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Abstract The authors report a case of primary aldosteronism (PA) with postoperative elevation of aldosterone treated effectively by finerenone. The patient was a hypertensive man with a 30‐year history of hypertension and sustained an acute myocardial infarction 5 years ago. Bilateral adrenal nodules with hyperplasia were detected and PA was confirmed. His blood potassium, direct renin concentration, and aldosterone level returned to normal after surgery of right adrenalectomy. However, 1 year after surgery, he experienced a decrease in blood potassium and an increase in aldosterone. A saline infusion test revealed an aldosterone level of 124.47 pg/mL. The patient consented to treatment with finerenone. His aldosterone and potassium levels and blood pressure have been controlled well during follow‐up. This case highlights the need to screen for secondary hypertension as early as possible. Finerenone may be effective for patients with PA who are not candidates for surgery and those not relieved after surgery.

Abstract Hepatocellular carcinoma (HCC) is the primary malignant tumor of the liver. c-Myc is one of the most common oncogenes in clinical settings, and amplified levels of c-Myc are frequently found in HCC. Histone deacetylase inhibitors (HDACi), such as Trichostatin A (TSA), hold enormous promise for the treatment of HCC. However, the potential and mechanism of TSA in the treatment of c-Myc-induced HCC are unclear. In this study, we investigated the effects of TSA treatment on a c-Myc-induced HCC model in mice. TSA treatment delayed the development of HCC, and liver function indicators such as ALT, AST, liver weight ratio, and spleen weight ratio demonstrated the effectiveness of TSA treatment. Oil red staining further demonstrated that TSA attenuated lipid accumulation in the HCC tissues of mice. Through mRNA sequencing, we identified that TSA mainly affected cell cycle and fatty acid degradation genes, with alcohol dehydrogenase 4 (ADH4) potentially being the core molecular downstream target. QPCR, immunohistochemistry, and western blot analysis revealed that ADH4 expression was repressed by c-Myc and restored after TSA treatment both in vitro and in vivo. Furthermore, we observed that the levels of total NAD+ and NADH, NAD+, NAD+/NADH, and ATP concentration increased after c-Myc transfection in liver cells but decreased after TSA intervention. The levels of phosphorylated protein kinase B (p-AKT) and p-mTOR were identified as targets regulated by TSA, and they governed the ADH4 expression and the downstream regulation of total NAD+ and NADH, NAD+, NAD+/NADH, and ATP concentration. Overall, our study suggests that TSA has a therapeutic effect on c-Myc-induced HCC through the AKT-mTOR-ADH4 pathway. These findings provide valuable insights into the potential treatment of HCC using TSA and shed light on the underlying molecular mechanisms involved.

Abstract Artificial intelligence has emerged as a technology to enhance productivity and improve life quality. However, its role in building energy efficiency and carbon emission reduction has not been systematically studied. This study evaluated artificial intelligence’s potential in the building sector, focusing on medium office buildings in the United States. A methodology was developed to assess and quantify potential emissions reductions. Key areas identified were equipment, occupancy influence, control and operation, and design and construction. Six scenarios were used to estimate energy and emissions savings across representative climate zones. Here we show that artificial intelligence could reduce cost premiums, enhancing high energy efficiency and net zero building penetration. Adopting artificial intelligence could reduce energy consumption and carbon emissions by approximately 8% to 19% in 2050. Combining with energy policy and low-carbon power generation could approximately reduce energy consumption by 40% and carbon emissions by 90% compared to business-as-usual scenarios in 2050.

Abstract Background Neither a TYRP1-mediated highly conserved genetic network underlying skin color towards optimum defense nor the pathological tendency of its mutation is well understood. The Oujiang Color Common Carp (Cyprinus carpio var. color) as a model organism, offering valuable insights into genetics, coloration, aquaculture practices, and environmental health. Here, we performed a comparative skin transcriptome analysis on TYRP1 mutant and wild fishes by applying a conservative categorical approach considering different color phenotypes. Results Our results reveal that an unusual color phenotype may be sensitized with TYRP1 mutation as a result of upregulating several genes related to an anti-inflammatory autoimmune system in response to the COMT-mediated catecholamine neurotransmitters in the skin. Particularly, catecholamines-derived red/brown, red with blue colored membrane attack complex, and brown/grey colored reduced eumelanin are expected to be aggregated in the regenerated cells. Conclusions It is, thus, concluded that the regenerated cells with catecholamines, membrane attack complex, and eumelanin altogether may contribute to the formation of the unusual (coffee-like) color phenotype in TYRP1 mutant.

Abstract Background Angiopoietin-like protein 3 (ANGPTL3) is secreted by hepatocytes and inhibits lipoprotein lipase and endothelial lipase activity. Previous studies reported the correlation between plasma ANGPTL3 levels and high-density lipoprotein (HDL). Recently ANGPTL3 was found to preferentially bind to HDL in healthy human circulation. Here, we examined whether ANGPTL3, as a component of HDL, modulates HDL function and affects HDL other components in human and mice with non-diabetes or type 2 diabetes mellitus. Methods HDL was isolated from the plasma of female non-diabetic subjects and type-2 diabetic mellitus (T2DM) patients. Immunoprecipitation, western blot, and ELISA assays were used to examine ANGPTL3 levels in HDL. Db/m and db/db mice, AAV virus mediated ANGPTL3 overexpression and knockdown models and ANGPTL3 knockout mice were used. The cholesterol efflux capacity induced by HDL was analyzed in macrophages preloaded with fluorescent cholesterol. The anti-inflammation capacity of HDL was assessed using flow cytometry to measure VCAM-1 and ICAM-1 expression levels in TNF-α-stimulated endothelial cells pretreated with HDL. Results ANGPTL3 was found to bind to HDL and be a component of HDL in both non-diabetic subjects and T2DM patients. Flag-ANGPTL3 was found in the HDL of transgenic mice overexpressing Flag-ANGPTL3. ANGPLT3 of HDL was positively associated with cholesterol efflux in female non-diabetic controls (r = 0.4102, p = 0.0117) but not in female T2DM patients (r = − 0.1725, p = 0.3224). Lower ANGPTL3 levels of HDL were found in diabetic (db/db) mice compared to control (db/m) mice and were associated with reduced cholesterol efflux and inhibition of VCAM-1 and ICAM-1 expression in endothelial cells (p

Burkholderia is the second largest source of natural product bacteria after Actinomyces and can produce many secondary metabolites including pyrrolnitrin (PRN). Natural products of microbial origin are usually found in trace amounts, so in metabolic engineering, promoter engineering is often used to regulate gene expression to increase yield. In this study, an endogenous strong promoter was identified based on RNA-seq to overexpress biosynthetic genes to increase the production of PRN. By analyzing the transcriptomic data of the antagonistic bacterium Burkholderia sp. JP2-270 in three different development periods, we screened 50 endogenous promoters with high transcriptional activity, nine of which were verified by an obvious fluorescent signal via fluorescence observation. Then, combined with RT-qPCR analysis, Php, the promoter of a hypothetical protein, was found to be significantly expressed in all three periods. In order to increase the suitability of endogenous promoters, the promoter Php was shortened at different lengths, and the results show that a sequence length of 173 bp was necessary for its activity. Moreover, this promoter was used to overexpress the PRN biosynthesis genes (prnA, prnB, prnC and prnD) in JP2-270, resulting in a successful increase in gene expression levels by 40–80 times. Only the overexpression of the prnB gene successfully increased PRN production to 1.46 times that of the wild type. Overall, the endogenous strong promoters screened in this study can improve gene expression and increase the production of secondary metabolites in JP2-270 and other strains.

