Associations between type 1 diabetes and pulmonary tuberculosis: a bidirectional mendelian randomization study.

BACKGROUND: Type 1 diabetes mellitus (T1DM) has been associated with higher pulmonary tuberculosis (PTB) risk in observational studies. However, the causal relationship between them remains unclear. This study aimed to assess the causal effect between T1DM and PTB using bidirectional Mendelian randomization (MR) analysis. METHODS: Single nucleotide polymorphisms (SNPs) of T1DM and PTB were extracted from the public genetic variation summary database. In addition, GWAS data were collected to explore the causal relationship between PTB and relevant clinical traits of T1DM, including glycemic traits, lipids, and obesity. The inverse variance weighting method (IVW), weighted median method, and MR‒Egger regression were used to evaluate the causal relationship. To ensure the stability of the results, sensitivity analyses assess the robustness of the results by estimating heterogeneity and pleiotropy. RESULTS: IVW showed that T1DM increased the risk of PTB (OR = 1.07, 95% CI: 1.03-1.12, P < 0.001), which was similar to the results of MR‒Egger and weighted median analyses. Moreover, we found that high-density lipoprotein cholesterol (HDL-C; OR = 1.28, 95% CI: 1.03-1.59, P = 0.026) was associated with PTB. There was no evidence of an effect of glycemic traits, remaining lipid markers, or obesity on the risk of PTB. In the reverse MR analysis, no causal relationships were detected for PTB on T1DM and its relevant clinical traits. CONCLUSION: This study supported that T1DM and HDL-C were risk factors for PTB. This implies the effective role of treating T1DM and managing HDL-C in reducing the risk of PTB, which provides an essential basis for the prevention and comanagement of concurrent T1DM and PTB in clinical practice.

Vascular Health Promotion Project and Vascular Medicine in China-CCVM2004-2023.

Cardiovascular disease(CVD) has become a major disease burden affecting people's health in China. Blood vessels are very important for human health and are the "sentinel" for the development of many cardiovascular and cerebrovascular diseases. The key to effectively preventing fatal, disabling heart, brain and peripheral vascular events lies in controlling traditional and non-traditional risk factors for vascular health from the source, and early assessment and intervention of early vascular lesions. Since 2004, China government promoted the early detection technology of vascular lesions and vascular medicine, and proposed the Beijing Vascular Health Stratification (BVHS) to provide suggestions for the examination, evaluation and management of risk factors, and to provide new ideas for lifelong maintenance of vascular health. This review mainly introduces the establishment and development of the clinical discipline of "vascular medicine" in the past 20 years in China, introduces the indicators for detecting vascular function and structure and the predictive value of vascular events, and carries out intelligent and digital management of vascular health throughout the life cycle of individualized prevention, treatment and rehabilitation for people with different parts or degrees of lesions, effectively reducing the occurrence and development of cardiovascular and cerebrovascular diseases, and the prospect of new technology in maintaining vascular health.

Efficacy and safety of Ophiocordyceps sinensis in the treatment of Hashimoto's thyroiditis: a systematic review and meta-analysis.

