Trends and patterns in stroke incidence, mortality, DALYs and case-fatality by sociodemographic index worldwide: an age-period-cohort analysis using the Global Burden of Disease 2019 study.

OBJECTIVES: Stroke is a significant public health burden worldwide. This study aimed to explore the trends and patterns of stroke incidence, mortality, disability-adjusted life years (DALYs) and case-fatality percent (CFP) worldwide from 1990 to 2019. STUDY DESIGN: Age-period-cohort analysis. METHODS: Trends in stroke burden worldwide were evaluated using data from the Global Burden of Disease 2019 study. In addition, the relationship between the burden of stroke and sociodemographic index (SDI) was examined by quantile regression. Age, period and cohort patterns in stroke burden across different SDI groups were estimated using age-period-cohort analysis. RESULTS: Between 1990 and 2019, the age-standardised rates (ASRs) of stroke incidence, mortality and DALYs declined significantly worldwide, with decreases of -16.89% (95% uncertainty interval [UI]: -18.41 to -15.29), -36.43% (95% UI: -41.65 to -31.20) and -35.23% (95% UI: -40.49 to -30.49), respectively. Regions with ASRs in the 75th percentile and below experienced significant decreases in ASRs with increasing SDI. After 2014, there was a stable or slightly increased period effect for stroke incidence in all groups, while mortality, DALYs and CFP increased only in the high SDI group. The cohort effect of stroke incidence remained constant in the high SDI group from the 1960-1964 cohort onwards. CONCLUSIONS: Although high SDI regions had a lower stroke burden and a faster overall decline in burden, the recent relative risk data suggest a potential deceleration in the progress of reducing stroke burden in these areas. There is a need for more active measures to reduce the stroke burden in areas with the highest incidence, mortality and DALYs, as increasing SDI alone cannot lower the burden in these regions.

The value of single-channel endoscopic traction and kiss suture technique in closing wounds caused by endoscopic resection of gastrointestinal muscularis propria tumors.

BACKGROUND: To investigate the value of single forceps endoscopic traction stapling suture technique (SFETSST) in closing wounds caused by endoscopic resection of gastrointestinal muscularis propria tumor (GMPT). METHODS: Consecutive patients who underwent submucosal tumor excavation (ESE) and endoscopic full-thickness resection (EFR) for GMPT in the Second Affiliated Hospital of Xiamen Medical College from January 2015 to January 2022 were retrospectively collected. They were divided into the SFETSST group and the standard group (patients who receive single forceps traction-free endoscopic suture technique). The healing effects were compared between the two groups. RESULTS: Seventy-seven patients were included in our study with 50 patients included in SFETSST group. The baseline characteristics had no significant difference between the two groups. The technical success rate of wound suture in SFETSST cluster was significantly upper than that within standard cluster (100% vs. 88.89%, P = 0.04). The wound suture time in SFETSST cluster was significantly lower than that within standard cluster (33.19 ± 10.64 min, P < 0.001). Moreover, the incidence rates of intra-operative and postoperative complications in SFETSST cluster were lower than standard cluster (0 vs. 7.41%, P = 0.051 and 0 vs. 11.11%, P = 0.016). Interestingly, the SFETSST cluster had lower cost of consumables (2485.40 ± 591.78 vs. 4098.52 ± 1903.06 Yuan, P = 0.01) and shorter hospital stay (4.96 ± 0.90 vs. 7.19 ± 2.45, P < 0.001) than standard cluster. CONCLUSION: Our study showed that to fully closure the full-thickness defects of digestive tract, SFETSST was effective, safe, and economical, which was worth popularizing.

Enhanced thermal stability of the ß-galactosidase BgaB from Bacillus circulans by cyclization mediated via SpyTag/SpyCatcher interaction and its use in galacto-oligosaccharides synthesis.