Rearrangements involving the neurotrophic-tropomyosin receptor kinase (NTRK) gene family (NTRK1, NTRK2, and NTRK3) have been identified as drivers in a wide variety of human cancers. However, the association between NTRK rearranged thyroid carcinoma and clinicopathological characteristics has not yet been established. In our study, we retrospectively reviewed medical records of thyroid cancer patients and identified 2 cases with NTRK rearrangement, no additional molecular alterations were observed in either of these cases. The fusion of the rearrangement in both cases was ETV6(E4)::NTRK3(E14). By analyzing the clinicopathological features of these two cases, we found that both were characterized by multiple tumor nodules, invasive growth, and central lymph node metastases, indicating the follicular subtype of papillary thyroid carcinoma. Immunohistochemical staining profiles showed CD56-, CK19+, Galectin-3+, HBME1+. These clinicopathological features suggest the possibility of ETV6-NTRK3 rearranged thyroid carcinoma and highlight the importance of performing gene fusion testing by FISH or NGS for these patients.

Purpose: As a major structural component of the outer membrane of Gram-negative bacteria, lipopolysaccharide (LPS) has been detected in the blood circulation and tissues in patients with chronic diseases and cancers, which plays a critical role in the tumor formation and progression. However, the biological role of LPS in human intrahepatic cholangiocarcinoma remains unclear. The aims of this study were to investigate the role of LPS in the malignant progression of intrahepatic cholangiocarcinoma. Methods: The cell migration and invasion capacities of cholangiocarcinoma cell lines were evaluated by Boyden chamber assays. Expression levels of the key molecules involved in the PI3K/AKT signaling and METTL3 were detected by qPCR and western blot. The molecular mechanism by which LPS promotes the malignant behaviors was investigated by using siRNAs, plasmids and small molecule inhibitors. Results: In vitro experiments showed that exogenous LPS treatment promoted cell migration and invasion capacities in both QBC939 and HUCCT1 cell lines, while did not affect cell proliferation and apoptosis. Mechanistically, exogenous LPS treatment had been proved to induce the increased expression of METTL3 and activate the downstream PI3K/AKTsignaling pathway. In addition, suppression of METTL3 expression reduced cell proliferation, migration and invasion capacities in both cell lines. Furthermore, inhibition of METTL3 expression or inhibition of PI3K/AKT signaling decreased LPS-induced cell migration and invasion capacities. Moreover, knockdown of METTL3 or inhibition of METTL3 significantly inhibited LPS-induced activation of the PI3K/AKT signaling. Conclusion: In general, these results suggest that the LPS-METTL3-PI3K/AKT signal axis promotes cell migration and invasion in ICC, which contributes to a reduced overall survival in patients with ICC. It may broaden the horizon of cancer therapy with potential therapeutic targets.

Abstract Presbyacusis, sudden sensorineural hearing loss (SNHL), noise‐induced hearing loss, and drug‐induced deafness are the most common types of acquired SNHL. At present, the diagnosis of these hearing disorders is mainly based on the medical history and audiological examination. Due to the lack of diagnostic biomarkers, diagnosis of acquired sensorineural hearing loss is difficult. Previous studies have suggested that microRNAs (miRNAs) serve essential roles in pathophysiological processes, and they are stable, tissue enriched, and could be determined in a quantitative manner. Therefore, they could be potential noninvasive biomarkers for acquired SNHL. This review provided a comprehensive overview of the similarities and differences in altered circulating miRNAs (cimiRNAs) (plasma, serum, whole blood, and perilymph) in various disorders, and highlighted the regulatory functions of cimiRNAs on the development, monitoring and prognosis of the four most common types of acquired SNHL.

Abstract Male breast cancer (MBC) is a rare but aggressive malignancy with cellular and immunological characteristics that remain unclear. Here, we perform transcriptomic analysis for 111,038 single cells from tumor tissues of six MBC and thirteen female breast cancer (FBC) patients. We find that that MBC has significantly lower infiltration of T cells relative to FBC. Metastasis-related programs are more active in cancer cells from MBC. The activated fatty acid metabolism involved with FASN is related to cancer cell metastasis and low immune infiltration of MBC. T cells in MBC show activation of p38 MAPK and lipid oxidation pathways, indicating a dysfunctional state. In contrast, T cells in FBC exhibit higher expression of cytotoxic markers and immune activation pathways mediated by immune-modulatory cytokines. Moreover, we identify the inhibitory interactions between cancer cells and T cells in MBC. Our study provides important information for understanding the tumor immunology and metabolism of MBC.

Abstract Background Diabetes mellitus (DM) is a chronic metabolic disease that could produce severe complications threatening life. Its early detection is thus quite important for the timely prevention and treatment. Normally, fasting blood glucose (FBG) by physical examination is used for large-scale screening of DM; however, some people with normal fasting glucose (NFG) actually have suffered from diabetes but are missed by the examination. This study aimed to investigate whether common physical examination indexes for diabetes can be used to identify the diabetes individuals from the populations with NFG. Methods The physical examination data from over 60,000 individuals with NFG in three Chinese cohorts were used. The diabetes patients were defined by HbA1c ≥ 48 mmol/mol (6.5%). We constructed the models using multiple machine learning methods, including logistic regression, random forest, deep neural network, and support vector machine, and selected the optimal one on the validation set. A framework using permutation feature importance algorithm was devised to discover the personalized risk factors. Results The prediction model constructed by logistic regression achieved the best performance with an AUC, sensitivity, and specificity of 0.899, 85.0%, and 81.1% on the validation set and 0.872, 77.9%, and 81.0% on the test set, respectively. Following feature selection, the final classifier only requiring 13 features, named as DRING (diabetes risk of individuals with normal fasting glucose), exhibited reliable performance on two newly recruited independent datasets, with the AUC of 0.964 and 0.899, the balanced accuracy of 84.2% and 81.1%, the sensitivity of 100% and 76.2%, and the specificity of 68.3% and 86.0%, respectively. The feature importance ranking analysis revealed that BMI, age, sex, absolute lymphocyte count, and mean corpuscular volume are important factors for the risk stratification of diabetes. With a case, the framework for identifying personalized risk factors revealed FBG, age, and BMI as significant hazard factors that contribute to an increased incidence of diabetes. DRING webserver is available for ease of application ( http://www.cuilab.cn/dring ). Conclusions DRING was demonstrated to perform well on identifying the diabetes individuals among populations with NFG, which could aid in early diagnosis and interventions for those individuals who are most likely missed.