Objective: To evaluate the efficacy and safety of Ophiocordyceps sinensis (OS) preparations for the treatment of Hashimoto's thyroiditis (HT). Methods: We searched eight databases to collect randomized controlled trials (RCTs) of OS combined with a low-iodine diet or levothyroxine for HT. The search period was from inception to June 2023. Meta-analysis was performed using Revman 5.3 software after two evaluators independently screened the literature, extracted data, and evaluated the risk of bias of the included studies. The GRADE system was used to assess the certainty of evidence. Results: A total of 14 RCTs involving 1,014 patients with HT were included. Meta-analysis showed that OS preparations combined with a low-iodine diet were more effective in reducing thyroid peroxidase antibody (TPOAb) [SMD = -3.81, 95% CI (-5.07, -2.54), p < 0.00001] and thyroglobulin antibody (TgAb) [SMD = -4.73, 95% CI (-6.86, -2.61), p < 0.00001] compared to a low-iodine diet. Compared with levothyroxine treatment alone, OS preparations combined with levothyroxine further reduced TPOAb [SMD = -2.04, 95% CI (-2.82, -1.26), p < 0.00001], TgAb [SMD = -2.01, 95% CI (-2.68, -1.33), p < 0.00001], tumor necrosis factor alpha (TNF-α) [SMD = -3.40, 95% CI (-5.66, -1.14), p = 0.003], interleukin-2 (IL-2) [SMD = -2.31, 95% CI (-3.98, -0.65), p = 0.006], and interleukin-6 (IL-6) [MD = -4.16, 95% CI (-6.17, -2.15), p < 0.0001], and elevated free thyroxine (FT4) [SMD = 1.34, 95% CI (0.59, 2.08), p = 0.0004], but no significant effect on free triiodothyronine (FT3) [SMD = 0.83, 95% CI (-0.12, 1.78), p = 0.09] and thyroid stimulating hormone (TSH) [SMD = -0.80, 95% CI (-1.71, 0.11), p = 0.08]. In terms of safety, three studies reported adverse reactions in 10 patients in each of the experimental and control groups. Conclusion: OS preparations in combination with other treatments (low-iodine diet or levothyroxine) may decrease thyroid autoantibodies and inflammatory responses in patients with HT. In HT patients with hypothyroidism, the combination of the OS preparations with levothyroxine also improved FT4. However, the quality of the included studies was generally low. Moreover, the safety of OS preparations remains unclear. Therefore, more high-quality, multicenter, large-sample RCTs are needed in the future to validate the efficacy and safety of OS preparations. Systematic Review Registration: https://www.crd.york.ac.uk/prospero, identifier CRD42023432663.

Effectiveness and safety of traditional Chinese medicine for diabetic retinopathy: A systematic review and network meta-analysis of randomized clinical trials.

BACKGROUND: Diabetic retinopathy (DR) is currently recognized as one of the most serious diabetic microangiopathies and a major cause of adult blindness. Commonly used clinical approaches include etiological control, microvascular improvement, and surgical intervention, but they are ineffective and have many side effects. Oral Chinese medicine (OCM) has been used for thousands of years to treat DR and is still widely used today, but it is unclear which OCM is more effective for DR. AIM: To estimate relative effectiveness and safety profiles for different classes of OCMs for DR, and provide rankings of the available OCMs. METHODS: The search time frame was from the creation of the database to January 2023. RevMan 5.3 and Stata 14.0 software were used to perform the systematic review and Network meta-analyses (NMA). RESULTS: A total of 107 studies and 9710 patients were included, including 4767 cases in the test group and 4973 cases in the control group. Based on previous studies and clinical reports, and combined with the recommendations of Chinese guidelines for the prevention and treatment of DR, 9 OCMs were finally included in this study, namely Compound Xueshuantong Capsules, Qiming Granules, Compound Danshen Dripping Pills, Hexue Mingmu Tablets (HXMM), Qiju Dihuang Pills (QJDH), Shuangdan Mingmu Capsules (SDMM), Danggui Buxue Decoction (DGBX), Xuefu Zhuyu Decoction and Buyang Huanwu Decoction. When these nine OCMs were analyzed in combination with conventional western medicine treatment (CT) compared with CT alone, the NMA results showed that HXMM + CT has better intervention effect on the overall efficacy of DR patients, HXMM + CT has better effect on improving patients' visual acuity, SDMM + CT has better effect on inhibiting vascular endothelial growth factor, DGBX + CT has better effect on reducing fundus hemorrhage area, HXMM + CT has better effect on reducing fasting blood glucose, and QJDH + CT has better effect on reducing glycated hemoglobin. When there are not enough clinical indicators for reference, SDMM + CT or HXMM + CT treatments can be chosen because they are effective for more indicators and demonstrate multidimensional efficacy. CONCLUSION: This study provides evidence that combining OCMs with CT leads to better outcomes in all aspects of DR compared to using CT alone. Based on the findings, we highly recommend the use of SDMM or HXMM for the treatment of DR. These two OCMs have demonstrated outstanding efficacy across multiple indicators.

Hydrothermal synthesis and formation mechanism of controllable magnesium silicate nanotubes derived from coal fly ash.

