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In recent years, gut microbiota has become a hot topic in the fields of medicine and life sciences. Short-chain fatty acids (SCFAs), the main metabolites of gut microbiota produced by microbial fermentation of dietary fiber, play a vital role in healthy and ill hosts. SCFAs regulate the process of metabolism, immune, and inflammation and have therapeutic effects on gastrointestinal and neurological disorders, as well as antitumor properties. This review summarized the production, distribution, and molecular mechanism of SCFAs, as well as their mechanisms of action in healthy and ill hosts. In addition, we also emphasized the negative effects of SCFAs, aiming to provide the public with a more comprehensive understanding of SCFAs., (© 2024 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Eggshell translucency is a widespread issue in the field of egg quality. Previous research has established that the heritability of eggshell translucency is relatively low or moderate. Scientists have also successfully identified SNP loci related to eggshell translucency on different chromosomes by using gene chips and single-variant GWAS. However, the specific impact of single or multiple genes on the trait of eggshell translucency remains unknown. In an effort to investigate this, we examined 170 SNPs associated with eggshell translucency obtained by our research group. We selected 966 half-sibling laying hens from 2 generations in 3 pure lines: Dwarf Layer-White, Rhode Island Red-White Strain, and Rhode Island Red. Eggs were collected from each hen over a period of 5 consecutive days, and eggshell translucency was measured using a grading method in which the hens were divided into 2 groups: an opaque group and a translucent group. We collected blood samples from the laying hens and extracted DNA. Time of flight mass spectrometry (TOF-MS) was used for genotyping to identify SNP loci that influence the trait of eggshell translucency. The results of our analysis revealed that using TOF-MS in 3 chicken strains, we were able to eliminate loci with low gene polymorphism, genetic effect contribution less than 1%, and deviation from Hardy-Weinberg equilibrium. Ultimately, 5 SNPs (Affx-50362599, rs15050262, rs312943734, rs316121113, and rs317389181) were identified on chromosomes 1, 5, and 19. Additionally, nine candidate genes (DCN, BTG1, ZFP92, POU2F1, NUCB2, FTL, GGNBP2, ACACA, and TADA2A) were found to be associated with these SNPs. No linkage disequilibrium relationship was observed between the 2 pairs of SNP loci on chromosomes 1 and 19. Based on previous studies on the formation mechanism of eggshell translucency, we hypothesize that NUCB2, FTL, and ACACA genes may be affecting the eggshell structure through different mechanisms, such as increase the water permeability or make thin of eggshell membrane, which promote moisture or part of other egg contents and ultimately lead to the formation of eggshell translucency. These findings validate and identify five SNP loci that regulate the translucency trait, and provide molecular markers for breeding non-translucent populations. Furthermore, this study serves as a reference for further investigation of the genetic regulatory mechanisms underlying eggshell translucency., Competing Interests: DISCLOSURES The authors declare no conflicts of interest., (Copyright © 2024. Published by Elsevier Inc.)

Objectives: The current meta-analysis was performed to gather available evidence regarding the incidence and risk factors of cement leakage (CL) in patients undergoing surgical procedures for spinal metastasis., Methods: Two authors independently searched the PubMed, Embase, and CENTRAL databases. Clinical studies reporting the incidence or risk factors of CL were included for analysis. The primary outcome analyzed was the incidence of various types of CL. Random-effects or fixed-effects single-proportion meta-analyses were conducted to pool the available evidence, based on the heterogeneity test. Subgroup analyses were conducted based on surgical procedures (percutaneous vertebroplasty, percutaneous kyphoplasty, and others). Risk factors of CL were synthesized narratively to identify the most commonly accepted factors., Results: A total of 26 studies, involving 2551 patients, were included. The number of operated spine segments was reported in 23 studies, accounting for 4101 vertebrae. The pooled incidences of general, intradiscal, paravertebral, spinal canal, and intravascular CLs were 0.18 (95% confidence interval [CI], 0.11-0.28), 0.14 (95% CI, 0.08-0.21), 0.13 (95% CI, 0.06-0.21), 0.11 (95% CI, 0.05-0.19), and 0.12 (95% CI, 0.08-0.17), respectively. Subgroup analyses revealed significantly different incidences of general CL (0.37 vs. 0.06 vs. 0.09, P < 0.01), intradiscal CL (0.22 vs. 0.06 vs. 0.12, P < 0.01), paravertebral CL (0.25 vs. 0.03 vs. 0.06, P < 0.01), and vascular CL (0.14 vs. 0.03 vs. 0.15, P < 0.01) among the three groups. Posterior wall disruption, pathologic fracture, and the number of treated vertebral levels were the most commonly identified independent risk factors for general CL. Posterior wall disruption was determined as a common significant risk factor for spinal canal CL., Conclusions: This review provides insights into the incidence and risk factors associated with CL in surgical procedures for spinal metastasis. Understanding these risk factors can contribute to the development of tailored strategies aimed at minimizing CL occurrence and optimizing surgical outcomes for patients undergoing spinal metastatic surgery., (Copyright © 2024 Elsevier Inc. All rights reserved.)

A nickel-catalyzed reductive tandem cyclization of the elaborated β-bromo acetal with a dibenzoxepin scaffold was invented to strategically construct the remaining two rings in linoxepin. The generated diasterodivergent intermediates could be easily converted to both enantiomers of this unique cyclolignan molecule via facile oxidations, thus realizing enantiodivergent total synthesis of linoxepin for the first time.

Four undescribed sesquiterpene-shikimates (1-4), eight undescribed monoterpene-shikimates (5-12), together with two known ones were isolated and identified from the 95% ethanol extract of the plant endophytic fungus Phyllosticta capitalensis cultured in rice medium. Capitalensis A (1) was identified as the first sesquiterpene-shikimate-conjugated spirocyclic meroterpenoid degradation product, while capitalensis B (2) is a sesquiterpene-shikimate-conjugated spirocyclic meroterpenoid with a unique D-ring formed by a C-2-O-C-9' connection. The structures of these previously undescribed compounds were elucidated by multiple techniques, including IR, HR-ESI-MS, and NMR analysis. Furthermore, their absolute configurations were established through the comprehensive approach that involved the calculations of ECD spectra, optical rotation values, and single-crystal X-ray analysis. Moreover, the anti-inflammatory activity of all isolated compounds was evaluated using a lipopolysaccharide (LPS)-induced inflammation model in BV2 microglial cells. Meanwhile, these compounds exhibited activity in inhibiting NO production. Four compounds, capitalensis C (3), capitalensis D (4), 15-hydroxyl tricycloalternarene 5b (13) and guignarenone A (14) showed strong inhibitory effects with IC 50 values of 21.6 ± 1.33, 12.2 ± 1.08, 18.6 ± 1.27, and 15.8 ± 1.20 μM, respectively. In addition, the structure-activity relationship of the anti-inflammatory activity of the compounds was discussed., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Objective: To investigate the effects of methionine restriction on proliferation, cell cycle and apoptosis of human acute leukemia cells., Methods: Cell Counting Kit-8 (CCK-8) assay was used to detect the effect of methionine restriction on HL-60 and Jurkat cells proliferation. The effect of methionine restriction on cell cycle of HL-60 and Jurkat cells was examined by PI staining. Annexin V-FITC / PI double staining was applied to detect apoptosis of HL-60 and Jurkat cells following methionine restriction. The expression of cell cycle-related proteins cyclin B1, CDC2 and apoptosis-related protein Bcl-2 was evaluated by Western blot assay., Results: Methionine restriction significantly inhibited the proliferation of HL-60 and Jurkat cells in a time-dependent manner (HL-60: r =0.7773, Jurkat: r =0.8725), arrested the cells at G2/M phase ( P < 0.001), and significantly induced apoptosis of HL-60 and Jurkat cells (HL-60: P < 0.001; Jurkat: P < 0.05). Furthermore, Western blot analysis demonstrated that methionine restriction significantly reduced the proteins expression of Cyclin B1 ( P < 0.05), CDC2 ( P < 0.01) and Bcl-2 ( P < 0.001) in HL-60 and Jurkat cells., Conclusion: Acute leukemia cells HL-60 and Jurkat exhibit methionine dependence. Methionine restriction can significantly inhibit the proliferation, promote cell cycle arrest and induce apoptosis of HL-60 and Jurkat cells, which suggests that methionine restriction may be a potential therapeutic strategy for acute leukemia.