PurposeThis study investigated the effect of miR-204-5p-mediated silencing of SIRT1 on the development of deafness in C57BL/6 mice and the roles of miR-204-5p and SIRT1 in deafness.MethodsAuditory brainstem response recordings, H&E staining, and immunohistochemistry were used to observe changes in hearing function and cochlear tissue morphology in 2-month-old and 15-month-old C57BL/6 mice. A senescence model was induced using H2O2 in inner ear cells (HEI-OC1). Changes in HEI-OC1 cell proliferation were detected using the CCK-8 assay, whereas flow cytometry was used to detect changes in apoptosis. MiR-204-5p expression was measured via RT‒qPCR. The SIRT1 agonist RSV and a miR-204-5p inhibitor were used to study changes in ER stress (ERS), proliferation, and apoptosis in HEI-OC1 cells. Western blotting was performed to detect changes in ATF4, CHOP, SIRT1, PERK, p-PERK, Bax, and Bcl-2 protein levels. A dual-luciferase reporter gene assay was carried out to assess the ability of miR-204-5p to target SIRT1.ResultsRelative miR-204-5p expression levels in the cochleae of aged C57BL/6 mice increased, whereas SIRT1 expression levels decreased, and miR-204-5p and SIRT1 expression levels were negatively correlated. ERS and increased 8-OHDG levels were observed in aged C57BL/6 mice. In a model of inner ear cell aging, H2O2 treatment induced increases in miR-204-5p expression and ERS-mediated apoptosis. MiR-204-5p was found to target SIRT1 and inhibit its expression. SIRT1 activation and a miR-204-5p inhibitor promoted HEI-OC1 cell proliferation and reduced apoptosis. The miR-204-5p inhibitor regulated expression of the ERS proteins PERK, ATF4, and CHOP to upregulate Bcl-2 and downregulate Bax.ConclusionThis study identified the roles of miR-204-5p and SIRT1 in deafness in C57BL/6 mice and investigated the loss of cochlear outer hair cells and the involvement of apoptosis and ERS in deafness.

Conclusion: Impaired central sensitivity to thyroid hormones was significantly associated with the reduction of VFA and SFA, while impaired peripheral sensitivity was associated with an increase of SFA in euthyroid individuals with T2DM.

Background. Diabetes mellitus is often accompanied by dyslipidemia. Sodium-glucose cotransporter-2 (SGLT2) inhibitors, as a novel therapeutic agent for the treatment of type 2 diabetes mellitus (T2DM), have been reported to exert effects on lipid, while the results remain controversial. This study is aimed at exploring the effect of SGLT2 inhibitor canagliflozin on lipid profile. Methods. This study was a single-center, open-label, nonrandomized, prospective study. Metformin (500 mg three times per day) or canagliflozin (100 mg, once daily) was administered for 12 weeks. Fasting blood samples were collected before and 12 weeks after treatment. Serum lipid profile levels and angiopoietin-like protein 3 (ANGPTL3) were determined. In animal experiment, C57BL/6 J mice were divided into three groups including control, STZ + HFD, and STZ + HFD + canagliflozin. Lipid profile and plasma ANGPTL3 level were measured after 12 week’s treatment. Moreover, the expression of ANGPTL3 was detected in the liver tissues. Results. There was a decreased trend in low-density lipoprotein cholesterol (LDL-c) and triglycerides (TG) after canagliflozin treatment, while canagliflozin significantly increased high-density lipoprotein cholesterol (HDL-c) level and decreased plasma ANGPTL3 level. In addition, the expression of ANGPTL3 in liver tissues decreased obviously in diabetic mice with canagliflozin treatment. Conclusions. Canagliflozin increases HDL-c level and suppresses ANGPTL3 expression in patients with T2DM and diabetic mice. The reduction of ANGPTL3 may contribute to the increase of HDL-c. However, the specific mechanism needs further research. This trial is registered with ChiCTR1900021231.

Uncertain events such as earthquakes, epidemics, and wars have increased the risk of supply chain disruption. Due to the needs of carbon reduction policies and environmental protection, a large number of enterprises have started to produce both traditional and green products. Studying the issue of supply chain disruption for such enterprises has significant practical significance. We have developed a system dynamics model for a substitutable dual product supply chain with two levels of supply sources. Through simulation analysis, we found that (1) supply chain disruption can cause fluctuations in the manufacturer’s inventory, and disruptions from second tier suppliers have a higher impact on the manufacturer’s inventory than that from primary suppliers. In addition, the disruption of traditional products will cause consumers to flow to the green product market, resulting in a sudden increase in order for green products and components in a short period of time, causing a delayed impact on the inventory of suppliers and manufacturers of green products. (2) The disruption of upstream suppliers in traditional products causes the highest profit losses for all traditional product suppliers, while the disruption of downstream suppliers in green products causes the highest profit losses for the manufacturer and all green product suppliers. (3) From the perspective of the service level, compared to other components, the disruption of critical components in traditional products poses the highest risk of out of stock in the supply chain, while the risk of out-of-stock in the intermediate component of green product is the smallest. (4) Common sense may suggest that the more the suppliers disrupt, the higher the damage of the supply chain. However, due to the ripple effect, this article finds that from the perspectives of profit, inventory, and service level, multisupplier disruption is not necessarily inferior to single supplier disruption.

Surface modification of nanoparticles by cell membrane (CM) coating to improve their bio-interface properties often results in partial coating. Here the authors show that partial coating is an intermediate state due to the absorption of CM fragments or vesicles and can be resolved by increasing CM fluidity with external phospholipids.

Abstract Objective Laryngeal cancer is a common malignancy in otorhinolaryngological head and neck surgery, accounting for approximately one-third of all head and neck malignancies. Terahertz time-domain spectroscopy (THz-TDS) has recently been found to be useful for the detection of tumors. This study was conducted to investigate the application of THz-TDS in the diagnosis of pathological resection margins of laryngeal cancer. Methods Fresh laryngeal cancer tissues from 10 patients with laryngeal cancer were extracted, and after simultaneous HE staining and terahertz imaging, the tumor area, paracancerous area, and normal tissue area of each laryngeal cancer tissue sample were located under a microscope according to the pathological results of HE staining. Results The shape contours of the tumor region revealed by terahertz imaging maps and HE staining were similar. In the terahertz spectrum in the frequency range of 0.5–1.9 THz, both the absorption coefficient and refractive index values followed the order tumor > para cancer > normal tissue, with statistically significant differences (P < 0.01). When the terahertz frequency was 1.5 THz, the absorption coefficient of terahertz light waves by laryngeal cancer tissue and the percentage of nuclei showed an extremely high positive correlation (P < 0.01, r = 0.971). In the frequency ranges of 0.5–1.2 THz and 1.6–1.9 THz, the absorption coefficients of the highly differentiated group were higher than those of the moderately differentiated group. In the frequency range of 1.2–1.6 THz, the results were reversed, with statistically significant differences (P < 0.05). In the frequency range of 0.5–1.9 THz, the highly differentiated group had a higher refractive index than the moderately differentiated group, with a statistically significant difference (P < 0.05). Conclusions THz-TDS can be used to determine the pathological margins of laryngeal cancer based on the absorption coefficient and refractive index, and the magnitudes of the absorption coefficient and refractive index are related to the percentage of nuclei. The degree of differentiation of laryngeal cancer tissue can be assessed by THz-TDS. The study shows that the terahertz time-domain system is promising for applications in the diagnosis of laryngeal cancer, especially for the more accurate identification of intraoperative margins.

