Serum Lipid Levels, Genetic Risk, and Lung Cancer Incidence: A Large Prospective Cohort Study.

BACKGROUND: Previous studies usually focused on the separate association of metabolism or genetic factors with lung cancer risk and have largely ignored their combined effect. We aimed to examine the associations between serum lipid levels, genetic risk, and lung cancer risk. METHODS: A total of 426,524 participants of the UK Biobank were included. The Cox proportional hazards models and restricted cubic splines were performed to assess the association between serum lipid and lung cancer risk. Polygenic risk score (PRS) was constructed to assess its joint effect and interaction with serum lipid on lung cancer risk. RESULTS: Higher level of apolipoprotein A was significantly correlated with lower lung cancer risk. An inverse-J-shaped relationship between high-density lipoprotein (HDL) and incident lung cancer was found. Individuals with low total cholesterol, HDL, low-density lipoprotein (LDL), apolipoprotein A, and apolipoprotein B, combined with high PRS, showed significantly elevated lung cancer risks. Compared to those with low PRS and low triglycerides, participants with high PRS and elevated triglyceride levels had a notably higher risk. The interaction effect of high PRS and low LDL [relative excess risk due to the interaction (RERI): 0.25, 95% confidence interval, 0.04-0.46], as well as the interaction effect of high PRS and low apolipoprotein B (RERI: 0.28, 95% confidence interval, 0.07-0.48), were both greater than the sum of their individual effects on lung cancer risk. CONCLUSIONS: Serum lipids were associated with lung cancer risk. LDL or apolipoprotein B interacting with genetic risk may affect lung cancer risk. IMPACT: Our findings emphasize the need for individuals with heightened genetic risk should pay more attention to their lipid levels to reduce lung cancer risk.

Corrigendum: Exploring the shared molecular mechanisms between systemic lupus erythematosus and primary Sjögren's syndrome based on integrated bioinformatics and single-cell RNA-seq analysis.

[This corrects the article DOI: 10.3389/fimmu.2023.1212330.].

Exploring the shared molecular mechanisms between systemic lupus erythematosus and primary Sjögren's syndrome based on integrated bioinformatics and single-cell RNA-seq analysis.

Background: Systemic lupus erythematosus (SLE) and primary Sjögren's syndrome (pSS) are common systemic autoimmune diseases that share a wide range of clinical manifestations and serological features. This study investigates genes, signaling pathways, and transcription factors (TFs) shared between SLE and pSS. Methods: Gene expression profiles of SLE and pSS were obtained from the Gene Expression Omnibus (GEO). Weighted gene co-expression network analysis (WGCNA) and differentially expressed gene (DEG) analysis were conducted to identify shared genes related to SLE and pSS. Overlapping genes were then subject to Gene Ontology (GO) and protein-protein interaction (PPI) network analyses. Cytoscape plugins cytoHubba and iRegulon were subsequently used to screen shared hub genes and predict TFs. In addition, gene set variation analysis (GSVA) and CIBERSORTx were used to calculate the correlations between hub genes and immune cells as well as related pathways. To confirm these results, hub genes and TFs were verified in microarray and single-cell RNA sequencing (scRNA-seq) datasets. Results: Following WGCNA and limma analysis, 152 shared genes were identified. These genes were involved in interferon (IFN) response and cytokine-mediated signaling pathway. Moreover, we screened six shared genes, namely IFI44L, ISG15, IFIT1, USP18, RSAD2 and ITGB2, out of which three genes, namely IFI44L, ISG15 and ITGB2 were found to be highly expressed in both microarray and scRNA-seq datasets. IFN response and ITGB2 signaling pathway were identified as potentially relevant pathways. In addition, STAT1 and IRF7 were identified as common TFs in both diseases. Conclusion: This study revealed IFI44L, ISG15 and ITGB2 as the shared genes and identified STAT1 and IRF7 as the common TFs of SLE and pSS. Notably, the IFN response and ITGB2 signaling pathway played vital roles in both diseases. Our study revealed common pathogenetic characteristics of SLE and pSS. The particular roles of these pivotal genes and mutually overlapping pathways may provide a basis for further mechanistic research.

Global, regional, and national trends in mesothelioma burden from 1990 to 2019 and the predictions for the next two decades.

