern coast, and drought change was characterized by an increase in the south and a decrease in the north. (2) The combined exposure to summer droughts and heat waves in Shandong Province showed a significant increasing trend (P < 0.05) at a rate of approximately 0.072/10a; the combined sensitivity significantly decreased (P < 0.05) at a rate of approximately 0.137/10a, and the combined adaptability continued to increase at a rate of approximately 0.481/10a. (3) The combined vulnerability to summer droughts and heat waves in the western inland area of Shandong Province was high and gradually decreased toward the southeastern coast. The overall decrease trend was nonsignificant with a decrease of approximately 0.126/10a, and the decline rate decreased from northwest to southeast, in which Laiwu, Yantai, Jinan, and Zibo cities exhibited a significant decreasing trend (P < 0.05). Although the compound vulnerability of Shandong Province has decreased insignificantly, the frequency of combined drought and heat wave events has increased, and the combined vulnerability will increase in the future.

Neovagina Creation: A Novel Improved Laparoscopic Vecchietti Procedure in Patients with Mayer-Rokitansky-Küster-Hauster Syndrome.

STUDY OBJECTIVE: To report a new improved laparoscopic Vecchietti vaginoplasty in patients with congenital vaginal agenesis and to investigate its efficacy and safety. DESIGN: A retrospective descriptive and case-control study. SETTING: Single academic institution. PATIENTS: Women who were diagnosed with Mayer-Rokitansky-Küster-Hauster (MRKH) syndrome and underwent our new improved laparoscopic Vecchietti procedure from July 2010 to June 2019 were selected as the study group. The eligible participants had congenital vaginal agenesis with normal 46,XX karyotype and ovarian function. Age-matched, nulliparous, sexually active women were selected as the control group. INTERVENTIONS: Women with MRKH syndrome in the study group underwent the novel improved laparoscopic Vecchietti procedure. All participants in both groups were required to complete Female Sexual Function Index and Female Genital Self-Image Scale questionnaires. MEASUREMENTS AND MAIN RESULTS: The effects of our procedure, including the anatomic and functional efficacy of the neovagina, were the primary outcomes. The secondary outcomes consisted of the perioperative complications, surgical morbidities, and long-term postoperative discomfort. A total of 79 patients with MRKH syndrome underwent our new improved Vecchietti vaginoplasty, of whom 44 (55.7%) were diagnosed as Type I MRKH syndrome, whereas 35 (44.3%) were Type II MRKH syndrome. At a 30-month follow-up after surgery, an anatomic neovagina measuring 10.44 cm in length and 1.30 cm in width was achieved. All 79 patients obtained anatomic success with 92.41% of functional efficacy. Compared with 81 age-matched, nulliparous women in the control group, there was no statistical difference regardless of individual measure or total Female Sexual Function Index scores (p >.05). The Female Genital Self-Image Scale assessment showed a significantly lower score in patients undergoing the vaginoplasty (20.14 ± 3.05 vs 22.95 ± 2.12; p <.001). There were no severe perioperative complications except 1 mild bladder injury and 1 transient fever. CONCLUSION: Our novel improved laparoscopic Vecchietti vaginoplasty is a relatively safe and effective method for surgical treatment of congenital vaginal agenesis. It may be an alternative to neovagina creation for reaching satisfying anatomic and functional efficacy and improving patients' sexual function.

A Novel Cerclage Insertion: Modified Laparoscopic Transabdominal Cervical Cerclage with Transvaginal Removing (MLTCC-TR).

