Efficient strategy for employing HN-AD bacterium enhanced biofilter reactors to remove NH3 and reduce secondary pollution.

Heterotrophic nitrification-aerobic denitrification (HN-AD) strain (Paracoccus denitrificans HY-1) was employed in this study to enhance the removal efficiency of NH3 in a biological trickling filter (BTF) reactor. The results demonstrated that inoculation with HY-1 and packed with bamboo charcoal as filler significantly improved the RE of NH3 in BTF, reaching 96.52 % under 27 s of empty bed residence time (EBRT) and 812.56 ppm of inlet gas concentration. Meanwhile, the titer of NH4+-N, NO2--N, and NO3--N in the circulating fluid were merely 8.52 mg/L, 5.14 mg/L, and 18.07 mg/L, respectively. Microbial community and metabolism analyses revealed that HY-1 have successfully colonized in the BTF, and the high expression of denitrification-related genes (nar, nap, nir, nor and nos) further confirmed that the inoculation of HY-1 greatly improved both nitrification and denitrification metabolism. Furthermore, the biofilter reactor inoculated with HY-1 was applied at a large-scale piggery and exhibited remarkable odor removal effect, in which 99.61 % of NH3 and 96.63 % of H2S were completely eliminated. In general, the HN-AD bacterium could strengthen the performance of BTF reactor and reduce the secondary pollution of circulating fluid during bio-deodorization.

Association between fatty liver index and cardiometabolic multimorbidity: evidence from the cross-sectional national health and nutrition examination survey.

Background: Metabolic dysfunction associated steatotic liver disease (MASLD) contributes to the cardiometabolic diseases through multiple mechanisms. Fatty liver index (FLI) has been formulated as a non-invasive, convenient, and cost-effective approach to estimate the degree of MASLD. The current study aims to evaluate the correlation between FLI and the prevalent cardiometabolic multimorbidity (CMM), and to assess the usefulness of FLI to improve the detection of the prevalent CMM in the general population. Methods: 26,269 subjects were enrolled from the National Health and Nutrition Examination Survey 1999-2018. FLI was formulated based on triglycerides, body mass index, γ -glutamyltransferase, and waist circumference. CMM was defined as a history of 2 or more of diabetes mellitus, stroke, myocardial infarction. Results: The prevalence of CMM was 10.84%. With adjustment of demographic, anthropometric, laboratory, and medical history covariates, each standard deviation of FLI leaded to a 58.8% risk increase for the prevalent CMM. The fourth quartile of FLI had a 2.424 times risk for the prevalent CMM than the first quartile, and a trend towards higher risk was observed. Smooth curve fitting showed that the risk for prevalent CMM increased proportionally along with the elevation of FLI. Subgroup analysis demonstrated that the correlation was robust in several conventional subpopulations. Receiver-operating characteristic curve analysis revealed an incremental value of FLI for detecting prevalent CMM when adding it to conventional cardiometabolic risk factors (Area under the curve: 0.920 vs. 0.983, P < 0.001). Results from reclassification analysis confirmed the improvement from FLI. Conclusion: Our study demonstrated a positive, linear, and robust correlation between FLI and the prevalent CMM, and our findings implicate the potential usefulness of FLI to improve the detection of prevalent CMM in the general population.

CRISPR/Cas12a-Based Indirect Competitive Enzyme-Linked Immunosorbent Assay for Sensitive Detection of Ochratoxin A.

The high toxicity and widespread contamination of ochratoxin A (OTA) make it urgent to develop a sensitive method to detect trace OTA in complex food matrices. Herein, an indirect competitive enzyme-linked immunosorbent assay (icELISA)-based on the CRISPR/Cas12a system is described. DNA amplicons with multiple activation sequences of the CRISPR/Cas12a system were pre-prepared to improve detection sensitivity. In the absence of OTA, streptavidin-mediated biotinylated DNA amplicons were captured by the biotinylated secondary antibody on the microplate. The captured DNA amplicons activated the CRISPR/Cas12a system, which thereby effectively cleaved the reporter DNA, producing strong fluorescence. The presence of OTA led to a decrease in DNA amplicons on the microplate, resulting in a decrease in activated Cas12a and ultimately a drop in fluorescence intensity. OTA in food matrices at nanogram per milliliter levels can be detected. Therefore, the new method has great potential in monitoring OTA.

Preparation of hapten and monoclonal antibody of hesperetin and establishment of enzyme-linked immunosorbent assay.

Hesperetin is the aglycone of hesperidin and is widely found in the Rutaceae plants and herbal medicines. It exhibits antioxidant, detoxifying, anti-inflammatory, and antimicrobial properties, similar to hesperidin. It has also shown potential in the regulation of certain diseases. In order to detect hesperetin in complex matrix samples such as citrus and herbal, we developed an anti-hesperetin monoclonal antibody and established an indirect competitive enzyme-linked immunosorbent assay (icELISA). The half maximal inhibitory concentration (IC50) was determined to be 2.03 ng/mL, the detection range was 0.39-12.73 ng/mL. In practical sample testing, the concentration of hesperidin measured by icELISA is consistent with the result of UPLC-MS/MS, and the correlation coefficient (R2) is 0.97. These results showed that the established method has good accuracy, reproducibility and broad application prospects, and can be used for the detection of hesperetin in complex matrix samples (such as citrus and herbal samples).

Quantitative assessment of Cd sources in rice grains through Cd isotopes and MixSIAR model in a typical e-waste dismantling area of Southeast China.

Identification of Cd sources and quantification of their contribution to rice grain Cd is crucial for controlling accumulation of this toxic metal in rice grains. However, accurate assessment of the contribution of different Cd sources to grain Cd concentration in rice under actual field conditions is a challenge. In this study, we determined Cd concentration and their isotopic compositions in rice grains with respect to three potential Cd sources around an e-waste dismantling area in Taizhou City, Zhejiang Province, China. Results demonstrated that average Cd concentrations in grains, surface soils, atmospheric deposition and surface water were 0.32, 0.91, 1.99 mg kg-1 and 2.02 µg L-1, respectively. The δ114/110Cd values of grains, surface soils, surface water and atmospheric deposition ranged from 0.00 ‰ to 0.31 ‰, -0.21 ‰ to 0.14 ‰, -0.04 ‰ to 0.47 ‰, and - 0.25 ‰ to -0.18 ‰, respectively. The MixSIAR model indicated that contribution of soils, irrigation water and atmospheric deposition to grain Cd was 56.8 %, 24.8 % and 18.4 %, respectively, demonstrating soils as the major source of grain Cd in the study area. This study also highlighted significant contribution of irrigation water and atmospheric deposition to Cd concentration in rice grains. The Cd isotopic analysis provides a practical approach for source apportionment of grain Cd and data support for controlling Cd accumulation in rice around the e-waste dismantling area.

Diallyl trisulfide alleviates dextran sulphate sodium-induced colitis in mice by inhibiting NLRP3 inflammasome activation via ROS/Trx-1 pathway.

Diallyl trisulfide (DATS), a sulphur-containing compound isolated from the medicinal food plant garlic, has been previously reported to attenuate experimental colitis induced by either dextran sodium sulphate (DSS) or 2,4,6-trinitrobenzenesulfonic acid (TNBS) in mice; however, the underlying mechanism remains to be identified. In this study, we deciphered the key mechanism by which DATS alleviates ulcerative colitis (UC). We showed that oral administration of DATS for 10 consecutive days greatly restrained the infiltration of macrophages and the pathological changes in colonic tissues of mice with DSS-induced colitis. DATS treatment notably dampened the content of IL-1ß and IL-18 and suppressed NLRP3 inflammasome activation in colon. Mechanistically, DATS effectively diminished the generation of ROS in macrophages. The suppressive effect of DATS on the activation of NLRP3 inflammasome and downregulation of IL-18 and IL-1ß levels was blunted by xanthine oxidase. Further studies revealed that DATS inhibited NF-κB pathway activation by suppressing the expression of Trx-1, thereby inhibiting NLRP3 inflammasome activation. Trx-1 overexpression and interference in macrophages promoted and diminished NLRP3 inflammasome activation, respectively. In summary, garlic and its main active ingredient DATS have potentials to prevent and treat UC, and DATS functions by inhibiting NLRP3 inflammasome activation via Trx-1/ROS pathway.

Pseudomonas fluorescens Inoculation Enhances Salix matsudana Growth by Modifying Phyllosphere Microbiomes, Surpassing Nitrogen Fertilization.

The enhancement of plant growth by soil fertilization and microbial inoculation involves different mechanisms, particularly by altering the phyllosphere microbiome. This study investigated how nitrogen (N) fertilization, Pseudomonas fluorescens strain R124 inoculation and their combined effects influence the growth of different-aged Salix matsudana cuttings by modulating N dynamics within the phyllosphere microbiome. Results showed that P. fluorescens inoculation was significantly more effective than N fertilization alone, enhancing biomass, plant nutrient uptake, soil nutrient content and root development by 90.51%, 18.18%, 72.74% and 126.20%, respectively. Crucially, the inoculation notably shifted the beta-diversity of the phyllosphere microbial community, with K-strategy fungi enhancing plant N fixation and subsequent plant growth. Cuttings from middle-aged forests displayed more robust growth than those from young-aged, associated with a varied impact on phyllosphere fungi, notably increasing the relative abundance of Myriangiales in young (76.37%) and Capnodiales in middle-aged cuttings (42.37%), which improve phyllosphere stability and plant health. These findings highlight the effectiveness of microbial inoculation over N fertilization in promoting plant growth and provide valuable insights for the sustainable management of willow plantations at different stages of development.

Medication-related osteonecrosis of the jaw: a retrospective single center study of recurrence-related factors after surgical treatment.

OBJECTIVES: To provide an overview of the features of patients with medication-related osteonecrosis of the jaw (MRONJ) and explore recurrence-related factors after surgery. MATERIALS AND METHODS: All pathological records of patients diagnosed with osteonecrosis or osteomyelitis of the jaw were reviewed. Only patients who had a history of use of medication related to bone turnover were included. All demographic and clinical characteristics were collected during review. Univariate and logistic regression analyses were performed to evaluate the associations between risk factors and recurrence. A p value < 0.05 was considered to indicate statistical significance in all analyses. RESULTS: A total of 313 patients were ultimately included. Most patients (89.14%) underwent bone turnover-related treatment due to malignancy. The breast and prostate were the most common locations of primary tumors in females and males, respectively. Almost all MRONJ patients experienced inflammatory symptoms. Recurrence occurred in 55 patients at 60 locations. The total recurrence rate was 16.85%, with no significant differences between the maxilla and mandible. Extensive surgery and flap transfer were strongly related to a lower recurrence risk. Nearly 80% of patients had recurrence-related symptoms within 6 months. CONCLUSION: When MRONJ is treated with surgical methods, extensive resection and flap transfer can reduce recurrence risk. Six-month follow-up is needed to exclude recurrence after surgery. CLINICAL RELEVANCE: This study revealed the surgical-related risk factors, such as extensive surgery and flap transfer, when treating MRONJ patients, and 6-month follow-up is needed to detect recurrence. This could provide clinical guidance for head and neck surgeons.

Surveillance of household foodborne disease outbreaks in Zhejiang Province, China, 2010-2022.

BACKGROUND: Foodborne diseases are a growing public health concern worldwide and households are a common setting. This study aimed to explore the epidemiological characteristics of household foodborne disease outbreaks in Zhejiang Province and propose targeted prevention and control measures. METHODS: Descriptive statistical methods were used to analyze household foodborne disease outbreak data collected from the Foodborne Disease Outbreaks Surveillance System in Zhejiang Province from 2010 to 2022. RESULTS: Household foodborne disease outbreaks showed an upward trend during the study period (Cox-Staurt trend test, p = 0.01563 < 0.05). These outbreaks mainly occurred from June to September, with 62.08% (352/567) of all reported outbreaks. The number of reported outbreaks varied in 11 prefectures, with a maximum of 100 and a minimum of only 7. Household foodborne disease outbreaks had a wide spectrum of etiologic factors. Mushroom toxins accounted for the largest proportion of all etiologies (43.39 %) and caused the highest proportion of hospitalization (54.18%) and death (78.26%). Such outbreaks are caused by accidently eating wild poisonous mushrooms. Bacterial infection (16.23%) was the second most common etiology, with Salmonella spp. and Vibrio parahaemolyticus being the primary pathogens. These outbreaks were caused by improper storage, improper processing or a combination of factors, and the foods involved were mainly aquatic animals, eggs and cooked meat. Other identified etiologies included plant toxins (9.52%), chemicals (7.23%), animal toxins (3.70%), and viruses (1.76%). Among the above-mentioned etiologies, mushroom toxins, bacteria, and animal toxins had seasonal characteristics. Analysis of regions and etiologies revealed that the proportion of various etiologies was different in 11 prefectures. Wild mushrooms (43.39%), aquatic animals (9.88%), and toxic plants (8.47%) were the top three foods involved in these outbreaks. The most common factors contributing to household foodborne disease outbreaks were inedibility and misuse (59.08%), followed by multiple factors (7.58%), improper storage (7.41%), and improper processing (7.41%). CONCLUSIONS: Household foodborne disease outbreaks were closely related to the lack of knowledge regarding foodborne disease prevention. Therefore, public health agencies should strengthen residents' surveillance and health education to improve food safety awareness and effectively reduce foodborne diseases in households. In addition, timely publicity and early warning by relevant government departments, the introduction of standards to control the contamination of pathogenic bacteria in raw materials, and strengthened supervision of the sale of substances that may cause health hazards, such as poisonous mushrooms and nitrites, will also help reduce such outbreaks.

In Vivo Silencing of Intestinal DMT1 Mitigates Iron Loading in ß-thalassemia Intermedia (Hbbth3/+) Mice.

ß-thalassemia is an iron-loading anemia caused by homozygous mutation of the hemoglobin subunit ß (HBB) gene. In ß-thalassemia intermedia (ßTI), a non-transfusion-dependent form of the disease, iron overload is caused by excessive absorption of dietary iron due to inappropriately low production of the iron-regulatory hormone hepcidin. Low hepcidin stabilizes the iron exporter ferroportin (FPN) on the basolateral membrane of enterocytes. High FPN activity may deplete intracellular iron and enhance expression of the predominant iron importer divalent metal-ion transporter 1 (DMT1). In mice, DMT1 mediates normal iron absorption under physiological conditions and excessive iron absorption in pathological iron overload (e.g., hereditary hemochromatosis). Here, we hypothesized that DMT1 drives elevated iron absorption in ßTI. Accordingly, we crossed Hbbth3/+ mice, a pre-clinical model of ßTI, with intestine-specific DMT1 KO mice. Ablation of intestinal DMT1 in Hbbth3/+ mice caused a pathophysiological shift from iron overload to an iron-deficiency phenotype with exacerbated anemia. DMT1 is thus required for iron absorption and iron loading in Hbbth3/+ mice. Based upon these outcomes, we further logically postulated that in vivo knockdown of intestinal DMT1 would mitigate iron loading in Hbbth3/+ mice. Ginger-derived, lipid nanoparticles carrying DMT1-specific (or control) siRNAs were administered by oral, intragastric gavage to 4-week-old Hbbth3/+ mice daily for 16 days. siRNA treatment reduced DMT1 expression by >80% and blunted iron loading, as indicated by significant reductions in liver iron and serum ferritin (which reflect body iron stores). These notable experimental outcomes establish intestinal DMT1 as a plausible therapeutic target to mitigate iron overload in ßTI.

Gender Disparities and Ultrasonographic Evaluation of Anatomic Features of Anterolateral Thigh Flap (ALT) in Individuals with Diverse BMI: A Retrospective Clinical Study.

Background: The anterolateral thigh (ALT) flap plays a crucial role in reconstructive surgeries, providing versatile and reliable soft-tissue coverage. Flap thickness is a critical determinant of tissue volume and quality. Vascular factors, including the vascular diameter of the perforators and the length of the vascular pedicle, significantly influence flap viability and postrepair outcomes. To enhance preoperative assessment, this study integrated gender and body mass index (BMI) to analyze the anatomical characteristics of ALT flaps. Methods: This study used somatic penetrating ultrasonography to examine bilateral ALT flaps in patients. This study analyzed the relationship between gender and ALT flap thickness, vascular diameter of the perforators, and vascular pedicle length. Chi-square test was used to assess variations in age and gender. Multiple t-tests compared flap thickness, vascular diameter, and pedicle length between men and women in different BMI groups. