Prevotella copri promotes vascular calcification via lipopolysaccharide through activation of NF-κB signaling pathway.

Emerging evidence indicates that alteration of gut microbiota plays an important role in chronic kidney disease (CKD)-related vascular calcification (VC). We aimed to investigate the specific gut microbiota and the underlying mechanism involved in CKD-VC. We identified an increased abundance of Prevotella copri (P. copri) in the feces of CKD rats (induced by using 5/6 nephrectomy followed by a high calcium and phosphate diet) with aortic calcification via amplicon sequencing of 16S rRNA genes. In patients with CKD, we further confirmed a positive correlation between abundance of P. copri and aortic calcification scores. Moreover, oral administration of live P. copri aggravated CKD-related VC and osteogenic differentiation of vascular smooth muscle cells in vivo, accompanied by intestinal destruction, enhanced expression of Toll-like receptor-4 (TLR4), and elevated lipopolysaccharide (LPS) levels. In vitro and ex vivo experiments consistently demonstrated that P. copri-derived LPS (Pc-LPS) accelerated high phosphate-induced VC and VSMC osteogenic differentiation. Mechanistically, Pc-LPS bound to TLR4, then activated the nuclear factor κB (NF-κB) and nucleotide-binding domain, leucine-rich-containing family, pyrin domain-containing-3 (NLRP3) inflammasome signals during VC. Inhibition of NF-κB reduced NLRP3 inflammasome and attenuated Pc-LPS-induced VSMC calcification. Our study clarifies a novel role of P. copri in CKD-related VC, by the mechanisms involving increased inflammation-regulating metabolites including Pc-LPS, and activation of the NF-κB/NLRP3 signaling pathway. These findings highlight P. copri and its-derived LPS as potential therapeutic targets for VC in CKD.

Characterization of biliary and duodenal microbiota in patients with primary and recurrent choledocholithiasis.

Purpose: To explore the biliary and duodenal microbiota features associated with the formation and recurrence of choledocholithiasis (CDL). Methods: We prospectively recruited patients with primary (P-CDL, n = 29) and recurrent CDL (R-CDL, n = 27) for endoscopic retrograde cholangiopancreatography (ERCP). Duodenal mucosa (DM), bile and bile duct stones (BDS) samples were collected in P- and R-CDL patients. DM samples were also collected in 8 healthy controls (HC). The microbiota profile analysis was performed with 16S rRNA gene sequencing. Results: Short-course antibiotic application before ERCP showed no significant effects in alpha and beta diversities of the biliary and duodenal microbiota in CDL. Alpha diversity showed no difference between DM and bile samples in CDL. The duodenal microbial richness and diversity was lower in both P- and R-CDL than HC. The biliary microbiota composition showed a high similarity between P- and R-CDL. Fusobacterium and Enterococcus were higher abundant in DM, bile, and BDS samples of R-CDL than P-CDL, as well as Escherichia and Klebsiella in bile samples of R-CDL. The enriched duodenal and biliary bacteria in CDL were closely associated with cholecystectomy, inflammation and liver dysfunction. The bile-associated microbiota of R-CDL expressed enhanced capacity of D-glucuronide and D-glucuronate degradation, implicating an elevated level of ß-glucuronidase probably produced by enriched Escherichia and Klebsiella in bile. Conclusions: The duodenal microbiota was in an imbalance in CDL. The duodenal microbiota was probably the main source of the biliary microbiota and was closely related to CDL formation and recurrence. Enterococcus, Fusobacterium, Escherichia and Klebsiella might contribute to CDL recurrence. Clinical trials: The study was registered at the Chinese Clinical Trial Registry (https://www.chictr.org.cn/index.html, ChiCTR2000033940). Supplementary Information: The online version contains supplementary material available at 10.1007/s13755-023-00267-2.

Cyclophosphamide reduces gene transcriptional activity and embryo in vitro development by inhibiting NF-κB expression through decreasing AcH4K12.

Cyclophosphamide (CTX), a widely used chemotherapeutic agent for cancer treatment, has been associated with long-term toxicity and detrimental effects on oocytes and ovaries, resulting in female reproductive dysfunction. This study aimed to investigate the potential impact of CTX on in vitro maturation (IVM) injury of porcine oocytes and subsequent embryonic development, as well as its effects on epigenetic modification and gene activation during early embryonic development. The results demonstrated that CTX treatment caused aberrant spindle structure and mitochondrial dysfunction during oocyte maturation, inducing DNA damage and early apoptosis, which consequently disrupted meiotic maturation. Indeed, CTX significantly reduced the in vitro developmental capacity of porcine embryos, and induced DNA damage and apoptosis in in vitro fertilization (IVF) blastocysts. Importantly, CTX induced abnormal histone modification of AcH4K12 in early porcine embryos. Moreover, addition of LBH589 before zygotic genome activation (ZGA) effectively increased AcH4K12 levels and restored the protein expression of NF-κB, which can effectively enhance the in vitro developmental potential of IVF embryos. The DNA damage and apoptosis induced by CTX compromised the quality of the blastocysts, which were recovered by supplementation with LBH589. This restoration was accompanied by down-regulation of BAX mRNA expression and up-regulation of BCL2, POU5F1, SOX2 and SOD1 mRNA expression. These findings indicated that CTX caused abnormal histone modification of AcH4K12 in early porcine embryos and reduced the protein expression of NF-κB, a key regulator of early embryo development, which may block subsequent ZGA processes.

Efficacy of N-acetylcysteine plus pirfenidone in the treatment of idiopathic pulmonary fibrosis: a systematic review and meta-analysis.

BACKGROUND: Numerous studies have demonstrated the potential of pirfenidone to enhance the prognosis of patients afflicted with idiopathic pulmonary fibrosis (IPF). Although N-acetylcysteine (NAC) is utilized as an antioxidant in IPF treatment, the combination of NAC and pirfenidone has produced inconsistent outcomes in certain studies. To assess the clinical effectiveness and safety of NAC plus pirfenidone (designated as the treatment group) versus pirfenidone monotherapy (designated as the control group), we conducted a systematic review and meta-analysis of randomized controlled trials (RCTs). METHODS: RCTs of NAC plus pirfenidone were reviewed searching from databases and networks of unpublished and published studies in any language. Using pair-wise meta-analysis, changes in pulmonary function test (PFT) parameters and safety were evaluated. RESULTS: Two independent reviewers selected and obtained data from 5 RCTs (n = 398), comprising 1 study from Japan, 1 from Europe, and 3 from China. NAS plus pirfenidone as compared to pirfenidone monotherapy for IPF may not reduce the incidence of skin effects(RR 1.26 [95%CI 0.64 to 2.45]) and mortality(RR 0.35 [95%CI 0.07 to 1.68])(both moderate certainty). NAS plus pirfenidone as compared to pirfenidone monotherapy for IPF may not reduce the incidence of at least one side effects(RR 1.00 [95%CI 0.84 to 1.19]; low certainty),severe side effects(RR 0.67 [95%CI 0.30 to 1.47]; low certainty) and gastrointestinal effects(RR 0.67 [95%CI 0.41 to 1.09]; low certainty) with possibly no effect in Δ%DLco(SMD -0.17 [95%CI -0.15 to 0.48]; low certainty). Meanwhile, the effect of NAS plus pirfenidone as compared to pirfenidone monotherapy on ΔFVC(SMD 0.18 [95%CI -0.68 to 1.05]), Δ%FVC(SMD -2.62 [95%CI -5.82 to 0.59]) and Δ6MWT(SMD -0.35 [95%CI -0.98 to 0.28]) is uncertain(extremely low certainty). CONCLUSION: Moderate certainty evidence suggests that NAS plus pirfenidone, compared to pirfenidone monotherapy for IPF, does not reduce the incidence of skin effects and mortality.

Clinical characteristics and outcome of autoimmune pancreatitis based on serum immunoglobulin G4 level: A single-center, retrospective cohort study.