Objective: JieZe-1 (JZ-1), a Chinese herbal prescription, has an obvious effect on genital herpes, which is mainly caused by herpes simplex virus type 2 (HSV-2). Our study aimed to address whether HSV-2 induces pyroptosis of VK2/E6E7 cells and to investigate the anti-HSV-2 activity of JZ-1 and the effect of JZ-1 on caspase-1-dependent pyroptosis., Methods: HSV-2-infected VK2/E6E7 cells and culture supernate were harvested at different time points after the infection. Cells were co-treated with HSV-2 and penciclovir (0.078125 mg/mL) or caspase-1 inhibitor VX-765 (24 h pretreatment with 100 μmol/L) or JZ-1 (0.078125-50 mg/mL). Cell counting kit-8 assay and viral load analysis were used to evaluate the antiviral activity of JZ-1. Inflammasome activation and pyroptosis of VK2/E6E7 cells were analyzed using microscopy, Hoechst 33342/propidium iodide staining, lactate dehydrogenase release assay, gene and protein expression, co-immunoprecipitation, immunofluorescence, and enzyme-linked immunosorbent assay., Results: HSV-2 induced pyroptosis of VK2/E6E7 cells, with the most significant increase observed 24 h after the infection. JZ-1 effectively inhibited HSV-2 (the 50% inhibitory concentration = 1.709 mg/mL), with the 6.25 mg/mL dose showing the highest efficacy (95.76%). JZ-1 (6.25 mg/mL) suppressed pyroptosis of VK2/E6E7 cells. It downregulated the inflammasome activation and pyroptosis via inhibiting the expression of nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing protein 3 (P < 0.001) and interferon-γ-inducible protein 16 (P < 0.001), and their interactions with apoptosis-associated speck-like protein containing a caspase recruitment domain, and reducing cleaved caspase-1 p20 (P < 0.01), gasdermin D-N (P < 0.01), interleukin (IL)-1β (P < 0.001), and IL-18 levels (P < 0.001)., Conclusion: JZ-1 exerts an excellent anti-HSV-2 effect in VK2/E6E7 cells, and it inhibits caspase-1-dependent pyroptosis induced by HSV-2 infection. These data enrich our understanding of the pathologic basis of HSV-2 infection and provide experimental evidence for the anti-HSV-2 activity of JZ-1. Please cite this article as: Liu T, Shao QQ, Wang WJ, Liu TL, Jin XM, Xu LJ, Huang GY, Chen Z. The Chinese herbal prescription JieZe-1 inhibits caspase-1-dependent pyroptosis induced by herpes simplex virus-2 infection in vitro. J Integr Med. 2023; 21(3): 277-288., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Shanghai Changhai Hospital. Published by Elsevier B.V. All rights reserved.)

Benzyl bromides have been widely used for fullerene functionalization. However, the use of benzyl chlorides, a more affordable but less reactive counterpart of benzyl bromides, has been rarely reported. Herein, a new metal-mediated benzylation of C 60 with benzyl chlorides is presented. In this method, with the combinatorial use of Mn powder and Cu(OAc) 2 , various benzyl chloride derivatives could react with C 60 to afford 1,4-dibenzylated products in 12-53% yields. A mechanistic study by in situ visible near infrared (vis-NIR) spectroscopy and various control experiments suggests that, unlike the conventional anionic pathway that uses benzyl bromides, the transition-metal-mediated benzylation of C 60 with benzyl chlorides proceeds via a metal-mediated iterative single electron transfer process.

Background: Ban-xia-xie-xin-tang (BXXXT) has been applied in treating metabolic diseases, such as nonalcohol fatty liver disease, diabetes mellitus, and obesity. However, the underlying molecular mechanism of BXXXT in treating diabetes mellitus is unknown., Purpose: To clarify the underlying molecular mechanism of BXXXT in alleviating hepatic steatosis in high-fat diet (HFD)-fed mice., Methods: After 12 weeks of HFD treatment, mice were administered BXXXT for 4 weeks. The main chemical components of BXXXT were identified by UPLC-TQ-MS/MS. Indicators associated with insulin resistance and lipid metabolism were detected. The effect of improving glucose and lipid metabolism between BXXXT and the different components was compared. Differentially expressed genes (DEGs) were identified by hepatic transcriptomics. Key DEGs and proteins were further detected by real-time quantitative polymerase chain reaction, western blotting, immunohistochemistry, and immunofluorescence staining. LDs and mitochondria were detected by transmission electron microscopy., Results: First of all, our data demonstrated that the capacity to improve glucose and lipid metabolism for BXXXT was significantly superior to different components of BXXXT. BXXXT was found to improve HFD-induced insulin resistance. Moreover, BXXXT decreased weight, serum/hepatic triglycerides, total cholesterol, and FFAs to alleviate HFD-induced hepatic steatosis. According to the results of the hepatic transcription, Cidea and Cidec were identified as critical DEGs for promoting LD fusion and reducing FFAs β-oxidation in mitochondria and peroxisome resulting in hepatic steatosis, which was reversed by BXXXT., Conclusion: BXXXT ameliorates HFD-induced hepatic steatosis and insulin resistance by increasing Cidea and Cidec-mediated mitochondrial and peroxisomal fatty acid oxidation, which may provide a potential strategy for therapy of NAFLD and T2DM., (Copyright © 2022 The Authors. Published by Elsevier GmbH.. All rights reserved.)

Depression is a high-incidence mental illness that seriously affects human health. AQP4 has been reported to be closely associated with depression, while the underlying mechanism is still unclear. This work aimed to investigate the functional role of AQP4 in depression. Depression mouse model was constructed by administration of chronic social defeat stress (CSDS). We found that AQP4 was highly expressed in the hippocampal tissues of CSDS mice. AQP4 knockdown alleviated depression and enhanced the expression of NR2B and PSD95 in CSDS mice. Moreover, primary hippocampal neurons were treated with N-methyl-d-aspartate (NMDA) to induce neuron injury. AQP4 overexpression repressed cell viability and promoted apoptosis of NMDA-treated primary hippocampal neurons. AQP4 up-regulation repressed the expression of NR2B (surface), and enhanced the expression of NR2B (intracellular), P-NR2B, CaMK II and CK2 in the NMDA-treated primary hippocampal neurons. The influence conferred by AQP4 up-regulation was abolished by KN-93 (CaMK II inhibitor) or TBB (CK2 inhibitor) treatment. Rapamycin treatment enhanced the expression of NR2B (surface), and repressed the expression of AQP4, NR2B (intracellular) and P-NR2B in the primary hippocampal neurons by activating autophagy. The activated autophagy alleviated depression in CSDS mice by repressing AQP4 expression. In conclusion, our data demonstrated that autophagy ameliorated depression by repressing AQP4 expression in mice, and AQP4 knockdown promoted membrane trafficking of NR2B and inhibited phosphorylation of NR2B via CaMK II/CK2 pathway. Thus, our work suggests that AQP4 may be a promising molecular target for the development of antidepressant drugs., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Aim: Older adults living alone is becoming the main family structure in rural China. This study aimed to explore the mediating effect of coping style on the relationship between perceived stress and mental health in rural older adults living alone in China., Methods: 356 rural older adults living alone were recruited in Huzhou, China. Subjects were investigated using the Chinese Perceived Stress Scale (CPSS), Chinese Coping Style Questionnaire (CCSQ), and Mental Health Questionnaire (MHQ). Data were analysed using a structural equation. Bootstrapping was used to validate the mediation effects., Results: Mental health showed significant correlations with a sense of nervousness, of uncontrollability, and with positive and negative coping styles (P < 0.05). The results of structural equation modeling showed a good fit for the total sample (χ 2 /df = 2.684, NFI = 0.927, GFI = 0.944, RMSEA = 0.069). Perceived stress (sense of nervousness and uncontrollability) impacted the mental health of rural older adults living alone mainly through two mediating variables, including positive and negative coping styles. The double mediating contribution rates were 42.11%, and 61.82%., Conclusion: Coping style partially mediated the relationship between perceived stress and mental health of rural older adults living alone in China. Consequently, to improve the mental health of rural older adults living alone, perceived stress and coping styles should be the focus. Geriatr Gerontol Int 2022; 22: 523-528., (© 2022 Japan Geriatrics Society.)

Objective: This study aimed to evaluate the effectiveness of therapeutic lumbar drainage (LD) compared to therapeutic lumbar puncture (LP) for the management of intracranial hypertension (ICH) among HIV-positive patients with cryptococcal meningitis (CM)., Methods: The study was a multicenter prospective non-randomized interventional clinical trial. One hundred and sixteen HIV-associated CM patients were identified who presented with ICH (≥250 mmH 2 O). The LP group comprised 76 cases, while the LD group consisted of 40 cases. We compared mortality, intracranial pressure (ICP) normalization rate, and clinical symptom remission at 10 weeks, between the two groups., Results: The cumulative mortality at week 10 was 22.4% in the LP group and 20% in the LD group ( p  = .927), without any significant difference in mortality between the two groups. Improvement after treatment at 2-weeks, ICP normalization, and headache reversal event occurrence in the two groups showed no significant difference ( p  > .05). The incidence of CSF Cryptococcus clearance at two weeks in the LD group was significantly higher than in the LP group ( p  < .05). The frequency of invasive lumbar therapeutic procedures in the LP group during the first week was higher than that of the LD group ( p  < .05). Localized infection at the puncture site occurred more frequently in the LD group than in the LP group ( p  < .05)., Conclusion: For HIV-positive CM patients with an elevated ICP, LD and LP are comparably effective and safe options to normalize ICP. LP increases the frequency of invasive lumbar therapeutic procedures but does not incur more risk of infection events at the puncture site, while LD may accelerate CSF Cryptococcus clearance but may induce more frequent localized infection., Trial Registration: This study was registered as one of 12 trials under a general project at the Chinese Clinical Trial Registry (ChiCTR1900021195).