STUDY OBJECTIVE: To report on our center's experience of a novel modified approach for laparoscopic cervical cerclage and to evaluate its safety and efficacy preliminarily. DESIGN: Retrospective descriptive study. SETTING: Single academic institution. PATIENTS: Pregnant and nonpregnant women who underwent the modified laparoscopic transabdominal cervical cerclage with transvaginal removing (MLTCC-TR) from June 2016 to April 2019. Eligible participants had multiple adverse obstetric histories or the short cervix and were not suitable for a second transvaginal cerclage. INTERVENTIONS: Preconceptional or postconceptional MLTCC-TR. MEASUREMENTS AND MAIN RESULTS: A total of 24 participants (including 3 first-trimester singleton pregnant women) underwent the MLTCC-TR, giving birth to 27 infants. Among 21 women who underwent preconceptional cerclage, 26 cases of postoperational pregnancies were noted, and the incidence of term labor was 73.07%, which was significantly higher than that in the precerclage group (p <.001). Their mean gestational age at delivery was 37.21 ± 5.05 weeks. Among 3 cases of postconceptional cerclage, the mean gestational age at cerclage was 10.90 ± 2.61 weeks, and all of them had term delivery. The overall neonatal survival rate was 100% (27/27), of which 81.48% (22/27) were term infants. There were no severe perioperative complications directly related to the insertion of cerclage. CONCLUSION: Our new approach of MLTCC-TR may be a relatively effective, feasible, and safe treatment for cervical insufficiency. It may be considered as an acceptable alternative to the traditional laparoscopic cervical cerclage with its superiority of transvaginal removing.

Lysyl Hydroxylase Inhibition by Minoxidil Blocks Collagen Deposition and Prevents Pulmonary Fibrosis via TGF-ß1/Smad3 Signaling Pathway.

BACKGROUND Idiopathic pulmonary fibrosis (IPF) is a deadly disease characterized by excessive collagen in the extracellular matrix (ECM) of the lungs. Collagen is the primary protein component of the ECM. However, the exact mechanisms underlying the formation and deposition of collagen in the ECM under normal and pathological conditions remain unclear. Previous studies showed that lysyl hydroxylase (LH) plays a crucial role in the formation of collagen. Minoxidil is an FDA-approved anti-hypertensive agent that inhibits LH that reduces fibrosis. In this study, we investigated the functional roles of LHs (LH1, LH2, and LH3) in pulmonary fibrosis and the anti-fibrotic effects of minoxidil. MATERIAL AND METHODS Patient serum samples were examined for their expression of procollagen-lysine, 2-oxoglutarate 5-dioxygenases (PLOD) 1-3, the genes encoding LH 1-3. Mice with bleomycin (BLM 2.5 mg/kg)-induced pulmonary fibrosis were administered a minoxidil solution (30 mg/kg) by oral gavage. RESULTS The PLOD mRNA levels were significantly higher in the IPF patients than in the healthy control subjects. Minoxidil suppressed the BLM-induced pulmonary fibrosis in vivo. These effects were associated with blocking TGF-ß1/Smad3 signal transduction and attenuating the expression and activity of LHs, resulting in decreased collagen formation, thus reducing the pulmonary fibrosis. The anti-fibrotic effects of minoxidil may be mediated through competitive inhibition of LHs activity, resulting in decreased pyridine cross-link formation and collagen production and deposition. CONCLUSIONS The results of this study suggest that LH represents a target to prevent or treat pulmonary fibrosis, and minoxidil may provide an effective agent to inhibit LHs.

Glabridin arrests cell cycle and inhibits proliferation of hepatocellular carcinoma by suppressing braf/MEK signaling pathway.

Glabridin, an isoflavone isolated from licorice, owns a variety of pharmacological effects. Several reports have demonstrated that glabridin could regulate multiple cellular signaling pathways to inhibit the progression of cancer. However, the target proteins have not been elucidated yet. We used shape screening and induced fit docking to screen the protein data bank against glabridin. Braf and MEK1/2, important intermediate molecules of the braf/MEK cascade, were identified as the potential targets of glabridin. The experimental data showed that glabridin could inhibit the phosphorylation of MEK1/2 and the phosphorylation levels of downstream molecules including ERK1/2 and transcription factors ATF1 and CREB, but had no effect on the phosphorylation of braf. In particular, the in vitro pull-down assay indicated that glabridin selectively bound to braf and MEK1/2. What is more, exposure to glabridin significantly suppressed the proliferation of hepatocellular carcinoma HepG2 cell line. In addition, glabridin might arrest cell cycle in G1 through downregulation of cyclinD3, CDK2, and CDK4. In conclusion, glabridin is a potential multi-molecule-targeting inhibitor in the field of clinical prevention or treatment of cancer.

New insights on the palate, lung, and nasal epithelium clone (PLUNC) proteins: Based on molecular and functional analysis of its homolog of YH1/SPLUNC1.

