[Genetic origin analysis of regions of homozygosity in three cases].

OBJECTIVE: To explore the genetic characteristics of three fetuses with regions of homozygosity (ROH). METHODS: Three fetuses with ROH diagnosed at Nanjing Drum Tower Hospital on December 2, 2020, March 19, 2021, and May 27, 2022, respectively were selected as the study subjects. Clinical data of the fetuses were collected. Chromosomal microarray analysis (CMA) was used to detect the ROH, and tandem repeat sequences (STR)-based multiplex PCR assay was used to identify the mosaicism status in fetus 1. RESULTS: Partial maternal isodisomy (iUPD) (16) was found in fetus 1, for which trisomy rescue may be accountable. Meanwhile, the fetus also has confined placental mosaicism (CPM) but not true mosaicism. The formation mechanism of ROH for fetus 2 was identity by descent. Partial maternal iUPD (7) was found in fetus 3, which may be due to gametic recombination. CONCLUSION: The ROH of the three fetuses were inherited from both parents or the mother. Above findings suggested that it is justified to detect ROH on imprinting disorder-related chromosomes when potential uniparental disomy is suspected.

NUPR1 induces autophagy and promotes the progression of Esophageal squamous cell carcinoma via the MAPK-mTOR pathway.

PURPOSE: Esophageal squamous cell carcinoma (ESCC) is a dominant pathological type in China. NUPR1 is a complex molecule implicated in various physiological and biological functions whose expression is upregulated in response to stress. Furthermore, autophagy is a vital physiological mechanism in the onset and metastasis of malignancies. This study aims to uncover the influence of NUPR1 on ESCC occurrence and development by regulating autophagy while also exploring its association with the MAPK signaling pathway. METHODS: First, the differences in NUPR1 between ESCC and normal tissues were analyzed through online databases. Subsequently, the pathological tissues of clinical samples were stained and scored using immunohistochemistry. And NUPR1 expression in ESCC cells was investigated, as was the function of NUPR1 in the modulation of ESCC's malignant behavior. Furthermore, a nude mouse ESCC xenograft model was developed. Finally, RNA sequencing was performed on NUPR1-downregulated ESCC cells, which was verified using WB. RESULTS: Our findings initially uncovered differences in the expression of NUPR1 in ESCC and normal tissues. In vitro experiments demonstrated that NUPR1 downregulation significantly inhibited ESCC cell proliferation, invasion, and migration, as well as promoted their apoptosis. Our xenograft model exhibited significant inhibition of ESCC tumors upon NUPR1 downregulation. Subsequently, RNA sequencing uncovered that NUPR1 regulates its malignant biological behavior through MAPK-mTOR signaling pathway. Finally, we found that NUPR1 downregulation can inhibit autophagic flux in ESCC. CONCLUSION: Collectively, our findings show that NUPR1 enhances the progression of ESCC by triggering autophagy and is associated with the MAPK-mTOR signaling pathway.

Low-dose BPA-induced neuronal energy metabolism dysfunction and apoptosis mediated by PINK1/parkin mitophagy pathway in juvenile rats.

Bisphenol A (BPA) is related to neurological disorders involving mitochondrial dysfunction, while the mechanism remains elusive. Therefore, we explored it through in vitro and in vivo experiments. In vitro, hippocampal neurons derived from neonatal rats of different genders were exposed to 1-100 nM and 100 µM BPA, autophagy activator Rapa and inhibitor 3-MA for 7 d. The results suggested that even nanomolar BPA (1-100 nM) disturbed Ca2+ homeostasis and damaged the integrity of mitochondrial cristae in neurons (p < 0.05). Furthermore, BPA increased the number of autophagic lysosomes, LC3II/LC3I ratio, and p62 expression, and decreased parkin expression (p < 0.05), suggesting that the entry of damaged mitochondria into autophagic pathway was prompted, while the autophagic degradation pathway was blocked. This further disrupts neuronal energy metabolism and promotes neuronal apoptosis. However, Rapa attenuated the adverse effects caused by BPA, while 3-MA exacerbated these reactions. In vivo, exposure of juvenile rats to 0.5, 50, 5000 µg/kg‧bw/day BPA during PND 7-21 markedly impaired the structure of hippocampal mitochondria, increased the number of autophagosomes, the rate of neuronal apoptosis, and the expression levels of pro-apoptotic proteins Cyt C, Bax, Bak1, and Caspase3, and decreased the expression of anti-apoptotic protein Bcl2 (p < 0.05). Particularly, male rats are more sensitive to low-dose BPA than females. Overall, environmental-doses BPA can induce the imbalance of energy metabolism in hippocampal neurons via PINK1/parkin mitophagy, thereby inducing their apoptosis. Importantly, this study provides a theoretical basis for attenuating BPA-related neurological diseases.