BACKGROUND: Autoimmune pancreatitis (AIP) has been linked with elevated immunoglobulin (Ig) G4 levels. The characteristics and outcomes of AIP based on serum markers have not been fully evaluated. AIM: To compare clinical features, treatment efficacy, and outcome of AIP based on serum IgG4 levels and analyze predictors of relapse. METHODS: A total of 213 patients with AIP were consecutively reviewed in our hospital from 2006 to 2021. According to the serum IgG4 level, all patients were divided into two groups, the abnormal group (n = 148) with a high level of IgG4 [> 2 × upper limit of normal (ULN)] and the normal group (n = 65). The t-test or Mann-Whitney U test was used to compare continuous variables. Categorical parameters were compared by the χ2 test or Fisher's exact test. Kaplan-Meier curves and log-rank tests were established to assess the cumulative relapse rates. Univariate and multivariate analyses were used to investigate potential risk factors of AIP relapse. RESULTS: Compared with the normal group, the abnormal group had a higher average male age (60.3 ± 10.4 vs 56.5 ± 12.9 years, P = 0.047); higher level of serum total protein (72.5 ± 7.9 g/L vs 67.2 ± 7.5 g/L, P < 0.001), IgG4 (1420.5 ± 1110.9 mg/dL vs 252.7 ± 106.6 mg/dL, P < 0.001), and IgE (635.6 ± 958.1 IU/mL vs 231.7 ± 352.5 IU/mL, P = 0.002); and a lower level of serum complement C3 (100.6 ± 36.2 mg/dL vs 119.0 ± 45.7 mg/dL, P = 0.050). In addition, a lower number of cases with abnormal pancreatic duct and pancreatic atrophy (23.6% vs 37.9%, P = 0.045; 1.6% vs 8.6%, P = 0.020, respectively) and a higher rate of relapse (17.6% vs 6.2%, P = 0.030) were seen in the abnormal group. Multivariate analyses revealed that serum IgG4 [(> 2 × ULN), hazard ratio (HR): 3.583; 95% confidence interval (CI): 1.218-10.545; P = 0.020] and IgA (> 1 × ULN; HR: 5.908; 95%CI: 1.199-29.120; P = 0.029) and age > 55 years (HR: 2.383; 95%CI: 1.056-5.378; P = 0.036) were independent risk factors of relapse. CONCLUSION: AIP patients with high IgG4 levels have clinical features including a more active immune system and higher relapse rate. Several factors, such as IgG4 and IgA, are associated with relapse.

Effects of interleukin-23 on the activation of mucosal-associated invariant T cells from oral lichen planus.

OBJECTIVE: Oral lichen planus (OLP) is a T cell-mediated inflammatory condition in the oral cavity. Mucosal-associated invariant T (MAIT) cells are gaining more relevance in immune diseases because they can be activated by cytokines without T cell receptor stimulation. Herein, we tested the effect of interleukin-23 (IL-23) on the activation status of OLP MAIT cells. METHODS: Peripheral blood mononuclear cells (PBMCs) isolated from OLP patients were stimulated by IL-23 in the absence or presence of phorbol myristate acetate (PMA) and ionomycin. The activation status of MAIT cells was analyzed by flow cytometry after staining for CD3, CD4, CD8, CD161, TCR Vα7.2, and CD69. RESULTS: The fraction of MAIT cells in OLP peripheral blood was approximately 0.38% to 3.97%, and CD8+ subpopulations overwhelmed CD4+ cells. The mean percentages of OLP MAIT cells in PBMCs and CD8+MAIT cells in MAIT cells were approximately 40%. PMA and ionomycin significantly increased CD69 expression on OLP T cells, MAIT cells, and CD8+MAIT cells. Cells with enhanced activation had different responsiveness to exogenous IL-23, showing increased CD69 expression on OLP T cells, decreased CD69 on OLP CD8+MAIT cells, and no significant change on OLP MAIT cells. CONCLUSIONS: IL-23 showed different effects on the activation status of OLP MAIT cells and CD8+MAIT cells.

Altered Expression of Vascular Cell Adhesion Molecule-1 in Oral Lichen Planus.

Oral lichen planus (OLP) is a T cell-mediated chronic inflammatory mucocutaneous disease affected by the interaction between keratinocytes and T cells. Recent evidence indicates that vascular cell adhesion molecule-1 (VCAM1) plays a vital role in mediating immune and inflammatory responses. In this study, the expression of VCAM1 in OLP was detected by immunohistochemical staining and its correlations with clinical features were analyzed. The disease severity of OLP was assessed by the reticular, atrophic, and erosive scoring system. We found that VCAM1 was generally localized in the cytoplasm of epithelial cells, and in nucleus, cytoplasm, and extracellular matrix of subepithelial infiltrated cells in superficial layer of lamina propria. Moreover, VCAM1 levels in epithelium and lamina propria of OLP were significantly higher than that in controls, respectively. In addition, VCAM1 level in epithelium was increased compared with that of lamina propria. There were no significant differences for VCAM1 expression between nonerosive and erosive forms of OLP. The expression of VCAM1 in OLP was not associated with the severity of disease, gender, and age. Thus, we speculated that spatial expression differences of VCAM1 in local lesions of OLP may involve the pathogenesis of OLP.