Cyclization of proteins using SpyTag/SpyCatcher is a novel approach to increase their thermal stability. In this paper, we test this approach on two ß-galactosidases from Bacillus circulans, BgaB and BgaC, and find that BgaB was stabilized while BgaC was not. Wild-type BgaB precipitated completely upon heating above 70 °C, but after SpyRing cyclization, it remained soluble after heating to 90 °C. Similarly, wild-type BgaB retained only 50 % activity after heating at 60 °C for 10 min, but this increased to 80 % after SpyRing cyclization. In contrast, cyclization decreased the stability of BgaC. After SpyRing cyclization, BgaC only retained 2 % activity after 20-min incubation at 55 °C, whereas the wild-type BgaC retained 25 % activity. One reason for the different effect of cyclization may the shorter distance between the N- and C-termini in BgaB (20.2 Å) as compared to BgaC (43.7 Å). The intrinsic fluorescence and circular dichroism spectra suggested that SpyRing cyclization of BgaB did not significantly change its conformation or secondary structure. SpyRing cyclized BgaB yielded similar amounts and compositions of galacto-oligosaccharides using a high initial lactose concentration (40 %, w/v), but a slightly higher amount at low initial lactose concentration (5 %, w/v) suggesting increased transgalactosylation activity.

A positive feedback regulatory loop, SA-AtNAP-SAG202/SARD1-ICS1-SA, in SA biosynthesis involved in leaf senescence but not defense response.

Salicylic acid (SA) is an important plant hormone that regulates defense responses and leaf senescence. It is imperative to understand upstream factors that regulate genes of SA biosynthesis. SAG202/SARD1 is a key regulator for isochorismate synthase 1 (ICS1) induction and SA biosynthesis in defense responses. The regulatory mechanism of SA biosynthesis during leaf senescence is not well understood. Here we show that AtNAP, a senescence-specific NAC family transcription factor, directly regulates a senescence-associated gene named SAG202 as revealed in yeast one-hybrid and in planta assays. Inducible overexpreesion of AtNAP and SAG202 lead to high levels of SA and precocious senescence in leaves. Individual knockout mutants of sag202 and ics1 have markedly reduced SA levels and display a significantly delayed leaf senescence phenotype. Furthermore, SA positively feedback regulates AtNAP and SAG202. Our research has uncovered a unique positive feedback regulatory loop, SA-AtNAP-SAG202-ICS1-SA, that operates to control SA biosynthesis associated with leaf senescence but not defense response.

The leaf senescence-promoting transcription factor AtNAP activates its direct target gene CYTOKININ OXIDASE 3 to facilitate senescence processes by degrading cytokinins.

Cytokinins (CKs) are a class of adenine-derived plant hormones that plays pervasive roles in plant growth and development including cell division, morphogenesis, lateral bud outgrowth, leaf expansion and senescence. CKs as a "fountain of youth" prolongs leaf longevity by inhibiting leaf senescence, and therefore must be catabolized for senescence to occur. AtNAP, a senescence-specific transcription factor has a key role in promoting leaf senescence. The role of AtNAP in regulating CK catabolism is unknown. Here we report the identification and characterization of AtNAP-AtCKX3 (cytokinin oxidase 3) module by which CKs are catabolized during leaf senescence in Arabidopsis. Like AtNAP, AtCKX3 is highly upregulated during leaf senescence. When AtNAP is chemically induced AtCKX3 is co-induced; and when AtNAP is knocked out, the expression of AtCKX3 is abolished. AtNAP physically binds to the cis element of the AtCKX3 promoter to direct its expression as revealed by yeast one-hybrid assays and in planta experiments. Leaves of the atckx3 knockout lines have higher CK concentrations and a delayed senescence phenotype compared with those of WT. In contrast, leaves with inducible expression of AtCKX3 have lower CK concentrations and exhibit a precocious senescence phenotype compared with WT. This research reveals that AtNAP transcription factor-AtCKX3 module regulates leaf senescence by connecting two antagonist plant hormones abscisic acid and CKs.

