Author Correction: A new coronavirus associated with human respiratory disease in China.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

A new coronavirus associated with human respiratory disease in China.

Emerging infectious diseases, such as severe acute respiratory syndrome (SARS) and Zika virus disease, present a major threat to public health1-3. Despite intense research efforts, how, when and where new diseases appear are still a source of considerable uncertainty. A severe respiratory disease was recently reported in Wuhan, Hubei province, China. As of 25 January 2020, at least 1,975 cases had been reported since the first patient was hospitalized on 12 December 2019. Epidemiological investigations have suggested that the outbreak was associated with a seafood market in Wuhan. Here we study a single patient who was a worker at the market and who was admitted to the Central Hospital of Wuhan on 26 December 2019 while experiencing a severe respiratory syndrome that included fever, dizziness and a cough. Metagenomic RNA sequencing4 of a sample of bronchoalveolar lavage fluid from the patient identified a new RNA virus strain from the family Coronaviridae, which is designated here 'WH-Human 1' coronavirus (and has also been referred to as '2019-nCoV'). Phylogenetic analysis of the complete viral genome (29,903 nucleotides) revealed that the virus was most closely related (89.1% nucleotide similarity) to a group of SARS-like coronaviruses (genus Betacoronavirus, subgenus Sarbecovirus) that had previously been found in bats in China5. This outbreak highlights the ongoing ability of viral spill-over from animals to cause severe disease in humans.

Al Foil-Supported Carbon Nanosheets as Self-Supporting Electrodes for High Areal Capacitance Supercapacitors.

Self-supporting electrode materials with the advantages of a simple operation process and the avoidance of the use any binders are promising candidates for supercapacitors. In this work, carbon-based self-supporting electrode materials with nanosheets grown on Al foil were prepared by combining hydrothermal reaction and the one-step chemical vapor deposition method. The effect of the concentration of the reaction solution on the structures as well as the electrochemical performance of the prepared samples were studied. With the increase in concentration, the nanosheets of the samples became dense and compact. The CNS-120 obtained from a 120 mmol zinc nitrate aqueous solution exhibited excellent electrochemical performance. The CNS-120 displayed the highest areal capacitance of 6.82 mF cm-2 at the current density of 0.01 mA cm-2. Moreover, the CNS-120 exhibited outstanding rate performance with an areal capacitance of 3.07 mF cm-2 at 2 mA cm-2 and good cyclic stability with a capacitance retention of 96.35% after 5000 cycles. Besides, the CNS-120 possessed an energy density of 5.9 µWh cm-2 at a power density of 25 µW cm-2 and still achieved 0.3 µWh cm-2 at 4204 µW cm-2. This work provides simple methods to prepared carbon-based self-supporting materials with low-cost Al foil and demonstrates their potential for realistic application of supercapacitors.

Haemoglobin A1c and serum glucose levels and risk of gastric cancer: a systematic review and meta-analysis.

BACKGROUND: This systematic review and meta-analysis examined associations between serum levels of haemoglobin A1c (HbA1c) and glucose and the risk of gastric cancer. METHODS: MEDLINE, Embase, and Cochrane Library were searched for studies examining associations between serum levels of HbA1c or glucose and the risk of gastric cancer. Inclusion of studies, quality assessment, and data extraction were conducted independently by two authors. Pooled hazard ratios (HR) with 95% confidence intervals (CI) were synthesised using random-effects models. Cochran's Q test and I2 statistic were used to assess heterogeneity. RESULTS: Among 3473 identified studies, 12 were included. Of these, 5 studies examined HbA1c levels and 7 studies examined serum glucose levels. Serum HbA1c levels >6% were associated with an increased risk of gastric cancer (HR 1.36, 95% CI 1.06-1.74). When compared with the lowest glucose categories, the highest glucose categories were associated with a borderline increased risk of gastric cancer (HR 1.11, 95% CI 0.98-1.26). In subgroup analyses, studies that adjusted for Helicobacter pylori infection indicated stronger associations between elevated HbA1c levels and gastric cancer (HR 2.08, 95% CI 1.46-2.98) than those without such adjustment (HR 1.10, 95% CI 0.91-1.32). CONCLUSIONS: Long-standing poor glycaemic control may increase the risk of gastric cancer. REGISTRATION NUMBER: PROSPERO CRD42020157453.

