Cardiovascular mortality risk attributable to ambient temperature in China.

OBJECTIVE: To examine cardiovascular disease (CVD) mortality burden attributable to ambient temperature; to estimate effect modification of this burden by gender, age and education level. METHODS: We obtained daily data on temperature and CVD mortality from 15 Chinese megacities during 2007-2013, including 1,936,116 CVD deaths. A quasi-Poisson regression combined with a distributed lag non-linear model was used to estimate the temperature-mortality association for each city. Then, a multivariate meta-analysis was used to derive the overall effect estimates of temperature at the national level. Attributable fraction of deaths were calculated for cold and heat (ie, temperature below and above minimum-mortality temperatures, MMTs), respectively. The MMT was defined as the specific temperature associated to the lowest mortality risk. RESULTS: The MMT varied from the 70th percentile to the 99th percentile of temperature in 15 cities, centring at 78 at the national level. In total, 17.1% (95% empirical CI 14.4% to 19.1%) of CVD mortality (330,352 deaths) was attributable to ambient temperature, with substantial differences among cities, from 10.1% in Shanghai to 23.7% in Guangzhou. Most of the attributable deaths were due to cold, with a fraction of 15.8% (13.1% to 17.9%) corresponding to 305,902 deaths, compared with 1.3% (1.0% to 1.6%) and 24,450 deaths for heat. CONCLUSIONS: This study emphasises how cold weather is responsible for most part of the temperature-related CVD death burden. Our results may have important implications for the development of policies to reduce CVD mortality from extreme temperatures

Bibliometric and visual analysis of intraoperative hypotension from 2004 to 2022

BackgroundIntraoperative hypotension (IOH) is a common complication occurring in surgical practice. This study aims to comprehensively review the collaboration and impact of countries, institutions, authors, journals, keywords, and critical papers on intraoperative hypotension from the perspective of bibliometric, and to evaluate the evolution of knowledge structure clustering and identify research hotspots and emerging topics.MethodsArticles and reviews related to IOH published from 2004 to 2022 were retrieved from the Web of Science Core Collection. Bibliometric analyses and visualization were conducted on Excel, CiteSpace, VOSviewer, and Bibliometrix (R-Tool of R-Studio).ResultsA total of 1,784 articles and reviews were included from 2004 to 2022. The number of articles on IOH gradually increased in the past few years, and peaked in 2021. These publications were chiefly from 1,938 institutions in 40 countries, led by America and China in publications. Sessler Daniel I published the most papers and enjoyed the highest number of citations. Analysis of the journals with the most outputs showed that most journals concentrated on perioperative medicine and clinical anesthesiology. Delirium, acute kidney injury and vasoconstrictor agents are the current and developing research hotspots. The keywords “Acute kidney injury”, “postoperative complication”, “machine learning”, “risk factors” and “hemodynamic instability” may also become new trends and focuses of the near future research.ConclusionThis study uses bibliometrics and visualization methods to comprehensively review the research on intraoperative hypotension, which is helpful for scholars to better understand the dynamic evolution of IOH and provide directions for future research

Silencing SOCS3 Markedly Deteriorates Spondyloarthritis in Mice Induced by Minicircle DNA Expressing IL23

Objective: Despite extensive studies, the precise mechanism underlying spondyloarthritis, especially ankylosing spondylitis, remains elusive. This study aimed to develop an ideal animal model for an insight into mechanism of spondyloarthritis and functional relevance of SOCS3 in spondyloarthritis.Methods: Since SOCS3 is a major regulator of IL23-STAT3 signaling, we generated SOCS3 knockdown transgenic (TG) mice for development of an animal model of spondyloarthritis. A hydrodynamic delivery method was employed to deliver minicircle DNA expressing IL23 (mc-IL23) into wild-type (WT) and the TG mice. Knockdown/overexpression systems mediated by lentivirus and retrovirus were used to determine whether SOCS3 regulated osteoblast differentiation.Results: Forced expression of IL23 induced severe joint destruction and extensive bone loss in SOCS3 knockdown TG mice, while this treatment only caused moderate symptoms in WT mice. Furthermore, severe spondyloarthritis was found in IL23-injected TG mice as compared to mild disease observed in WT controls under same condition. Moreover, our studies showed that IL23 promoted osteoblast differentiation via activation of STAT3 pathway and disruption of SOCS3 expression greatly increased phosphorylation of STAT3. In addition, silencing SOCS3 resulted in enhanced osteoblast differentiation through activation of Smad1/5/9 signaling, as evidenced by elevated phosphorylation level of Smad1/5/9. Experiments further demonstrated that SOCS3 interacted with Smad1 and thus suppressed the BMP2-Smad signaling.Conclusions: The results reveal that SOCS3 is involved in IL23-induced spondyloarthritis and acts as a key regulator of osteoblast differentiation, and suggest that SOCS3 knockdown TG mice may be an ideal animal model for further studies of spondyloarthritis

