Outdoor walking, genetic predisposition, and the risk of incident osteoporosis among older adults: A prospective large population-based cohort study.

This large-scale prospective study showed that a significant association between longer duration of daily outdoor walking and reduced osteoporosis risk was found among older adults, particularly among those with a low genetic predisposition to osteoporosis, which highlighted the importance of outdoor walking as a simple, cost-effective adjunct for preventing osteoporosis. PURPOSE: The available cross-sectional data and small-scale studies indicate that outdoor walking benefits bone metabolism. Nevertheless, there is a scarcity of comprehensive prospective research investigating the enduring correlation between outdoor walking and osteoporosis. This study aims to conduct a prospective analysis of the correlation between outdoor walking and osteoporosis while also examining potential variations influenced by genetic susceptibility to osteoporosis. METHODS: 24,700 older adults without osteoporosis at baseline were enrolled. These individuals were followed up until December 31, 2021, during which data on outdoor walking was gathered. The genetic risk score for osteoporosis was comprised of 14 single-nucleotide polymorphisms. RESULTS: 4,586 cases of osteoporosis were identified throughout a median follow-up period of 37.3 months. Those who walked outside for > 30 but ≤ 60 min per day had a hazard ratio (HR) of 0.83 (95% confidence interval (CI): 0.72-0.95) for incident osteoporosis, whereas those who walked outside for > 60 min per day had an HR of 0.60 (95% CI: 0.39-0.92). We found that osteoporosis risk exhibited a declining trend in individuals with low genetic risk. Individuals walking outside for > 60 min per day tended to have the lowest overall osteoporosis risk among those with high genetic risk. CONCLUSIONS: A significant negative correlation exists between an extended period of daily outdoor walking and osteoporosis incidence risk. This correlation is particularly pronounced among individuals with low genetic risk. The results above underscore the significance of outdoor walking as a simple and economical adjunct to public health programs to prevent osteoporosis.

Indole alkaloids isolated from the Nicotiana tabacum-derived Aspergillus fumigatus 0338 as potential inhibitors for tobacco powdery mildew and their mode of actions.

To explore active natural products against tobacco powdery mildew caused by Golovinomyces cichoracearum, an extract from the fermentation of endophytic Aspergillus fumigatus 0338 was investigated. The mechanisms of action for active compounds were also studied in detail. As a result, 14 indole alkaloid derivatives were isolated, with seven being newly discovered (1-7) and the remaining seven previously described (8-14). Notably, compounds 1-3 are rare linearly fused 6/6/5 tricyclic prenylated indole alkaloids, with asperversiamide J being the only known natural product of this kind. The isopentenyl substitutions at the 5-position in compounds 4 and 5 are also rare, with only compounds 1-(5-prenyl-1H-indol-3-yl)-propan-2-one (8) and 1-(6-methoxy-5-prenyl-1H-indol3-yl)-propan-2-one currently available. In addition, compounds 6 and 7 are new framework indole alkaloid derivatives bearing a 6-methyl-1,7-dihydro-2H-azepin-2-one ring. The purified compounds were evaluated for their activity against G. cichoracearum, and the results revealed that compounds 7 and 9 demonstrated obvious anti-G. cichoracearum activities with an inhibition rate of 82.6% and 85.2%, respectively, at a concentration of 250 µg/mL, these rates were better than that of the positive control agent, carbendazim (78.6%). The protective and curative effects of compounds 7 and 9 were also better than that of positive control, at the same concentration. Moreover, the mechanistic study showed that treatment with compound 9 significantly increased the structural tightness of tobacco leaves and directly affect the conidiospores of G. cichoracearum, thereby enhancing resistance. Compounds 7 and 9 could also induce systemic acquired resistance (SAR), directly regulating the expression of defense enzymes, defense genes, and plant semaphorins, which may further contribute to increased plant resistance. Based on the activity experiments and molecular dockings, the indole core structure may be the foundation of these compounds' anti-G. cichoracearum activity. Among them, the indole derivative parent structures of compounds 6, 7, and 9 exhibit strong effects. Moreover, the methoxy substitution in compound 7 can enhance their activity. By isolating and structurally identifying the above indole alkaloids, new candidates for anti-powdery mildew chemical screening were discovered, which could enhance the utilization of N. tabacum-derived fungi in pesticide development.