Transforaminal Interbody Fusion Using the Unilateral Biportal Endoscopic Technique Compared With Transforaminal Lumbar Interbody Fusion for the Treatment of Lumbar Spine Diseases: Analysis of Clinical and Radiological Outcomes.

BACKGROUND: There has been a widespread application of minimally invasive spinal surgery techniques in the past few years. Unilateral biportal endoscopic has been successfully used in a variety of lumbar spine diseases, but there are few studies on lumbar fusion assisted by unilateral biportal endoscopy. OBJECTIVE: To compare the clinical and radiological outcomes of transforaminal interbody fusion using the unilateral biportal endoscopic technique (UBEIF) and transforaminal lumbar interbody fusion (TLIF) in patients with lumbar disease. METHODS: We studied 128 patients, 58 in the UBEIF group and 70 in the TLIF group. The Oswestry disability index, creatine kinase, visual analog score (VAS) for leg and back pain were used to assess clinical outcomes. Radiographic outcomes were assessed using the fusion rate, internal fixation loosening, and adjacent segment degeneration. RESULTS: Back and leg pain VAS scores in both groups were significantly lower 3, 6, and 12 months after surgery ( P < .05). A significant reduction in Oswestry disability index in both groups was observed 6 and 12 months after surgery ( P < .05). Compared with the TLIF group at 1 week after surgery, UBEIF patients' VAS score for back pain significantly improved ( P < .05). There was no difference in fusion rate between the 2 groups (98.27% vs 98.57%). CONCLUSION: UBEIF and TLIF have similar clinical and radiographic outcomes in the treatment of single-segment lumbar disease with lumbar instability, including improved back and leg pain, improved disability, and high fusion rates. Furthermore, with UBEIF, less blood is lost, there is better relief of early back pain, and hospital stays are shorter.

The ginsenoside Rh2 protects porcine oocytes against aging and oxidative stress by regulating SIRT1 expression and mitochondrial activity.

Post-ovulatory aging, a major problem faced by oocytes cultured in vitro, causes oxidative damage and mitochondrial dysfunction in oocytes. The ginsenoside Rh2 is one of the main monomeric components of ginseng, but its effects on porcine oocytes are unknown. In the present study, in vitro aging (IVA) and accelerated induction of aging using H2O2 resulted in DNA damage and an increased incidence of abnormal spindle formation in porcine oocytes. Rh2 supplementation increased the antioxidant capacity, reduced the occurrence of early apoptosis, and improved the development of in vitro fertilized blastocysts. It also rescued the abnormal aggregation of mitochondria and the decrease of the mitochondrial membrane potential under mitochondrial dysfunction. Meanwhile, Rh2 enhanced mRNA expression of the anti-aging and mitochondrial biogenesis-related genes silent information regulator of transcription 1 (SIRT1) and peroxisome proliferator-activated receptor coactivator 1-α (PGC-1α), and the antioxidant gene superoxide dismutase 1 (SOD1). The protection of porcine oocytes against aging and oxidative stress by Rh2 was confirmed using the SIRT1-specific inhibitor EX-527. Our results reveal that Rh2 upregulates SIRT1/PGC-1α to enhance mitochondrial function in porcine oocytes and improve their quality. Our study indicates that Rh2 can be used to prevent mitochondrial dysfunction in oocytes.

Effect of thimerosal on vaccine antigen activity and its mechanism / 中国生物制品学杂志

@#Abstract： Thimerosal is commonly used as a preservative in biological products，especially in vaccines. Although it has been removed from single ⁃ dose vaccines in most countries，thimerosal is still widely used in multi ⁃ dose vaccines at present. Thimerosal，as a component in vaccine preparation，should be compatible with other components，especially should not damage the activity of antigen. However，in recent years，many studies have reported that thiomersal can reduce the antigenicity and immunogenicity of vaccine antigens，especially protein antigens containing or rich in cysteine（Cys）， suggesting that the effect of thimerosal on vaccine antigen activity should be fully evaluated when it is used as a vaccine preservative. In this paper，the effects of thimerosal on antigenicity and immunogenicity of two inactivated vaccines and three recombinant protein vaccines and the possible mechanisms were reviewed，in order to provide reference for rational selection of vaccine preservatives.

