Circadian clock-related genome-wide mendelian randomization identifies putatively genes for ulcerative colitis and its comorbidity.

BACKGROUND: Circadian rhythm is crucial to the function of the immune system. Disorders of the circadian rhythm can contribute to inflammatory diseases such as Ulcerative colitis (UC). This Mendelian Randomization (MR) analysis applies genetic tools to represent the aggregated statistical results of exposure to circadian rhythm disorders and UC and its comorbidities, allowing for causal inferences. METHODS: Summary statistics of protein, DNA methylation and gene expression quantitative trait loci in individuals of European ancestry (pQTL, mQTL, and eQTL, respectively) were used. Genetic variants located within or near 152 circadian clock-related genes and closely related to circadian rhythm disorders were selected as instrumental variables. Causal relationships with UC and its comorbidities were then estimated through employed Summary data-based Mendelian Randomization (SMR) and Inverse-Variance-Weighted MR (IVW-MR). RESULTS: Through preliminary SMR analysis, we identified a potential causal relationship between circadian clock-related genes and UC along with its comorbidities, which was further confirmed by IVW-MR analysis. Our study identified strong evidence of positive correlation involving seven overlapping genes (CSNK1E, OPRL1, PIWIL2, RORC, MAX, PPP5C, and AANAT) through MWAS and TWAS in UC, four overlapping genes (OPRL1, CHRNB2, FBXL17, and SIRT1) in UC with PSC, and three overlapping genes (ARNTL, USP7, and KRAS) in UC with arthropathy. CONCLUSIONS: This SMR study demonstrates the causal effect of circadian rhythm disorders in UC and its comorbidities. Furthermore, our investigation pinpointed candidate genes that could potentially serve as drug targets.

Efficacy of adjunctive photodynamic therapy to conventional mechanical debridement for peri-implant mucositis.

OBJECTIVE: This meta-analysis was conducted to assess the effectiveness of photodynamic therapy (PDT) as an adjunct to conventional mechanical debridement (CMD) for the management of peri-implant mucositis (p-iM). METHODS: We systematically searched four databases (PubMed, Embase, Web of Science, and Cochrane Library) for randomized controlled trials (RCTs) investigating PDT + CMD for p-iM from their inception to March 13, 2023. Meta-analysis was performed using RevMan 5.4 software. RESULTS: Seven RCTs met the inclusion criteria. The meta-analysis revealed that PDT + CMD treatment was more effective than CMD alone in reducing probing depth (PD) (Mean Difference [MD]: -1.09, 95% Confidence Interval [CI]: -1.99 to -0.2, P = 0.02) and plaque index (PI) (MD: -2.06, 95% CI: -2.81 to -1.31, P < 0.00001). However, there was no statistically significant difference in the improvement of bleeding on probing (BOP) between the PDT + CMD groups and CMD groups (MD: -0.97, 95% CI: -2.81 to 0.88, P = 0.31). CONCLUSIONS: Based on the current available evidence, this meta-analysis indicates that the addition of PDT to CMD significantly improves PD and PI compared to CMD alone in the treatment of p-iM. However, there is no significant difference in improving BOP.

Drug treatment for oral submucous fibrosis: an update.

OBJECTIVE: The aim of this review is to evaluate the different medicinal interventions available for the management of oral submucous fibrosis (OSF). MATERIALS AND METHODS: We conducted a comprehensive electronic search on PubMed, Web of Science, and Cochrane Library databases for articles related to OSF patients treated with medications from December 2011 to September 2022. GRADE system was used to evaluate the evidence quality. The reporting of the systematic review is in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) protocol. The main outcomes were the improvement of maximum mouth opening, burning sensation, cheek flexibility, and tongue protrusion. RESULTS: Twenty-nine randomized controlled trials (RCTs), five clinical trials (CCTs) were included, and the use of drugs for OSF treatment were evaluated. Drugs like steroids, hyaluronidase, pentoxifylline, lycopene, curcumin, dpirulina, aloe vera, omega3, oxitard, allicin, colchicine have been used. It was found that drugs with evidence high quality were salvia miltiorrhiza combined with triamcinolone acetonide, lycopene, pentoxifylline, curcumin, and aloe vera, and those with evidence moderate quality were allicin, colchicine, omega 3, and oxitard. CONCLUSION: Based on the results of our comprehensive analysis, for long-term treatment, we found lycopene with low side effects, whereas for relieving the symptoms of severe burning sensation, aloe vera is the most effective. Although the recent review has made some progress, drug therapy for OSF remains unclear, and more high-quality RCTs are needed to identify better treatments for OSF.