Identification of immune-associated biomarker for predicting lung adenocarcinoma: bioinformatics analysis and experiment verification of PTK6.

BACKGROUND: Abnormal expression of protein tyrosine kinase 6 (PTK6) has been proven to be involved in the development of gynecological tumors. However, its immune-related carcinogenic mechanism in other tumors remains unclear. OBJECTIVE: The aim of this study was to identify PTK6 as a novel prognostic biomarker in pan-cancer, especially in lung adenocarcinoma (LUAD), which is correlated with immune infiltration, and to clarify its clinicopathological and prognostic significance. METHODS: The prognostic value and immune relevance of PTK6 were investigated by using bio-informatics in this study. PTK6 expression was validated in vitro experiments (lung cancer cell lines PC9, NCI-H1975, and HCC827; human normal lung epithelial cells BEAS-2B). Western blot (WB) revealed the PTK6 protein expression in lung cancer cell lines. PTK6 expression was inhibited by Tilfrinib. Colony formation and the Cell Counting Kit-8 (CCK-8) assay were used to detect cell proliferation. The wound healing and trans-well were performed to analyze the cell migration capacity. Then flow cytometry was conducted to evaluate the cell apoptosis. Eventually, the relationship between PTK6 and immune checkpoints was examined. WB was used to estimate the PD-L1 expression at different Tilfrinib doses. RESULTS: PTK6 was an independent predictive factor for LUAD and was substantially expressed in LUAD. Pathological stage was significantly correlated with increased PTK6 expression. In accordance with survival analysis, poor survival rate in LUAD was associated with a high expression level of PTK6. Functional enrichment of the cell cycle and TGF-ß signaling pathway was demonstrated by KEGG and GSEA analysis. Moreover, PTK6 expression considerably associated with immune infiltration in LUAD, as determined by immune analysis. Thus, the result of vitro experiments indicated that cell proliferation and migration were inhibited by the elimination of PTK6. Additionally, PTK6 suppression induced cell apoptosis. Obviously, PD-L1 protein expression level up-regulated while PTK6 was suppressed. CONCLUSION: PTK6 has predictive value for LUAD prognosis, and could up regulated PD-L1.

Porcine Brain Enzyme Hydrolysate Enhances Immune Function and Antioxidant Defense via Modulation of Gut Microbiota in a Cyclophosphamide-Induced Immunodeficiency Model.

This study examined how consuming porcine brain enzyme hydrolysate (PBEH) affects the immune function and composition of the gut microbiota in an immunodeficient animal model. Male Wistar rats aged 6 weeks were fed casein (control), 100 mg/kg body weight (BW), red ginseng extract (positive-control), and 6, 13, and 26 mg PBEH per kg BW (PBEH-L, PBEH-M, and PBEH-H, respectively) daily for 4 weeks. At 30 min after consuming assigned compounds, they were orally administered cyclophosphamide (CTX; 5 mg/kg BW), an immunosuppressive agent, to suppress the immune system by inhibiting the proliferation of lymphocytes. The normal-control rats were fed casein and water instead of CTX. Natural killer cell activity and splenocyte proliferation induced by 1 µg/mL lipopolysaccharide were lower in the control group than the normal-control group, and they significantly increased with PBEH consumption, particularly at high doses. The PBEH consumption increased dose-dependently in the Th1/Th2 ratio compared to the control. The lipid peroxide contents were lower in the PBEH group than in the control group. Moreover, PBEH m and PBEH-H consumption mitigated white pulp cell damage, reduced red pulp congestion, and increased spleen mast cells in the histological analysis. Intestinal microbiota composition demonstrated differences between the groups at the genus levels, with Akkermansia being more abundant in the control group than the normal-control group and the PBEH-H group showing a decrease. However, Bifidobacterium decreased in the control group but increased in the PBEH-H group. The ß-diversity revealed distinct microbial communities of PBEH and positive-control groups compared to the control group (p < 0.05). The metagenome predictions revealed that PBEH-H influenced amino acid metabolism, antioxidant defense, insulin sensitivity, and longevity pathways. In conclusion, PBEH-H intake boosted immune responses and reduced lipid peroxides by modulating gut microbiota composition. These findings suggest that PBEH-H has the potential as a dietary supplement for improving immune function and gut health in individuals with immunodeficiency.