Study on the Influencing Factors of Farmers’ Adoption of Conservation Tillage Technology in Black Soil Region in China: A Logistic-ISM Model Approach

The adoption of conservation tillage technology can improve the production efficiency of black soils (mollisols), and it has great significance to ensure the sustainable development of agriculture. This paper takes farmers in the black soil region of Jilin Province as the research object, uses 442 survey data of farmers in seven municipal areas in the black soil region of Jilin Province, constructs a logistic-ISM model, first determines the influencing factors of farmers’ adoption of conservation tillage technology, and then analyzes the hierarchical structure of each influencing factor. The results show that: (1) among the eight significant influencing factors of farmers’ adoption of conservation tillage technology, age, whether they know the government’s subsidies for conservation tillage and the number of labor force are the deep-rooted factors; (2) Education level, whether you know that the government is promoting conservation tillage, and the planting area are intermediate level factors; (3) whether they have received the technical services of conservation tillage and whether the cultivated land is scattered is the direct factors. Based on the significance analysis of the influencing factors of farmers’ adoption of conservation tillage technology and the research on the action mechanism of the influencing factors of farmers’ adoption of conservation tillage technology, this paper puts forward policy suggestions to improve the extension system of conservation tillage technology, improve the implementation of land transfer and subsidy policies, strengthen the ability of rural socialized services, and strengthen the publicity of black soils protection

A Requirement for SOCS-1 and SOCS-3 Phosphorylation in Bcr-Abl-Induced Tumorigenesis

Suppressors of cytokine signaling 1 and 3 (SOCS-1 and SOCS-3) are inhibitors of the Janus tyrosine kinase (JAK)/signal transducers and activators of transcription (STAT) pathway and function in a negative feedback loop during cytokine signaling. Abl transformation is associated with constitutive activation of JAK/STAT-dependent signaling. However, the mechanism by which Abl oncoproteins bypass SOCS inhibitory regulation remains poorly defined. Here, we demonstrate that coexpression of Bcr-Abl with SOCS-1 or SOCS-3 results in tyrosine phosphorylation of these SOCS proteins. Interestingly, SOCS-1 is highly tyrosine phosphorylated in one of five primary chronic myelogenous leukemia samples. Bcr-Abl-dependent tyrosine phosphorylation of SOCS-1 and SOCS-3 occurs mainly on Tyr 155 and Tyr 204 residues of SOCS-1 and on Tyr 221 residue of SOCS-3. We observed that phosphorylation of these SOCS proteins was associated with their binding to Bcr-Abl. Bcr-Abl-dependent phosphorylation of SOCS-1 and SOCS-3 diminished their inhibitory effects on the activation of JAK and STAT5 and thereby enhanced JAK/STAT5 signaling. Strikingly, disrupting the tyrosine phosphorylation of SOCS-1 or SOCS-3 impaired the expression of Bcl-XL protein and sensitized K562 leukemic cells to undergo apoptosis. Moreover, selective mutation of tyrosine phosphorylation sites of SOCS-1 or SOCS-3 significantly blocked Bcr-Abl-mediated tumorigenesis in nude mice and inhibited Bcr-Abl-mediated murine bone marrow transformation. Together, these results reveal a mechanism of how Bcr-Abl may overcome SOCS-1 and SOCS-3 inhibition to constitutively activate the JAK/STAT-dependent signaling, and suggest that Bcr-Abl may critically requires tyrosine phosphorylation of SOCS-1 and SOCS-3 to mediate tumorigenesis when these SOCS proteins are present in cells

Dietary tea tree (Melaleuca alternifolia) oil supplementation enhances the expressions of amino acid transporters in goat ileal mucosa and improves intestinal immunity