Gut microbiome alterations and gut barrier dysfunction are associated with host immune homeostasis in COVID-19 patients.

BACKGROUND: COVID-19 is an infectious disease characterized by multiple respiratory and extrapulmonary manifestations, including gastrointestinal symptoms. Although recent studies have linked gut microbiota to infectious diseases such as influenza, little is known about the role of the gut microbiota in COVID-19 pathophysiology. METHODS: To better understand the host-gut microbiota interactions in COVID-19, we characterized the gut microbial community and gut barrier function using metagenomic and metaproteomic approaches in 63 COVID-19 patients and 8 non-infected controls. Both immunohematological parameters and transcriptional profiles were measured to reflect the immune response in COVID-19 patients. RESULTS: Altered gut microbial composition was observed in COVID-19 patients, which was characterized by decreased commensal species and increased opportunistic pathogenic species. Severe illness was associated with higher abundance of four microbial species (i.e., Burkholderia contaminans, Bacteroides nordii, Bifidobacterium longum, and Blautia sp. CAG 257), six microbial pathways (e.g., glycolysis and fermentation), and 10 virulence genes. These severity-related microbial features were further associated with host immune response. For example, the abundance of Bu. contaminans was associated with higher levels of inflammation biomarkers and lower levels of immune cells. Furthermore, human-origin proteins identified from both blood and fecal samples suggested gut barrier dysfunction in COVID-19 patients. The circulating levels of lipopolysaccharide-binding protein increased in patients with severe illness and were associated with circulating inflammation biomarkers and immune cells. Besides, proteins of disease-related bacteria (e.g., B. longum) were detectable in blood samples from patients. CONCLUSIONS: Our results suggest that the dysbiosis of the gut microbiome and the dysfunction of the gut barrier might play a role in the pathophysiology of COVID-19 by affecting host immune homeostasis.

Activation of TRPV4 Induces Exocytosis and Ferroptosis in Human Melanoma Cells.

TRPV4 (transient receptor potential vanilloid 4), a calcium permeable TRP ion channel, is known to play a key role in endocytosis. However, whether it contributes to exocytosis remains unclear. Here, we report that activation of TRPV4 induced massive exocytosis in both melanoma A375 cell and heterologous expression systems. We show here that, upon application of TRPV4-specific agonists, prominent vesicle priming from endoplasmic reticulum (ER) was observed, followed by morphological changes of mitochondrial crista may lead to cell ferroptosis. We further identified interactions between TRPV4 and folding/vesicle trafficking proteins, which were triggered by calcium entry through activated TRPV4. This interplay, in turn, enhanced TRPV4-mediated activation of folding and vesicle trafficking proteins to promote exocytosis. Our study revealed a signaling mechanism underlying stimulus-triggered exocytosis in melanoma and highlighted the role of cellular sensor TRPV4 ion channel in mediating ferroptosis.

[Laparoscopic Common Bile Duct Exploration for Treatment of Common Bile Duct Stones:Clinical Analysis of 158 Cases].

Objective To evaluate the safety and effectiveness of laparoscopic common bile duct exploration in the treatment of common bile duct stones. Methods A retrospective analysis was conducted for 158 patients with cholecystolithiasis and choledocholithiasis admitted to the Number One Hospital of Zhangjiakou from January 2015 to December 2019.The patients were assigned into three groups according to the diameters of cystic duct and common bile duct,degrees of abdominal infection and tissue edema,and operation method.Group A(16 cases):laparoscopic cholecystectomy,transcystic choledochoscopic exploration for stone removal;Group B(94 cases):laparoscopic cholecystectomy,common bile duct incision exploration combined with choledochoscopy for stone removal,T tube drainage;Group C(48 cases):laparoscopic cholecystectomy,common bile duct incision exploration combined with choledochoscopy for stone removal,primary closure of the common bile duct.The operation time,residual rate of stones,and complication(bleeding,bile leakage,and wound infection) rate were compared between groups. Results The operation time of groups A,B,and C was(95.1±14.7),(102.2±18.1),(110.1±16.4) minutes,respectively,which showed no statistical difference between each other(F=0.020,P=0.887).One case in group A had residual stones,while no residual stone appeared in groups B and C.The overall stone clearance rate was 99.4% and the overall complication rate was 1.9%.There was no perioperative death. Conclusion It is generally safe and effective to carry out laparoscopic cholecystectomy and common bile duct exploration for stone removal in suitable populations.