A novel controllable magnesium silicate nanotube (MSN) material derived from coal fly ash was successfully synthesized via a hydrothermal process for the first time, and the reaction conditions and mechanism of synthesizing MSN materials from magnesium oxide and sodium silicate extracted from the fly ash were studied. The optimal preparation conditions are temperature = 220 °C, pH = 13.5, and Mg: Si molar ratio = 3:2, and the tubular structure gradually appeared and showed controllable and regular growth with the increase of synthesis time. The mechanism revealed that with the gradual dissolution of brucite into the sodium silicate solution, the reaction product begins to crystallize and transform from an initial sheet-like structure to a tubular structure, and finally becomes a uniformly arranged nanotube. The formation process of MSN follows Pauling's fourth rule, Si-O tetrahedral coordination and Mg-OH octahedral coordination is further condensed to form a two-layer structure by the action of active oxygen, then the sheet is rolled into a tube under its structural stress. The growth of both outer tubular diameter and inner tubular diameter has good linear law and controllable, and the growth rate are 0.289 nm h-1and 0.071 nm h-1, respectively.

The Improvement of Kaolinite Supported Cerium Oxide for Styrene-Butadiene Rubber Composite: Mechanical, Ageing Properties and Mechanism.

Kaolinite supported cerium oxide (CeOx/Kaol) was successfully prepared via a deposition method and used to improve the mechanical and aging properties of styrene-butadiene rubber (SBR) composite. The scanning electron microscopy (SEM) and transmission electron microscopy (TEM) results showed that cerium oxide has a successfully loading and fine distribution on the edge and surface of kaolinite. Fourier transform infrared (FT-IR) spectroscopy indicated that cerium oxide may interact with the surface hydroxyls of kaolinite. The CeOx/Kaol material had a uniform dispersion in the resulting SBR composite. The loading of cerium oxide on Kaol increases the scorch time (t10) and curing time (t90) of the filled SBR composites relative to the pure SBR. The mechanical parameters of the filled SBR composites were increased significantly. The tensible strength and tear strength at 40 phr content with 4% CeOx loading reached 12.85 Mpa and 51.16 kN/m, which were increases of 35.9% and 38.3%, respectively, relative to that of the SBR filled with raw Kaol. The anti-ageing characteristic of the resulting composite showed an obvious improvement with the loading of CeOx. Meanwhile, the reinforcement and anti-ageing mechanisms of the CeOx/Kaol were proposed. These results were attributed to the complexation between Ce elements on the surface of Kaol and rubber chains through a double bond. This could improve the incorporation between rubber molecules and filler particles, and restrict rubber chain motion via trapping rubber chains.

A bibliometric analysis of RNA methylation in diabetes mellitus and its complications from 2002 to 2022.

Background: RNA methylation has emerged as an active research field in diabetes mellitus (DM) and its complications, while few bibliometric analyses have been performed. We aimed to visualize the hotspots and trends using bibliometric analysis to provide a comprehensive and objective overview of the current search state in this field. Methods: The articles and reviews regarding RNA methylation in DM and its complications were from the Web of Science Core Collection. A retrospective bibliometric analysis and science mapping was performed using the CiteSpace software to plot the knowledge maps and predict the hotspots and trends. Results: Three hundred seventy-five qualified records were retrieved. The annual publications gradually increased over the past 20 years. These publications mainly came from 66 countries led by Canada and 423 institutions. Leiter and Sievenpiper were the most productive authors, and Jenkins ranked first in the cited authors. Diabetes Care was the most co-cited journal. The most common keywords were "Type 2 diabetes", "cardiovascular disease", "diabetes mellitus", and "n 6 methyladenosine". The extracted keywords mainly clustered in "beta-cell function", "type 2 diabetes", "diabetic nephropathy", "aging", and "n6-methyladenosine". N6-methyladenosine (m6A) in DM and its complications were the developing areas of study. Conclusion: Studies on RNA methylation, especially m6A modification, are the current hotspots and the future trends in type 2 diabetes (T2D) and diabetic nephropathy (DN), as well as a frontier field for other complications of DM. Strengthening future cooperation and exchange between countries and institutions is strongly advisable to promote research developments in this field.

Evolution of complex genome architecture in gymnosperms.