Abstract Tea tree oil (TTO) is a plant‐derived additive with anti‐inflammatory, bactericidal, and growth‐promoting properties. However, little is known about the effects of TTO on intestinal amino acid transport and immune function in goats. Twenty‐four Ganxi goats (initial body weight of 13.5 ± 0.70 kg) were randomly allotted two treatments and fed either control (CON) or CON+TTO (0.2 ml/kg) diet. The addition of TTO to the diet significantly decreased (p < .05) tumor necrosis factor‐α content and increased (p < .05) interleukin‐2 (IL‐2) content in goat serum; significantly decreased (p < .05) IL‐12, and increased (p < .05) IL‐2 content in goat ileal mucosa; significantly increased (p < .05) secreted IgA content in the jejunal and ileal mucosa; significantly upregulated (p < .05) IL‐2 and downregulated (p < .05) IL‐12 at the mRNA level in the ileal mucosa; significantly elevated the levels of serine, arginine, and total amino acids in the ileal mucosa (p < .05); significantly upregulated (p < .05) SLC1A1 and SLC7A1 in the ileum; and significantly enhanced (p < .05) the protein expression of Claudin‐1 in the ileal mucosa. In summary, adding 0.2 ml/kg of TTO to the diet enhanced SLC1A1 and SLC7A1 mRNA expression in the ileal mucosa, and SLC1A1 and SLC7A1 could transport serine and arginine from the chyme to the ileal mucosa. Thus, increased serine and arginine content in the mucosa could improve intestinal immunity. TTO supplementation upregulated the expression of IL‐2 and Claudin‐1 in goat ileal mucosa, and enhanced immune function in the intestine

Interaction of Abl Tyrosine Kinases with SOCS3 Impairs Its Suppressor Function in Tumorigenesis

Suppressor of cytokine signaling 3 (SOCS3) is involved in Bcr-Abl–induced tumorigenesis. However, how SOCS3 interacts with Bcr-Abl and is regulated by Abl kinases remains largely unknown. Since c-Abl plays a critical role in tumorigenesis, we asked whether SOCS3 is regulated by c-Abl–dependent phosphorylation. Here, we found that SOCS3 interacted with all three Abl kinases (Bcr-Abl, v-Abl, and c-Abl), and SH1 domain of the Abl kinases was critically required for such interaction. Furthermore, the SH2 domain of SOCS3 was sufficient to pull down the SH1 domain but not the full length of Bcr-Abl. Importantly, SOCS3 was highly tyrosine phosphorylated by c-Abl, leading to impairment of its ability to suppress JAK8+72 activity. In addition, disrupting the tyrosine phosphorylation of SOCS3 promoted apoptosis of c-Abl–expressing cells and impeded xenograft growth of these tumor cells in nude mice. The results demonstrate that SOCS3 is highly tyrosine phosphorylated by c-Abl and that tyrosine phosphorylation of SOCS3 is required for the survival and tumorigenesis of certain cells. Our findings provide novel insights into complicated mechanisms underlying the oncogenic function of Abl kinases

A critical role of CDKN3 in Bcr-Abl-mediated tumorigenesis.

CDKN3 (cyclin-dependent kinase inhibitor 3), a dual specificity protein phosphatase, dephosphorylates cyclin-dependent kinases (CDKs) and thus functions as a key negative regulator of cell cycle progression. Deregulation or mutations of CDNK3 have been implicated in various cancers. However, the role of CDKN3 in Bcr-Abl-mediated chronic myelogenous leukemia (CML) remains unknown. Here we found that CDKN3 acts as a tumor suppressor in Bcr-Abl-mediated leukemogenesis. Overexpression of CDKN3 sensitized the K562 leukemic cells to imanitib-induced apoptosis and dramatically inhibited K562 xenografted tumor growth in nude mouse model. Ectopic expression of CDKN3 significantly reduced the efficiency of Bcr-Abl-mediated transformation of FDCP1 cells to growth factor independence. In contrast, depletion of CDKN3 expression conferred resistance to imatinib-induced apoptosis in the leukemic cells and accelerated the growth of xenograph leukemia in mice. In addition, we found that CDKN3 mutant (CDKN3-C140S) devoid of the phosphatase activity failed to affect the K562 leukemic cell survival and xenografted tumor growth, suggesting that the phosphatase of CDKN3 was required for its tumor suppressor function. Furthermore, we observed that overexpression of CDKN3 reduced the leukemic cell survival by dephosphorylating CDK2, thereby inhibiting CDK2-dependent XIAP expression. Moreover, overexpression of CDKN3 delayed G1/S transition in K562 leukemic cells. Our results highlight the importance of CDKN3 in Bcr-Abl-mediated leukemogenesis, and provide new insights into diagnostics and therapeutics of the leukemia