Improved prognosis in gastric adenocarcinoma among metformin users in a population-based study.

BACKGROUND: Metformin may improve the prognosis in gastric adenocarcinoma, but the existing literature is limited and contradictory. METHODS: This was a Swedish population-based cohort study of diabetes patients who were diagnosed with gastric adenocarcinoma in 2005-2018 and followed up until December 2019. The data were retrieved from four national health data registries: Prescribed Drug Registry, Cancer Registry, Patient Registry and Cause of Death Registry. Associations between metformin use before the gastric adenocarcinoma diagnosis and the risk of disease-specific and all-cause mortality were assessed using multivariable Cox proportional hazard regression. The hazard ratios (HRs) and 95% confidence intervals (CIs) were adjusted for sex, age, calendar year, comorbidity, use of non-steroidal anti-inflammatory drugs or aspirin, and use of statins. RESULTS: Compared with non-users, metformin users had a decreased risk of disease-specific mortality (HR 0.79, 95% CI 0.67-0.93) and all-cause mortality (HR 0.78, 95% CI 0.68-0.90). The associations were seemingly stronger among patients of female sex (HR 0.66, 95% CI 0.49-0.89), patients with tumour stage III or IV (HR 0.71, 95% CI 0.58-0.88), and those with the least comorbidity (HR 0.71, 95% CI 0.57-0.89). CONCLUSIONS: Metformin use may improve survival in gastric adenocarcinoma among diabetes patients.

Metformin use and risk of gastric adenocarcinoma in a Swedish population-based cohort study.

BACKGROUND: Whether or not the use of metformin decreases the risk of gastric adenocarcinoma is unclear. METHODS: This was a population-based cohort study in 2005-2015. Associations between metformin use and gastric non-cardia and cardia adenocarcinomas were examined within two cohorts; a diabetes cohort of participants using anti-diabetes medications, and a matched cohort of common-medication users, where metformin non-users were frequency matched (10:1) with metformin users for sex and age. Multivariable Cox proportional hazard regression analyses provided hazard ratios (HR) and 95% confidence intervals (CI), adjusting for sex, age, calendar year, comorbidity, Helicobacter pylori eradication treatment, use of non-steroidal anti-inflammatory drugs or aspirin and use of statins. RESULTS: During the follow-up for a median of 5.8 years, 892 (0.1%) participants in the diabetes cohort and 6395 (0.1%) participants in the matched cohort of common-medication users developed gastric adenocarcinoma. Metformin users had no significantly decreased risk of gastric non-cardia adenocarcinoma (diabetes cohort: HR 0.93, 95% CI 0.78-1.12; matched cohort: HR 1.30, 95% CI 1.18-1.42) or cardia adenocarcinoma (diabetes cohort: HR 1.49, 95% CI 1.09-2.02; matched cohort: HR 1.58, 95% CI 1.38-1.81) compared with non-users in both cohorts. CONCLUSIONS: This cohort study with <10 years of follow-up suggests metformin use may not prevent gastric adenocarcinoma.

Prediabetes and diabetes in relation to risk of gastric adenocarcinoma.