Background: Gastric cancer is the third deadliest cancer in the world and ranks second in incidence and mortality of cancers in China. Despite advances in prevention, diagnosis, and therapy, the absolute number of cases is increasing every year due to aging and the growth of high-risk populations, and gastric cancer is still a leading cause of cancer-related death. Gastric cancer is a consequence of the complex interaction of microbial agents, with environmental and host factors, resulting in the dysregulation of multiple oncogenic and tumor-suppressing signaling pathways. Global efforts have been made to investigate in detail the genomic and epigenomic heterogeneity of this disease, resulting in the identification of new specific and sensitive predictive and prognostic biomarkers. Trastuzumab, a monoclonal antibody against the HER2 receptor, is approved in the first-line treatment of patients with HER2+ tumors, which accounts for 13%-23% of the gastric cancer population. Ramucirumab, a monoclonal antibody against VEGFR2, is currently recommended in patients progressing after first-line treatment. Several clinical trials have also tested novel agents for advanced gastric cancer but mostly with disappointing results, such as anti-EGFR and anti-MET monoclonal antibodies. Therefore, it is still of great significance to screen specific molecular targets for gastric cancer and drugs directed against the molecular targets., Aim: To investigate the effect and mechanism of berberine against tumor growth in gastric cancer xenograft models and to explore the role of hepatocyte nuclear factor 4α (HNF4α)-WNT5a/β-catenin pathways played in the antitumor effects of berberine., Methods: MGC803 and SGC7901 subcutaneous xenograft models were established. The control group was intragastrically administrated with normal saline, and the berberine group was administrated intragastrically with 100 mg/kg/d berberine. The body weight of nude mice during the experiment was measured to assess whether berberine has any adverse reaction. The volume of subcutaneous tumors during this experiment was recorded to evaluate the inhibitory effect of berberine on the growth of MGC803 and SGC7901 subcutaneous transplantation tumors. Polymerase chain reaction assays were conducted to evaluate the alteration of transcriptional expression of HNF4α, WNT5a and β-catenin in tumor tissues and liver tissues from the MGC803 and SGC7901 xenograft models. Western blotting and IHC were performed to assess the protein expression of HNF4α, WNT5a and β-catenin in tumor tissues and liver tissues from the MGC803 and SGC7901 xenograft models., Results: In the both MGC803 and SGC7901 xenograft tumor models, berberine significantly reduced tumor volume and weight and thus retarded the growth rate of tumors. In the SGC7901 and MGC803 subcutaneously transplanted tumor models, berberine down-regulated the expression of HNF4α, WNT5a and β-catenin in tumor tissues from both transcription and protein levels. Besides, berberine also suppressed the protein expression of HNF4α, WNT5a and β-catenin in liver tissues., Conclusion: Berberine retarded the growth of MGC803 and SGC7901 xenograft model tumors, and the mechanism behind these anti-growth effects might be the downregulation of the expression of HNF4α-WNT5a/β-catenin signaling pathways both in tumor tissues and liver tissues of the xenograft models., Competing Interests: Conflict-of-interest statement: The authors declare no conflicts of interest regarding the publication of this paper., (©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.)

Background: Segmental testicular infarction is a rare condition that often occurs in the upper pole of the left testicle and usually presents with acute onset of scrotal pain. Contrast-enhanced ultrasound and MR are essential for diagnosing and differentiating segmental testicular infarction in clinical practice, and conservative treatment can only be adopted after a definitive diagnosis. In the present case, after conservative treatment, the infarct volume was reduced, the blood flow around the infarct was increased, and blood flow signals appeared in the infarct. We performed a correlation analysis to investigate the causes of these changes., Case Presentation: A 33-year-old male, without any specific disease history, was admitted to the hospital with a 5-day history of left testicular pain, and the imaging showed focal necrosis of the left testicle with hemorrhage. He was diagnosed with segmental testicular infarction after differentiating and excluding it from malignant tumors. Conservative medical treatment was given, and the symptoms of testicular pain were relieved after treatment. After discharge, regular reexamination at follow-ups showed that the infarct's size was reduced, the blood flow around the infarct was increased, and blood flow signals appeared in the infarct., Conclusion: Conservative treatment has become the standard treatment currently adopted after confirming the diagnosis of segmental testicular infarction through contrast-enhanced ultrasound and MR. The blood flow changes in and around the focus of testicular infarction can be related to various factors. At present, relevant conclusions of the underlying mechanisms were mainly deduced from infarction studies of other related organs such as the heart and brain; thus, the specific pathological mechanism needs further experimental verification., (© 2022. The Author(s).)

The Grubbs G-I or G-II catalyst gives the ruthenium ethoxy carbene complex, which catalyzes ring-opening cross metathesis (ROCM) of a strained cyclic alkene to give a diene where one of the two alkene moieties in the product contains an ethoxy substituent. No polymeric products are detected. Hydrocarbons such as parent norbornene or substituted cyclopropenes can proceed with the reaction smoothly. Tertiary amines, N -alkylimides, esters, and aryl or alkyl bromides remain intact under the reaction conditions. In addition to vinyl ethers, vinylic esters can also be used. The time required to reach a 50% yield of the ROCM product t 50 varies from 0.01 to 140 h depending on the strain and nucleophilicity of the double bond. Anchimeric participation of an electron-rich group would result in significant enhancement of the reactivity, and the t 50 could be as short as several minutes. A similar substrate without such a neighboring group shows a much slower rate. An exo -norborne derivative reacts much faster than the corresponding endo -isomer. Alkenes with poor nucleophilicity are less favored for the ROCM process, so is less strained cyclooctene.

Background: Group B streptococcus (GBS) is a leading cause of serious infection in infants. Understanding its regional molecular epidemiology is helpful for regulating efficient prevention practice., Methods: A retrospective study was conducted to collected data from infants and pregnant women with culture-proven GBS disease in the largest women and children's medical center in Shanxi between January 2017 and September 2019. All GBS isolates were analyzed by multi-locus sequence typing (MLST) as well as distribution of pilus island (PI) genes., Results: A total of 54 GBS isolates were obtained from 36 (66.7%) pregnant women and 18 (33.3%) infants with invasive disease. Among invasive GBS strains, the most common sequence type was ST10 (72.2%, P < 0.05), followed by ST23 and ST19. The ST10 strain was also the leading sequence type in colonizing pregnant women (44.4%, P < 0.05). All of the isolates carried at least one pilus island. The most frequently detected pilus island was PI-1+PI-2a (85.2%, P < 0.05), followed in turn by PI-2a and PI-2b., Conclusions: Our study demonstrates that one hypervirulent clone, sequence type 10, accounts for a large proportion of invasive GBS disease in infants and colonizing pregnant women, and the PI-1+PI-2a sub-lineages should be noted in infant infections., Competing Interests: Declaration of Competing Interest No potential conflict of interest was reported by the authors., (Copyright © 2020. Published by Elsevier B.V.)

Chicken coccidiosis is a kind of parasitic protozoosis caused by Eimeria parasitizing in the chicken intestinal epithelial cells. Eimeria tenella is considered as a significantly virulent and harmful parasite. At present, drug resistance remains a major problem and a large number of drug residues have been found to be produced in the treatment of the disease. Hence, novel strategies are needed to avoid the harmful effects caused by the generation of various chemical drug residues to the human body and also reduce the economic loss caused by coccidiosis to the chicken industry. In this study, natural garlic essential oil was used to control Eimeria tenella infection. The anticoccidial index (ACI) was calculated according to the clinical symptoms, body weight gain, oocyst excretion and cecal lesions. The immune organ index and serum biochemical indexes were measured to verify the possible anticoccidial effects. The results showed that: compared with the infected group, continuous feeding of different doses of natural garlic essential oil could significantly reduce the clinical symptoms, cecal lesions, the number of oocysts, but increase the weight of sick chickens, and effectively improve the intestinal functions. Moreover, compared with diclazuril control group, 0.06 mL/L garlic essential oil exhibited similar anticoccidial index. The content of immune organ index, serum biochemical index IgM, IgG and IgA in 0.06 mL/L garlic essential oil group was the highest, which indicated that garlic essential oil had a significant tendency to improve the immune function of the chickens. This study also showed that the natural garlic essential oil exhibited the same beneficial effects as that of diclazuril on chicken coccidiosis, and the anti-coccidiosis index of 0.06 mL/L garlic essential oil was favorable. Thus based on the above evidences and its relatively low cost, garlic essential oil can be potentially be used as an efficient anti parasitic drug., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Epidemiological studies have demonstrated that the genetic factors partly influence the development of same-sex sexual behavior, but most genetic studies have focused on people of primarily European ancestry, potentially missing important biological insights. Here, we performed a two-stage genome-wide association study (GWAS) with a total sample of 1478 homosexual males and 3313 heterosexual males in Han Chinese populations and identified two genetic loci (rs17320865, Xq27.3, FMR1NB, P meta  = 8.36 × 10 -8 , OR = 1.29; rs7259428, 19q12, ZNF536, P meta  = 7.58 × 10 -8 , OR = 0.75) showing consistent association with male sexual orientation. A fixed-effect meta-analysis including individuals of Han Chinese (n = 4791) and European ancestries (n = 408,995) revealed 3 genome-wide significant loci of same-sex sexual behavior (rs9677294, 2p22.1, SLC8A1, P meta  = 1.95 × 10 -8 ; rs2414487, 15q21.3, LOC145783, P meta  = 4.53 × 10 -9 ; rs2106525, 7q31.1, MDFIC, P meta  = 6.24 × 10 -9 ). These findings may provide new insights into the genetic basis of male sexual orientation from a wider population scope. Furthermore, we defined the average ZNF536-immunoreactivity (ZNF536-ir) concentration in the suprachiasmatic nucleus (SCN) as lower in homosexual individuals than in heterosexual individuals (0.011 ± 0.001 vs 0.021 ± 0.004, P = 0.013) in a postmortem study. In addition, compared with heterosexuals, the percentage of ZNF536 stained area in the SCN was also smaller in the homosexuals (0.075 ± 0.040 vs 0.137 ± 0.103, P = 0.043). More homosexual preference was observed in FMR1NB-knockout mice and we also found significant differences in the expression of serotonin, dopamine, and inflammation pathways that were reported to be related to sexual orientation when comparing CRISPR-mediated FMR1NB knockout mice to matched wild-type target C57 male mice., (© 2021. The Author(s).)