Inhibition of astrocytic DRD2 suppresses CNS inflammation in an animal model of multiple sclerosis.

Astrocyte activation is associated with progressive inflammatory demyelination in multiple sclerosis (MS). The molecular mechanisms underlying astrocyte activation remain incompletely understood. Recent studies have suggested that classical neurotransmitter receptors are implicated in the modulation of brain innate immunity. We investigated the role of dopamine signaling in the process of astrocyte activation. Here, we show the upregulation of dopamine D2 receptor (DRD2) in reactive astrocytes in MS brain and noncanonical role of astrocytic DRD2 in MS pathogenesis. Mice deficient in astrocytic Drd2 exhibit a remarkable suppression of reactive astrocytes and amelioration of experimental autoimmune encephalomyelitis (EAE). Mechanistically, DRD2 regulates the expression of 6-pyruvoyl-tetrahydropterin synthase, which modulates NF-κB activity through protein kinase C-δ. Pharmacological blockade of astrocytic DRD2 with a DRD2 antagonist dehydrocorybulbine remarkably inhibits the inflammatory response in mice lacking neuronal Drd2. Together, our findings reveal previously an uncharted role for DRD2 in astrocyte activation during EAE-associated CNS inflammation. Its therapeutic inhibition may provide a potent lever to alleviate autoimmune diseases.

Menisperdaurines A-W, structurally diverse isoquinoline alkaloids from Menispermum dauricum and their dopamine D1 receptor activities.

A total of 33 structurally diverse isoquinoline alkaloids were isolated from the rhizomes of Menispermum dauricum, including seventeen benzylisoquinoline analogues (menisperdaurines A-Q, 1-17), five protoberberine analogues (menisperdaurines R-V, 18-22), a quaternary phenanthrene alkaloid (menisperdaurine W, 23) and ten known compounds (24-33). Compound structures, including absolute configurations, were determined by extensive spectroscopic methods, quantum chemical calculations of chemical shifts, and calculated and experimental electronic circular dichroism (ECD) data. Compounds 1-5 were glycosidic benzylisoquinolines with glucose moieties attached at the C-12 position. Compound 8 was the first example that was isolated from the rhizomes of Menispermum dauricum, benzylisoquinoline and an aromatic unit connected by a sugar bridge. Compounds were evaluated for their inhibitory effects on the dopamine D1 receptor. Compounds 1, 8, 21, 24 and 29 showed potent D1 antagonistic activities, with IC50 values ranging from 1.0 to 4.5 µM. Compound 1 exhibited the highest antagonistic activity with an IC50 value of 1.0 ± 0.2 µM.

Isoquinoline alkaloid dimers with dopamine D1 receptor activities from Menispermum dauricum DC.

A phytochemical investigation on chemical constituents from the rhizomes of Menispermum dauricum DC. identified eight undescribed dimeric alkaloids with structurally diverse monomeric isoquinoline. Alkaloid structures were elucidated by a combination of spectroscopic data analyses and time-dependent density functional theory (TDDFT) ECD calculation. The isolates were evaluated for inhibitory effect on dopamine D1 receptor and compound 1 exhibited potent D1 receptor antagonistic activity with an IC50 value of 8.4 ± 2.0 µM.

Epithelial cell adhesion molecule promotes breast cancer resistance protein-mediated multidrug resistance in breast cancer by inducing partial epithelial-mesenchymal transition.

Overexpression of breast cancer resistance protein (BCRP) plays a crucial role in the acquired multidrug resistance (MDR) in breast cancer. The elucidation of molecular events that confer BCRP-mediated MDR is of major therapeutic importance in breast cancer. Epithelial cell adhesion molecule (EpCAM) has been implicated in tumor progression and drug resistance in various types of cancers, including breast cancer. However, the role of EpCAM in BCRP-mediated MDR in breast cancer remains unknown. In the present study, we revealed that EpCAM expression was upregulated in BCRP-overexpressing breast cancer MCF-7/MX cells, and EpCAM knockdown using siRNA reduced BCRP expression and increased the sensitivity of MCF-7/MX cells to mitoxantrone (MX). The epithelial-mesenchymal transition (EMT) promoted BCRP-mediated MDR in breast cancer cells, and EpCAM knockdown partially suppressed EMT progression in MCF-7/MX cells. In addition, Wnt/ß-catenin signaling was activated in MCF-7/MX cells, and the inhibition of this signaling attenuated EpCAM and BCRP expression and partially reversed EMT. Together, this study illustrates that EpCAM upregulation by Wnt/ß-catenin signaling induces partial EMT to promote BCRP-mediated MDR resistance in breast cancer cells. EpCAM may be a potential therapeutic target for overcoming BCRP-mediated resistance in human breast cancer.