[Effects of α1-antitrypsin on motor function in mice with immature brain white matter injury]. / α1-æŠ—èƒ°è›‹ç™½é ¶å¯¹æœªæˆç†Ÿè„‘ç™½è´¨æŸä¼¤å°é¼ è¿åŠ¨åŠŸèƒ½çš„å½±å“.

OBJECTIVES: To investigate the effects of α1-antitrypsin (AAT) on motor function in adult mice with immature brain white matter injury. METHODS: Five-day-old C57BL/6J mice were randomly assigned to the sham surgery group (n=27), hypoxia-ischemia (HI) + saline group (n=27), and HI+AAT group (n=27). The HI white matter injury mouse model was established using HI methods. The HI+AAT group received intraperitoneal injections of AAT (50 mg/kg) 24 hours before HI, immediately after HI, and 72 hours after HI; the HI+saline group received intraperitoneal injections of the same volume of saline at the corresponding time points. Brain T2-weighted magnetic resonance imaging scans were performed at 7 and 55 days after modeling. At 2 months of age, adult mice were evaluated for static, dynamic, and coordination parameters using the Catwalk gait analysis system. RESULTS: Compared to the sham surgery group, mice with HI injury showed high signal intensity on brain T2-weighted magnetic resonance imaging at 7 days after modeling, indicating significant white matter injury. The white matter injury persisted at 55 days after modeling. In comparison to the sham surgery group, the HI+saline group exhibited decreased paw print area, maximum contact area, average pressure, maximum pressure, paw print width, average velocity, body velocity, stride length, swing speed, percentage of gait pattern AA, and percentage of inter-limb coordination (left hind paw → left front paw) (P<0.05). The HI+saline group showed increased inter-paw distance, percentage of gait pattern AB, and percentage of phase lag (left front paw → left hind paw) compared to the sham surgery group (P<0.05). In comparison to the HI+saline group, the HI+AAT group showed increased average velocity, body velocity, stride length, and swing speed (right front paw) (P<0.05). CONCLUSIONS: The mice with immature brain white matter injury may exhibit significant motor dysfunction in adulthood, while the use of AAT can improve some aspects of their motor function.

ANOPOW FOR REPLICATED NONSTATIONARY TIME SERIES IN EXPERIMENTS.

We propose a novel analysis of power (ANOPOW) model for analyzing replicated nonstationary time series commonly encountered in experimental studies. Based on a locally stationary ANOPOW Cramér spectral representation, the proposed model can be used to compare the second-order time-varying frequency patterns among different groups of time series and to estimate group effects as functions of both time and frequency. Formulated in a Bayesian framework, independent two-dimensional second-order random walk (RW2D) priors are assumed on each of the time-varying functional effects for flexible and adaptive smoothing. A piecewise stationary approximation of the nonstationary time series is used to obtain localized estimates of time-varying spectra. Posterior distributions of the time-varying functional group effects are then obtained via integrated nested Laplace approximations (INLA) at a low computational cost. The large-sample distribution of local periodograms can be appropriately utilized to improve estimation accuracy since INLA allows modeling of data with various types of distributions. The usefulness of the proposed model is illustrated through two real data applications: analyses of seismic signals and pupil diameter time series in children with attention deficit hyperactivity disorder. Simulation studies, Supplementary Materials (Li, Yue and Bruce, 2023a), and R code (Li, Yue and Bruce, 2023b) for this article are also available.

Therapeutic potential for renal fibrosis by targeting Smad3-dependent noncoding RNAs.

Renal fibrosis is a characteristic hallmark of chronic kidney disease (CKD) that ultimately results in renal failure, leaving patients with few therapeutic options. TGF-ß is a master regulator of renal fibrosis and mediates progressive renal fibrosis via both canonical and noncanonical signaling pathways. In the canonical Smad signaling, Smad3 is a key mediator in tissue fibrosis and mediates renal fibrosis via a number of noncoding RNAs (ncRNAs). In this regard, targeting Smad3-dependent ncRNAs may offer a specific therapy for renal fibrosis. This review highlights the significance and innovation of TGF-ß/Smad3-associated ncRNAs as biomarkers and therapeutic targets in renal fibrogenesis. In addition, the underlying mechanisms of these ncRNAs and their future perspectives in the treatment of renal fibrosis are discussed.