Abstract As an important second messenger, calcium (Ca2+) regulates a wide variety of physiological processes. Disturbance of intracellular calcium homeostasis implicated in the occurrence of multiple types of diseases. Orai1 is the major player in mediating store-operated calcium entry (SOCE) and regulates calcium homeostasis in non-excitable cells. Over-expression and activation of Orai1 have been reported in breast cancer. However, its molecular mechanisms are still not very clear. Here, we demonstrated that Nucleolin (NCL) was a novel interacting partner of Orai1. NCL is a multifunctional nucleocytoplasmic protein and is upregulated in human breast tumors. The binding of C-termini of NCL (NCL-CT) to N-termini of Orai1 (Orai1-NT) is critical for mediating calcium influx and proliferation of breast cancer cells. Blocking the NCL-Orai1 interaction by synthesized Orai1 peptide can effectively reduce the intracellular calcium influx and suppress the proliferation of breast cancer cells in vitro and in vivo. Our findings reveal a novel activation mechanism of Orai1 via direct interaction with NCL, which may lead to calcium homeostasis imbalance and promote the proliferation of breast cancer cells. Blocking NCL-Orai1 interaction might be an effective treatment of breast cancer.

BackgroundA data-based study reported the linear relationship between body mass index (BMI) and low-density lipoprotein cholesterol (LDL-C) in a normal population. However, there were no studies giving the suggestion for diabetes patients limited by sample size. This study aimed to investigate the non-linear dose-response relationship between BMI and LDL-C in type 2 diabetes mellitus (T2DM).MethodThe study participants registered at the National Metabolic Management Center (MMC) of Beijing Luhe hospital from June 2017 to June 2021. T2DM was diagnosed according to the 1999 World Organization criteria. The generalized additive models (GAMs) were used to investigate the non-linear association between BMI and LDL-C. The relationship between BMI and LDL-C was visualized via the smooth splines function plot by sex. Segmented regressions were fitted to calculate the slopes with different estimated breakpoints.ResultsAfter data cleaning, a total of 2500 participants with T2DM aged 30 to 70 years were included in this study. Compared with females, the spline between BMI and LDL-C showed an Inverted U shape in males. In males, the slopes below and above the breakpoint (26.08. 95% CI: 24.13 to 28.03) were 2.38 (95%CI: 1.06, 3.70) and -0.36 (95%CI: -1.20, 0.48), respectively.ConclusionThere was an Inverted U shape association between BMI and LDL-C in male participants with T2DM, for which the LDL-C was increased with BMI in the lean population, while LDL-C gradually tended to be flat or even decreased in the obese population. However, the Inverted U-shape between BMI and LDL-C was not found in female patients with T2DM.

ObjectivesThis study aimed to compare the expressed microRNA (miRNA) profiles of serum-derived exosomes of patients with sudden sensorineural hearing loss (SSNHL) and normal hearing controls to identify exosomal miRNAs that may be associated with SSNHL or serve as biomarkers for SSNHL.MethodsPeripheral venous blood of patients with SSNHL and healthy controls was collected to isolate exosomes. Nanoparticle tracking analysis, transmission electron microscopy, and Western blotting were used to identify the isolated exosomes, after which total RNA was extracted and used for miRNA transcriptome sequencing. Differentially expressed miRNAs (DE-miRNAs) were identified based on the thresholds of P < 0.05 and |log2fold change| > 1 and subjected to functional analyses. Finally, four exosomal DE-miRNAs, including PC-5p-38556_39, PC-5p-29163_54, PC-5p-31742_49, and hsa-miR-93-3p_R+1, were chosen for validation using quantitative real-time polymerase chain reaction (RT-qPCR).ResultsExosomes were isolated from serum and identified based on particle size, morphological examination, and expression of exosome-marker proteins. A total of 18 exosomal DE-miRNAs, including three upregulated and 15 downregulated miRNAs, were found in SSNHL cases. Gene ontology (GO) functional annotation analysis revealed that target genes in the top 20 terms were mainly related to “protein binding,” “metal ion binding,” “ATP binding,” and “intracellular signal transduction.” Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis revealed that these target genes were functionally enriched in the “Ras,” “Hippo,” “cGMP-PKG,” and “AMPK signaling pathways.” The expression levels of PC-5p-38556_39 and PC-5p-29163_54 were significantly downregulated and that of miR-93-3p_R+1 was highly upregulated in SSNHL. Consequently, the consistency rate between sequencing and RT-qPCR was 75% and sequencing results were highly reliable.ConclusionThis study identified 18 exosomal DE-miRNAs, including PC-5p-38556_39, PC-5p-29163_54, and miR-93-3p, which may be closely related to SSNHL pathogenesis or serve as biomarkers for SSNHL.

Abstract Background Obesity is an important risk factor for hyperuricemia. We aimed to explore the relationship between perirenal fat thickness (PrFT) and paranephric fat thickness (PnFT) and serum uric acid (SUA) in patients with type 2 diabetes mellitus (T2DM). Methods This was a cross-sectional study involving 257 patients with T2DM recruited from Beijing Luhe Hospital from September 2019 to May 2020. The basic and clinical information such as age, gender, duration of diabetes was collected through the medical records. All patients underwent a physical examination including height, weight, waist circumference, hip circumference, systolic blood pressures and diastolic blood pressure. The venous blood and urine samples were collected to measure SUA, fasting blood glucose, total cholesterol, triglyceride, low-density lipoprotein-cholesterol, high-density lipoprotein-cholesterol, serum creatinine, blood urea nitrogen and glycosylated hemoglobin. PrFT and PnFT were measured via ultrasonography. Pearson correlation test and linear regression analysis were used to analyze the association between PrFT and PnFT and SUA. Results We found that PrFT and PnFT increased according to the tertiles of SUA level (P = 0.001 and P = 0.009, respectively). In addition, the PrFT and PnFT were positively associated with SUA level (r = 0.25, P

Abstract Background Although the prognosis for most patients with papillary thyroid cancer (PTC) is good, the present treatment is ineffective for 5–10% patients. Several studies found sodium–glucose cotransporter 2 (SGLT2) inhibitors may inhibit the growth of tumors. However, whether SGLT2 inhibitors have therapeutic effect on thyroid cancer remains unclear. Materials and methods The levels of SGLT2 in PTC and normal thyroid tissue were assessed by immunohistochemistry and clinical dataset analysis. Cell growth was detected by the CCK-8 and colony formation. Glucose uptake into thyroid cancer cell was evaluated by 2-DG uptake assay. Glycolysis were analyzed by Seahorse XF Extracellular Flux Analysis. RNA-seq were used to screen differentially expressed genes of cells treated with/without canagliflozin (a SGLT2 inhibitor). Furthermore, flow cytometry, western blot, and gene set enrichment analysis were employed to elucidate cell cycle, apoptosis and the underlying mechanism of the anticancer effect of canagliflozin. The effect of canagliflozin on thyroid cancer growth was further confirmed in vivo through xenograft formation assay. Results SGLT2 inhibition attenuated the growth of thyroid cancer cells in vitro and in vivo. Canagliflozin inhibited glucose uptake, glycolysis and AKT/mTOR signaling activation, and increased AMPK activation in thyroid cancer cell. Furthermore, canagliflozin inhibited G1/S phase transition and cyclin D1, cyclin D3, cyclin E1, cyclin E2, and E2F1 expression levels in thyroid cancer cell. In addition, canagliflozin increased apoptosis of thyroid cancer cell. Further investigation revealed that canagliflozin could increase γ-H2AX expression levels and DNA damage response signaling ATM/CHK2 activation. In thyroid cancer patients, SGLT2 was increased in thyroid cancer and positively related to cyclin D3. Conclusions SGLT2 inhibition may limit glucose uptake resulting in energetic crisis, following oxidative stress mediated DNA damage and cell cycle arrest, which resulted to the increased cell apoptosis and decreased proliferation of thyroid cancer cells, suggesting a potential use for SGLT2 inhibitors as thyroid cancer therapeutics.