New Thiodiketopiperazine and 3,4-Dihydroisocoumarin Derivatives from the Marine-Derived Fungus Aspergillus terreus.

Aspergillus terreus has been reported to produce many secondary metabolites that exhibit potential bioactivities, such as antibiotic, hypoglycemic, and lipid-lowering activities. In the present study, two new thiodiketopiperazines, emestrins L (1) and M (2), together with five known analogues (3-7), and five known dihydroisocoumarins (8-12), were obtained from the marine-derived fungus Aspergillus terreus RA2905. The structures of the new compounds were elucidated by analysis of the comprehensive spectroscopic data, including high-resolution electrospray ionization mass spectrometry (HRESIMS), one-dimensional (1D) and two-dimensional (2D) nuclear magnetic resonance (NMR), and electronic circular dichroism (ECD) data. This is the first time that the spectroscopic data of compounds 3, 8, and 9 have been reported. Compound 3 displayed antibacterial activity against Pseudomonas aeruginosa (minimum inhibitory concentration (MIC) = 32 µg/mL) and antifungal activity against Candida albicans (MIC = 32 µg/mL). In addition, compound 3 exhibited an inhibitory effect on protein tyrosine phosphatase 1 B (PTP1B), an important hypoglycemic target, with an inhibitory concentration (IC)50 value of 12.25 µM.

Epigenetic Agents Trigger the Production of Bioactive Nucleoside Derivatives and Bisabolane Sesquiterpenes From the Marine-Derived Fungus Aspergillus versicolor.

Epigenetic agents, histone deacetylase inhibitor (SAHA) and DNA methyltransferase inhibitor (5-Aza), were added to Czapek-Dox medium to trigger the chemical diversity of marine-derived fungus Aspergillus versicolor XS-20090066. By HPLC and 1H NMR analysis, the diversity of fungal secondary metabolites was significantly increased compared with the control. With the aid of MS/MS-based molecular networking, two new nucleoside derivatives, kipukasins K (1) and L (2) were obtained. Meanwhile, the yields of four known nucleoside derivatives were significantly enhanced. In addition, one new bisabolane sesquiterpene, aspergillusene E (7), along with ten known derivatives were also isolated. The structures were elucidated by comprehensive spectroscopic methods of NMR and HRESIMS analysis. Compounds 1 and 7 displayed antibacterial activities against Staphylococcus epidermidis and Staphylococcus aureus with the MIC values of 8-16 µg/mL. Our study revealed that the fungus A. versicolor XS-20090066 has been effectively induced by chemical epigenetic manipulation with a combination of SAHA and 5-Aza to produce new metabolites.

Efficacy of travoprost for the treatment of patients with glaucoma.

BACKGROUND: This study will evaluate the efficacy of travoprost for patients with glaucoma systematically. METHODS: A comprehensive literature search will be carried from following literature sources from inception to the present: Cochrane Library, MEDLINE, EMBASE, Web of Science, Google scholar, Chinese Biomedical Literature Database, and China National Knowledge Infrastructure. We will only consider randomized controlled trials on assessing the efficacy and safety of travoprost for glaucoma for inclusion. We will use Cochrane risk of bias tool for the methodological quality assessment for each qualified study. If it is possible, we will pool the outcome data, and will perform meta-analysis. RESULTS: This study will systematically evaluate the efficacy and safety of travoprost for glaucoma. Primary outcomes include intraocular pressure (IOP), mean IOP, and mean reduction of IOP. Secondary outcomes consist of diastolic ocular perfusion pressure, central corneal thickness, and quality of life, as measured by 36-Item Short Form Health Survey, and treatment-related adverse events included hyperemia, eye pain, and eye pruritus. CONCLUSION: The findings of the present study will summarize the updated evidence of travoprost for patients with glaucoma.PROSPERO registration number: PROSPERO CRD42019126956.