The palate, lung, and nasal epithelium clone (PLUNC) proteins are intricate immune molecules and arisen questions from them are still unresolved. In order to identify the role of PLUNC family proteins, we had analyzed its homolog protein YH1/SPLUNC1, which highly expresses in nontumor nasopharyngeal epithelium while expresses weakly in nasopharyngeal carcinoma (NPC) tissues. It is found that YH1/SPLUNC1 protein expression level was higher in chronic normal nasopharynx inflammatory cells compared to NPC tissue cells. An approach to produce active YH1/SPLUNC1 protein had been established and recombinant YH1/SPLUNC1 protein could bind to all four Gram-positive and four Gram-negative bacteria we tested, and triggered the aggregation of those bacteria. Interestingly, YH1/SPLUNC1 protein has antimicrobial activity, and it can directly kill Escherichia coli and Acinetobacter haemolyticus. The microorganism cell showed morphological changes in cell wall such as cell damage and cytoplasmic leakage after exposure to YH1/SPLUNC1 protein, indicating that YH1/SPLUNC1 directly killed the microorganisms by cell wall permeabilization. All these results indicated that YH1/SPLUNC1 might be an important antimicrobial protein involved in innate immunity defense.

Mitogen- and stress-activated Kinase 1 mediates Epstein-Barr virus latent membrane protein 1-promoted cell transformation in nasopharyngeal carcinoma through its induction of Fra-1 and c-Jun genes.

BACKGROUND: Mitogen- and Stress-Activated Kinase 1 (MSK1) is a nuclear kinase that serves as active link between extracellular signals and the primary response of gene expression. However, the involvement of MSK1 in malignant transformation and cancer development is not well understood. In this study, we aimed to explore the role of MSK1 in Epstein-Barr virus (EBV) latent membrane protein 1 (LMP1)-promoted carcinogenesis of nasopharyngeal carcinoma (NPC). METHODS: The level of MSK1 phosphorylation at Thr581 was detected by the immunohistochemical analysis in NPC tissues and normal nasopharynx tissues, and its correlation with LMP1 was analyzed in NPC tissues and cell lines. Using MSK1 inhibitor H89 or small interfering RNA (siRNA)-MSK1, the effects of MSK1 on LMP1-promoted CNE1 cell proliferation and transformation were evaluated by CCK-8 assay, flow cytometry and focus-forming assay respectively. Furthermore, the regulatory role of MSK1-mediated histone H3 phosphorylation at Ser10 on the promoter activity and expression of Fra-1 or c-Jun was determined by reporter gene assay and western blotting analysis. RESULTS: Immunohistochemical analysis revealed that the level of MSK1 phosphorylation at Thr581 was significantly higher in the poorly differentiated NPC tissues than that in normal nasopharynx tissues (P < 0.001). Moreover, high level of phosphorylated MSK1 was positively correlated with the expression of LMP1 in NPC tissues (r = 0.393, P = 0.002) and cell lines. MSK1 inhibitor H89 or knockdown of MSK1 by siRNA dramatically suppressed LMP1-promoted CNE1 cell proliferation, which was associated with the induction of cell cycle arrest at G0/G1 phase. In addition, the anchorage-independent growth promoted by LMP1 was blocked in MSK1 knockdown cells. When the activity or expression of MSK1 was inhibited, LMP1-induced promoter activities of Fra-1 and c-Jun as well as their protein levels were greatly reduced. It was found that only H3 WT, but not mutant H3 S10A, dramatically increased LMP1 induction of Fra-1 and c-Jun genes compared with mock cells. CONCLUSION: Increased MSK1 activity is critically important for LMP1-promoted cell proliferation and transformation in NPC, which may be correlated with its induction of Fra-1 and c-Jun through phosphorylation of histone H3 at Ser10.

Pathological features of gastric­type endocervical adenocarcinoma: A report of two cases.