Abstract Background Most of malignant melanomas originate from skin and often metastasize to the lungs, rarely metastasizes to the liver and bone. However, imageology characters of lung metastasis tumor are commonly similar to those of fungal infections. Case presentation A patient was admitted with unhealed plantar puncture wound for 3 years, and cough and expectoration for 2 years. The chest computed tomography (CT) revealed multiple nodules with cavities, and the patient was diagnosed of pulmonary fungal infection in another hospital and received antifungal therapy for more than 8 months, but the clinical symptoms and chest imaging findings continue to progress. After admission, the pathological results of both lung biopsy and biopsy of the plantar wound 3 years ago indicated malignant melanoma. Conclusions The diagnosis of lung lesions cannot rely solely on imaging diagnosis, lung biopsy should be performed if necessary.

Objective: The objective of this study was to assess the expression of serum complement component 1q tumor necrosis factor-related protein 3 (CTRP3) and CTRP9 in rheumatoid arthritis (RA) patients, and further explore their correlation with disease activity and the predictive value of RA. Methods: RA group (n = 60) and healthy group (n = 60) were enrolled in Beijing Luhe Hospital, Capital Medical University. We collected the clinical data, including the basic information, laboratory parameters as well as the Disease Activity Score using 28 joint counts (DAS28) scores, and measured the expression of serum CTRP3 and CTRP9 in two groups by enzyme-linked immunosorbent assay. To analyze the correlation between serum CTRP3 and CTRP9 and RA. We explored the predictive value of the serum CTRP3 and CTRP9 for RA. Results: Compared to the healthy group, the expression of serum CTRP3 and CTRP9 was higher in the RA group (P < 0.05). Except rheumatoid factor (serum CTRP9: r = −0.310, P = 0.018), and immunoglobulin (serum CTRP9: r = 0.338, P = 0.010), platelet, erythrocyte sedimentation rate, C-reactive protein, DAS28, anti-cyclic citrullinated peptide antibody, triglyceride, total cholesterol, high-density lipoprotein, low-density lipoprotein, etc., of RA patients were not related to the levels of serum CTRP3 and CTRP9. The best cutoff value of serum CTRP3 and CTRP9 was 31.66 and 34.39 ng/ml, respectively. In terms of sensitivity, negative predictive value, and accuracy, compared with single detection of serum CTRP3 or CTRP9, combined detection has more predictive value for RA. Conclusion: CTRP3 and CTRP9 may become two candidate biomarkers for RA. The serum CTRP3 and CTRP9 may have certain predictive values for RA.

Abstract Background Atherosclerosis is a common complication in patients with type 2 diabetes (T2DM). Multiple factors are involved in the development and progress of atherosclerosis. We evaluated the association of weekly sedentary time (WST) with carotid plaque formation. Methods After data cleaning, a total of 26 664 participants with T2DM from 10 National Metabolic Management Centers (MMCs) from June 2017 to April 2021 were enrolled. Self‐reported lifestyle data including WST, sleeping time, smoking and drinking information, carotid artery ultrasound, and biochemical parameters were obtained. The independent association of carotid plaue with sedentary and other lifestyle behaviors was evaluated using multivariable logistic regression models, and odds ratio (OR) with 95% confidence interval (CI) were reported. Moreover, stratified analysis was conducted to demonstrate the influence of confounding factors. Results The mean (SD) age of the participants was 54.0 (11.6) years, and the median (interquartile range) WST was 35.0 (21.0, 42.0) h. Comparing with participants in the first tertile of WST, those in the second or third tertile of WST were younger and with a shorter duration of diabetes. There were positive associations between longer sedentary time and odds of artery plaque after adjustment, with corresponding ORs in the second and third tertile were 1.40 (95% CI: 1.31–1.50) and 1.67 (95% CI: 1.56–1.79), respectively. However, the effect of WST on plaque in patients aged 18–40 years old had no statistical significance; the p value in the third tertile was 0.163. Conclusions In summary, higher WST appears to be associated with higher prevalence of carotid plaque in patients with T2DM, especially in aged populations.

Abstract Background AK098656 may be an adverse factor for coronary heart disease (CHD), especially in patients with hypertension. This study aimed to analyze the effect of AK098656 on CHD and CHD with various complications. Methods A total of 117 CHD patients and 27 healthy control subjects were enrolled in the study. Plasma AK098656 expression was determined using the quantitative real-time polymerase chain reaction. Student’s t-test was used to compare AK098656 expression levels in different groups. Receiver operating characteristic (ROC) curve and area under the curve (AUC) were used to quantify the discrimination ability between CHD patients and health controls and between CHD and CHD + complications patients. The relationship between AK098656 and coronary stenosis was analyzed using Spearman’s correlation. Results AK098656 expression was remarkably higher in CHD patients than in healthy controls (P = 0.03). The ROC curve revealed an effective predictive AK098656 expression value for CHD risk, with an AUC of 0.656 (95% CI 0.501–0.809). Moreover, AK098656 expression was increased in CHD + complications patients compared to CHD patients alone (P = 0.005), especially in patients with hypertension (CHD + hHTN, P = 0.030). The ROC curve revealed a predictive AK098656 prognostic value for discriminating between CHD and CHD + hHTN patients, with an AUC of 0.666 (95% CI 0.528–0.805). There was no significant difference in AK098656 expression in CHD patients with diabetes mellitus compared to CHD patients alone. In addition, AK098656 expression in CHD patients was positively correlated with stenosis severity (R = 0.261, P = 0.006). Conclusion AK098656 expression was significantly increased in patients with CHD, especially those with hypertension, and its expression level was positively correlated with the degree of coronary stenosis. This implied that AK098656 may be a risk factor for CHD and can potentially be applied in clinical diagnosis or provide a novel target for treatment.