Long-Term Trends in Unintentional Fall Mortality in China: A Population-Based Age-Period-Cohort Study.

Background: Unintentional falls seriously threaten the life and health of people in China. This study aimed to assess the long-term trends of mortality from unintentional falls in China and to examine the age-, period-, and cohort-specific effects behind them. Methods: This population-based multiyear cross-sectional study of Chinese people aged 0-84 years was a secondary analysis of the mortality data of fall injuries from 1990 to 2019, derived from the Global Burden of Disease Study 2019. Age-standardized mortality rates of unintentional falls by year, sex, and age group were used as the main outcomes and were analyzed within the age-period-cohort framework. Results: Although the crude mortality rates of unintentional falls for men and women showed a significant upward trend, the age-standardized mortality rates for both sexes only increased slightly. The net drift of unintentional fall mortality was 0.13% (95% CI, -0.04 to 0.3%) per year for men and -0.71% (95% CI, -0.96 to -0.46%) per year for women. The local drift values for both sexes increased with age group. Significant age, cohort, and period effects were found behind the mortality trends of the unintentional falls for both sexes in China. Conclusions: Unintentional falls are still a major public health problem that disproportionately threatens the lives of men and women in China. Efforts should be put in place urgently to prevent the growing number of fall-related mortality for men over 40 years old and women over 70 years old. Gains observed in the recent period, relative risks (RRs), and cohort RRs may be related to improved healthcare and better education.

Current research progress in the role of reactive oxygen species in esophageal adenocarcinoma.

In the past few decades, the incidence of esophageal adenocarcinoma has increased by six-fold in western countries, as the proton pump inhibitor targeting the gastric acid reflux has failed to control the disease. It is currently suggested that deoxycholic acid reflux leads to esophageal adenocarcinoma. As an inflammation-related cancer, the formation and progression of esophageal adenocarcinoma are closely related to the concentration of reactive oxygen species (ROS). Meanwhile, the critical developmental stage of esophageal adenocarcinoma involves characteristic pathological changes in which the distal esophageal squamous epithelial cells are replaced by intestinal columnar epithelial cells, suggesting the involvement of cancer stem cells. Thus, esophageal adenocarcinoma is a good model to study the interplay between ROS and stem cells in cancer. Until now, some important questions related to ROS in esophageal adenocarcinoma remain unanswered. For example, the molecular mechanism by which deoxycholic acid induces malignant transformation in esophageal adenocarcinoma remains unclear. In addition, whether ROS are involved in the induction of cancer stem cell formation by chemotherapeutic drugs and deoxycholic acid stimulation in esophageal adenocarcinoma remains to be further explored. This review summarizes current research progress on ROS and stemness activity, regulation of ROS by stanniocalcin-1 (STC1)/uncoupling protein 2 (UCP2), and inspiration for ROS in esophageal adenocarcinoma to guide further research and provide insight into the clinical treatment of esophageal adenocarcinoma.

Genome sequence of the psychrophilic Cryobacterium sp. LW097 and characterization of its four novel cold-adapted ß-galactosidases.

A psychrophilic strain Cryobacterium sp. LW097 was isolated from the subglacial sediments and discovered to show considerable ß-galactosidases activity at low temperatures. To provide access to genes predicted to encode cold-adapted glycoside hydrolases with biotechnological relevance, we have sequenced the genome of Cryobacterium sp. LW097. Annotation with CAZy database revealed four ß-galactosidase genes, bgal322, bgal435, bgal436, and bgal2567 belonging to the GH-42 family and GH-35 family. All the four ß-galactosidases recombinantly expressed retained a high level of relative activity at 5 °C and showed different optimum temperatures ranging from 25 °C to 40 °C. The enzyme kinetics proved that Bgal322, Bgal436, and Bgal2567 had lower Km to both oNPG and lactose at 5 °C, further proving their adaption to low temperature. Substrate specificity analysis showed that these four ß-galactosidases owned different preferences. The novel GH-42 ß-galactosidases Bgal435 showed ß-D-glucosidase activity (33.67 ± 0.28%) in addition to ß-D-galactosidase activity. Bgal322 preferred ß-D-(1,4)-galactobiose, whereas the other three preferred lactulose. Bgal435 showed the highest kcat value of 68.2 ± 1.7 s -1 at 5 °C toward lactose among these four enzymes. The exquisite substrate specificity of Bgal436 in milk made it a potential candidate for applications in milk lactulose quantification.