Background: Wutou Decoction (WTD), as a classic prescription, has been generally used to treat rheumatoid arthritis (RA) for two thousand years in China. However, the potential protective effects of WTD on rheumatoid arthritis and its possible mechanism have rarely been reported. Purpose: The aim of this study was to explore the possible mechanism of WTD against RA and a promising alternative candidate for RA therapy. Methods: A model of collagen-induced arthritis (CIA) was constructed in rats to assess the therapeutic effects of WTD. Histopathological staining, immunofluorescence, and western blotting of synovial sections were conducted to detect the antiangiogenic effects of WTD. Then, cell viability assays, flow cytometry, scratch healing assays, and invasion assays were conducted to explore the effects of WTD on MH7A human fibroblast-like synoviocyte (FLS) cell proliferation, apoptosis, migration, and invasion in vitro . The ability of WTD to induce blood vessel formation after MH7A cell and human umbilical vein endothelial cell line (HUVEC) coculture with WTD intervention was detected by a tube formation assay. The mechanisms of WTD were screened by network pharmacology and confirmed by in vivo and in vitro experiments. Results: WTD ameliorated the symptoms and synovial pannus hyperplasia of CIA rats. Treatment with WTD inhibited MH7A cell proliferation, migration, and invasion and promoted MH7A apoptosis. WTD could inhibit MH7A cell expression of proangiogenic factors, including VEGF and ANGI, to induce HUVEC tube formation. Furthermore, the PI3K-AKT-mTOR-HIF-1α pathway was enriched as a potential target of WTD for the treatment of RA through network pharmacology enrichment analysis. Finally, it was confirmed in vitro and in vivo that WTD inhibits angiogenesis in RA by interrupting the PI3K-AKT-mTOR-HIF-1α pathway. Conclusion: WTD can inhibit synovial hyperplasia and angiogenesis, presumably by inhibiting the migration and invasion of MH7A cells and blocking the production of proangiogenic effectors in MH7A cells. The possible underlying mechanism by which WTD ameliorates angiogenesis in RA is the PI3K-AKT-mTOR-HIF-1α pathway., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Ba, Huang, Shen, Huang, Wang, Han, Lin, Yan, Xu, Qin, Chen and Tu.)

Objective: To explore the protective effect and the underlying mechanism of Hu-Lu-Ba-Wan (, HLBW) on the testis of diabetic rats., Methods: Twenty-four male Wistar rats (160-180 g) were randomly divided into 3 groups according to a random number table, including a control group (n=8), diabetic group (n=8), and HLBW group (n=8). Diabetic rat model was established by high-fat-diet administration and single intravenous injection of streptozotocin (26 mg/kg). Then HLBW granule was administrated for 12 weeks. Fasting blood glucose and insulin levels as well as serum total testosterone level and testicular testosterone content were examined. Oxidative stress markers in both serum and testis were tested. Meanwhile, testicular morphology was observed under hematoxylin and eosin (HE) and the ultrastructure of Leydig cell was observed by electron microscope. The superoxide anion level was detected by DHE, and TUNEL-positive cells of testis was evaluated by TUNEL assay. The gene and protein expression of protein kinase C (PKCα), phosphorylated PKCα (P-PKCα) and P47phox in testicular tissues were determined by quantitative RT-PCR analysis and Western bolt analysis., Results: Compared with the diabetic group, HLBW treatment significantly reduced the fasting glucose levels and increased the levels of fasting insulin and testosterone in serum (P<0.01). HLBW administration also reduced the levels of reactive oxygen species (ROS) in plasma and alleviated the damage of oxidative stress in the testis of diabetic rats. Additionally, HLBW down-regulated the protein and mRNA levels of PKCα, P-PKCα and P47phox in testicular tissues., Conclusion: HLBW may attenuate the oxidative stress in the testis of diabetic rats via PKCα /NAPDH oxidase signaling pathway.

Background: Group B streptococcus (GBS) is a leading cause of serious infections in infants. The extensive use of tetracycline has led to the selection of specific resistant and infectious GBS clones. The sequence type (ST) 10 GBS strain, causing invasive infections in infants, is becoming prevalent in China. We aimed to understand the clinical and microbiological characteristics of this GBS strain., Methods: We conducted a retrospective study on infants with invasive GBS disease from the largest women's and children's medical center in Shanxi and collected data between January 2017 and October 2020. GBS isolates were analyzed by capsule serotyping, genotyping, antibiotic resistance, and surface protein genes., Results: All ST10 isolates belonged to serotype Ib; type Ib/ST10 strains were responsible for 66.7% (14/21, P < 0.05) of infant invasive GBS infections during the period and all resulted in late-onset (LOD) and late LOD disease (14/14). Infants with type Ib/ST10 GBS disease had significantly higher rates of meningitis (9/14, 64.3%, p < 0.05) and clinical complications (5/14, 35.7%, p < 0.05). The Ib/ST10 GBS isolates had limited genetic diversity, clustered in the CC10/bca/PI-1 + PI-2a genetic lineage, showed resistance to erythromycin, lincomycin, and fluoroquinolones and sensitivity to tetracycline, and possessed genes ermT , ermB , and amino acid changes in gyrA and parC ., Conclusions: The probable clonal expansion can result in severe infections in infants and ongoing emergence of multi-drug resistant isolates. Continued monitoring for type Ib/ST10 GBS infections is warranted., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Zhang, Kang, Zhu, Xu, Guo, Zhang, Liu and Ma.)

A high anterior lip on a total knee prosthesis is an effective way of reducing anterior translation, but the effect on joint wear is unclear. Using finite element analysis (FEA), this study quantitatively compared wear rates and anterior contact stresses in three posterior stabilized knee prostheses with different heights for the anterior lip during six daily activities (walking, stair ascent, stair descent, sit-to-stand, pivot turn and crossover turn). The wear rate and location of maximum wear depth were similar for the three lip heights tested, but the knee with the highest anterior lip also showed slight anterior wear scaring due to articular contact stress during swing phase, which was highly dependent on the shape of the contact interface. This study illustrates that tibial inserts with a high anterior lip maintain a wear rate similar to moderate and low lip posterior stabilized designs., Competing Interests: Declaration of Competing Interest We confirm that there are no known conflicts of interest associated with this publication and there has been no significant financial support for this work that could have influenced its outcome., (Copyright © 2021 IPEM. Published by Elsevier Ltd. All rights reserved.)

Aim: To observe the findings of spectral domain optical coherence tomography (SD-OCT) scan in cytomegalovirus retinitis (CMVR)., Methods: Forty-six eyes of 33 patients with acquired immunodeficiency syndrome and CMVR were enrolled in the study. Complete ophthalmologic examinations, color fundus photography, SD-OCT and fundus autofluorescence (FAF) were performed for all patients at the first visit and each follow-up visit. Retinal necrosis in CMVR was analyzed on SD-OCT and classified into two types, the typical type and the atypical type., Results: Forty-one eyes of active CMVR and 4 eyes of recurrent CMVR were classified into typical type, and 4 eyes with graying retinal lesion without hemorrhage or only punctate hemorrhage were classified into atypical type. In active stage of CMVR, the retina in typical type was significant thickened with hyperreflective lesion and full-thickness disruption of retinal architecture with enlarged vessel; while in atypical type, the retina was also destroyed in all layers but without thickening or slightly thinned. The choroid, vitreous and retinal vessels were not significantly involved. In healed stage, the retina was thin with destroyed layers in both types. In typical type, FAF showed mottled hypofluorescence mixed with punctuate hyperfluorescence. In atypical type, the retina showed some "cavity" in outer nuclear layer, and FAF showed mild hyperfluorescence., Conclusion: SD-OCT show different changes in the retina in typical type and atypical type of CMVR, which should be useful in assisting diagnosis and follow-up management of the disease., (International Journal of Ophthalmology Press.)