Gymnosperms represent an ancient lineage that diverged from early spermatophytes during the Devonian. The long fossil records and low diversity in living species prove their complex evolutionary history, which included ancient radiations and massive extinctions. Due to their ultra-large genome size, the whole-genome assembly of gymnosperms has only generated in the past 10 years and is now being further expanded into more taxonomic representations. Here, we provide an overview of the publicly available gymnosperm genome resources and discuss their assembly quality and recent findings in large genome architectures. In particular, we describe the genomic features most related to changes affecting the whole genome. We also highlight new realizations relative to repetitive sequence dynamics, paleopolyploidy, and long introns. Based on the results of relevant genomic studies of gymnosperms, we suggest additional efforts should be made toward exploring the genomes of medium-sized (5-15 gigabases) species. Lastly, more comparative analyses among high-quality assemblies are needed to understand the genomic shifts and the early species diversification of seed plants.

Efficacy and safety of Keluoxin capsule in combination with Western medicine for diabetic kidney disease: A systematic review and meta-analysis.

Objective: Keluoxin capsule (KLXC) has been widely used in diabetic kidney disease (DKD), but its efficacy and safety have not yet been clarified. A systematic review and meta-analysis were performed to assess the efficacy and safety of KLXC for DKD. Methods: The randomized control trials (RCTs) included KLXC searched from seven major English and Chinese databases up until 3 June 2022. The methodological quality and risk of bias were assessed by version 2 of the Cochrane risk-of-bias tool (RoB 2) for the RCTs from the Cochrane Handbook. The analyses were conducted by RevMan 5.4 and Stata 17.0. Results: A total of 20 trials with 1,500 participants were identified. The meta-analysis showed that KLXC combined with Western medicine was superior to the use of Western medicine alone for DKD which included improvements in the estimated glomerular filtration rate (eGFR) [MD = 3.04, 95% CI (0.30, 5.78), p = 0.03], reduction in microalbuminuria (mALB) [MD = -25.83, 95% CI (-41.20, -10.47), p = 0.001], urinary albumin excretion rate (UAER) [SMD = -0.97, 95% CI (-1.50, -0.44), p = 0.0003], 24-h urine protein (24hUpro) [SMD = -1.31, 95% CI (-1.82, -0.80), p < 0.00001], serum creatinine (Scr) [MD = -11.39, 95% CI (-18.76, -4.02), p = 0.002], blood urea nitrogen (BUN) [MD = -1.28, 95% CI (-1.67, -0.88), p < 0.00001], fasting blood glucose (FBG) [MD = -0.51, 95% CI (-0.90, -0.11), p = 0.01], total cholesterol (TC) [MD = -1.04, 95% CI (-1.40, -0.68), p < 0.00001], triglycerides (TG) [MD = -0.36, 95% CI (-0.50, -0.23), p < 0.00001], and low-density lipoprotein cholesterol (LDL) [MD = -0.39, 95% CI (-0.71, -0.07), p = 0.02]. Results showed no statistically significant difference in glycated hemoglobin (HbA1c) (p = 0.14) or adverse events (p = 0.81) between the two groups. Conclusion: The combination of KLXC and Western medicine had a positive effect on DKD. However, due to the high clinical heterogeneity and low quality of included studies, further standardized, large-scale, rigorously designed RCTs for DKD in the definitive stage are still necessary to achieve more accurate results. Systematic Review Registration: https://inplasy.com/inplasy-2021-11-0067/, identifier INPLASY 2021110067.

Literary runaway: Increasingly more references cited per academic research article from 1980 to 2019.

References are employed in most academic research papers to give credits and to reflect scholarliness. With the upsurge in academic publications in recent decades, we are curious to know how the number of references cited per research article has changed across different disciplines over that time. The results of our study showed significant linear growth in reference density in eight disciplinary categories between 1980 and 2019 indexed in Web of Science. It appears that reference saturation is not yet in sight. Overall, the general increase in the number of publications and the advanced accessibility of the Internet and digitized documents may have promoted the growth in references in certain fields. However, the seemingly runaway tendency should be well appreciated and objectively assessed. We suggest that authors focus on their research itself rather than on political considerations during the process of writing, especially the selection of important references to cite.

The Welwitschia genome reveals a unique biology underpinning extreme longevity in deserts.