Study of discrepancy in subjective and objective cognitive function in patients with depressive disorder / 四川精神卫生

BackgroundThere exist differences in the subjective and objective cognitive functions of patients with depressive disorder， ane there are limited research on influencing factors of such phenomenon currently. ObjectiveTo explore the differences in subjective and objective cognitive function in patients with depressive disorder as well as influencing factors， and to provide references for further understanding of cognitive impairment in patients with depressive disorder. MethodsA total of 77 patients with depressive disorder who received outpatient or inpatient treatment in the Fourth People's Hospital of Chengdu from January 13， 2022 to December 11， 2023 were selected for the study. These patients also met the diagnostic criteria of Diagnostic and Statistical Manual of Mental Disorders， fifth edition（DSM-5）. Various tools were employed to assess patients in this study： Montgomery-Asberg Depression Rating Scale （MADRS） for the depressive symptoms， Perceived Deficits Questionnaire for Depression （PDQ-D） and Chinese Version of Brief Neurocognitive Test Battery （C-BCT） for the subjective and objective cognitive function， Sheehan Disability Scale （SDS） for the social function， and Clinical Global Impression-Severity of Illness（CGI-SI） for the severity of patient's condition. Pearson correlation analysis was used to examine the correlation of subjective and objective cognitive function and their differences with age， years of education， MADRS total score， SDS total score， and CGI-SI score. Multiple linear regression was used to explore the influencing factors of the differences between subjective and objective cognitive function. ResultsThere was a statistically significant difference in the total PDQ-D scores and the difference of subjective and objective cognitive function （D value） between depressive patients with and without medication （t=-4.228， -2.392， P<0.05 or 0.01）. There was no statistically significant correlation in subjective and objective cognitive function in patients with depressive disorder （r=-0.148， P>0.05）. Negative correlations can be observed between the PDQ-D total score and age or years of education （r=-0.333， -0.369， P<0.01）. The PDQ-D total score was positively correlated with MADRS total score， SDS total score and CGI-SI score （r=0.487， 0.637， 0.434， P<0.01）. D value was negatively correlated with age and years of education （r=-0.411， -0.362， P<0.01）， while positively correlated with MADRS total score， SDS total score and CGI-SI score （r=0.259， 0.468， 0.299， P<0.05 or 0.01）. Age （β=-0.328， P<0.01） and SDS total score （β=0.409， P<0.01） were two predictive factors for D value. ConclusionThe difference between subjective and objective cognitive function among patients with depressive disorder is related to several factors including age， years of education， severity of symptoms and impairment of social function. ［Funded by Surface Project of National Natural Science Foundation of China （number， 62173069）； Technological Innovation 2030-Major Project of "Brain Science and Brain-Like Research" （number， 2022ZD0211700）； Key R&D Support Program and Major Application Demonstration Project of Chengdu Science and Technology Bureau （number， 2022-YF09-00023-SN）］

Comprehensive analysis of cuproptosis-associated LncRNAs predictive value and related CeRNA network in acute myeloid leukemia.

Background: Acute myeloid leukemia (AML) is characterized by a high recurrence and mortality rate. Cuproptosis is involved in cell death regulation in in a variety of solid tumors. Long non-coding RNAs that regulate cuproptosis genes in the pathogenesis of acute leukemia have yet to be explored. Methods: First, cuproptosis genes with distinct expression levels were discovered by contrasting AML with normal samples from the TCGA and GTEx cohorts. Pearson correlation and univariate Cox-regression analysis were performed to identify cuproptosis-associated lncRNAs with significant prognostic values. Then the least absolute shrinkage and selection operator (LASSO) Cox regression was utilized to establish a multi-gene signature to predict AML prognosis. Next, Kaplan-Meier estimator, receiver operating characteristic curve, and a nomogram were performed to evaluate the predictive capacity of the risk signature. Functional enrichment analyses were employed to assess their function. Moreover, qRT-PCR testing of lncRNA expression in AML samples was conducted. The competing endogenous RNA (ceRNA) network was constructed to find the target genes. Results: A risk model based on the signature of three cuproptosis-associated lncRNAs was developed. The results showed that the model possessed excellent prognostic potential. The nomogram raised the accuracy in predicting AML survival. In addition, functional enrichment analyses demonstrated an enrichment of inflammatory and immune-related pathways. Moreover, correlations between the risk signature and clinicopathological variables, tumor mutational burden, RNA stemness score, immune profile, and drug sensitivity were observed. Furthermore, we discovered that TRAF3IP2-AS1 may function as a ceRNA to regulate cuproptosis and ferroptosis gene expression. Conclusion: The risk signature established in this study could serve as a reliable biosignature for AML prognosis. And the findings presented here may facilitate research on cuproptosis in AML.