Background. Accumulating evidence has suggested a link between adipokines and diabetic retinopathy (DR). This study is aimed at investigating the risk factors for sight-threatening DR (STDR) and establishing a prognostic model for predicting STDR among a high-risk population of patients with type 2 diabetes mellitus (T2DM). Methods. Plasma concentrations of adipokines were determined by enzyme-linked immunosorbent assay. In the case-control set, principal component analysis (PCA) was performed to select optimal predictive cytokines for STDR, involving severe nonproliferative DR (NPDR) and proliferative DR. Support vector machine (SVM) was used to examine the possible combination of baseline plasma adipokines to discriminate the patients with mild NPDR who will later develop STDR. An individual prospective cohort with a follow-up period of 3 years was used for the external validation. Results. In both training and testing sets, involving 306 patients with T2DM, median levels of plasma adiponectin (APN), leptin, and fatty acid-binding protein 4 (FABP4) were significantly higher in the STDR group than those in mild NPDR. Except for adipsin, the other three adipokines, FABP4, APN, and leptin, were selected by PCA and integrated into SVM. The accuracy of the multivariate SVM classification model was acceptable in both the training set (AUC=0.81, sensitivity=71%, and specificity=91%) and the testing set (AUC=0.77, sensitivity=61%, and specificity=92%). 110 T2DM patients with mild NPDR, the high-risk population of STDR, were enrolled for external validation. Based on the SVM, the risk of each patient was calculated. More STDR occurred in the high-risk group than in the low-risk group, which were grouped by the median value of APN, FABP4, and leptin, respectively. The model was validated in an individual cohort using SVM with the AUC, sensitivity, and specificity reaching 0.77, 64%, and 91%, respectively. Conclusions. Adiponectin, leptin, and FABP4 were demonstrated to be associated with the severity of DR and maybe good predictors for STDR, suggesting that adipokines may play an important role in the pathophysiology of DR development.

Background: Obesity is known as a common risk factor for osteoporosis and type 2 diabetes mellitus (T2DM). Perirenal fat, surrounding the kidneys, has been reported to be unique in anatomy and biological functions. This study aimed to explore the relationship between perirenal fat and bone metabolism in patients with T2DM. Methods: A total of 234 patients with T2DM were recruited from September 2019 to December 2019 in the cross-sectional study. The biochemical parameters and bone turnover markers (BTMs) were determined in all participants. Perirenal fat thickness (PrFT) was performed by ultrasounds via a duplex Doppler apparatus. Associations between PrFT and bone metabolism index were determined via correlation analysis and regression models. Results: The PrFT was significantly correlated with β-C-terminal telopeptides of type I collagen (β-CTX) (r = −0.14, P < 0.036), parathyroid hormone (iPTH) (r = −0.18, P ≤ 0.006), and 25 hydroxyvitamin D (25-OH-D) (r = −0.14, P = 0.001). Multivariate analysis confirmed that the association of PrFT and β-CTX (β = −0.136, P = 0.042) was independent of other variables. Conclusion: This study showed a negative and independent association between PrFT and β-CTX in subjects with T2DM, suggesting a possible role of PrFT in bone metabolism. Follow-up studies and further research are necessary to validate the associations and to elucidate the underlying mechanisms.

Abstract As a common chronic metabolic disease, the development of diabetes mellitus (DM) may also be accompanied by liver damage and inflammatory disorders. Sitagliptin is an inhibitor of dipeptidyl peptidase-4 (DPP4, also known as CD26), which is clinically used for DM treatment. However, the mechanism of sitagliptin’s efficiency in liver diseases is largely unknown. In this study, mice suffering from streptozotocin (STZ) exhibit elevated liver DPP4 expression and activity, as well as inflammatory and chronic liver injury phenotype, whereas specifically inhibiting the activity of DPP4 in mouse liver tissues and hepatocytes by sitagliptin contributes to decreased cytokines, oxidative stress, cell apoptosis, and inflammation in STZ-induced diabetic mice. Moreover, sitagliptin reduced TNFα or LPS-induced cellular reactive oxygen species (ROS) level, cell apoptosis, and protein expression in the NFκB signaling pathway in HepG2 cells or primary mouse hepatocytes. Altogether, our study confirms that sitagliptin may protect liver tissue by alleviating ROS production and NFκB signaling activation, providing a putative mechanism for preventing the development of diabetic liver disease.

Objective Decreased serum dipeptidyl peptidase-IV (sDPPIV) levels have been reported in patients with autoimmune diseases. However, few studies have analyzed the association between sDPPIV levels and autoimmune thyroid disease (AITD). This study aimed to evaluate the association between sDPPIV levels and three types of AITD: Graves’ disease (GD), Graves’ ophthalmopathy (GO), and Hashimoto’s thyroiditis (HT). Methods Patients newly diagnosed with GD (n = 65), GO (n = 22), and HT (n = 27) and healthy individuals (n = 30) were recruited. Clinical characteristics and thyroid function data were collected. sDPPIV was measured using enzyme-linked immunosorbent assays. Results Compared with controls (786.3 ± 46.95), patients with GD and GO had significantly lower sDPPIV levels (662.2 ± 38.81 and 438.4 ± 31.78). Additionally, sDPPIV levels were negatively associated with antithyroid peroxidase antibody (r = −0.20) and antithyroglobulin antibody (r = −0.19), but there was no significant relationship between thyroid hormone and sDPPIV levels. GO cases were divided by proptosis with and without muscle thickening; sDPPIV levels were lower in the muscle thickening group than those in the without muscle thickening group. Logistic regression analysis showed that sDPPIV was negatively correlated with GO and GD. Conclusions sDPPIV concentrations were abnormal in patients with GD and GO, and reduced sDPPIV expression may be involved in the progression of GO and GD.

Abstract Background Omega-3 polyunsaturated fatty acids (PUFAs) produce lipid mediators with both anti-inflammatory and pro-resolution properties, including resolvins. The purpose of this study was to detect serum resolvin E1 (RVE1) levels in Hashimoto’s thyroiditis (HT) patients and healthy controls (HCs) and to evaluate the relationship of RVE1 with thyroid autoimmunity. Methods A total of 57 participants were recruited, including 30 untreated HT patients and 27 age- and sex‐matched HCs. The levels of RVE1 in serum were measured via enzyme-linked immunosorbent assay (ELISA). An electrochemiluminescence immunoassay was used for the measurement of thyroid-stimulating hormone (TSH), total T4 (TT4), TT3, free T4 (FT4), FT3, anti-thyroid peroxidase antibody (TPOAb) and anti-thyroglobulin antibody (TgAb) levels. Hemogram tests and routine biochemical analyses were performed on each sample. Results The serum level of RVE1 of HT patients (24.09, 15.76–34.38 pg/mL) was significantly lower than that of healthy controls (28.51, 20.76–51.23 pg/mL) (P = 0.027). RVE1 levels showed a downward trend with increasing TgAb levels (P for trend = 0.001). Multivariable ordinal logistic regression analysis showed that RVE1 levels were negatively correlated with increasing TgAb levels in both the unadjusted (OR = 0.9446, 95 % CI = 0.9111–0.9782, P = 0.002) and adjusted models (OR = 0.9380, 95 % CI = 0.8967–0.9811, P = 0.005). Conclusions Decreased RVE1 levels might be a sign that HT is associated with inflammatory resolution dysfunction. RVE1 may serve as a protective factor against increased TgAb levels.