The gymnosperm Welwitschia mirabilis belongs to the ancient, enigmatic gnetophyte lineage. It is a unique desert plant with extreme longevity and two ever-elongating leaves. We present a chromosome-level assembly of its genome (6.8 Gb/1 C) together with methylome and transcriptome data to explore its astonishing biology. We also present a refined, high-quality assembly of Gnetum montanum to enhance our understanding of gnetophyte genome evolution. The Welwitschia genome has been shaped by a lineage-specific ancient, whole genome duplication (~86 million years ago) and more recently (1-2 million years) by bursts of retrotransposon activity. High levels of cytosine methylation (particularly at CHH motifs) are associated with retrotransposons, whilst long-term deamination has resulted in an exceptionally GC-poor genome. Changes in copy number and/or expression of gene families and transcription factors (e.g. R2R3MYB, SAUR) controlling cell growth, differentiation and metabolism underpin the plant's longevity and tolerance to temperature, nutrient and water stress.

Shen-Yuan-Dan Capsule Attenuates Verapamil-Induced Zebrafish Heart Failure and Exerts Antiapoptotic and Anti-Inflammatory Effects via Reactive Oxygen Species-Induced NF-κB Pathway.

Background: Heart failure (HF) is the end stage of ischemic cardiovascular diseases; nonetheless, safe and effective therapeutic agents for HF are still lacking, and their discovery remains challenging. Our previous studies demonstrated that Shen-Yuan-Dan Capsule (SYDC), a hospital preparation of traditional Chinese herbal, effectively protected ischemic injury in cardiovascular diseases. However, its therapeutic effects and possible mechanisms on HF remain unclear. Methods: A zebrafish HF model treated with verapamil was developed to assess the therapeutic effect of SYDC on HF zebrafish. Zebrafish were administered with SYDC and digoxin (positive control) by direct soaking. After drug treatment, zebrafish were randomly assigned to the visual observation and image acquisition using a Zebralab Blood Flow System. The reactive oxygen species (ROS), MDA, and SOD levels were determined by fluorescence signal detection, TBA, and WST-8 methods. RT-PCR determined the mRNA expressions of Caspase-3, Caspase-1, Bcl-2, Bax, IL-1ß, NF-κB, and TNF-α. Results: SYDC significantly inhibited the levels of heart dilatation and venous congestion and markedly increased the levels of cardiac output, blood flow dynamics, and heart rates in HF zebrafish (p < 0.05, p < 0.01, and p < 0.001). Moreover, SYDC also significantly decreased the levels of MDA and ROS and increased the level of SOD in HF zebrafish. The RT-PCR results revealed that SYDC decreased the expression of Caspase-1, Caspase-3, Bax, IL-1ß, NF-κB, and TNF-α but increased the expression of Bcl-2 in HF zebrafish (p < 0.05, p < 0.01, and p < 0.001). Conclusions: SYDC improved the heart function in verapamil-induced HF zebrafish and alleviated inflammation and apoptosis by inhibiting the ROS-mediated NF-κB pathway.

Treatment with Tang-luo-ning altered the microRNA expression profile in rats with diabetic peripheral neuropathy.

Tang-luo-ning (TLN) is a traditional Chinese herbal recipe that has been used to treat diabetic peripheral neuropathy (DPN); nevertheless, the underlying mechanism remains unclear. This study was aimed to investigate the microRNA (miRNA) expression profile in diabetic rats treated with TLN, and the target genes were predicted. Male Sprague-Dawley rats were randomly divided into control, diabetes, and TLN-treated diabetes groups. Diabetes was induced with streptozotocin, and TLN (5 g/kg/day) was orally given for eight weeks. Then, the sciatic nerves were harvested for miRNA microarray analyses. The differentially expressed miRNAs and their target genes were analyzed. Compared with the control rats, 24 miRNAs were significantly upregulated, and 59 were downregulated in the sciatic nerves of the diabetic rats by more than two folds (all P < 0.05). In TLN-treated diabetes rats, 26 miRNAs were upregulated, and 14 were downregulated compared with diabetic rats without TLN treatment (all P < 0.05). DPN-induced alterations of the miRNA profile were reversed by the TLN treatment. A total of 1402 target genes were screened. In GO analysis, genes in localization, cytoplasm, and protein binding processes were enriched, and the most significantly enriched pathways included the neurotrophin, Fc epsilon RI, and Wnt signaling pathways. Further analyses revealed that DVL1 and NTF3 genes were involved in these pathways. Our findings indicate that TLN may affect the Wnt and neurotrophin pathways by acting on DVL1 and NTF3 genes.

Glutamate dehydrogenase plays an important role in ammonium detoxification by submerged macrophytes.