Extraction and characterization of anti-virus anthraquinones from Nicotiana tabacum-derived Aspergillus oryzae YNCA1220.

In this study, seven novel anthraquinones (1-7) and four described anthraquinones (8-11) were purified from Nicotiana tabacum-derived Aspergillus oryzae YNCA1220. It is worth noting that only analogs of 4 and 5 have been reported as natural products to date, while the nuclei of compounds 1-3, 6 and 7 were isolated for the first time in nature. Among them, compounds 1-3 bear an unusual anthra[2,3-b]furan-9,10-dione nucleus, 4 and 5 possess a rare 3-methyl-1H-pyrrol-2-yl substituent, and 6 and 7 are new framework anthraquinones bearing a 6-methyl-1,7-dihydro-2H-azepin-2-one ring. Interestingly, the in vivo assays indicated that 1, 4 and 5 had inactivation effects against tobacco mosaic virus (TMV) with inhibition rates of 41.6%, 55.4% and 38.6%, respectively, at a concentration of 50 µg/mL, which were better than that of the positive control agent, ningnanmycin (33.8%). Compounds 1, 4 and 5 also had protective effects with inhibition rates of 48.7%, 60.2% and 43.5% at the same concentration, while 4 had a better curative effect than ningnanmycin at a concentration of 100 µg/mL. In addition, mechanistic studies also revealed that a potent direct effect on TMV, the induction of SAR in tobacco plants, and the effective regulation of defense enzymes, defense genes, and defense hormones may be the reasons for the significant effects of 4 against TMV. At the same time, downregulation of the expression of total NtHsp70 protein by inhibiting the related Hsp70 genes may also be involved in tobacco resistance to TMV. To evaluate whether compounds have broader antiviral activities, the antirotavirus activities of new isolates were also evaluated and found to be highly effective with a therapeutic index (TI) value ranging from 11.6 to 17.7. This study suggests that the above anthraquinone compounds, particularly 4, have broad spectrum antiviral activities. The successful isolation and structure identification of the above anthraquinones provide new materials for the screening of anti-TMV agents and contribute to the improved utilization of N. tabacum-derived fungi.

Nitric oxide synthase and its function in animal reproduction: an update.

Nitric oxide (NO), a free radical labile gas, is involved in the regulation of various biological functions and physiological processes during animal reproduction. Recently, increasing evidence suggests that the biological role and chemical fate of NO is dependent on dynamic regulation of its biosynthetic enzyme, three distinct nitric oxide synthase (NOS) according to their structure, location and function. The impact of NOS isoforms on reproductive functions need to be timely elucidated. Here, we focus on and the basic background and latest studies on the development, structure, importance inhibitor, location pattern, complex functions. Moreover, we summarize the exactly mechanisms which involved some cell signal pathways in the regulation of NOS with cellular and molecular level in the animal reproduction. Therefore, this growing research area provides the new insight into the important role of NOS male and female reproduction system. It also provides the treatment evidence on targeting NOS of reproductive regulation and diseases.

Marinihelvus fidelis gen. nov., sp. nov., isolated from marine sediment, and genomic comparison with multiple genera.