The aim of this study was to assess the underlying impact of Tetramethylpyrazine (TMP), which is the main activity compound of Ligusticum chuanxiong Hort, on the blood-brain barrier, inflammatory and nitrous oxide systems in a rat model of lipopolysaccharide (LPS)-induced sepsis. The SD rats were divided into control group, LPS treatment group, and LPS + TMP treatment group. TMP administered by tail vein injection. The mortality of experimental rats was recorded during the experiment. Rats were sacrificed after 14 days. Peripheral blood was collected and the expression levels of inflammatory factors TNF-α, IL-1β, and IL-6 were detected by ELISA. The integrity of blood-brain barrier was detected by sodium fluorescein staining. Lung and brain tissues were taken to detect the infiltration of immune cells. Immunohistochemistry was performed to detect the expression of tight junctions related proteins and oxidative stress-related proteins. The results showed that TMP treatment for 14 days significantly decreased the weight loss and increased the survival rate of the septic rats significantly. TMP decreased the infiltration of inflammatory cells and alleviated the sepsis-induced damage in both the lung and brain tissues. The inflammatory cytokines TNF-α, IL-1β, and IL-6, were significantly decreased post-TMP treatment. Histopathological analysis with sodium fluorescein staining density showed that TMP had a protective effect on the basal lamina and cerebral cortex. Also, TMP significantly increased expression of the tight junction-related proteins claudin-5 and occludin in the brain tissue and increased the expression of the ZO-1 , Occludin , and Claudin-5 genes, indicating alleviated the degree of blood-brain barrier destruction. Furthermore, immunohistochemistry (IHC) and immunoblotting confirmed that TMP could inhibit the indicators of the nitrous oxide system, iNOS and eNOS; in addition, TMP significantly decreased the levels of MDA and NO. The findings showed that TMP treatment during sepsis was associated with the protection of the blood-brain barrier and the suppression of inflammatory reactions and the nitrous oxide system. This study reveals a promising protective role of TMP in septic encephalopathy and may suggest a therapeutic approach for fighting the deadly disease of sepsis in the clinic., (Copyright © 2020 Huang, Xie, Xu, Huang, Zheng, Chen and Cao.)

Microglia polarization is associated with the pathogenesis of depression. A previous study shows that long non-coding RNA uc.80- is down-regulated in the hippocampus of depressed rats. Thus, this article aims to investigate the role of uc.80- in microglia polarization in depression. We first established depression model rats by chronic unpredictable mild stress (CUMS) regiment. We found that hippocampus of depressed rats exhibited an increase of M1 microglias and a decrease of M2 microglias. uc.80- was down-regulated in hippocampus of depressed rats. Furthermore, the detection of behaviouristics of depressed rats showed that uc.80- overexpression alleviated depression of rats. In addition, uc.80- overexpression promoted M2 polarization of microglias in vivo and in vitro. uc.80- overexpression led to a decrease in apoptosis of hippocampal neurons in vivo and in vitro. In conclusion, our study confirms that lncRNA uc.80- overexpression ameliorates depression in rats by promoting M2 polarization of microglias. Thus, our work suggests that uc.80- may be a target gene for depression treatment., (© 2020 International Union of Biochemistry and Molecular Biology.)

Some researches have shown the associations between air pollution and hospital-based emergency department visits, while the evidence about the acute effects of air pollution on emergency ambulance dispatches for the whole population is rarely available, especially on an hourly time scale. This paper aimed to investigate the effects of hourly concentrations of ambient air pollution on hourly number of ambulance emergency call-outs (AECOs) in Shenzhen, China. AECO data were collected from Shenzhen Emergency Center from January 2013 to December 2016. A time-stratified case-crossover design with conditional Poisson regression was performed to fit the relationship between hourly air pollution and AECOs. The distributed lag model was applied to determine lag structure of the effects of air pollutants. There were a total of 502,862 AECOs during the study period. The significant detrimental effects of SO 2 , PM 2.5 , and PM 10 appeared immediately with a following harvesting effect after 5 h and the effects lasted for about 96 h. The cumulative effect estimates of four pollutants over 0-96 h were 13.99% (95% CI 7.52-20.85%), 2.07% (95% CI 0.72-3.43%), 1.20% (95% CI 0.54-1.87%), and 2.46% (95% CI 1.63-3.29%), respectively. We did not observe significant effects of O 3 . This population-based study quantifies the adverse effects of air pollution on ambulance dispatches and provides evidence of the lag structure of the effects on an hourly time scale.

In this study, methanofullerenes and 2',3'-dihydrofuran C 60 derivatives were selectively synthesized in high yields via the reactions of C 60 with β-keto esters under mild conditions by controlling the addition sequence and molar ratio of iodine and base. The structures of the products were determined by spectroscopic characterization. Moreover, a possible reaction mechanism for the selective formation of fullerene derivatives was proposed., Competing Interests: There are no conflicts of interest to declare., (This journal is © The Royal Society of Chemistry.)

Background: Although road traffic casualty (RTC) is preventable, it remains the eighth leading cause of death globally, especially in developing countries. Previous studies suggested the association between RTC and monthly or daily weather conditions, while the acute effects of weather conditions on an hourly timescale remains unknown. This study aims to quantify hourly effects of precipitation and temperature on RTC., Methods: Using ambulance records on RTC during 2010-2016 for the whole population in Shenzhen, China, we conducted a time-stratified case-crossover design which can inherently control for hour of the day, day of the week, seasonality, time trends and potential time-invariant confounders. Conditional quasi-Poisson regression with distributed lag nonlinear model was used to determine the effects of hourly precipitation and temperature on RTC., Results: Light and heavy precipitation increased RTC in current and following 2 h by 8.09% (95% CI: 4.20-12.12%) and 11.62% (95% CI: 5.93-17.62%), respectively. A J-shaped temperature-RTC curve revealed that each 1 °C increment above 17 °C were associated with a 0.87% (0.52-1.22%) increase in RTC. High temperature accounted for 6.44% (95% CI: 3.95-8.91%) of all RTC, with a high fraction of 10.64% (95% CI: 4.33-15.96%) during warm season and 8.30% (95% CI: 4.26-12.66%) in traffic peak hours. Precipitation contributed to 0.68% (95% CI: 0.44-0.92%) of RTC within 3 h. The middle-aged and female suffered more from precipitation-associated RTC, and the younger suffered more from high temperature-associated RTC., Conclusions: High temperature increased substantially hourly RTC. Precipitation was also a risk factor of RTC and the adverse effect lasted for 3 h. The findings would be helpful to guide the development of targeted intervention to accelerate progress in road traffic safety., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

The effect and potential molecular mechanisms of berberine on gluconeogenesis in skeletal muscles and adipose tissues were investigated. After adaptive feeding for one week, 8 rats were randomly selected as the normal group and fed on a standard diet. The remaining 32 rats were fed on a high-fat diet and given an intravenous injection of streptozotocin (STZ) for 2 weeks to induce the diabetic models. The diabetic rat models were confirmed by oral glucose tolerance test (OGTT) and randomly divided into 4 groups (n=8 each), which were all fed on a high-fat diet. Berberine (3 g/kg per day) or metformin (183 mg/kg per day) was intragastrically administered to the diabetic rats for 12 weeks, serving as berberine group and metformin group respectively. 5-aminoimidazole-4-carboxamide1-β-D-ribofuranoside [AICAR, an agonist of AMP-activated protein kinase (AMPK), 0.5 mg/kg per day] was subcutaneously injected to the diabetic rats for 12 weeks, serving as AICAR group. The remaining 8 diabetic rats served as the model group, which was given a 0.5% carboxyl methylcellulose solution by oral gavage. Fasting serum insulin (FINS), OGTT as well as lipid parameters were tested by commercial kit. The protein levels of liver kinase B1 (LKB1), AMPK, phosphorylated AMP-activated protein kinase (p-AMPK), transducer of regulated CREB activity 2 (TORC2), phosphorylated transducer of regulated CREB activity 2 (p-TORC2), phosphoenolpyruvate carboxykinase (PEPCK), and glucose-6-phosphatase (G6Pase) in skeletal muscles and adipose tissues were examined by Western blotting. The results showed that berberine significantly decreased the body weight, plasma glucose, insulin levels, and homeostatic model assessment for insulin resistance (HOMA-IR) of diabetic rats compared with those in the model group. Meanwhile, the serum total triglyceride (TG), total cholesterol (TC), and low-density lipoprotein cholesterol (LDL-C) levels were markedly decreased and high-density lipoprotein cholesterol (HDL-C) level was significantly increased after the treatment with berberine. In addition, we found that berberine significantly increased the expression of p-AMPK and LKB1, while decreasing the p-TORC2 levels in skeletal muscles and adipose tissues. Moreover, the expression of PEPCK and G6Pase was significantly down-regulated after the treatment with berberine compared to the model group. It was suggested that the mechanism by which berberine inhibited peripheral tissue gluconeogenesis may be attributed to the activation of the LKB1-AMPK-TORC2 signaling pathway.

Ultrafine nanoporous copper (UNP Cu) with a characteristic pore size of about 12 nm and a ligament size of about 14 nm was fabricated from amorphous Mg 65 Cu 25 Y 10 precursor alloys after dealloying in a 0.1 M H₂SO₄ solution modified by poly(vinyly alcohol) polymers with a molecular weight of 105000 g/mol (PVA-124). The suppression of the surface diffusion from PVA-124 reduced the size of the nanopores and ligaments to 20 nm when the concentration of the added PVA-124 exceeded 0.1 g L -1 . When the concentration of the added PVA-124 exceeded 2 g L -1 , PVA-124 triggered the polymerization process. The resultant polymer surface layer on the fcc Cu ligaments was shown to reduce the rate of selective dissolution. It was also shown that extending the immersion time resulted in a suppression of coarsening. The introduction of PVA-124 polymer into acids resulted in a higher viscosity of the dealloying solutions, particularly when the concentration of PVA-124 was higher than 1.0 g L -1 . This viscosity was shown not only to reduced rate of diffusion of Cu adatoms in PVA-124 solutions, but also forced the accumulation of Cu adatoms to form small scale UNP Cu.