BACKGROUND: Whether prediabetes or diabetes increases the risk of gastric adenocarcinoma is not clear. METHODS: This cohort study included 111,198 participants in the Northern Swedish Health and Disease Study. The participants were followed up from November 1985 to April 2017. The exposure to prediabetes or diabetes was assessed by oral glucose tolerance tests and self-reports. The incidence of the outcome gastric adenocarcinoma was identified from the Swedish Cancer Registry. Multivariable Cox regressions were used to analyse the associations between prediabetes or diabetes and the risk of gastric adenocarcinoma, providing hazard ratios (HR) with 95% confidence intervals (CI), with adjustment for sex, age, calendar year, body mass index, tobacco smoking and education level. RESULTS: Compared with normoglycaemic participants, the risk of gastric adenocarcinoma was not increased among participants with prediabetes (HR 1.07, 95% CI 0.79-1.44), diabetes (HR 0.77, 95% CI 0.46-1.29) or any of these exposures (HR 0.96, 95% CI 0.73-1.27). No associations were identified between prediabetes or diabetes and the risk of gastric adenocarcinoma in stratified analyses or in analyses separating cardia and non-cardia gastric adenocarcinoma. CONCLUSIONS: This study does not support the hypothesis that prediabetes or diabetes increases the risk of gastric adenocarcinoma.

Loss of nucleolar localization of NAT10 promotes cell migration and invasion in hepatocellular carcinoma.

NAT10, a nucleolar acetyltransferase, participates in a variety of cellular processes including ribosome biogenesis and DNA damage response. Immunohistochemistry staining showed that cytoplasmic and membranous NAT10 is related to the clinical pathologic characteristics in human cancer tissues. However, the mechanism about how NAT10 translocates from the nucleolus to cytoplasm and membrane is unclear. Here, we obtain a NAT10 deletion mutant localizing in cytoplasm and membrane. Bioinformatics analysis showed that residues 68-75 and 989-1018 are two potential nuclear localization signals (NLS) of NAT10. GFP-NAT10 deletion mutant (Δ989-1018) predominantly translocates into cytoplasm with faint signal retained in the nucleolus, while GFP-NAT10(Δ68-75) still remains in the nucleolus and nucleoplasm, indicating residues 989-1018 is the main nucleolar localization signal (NuLS). GFP-NAT10-D3, with both fragments (residues 68-75 and 989-1018) deleted, completely excludes from the nucleolus and translocates to cytoplasm and membrane. Therefore, complete NuLSs of NAT10 should include residues 68-75 and 989-1018. The cytoplasmic and membranous NAT10 mutant (Flag-NAT10-D3) colocalizes with α-tubulin in cytoplasm and with integrin on cell membrane. Importantly, Flag-NAT10-D3 promotes α-tubulin acetylation and stabilizes microtubules. Consequently, Flag-NAT10-D3 promotes migration and invasion in hepatocellular carcinoma (HCC) cells. Statistical analysis of immunohistochemistry staining of NAT10 in HCC tissues demonstrates that the cytoplasmic NAT10 is correlated with poorer prognosis compared with nuclear NAT10, while the membranous NAT10 predicts the poorest clinical outcome of the patients. We thus provide the evidence for the function of cytoplasmic and membranous NAT10 in the metastasis and prognosis of HCC patients.

Nanocluster-Mediated Synthesis of Diverse ZnTe Nanostructures: from Nanocrystals to 1D Nanobelts.

Liquid phase one-pot synthesis of semiconductor nanocrystals, by direct nucleation-growth crystallization, is unsuccessful for synthesis of some kinds of semiconductors. Using ZnTe as an example here, highly disperse ZnTe nanoclusters with diameters of 2-3 nm were first synthesized by a facile solvothermal method. Then the ZnTe nanoclusters were chosen as starting crystallization seeds to mediate the synthesis of flexible semiconductor nanostructures. Three-dimensional (3D) oriented assembly of ZnTe nanoclusters to monodisperse dendrimer-like nanocrystals (DLNCs), and one-dimensional (1D) ZnTe nanobelts with cubic phase, have been achieved successfully. Supported by TEM characterization of time-dependent morphology evolution, the oriented attachment assisted seed growth, based on ZnTe nanoclusters, enabled the 1D flexible ZnTe nanobelts formation, which could reach to ≈10 micrometers length.

Common genetic variant on 14q13.3 contributes to thyroid cancer susceptibility: evidence based on 12 studies.