Investigation of Metabolic and Inflammatory Disorder in the Aging FGF21 Knockout Mouse.

Aging is a physiological condition accomplished with persistent low-grade inflammation and metabolic disorders. FGF21 has been reported to act as a potent longevity determinant, involving inflammatory response and energy metabolism. In this study, we engineered aging FGF21 knockout mice of 36-40 weeks and observed that FGF21 deficiency manifests a spontaneous inflammatory response of lung and abnormal accumulation of lipids in liver. On one hand, inflamed state in lungs and increased circulating inflammatory cytokines were found in FGF21 knockout mice of 36-40 weeks. To evaluate the ability of FGF21 to suppress inflammation, a subsequent study found that FGF21 knockout aggravated LPS-induced pulmonary exudation and inflammatory infiltration in mice, while exogenous administration of FGF21 reversed these malignant phenotypes by enhancing microvascular endothelial junction. On the other hand, FGF21 knockout induces fatty liver in aging mice, characterized by excessive accumulation of triglycerides within hepatocytes. Further quantitative metabolomics and lipidomics analysis revealed perturbed metabolic profile in liver lacking FGF21, including disrupted glucose and lipids metabolism, glycerophospholipid metabolism, and amino acid metabolism. Taken together, this investigation reveals the protective role of FGF21 during aging by weakening the inflammatory response and balancing energy metabolism.

Clinical outcomes of treatment-naïve HBeAg-negative patients with chronic hepatitis B virus infection with low serum HBsAg and undetectable HBV DNA.

Serum hepatitis B surface antigen (HBsAg) level < 100 IU/ml and undetectable hepatitis B virus (HBV) DNA have been recently proposed as an alternate endpoint of "partial cure" in chronic hepatitis B (CHB). We investigated clinical outcomes of hepatitis B e antigen (HBeAg)-negative CHB patients with HBsAg <100 IU/ml and undetectable HBV DNA. Treatment-naïve HBeAg-negative CHB patients with undetectable HBV DNA and normal alanine aminotransferase were retrospectively included from three institutions. Patients were classified into the low HBsAg group (<100 IU/ml) and the high HBsAg group (≥100 IU/ml). Liver fibrosis was evaluated by noninvasive tests (NITs). A total of 1218 patients were included and the median age was 41.5 years. Patients with low HBsAg were older (45.0 vs. 40.0 years, P < 0.001) than those in the high HBsAg group, while the NIT parameters were comparable between groups. During a median follow-up of 25.7 months, patients with low HBsAg achieved a higher HBsAg clearance rate (13.0% vs. 0%, P < 0.001) and a lower rate of significant fibrosis development (2.2% vs. 7.0%, P = 0.049) compared to patients with high HBsAg. No patient developed HCC in either group. HBsAg level was negatively associated with HBsAg clearance (HR 0.213, P < 0.001) and patients with HBsAg < 100 IU/ml had a low risk of significant fibrosis development (HR 0.010, P = 0.002). The optimal cutoff value of HBsAg for predicting HBsAg clearance was 1.1 Log10 IU/ml. Treatment-naïve HBeAg-negative CHB patients with HBsAg <100 IU/ml and undetectable HBV DNA had favourable outcomes with a high rate of HBsAg clearance and a low risk of fibrosis progression.

Icariside II alleviates lipopolysaccharide-induced acute lung injury by inhibiting lung epithelial inflammatory and immune responses mediated by neutrophil extracellular traps.