Objectives: We aimed to analyze the secular trends in mesothelioma burden, the effect of age, period, and birth cohort, and project the global burden over time. Material and methods: Based on the mesothelioma incidence, mortality, and Disability-Adjusted Life Years (DALYs) data from 1990 to 2019 in Global Burden of Diseases (GBD) database, the annual percentage change (APC) and average annual percent change (AAPC), calculated from joinpoint regression model, was used to describe the burden trends. An age-period-cohort model was utilized to disentangle age, period, and birth cohort effects on mesothelioma incidence and mortality trends. The mesothelioma burden was projected by the Bayesian age-period-cohort (BAPC) model. Results: Globally, there were the significant declines in age-standardized incidence rate (ASIR) (AAPC = -0.4, 95%CI: -0.6,-0.3, P < 0.001), age-standardized mortality rate (ASMR) (AAPC = -0.3, 95%CI: -0.4,-0.2, P < 0.001), and age-standardized DALY rate (ASDR) (AAPC = -0.5, 95%CI: -0.6,-0.4, P < 0.001) of mesothelioma overall 30 years. For regions, Central Europe presented the most distinct increases and the most substantial decrease was observed in Andean Latin America on all ASRs (age-standardized rates) from 1990 to 2019. At national level, the largest annualized growth for full-range trends of incidence, mortality, and DALYs was in Georgia. Conversely, the fastest descent of all ASRs was observed in Peru. The ASIR, ASMR, and ASDR in 2039 predicted 0.33, 0.27, and 6.90 per 100,000, respectively. Conclusions: The global burden of mesothelioma declined over the past 30 years, with variability across regions and countries/territories, and this trend will continue in the future.

Global, region and national trends and age-period-cohort effects in colorectal cancer burden from 1990 to 2019, with predictions to 2039.

Nowadays, colorectal cancer (CRC) is the second leading cause of cancer deaths and contributes to a gradually increasing disease burden. We aimed to estimate the secular trends of global CRC burden, the effect of age, period, and birth cohort, and project the global burden over time. Based on the epidemiological CRC data from 1990 to 2019 in 204 countries and territories from GBD 2019, the estimated annual percentage change (EAPC), was calculated from a linear model and joinpoint regression model. We utilized an age-period-cohort model to reckon age, period, and birth cohort effects on CRC age-standardized rate. The burden of CRC was projected by conducting the BAPC model. Globally, there was a slight decline in the age-standardized DALY rate, which was more apparent in females, with high SDI regions and in Australia and Western Europe areas. Meanwhile, our model predicts a weaker increase in morbidity (EAPC of 0.37) and a speedier reduction in mortality (EAPC of -0.66) by the next 20 years. The relative risk of period for high SDI regions decreased from 1.08 (95%UI: 1.06-1.1) in 1990-1994 to 0.85 (95%UI:0.83-0.88) in 2015-2019, but worsens in low and middle SDI regions. The local drifts were more than 1 in the 30-34 and 35-39 age groups, indicating the rising tide of early-onset CRC. Given the gender and region-specific CRC, targeted efforts to reduce the prevalence of risk factors, improve screening coverage rates, and strengthen foundational medical facilities are necessary.

Development of nitric acid-modified activated carbon electrode for removal of Co2+/Mn2+/Ni2+ by electrosorption.

In this paper, nitric acid-modified activated carbon was used as an electrode in the electrosorption process for the removal of Co2+, Mn2+, and Ni2+ from wastewater. The effects of applied voltage, initial pH, and coexisting ions on removal efficiency were investigated. The adsorption process was evaluated by adsorption isotherm models. The results indicated that the electrosorption process was consistent with the Langmuir model, proving that the electrosorption process was a monolayer adsorption process. The maximum adsorption capacities of Co2+, Mn2+, and Ni2+ were 131.58 mg/g, 102.04 mg/g, and 103.09 mg/g. Electrochemical tests revealed that the specific capacitance of AC-HNO3 was 54.11 F/g when the scanning rate was 5 mV/s, while the specific capacitance of AC was 36.51 F/g. The Fourier transform infrared spectroscopy (FT-IR) and X-ray photoelectron spectroscopy (XPS) confirmed that the content of oxygen groups on the surface of activated carbon increased after modification, which provided more adsorption sites for electrosorption. When the selected concentration of HCl was used as the eluent, the elution efficiency of Co2+, Mn2+, and Ni2+ could reach 94.23%, 93.65%, and 90.61%. The removal efficiency could reach more than 95% after three cycles. The results of the study can be used as a reference significance for the removal of cobalt, manganese, and nickel ions from heavy metal wastewater by electrosorption.

Dual functions of microRNA-17 in maintaining cartilage homeostasis and protection against osteoarthritis.