Several genome-wide association studies on thyroid cancer (TC) have reported similar findings of a new susceptibility locus, 14q13.3. After that, a number of studies reported that rs944289 polymorphism at chromosome 14q13.3 has been implicated in TC risk. However, these studies have yielded inconsistent results. To investigate this inconsistency, we performed a meta-analysis of 12 studies involving a total of 7,598 TC cases, 53,613 controls, and 239 nuclear families for 14q13.3-rs944289 polymorphism to evaluate its effect on genetic susceptibility for TC. An overall random-effect per-allele OR of 1.30 (95 % CI 1.21-1.40, P < 10(-5)) was found for the polymorphism. Significant results were also observed for under dominant and recessive genetic models. In the subgroup analysis by ethnicity, we found similar significant results for both Caucasians (T allele: OR 1.29, 95 % CI 1.17-1.42, P < 10(-5)) and East Asians (T allele: OR 1.33, 95 % CI 1.18-1.49, P < 10(-5)). Further in stratified analyses according to study design and sample size, evidence of gene-disease association was also obtained. In addition, we found that rs944289 confers its risk, for both papillary thyroid carcinoma and follicular thyroid carcinoma when stratified by histological types of TC. Furthermore, our results on stratified analysis according to radiation exposure status showed an increased sporadic TC risk, while no associations were detected among radiation-related TCs for rs944289 polymorphism. Our result demonstrated that rs944289 polymorphism on 14q13.3 is a low penetrant risk factor for developing TC.

Analysis and risk factors of deep vein catheterization-related bloodstream infections in neonates.

To investigate the incidence, risk factors, and pathogenic characteristics of catheter-related bloodstream infection caused by peripherally inserted central venous catheter in neonates, and to provide references for reducing the infection rate of peripherally inserted central venous catheter. The clinical data of 680 neonates who underwent peripherally inserted central catheter (PICC) in the neonatal intensive care unit from June 2020 to June 2023 were retrospectively analyzed. The risk factors and independent risk factors of catheter-related bloodstream infection caused by PICC were determined by univariate and multivariate analysis, respectively. Catheter-related bloodstream infection occurred in 38 of 680 neonates who underwent PICC. The infection rate was 4.74%. The proportions of fungi, gram-positive bacteria, and gram-negative bacteria were 42.11%, 36.84%, and 21.05%, respectively. Candida parapsilosis was the main fungus (18.42%), coagulase negative Staphylococcus was the main gram-positive bacteria (23.68%), and Klebsiella pneumoniae and Escherichia coli were the main gram-negative bacteria (7.89%). Univariate analysis showed that gestational age ≤32 weeks, birth weight ≤1500 g, congenital diseases, nutritional support, catheterization time, 5-minute APGAR score ≤7, and neonatal respiratory distress syndrome were associated with catheter-related bloodstream infection caused by PICC. Multivariate analysis showed that premature delivery, low birth weight, parenteral nutrition, long catheterization time, and 5-minute APGAR score ≤7 were associated with catheter-related bloodstream infection caused by PICC. Among the pathogens detected, there were 6 cases of K pneumoniae, 5 cases of coagulase negative staphylococci, and 2 cases of fungi. Low birth weight, premature delivery, off-site nutrition, long catheterization time, and 5-minute APGAR score ≤7 are independent risk factors for catheter-related bloodstream infection in neonates with peripherally inserted central venous catheters. The pathogenic bacteria are fungi and multidrug-resistant bacteria.

Dual-Stage Surficial Microstructure to Enhance the Sensitivity of MXene Pressure Sensors for Human Physiological Signal Acquisition.