A Gram-stain-negative, rod-shaped, non-gliding, non-flagellated, yellow, facultatively aerobic bacterial strain, designated as W260T, was isolated from marine sediment of Xiaoshi Island, Weihai, PR China. The cells of W260T were 0.3-0.5 µm wide and 1.5-2.0 µm long. Strain W260T grows optimally at a temperature of 33 °C (range, 15-37 °C), pH 8 (range, pH 6.5-9.5) and witha NaCl concentration of 3.0 % (w/v; range, 1-8 %). It has the highest sequence similarity to Thiohalobacter thiocyanaticus DSM 21152T (91.7 %), followed by Wenzhouxiangella marina MCCC 1K00261T (91.4 %) and Thiohalospira alkaliphila DSM 17116T (90.7 %). The similarity between strain W260T and the species Thiohalophilus thiocyanatoxydans DSM 16326T was 89.4 %. Genome sequencing revealed a genome size of 3 430 000 bp and a DNA G+C content of 64.5 mol%. The average nucleotide identity and digital DNA-DNA hybridization values between strain W260T and W. marina MCCC 1K00261T were 69.6 and 16.1-20.6 %, respectively. The predominant quinone was ubiquitin-8, and the major fatty acids were iso-C14 : 0 and iso-C16 : 0. The polar lipids consisted of phosphatidylethanolamine, phospholipid, phosphatidylglycerol, diphosphatidylglycerol and four unidentified lipids. Based on phenotypic, phylogenetic and chemotaxonomic information, it was determined that strain W260T represents a novel genus and species and it was given the name Marinihelvus fidelis sp. nov. The type strain is W260T (=MCCC 1H00471T=KCTC 92639T).

Penicopeptide A (PPA) from the deep-sea-derived fungus promotes osteoblast-mediated bone formation and alleviates ovariectomy-induced bone loss by activating the AKT/GSK-3ß/ß-catenin signaling pathway.

The potential of marine natural products as effective drugs for osteoporosis treatment is an understudied area. In this study, we investigated the ability of lead compounds from deep-sea-derived Penicillium solitum MCCC 3A00215 to promote bone formation in vitro and in vivo. We found that penicopeptide A (PPA) promoted osteoblast mineralization among bone marrow mesenchymal stem cells (BMSCs) in a concentration-dependent manner, and thus, we selected this natural peptide for further testing. Our further experiments showed that PPA significantly promoted the osteogenic differentiation of BMSCs while inhibiting their adipogenic differentiation and not affecting their chondrogenic differentiation. Mechanistic studies showed that PPA binds directly to the AKT and GSK-3ß and activates phosphorylation of AKT and GSK-3ß, resulting in the accumulation of ß-catenin. We also evaluated the therapeutic potential of PPA in a female mouse model of ovariectomy-induced systemic bone loss. In this model, PPA treatment prevented decreases in bone volume and trabecular thickness. In conclusion, our in vitro and in vivo results demonstrated that PPA could promote osteoblast-related bone formation via the AKT, GSK-3ß, and ß-catenin signaling pathways, indicating the clinical potential of PPA as a candidate compound for osteoporosis prevention.

Halocynthiibacter halioticoli sp. nov., isolated from the viscera of abalone Haliotis discus hannai.

A Gram-stain-negative, rod-shaped, glide, non-flagellated, and facultatively anaerobic bacterial strain, designated as Z654T, was isolated from the gut of abalone Haliotis discus hannai from Rongcheng, Shandong province, China. Cells are 0.2-0.8 µm in width and 0.7-3.4 µm in length. Cells grew best at 30 °C (range, 15-37 °C), pH 7.0 (range, 6.0-8.5) and NaCl concentration of 2.0% (w/v) (range, 1-10%). According to the phylogenetic analysis of 16S rRNA gene sequence, the strain belongs to the genus Halocynthiibacter and the closest strain is Halocynthiibacter arcticus KCTC 42129 T (97.12%). The genome size of strain Z654T was 3,296,250 bp and the DNA G + C content was 54.2 mol%. The average nucleotide identity (ANI) scores and digital DNA-DNA hybridization (dDDH) scores with H. arcticus KCTC 42129 T were 70% and 14.6-18.2%, respectively. The predominant quinone was Q-10 and the major fatty acids were C18:0, C18:1 ω7c 11-methyl and summed feature 8. The polar lipids consisted of phosphatidylcholine, phosphatidylglycerol, unidentified aminolipid and unidentifed lipids. Based on the phenotypic, phylogenetic and chemotaxonomic data, strain Z654T was considered to represent a novel species of the genus Halocynthiibacter, for which the name Halocynthiibacte halioticoli sp. nov., is proposed. The type strain is Z654T (= MCCC 1H00503T = KCTC 92003 T).

Association between inflammatory cytokines and oxidative stress levels in aqueous humor with axial length in human myopia.