Damaged hyaline cartilage has no capacity for self-healing, making osteoarthritis (OA) "difficult-to-treat". Cartilage destruction is central to OA patho-etiology and is mediated by matrix degrading enzymes. Here we report decreased expression of miR-17 in osteoarthritic chondrocytes and its deficiency contributes to OA progression. Supplementation of exogenous miR-17 or its endogenous induction by growth differentiation factor 5, effectively prevented OA by simultaneously targeting pathological catabolic factors including matrix metallopeptidase-3/13 (MMP3/13), aggrecanase-2 (ADAMTS5), and nitric oxide synthase-2 (NOS2). Single-cell RNA sequencing of hyaline cartilage revealed two distinct superficial chondrocyte populations (C1/C2). C1 expressed physiological catabolic factors including MMP2, and C2 carries synovial features, together with C3 in the middle zone. MiR-17 is highly expressed in both superficial and middle chondrocytes under physiological conditions, and maintains the physiological catabolic and anabolic balance potentially by restricting HIF-1α signaling. Together, this study identified dual functions of miR-17 in maintaining cartilage homeostasis and prevention of OA.

Temporal and spatial cellular and molecular pathological alterations with single-cell resolution in the adult spinal cord after injury.

Spinal cord injury (SCI) involves diverse injury responses in different cell types in a temporally and spatially specific manner. Here, using single-cell transcriptomic analyses combined with classic anatomical, behavioral, electrophysiological analyses, we report, with single-cell resolution, temporal molecular and cellular changes in crush-injured adult mouse spinal cord. Data revealed pathological changes of 12 different major cell types, three of which infiltrated into the spinal cord at distinct times post-injury. We discovered novel microglia and astrocyte subtypes in the uninjured spinal cord, and their dynamic conversions into additional stage-specific subtypes/states. Most dynamic changes occur at 3-days post-injury and by day-14 the second wave of microglial activation emerged, accompanied with changes in various cell types including neurons, indicative of the second round of attacks. By day-38, major cell types are still substantially deviated from uninjured states, demonstrating prolonged alterations. This study provides a comprehensive mapping of cellular/molecular pathological changes along the temporal axis after SCI, which may facilitate the development of novel therapeutic strategies, including those targeting microglia.

Bio-C (Modified Hyaluronic Acid-Coated-Collagen Tube) Implants Enable Functional Recovery after Complete Spinal Cord Injury.

Neural repair within the central nervous system (CNS) has been extremely challenging due to limited abilities of adult CNS neurons to regenerate, particularly in a highly inflammatory injury environment that is also filled with myelin debris. Spinal cord injury (SCI) is a serious medical condition that often leads to paralysis and currently has no effective treatment. Here we report the construction of a novel biocompatible and biodegradable material, Bio-C, through coating of acid-desalted-collagen (ADC) tube with pre-modified hyaluronic acid, which, after implantation, can elicit quite robust neural regeneration and functional recovery after complete spinal-cord transection with a 2 mm-spinal-cord-segment removal in mice. We combined morphological, electrophysiological, and objective transcriptomic analyses, in addition to behavioral analyses, to demonstrate neural tissue regeneration and functional recovery through the establishment of Bio-C-induced anti-inflammatory, neurogenic, and neurotrophic microenvironment. Through this study, we unveiled the underlying logic for CNS neural repair.

Comprehensive investigations revealed consistent pathophysiological alterations after vaccination with COVID-19 vaccines.

Large-scale COVID-19 vaccinations are currently underway in many countries in response to the COVID-19 pandemic. Here, we report, besides generation of neutralizing antibodies, consistent alterations in hemoglobin A1c, serum sodium and potassium levels, coagulation profiles, and renal functions in healthy volunteers after vaccination with an inactivated SARS-CoV-2 vaccine. Similar changes had also been reported in COVID-19 patients, suggesting that vaccination mimicked an infection. Single-cell mRNA sequencing (scRNA-seq) of peripheral blood mononuclear cells (PBMCs) before and 28 days after the first inoculation also revealed consistent alterations in gene expression of many different immune cell types. Reduction of CD8+ T cells and increase in classic monocyte contents were exemplary. Moreover, scRNA-seq revealed increased NF-κB signaling and reduced type I interferon responses, which were confirmed by biological assays and also had been reported to occur after SARS-CoV-2 infection with aggravating symptoms. Altogether, our study recommends additional caution when vaccinating people with pre-existing clinical conditions, including diabetes, electrolyte imbalances, renal dysfunction, and coagulation disorders.

Comparison of twelve single-drug regimens for the treatment of type 2 diabetes mellitus.