Ammonium is a paradoxical chemical because it is a nutrient but also damages ecosystems at high concentration. As the most eco-friendly method of water restoration, phytoremediation technology still faces great challenges. To provide more theoretical support, we exploited six common submerged macrophytes and selected the most ammonium-tolerant and -sensitive species; then further explored and compared the mechanisms underlying ammonium detoxification. Our results showed the activity of glutamate dehydrogenase (GDH) in the ammonium-tolerant species Myriophyllum spicatum leaves performed a dose-response curve (increased 169% for NADH-dependent GDH and 103% for NADPH-dependent GDH) with the [NH4+-N] increasing from 0 to 100 mg/L while glutamine synthetase (GS) activity slightly changed. But for the ammonium-sensitive species, Potamogeton lucens, the activity of GDH recorded no major changes, while the GS increased slightly (17%). Based on this, we conclude that the alternative pathway of GDH is more important than the pathway catalyzed by GS in determining the tolerance of submerged macrophytes to high ammonium concentration (up to 100 mg N/L). Our present study identifies submerged macrophytes that are tolerant of high concentrations of ammonium and provides mechanistic support for practical water restoration by aquatic plants.

9,9-Dimethylxanthene Derivatives with Room-Temperature Phosphorescence: Substituent Effects and Emissive Properties.

Room-temperature phosphorescence (RTP) emitters with ultralong lifetimes are emerging as attractive targets because of their potential applications in bioimaging, security, and other areas. But their development is limited by ambiguous mechanisms and poor understanding of the correlation of the molecular structure and RTP properties. Herein, different substituents on the 9,9-dimethylxanthene core (XCO) result in compounds with RTP lifetimes ranging from 52 to 601 ms, which are tunable by intermolecular interactions and molecular configurations. XCO-PiCl shows the most persistent RTP because of its reduced steric bulk and multiple sites of the 1-chloro-2-methylpropan-2-yl (PiCl) moiety for forming intermolecular interactions in the aggregated state. The substituent effects reported provide an efficient molecular design of organic RTP materials and establishes relationships among molecular structures, intermolecular interactions, and RTP properties.

Danhong Injection Attenuates High-Fat-Induced Atherosclerosis and Macrophage Lipid Accumulation by Regulating the PI3K/AKT Insulin Pathway.

BACKGROUND AND AIMS: High-fat diet (HFD) is reported to induce atherosclerosis and insulin resistance. Macrophage lipid accumulation has been implicated as key mediators during the development of HFD-induced atherosclerosis. Traditional Chinese formula, which has long been used to improve disorder of glucose and lipid metabolism of patients, is now gradually being used as complementary therapy. This study aimed to investigate the effect of Danhong injection (DHI), a Chinese medicine used for the treatment of coronary artery disease, on atherosclerosis and its underlying mechanisms. METHODS AND RESULTS: We observed the effects of DHI on HFD-induced atherosclerosis in a mice model, macrophage lipid accumulation in an ox-LDL-stimulated macrophage model, and the role of PI3K/AKT insulin pathway in the process of DHI ameliorating atherosclerosis. The data demonstrated that DHI attenuated atherosclerosis by ameliorating blood lipids, reducing the atherosclerotic index and atherosclerotic plaque area in HFD-induced atherosclerotic mice, and inhibiting TC levels in an ox-LDL-induced macrophage model. By estimating the levels of serum insulin resistance-related indexes and protein expression of GLUT-4, DHI treatment dramatically inhibited the levels of fasting serum NEFA and fasting serum insulin and promoted the protein expression of GLUT-4 in aortas of the HFD-induced atherosclerotic mice. Moreover, according to the hints provided by microarray-based transcriptional profiling, the results demonstrated that DHI treatment also promoted the activation of PI3K/AKT insulin signaling pathway induced by IRS-1 in aortas of HFD-induced atherosclerotic mice. Furthermore, in an ox-LDL-induced macrophage model, the activation of PI3k/AKT signaling pathway also effectively functioned in the process of DHI inhibiting macrophage lipid accumulation. CONCLUSIONS: These results highlight that DHI treatment attenuates atherosclerosis and macrophage lipid accumulation by promoting the activation of PI3K/AKT insulin signaling pathway. It provides new insights into the molecular mechanism of DHI and its therapeutic potential in the treatment of atherosclerosis.