Gastric-type endocervical adenocarcinoma (GEA) is an uncommon form of uterine cervical adenocarcinoma with an unfavorable prognosis. The tumor consists of glands exhibiting a morphological resemblance to gastric cells and occasionally manifests features akin to pancreaticobiliary mucinous adenocarcinoma. GEA differs from the typical cervical cancer, particularly in its lack of association with the human papillomavirus. Immunophenotypic analysis suggests intestinal differentiation. The present study reports two cases of GEA occurring in postmenopausal individuals who were diagnosed in Lishui Central Hospital (Lishui, China) between January 2015 and January 2023. Microscopic examination revealed cysts lined with mucinous cells within the tumors. Immunohistochemical assays confirmed the positivity of the tumors for cytokeratin 7, mucin (MUC)5AC, and mutant tumor protein p53, while the results were negative for tumor suppressor p16, and in one case for paired box protein 8, consistent with characteristics of mucinous adenocarcinoma originating from the gastrointestinal tract. Programmed death-ligand 1 expression was also negative. The proto-oncogene K-ras was identified using amplification refractory mutation system polymerase chain reaction. Both cases were negative for mutations in codons 12 and 13 of exon 2, codon 61 of exon 3 and codon 146 of exon 4, but were positive for wild-type K-ras. Clinical follow-up revealed a potential association between histopathological features and resistance to chemotherapeutic drugs. The infrequency of this tumor type may contribute to diagnostic challenges.

Essential contribution of the JAK/STAT pathway to carcinogenesis, lytic infection of herpesviruses and pathogenesis of COVID­19 (Review).

The intracellular pathway of Janus kinase/signal transducer and activator of transcription (JAK/STAT) and modification of nucleosome histone marks regulate the expression of proinflammatory mediators, playing an essential role in carcinogenesis, antiviral immunity and the interaction of host proteins with Herpesviral particles. The pathway has also been suggested to play a vital role in the clinical course of the acute infection caused by severe acute respiratory syndrome coronavirus type 2 (SARS­CoV­2; known as coronavirus infection­2019), a novel human coronavirus initially identified in the central Chinese city Wuhan towards the end of 2019, which evolved into a pandemic affecting nearly two million people worldwide. The infection mainly manifests as fever, cough, myalgia and pulmonary involvement, while it also attacks multiple viscera, such as the liver. The pathogenesis is characterized by a cytokine storm, with an overproduction of proinflammatory mediators. Innate and adaptive host immunity against the viral pathogen is exerted by various effectors and is regulated by different signaling pathways notably the JAK/STAT. The elucidation of the underlying mechanism of the regulation of mediating factors expressed in the viral infection would assist diagnosis and antiviral targeting therapy, which will help overcome the infection caused by SARS­CoV­2.

Increased phosphorylation of histone H3 at serine 10 is involved in Epstein-Barr virus latent membrane protein-1-induced carcinogenesis of nasopharyngeal carcinoma.

BACKGROUND: Increased histone H3 phosphorylation is an essential regulatory mechanism for neoplastic cell transformation. We aimed to explore the role of histone H3 phosphorylation at serine10 (p-H3Ser10) in Epstein-Barr virus (EBV) latent membrane protein-1 (LMP1)-induced carcinogenesis of nasopharyngeal carcinoma (NPC). METHODS: The expression of p-H3Ser10 was detected by the immunohistochemical analysis in NPC, chronic nasopharyngitis and normal nasopharynx tissues, and its correlation with LMP1 was analyzed in NPC tissues and cell lines. Using the small interfering RNA (siRNA)-H3 and histone H3 mutant (S10A), the effect of histone H3 Ser10 motif on LMP1-induced CNE1 cell proliferation, transformation and activator protein-1 (AP-1) activation were evaluated by CCK-8, focus-forming and reporter gene assay respectively. Mitogen- and stress-activated kinase 1 (MSK1) kinase activity and phosphorylation were detected by in vitro kinase assay and western blot. Using MSK1 inhibitor H89 or siRNA-MSK1, the regulatory role of MSK1 on histone H3 phosphorylation and AP-1 activation were analyzed. RESULTS: Immunohistochemical analysis revealed that the expression of p-H3Ser10 was significantly higher in the poorly differentiated NPC tissues than that in chronic nasopharyngitis (p <0.05) and normal nasopharynx tissues (p <0.001). Moreover, high level of p-H3Ser10 was positively correlated with the expression of LMP1 in NPC tissues (χ2=6.700, p =0.01; C=0.350) and cell lines. The knockdown and mutant (S10A) of histone H3 suppressed LMP1-induced CNE1 cell proliferation, foci formation and AP-1 activation. In addition, LMP1 could increase MSK1 kinase activity and phosphorylation. MSK1 inhibitor H89 or knockdown of MSK1 by siRNA blocked LMP1-induced phosphorylation of histone H3 at Ser10 and AP-1 activation. CONCLUSION: EBV-LMP1 can induce phosphorylation of histone H3 at Ser10 via MSK1. Increased phosphorylation of histone H3 at Ser10 is likely a crucial regulatory mechanism involved in LMP1-induced carcinogenesis of NPC.

An update on viral association of human cancers.

Up to now, seven viruses that infect humans have been identified as oncogenic and are closely associated with different human cancers. Most of them encode oncogenes whose products play important roles in the development of cancers in the context of environmental and genetic factors; others may act via indirect mechanisms. The transforming activities of the human oncogenic viruses have much in common with the well-studied tumorigenic processes elicited by the acutely transforming murine retroviruses. Many of these mechanisms have been elucidated for or are represented in the successive steps leading to the efficient in vitro immortalization by the lymphotropic herpesvirus Epstein-Barr virus, although the establishment of malignancy in vivo takes longer. The development of cancer is a complicated process involving multiple factors, from the host and the environment. Although any one of these etiologic factors may exert an effect on the carcinogenic process, vaccination against the viral pathogen in several cases has shown efficacy in preventing the spread of the virus and, in turn, the development of the associated cancers. Modern laboratory techniques can be expected to facilitate the identification of new emerging viruses whose association with malignancies is suggested by epidemiologic and clinical data.

Synthesis, insecticidal activity, and structure-activity relationship (SAR) of anthranilic diamides analogs containing oxadiazole rings.

A series of anthranilic diamides analogs (3­11, 16­24) containing 1,2,4- or 1,3,4-oxadiazole rings were synthesized and characterized by (1)H NMR, MS and elemental analyses. The structure of 3-bromo-N-(2-(3-(4-bromophenyl)-1,2,4-oxadiazol-5-yl)-4-chloro-6-methylphenyl)-1-(3-chloropyridin-2-yl)-1H-pyrazole-5-carboxamide (18, CCDC-) was determined by X-ray diffraction crystallography. The insecticidal activities against Plutella xylostella and Spodoptera exigua were evaluated. The results showed that most of title compounds displayed good larvicidal activities against P. xylostella, especially compound 3-bromo-N-(4-chloro-2-methyl-6-(5-(methylthio)-1,3,4-oxadiazol-2-yl)phenyl)-1-(3-chloropyridin-2-yl)-1H-pyrazole-5-carboxamide (6), which displayed 71.43% activity against P. xylostella at 0.4 µg mL(-1) and 33.33% against S. exigua at 1 µg mL(-1). The structure-activity relationship showed that compounds decorated with a 1,3,4-oxadiazole were more potent than compounds decorated with a 1,2,4-oxadiazole, and different substituents attached to the oxadiazole ring also affected the insecticidal activity. This work provides some hints for further structure modification and the enhancement of insecticidal activity.

Increased glutathione and mitogen-activated protein kinase phosphorylation are involved in the induction of doxorubicin resistance in hepatocellular carcinoma cells.

AIM: The human hepatocellular carcinoma (HCC) cell line HepG2 can easily acquire resistance to doxorubicin. However, the mechanism of action is unclear. METHODS: In the present study, we used confocal microscopy, flow cytometry and other methods to reveal the mechanisms by which HepG2 cells acquire doxorubicin resistance. RESULTS: Our results showed that R-HepG2 cells, a doxorubicin-resistant sub-line of HepG2, exhibited decreased intracellular accumulation of doxorubicin and increased expression of P-glycoprotein (P-gp) and multidrug resistance-associated protein 1 when compared with HepG2 cells. R-HepG2 cells also harbored higher levels of glutathione and increased expression of glutathione peroxidase. Furthermore, we demonstrated that the phosphorylation of mitogen-activated protein kinases (p38 and c-jun-N-terminal kinases), IkBα and CREB were increased in R-HepG2 cells. Specific p38 inhibitor SB203580 decreased P-gp expression. The multi-kinase inhibitor sorafenib tosylate also significantly suppressed the phosphorylation of these proteins and inhibited the expression of P-gp. CONCLUSION: These findings reveal that the drug resistance could be acquired through mitogen-activated protein kinase-dependent upregulation of P-gp. This mechanism protects R-HepG2 cells from the anticancer action of doxorubicin.

The impact of the COVID-19 pandemic on physical activity and sleep among healthy adults: a systematic review and meta-analysis.

Background: The COVID-19 pandemic has had a significant impact on physical and mental health, while physical activity and sleep are two important indicators of the impact that have been explored in recent studies. However, the results of studies with different measurement methods and populations with different levels of physical activity have been diverse in that physical activity and sleep are affected by the COVID-19 pandemic in some studies but not in others. Our study aimed to investigate the impact of the COVID-19 pandemic on physical activity and sleep and the role of measurement methods and populations on results. Methods: PubMed, Web of Science, and CNKI databases were used to search for related studies systematically. Study characteristics and data on physical activity and sleep were collected and analyzed from each included study. Standardized mean differences (SMDs) with 95% confidence intervals (CIs) were used to estimate pooled effect sizes. Results: A total of 13 articles were included in the systematic review, 11 of which were included in the meta-analysis. We found that moderate-to-vigorous physical activity (MVPA) time was 0.33 (95% CI 0.07 to 0.59) and sleep quality was 0.37 (95% CI 0.21 to 0.53) decreased, while sleep duration was -0.24 (95% CI -0.28 to -0.20) increased during the lockdown; overall physical activity time had no significant difference (p = 0.07) during the lockdown. The "wearables" subgroup had no heterogeneity (p = 0.89, I2 = 0) in sleep duration, while MVPA time measured by subjective scales was not significantly changed. The "elite athletes" subgroup had lower heterogeneity (p = 0.69, I2 = 0) in sleep duration than general adults, while the results of sleep quality for population subgroups were significant and there was no heterogeneity within either. Conclusion: The COVID-19 pandemic had a significant impact on MVPA time, sleep duration, and sleep quality, instead of overall physical activity time among healthy adults. The results of MVPA time and sleep duration were greatly influenced by the measurement methods, and sleep behavior differed among populations with varying physical activity levels. Thus, when researching physical activity, especially MVPA time, should consider measurement methods, and more attention should be given to differences in populations when researching sleep behavior.

Epithelial-mesenchymal transition-related gene signature for prognosis of lung squamous cell carcinoma.

Epithelial-mesenchymal transition (EMT) is associated with tumor invasion and progression, and is regulated by DNA methylation. A prognostic signature of lung squamous cell carcinoma (LUSC) with EMT-related gene data has not yet been established. In our study, we constructed a co-expression network using differentially expressed genes (DEGs) obtained from The Cancer Genome Atlas (TCGA) to identify hub genes. We conducted a correlation analysis between the differentially methylated hub genes and differentially expressed EMT-related genes to screen EMT-related differentially methylated genes (ERDMGs). Functional enrichment was performed to annotate the ERDMGs. The least absolute shrinkage and selection operator (LASSO) and stepwise Cox regression analyses were performed to build a survival prognosis prediction model. Additionally, druggability analysis was performed to predict the potential drug targets of ERDMGs. We screened 11 ERDMGs that were enriched in cell adhesion molecules and other signaling pathways. Finally, we constructed a 4-ERDMG model, which showed good ability to predict survival prognosis in the training and validation sets. The model could serve as an independent predictive factor for patients with LUSC. Additionally, our druggability analysis predicted that CC chemokine ligand 23 (CCL23) and Hepatocyte nuclear factor 1b (HNF1B) may be the underlying drug targets of LUSC. We established a new risk score (RS) system as a prognostic indicator to predict the outcome of patients with LUSC, which will help in the improvement of treatment strategies.

Designing Robust Superhydrophobic Materials for Inhibiting Nucleation of Clathrate Hydrates by Imitating Glass Sponges.