Ceramides are significant metabolic products of sphingolipids in lipid metabolism and are associated with insulin resistance and hepatic steatosis. In chronic inflammatory pathological conditions, hypoxia occurs, the metabolism of ceramide changes, and insulin resistance arises. Hypoxia-inducible factors (HIFs) are a family of transcription factors activated by hypoxia. In hypoxic adipocytes, HIF-1α upregulates pla2g16 (a novel HIF-1α target gene) gene expression to activate the NLRP3 inflammasome pathway and stimulate insulin resistance, and adipocyte-specific Hif1a knockout can ameliorate homocysteine-induced insulin resistance in mice. The study on the HIF-2α-NEU3-ceramide pathway also reveals the role of ceramide in hypoxia and insulin resistance in obese mice. Under obesity-induced intestinal hypoxia, HIF-2α increases the production of ceramide by promoting the expression of the gene Neu3 encoding sialidase 3, which is a key enzyme in ceramide synthesis, resulting in insulin resistance in high-fat diet-induced obese mice. Moreover, genetic and pathophysiologic inhibition of the HIF-2α-NEU3-ceramide pathway can alleviate insulin resistance, suggesting that these could be potential drug targets for the treatment of metabolic diseases. Herein, the effects of hypoxia and ceramide, especially in the intestine, on metabolic diseases are summarized., Competing Interests: Conflict-of-interest statement: There is no conflict of interest associated with any of the senior author or other coauthors who contributed their efforts in this manuscript., (©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.)

The PI3K-AKT-mTOR cascade is required for renal cell carcinoma (RCC) progression. SC66 is novel AKT inhibitor. We found that SC66 inhibited viability, proliferation, migration and invasion of RCC cell lines (786-O and A498) and patient-derived primary RCC cells. Although SC66blocked AKT-mTORC1/2 activation in RCC cells, it remained cytotoxic in AKT-inhibited/-silenced RCC cells. In RCC cells, SC66 cytotoxicity appears to occur via reactive oxygen species (ROS) production, sphingosine kinase 1inhibition, ceramide accumulation and JNK activation, independent of AKT inhibition. The ROS scavenger N-acetylcysteine, the JNK inhibitor (JNKi) and the anti-ceramide sphingolipid sphingosine-1-phosphate all attenuated SC66-induced cytotoxicity in 786-O cells. In vivo, oral administration of SC66 potently inhibited subcutaneous 786-O xenograft growth in SCID mice. AKT-mTOR inhibition, SphK1 inhibition, ceramide accumulation and JNK activation were detected in SC66-treated 786-O xenograft tumors, indicating that SC66 inhibits RCC cell progression through AKT-dependent and AKT-independent mechanisms.

Porous materials have attracted great interest in recent years, and a variety of surface modification methods have been developed to endow porous materials with multifunctional applications. Herein, multifunctional porous materials are fabricated based on surface metallization. Metallized sponges with Ag and Cu are highly hydrophobic and are still hydrophobic under oil. The metallized sponges selectively adsorb oils from oil/water mixtures and can completely remove oils from water. We further demonstrate continuous oil-water separation by the metallized sponges with the aid of a peristaltic pump. The Ag-metallized materials show high catalytic performance for both chemical reduction and dye degradation. The catalytic reduction efficiency of 4-nitrophenol reaches 97.7% within 60 min and remains as high as 96% after 15 cycles. Moreover, the metallized materials show 99.99% bactericidal efficiency for both Staphylococcus aureus and Escherichia coli . Particularly, the Cu-metallized materials exhibit stable conductivity under deformation; and metal patterns are realized via the metallization method combined with a patterned mask, which may provide a feasible approach for flexible electronics. This work provides a versatile method to introduce metal coatings to porous materials, broadening the applications of porous materials.

Background: Longer ambulance response time (ART) delaying treatment would worsen conditions of seriously ill or injured patients, but limited evidence is available on the effects of weather factors on ART. This study aims to assess precipitation- and temperature-ART associations and their potential lagged effects using a novel modeling strategy., Methods: Based on 779,156 emergency records during 2010-2016 from the whole population in Shenzhen, China, we creatively combined quantile regression with distributed-lag nonlinear models to examine the non-linear and lagged effects of hourly precipitation and temperature on ART at the 50th and 90th percentiles., Results: A linear precipitation-ART association with a delay of 9.01 (95%CI, 7.82-10.20) seconds at median ART for a 1 mm increase in hourly precipitation, and the effects lasted for 5 h with the greatest effect at the current hour. A two linear thresholds temperature-ART association revealed 1 °C decrease below 19 °C caused 1.68 (95%CI, 0.92-2.44) seconds delay in total ART over lag 0-7 h, and 1 °C increase above 24 °C caused 2.44 (95%CI, 1.55-3.33) seconds delay. The hourly call volumes exceeding 54 calls caused 8.79 (95%CI, 8.71-8.86) seconds delay in total ART for 1 more call, but not affected the effects of weather factors. The internal ART suffered more from the hourly call volumes, while the external ART suffered more from precipitation and temperature. The effects were apparently greater on ART at the 90th percentile than median., Conclusions: Precipitation and temperature are independent risk factors for ambulance services performance, and their lagged effects are notable. The external ART and patients with long ART are vulnerable. More attention should be paid to weather and ART, and these findings may have implications for effective policies to reduce ART to protect public health., Competing Interests: Declaration of competing interest The authors declare they have no actual or potential competing financial interests., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Biodegradable suture anchors are commonly used for repairing torn rotator cuffs, but these biodegradable materials still suffer from low mechanical strength, poor osteointegration, and the generation of acidic degradation byproducts., Method: The purpose of this study was to evaluate the long-term mechanical behavior and osteogenetic capabilities of a biocomposite anchor injection molded with 30% β-tricalcium phosphate microparticles blended with 70% poly (L-lactide-co-glycolide) (85/15). This study investigated in vitro degradation and in vivo bone formation in a canine model. The initial mechanical behavior, mechanical strength retention with degradation time, and degradation features were investigated., Results: The results showed that the biocomposite anchor had sufficient initial mechanical stability confirmed by comparing the initial shear load on the anchor with the minimum shear load borne by an ankle fracture fixation screw, which is considered a worst-case implantation site for mechanical loading. The maximum shear load retention of the biocomposite anchor was 83% at 12 weeks, which is desirable, as it aligns with the rate of bone healing. The β-tricalcium phosphate fillers were evenly dispersed in the polymeric matrix and acted to slow the degradation rate and improve the mechanical strength of the anchor. The interface characteristics between the β-tricalcium phosphate particles and the polymeric matrix changed the degradation behavior of the biocomposite. Phosphate buffer saline was shown to diffuse through the interface into the biocomposite to inhibit the core accelerated degradation rate. In vivo , the addition of β-tricalcium phosphate induced new bone formation. The biocomposite material developed in this study demonstrated improved osteogenesis in comparison to a plain poly (L-lactide-co-glycolide) material. Neither anchor produced adverse tissue reactions, indicating that the biocomposite had favorable biocompatibility following long-term implantation., Conclusion: In summary, the new biocomposite anchor presented in this study had favorable osteogenetic capability, mechanical property, and controlled degradation rate for bone fixation., Translational Potential of This Article: The new biocomposite anchor had sufficient initial and long-term fixation stability and bone formation capability in the canine model. It is indicated that the new biocomposite anchor has a ​potential for orthopedic application., Competing Interests: The authors have no conflicts of interest to disclose in relation to this article., (© 2020 The Authors.)