This study investigated the content of inflammatory cytokines and oxidative stress levels in the aqueous humor (AH) of patients with high myopia (HM) and explored the relationship between these factors and the axial length (AL) of the eye, to explore the roles of mild intraocular inflammation and oxidative stress imbalance in the occurrence and development of myopia. AH samples from 40 patients (70 eyes) were collected during implantable collamer lens (ICL-V4c) surgery. The subjects were divided into three groups according to AL: group A (AL ≤ 26 mm), group B (26 < AL ≤ 28 mm), and group C (AL ≥ 28 mm). The concentrations of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), matrix metalloproteinase-2 (MMP-2), and interleukin-1ß (IL-1ß) in the AH of the three groups were measured using the Luminex system. Oxidative stress levels were measured using reagent kits targeting total antioxidant capacity (T-AOC), catalase (CAT), and nitric oxide (NO) and malonaldehyde (MDA) content. The results showed compared with group A, IL-1ß, MMP-2, and IL-6 concentrations were significantly higher and T-AOC levels were significantly lower in group C. There were no significant differences in CAT, NO, MDA, or TNF-α levels among the groups. The concentrations of IL-6 (r = 0.379, p = 0.016), MMP-2 (r = 0.469, p = 0.002), and MDA (r = 0.354, p = 0.025) in AH were positively correlated with the AL, whereas T-AOC (r = -0.678, p = 0.000) was negatively correlated with AL. These results suggest that mild intraocular inflammation and oxidative stress imbalance may be associated with myopia. Further experiments are needed to confirm the role of mild intraocular inflammation and oxidative stress imbalance in the occurrence and development of myopia.

Dual hypoxia-responsive supramolecular complex for cancer target therapy.

The prognosis with pancreatic cancer is among the poorest of any human cancer. One of the important factors is the tumor hypoxia. Targeting tumor hypoxia is considered a desirable therapeutic option. However, it has not been translated into clinical success in the treatment of pancreatic cancer. With enhanced cytotoxicities against hypoxic pancreatic cancer cells, BE-43547A2 (BE) may serve as a promising template for hypoxia target strategy. Here, based on rational modification, a BE prodrug (NMP-BE) is encapsulated into sulfonated azocalix[5]arene (SAC5A) to generate a supramolecular dual hypoxia-responsive complex NMP-BE@SAC5A. Benefited from the selective load release within cancer cells, NMP-BE@SAC5A markedly suppresses tumor growth at low dose in pancreatic cancer cells xenograft murine model without developing systemic toxicity. This research presents a strategy for the modification of covalent compounds to achieve efficient delivery within tumors, a horizon for the realization of safe and reinforced hypoxia target therapy using a simple approach.

Three new isoquinoline alkaloids from the fermentation of Aspergillus sp. 0338 and their anti-MRSA activities.

There is growing evidence that bioactive substances produced by microbial endophytes have applicability in medicine, agriculture and industry. To enrich the bioactive substances, in our search for new bioactive metabolites from fungi Aspergillus, the phytochemical reinvestigation on the Aspergillus sp. 0338 was carried out, and this led to the isolation of three new (1-3) and five known alkaloids (4-8). Their structures were elucidated by spectroscopic analysis, including extensive 1D and 2D NMR techniques, as well as comparison with literature values. Additionally, compounds 1-3 were evaluated for their anti-MRSA activities. The results revealed that compounds 1-3 exhibited good inhibitions with IZD of 15.2 ± 1.8, 14.6 ± 2.0, and 13.4 ± 2.2 mm, respectively.

Dynamic Phosphorylation of G9a Regulates its Repressive Activity on Chromatin Accessibility and Mitotic Progression.

Phosphorylation of Ser10 of histone H3 (H3S10p), together with the adjacent methylation of Lys9 (H3K9me), has been proposed to function as a 'phospho-methyl switch' to regulate mitotic chromatin architecture. Despite of immense understanding of the roles of H3S10 phosphorylation, how H3K9me2 are dynamically regulated during mitosis is poorly understood. Here, it is identified that Plk1 kinase phosphorylates the H3K9me1/2 methyltransferase G9a/EHMT2 at Thr1045 (pT1045) during early mitosis, which attenuates its catalytic activity toward H3K9me2. Cells bearing Thr1045 phosphomimic mutant of G9a (T1045E) show decreased H3K9me2 levels, increased chromatin accessibility, and delayed mitotic progression. By contrast, dephosphorylation of pT1045 during late mitosis by the protein phosphatase PPP2CB reactivates G9a activity and upregulates H3K9me2 levels, correlated with decreased levels of H3S10p. Therefore, the results provide a mechanistic explanation of the essential of a 'phospho-methyl switch' and highlight the importance of Plk1 and PPP2CB-mediated dynamic regulation of G9a activity in chromatin organization and mitotic progression.