Experimental study on inhibitory effects of diallyl sulfide on growth and invasion of human osteosarcoma MG-63 cells.

The inhibitory effects of diallyl sulfide (DAS) derived from allicin on in vitro and in vivo proliferation of human osteosarcoma MG-63 cells and the action mechanism, and the influence of DAS on invasive capability of MG-63 cells were investigated in order to search for the novel medicines for osteosarcoma. In the in vitro experiment, MG-63 cells were treated with different concentrations of DSA, and the morphological changes of MG-63 cells were observed under an inverted phase microscope. MTT method was used to assay the proliferation of MG-63 cells. Semi-quantitative reverse transcription polymerase chain reaction (RT-PCR) was used to detect the VEGF mRNA expression level in MG-63 cells. By using Transwell invasion assay, the influence of DAS on invasive ability of MG-63 cells was tested. In the in vivo experiment, the nude mice MG-63 cells tumor-bearing model was established, and different concentrations of DAS were injected beside the tumor. Twenty-one days after treatment, the mice were killed, the tumor size and tumor inhibition rate were calculated. The microvessel density (MVD) was determined by using immunohistochemistry. In the in vitro experiment, different concentrations of DAS could obviously inhibit proliferation of MG-63 cells in a time- and concentration-dependent manner. RT-PCR revealed that the expression levels of VEGF mRNA in DSA groups (different concentrations) were significant reduced as compared with those in control group (all P<0.05). Transwell invasion assay indicated that in 20 and 40 µg/mL DAS groups, the number of migratory cells was 91.4±8.3 and 81.8±7.4 respectively, which was significantly declined as compared with that in control group (150.4±14.7, both P<0.05). In the in vivo experiment, DAS could significantly suppress the growth of MG-63 tumor-bearing tissue. Immunohistochemistry demonstrated that different concentrations (20 and 40 µg/mL) of DAS could significantly decrease MVD of MG-63 tumor-bearing tissue (all P<0.05). It was suggested that DAS could inhibit the growth of MG-63 cells probably by suppressing the expression of VEGF mRNA.

Molecular characterization and functional analysis of a vacuolar Na(+)/H(+) antiporter gene (HcNHX1) from Halostachys caspica.

According to sequences of several vacuolar Na(+)/H(+) antiporter genes from Xinjiang halophytic plants, a new vacuolar Na(+)/H(+) antiporter gene (HcNHX1) from the halophyte Halostachys caspica was obtained by RACE and RT-PCR using primers corresponding to conserved regions of the coding sequences. The obtained HcNHX1 cDNA was 1,983 bp and contained a 1,656 bp open reading frame encoding a deduced protein of 551 amino acid residues. The deduced amino acid sequence showed high identity with other NHX1 we have cloned previously from halophyte in Xinjiang desert area. The phylogenetic analysis showed that HcNHX1 formed a clade with NHX homologs of Chenopodiaceae. Expression profiles under salt treatment and ABA induction were investigated, and the results revealed that expression of HcNHX1 was induced by NaCl and ABA. To compare the degree of salt tolerance, we over-expressed HcNHX1 in Arabidopsis. Two transgenic lines grew more vigorously than the wild type (WT) under salt stress. The analysis of ion contents indicated that under salt stress, the transgenic plants compartmentalized more Na(+) in the leaves compared with wild-type plants. Together, these results suggest that the products of the novel gene HcNHX1 from halophyte Halostachys caspica is a functional tonoplast Na(+)/H(+) antiporter.