Objective: Ambient particulate pollution, especially PM 2.5 , has adverse impacts on health and welfare. To manage and control PM 2.5 pollution, it is of great importance to determine the factors that affect PM 2.5 levels. Previous studies commonly focused on a single or several cities. This study aims to analyze the impacts of meteorological and socio-economic factors on daily concentrations of PM 2.5 in 109 Chinese cities from January 1, 2015 to December 31, 2015., Methods: To evaluate potential risk factors associated with the spatial and temporal variations in PM 2.5 levels, we developed a Bayesian spatio-temporal model in which the potential temporal autocorrelation and spatial autocorrelation of PM 2.5 levels were taken into account to ensure the independence of the error term of the model and hence the robustness of the estimated parameters., Results: Daily concentrations of PM 2.5 peaked in winter and troughed in summer. The annual average concentration reached its highest value (79 μg/m 3 ) in the Beijing-Tianjin-Hebei area. The city-level PM 2.5 was positively associated with the proportion of the secondary industry, the total consumption of liquefied petroleum gas and the total emissions of industrial sulfur dioxide (SO 2 ), but negatively associated with the proportion of the primary industry. A reverse U-shaped relationship between population density and PM 2.5 was found. The city-level and daily-level of weather conditions within a city were both associated with PM 2.5 ., Conclusion: PM 2.5 levels had significant spatio-temporal variations which were associated with socioeconomic and meteorological factors. Particularly, economic structure was a determinant factor of PM 2.5 pollution rather than per capita GDP. This finding will be helpful for the intervention planning of particulate pollution control when considering the environmental and social-economic factors as part of the strategies., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Background: Drought is a major natural disaster that causes severe social and economic losses. The prediction of regional droughts may provide important information for drought preparedness and farm irrigation. The existing drought prediction models are mainly based on a single weather station. Efforts need to be taken to develop a new multistation-based prediction model., Objectives: This study optimizes the predictor selection process and develops a new model to predict droughts using past drought index, meteorological measures and climate signals from 32 stations during 1961 to 2016 in Shaanxi province, China., Methods: We applied and compared two methods, including a cross-correlation function and a distributed lag nonlinear model (DLNM), in selecting the optimal predictors and specifying their lag time. Then, we built a DLNM, an artificial neural network model and an XGBoost model and compared their validations for predicting the Standardized Precipitation Evapotranspiration Index (SPEI) 1-6 months in advance., Results: The DLNM was better than the cross-correlation function in predictor selection and lag effect determination. The XGBoost model more accurately predicted SPEI with a lead time of 1-6 months than the DLNM and the artificial neural network, with cross-validation R 2 values of 0.68-0.82, 0.72-0.89, 0.81-0.92, and 0.84-0.95 at 3-, 6-, 9- and 12-month time scales, respectively. Moreover, the XGBoost model had the highest prediction accuracy for overall droughts (89%-97%) and for three specific drought categories (i.e., moderate, severe, and extreme) (76%-94%)., Conclusion: This study offers a new modeling strategy for drought predictions based on multistation data. The incorporation of nonlinear and lag effects of predictors into the XGBoost method can significantly improve prediction accuracy of SPEI and drought., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: People are exposed to mixtures of highly correlated gaseous, liquid and solid pollutants. However, in previous studies, the assessment of air pollution effects was mainly based on single-pollutant models or was simultaneously included as multiple pollutants in a model. It is essential to develop appropriate methods to accurately estimate the health effects of multiple pollutants in the presence of a high correlation between pollutants., Methods: The flexible tensor product smooths of multiple pollutants was applied for the first time in a quasi-Poisson model to estimate the health effects of SO 2 , NO 2 and PM 10 on daily all-cause deaths during 2005-2012 in Guangzhou, China. The results were compared with those from three other conventional models, including the single-pollutant model and the three-pollutant model with and without first-order interactions., Results: The tensor product model revealed a complex interaction among three pollutants and significant combined effects of PM 10 , NO 2 and SO 2 , which revealed a 2.53% (95%CI: 1.03-4.01%) increase in mortality associated with an interquartile-range (IQR) increase in the concentrations of all three pollutants. The combined effect estimated by the single-pollutant model was 5.63% (95% CI: 3.96-7.34%). Although the conventional three-pollutant models produced combined effect estimates (2.20, 95%CI, 1.18-3.23%; 2.78, 95%CI: 1.35-4.23%) similar to those of the tensor product model, they distorted the estimates and inflated the variances of the estimates when attributing the combined health effects to individual pollutants., Conclusions: The single-pollutant model or conventional multi-pollutant model may yield misleading results in the presence of collinearity. The tensor product quasi-Poisson regression provides a novel approach to the assessment of the health impacts of multiple pollutants by flexibly fitting the interaction effects and avoiding the collinearity problem.

This study aims to explore the effect and mechanism of Jiao-tai-wan (JTW) on systemic and tissue-specific inflammation and insulin resistance in obesity-resistant (OR) rats with chronic partial sleep deprivation (PSD). OR rats with PSD were orally given JTW and Estazolam for 4 weeks. The amount of food intake and metabolic parameters such as body weight increase rate, fasting plasma glucose (FPG), fasting insulin (FINS), homeostasis model assessment-insulin resistance (HOMA-IR) and plasma inflammatory markers were measured. The expression levels of circadian proteins cryptochrome 1 (Cryl) and cryptochrome 2 (Cry2) in hypothalamus, adipose and liver tissues were also determined. Meanwhile, the mRNA expression of inflammatory markers, activity of nuclear factor kappa B (NF-κB) p65 protein, as well as the expression levels of insulin signaling pathway proteins in hypothalamus, adipose and liver tissues were measured. Additionally, cyclic adenosine 3', 5'-monophosphate (cAMP) and activity of vasodilator-stimulated phosphoprotein (VASP) in hypothalamus tissue were measured. JTW significantly decreased the body weight increase rate and food intake, ameliorated systemic inflammation and insulin resistance. JTW effectively ameliorated inflammation and increased PI3K/AKT signaling activation in hypothalamus, adipose and liver. Interestingly, all these changes were associated with the up-regulation of circadian gene Cryl and Cry2 protein expression. We also found that in hypothalamus tissue of PSD rats, down-regulation of Cryl and Cry2 activated cAMP/PKA signaling and then led to inflammation, while JTW inhibited this signaling. These results suggested that JTW has the beneficial effect on ameliorating inflammation and insulin resistance in partially sleep-deprived rats by up-regulating Cry expression.

Castration‑resistant prostate cancer (CRPC) is difficult to treat in current clinical practice. Hypoxia is an important feature of the CRPC microenvironment and is closely associated with the progress of CRPC invasion. However, no research has been performed on the immune escape of CRPC from NK cells. The present study focused on this subject. Firstly, when the CRPC cell lines C4‑2 and CWR22Rv1 were induced by hypoxia, the expression of the UL16 binding protein (ULBP) ligand family of natural killer (NK) group 2D (NKG2D; ULBP‑1, ULBP‑2 and ULBP‑3) and MHC class I chain‑related proteins A and B (MICA/MICB) decreased. NKG2D is the main activating receptor of NK cells. Tumor cells were then co‑cultured with NK cells to conduct NK cell‑mediated cytotoxicity experiments, which revealed the decreased immune cytolytic activity of NK cells on hypoxia‑induced CRPC cells. In exploring the mechanism behind this observation, an increase in programmed death‑ligand 1 (PD‑L1) expression in CRPC cells induced by hypoxia was observed, while the addition of PD‑L1 antibody effectively reversed the expression of NKG2D ligand and enhanced the cytotoxic effect of NK cells on CRPC cells. In the process of exploring the upstream regulatory factors of PD‑L1, inhibition of the Janus kinase (JAK)1,2/signal transducer and activator of transcription 3 (Stat3) signaling pathway decreased the expression of PD‑L1 in CRPC cells. Finally, it was observed that combined inhibition of JAK1,2/PD‑L1 or Stat3/PD‑L1 was more effective than inhibition of a single pathway in enhancing the immune cytolytic activity of NK cells. Taking these results together, it is thought that combined inhibition of the JAK1,2/PD‑L1 and Stat3/PD‑L1 signaling pathways may enhance the immune cytolytic activity of NK cells toward hypoxia‑induced CRPC cells, which is expected to provide novel ideas and targets for the immunotherapy of CRPC.

Castration-resistant prostate cancer (CRPC), also known as androgen-independent prostate cancer, frequently develops local and distant metastases, the underlying mechanisms of which remain undetermined. In the present study, surgical specimens obtained from patients with clinical prostate cancer were investigated, and it was revealed that the expression levels of ataxia telangiectasia mutated kinase (ATM) were significantly enhanced in prostate cancer tissues isolated from patients with CRPC compared with from patients with hormone‑dependent prostate cancer. CRPC C4‑2 and CWR22Rv1 cells lines were subsequently selected to establish prostate cancer models, and ATM knockout cells were established via lentivirus infection. The results of the present study demonstrated that the migration and epithelial‑mesenchymal transition (EMT) of ATM knockout cells were significantly decreased, which suggested that ATM is closely associated with CRPC cell migration and EMT. To further investigate the mechanisms underlying this process, programmed cell death 1 ligand 1 (PD‑L1) expression was investigated in ATM knockout cells. In addition, inhibitors of Janus kinase (JAK) and signal transducer and activator of transcription 3 (STAT3; Stattic) were added to C4‑2‑Sc and CWR22Rv1‑Sc cells, and the results demonstrated that PD‑L1 expression was significantly decreased following the addition of JAK inhibitor 1; however, no significant change was observed following the addition of Stattic. Furthermore, a PD‑L1 antibody and JAK inhibitor 1 were added to C4‑2‑Sc and CWR22Rv1‑Sc cells, and it was revealed that cell migration ability was significantly decreased and the expression of EMT‑associated markers was effectively reversed. The results of the present study suggested that via inhibition of the ATM‑JAK‑PD‑L1 signaling pathway, EMT, metastasis and progression of CRPC may be effectively suppressed, which may represent a novel therapeutic approach for targeted therapy for patients with CRPC.

Traditional Chinese medicine(TCM) modernization has gradually become a worldwide trend. Reverse docking technology has also gradually become a useful tool for TCM modernization. It involves docking a small-molecule drug in the potential binding cavities of a set of clinically relevant macromolecular targets. Detailed analysis of the binding characteristics was used for the ranking of the targets according to the tightness of binding. This process can be used to potentially identify the novel molecular targets for the drug which may be relevant to its mechanism of action or side effect. In order to explore the action mechanism, screen the active ingredients and seek the treating target of TCM, reverse molecular docking technology has been widely used and has achieved remarkable results in recent years. In this review, we summarized the application of reverse molecular docking technology in the target seeking, active ingredients screening and potential mechanism exploration of TCM, which may provide more scientific basis for the clinical research and development of new herbal drugs., Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose., (Copyright© by the Chinese Pharmaceutical Association.)