We performed a network meta-analysis to compare the efficacy of 12 single-drug regimens (Glibenclamide, Glimepiride, Pioglitazone, Rosiglitazone, Repaglinide, Metformin, Sitaglitin, Exenatide, Liraglutide, Acarbose, Benfluorex, and Glipizide) in the treatment of type 2 diabetes mellitus (T2DM). Fifteen relevant randomized controlled trials (RCTs) were included; direct and indirect evidence from these studies was combined, and weighted mean difference (WMD) and surface under the cumulative ranking curves (SUCRAs) were examined to evaluate the monotherapies. Liraglutide was more effective than Glimepiride, Pioglitazone, Sitaglitin, Exenatide, and Glipizide at reducing glycated hemoglobin (HbA1c) levels. In contrast, Acarbose was less effective than Glibenclamide, Glimepiride, Pioglitazone, Rosiglitazone, Repaglinide, Metformin, and Liraglutide at decreasing HbA1c levels. Reductions in fasting plasma glucose (FPG) levels were similar after all treatments. Rosiglitazone was less effective than Glibenclamide and Repaglinide at reducing total cholesterol (TC) levels. High density lipoprotein (HDL), low density lipoprotein (LDL), and triglyceride levels did not differ after treatment with any of the monotherapies. HbA1c and FPG SUCRA values were highest for Liraglutide, while HbA1c and FPG values were lowest for Acarbose, and TC and LDL values were lowest for Rosiglitazone. These results suggest that Liraglutide may be most effective, and Acarbose least effective, at reducing blood glucose levels, while Glibenclamide, Repaglinide, and Metformin may be most effective, and Rosiglitazone least effective, at reducing lipoidemia, in T2DM patients.

(E)-2-[2-(4-Chloro-benzyl-idene)hydrazin-yl]-4-[3-(morpholin-4-ium-4-yl)propyl-amino]-quinazolin-1-ium bis-(perchlorate).

In the title compound, C(22)H(27)ClN(6)O(2) (2+)·2ClO(4) (-), the mol-ecule adopts an E conformation about the C=N double bond. The quinazoline ring is approximately planar, with an r.m.s. deviation of 0.0432 Å, and forms a dihedral angle of 5.77 (4)° with the chloro-phenyl ring. The crystal packing features N-H⋯O hydrogen bonds.

In vitro differentiation of rat embryonic stem cells into functional cardiomyocytes.

The recent breakthrough in the generation of rat embryonic stem cells (rESCs) opens the door to application of gene targeting to create models for the study of human diseases. In addition, the in vitro differentiation system from rESCs into derivatives of three germ layers will serve as a powerful tool and resource for the investigation of mammalian development, cell function, tissue repair, and drug discovery. However, these uses have been limited by the difficulty of in vitro differentiation. The aims of this study were to establish an in vitro differentiation system from rESCs and to investigate whether rESCs are capable of forming terminal-differentiated cardiomyocytes. Using newly established rESCs, we found that embryoid body (EB)-based method used in mouse ESC (mESC) differentiation failed to work for the serum-free cultivated rESCs. We then developed a protocol by combination of three chemical inhibitors and feeder-conditioned medium. Under this condition, rESCs formed EBs, propagated and differentiated into three embryonic germ layers. Moreover, rESC-formed EBs could differentiate into spontaneously beating cardiomyocytes after plating. Analyses of molecular, structural, and functional properties revealed that rESC-derived cardiomyocytes were similar to those derived from fetal rat hearts and mESCs. In conclusion, we successfully developed an in vitro differentiation system for rESCs through which functional myocytes were generated and displayed phenotypes of rat fetal cardiomyocytes. This unique cellular system will provide a new approach to study the early development and cardiac function, and serve as an important tool in pharmacological testing and cell therapy.

[Study on the upper limit and its revision method of normal thyroid volume of children of 8-10 years-old in Zhejiang Province].

OBJECTIVE: To study the upper limit of normal thyroid volume based children 8-10 years old in Zhejiang Province. At the same time, the revision methods of thyroid volume were discussed. METHODS: The thyroid volume of 1110 children 8-10 years old in Zhejiang province, was measured by ultrasonography during the fifth national survey of IDD in 2002 and was analyzed by using SPSS 10.0 for Windows. RESULTS: 1. Children's thyroid volume was progressively increased with age. But there was no significant difference between boys and girls. 2. The upper limit of normal thyroid volume of children at the age of 8, 9 and 10 years old in a province were 4.7, 5.3 and 6.0ml respectively. The upper limit of normal thyroid volume in children at the age of 8 and 9 is higher than the corresponding criteria of GB16398-1996. 3. Of all the four revision methods of thyroid volume, HVI was better than others. CONCLUSIONS: 1. The upper limit of normal thyroid volume of children at the age of 8-10 years old in a province was reasonable, and these normative values were useful for the IDD surveillance in a province and were also referential for revision of Chinese national normative values for schoolchildren. 2. HVI maybe the best method to adjust the thyroid volume at present.