AIMS: Acute lung injury (ALI) is a life-threatening lung disease characterized by inflammatory cell infiltration and lung epithelial injury. Icariside II (ICS II), one of the main active ingredients of Herba Epimedii, exhibits anti-inflammatory and immunomodulatory effects. However, the effect and mechanism of ICS II in ALI remain unclear. The purpose of the current study was to investigate the pharmacological effect and underlying mechanism of ICS II in ALI. MAIN METHODS: Models of neutrophil-like cells, human peripheral blood neutrophils, and lipopolysaccharide (LPS)-induced ALI mouse model were utilized. RT-qPCR and Western blotting determined the gene and protein expression levels. Protein distribution and quantification were analyzed by immunofluorescence. KEY FINDINGS: ICS II significantly reduced lung histopathological damage, edema, and inflammatory cell infiltration, and it reduced pro-inflammatory cytokines in ALI. There is an excessive activation of neutrophils leading to a significant production of NETs in ALI mice, a process mitigated by the administration of ICS II. In vivo and in vitro studies found that ICS II could decrease NET formation by targeting neutrophil C-X-C chemokine receptor type 4 (CXCR4). Further data showed that ICS II reduces the overproduction of dsDNA, a NETs-related component, thereby suppressing cGAS/STING/NF-κB signalling pathway activation and inflammatory mediators release in lung epithelial cells. SIGNIFICANCE: This study suggested that ICS II may alleviate LPS-induced ALI by modulating the inflammatory response, indicating its potential as a therapeutic agent for ALI treatment.

Study on the mechanism and degradation behavior of Encifer adhaerens DNM-S1 capturing dimethyl phthalate.

The global concern surrounding pollution caused by phthalates is escalating, with dimethyl phthalate (DMP) emerging as one of the most prevalent contaminants within the phthalates (PAEs) category. Although the biodegradation of DMP is considered both safe and efficient, its underlying degradation mechanism is not yet fully elucidated, and the degradation performance can be somewhat inconsistent. To address this issue, our study isolated a DMP-degrading bacterium (DNM-S1) from a vegetable greenhouse. The resulting data revealed that DNM-S1 exhibited a remarkable degradation performance, successfully degrading 84.98% of a 2000 mg L-1 DMP solution within 72 h. Remarkably, it achieved complete degradation of a 50 mg L-1 DMP solution within just 3 h. DMP degradation by DNM-S1 was also found to be efficient even under low-temperature conditions (10 °C). Our research further indicates that DNM-S1 is capable of capturing DMP through the ester bond in the bacterium's cell wall fatty acids, forming hydrogen bonds through hydrophobic interactions. The DMP was then transported into the DNM-S1 protoplasm using an active transport mechanism. Interestingly, the secondary metabolites of DNM-S1 contained natural carotenoids, which could potentially counteract the damaging effects of PAEs on cell membrane permeability. In summary, these findings highlight the potential of DNM-S1 in addressing PAEs pollution and provide new insights into the metabolic mechanism of PAEs degradation.

Clinical value of coagulation parameters in predicting the severity of severe fever with thrombocytopenia syndrome.

Introduction: Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease caused by a novel bunyavirus infection with a high lethality rate. The purpose of this study was to investigate the changes in coagulation parameters in patients with SFTS, aiming to provide clinical evidence for early diagnosis, treatment, and disease analysis. Methods: A total of 40 patients with SFTS attended from April 1, 2020 to May 21, 2022 in Nanjing Drum Tower Hospital were selected and grouped according to the duration of the disease, mild and severe disease, cure and death, with 50 healthy physical examiners as controls, and the risk of severe and death disease was predicted using ROC curves. Results: Comparison between the healthy, mild and severe groups revealed that PT, INR, APTT, TT, D-D and vWF levels were higher than those in the healthy control group, and FII, FIX, FX, FXI, FXII, PC and PS levels were lower than those in the healthy control group, the differences were statistically significant (p < 0.05). Comparing the results of SFTS patients with different course times, the results of Fib, FV, FVII, FVIII, FIX, FX, FXI were statistically significant (p < 0.05). Among the survived and deceased patients, the PT, INR, DD and PS results of the deceased patients were higher than those of the survived patients, and the FVIII, FIX, FXI, FXII and PC were lower than those of the survived patients. The area under the ROC curve showed that D-D had higher predictive ability for the risk of severe disease (AUROC 0.93, sensitivity and specificity at a Cut-off value of 1.50 mg/L were 90.0 and 86.5%, respectively) and the risk of death occurring (AUROC 0.84, sensitivity and specificity at a Cut-off value of 3.39 mg/L were 87.5 and 80.0%, respectively). Discussion: The monitoring of the coagulation parameters in patients with SFTS is great significance for identifying the severity and death of the patient's condition, and it is of great clinical value to provide early attention, timely intervention and maximum reduction of the mortality rate for patients at risk of severe disease.