Objective: To explore the effect and mechanism of Jiaotai Pill (, JTW) on intestinal mucosal damage in rats with chronic partial sleep deprivation (PSD)., Methods: Obesity resistant (OR) rats were selected, and underwent 4 h PSD by being exposed to environmental noise for 4 weeks. During the whole PSD period, JTW and estazolam were orally given to the rats respectively in the treating groups. Plasma concentration of lipopolysaccharide (LPS) which is the marker of gut-origin endotoxemia was examined. Intestinal morphology changes were observed by optical microscopy. The protein expression of occludin (Ocln) in the intestine was measured by immunofluorescence technique and Western blot. The expressions of circadian proteins cryptochromes (Cry1 and Cry2) in the intestine were also determined., Results: The treatment of JTW significantly decreased LPS level in OR rats with PSD (P<0.05). JTW also attenuated insomnia-induced intestinal injury like shorter, sparse and incomplete villus, wide gap between the villus, mucosal swelling and congesting (P<0.05). These changes were associated with the effect of JTW on up-regulating the expressions of Cry1 protein, Cry2 protein and Ocln protein in the intestine., Conclusions: JTW has the beneficial effect on improving intestinal mucosal damage caused by PSD. The mechanism appears to be related to the modulation of the expressions of circadian proteins and Ocln protein in the intestine, thereby attenuating inflammation and improving insulin resistance in insomnia rats.

Major progress has been made clinically in inhibiting the programmed death receptor 1 (PD-1)/PD-L1 interaction to enhance T cell-mediated immune function, yet the effectiveness of anti-PD-L1/PD-1 agents in enhancing natural killer (NK) cell's function remains largely unknown. Susceptibilities of cisplatin-resistant A549CisR and H157CisR cells vs. parental cells to the cytotoxic action of NK cells were examined. We found cisplatin-resistant cells more resistant to NK cell cytotoxicity than parental cells. There were constitutively higher expressions of PD-L1 in A549CisR and H157CisR cells than in parental cells in vitro, as well as in H157CisR cell-derived tumors than H157P cell-derived tumors. In contrast, we observed that the expression of PD-1 in NK cells was induced after co-culture with cisplatin-resistant cells. We also observed increased susceptibility of cisplatin-resistant cells to NK cell cytotoxicity when neutralizing antibody of PD-1 or PD-L1 was added. Further, we found that the NK group 2, member D (NKG2D) ligand levels were lower in A549CisR and H157CisR cells than in parental cells. Meanwhile, we discovered that the MEK/Erk signaling pathway played a significant role in this regulation, and the addition of a MEK/Erk pathway inhibitor significantly enhanced the PD-L1 Ab effect in enhancing NK cell cytotoxicity to cisplatin-resistant cells.

We investigated whether radiation influences the susceptibility of non-small cell lung cancer (NSCLC) cells to NK cell mediated cytotoxicity. We found radiation treatment increased expression of programmed cell death ligand 1 (PD-L1), but decreased NK group 2, member D (NKG2D) ligand expressions in A549 and H157 NSCLC cells. Both types of changes would have protected tumor cells from the cytotoxic action of NK cells. Consistently, we detected similar alteration in these molecules in radioresistant A549R26-1 and H157R24-1 subline cells. Higher PD-L1 level was also observed in tumors of A549R26-1 cell-derived xenografts than tumors of parental A549 (A549P) cell-derived xenografts. Accordingly, we found radioresistant cells were more resistant to the cytotoxic action of NK cells than parental cells, and such resistance was decreased when neutralizing antibody (Ab) of PD-L1 was added to the radioresistant cell/NK cell co-cultures. In mechanism studies, we found that IL-6-MEK/Erk signaling contributed most significantly to the up-regulation of PD-L1/down-regulation of NKG2D ligands in radioresistant cells. The addition of the MEK/Erk inhibitor increased the susceptibility of A549R26-1 and H157R24-1 cells to NK-cell cytotoxicity while no significant effect was observed in parental cells. Moreover, we detected enhanced NK-cell cytotoxicity to radioresistant cells when PD-L1 Ab and MEK/Erk inhibitor were added together to co-cultures of tumor/NK cells compared to when PD-L1 Ab was used alone. We suggest that combined use of PD-L1 Ab and MEK/Erk inhibitor may offer better therapeutic benefits than PD-L1 Ab alone to treat NSCLC patients who are receiving radiotherapy or who are at the radioresistant stage., Competing Interests: CONFLICTS OF INTEREST none.

To evaluate the safety and efficacy of gabapentin in comparison with carbamazepine in the treatment of trigeminal neuralgia, a meta-analysis of randomized controlled trials was performed. Two reviewers independently selected studies, assessed study quality, and extracted data. Sixteen randomized controlled trials that included 1,331 patients were assessed. The meta-analysis showed that the total effective rate of gabapentin therapy group was similar with carbamazepine therapy group (OR = 1.600, 95% CI 1.185, 2.161, P = 0.002). While the effective rate of gabapentin therapy for 4 weeks was higher than that of carbamazepine therapy (OR = 1.495, 95% CI 1.061, 2.107, P = 0.022, heterogeneity: x 2 = 7.12, P = 0.625, I 2 = 0.0%), the life satisfaction improvement is also better in the gabapentin therapy group after a 4-week treatment (SMD = 0.966, 95% CI 0.583, 1.348, P < 0.001). Furthermore, our meta-analysis suggested that the adverse reaction rate of gabapentin therapy group was significantly lower than that of carbamazepine therapy group (OR = 0.312, 95% CI 0.240, 0.407, P < 0.001). In conclusion, present trials comparing gabapentin with carbamazepine are all poor in terms of methodological quality. Based on the available evidence, it is not possible to draw conclusions regarding the efficacy and side effects of gabapentin being superior to carbamazepine., (© 2016 World Institute of Pain.)

Increasing evidence suggests that disruptions of synaptic functions correlate with the severity of cognitive deficit in Alzheimer's disease (AD). Our previous study demonstrated that baicalein enhances long-term potentiation (LTP) in acute rat hippocampal slices and improves hippocampus-dependent contextual fear conditioning in rats. Given that baicalein possess various biological activities, especially its effects on synaptic plasticity and cognitive function, we examined the effect of baicalein on synaptic function both in vitro and in vivo in AD model. The effect of baicalein on Aβ42 oligomer impaired LTP was investigated by electrophysiological methods. Baicalein was administered orally via drinking water to the APP/PS1 mice and sex- and age-matched wild-type mice. Treatment started at 5 months of age and mice were assessed for cognition and AD-like pathology at 7-month-old. Cognition was analyzed by Morris water maze test, fear conditioning test, and novel object recognition test. Changes in hippocampal 12/15 Lipoxygenase (12/15LO) and glycogen synthase kinase 3β (GSK3β) activity, Aβ production, tau phosphorylation, synaptic plasticity, and dendritic spine density were evaluated. Baicalein prevented Aβ-induced impairments in hippocampal LTP through activation of serine threonine Kinase (Akt) phosphorylation. Long-term oral administration of baicalein inhibited 12/15LO and GSK3β activity, reduced β-secretase enzyme (BACE1), decreased the concentration of total Aβ, and prevented phosphorylation of tau in APP/PS1 mice. Meanwhile, baicalein restored spine number, synaptic plasticity, and memory deficits. Our results strengthen the potential of the flavonoid baicalein as a novel and promising oral bioactive therapeutic agent that prevents memory deficits in AD., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Objective: To investigate the effects of berberine (BBR) and cinnamic acid (CA), the main active components in Jiaotai Pill (, JTP), on palmitic acid (PA)-induced intracellular triglyceride (TG) accumulation in NIT-1 pancreatic β cells., Methods: Cells were incubated in culture medium containing PA (0.25 mmol/L) for 24 h. Then treatments with BBR (10 μmol/L), CA (100 μmol/L) and the combination of BBR and CA (BBR+CA) were performed respectively. Intracellular lipid accumulation was assessed by Oil Red O staining and TG content was measured by colorimetric assay. The expression of adenosine monophosphate-activated protein kinase (AMPK) protein and its downstream lipogenic and fatty acid oxidation genes, including fatty acid synthase (FAS), acetyl-coA carboxylase (ACC), phosphorylation acetyl-coA carboxylase (pACC), carnitine acyl transferase 1 (CPT-1) and sterol regulating element binding protein 1c (SREBP-1c) were determined by Western blot or real time polymerase chain reaction., Results: PA induced an obvious lipid accumulation and a significant increase in intracellular TG content in NIT-1 cells. PA also induced a remarkable decrease in AMPK protein expression and its downstream targets such as pACC and CPT-1. Meanwhile, AMPK downstream lipogenic genes including SREBP-1c mRNA, FAS and ACC protein expressions were increased. Treatments with BBR and BBR+CA, superior to CA, significantly reversed the above genes changes in NIT-1 pancreatic β cells. However, the synergistic effect of BBR and CA on intracellular TG content was not observed in the present study., Conclusion: It can be concluded that in vitro, BBR and BBR+CA could inhibit PA-induced lipid accumulation by decreasing lipogenesis and increasing lipid oxidation in NIT-1 pancreatic β cells.