Winogradskyella vincentii sp. nov. and Winogradskyella alexanderae sp. nov., two novel bacteria isolated from intertidal sediment.

Two novel Gram-stain-negative, facultative anaerobic, chemoheterotrophic, non-motile and rod-shaped strains were isolated from intertidal sediment sampled at Xiaoshi Island, Weihai, PR China. Full sequence analysis of the 16S rRNA genes showed that the two strains were closely related to members of the genus Winogradskyella and the phylogenetic similarities to their closest relative, Winogradskyella aquimaris, were 96.7 and 95.8 %, respectively. The DNA G+C contents of strains 2Y89T and D23T were 33.3 and 35.1 mol%, respectively. The respiratory quinone detected in both strains was MK-6. The major fatty acids detected in strain 2Y89T were iso-C15 : 0 and iso-C15 : 1G, and in strain D23T they were iso-C15 : 1G, iso-C15 : 0 and iso-C17 : 03-OH. The principal polar lipids of strain 2Y89T mainly included phosphatidylethanolamine, aminoglycolipids, unidentified aminolipids, unidentified glycolipids and unidentified lipids; strain D23T was the same as strain 2Y89T except that it did not contain aminoglycolipids. Based on the phenotypic, chemical taxonomic, genotypic and phylogenetic features established in this study, we suggest that the new strains represent two novel species of the genus Winogradskyella, for which the names Winogradskyella vincentii sp. nov. (type strain 2Y89T=MCCC 1H00477T=KCTC 92034T) and Winogradskyella alexanderae sp. nov. (type strain D23T=MCCC 1H00462T=KCTC 92023T) are proposed.

Protective Effect of Long-Term Fermented Soybeans with Abundant Bacillus subtilis on Glucose and Bone Metabolism and Memory Function in Ovariectomized Rats: Modulation of the Gut Microbiota.

We investigated the effects of different types of long-term fermented soybeans (traditionally made doenjang; TMD) on glucose and bone metabolism and memory function in ovariectomized (OVX) rats. The rats were categorized into six groups: Control, cooked unfermented soybeans (CSB), and four TMDs based on Bacillus subtilis (B. subtilis) and biogenic amine contents analyzed previously: high B. subtilis (HS) and high biogenic amines (HA; HSHA), low B. subtilis (LS) and HA (LSHA), HS and low biogenic amines (LA; HSLA), and LS and LA (LSLA). The rats in the CSB and TMD groups fed orally had a 4% high-fat diet for 12 weeks. Rats in the Control (OVX rats) and Normal-control (Sham-operated rats) groups did not consume CSB or TMD, although macronutrient contents were the same in all groups. Uterine weight and serum 17ß-estradiol concentrations were much lower in the Control than the Normal-control group, but CSB and TMD intake did not alter them regardless of B. subtilis and biogenic amine contents. HOMA-IR, a measure of insulin resistance, decreased with TMD with high B. subtilis (HSLA and HSHA) compared to the Control group. In OGTT and IPGTT, serum glucose concentrations at each time point were higher in the Control than in the Normal-control, and HSLA and HSHA lowered them. Memory function was preserved with HSHA and HSLA administration. Bone mineral density decline measured by DEXA analysis was prevented in the HSHA and HSLA groups. Bone metabolism changes were associated with decreased osteoclastic activity, parathyroid hormone levels, and osteoclastic activity-related parameters. Micro-CT results demonstrated that TMD, especially HSLA and HSHA, preserved bone structure in OVX rats. TMD also modulated the fecal bacterial community, increasing Lactobacillus, Ligalactobacillus, and Bacillus. In conclusion, through gut microbiota modulation, TMD, particularly with high B. subtilis content, acts as a synbiotic to benefit glucose, bone, and memory function in OVX rats. Further research is needed to make specific recommendations for B. subtilis-rich TMD for menopausal women.