Accompanying the rapid growth of wearable electronics, flexible pressure sensors have received great interest due to their promising application in health monitoring, human-machine interfaces, and intelligent robotics. The high sensitivity over a wide responsive range, integrated with excellent repeatability, is a crucial requirement for the fabrication of reliable pressure sensors for various wearable scenes. In this work, we developed a highly sensitive and long-life flexible pressure sensor by constructing surficial microarrayed architecture polydimethylsiloxane (PDMS) film as a substrate and Ti3C2TX MXene/bacterial cellulose (BC) hybrid as an active sensing layer. The specific surficial morphology of PDMS couples with nanointercalated structure of Ti3C2Tx MXene/BC can effectively improve the sensitivity through controlling the stress distribution and layer spacing under different levels of pressure loading. In addition, abundant spontaneous hydrogen bonds between BC and Ti3C2Tx MXene nanosheets endow the MXene coating with highly adhesive strength on the PDMS surface; hence, the cyclic stability of the pressure sensor is greatly boosted. As a result, the obtained MXene/BC/PDMS (MBP) pressure sensor delivers high sensitivity (528.87 kPa-1), fast response/recovery time (45 ms/29 ms), low detection limit (0.6 Pa), and outstanding repeatability of up to 8000 cycles. Those excellent sensing properties of the MBP sensor allow it to serve as a reliable wearable device to monitor full-range human physiological motions, and it is expected to be applied in next-generation portable electronics, such as E-skins, smart healthcare, and the Internet of Things technology.

New evidence that vitamin D prevents headache: a bidirectional two-sample Mendelian randomization analysis.

Background: Previous observational clinical studies and meta-analyses have yielded inconsistent results regarding the relationship between vitamin D and headache, and the causal relationship remains unclear. The aim of this study was to investigate the causal relationship between vitamin D and headache by bidirectional two-sample Mendelian randomisation (MR) analysis. Methods: The relationship between high levels of vitamin D and headache was investigated by two-sample MR analysis using publicly available genome-wide association study (GWAS) data. The primary method was inverse variance weighting (IVW), and secondary methods were weighted median and MR-Egger methods. No heterogeneity or horizontal multidirectionality was found in the MR results. The robustness and validity of the findings were assessed using the leave-behind method. Results: A significant causal relationship was found between high vitamin D levels and headache using the IVW method (OR = 0.848; p = 0.007; 95% CI = 0.752-0.956). However, in a reverse analysis, no evidence of a causal relationship between headache and high levels of vitamin D was found using the IVW method (OR = 1.001; p = 0.906; 95% CI = 0.994-1.006). Our MR analyses showed no significant horizontal multidimensionality or heterogeneity (p > 0.05). Sensitivity analyses confirmed that MR estimates were not affected by single nucleotide polymorphisms (SNPs). Confirmation that our results are robust and valid has been obtained by the leave-one-out method. Conclusion: Our study suggests that high levels of vitamin D prevent the risk of headache. However, there is no evidence of a causal relationship between headache and high levels of vitamin D. Vitamin D may reduce the risk of headache.

Inactivated whole-virion SARS-CoV-2 vaccines and long-term clinical outcomes in patients with coronary atherosclerosis disease in China: a prospective cohort study.

AIMS: Publicized adverse events after vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) raised concern among patients with coronary atherosclerosis disease (CAD). We sought to study the association between SARS-CoV-2 vaccines and long-term clinical outcomes including ischaemic and bleeding events among patients with CAD. METHODS AND RESULTS: Inpatients diagnosed with CAD by coronary angiography, without a history of SARS-CoV-2 infection and vaccination, were included between 1 January and 30 April 2021, and underwent follow-up until 31 January 2022. Two doses of inactivated whole-virion SARS-CoV-2 vaccine (CoronaVac, BBIBPCorV, or WIBP-CorV) were available after discharge, and the group was stratified by vaccination. The primary composite outcomes were cardiovascular death, non-fatal myocardial infarction, stent thrombosis, unplanned revascularization, ischaemic stroke, venous thrombo-embolism, or peripheral arterial thrombosis. The bleeding outcomes were Bleeding Academic Research Consortium (BARC) type 3 or 5 bleeding. Cox regression models with vaccination status as a time-dependent covariate were used to calculate the hazard ratio (HR) for the outcomes. A propensity score matching method was used to reduce confounding biases. This prospective cohort study included 2078 individuals with CAD, 1021 (49.1%) were vaccinated. During a median follow-up of 9.1 months, 45 (4.3%) primary composite outcomes occurred in the unvaccinated group, and 33 (3.2%) in the vaccinated group. In Cox regression, the adjusted HR was 1.13 [95% confidence interval (CI) 0.65-1.93]. The adjusted HR for the bleeding outcomes associated with vaccination was 0.81 [95% CI 0.35-1.19]. After matching, the adjusted HR for the primary composite outcomes associated with vaccination was 1.06 [95% CI 0.57-1.99] and for the bleeding outcomes was 0.91 [95% CI 0.35-2.38]. Similar results were found in the seven prespecified subgroups. No grade 3 adverse reactions after vaccination were recorded. CONCLUSION: Our results indicated no evidence of an increased ischaemic or bleeding risk after vaccination with inactivated SARS-CoV-2 vaccine among Chinese patients with CAD, with limited statistical power.