Soluble Programmed Cell Death 1 Protein Is a Promising Biomarker to Predict Severe Liver Inflammation in Chronic Hepatitis B Patients.

Background and Aims: Liver inflammation is important in guiding the initiation of antiviral treatment and affects the progression of chronic hepatitis B(CHB). The soluble programmed cell death 1 protein (sPD-1) was upregulated in inflammatory and infectious diseases and correlated with disease severity. We aimed to investigate the correlation between serum sPD-1 levels and liver inflammation in CHB patients and their role in indicating liver inflammation. Methods: 241 CHB patients who underwent liver biopsy were enrolled. The correlation between sPD-1 levels and the degree of liver inflammation was analyzed. Univariate and multivariate logistic regression analyses were performed to analyze independent variables of severe liver inflammation. Binary logistic regression analysis was conducted to construct a predictive model for severe liver inflammation, and the receiver operating characteristic curve (ROC) was used to evaluate the diagnostic accuracy of the predictive model. Results: sPD-1 was highest in CHB patients with severe liver inflammation, which was higher than that in CHB patients with mild or moderate liver inflammation (P < 0.001). Besides, sPD-1 was weakly correlated with AST (r = 0.278, P < 0.001). Multivariable analysis showed that sPD-1 was an independent predictor of severe liver inflammation. The predictive model containing sPD-1 had areas under the ROC (AUROCs) of 0.917 and 0.921 in predicting severe liver inflammation in CHB patients and CHB patients with ALT ≤ 1× upper limit of normal (ULN), respectively. Conclusions: Serum sPD-1 level is associated with liver inflammation in CHB patients, and high levels of sPD-1 reflect severe liver inflammation. Serum sPD-1 is an independent predictor of severe liver inflammation and shows improved diagnostic accuracy when combined with other clinical indicators.

Azithromycin reduces bronchial wall thickening in infants with cystic fibrosis.

BACKGROUND: COMBAT-CF showed that children aged 0-3 years treated with azithromycin did clinically better than placebo but there was no effect on CT-scores. We reanalysed CTs using an automatic bronchus-artery (BA) analysis. METHOD: Inspiratory and expiratory CTs at 12 and 36 months were analysed. BA-analysis measures BA-diameters: bronchial outer wall (Bout), bronchial inner wall (Bin), artery (A), and bronchial wall thickness (Bwt) and computes BA-ratios: Bout/A and Bin/A for bronchial widening, Bwt/A and Bwa/Boa (bronchial wall area/bronchial outer area) for bronchial wall thickening. Low attenuation regions (LAR) were analysed using an automatic method. Mixed-effect model was used to compare BA-outcomes at 36 months between treatment groups. RESULTS: 228 CTs (59 placebo; 66 azithromycin) were analysed. The azithromycin group had lower Bwa/Boa (p = 0.0034) and higher Bin/A (p = 0.001) relative to placebo. Bout/A (p = 0.0088) was higher because of a reduction in artery diameters which correlated to a reduction in LAR. CONCLUSION: Azithromycin-treated infants with CF show a reduction in bronchial wall thickness and possibly a positive effect on lung perfusion.

Genicular artery embolization for the treatment of knee pain secondary to mild to severe knee osteoarthritis: One year clinical outcomes.

OBJECTIVE: To evaluate the safety and efficacy of genicular artery embolization (GAE) in patients with mild-to-severe knee osteoarthritis up to 12 months after GAE. MATERIALS & METHODS: This prospective single-center study included patients who had knee osteoarthritis for >1 year with moderate-to-severe pain after failed conservative treatment for >6 months. Baseline imaging features were evaluated to determine Kellgren-Lawrence (KL) grade and magnetic resonance imaging (MOAKS) scores. GAE was performed using 150-350 µm embolic polyvinyl alcohol particles. The visual analog scale (VAS) and the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scores were used to evaluate knee pain, stiffness, and function at baseline and follow-up. The primary endpoints were changes in VAS and WOMAC scores at 12 months. RESULTS: Thirty-three patients (n = 37 knees) aged 66.6 ± 8.7 years were enrolled. The patients were categorized into two groups: mild-to-moderate osteoarthritis (n = 28, KL grades 2-3) and severe osteoarthritis (n = 9, KL grade 4). GAE was successfully performed in all patients, with no major adverse events. Three to six branches of the genicular artery were embolized. The mean VAS and WOMAC scores in the mild-to-moderate group significantly decreased (6.6 at baseline vs. 3.0 at 12 months and 49.4 vs. 27.4, respectively, all P < 0.001). The mean VAS and WOMAC scores in the severe group significantly decreased at 12 months (7.3 vs. 4.4 and 58.1 vs. 40.6, respectively, all P < 0.001). CONCLUSION: GAE is a well-tolerated and effective treatment that significantly improves pain symptoms and function in patients with mild-to-severe knee osteoarthritis.