Objective To investigate the prognostic value of the co-chaperone protein DnaJ Heat Shock Protein Family (Hsp40) Member B11 (DNAJB11) in thyroid carcinoma (THCA). Methods This bioinformatics analysis study evaluated the prognostic value of DNAJB11 mRNA levels in THCA based on data from The Cancer Genome Atlas (TCGA). The levels of DNAJB11 mRNA in THCA and normal tissues were compared with Wilcoxon signed rank test. Kaplan–Meier survival curve analysis and Cox regression analysis were performed to evaluate the correlation between DNAJB11 mRNA levels and survival. Gene Ontology (GO) enrichment analysis was used to elucidate the functional enrichment difference. Results Data from the 502 patients with THCA from the TCGA database were analysed. DNAJB11 mRNA was downregulated in THCA tissues compared with normal tissues. Decreased levels of DNAJB11 mRNA were significantly correlated with T stage, N stage, pathological stage, histological type, extrathyroidal extension and BRAF gene status. The low levels of DNAJB11 mRNA were associated with a shorter progression-free interval. GO enrichment analysis showed that DNAJB11 was involved in immune-related biological processes. Conclusion Low levels of DNAJB11 mRNA were associated with poor prognosis in THCA.

Chronic hepatitis B (CHB) patients with severe liver fibrosis would be more likely to progress to a poorer prognosis. Treatment is considered once the liver fibrosis reaches significant liver fibrosis (≥S2). Leukocyte cell-derived chemotaxin-2 (LECT2) has been shown to contribute to liver fibrosis progression. No research has focused on the role of LECT2 in liver fibrosis in CHB patients. This study enrolled 227 CHB patients and divided them into the training group (n = 147) and validation group (n = 80), respectively. The expression of LECT2 in serum, protein and mRNA of the human liver tissues was detected to analyze the possible associations between LECT2 and liver fibrosis. A receiver operating characteristic curve (ROC) was used to estimate the efficacy of LECT2 for predicting liver fibrosis. The data showed that there was a positive relationship between LECT2 and the progression of liver fibrosis. In the training group, LECT2 was demonstrated to have better effectiveness than APRI and FIB-4. The AUC was 0.861, 0.698, and 0.734 for significant liver fibrosis, and 0.855, 0.769, and 0.752 for advanced liver fibrosis. Besides, the efficacy of LECT2 in different statuses of patients with CHB was examined and the effectiveness of LECT2 had also been confirmed in the validation group. All the results confirmed that LECT2 could act as a perfect predictor and thus offers a novel and direct biomarker to estimate liver fibrosis more accurately.

Infantile hemangioma (IH) is a common benign tumor of endothelial cells in infants. Most hemangiomas are self-limited, but a few may develop and lead to serious complications that affect the normal life of children. Therefore, finding an effective treatment strategy for IH is a pressing need. Recent studies have demonstrated that non-coding RNAs affect the progression of multiple tumors. This study aims to investigate the mechanism by which LncRNA-MCM3AP-AS1 promotes glycolysis in the pathogenesis of IH. We first documented that the expression of LncRNA MCM3AP-AS1 was significantly upregulated in IH. Furthermore, we demonstrated that MCM3AP-AS1 bound to miR-106b-3p which promotes glycolysis in IH. In addition, we found that inhibition of HIF-1α contributed to the transformation of glycolysis to normal aerobic oxidation, partially reversed the promoting effect on glycolysis by the up-regulation of LncRNA MCM3AP-AS1 in IH disease. More importantly, we demonstrated this phenomenon existed in IH patients. Taken together, we demonstrate that LncRNA-MCM3AP-AS1 promotes the progression of infantile hemangiomas by increasing the glycolysis via regulating miR-138-5p/HIF-1α axis.

Frequency multiplier is a nonlinear circuit that can realize frequency multiplication of input signal with wide application in communication, navigation, radar, and other fields. This paper proposes a frequency multiplication method based on extracting harmonic from a narrow pulse. Then, in accordance with this means, it develops a ten times frequency multiplier, finally achieving frequency multiplication taking the rubidium atomic frequency standard as a reference. The frequency multiplier possesses some features of high-efficient multiplication, low noise floor, simple structure, easy implementation, and cheaper cost. Based on the experimental results, if PRS10, the rubidium atomic frequency standard, is regarded as a reference, the noise floor of frequency multiplier is superior to 1.60E−12/s. Additionally, the relative frequency error of the output ten times the frequency multiplication signal (100 MHz) is less than 8.00E−12.

Purpose: Ectopic adrenocorticotropic hormone (ACTH)-secreting syndrome (EAS) is a relatively rare disease. EAS could not be inhibited by endogenous or exogenous glucocorticoid, which may be its most important characteristic. We aimed to explore the expression of glucocorticoid receptor (GR) in small cell lung cancer (SCLC) with or without EAS. Materials and Methods: In this study, we first reported one patient with EAS caused by SCLC, and we examined the expression of ACTH and GR on pulmonary tissue in normal people and SCLC patients with or without EAS. Results: Immunochemistry analysis showed that there was no obvious difference in the expression of GR in SCLC without EAS compared with normal people. While in the EAS patient, GR expression was absent in the tissue. Conclusions: Therefore, our study found that lower expression of GR in small cell lung cancer (SCLC) with EAS, which may contribute to the no inhibition by endogenous or exogenous glucocorticoid.

Background. Para and perirenal fat is a fat pad surrounding the kidneys. Recent studies showed the association between para and perirenal fat and cardiovascular diseases including atherosclerosis and hypertension. We aimed to assess the relationship between para-perirenal ultrasonographic fat thickness and serum high-density lipoprotein (HDL) level and cholesterol efflux capacity of HDL in patients with type 2 diabetes mellitus (T2DM). Methods. We recruited 58 subjects with T2DM and collected anthropometric indices including height, weight, waist circumference, and other clinical data. Para-perirenal ultrasonographic fat thickness (PUFT) was measured via ultrasound. Serum lipid profile and other metabolic indices were determined as well. Correlation analysis and regression analysis were performed to analyze the relationship between PUFT and HDL level and cholesterol efflux capacity in all patients and subgroups. Results. Patients with higher PUFT have lower serum HDL level but increased cholesterol efflux capacity. Further analysis showed that PUFT negatively correlated with the serum HDL level in all patients, with no difference in groups divided by body mass index (BMI). In addition, PUFT was positively correlated with cholesterol efflux capacity in all patients. Multiple stepwise regression analysis showed an independent association of PUFT and serum HDL level and cholesterol efflux capacity. Conclusions. PUFT is closely correlated with the serum HDL level and cholesterol efflux capacity in patients with T2DM.

Objective. To investigate the effect of matrine on rats with collagen-induced arthritis (CIA) and its regulatory effect on receptor activator of nuclear factor-κB ligand (RANKL) and osteoprotegerin (OPG) expression. Methods. Wistar rats (n=6) and CIA rats (n=30) were randomly divided into six groups: healthy, CIA control, low/medium/high matrine (25, 50, or 100 mg/kg, once per day for six weeks), and methotrexate (MTX) (2 mg/kg, once per week for six weeks). The degree of joint damage was evaluated by X-ray and HE staining. Bone marrow suppression was assessed by routine blood analysis. In addition, the levels of serum RANKL and OPG in the rats were measured by ELISA. Results. The level of joint swelling and degree of joint damage assessed by ankle swelling measurements, AI score, X-ray, and HE staining were alleviated in the CIA rats treated with MTX or different doses of matrine. Furthermore, no obvious inhibitory effect was observed on the bone marrow of the CIA rats, regardless of the dose of matrine or treatment with 2 mg/kg MTX (P>0.05). The levels of OPG in serum and the ratio of OPG/RANKL were higher, and RANKL expression was lower in the low/medium/high matrine group compared with that of the CIA control group. The serum levels of OPG and OPG/RANKL ratio increased with the matrine dose, while the opposite was observed for RANKL expression. Conclusion. Matrine treatment was associated with a lower degree of bone destruction, increased OPG expression and OPG/RANKL ratio, and decreased RANKL expression in CIA rats. Thus, matrine may represent a novel drug candidate for the treatment of RA.