The significance of galactose-deficient immunoglobulin A1 staining in kidney diseases with IgA deposition.

BACKGROUND: This study investigated the significance of galactose-deficient immunoglobulin A1 staining in kidney diseases with IgA deposition. METHODS: A total of 120 patients with IgA-dominant deposition in kidney tissues were enrolled and divided into four groups: primary IgA nephropathy (PIgAN), secondary IgA nephropathy (SIgAN), monotypic IgA nephropathy (MIgAN), and IgA variant monoclonal gammopathy of renal significance (IgA-MGRS). KM55 (the antibody of galactose-deficient immunoglobulin A1), IgA subtypes, and complement pathway factors (properdin, C4d, and C1q) were detected through immunofluorescence or immunohistochemistry analysis. RESULTS: KM55 and IgA double staining showed colocalization within glomeruli in all cases except for IgA-MGRS, which showed negative or weak staining of KM55 but strong staining of IgA. The PIgAN group showed the highest intensity of KM55 and KM55/IgA ratio, while these values in the IgA-MGRS group were the lowest (P < 0.01). A KM55/IgA quantified ratio of 0.78 was the optimal cut-off value to distinguish PIgAN from SIgAN, whereas a cut-off value of 0.21 was optimal to distinguish between MIgAN and IgA-MGRS. The clinicopathological characteristics showed significant differences as the groups were divided by diseases with optimal cut-off values, and these differences corresponded to the pathogenesis of each disease entity. CONCLUSIONS: PIgAN, SIgAN, and MIgAN are caused by the deposition of abnormally glycosylated IgA1 whereas IgA-MGRS is not. The KM55/IgA quantified ratio is valuable in distinguishing PIgAN from SIgAN, as well as MIgAN from IgA-MGRS.

Insight of novel biomarkers for papillary thyroid carcinoma through multiomics.

Introduction: The overdiagnosing of papillary thyroid carcinoma (PTC) in China necessitates the development of an evidence-based diagnosis and prognosis strategy in line with precision medicine. A landscape of PTC in Chinese cohorts is needed to provide comprehensiveness. Methods: 6 paired PTC samples were employed for whole-exome sequencing, RNA sequencing, and data-dependent acquisition mass spectrum analysis. Weighted gene co-expression network analysis and protein-protein interactions networks were used to screen for hub genes. Moreover, we verified the hub genes' diagnostic and prognostic potential using online databases. Logistic regression was employed to construct a diagnostic model, and we evaluated its efficacy and specificity based on TCGA-THCA and GEO datasets. Results: The basic multiomics landscape of PTC among local patients were drawn. The similarities and differences were compared between the Chinese cohort and TCGA-THCA cohorts, including the identification of PNPLA5 as a driver gene in addition to BRAF mutation. Besides, we found 572 differentially expressed genes and 79 differentially expressed proteins. Through integrative analysis, we identified 17 hub genes for prognosis and diagnosis of PTC. Four of these genes, ABR, AHNAK2, GPX1, and TPO, were used to construct a diagnostic model with high accuracy, explicitly targeting PTC (AUC=0.969/0.959 in training/test sets). Discussion: Multiomics analysis of the Chinese cohort demonstrated significant distinctions compared to TCGA-THCA cohorts, highlighting the unique genetic characteristics of Chinese individuals with PTC. The novel biomarkers, holding potential for diagnosis and prognosis of PTC, were identified. Furthermore, these biomarkers provide a valuable tool for precise medicine, especially for immunotherapeutic or nanomedicine based cancer therapy.