Superhydrophobic surfaces are suggested to deal with hydrate blockage because they can greatly reduce adhesion with the formed hydrates. However, they may promote the formation of fresh hydrate nuclei by inducing an orderly arrangement of water molecules, further aggravating hydrate blockage and meanwhile suffering from their fragile surfaces. Here, inspired by glass sponges, we report a robust anti-hydrate-nucleation superhydrophobic three-dimensional (3D) porous skeleton, perfectly resolving the conflict between inhibiting hydrate nucleation and superhydrophobicity. The high specific area of the 3D porous skeleton ensures an increase in terminal hydroxyl (inhibitory groups) content without damaging the superhydrophobicity, achieving the inhibition to fresh hydrates and antiadhesion to formed hydrates. Molecular dynamics simulation results indicate that terminal hydroxyls on a superhydrophobic surface can inhibit the formation of hydrate cages by disordering the arrangement of water molecules. And experimental data prove that the induction time of hydrate formation was prolonged by 84.4% and the hydrate adhesive force was reduced by 98.7%. Furthermore, this porous skeleton still maintains excellent inhibition and antiadhesion properties even after erosion for 4 h at 1500 rpm. Therefore, this research paves the way toward developing novel materials applied in the oil and gas industry, carbon capture and storage, etc.

Advances in the Mechanistic Study of the Control of Oxidative Stress Injury by Modulating HDAC6 Activity.

Oxidative stress is defined as an injury resulting from a disturbance in the dynamic equilibrium of the redox environment due to the overproduction of active/radical oxygen exceeding the antioxidative ability of the body. This is a key step in the development of various diseases. Oxidative stress is modulated by different factors and events, including the modification of histones, which are the cores of nucleosomes. Histone modification includes acetylation and deacetylation of certain amino acid residues; this process is catalyzed by different enzymes. Histone deacetylase 6 (HDAC6) is a unique deacetylating protease that also catalyzes the deacetylation of different nonhistone substrates to regulate various physiologic processes. The intimate relationship between HDAC6 and oxidative stress has been demonstrated by different studies. The present paper aims to summarize the data obtained from a mechanistic study of HDAC6 and oxidative stress to guide further investigations on mechanistic characterization and drug development.

The effect of Tianjiang Xueshuantong Wan pills on ischemia-reperfusion injury after thrombolysis in acute cerebral infarction.

OBJECTIVE: The aim of this study is to investigate the effect of Tianjiang Xueshuantong Wan pills on reperfusion injury after venous thrombolysis in acute cerebral infarction. METHODS: The strategy used in this study is a randomised controlled clinical trial. In total, 72 cases were included, with 36 in the trial group and 36 in the control group, with a 1:1 ratio. Both groups were given standardised treatment for acute cerebral infarction. Based on the rt-PA intravenous thrombolysis, the test group took Tianjiang Xueshuantong Wan pills orally, whereas the control group solely utilised rt-PA for intravenous thrombolysis and did not take the test medicine orally. The patients' intracranial hemorrhage was clarified by head CT scan, and the occurrence of reperfusion injury was recorded during the entire trial. RESULTS: There were no significant differences in serum IL-6, MDA, SOD and TNF concentrations and NIHSS scores between the two groups before therapy (P > 0.05). After treatment, the serum concentrations of IL-6, MDA and TNF in the experimental group were significantly decreased compared with the control group, while the serum concentrations of SOD were significantly increased compared with the control group, with statistical significance (P > 0.05). After seven days of treatment, the total effective rate in the experimental group was 88.89%, while the data in the control group was 75%. There was a statistically significant difference between the experimental and control groups. CONCLUSION: Tianjiang Xueshuantong Wan pills can effectively prevent reperfusion injury following intravenous thrombolysis in individuals with cerebral infarction while improving patients' neurological deficits.

Vemurafenib induces a noncanonical senescence-associated secretory phenotype in melanoma cells which promotes vemurafenib resistance.