Downregulation of VAP-1 in OSCC suppresses tumor growth and metastasis via NF-κB/IL-8 signaling and reduces neutrophil infiltration.

BACKGROUND: Vascular adhesion protein-1 (VAP-1) is believed to play a role in inflammation. Studies have suggested that VAP-1-mediated activation of inflammation is dependent on NF-κB, leading to secretion of the interleukin (IL)-8; however, no reports have addressed the association between VAP-1 and NF-κB/IL-8 signaling in oral squamous cell carcinoma (OSCC). This study aimed to investigate the role of VAP-1 in OSCC and further explore whether VAP-1 is involved in the regulation of neutrophil infiltration in the tumor microenvironment (TME). METHODS: Immunochemistry staining was used to observe VAP-1 expression. CCK-8 and Transwell assays were used to measure cell proliferation, migration, and invasion. OSCC xenograft mouse models were used for in vivo verification of the VAP-1 function. The expression of NF-κB and IL-8 were determined by qRT-PCR and western blot. ELISA for IL-8 was also conducted. The relationship between VAP-1 expression and neutrophil infiltration was analyzed by immunofluorescence. RESULTS: VAP-1 was overexpressed in human OSCC tissues. Downregulation of VAP-1 suppressed OSCC cells proliferation, migration, and invasion in vitro and inhibited tumor proliferation and metastasis in vivo. Additionally, downregulation of VAP-1 inhibited NF-κB/IL-8 signaling in vitro and in vivo. VAP-1 expression was positively correlated with neutrophil infiltration in human OSCC tissues. Moreover, blocking VAP-1 decreased neutrophil infiltration by reducing IL-8 production. CONCLUSIONS: VAP-1 downregulation in OSCC suppresses tumor growth and metastasis by inhibiting NF-κB/IL-8 signaling and reducing neutrophil infiltration in the TME, suggesting that VAP-1 may be a potential therapeutic target for OSCC.

TGF-ß1 and IL-17A comediate the protumor phenotype of neutrophils to regulate the epithelial-mesenchymal transition in oral squamous cell carcinoma.

BACKGROUND: The role of neutrophils in cancer has been the subject of intense research in recent years. One major theme that has emerged is that not all neutrophils are equal in the field of cancer. However, it remains unclear what induces the protumorigenic or antitumorigenic phenotype predominate in tumor. Therefore, this study aimed to investigate what factors induce which of these two phenotypes of neutrophil predominate in OSCC and to explore the role of neutrophil polarization on tumor. METHODS: Immunofluorescence and immunohistochemistry staining were used to observe neutrophil infiltration and the expression of TGF-ß1 and IL-17A in OSCC tissues. Recombinant human TGF-ß1 and IL-17A were used to modulate neutrophil polarization. OSCC cell (SCC9 and SAS cell lines) migration, proliferation, invasion, stemness, and EMT were analyzed after treatment with conditioned medium from TGF-ß1/IL-17A-activated neutrophils. The levels of neutrophil-associated markers in OSCC tissues and peripheral blood were examined by immunofluorescence staining and quantitative PCR. RESULTS: Our data showed neutrophil infiltration and elevated expression of TGF-ß1 and IL-17A in OSCC tissues. The cooperative effect of TGF-ß1 and IL-17A promoted neutrophils to take on a protumor phenotype in vitro. TGF-ß1/IL-17A-activated neutrophils remarkably induced cell migration, proliferation, invasion, stemness, and EMT in OSCC cells. Additionally, OSCC patients showed increased expression of MMP9 and decreased expression of CCL3 in circulating neutrophils. CONCLUSION: TGF-ß1 and IL-17A cooperated to augment the protumor functions of neutrophils, thereby promoting the progression of OSCC cells. In addition, the combination of neutrophil-associated markers may serve as a predictive method to screen for patients with OSCC.

Nanoplastics aggravate the toxicity of arsenic to AGS cells by disrupting ABC transporter and cytoskeleton.

The coexistence of nanoplastics (NPs) and pollutants such as arsenic (As) has become an unignorable environmental problem. However, there is still a considerable knowledge gap about the impact of NPs and pollutants on human health risks. In this study, the human gastric adenocarcinoma (AGS) cells were used as a model to investigate the toxicity of NPs with different particle sizes and As by MTT assay, western blotting, immunofluorescence and so on. The results showed that 20 nm (8 µg/mL), 50 nm (128 µg/mL), 200 nm (128 µg/mL), 500 nm (128 µg/mL), 1000 nm (128 µg/mL) polystyrene (PS) did not affect cell viability, ROS, intracellular calcium and activate apoptosis pathway in AGS cells. However, noncytotoxic concentration of NPs enhanced the cytotoxicity and intracellular accumulation of As. NPs destroys the fluidity of cell membrane and cytoskeleton, inhibits the activity of ABC transporter, and leads to the accumulation of As in cells. This work highlights that the damage caused by NPs, especially at the level of noncytotoxicity, joint with As cannot be ignored and provides a specific toxicological mechanism of NPs accompanied by exposure to As.

The association between the socioeconomic status and systemic comorbidities in patients with oral cancers: a retrospective study in Guangxi Province.

BACKGROUND: It is unclear whether and how the prevalence of systemic comorbidities in oral cancer patients would change with socioeconomic development. MATERIALS AND METHODS: A retrospective study of association between socioeconomy and prevalence of systemic comorbidities in oral cancer patients from 2003 to 2017 was performed in Guangxi Province, a southwestern part of China. According to the Union for International Cancer Control (UICC) classification, 2814 patients with squamous cell carcinoma (SCC) of the lip, oral cavity, and oropharynx and 423 patients with ameloblastoma were collected and assigned to the oral cancer group and control group, respectively. Then, comparisons between the socioeconomy and healthcare expenditure in Guangxi Province, the whole China, and the USA were carried out. RESULTS: The prevalence of systemic comorbidities in oral cancer patients increased from 0.820% in 2003 to 32.302% in 2017, which was significantly higher than that in non-cancer patients(P < 0.001) and was positively correlated with the increase in gross regional product (GRP) (r = 0.911, P < 0.001) and per capita GRP (r = 0.910, P < 0.001) of Guangxi Province. In addition, the prevalence of cardiovascular diseases has the largest correlation coefficient with GRP(r = 0.957, P < 0.001) and per capita GRP(r = 0.959, P < 0.001). And the prevalence of endocrine diseases increased by 13.402% and exhibited the most significant increase in 15 years. The per capita health care expenditure of Guangxi Province and whole China was nearly equal (P = 0.353). Although the health care expenditure of Guangxi Province had been increasing year by year, its proportion in GRP remains far below that of the USA. CONCLUSIONS: With socioeconomic growth, oral cancer patients in Guangxi Province are more common to comorbid with systemic diseases. Cardiovascular and endocrine diseases may be the most susceptible systemic comorbidities in oral cancer patients to the socioeconomic status. In order to control the prevalence of systemic diseases, the government of Guangxi Province may need to expend more budgets in the health care. CLINICAL RELEVANCE: Clinicians need to pay more attention to the detection of systemic comorbidities and the concept of multidisciplinary collaboration. Instructing oral cancer patients to treat and control systemic comorbidities is also an indispensable part in the treatment of oral cancer.

Association between condylar position changes and functional outcomes after condylar reconstruction by free fibular flap.

OBJECTIVES: Stable and appropriate condyle positioning is necessary for maintaining temporomandibular joint function. It is unclear if this position remains stable in patients after free fibular flap (FFF) condylar reconstruction. We investigated whether condylar position deviated after reconstruction, and whether this affected functional recovery. MATERIALS AND METHODS: We retrospectively reviewed 43 patients who underwent conventional FFF condylar reconstruction, and 5 patients who underwent reconstruction by computer-assisted three-dimensional (3D) printing methods. Three-dimensional models were built from cone-beam computed tomography images obtained immediately postoperatively and 1-year postoperatively. The glenoid fossa and fibular condyle centers were used to measure the fibular condyle position in the models. Clinical examination indices, including maximum mouth opening (MMO), pain during chewing/mouth opening, and patient satisfaction with mastication and 1-year outcomes were assessed. RESULTS: Fibular condyle position changed significantly over 1 year in both groups (P < 0.05). Clinical examination at 1 year after the surgery showed that in the conventional group, the MMO range was ≥ 35 mm in 76.7% of patients and < 35 mm in 23.3% of patients; 4.7% experienced pain during chewing/mouth opening, and 7% were dissatisfied with treatment outcomes. In the 3D printing group, all patients had an MMO range exceeding 35 mm, none had pain, and all were satisfied with functional outcomes. CONCLUSIONS: The position of the fibular condyle deviates after reconstructive surgery, but it is unlikely to affect functional recovery. CLINICAL RELEVANCE: These findings can form the basis for evaluation of functional outcomes of patients who have previously undergone condylar reconstruction by FFF.

A seven-gene signature model predicts overall survival in kidney renal clear cell carcinoma.

BACKGROUND: Kidney renal clear cell carcinoma (KIRC) is a potentially fatal urogenital disease. It is a major cause of renal cell carcinoma and is often associated with late diagnosis and poor treatment outcomes. More evidence is emerging that genetic models can be used to predict the prognosis of KIRC. This study aimed to develop a model for predicting the overall survival of KIRC patients. RESULTS: We identified 333 differentially expressed genes (DEGs) between KIRC and normal tissues from the Gene Expression Omnibus (GEO) database. We randomly divided 591 cases from The Cancer Genome Atlas (TCGA) into training and internal testing sets. In the training set, we used univariate Cox regression analysis to retrieve the survival-related DEGs and futher used multivariate Cox regression with the LASSO penalty to identify potential prognostic genes. A seven-gene signature was identified that included APOLD1, C9orf66, G6PC, PPP1R1A, CNN1G, TIMP1, and TUBB2B. The seven-gene signature was evaluated in the training set, internal testing set, and external validation using data from the ICGC database. The Kaplan-Meier analysis showed that the high risk group had a significantly shorter overall survival time than the low risk group in the training, testing, and ICGC datasets. ROC analysis showed that the model had a high performance with an AUC of 0.738 in the training set, 0.706 in the internal testing set, and 0.656 in the ICGC external validation set. CONCLUSION: Our findings show that a seven-gene signature can serve as an independent biomarker for predicting prognosis in KIRC patients.

Sidt2 regulates hepatocellular lipid metabolism through autophagy.

SID1 transmembrane family member 2 (Sidt2) is an integral lysosomal membrane protein. To investigate its explicit function, we generated a global Sidt2 knockout mouse model (Sidt2-/-). Compared with the littermate controls, Sidt2-/- mice exhibited a remarkable accumulation of lipid droplets in liver. First, it was observed that food consumption, hepatocyte fatty acid uptake and de novo lipogenesis, hepatocyte lipolysis, and TG secretion in the form of very low density lipoprotein were comparable between Sidt2-/- and WT mice. However, the hepatic ß-oxidation of fatty acids decreased significantly as revealed by a low level of serum ß-hydroxybutyrate in the Sidt2-/- mice along with normal mRNA expression of genes involved in fatty acid oxidation. In addition, the classical autophagy pathway marker proteins, p62 and LC3-II, increased in liver, along with compromised autophagic flux in primary hepatocytes, indicating a block of autophagosome maturation due to Sidt2 deficiency, which was also supported by electron microscopy image analysis both in livers and in primary hepatocytes from Sidt2-/- mice. It was concluded that Sidt2 plays an important role in mouse hepatic lipid homeostasis by regulating autophagy at the terminal stage.

Comprehensive assessment of peripheral blood TCRß repertoire in infectious mononucleosis and chronic active EBV infection patients.

Epstein-Barr virus (EBV) primary infection is usually asymptomatic, but it sometimes progresses to infectious mononucleosis (IM). Occasionally, some people develop chronic active EBV infection (CAEBV) with underlying immunodeficiency, which belongs to a continuous spectrum of EBV-associated lymphoproliferative disorders (EBV+ LPD) with heterogeneous clinical presentations and high mortality. It has been well established that T cell-mediated immune response plays a critical role in the disease evolution of EBV infection. Recently, high-throughput sequencing of the hypervariable complementarity-determining region 3 (CDR3) segments of the T cell receptor (T cell receptor ß (TCRß)) has emerged as a sensitive approach to assess the T cell repertoire. In this study, we fully characterized the diversity of peripheral blood TCRß repertoire in IM (n = 6) and CAEBV patients (n = 5) and EBV-seropositive controls (n = 5). Compared with the healthy EBV-seropositive controls, both IM and CAEBV patients demonstrate a significant decrease in peripheral blood TCRß repertoire diversity, basically, including narrowed repertoire breadth, highly expanded clones, and skewed CDR3 length distribution. However, there is no significant difference between IM and CAEBV patients. Furthermore, we observed some disease-related preferences in TRBV/TRBJ usage and combinations, as well as lots of T cell clones shared by different groups (unique or overlapped) involved in public T cell responses, which provide more detailed insights into the divergent disease evolution.

Demographic characteristics and distribution of lysosomal storage disorder subtypes in Eastern China.

Lysosomal storage disorders (LSDs) are a group of >50 different types of inherited metabolic disorders that result from defects in the lysosome. The aim of this study was to investigate the distribution and demographic characteristics of the different subtypes of LSDs in Eastern China. From 2006 to 2012, 376 out of 1331 clinically suspected patients were diagnosed with 17 different subtypes of LSDs at our hospital. Mucopolysaccharidoses (MPS) were the most common group of LSDs (50.5%), followed by sphingolipidoses (25.4%) and Pompe disease (19.8%). Mucolipidosis type II/III accounted for the remaining 4% of diagnosed LSDs. MPS II was the most common form of MPS, comprising 47.4% of all MPS cases diagnosed, followed by MPS IVA (26.8%) and MPS I (16.3%). Gaucher disease and Niemann-Pick disease type A/B were the two most common forms of sphingolipidoses. There was a large variation in the time between disease onset and eventual diagnosis, from 0.3 years in infantile-onset Pompe disease to 30 years in Fabry disease, highlighting timely and accurate diagnosis of LSDs as the main challenge in China.

Association of osteoprotegerin with impaired glucose regulation and microalbuminuria: the REACTION study.

BACKGROUND: High osteoprotegerin (OPG) has been reported in association with insulin resistance and type 2 diabetes. We aimed to evaluate the association of serum OPG with impaired glucose regulation (IGR) and microalbuminuria among middle-aged and older Chinese. METHODS: Serum OPG was measured in 599 individuals with normal glucose regulation, 730 with impaired glucose regulation and 327 newly diagnosed patients with diabetes. Serum OPG was measured using ELISA methods and urine albumin/creatinine ratio was used to determine the urinary albumin excretion. RESULTS: Serum OPG levels were significantly higher in subjects with isolated impaired fasting glucose, isolated impaired glucose tolerance, combined impaired fasting glucose/impaired glucose tolerance and diabetes than in those with normal glucose regulation, whereas serum OPG levels were not different in the four groups with dysregulation of glucose metabolism. OPG was associated with a higher risk for IGR (OR 1.108 for each 0.1 µg/l increase in OPG, 95% CI 1.009-1.117, p = 0.01) after adjustment for gender, age, BMI, current smoking and alcohol intake, family history of diabetes, homeostasis model assessment of insulin resistance (HOMA-IR), lipid profile; the corresponding OR of combined impaired glucose regulation and type 2 diabetes was 1.121 (95% CI 1.101-1.141, p = 0.0005). OPG was associated with the risk of microalbuminuria (OR 1.025, 95% CI 1.006-1.044, p = 0.02) after adjustment for gender, age, current smoking, current alcohol intake, family history of diabetes, BMI, waist/hip ratio, HOMA-IR, eGFR and lipid profile. CONCLUSIONS: Serum OPG level is closely and independently associated with IGR and is an independent risk factor for microalbuminuria.

Salivary and serum levels of lactate dehydrogenase in oral submucous fibrosis: A meta-analysis.

BACKGROUND: The occurrence of oral submucous fibrosis (OSF) is often accompanied by an increase in lactate dehydrogenase (LDH) levels. In this meta-analysis, we compared the salivary and serum levels of LDH levels between OSF patients and controls. MATERIAL AND METHODS: A comprehensive search was conducted in PubMed, Embase, Web of Science, and Cochrane Library from the establishment of the database to June 2023, and the quality of the studies was checked by the Newcastle-Ottawa Quality Assessment scale. The mean difference (MD) and 95% confidence interval (CI) were calculated using RevMan 5.4 software. RESULTS: A total of 28 studies were retrieved from the database, and we included 5 studies in this meta-analysis. The salivary LDH level of OSF patients was higher than healthy controls (MD: 423.10 pg/L 95%CI: 276.42-569.77 pg/mL, P < .00001), the serum LDH level of OSF patients was also higher than that of healthy controls (MD: 226.20 pg/mL, 95%CI: 147.71-304.69 pg/mL, P < .00001). CONCLUSIONS: This meta-analysis showed that salivary and serum LDH levels were higher in OSF patients than in healthy controls, suggesting that LDH may be a potential biomarker for OSF.

The causal role of gut microbiota in susceptibility of Long COVID: a Mendelian randomization study.

Background: Long COVID is a major challenge facing the public. Gut microbiota is closely related to Long COVID. However, the causal effects between gut microbiota and Long COVID remains unclear. Methods: Using summary statistics from Genome-Wide Association Studies (GWAS), Mendelian randomization (MR) analyses were performed to investigate the relationship between gut microbiota and Long COVID. The primary statistical method employed was Inverse Variance Weighted (IVW). Sensitivity analyses were then conducted to evaluate the reliability of the findings and account for potential confounding variables. Finally, a reverse MR analysis was conducted to examine potential associations between Long COVID and genetically predicted gut microbiota compositions. Results: There were 2 positive and 1 negative causal effect between gut microbiota and Long COVID. Meta-analysis results show that genus Parasutterella (OR = 1.145, 95%CI = 1.035 ∼ 1.266, P = 0.008) and genus Oscillospira (OR = 1.425, 95%CI = 1.235 ∼ 1.645, P < 0.001) significantly increased the risk of Long COVID. And genus Eisenbergiella (OR = 0.861, 95%CI = 0.785 ∼ 0.943, P = 0.001) significantly decreased the risk of Long COVID. Neither the pleiotropy nor the heterogeneity was observed. Reverse causal effect does not hold. Conclusion: Our research has provided genetic evidence that establishes multiple causal relationships between the gut microbiota and Long COVID, supporting the role of the gut microbiota in Long COVID. It is possible that different taxa play a role in the development of Long COVID. The causal relationships identified in this study require further investigation.

Assessing the causal associations of sleep apnea with mental health and socioeconomic status: a bidirectional two-sample Mendelian randomization.

OBJECTIVE: Traditional observational research has suggested a connection between socioeconomic position, mental health, and sleep apnea (SA), but the specifics of this connection are still unclear. Using the Mendelian randomization approach, we intended to evaluate the potential causal link between mental health, socioeconomic status, and SA. METHODS: Our research employed summary statistics data from large-scale genome-wide association studies (GWAS) on mental health, socioeconomic status, and SA. In the main study, the connection between mental health, socioeconomic status, and SA was examined using the inverse variance weighted approach. In addition, as a supplement, we also used other Mendelian randomization methods, including MR Egger, weighted median, simple mode, and weighted mode. RESULTS: The primary analysis showed that educational attainment, including longer years of schooling, college or university degree, and higher intelligence was associated with a lower risk of SA (OR = 0.750, 95%CI = 0.653-0.862; OR = 0.558, 95%CI = 0.423-0.735; OR = 0.871, 95%CI = 0.760-0.999, respectively), while social deprivation was associated with a higher risk of SA (OR = 1.821, 95%CI = 1.075-3.085). And the income was not associated with the risk of sleep apnea (OR = 0.877, 95%CI = 0.682-1.129). In mental health exposure, major depressive disorder was associated with a higher risk of sleep apnea (OR = 1.196, 95%CI = 1.015-1.409), while attention-deficit hyperactivity disorder, bipolar disorder, and schizophrenia were not associated with the risk of sleep apnea (OR = 1.064, 95%CI = 0.958-1.181; OR = 1.030, 95%CI = 0.942-1.127; OR = 0.990, 95%CI = 0.957-1.025, respectively). Reverse MR analysis failed to find a causal effect from SA on mental health and socioeconomic status. CONCLUSIONS: This MR investigation offers proof of a possible causal relationship between SA, socioeconomic level, and mental health.

A genome-wide cross-trait analysis identifies shared loci and causal relationships of obesity and lipidemic traits with psoriasis.

Background: Obesity and dyslipidemia, major global health concerns, have been linked to psoriasis, but previous studies faced methodological limitations and their shared genetic basis remains unclear. This study examines various obesity-related and lipidemic traits as potential contributors to psoriasis development, aiming to clarify their genetic associations and potential causal links. Methods: Summary statistics from genome-wide association studies (GWAS) conducted for obesity-related traits (body mass index (BMI), waist-to-hip ratio (WHR), and waist-to-hip ratio adjusted for the body mass index (WHRadjBMI)) and lipidemic traits (high-density lipoprotein (HDL), LDL, triglyceride (TG), total Cholesterol (TC), apolipoprotein A1 (apoA1), apolipoprotein B (apoB), and apolipoprotein E (apoE)) and psoriasis, all in populations of European ancestry, were used. We quantified genetic correlations, identified shared loci and explored causal relationship across traits. Results: We found positive genetic correlation between BMI and psoriasis (rg=0.22, p=2.44×10-18), and between WHR and psoriasis (rg=0.19, p=1.41×10-12). We further found the positive genetic correlation between psoriasis and WHRadjBMI(rg=0.07, p=1.81×10-2) the genetic correlation, in while the effect of BMI was controlled for. We identified 14 shared loci underlying psoriasis and obesity-related traits and 43 shared loci between psoriasis and lipidemic traits via cross-trait meta-analysis. Mendelian randomization (MR) supported the causal roles of BMI (IVW OR=1.483, 95%CI=1.333-1.649), WHR (IVW OR=1.393, 95%CI=1.207-1.608) and WHRadjBMI (IVW OR=1.18, 95%CI=1.047-1.329) in psoriasis, but not observe any significant association between lipidemic traits and the risk of psoriasis. Genetic predisposition to psoriasis did not appear to affect the risk of obesity and lipidemic traits. Conclusions: An intrinsic link between obesity-related traits and psoriasis has been demonstrated. The genetic correlation and causal role of obesity-related traits in psoriasis highlight the significance of weight management in both the prevention and treatment of this condition.

Conversion of Polyethylene to High-Yield Fuel Oil at Low Temperatures and Atmospheric Initial Pressure.

The transformation of waste plastics into fuels via energy-efficient and low-cost pyrolysis could incentivize better waste plastic management. Here, we report pressure-induced phase transitions in polyethylene, which continue to heat up without additional heat sources, prompting the thermal cracking of plastics into premium fuel products. When the nitrogen initial pressure is increased from 2 to 21 bar, a monotonically increasing peak temperature is observed (from 428.1 °C to 476.7 °C). At 21 bar pressure under different atmosphere conditions, the temperature change driven by high-pressure helium is lower than that driven by nitrogen or argon, indicating that phase transition is related to the interaction between long-chain hydrocarbons and intercalated high-pressure medium layers. In view of the high cost of high-pressure inert gases, the promotion or inhibition effect of low-boiling hydrocarbons (transitioning into the gaseous state with increasing temperature) on phase transition is explored, and a series of light components are used as phase transition initiators to replace high-pressure inert gases to experiment. The reason that the quantitative conversion of polyethylene to high-quality fuel products is realized through the addition of 1-hexene at a set temperature of 340 °C and the initial atmospheric pressure. This discovery provides a method for recycling plastics by low energy pyrolysis. In addition, we envisage recovering some of the light components after plastic pyrolysis as phase change initiators for the next batch of the process. This method is able to reduce the cost of light hydrocarbons or high-pressure gas insertion, reduce heat input, and improve material and energy utilization.

Synergistic Effects on the Co-pyrolysis of Agricultural Wastes and Sewage Sludge at Various Ratios.

This study investigated the co-pyrolysis of blends of sewage sludge (SS) with rice husk (RH) and with hemp straw (HS) at different ratios by using thermogravimetry (TG) and its rate (DTG, derivative TG) analysis at heating rates of 10, 20, and 30 K/min. The resulting kinetic parameters of activation energy (E a) were calculated by both Flynn-Wall-Ozawa and Kissinger-Akahira-Sunose models, followed by comparison of experimental values with calculated values to reveal the synergistic effects of SS/RH and SS/HS. With increasing additions of RH or HS to SS, a gradual decreasing trend in the experimental pyrolysis temperature range was evident, ranging from 144.5 to 95.2 °C for SS/RH and from 144.5 to 88.8 °C for SS/RH. Moreover, such temperature ranges were 6.7-20.4 °C less than the calculated values at the same blending ratio. The fitting results of the two kinetic models showed that with the same SS mass ratio, the experimental E a * (average activation energy) of both SS/RH and SS/HS were less than the calculated E a *. Especially, the experimental E a * of 7SS-3RH was lower around 43.8% than the calculated E a *, whereas the experimental E a * of 3SS-7HS was lower by about 39.4% than the calculated E a *. Synergistic analysis demonstrated that the co-pyrolysis of RH or HS with SS at various mass ratios presented obvious synergistic effects and then the decrease of E a. The mechanism experiment showed that the co-pyrolysis of SS/HS may promote the decrease of E a by changing the co-pyrolysis gas products or by increasing the overflow of volatile matter and then forming intermediate transition products, while SS/RH may accelerate the decrease of the E a by using an appropriate K addition ratio from RH as a metal catalyst.

Identification and Validation of an Endoplasmic Reticulum Stress-Related lncRNA Signature for Colon Adenocarcinoma Patients.

Purpose: Endoplasmic reticulum (ER) stress has a significant effect on cancer cells. Increasing numbers of studies indicate that long non-coding RNAs (lncRNAs) promote the development of colon adenocarcinoma (COAD), but the relationship between ER stress-related lncRNAs and the prognosis of COAD remains unclear. The aim of the current study was to construct and validate an ER stress-related lncRNA prognostic signature to predict COAD prognoses. Methods: Gene expression data and clinical information from the Cancer Genome Atlas and the Gene Expression Omnibus with COAD were downloaded and analyzed. Cox regression and least absolute shrinkage and selection operator regression were then used to develop an ER stress-related lncRNA signature. COAD patients were then divided into high-risk and low-risk groups based on the median risk score to analyze prognoses. Tumor mutation burdens (TMBs) and the differences in copy number variations (CNVs) between the two groups were also analyzed. Lastly, gene set enrichment analysis (GSEA) was used to explore the enrichment pathways and biological processes associated with differentially expressed genes in the high-risk and low-risk groups, and lncRNA expression in the model was validated via quantitative real-time PCR in colon cancer and paracancerous tissues. Results: A signature including 8 ER stress-related lncRNAs was constructed. COAD prognoses were significantly poorer in the high-risk group than in the low-risk group. There were few differences in TMBs and CNVs between the two groups. In GSEA analysis, in the high-risk group highly expressed genes associated with extracellular matrix pathways were significantly enriched. Conclusion: The 8-ER stress-related lncRNA derived from the present study is a potential indicator of COAD prognosis.