[Responses of soil microbial communities in mulberry rhizophere to intercropping and nitrogen application.] / æ¡‘æ ‘æ ¹é™ åœŸå£¤å¾®ç”Ÿç‰©å¯¹é—´ä½œå’Œæ–½æ°®çš„å“åº”.

In this study, the effects of intercropping with alfalfa and nitrogen application on the functional diversity of soil microbial community in mulberry rhizosphere were examined by Biolog-EcoplateTM technique, and principal component and canonical analyses. Compared to monoculture with no nitrogen (N) addition, monoculture with N application and intercropping with alfalfa remarkably reduced soil pH and significantly increased the contents of soil organic matter, soil available N, soil water content, and activities of peroxidase and urease. Monoculture with N application and intercropping with alfalfa (with or without N application) increased the AWCD values, diversity index, and the carbon source utilization ratios of soil microbes. Higher increments of these parameters were detected in the treatment of intercropping plus N application. The results of principal component analysis showed that N application and intercropping changed the capacity of the rhizosphere microbial community for utilizing carbon sources. The utilization of carbon sources highly related to the principal components by the rhizosphere microbial communities was similar in the treatments of monoculture with N application and intercropping without N application. The utilization of itaconic acid and D-glucamaminic acid in the latter was more than 4% and was significantly higher than that in the former. The results from redundancy analysis showed that the soil microbial diversity in mulberry rhizosphere of the treatment of monoculture without N application was positively correlated with polyphenol oxidase activity and negatively correlated with soil water content, whereas that of monoculture with N application and intercropping without N application was significantly positively correlated with soil pH and soil water content and negatively correlated with soil N avalaibility. The diversity of the microbes in the rhizosphere soil of mulberries under the treatment of intercropping with N application showed positive correlation with soil N availability and was significantly negatively correlated with soil pH.

[Research progress on the effects of atmospheric nitrogen dioxide on plant growth and metabo-lism]. / 大气NO2å½±å“æ¤ç‰©ç”Ÿé•¿ä¸Žä»£è°¢çš„ç ”ç©¶è¿›å±•.

Nitrogen dioxide (NO2) is one type of the atmospheric nitrogen oxides, which is the main component of atmospheric aerosol particles. Reducing the concentration of atmospheric NO2 can decrease the haze in the air. Atmospheric NO2 deposits on plant leaves by both dry and wet deposition. After leaf absorption, atmospheric NO2 was reduced by two metabolism ways: one was the nitrogen metabolism by reductase mainly in cytoplasm and chloroplast, and the other was the pathway of NO2 decomposition reaction in the apoplast and cytoplasm. Plant absorption of NO2 disturbs plant normal growth and physiological metabolism, including vegetative growth and reproductive growth, nitrate reductase (NaR) activity, nitrite reductase (NiR) activity, nitrogen uptake, photosynthetic and other physiological metabolic processes. Here, we reviewed the research progress on the effects of atmospheric NO2 on plant growth and metabolism, and proposed the future research direction of physiological and molecular mechanism of atmospheric NO2 absorption by plants.

Gender, Age, and Concomitant Diseases of Colorectal Diverticulum in China: A Study of 7,964 Cases.

AIM: To analyze the epidemiological features of colorectal diverticulum (CRD) in China. METHODS: We retrospectively analyzed CRD patients in 8 tertiary hospitals located in 5 regions of China from 2000 to 2016. The detection rates, number and distribution, demographic information, concomitant disorders, and their associations were investigated. RESULTS: Of 3,446,118 cases, 7,964 (2.3%) were CRD with a mean age of 56 years (11-92 years). The detection rate increased yearly and with increasing age. Males had a higher detection rate than females (3.0 vs. 1.47%, p < 0.01) and 1.8-times higher increase rate. The detection rate increased with age; however, females of > 60 years had a 2.8-times increasing rate than males. CRD occurred most frequently in the right-side colon, followed by rectum. Multiple diverticula were common in males and increased with age, with a 3-times higher increase rate than single lesion. Single-segment CRD occurred more frequently in males than in females (80.1 vs. 76.4%, p < 0.01). Concurred colon polyps were seen in 51.05% cases. CONCLUSION: CRD detection rates increased annually and with age, particularly in senior females in China. Multiple diverticula were common in males and increased with age. CRD was predominant in the right-side colon. Polyps are the most common comorbidity associated with CRD.