More than one half melanoma patients have BRAF gene mutation. BRAF inhibitor vemurafenib is an effective medication for these patients. However, acquired resistance is generally inevitable, the mechanisms of which are not fully understood. Cell senescence and senescence-associated secretory phenotype (SASP) are involved in extensive biological functions. This study was designed to explore the possible role of senescent cells in vemurafenib resistance. The results showed that vemurafenib treatment induced BRAF-mutant but not wild-type melanoma cells into senescence, as manifested by positive ß-galactosidase staining, cell cycle arrest, enlarged cellular morphology, and cyclin D1/p-Rb pathway inhibition. However, the senescent cells induced by vemurafenib (SenV) did not display DNA damage response, p53/p21 pathway activation, reactive oxygen species accumulation, decline of mitochondrial membrane potential, or secretion of canonical SASP cytokines. Instead, SenV released other cytokines, including CCL2, TIMP2, and NGFR, to protect normal melanoma cells from growth inhibition upon vemurafenib treatment. Xenograft experiments further confirmed that vemurafenib induced melanoma cells into senescence in vivo. The results suggest that vemurafenib can induce robust senescence in BRAFV600E melanoma cells, leading to the release of resistance-conferring cytokines. Both the senescent cells and the resistant cytokines could be potential targets for tackling vemurafenib resistance.

[Effects of Chinese Milk Vetch Returning Incorporated with Chemical Fertilizer Reduction on the Composition and Function of Soil Bacterial Communities in Paddy Fields].

Chinese milk vetch (Astragalus sinicus L.) is an important organic nutrient resource in the southern Henan rice-growing area. Thus, the effects of Chinese milk vetch (MV) returning incorporated with reduced chemical fertilizer on the physicochemical properties and bacterial community characteristics in paddy soil were studied. These results can provide a certain theoretical basis for the improvement of soil fertility and reduction of chemical fertilizer in this area. A field experiment was conducted for 12 consecutive years, involving six fertilization treatments (blank control, CK; 100% chemical fertilizer, F100; 80% chemical fertilizer+22.5 t·hm-2 MV, MV1F80; 80% chemical fertilizer+45 t·hm-2 MV, MV2F80; 60% chemical fertilizer+22.5 t·hm-2 MV, MV1F60; and 60% chemical fertilizer+45 t·hm-2 MV, MV2F60). The high-throughput sequencing method was used to compare the effects of different fertilization treatments on soil bacterial community diversity, composition, and structural characteristics. The FAPROTAX function prediction method was used to analyze the abundance differences of functional groups between different fertilization treatments. Additionally, combined with soil physicochemical properties and bacterial community characteristics, we explored the key soil environmental factors that changed the structure and functional characteristics of the soil bacterial community. Compared with that under CK, the soil bulk density (BD) under the MV returning incorporated with reduced chemical fertilizer treatment was decreased, whereas soil organic carbon (SOC), total nitrogen (TN), total phosphorus (TP), and total potassium (TK) were increased by 12.7%-35.5%, 38.2%-65.7%, 66.7%-95.2%, and 20.3%-31.6%, respectively. Compared with that under the F100 treatment, the Sobs index and Shannon diversity index of the bacterial community under the MV returning incorporated with reduced chemical fertilizer were decreased, and the Sobs index and Shannon diversity index were significantly positively correlated with BD (P<0.05) but significantly negatively correlated with SOC and TN (P<0.05). Compared with that under the F100 treatment, the relative abundances of Firmicutes under the MV1F80 and MV2F60 treatments were significantly increased by 82.2% and 67.4% (P<0.05), but the relative abundances of Acidobacteria were significantly reduced by 32.6% and 40.5% (P<0.05), respectively. The relative abundance of Actinobacteria under the MV2F60 treatment was significantly increased by 30.0% (P<0.05) compared with that under the F100 treatment. According to RDA analysis, soil SOC, TN, and TK were the main soil environmental factors that significantly affected bacterial community (P<0.05). Compared with that under CK and the F100 treatment, the abundance of functional groups of chemoheterotrophy, nitrogen fixation, fermentation, and ureolysis under the MV returning incorporated with reduced chemical fertilizer treatment were improved, whereas the abundance of functional groups of animal parasites or symbionts, all human pathogens, and human pathogen pneumonia were reduced, particularly under MV1F80 and MV2F60. To summarize, the long-term MV returning to the field incorporated with reduced chemical fertilizer improved the soil physical and chemical properties, thus changing the structure and functional characteristics of the soil bacterial communities, contributing to the improvement in the soil fertility, stability, and health of micro-ecosystems in paddy fields, thus ensuring the green and sustainable development of regional agriculture.