Introduction. Brachial–ankle pulse wave velocity (baPWV), an indicator of arterial stiffness, has been demonstrated to be associated with type 2 diabetes mellitus (T2DM) and its vascular complications. This study was aimed at investigating the correlations of baPWV with both the presence and severity of diabetic retinopathy (DR) at baseline and at exploring the predictive role of baPWV in the new onset/progression of DR in the follow-up analysis. Methods. The prospective cohort study recruited 2,473 Chinese patients with T2DM, of whom 663 participants were finally included in the follow-up analysis. The presence and grading of DR were performed by the modified Early Treatment Diabetic Retinopathy Study. Uni- or multivariate linear and logistic regression models and Cox proportional-hazards regression analysis were conducted. Results. Of 2,473 patients with T2DM at baseline, 734 individuals were assessed to have DR and further categorized into 630 with non-sight-threatening DR (NSTDR) and 104 with STDR. In addition to the positive relationship between increased baPWV and the presence of DR, multinominal logistic regression analysis revealed that higher tertiles of baPWV were significantly related to the NSTDR (T2: OR=1.62 (1.22, 2.15), p

Background. Obesity has been considered as an important factor in the development and progression of chronic kidney diseases (CKD). Perirenal fat, which is surrounding the kidneys, has been reported to be unique in anatomy and biological functions. This study is aimed at assessing the relationship between perirenal fat thickness (PrFT) and estimated glomerular filtration rate (eGFR) in patients with type 2 diabetes (T2DM). Methods. A total of 171 patients with T2DM were recruited in the study. The basic and clinical characteristics including sex, age, diabetes duration, body mass index (BMI), waist circumference (WC), visceral fat area (VFA), glycated hemoglobin (HbA1c), serum uric acid (UA), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-c), and high-density lipoprotein cholesterol (HDL-c) were collected. PrFT was measured via ultrasound. eGFR was calculated using the Modification of Diet in Renal Disease (MDRD) formula. Results. Patients were divided into three groups according to PrFT, and we found patients with higher PrFT had lower eGFR. PrFT was significantly correlated with eGFR in all patients r=−0.181,P

Aims. Hashimoto’s thyroiditis (HT), a type of autoimmune disease, occurs due to genetic predisposition and environmental factors. It is well known that thyroid function may affect the gut microbiota. However, the composition of gut microbiota in HT patients with different thyroid function status has been less highlighted. Therefore, we focused on the alterations in the composition of gut microbiota in HT patients with euthyroidism and hypothyroidism. Methods. We performed a cross-sectional study, including 45 HT patients with euthyroidism, 18 HT patients with hypothyroidism, and 34 healthy controls. Fecal samples were collected, and microbiota was examined by using 16S RNA ribosomal RNA gene sequencing. Then, we analyzed the possible pathways in relation to the enriched bacteria by linear discriminant analysis (LDA) effect size (LEfSe). Results. Compared with the controls, bacterial richness and diversity were significantly lower in patients with HT, especially in hypothyroidism. Moreover, Lachnospiraceae_incertae_sedis, Lactonifactor, Alistipes, and Subdoligranulum were more enriched in HT patients with euthyroidism, while Phascolarctobacterium was more abundant in those with hypothyroidism. Further analysis suggested that Phascolarctobacterium was negatively related to several pathways, including environmental information processing and metabolism. Conclusion. In summary, our study demonstrated the altered composition of gut microbiota in HT patients with different thyroid function status. Moreover, Phascolarctobacterium may be involved in the development of HT.

Abstract Herein, triphenyltin (TPT) biodegradation efficiency and its transformation pathway have been elucidated. To better understand the molecular mechanism of TPT degradation, the interactions between amino acids, primary structures, and quaternary conformations of effector proteins and TPT were studied. The results verified that TPT recognition and binding depended on amino acid sequences but not on secondary, tertiary or quaternary protein structure. During this process, TPT could change the molecular weight and isoelectric point of effector proteins, induce their methylation or demethylation, and alter their conformation. The effector proteins, alkyl hydroperoxide reductase and acetyl-CoA acetyltransferase, recognizing TPT were crucial to TPT degradation. Electron transfer flavoprotein subunit alpha, phosphoenolpyruvate carboxykinase, aconitate hydratase, branched-chain alpha-keto acid dehydrogenase E1 component, biotin carboxylase and superoxide dismutase were related to energy and carbon metabolism, which was consistent with the results in vivo. The current findings develop a new approach for investigating the interactions between proteins and target compounds.

This work investigated concatenated coding schemes for Global Navigation Satellite System (GNSS) signals in order to increase their error correction capability in urban environments. In particular, a serial concatenated code that combines an outer Reed–Solomon (RS) code with an inner low-density parity-check (LDPC) code was designed, and the performance was investigated over the land mobile satellite (LMS) channel for characterizing multipath and shadow fading in urban environments. The performance of the proposed concatenated coding scheme was compared to that of a B-CNAV1 message, in which two interleaved 64-ary LDPC codes were employed. The simulation results demonstrate that the proposed concatenated code can obtain a similar error correction performance to the two interleaved 64-ary LDPC codes in both the additive white Gaussian noise (AWGN) and LMS channels at a lower complexity level.

Either metformin or liraglutide has been reported to have anti-tumor effects on pancreatic cancer cells. However, it is not clear whether their combined treatment has additive or synergistic anti-tumor effects on pancreatic cancer cells. In this study, the human pancreatic cancer cell line MiaPaca-2 was incubated with liraglutide and/or metformin. The cell Counting Kit-8 (CCK-8), colony formation, flow cytometry, and wound-healing and transwell migration assays were used to detect cell viability, clonogenic survival, cell cycle and cell migration, respectively. RT-PCR and western blot analyses were used to determine the mRNA and protein levels of related molecules. Results showed that combination treatment with liraglutide (100 nmol/L) and metformin (0.75 mmol/L) significantly decreased cell viability and colony formation, caused cell cycle arrest, upregulated the level of pro-apoptotic proteins Bax and cleaved caspase-3, and inhibited cell migration in the cells, although their single treatment did not exhibit such effects. Combination index value for cell viability indicated a synergistic interaction of liraglutide and metformin. Moreover, the combined treatment with liraglutide and metformin could activate the phosphorylation of AMP-activated protein kinase (AMPK) more potently than their single treatment in the cells. These results suggest that liraglutide in combination with metformin has a synergistic anti-tumor effect on the pancreatic cancer cells, which may be at least partly due to activation of AMPK signaling. Our study provides new insights into the treatment of patients with type 2 diabetes and pancreatic cancer.