Mechanistic Insights into Surfactant-Modulated Electrode-Electrolyte Interface for Steering H2O2 Electrosynthesis.

Electrocatalytic reactions taking place at the electrified electrode-electrolyte interface involve processes of proton-coupled electron transfer. Interfacial protons are delivered to the electrode surface via a H2O-dominated hydrogen-bond network. Less efforts are made to regulate the interfacial proton transfer from the perspective of interfacial hydrogen-bond network. Here, we present quaternary ammonium salt cationic surfactants as electrolyte additives for enhancing the H2O2 selectivity of the oxygen reduction reaction (ORR). Through in situ vibrational spectroscopy and molecular dynamics calculation, it is revealed that the surfactants are irreversibly adsorbed on the electrode surface in response to a given bias potential range, leading to the weakening of the interfacial hydrogen-bond network. This decreases interfacial proton transfer kinetics, particularly at high bias potentials, thus suppressing the 4-electron ORR pathway and achieving a highly selective 2-electron pathway toward H2O2. These results highlight the opportunity for steering H2O-involved electrochemical reactions via modulating the interfacial hydrogen-bond network.

A perovskite-based electrochemiluminescence aptasensor for tetracycline screening.

Tetracyclines are currently the most commonly used class of antibiotics, and their residue issue significantly impacts public health safety. In this study, a surface modification of perovskite with cetyltrimethylammonium bromide led to the generation of stable electrochemiluminescence (ECL) emitters in aqueous systems and improved the biocompatibility of perovskite. A perovskite quantum dot-based ECL sensing strategy was developed. Utilizing the corresponding aptamer of the antibiotics, strain displacement reactions were triggered, disrupting the ECL quenching system composed of perovskite and Ag nanoclusters (Ag NCs) on the electrode surface, generating a signal to achieve quantitative detection of several common tetracycline antibiotics. The perovskite quantum dot provided a strong and stable initial signal, while the efficient catalytic activity of the silver cluster enhanced the recognition sensitivity. Tetracycline, chlortetracycline, and oxytetracycline were used as examples to demonstrate the differentiation and quantitative detection through this method. In addition, the aptasensor exhibited analytical performance with the linear range (0.1-10 µM OTC) and good recovery rates of 94.7% to 101.6% in real samples. This approach has the potential to become a sensitive and practical approach for assessing antibiotic residues.

Corrosion Behavior of 10 ppi TAD3D/5A05Al Composite in a Chloride Environment.

This study utilizes desalted and denitrated treated aluminum dross (TAD) as a raw material, along with kaolin and 10 ppi (pores per inch) polyurethane foam as a template. The slurry is converted into an aluminum dross green body with a three-dimensional network structure using the impregnation method. A three-dimensional network aluminum dross ceramic framework (TAD3D) is created at a sintering temperature of 1350 °C. The liquid 5A05 aluminum alloy at a temperature of 950 °C infiltrates into the voids of TAD3D through pressureless infiltration, resulting in TAD3D/5A05Al composite material with an interpenetrating phase composite (IPC) structure. The corrosion behavior of TAD3D/5A05 composite material in sodium chloride solution was examined using the salt spray test (NSS) method. The study shows that the pores of the TAD3D framework, produced by sintering aluminum dross as raw material, are approximately 10 ppi. The bonding between TAD3D and 5A05Al interfaces is dense, with strong interfacial adhesion. The NSS corrosion time ranged from 24 h to 360 h, during which the composite material underwent pitting corrosion, crevice corrosion and self-healing processes. Results from Potentiodynamic Polarization (PDP) and Electrochemical Impedance Spectroscopy (EIS) indicate that, as corrosion progresses, the Ecorr of TAD3D/5A05Al decreases from -0.718 V to -0.786 V, and Icorr decreases from 0.398 µA·cm-2 to 0.141 µA·cm-2. A dense oxide film forms on the surface of the composite material, increasing the anodic Tafel slope and decreasing the cathodic Tafel slope, thus slowing down the rates of cathodic and anodic reactions. Factors such as lower interface corrosion resistance or a relatively weak passivation film at the interface do not significantly diminish the corrosion resistance of TAD3D and 5A05Al. The corrosion resistance of the composite material initially decreases and then increases.

SARS-CoV-2 Omicron infection augments the magnitude and durability of systemic and mucosal immunity in triple-dose CoronaVac recipients.

The inactivated whole-virion vaccine, CoronaVac, is one of the most widely used coronavirus disease 2019 (COVID-19) vaccines worldwide. There is a paucity of data indicating the durability of the immune response and the impact of immune imprinting induced by CoronaVac upon Omicron infection. In this prospective cohort study, 41 recipients of triple-dose CoronaVac and 14 unvaccinated individuals were recruited. We comprehensively profiled adaptive immune parameters in both groups, including spike-specific immunoglobulin (Ig) G and IgA titers, neutralizing activity, B cells, circulating follicular helper T (cTfh) cells, CD4+ and CD8+ T cells, and their memory subpopulations at 12 months after the third booster dose and at 4 and 20 weeks after Omicron BA.5 infection. Twelve months after the third CoronaVac vaccination, spike-specific antibodies and cellular responses were detectable in most vaccinated individuals. BA.5 infection significantly augmented the magnitude, cross-reactivity, and durability of serum neutralization activities, Fc-mediated phagocytosis, nasal spike-specific IgA responses, memory B cells, activated cTfh cells, memory CD4+ T cells, and memory CD8+ T cells for both the ancestral strain and Omicron subvariants, compared to unvaccinated individuals. Notably, the increase in BA.5-specific immunity after breakthrough infection was consistently comparable to or higher than that of the ancestral strain, suggesting no evidence of immune imprinting. Immune landscape analyses showed that vaccinated individuals have better synchronization of multiple immune components than unvaccinated individuals upon heterologous infection. Our data provide detailed insight into the protective role of the inactivated COVID-19 vaccine in shaping humoral and cellular immunity to Omicron infection. IMPORTANCE: There is a paucity of data indicating the durability of the immune response and the impact of immune imprinting induced by CoronaVac upon Omicron breakthrough infection. In this prospective cohort study, the anti-severe acute respiratory syndrome coronavirus 2 adaptive responses were analyzed before and after the Omicron BA.5 infection. Our data provide detailed insight into the protective role of the inactivated COVID-19 vaccine in shaping humoral and cellular immune responses to heterologous Omicron infection. CLINICAL TRIAL: This study is registered with ClinicalTrials.gov as NCT05680896.

Discovery of novel biphenyl-sulfonamide analogues as NLRP3 inflammasome inhibitors.

The aberrant activation of NLRP3 inflammasome has been observed in various human diseases. Targeting the NLRP3 protein with small molecule inhibitors shows immense potential as an effective strategy for disease intervention. Herein, a series of novel biphenyl-sulfonamide NLRP3 inflammasome inhibitors were designed and synthesized. The representative compound H28 was identified as potent and specific NLRP3 inflammasome inhibitor with IC50 values of 0.57 µM. Preliminary mechanistic studies have revealed that compound H28 exhibits direct binding to the NLRP3 protein (KD: 1.15 µM), effectively inhibiting the assembly and activation of the NLRP3 inflammasome. The results in a mouse acute peritonitis model revealed that H28 effectively inhibit the NLRP3 inflammasome pathway, demonstrating their anti-inflammatory properties. Our findings strongly support the further development of H28 as potential lead compound for treating NLRP3-related diseases.

Identification of potential biomarkers for neuromyelitis optica by quantitative proteomics.

OBJECTIVE: Neuromyelitis optica (NMO) was a serious autoimmune inflammatory condition affecting the central nervous system. Currently, there was a lack of diagnostic biomarkers for AQP4-IgG-negative NMO patients. METHODS: A comparative proteomic analysis was conducted on the CSF of 10 patients with NMO and 10 patients with non-inflammatory neurological disorders (NND) using tandem mass tagging technology. Differentially expressed proteins (DEPs) were analyzed using bioinformatic methods. The candidate proteins were then validated through ELISAs in a subsequent cohort of 160 samples, consisting of paired CSF and plasma samples from 50 NMO patients, CSF samples from 30 NND patients, and plasma samples from 30 healthy individuals. RESULTS: We identified 389 proteins via proteomics, screening 79 DEPs. NCAM1, SST and AHSG were selected as candidate molecules for further validation. Compared to NND patients, there were decreased levels of AHSG in CSF and increased levels of NCAM1 and SST in NMO patients. The ELISA results revealed significantly higher levels of AHSG, SST and NCAM1 in the CSF of the NMO group compared to the NND group. Similarly, the serum levels of these three proteins were also higher in the NMO group compared to the healthy control group. It was found that serum NCAM1 levels significantly decreased in patients with non-relapsed NMO compared to patients with relapsed NMO and CSF NCAM1 level increased in patients with bilateral NMO compared to patients with unilateral NMO. Furthermore, CSF SST levels increased in AQP4 antibody-positive NMO patients compared to AQP4 antibody-negative patients. INTERPRETATION: CSF NCAM1, serum NCAM1 and serum SST may serve as potential biomarkers for NMO patients and aid in the diagnosis of AQP4 antibody-negative NMO patients.

DNA Bloom Filter enables anti-contamination and file version control for DNA-based data storage.

DNA storage is one of the most promising ways for future information storage due to its high data storage density, durable storage time and low maintenance cost. However, errors are inevitable during synthesizing, storing and sequencing. Currently, many error correction algorithms have been developed to ensure accurate information retrieval, but they will decrease storage density or increase computing complexity. Here, we apply the Bloom Filter, a space-efficient probabilistic data structure, to DNA storage to achieve the anti-error, or anti-contamination function. This method only needs the original correct DNA sequences (referred to as target sequences) to produce a corresponding data structure, which will filter out almost all the incorrect sequences (referred to as non-target sequences) during sequencing data analysis. Experimental results demonstrate the universal and efficient filtering capabilities of our method. Furthermore, we employ the Counting Bloom Filter to achieve the file version control function, which significantly reduces synthesis costs when modifying DNA-form files. To achieve cost-efficient file version control function, a modified system based on yin-yang codec is developed.

First Family Case of Hemoglobinopathy Titusville in China with Falsely Low SpO2 and Unmeasurable SaO2.

BACKGROUND: Normal hemoglobin is a tetrameric structure, consisting of two alpha-globin chains and two nonalpha (beta, gamma, delta) chains. Hemoglobinopathies occur when the presence of gene mutations affect the molecular structure or expression of the globin chains. METHODS: We reported the case of a 9-year-old Chinese girl who presented with abnormal low oxygen saturation values on pulse oximetry and no oximetry results were obtained during blood gas analysis (BGA). RESULTS: High-performance liquid chromatography (HPLC) and capillary electrophoresis demonstrated that the presence of a low oxygen affinity hemoglobin variant, characterized as hemoglobin Titusville, was proven by gene sequencing. The patient's mother and aunt also carry the hemoglobin variant, representing the first Chinese family case reported. CONCLUSIONS: Hemoglobin Titusville is a rare genetic hemoglobin structural defect. early diagnosis can help patients and clinicians avoid unnecessary anxiety and costly or excessive clinical investigations.

Trophic interactions in soil micro-food webs drive ecosystem multifunctionality along tree species richness.

Rapid biodiversity losses under global climate change threaten forest ecosystem functions. However, our understanding of the patterns and drivers of multiple ecosystem functions across biodiversity gradients remains equivocal. To address this important knowledge gap, we measured simultaneous responses of multiple ecosystem functions (nutrient cycling, soil carbon stocks, organic matter decomposition, plant productivity) to a tree species richness gradient of 1, 4, 8, 16, and 32 species in a young subtropical forest. We found that tree species richness had negligible effects on nutrient cycling, organic matter decomposition, and plant productivity, but soil carbon stocks and ecosystem multifunctionality significantly increased with tree species richness. Linear mixed-effect models showed that soil organisms, particularly arbuscular mycorrhizal fungi (AMF) and soil nematodes, elicited the greatest relative effects on ecosystem multifunctionality. Structural equation models revealed indirect effects of tree species richness on ecosystem multifunctionality mediated by trophic interactions in soil micro-food webs. Specifically, we found a significant negative effect of gram-positive bacteria on soil nematode abundance (a top-down effect), and a significant positive effect of AMF biomass on soil nematode abundance (a bottom-up effect). Overall, our study emphasizes the significance of a multitrophic perspective in elucidating biodiversity-multifunctionality relationships and highlights the conservation of functioning soil micro-food webs to maintain multiple ecosystem functions.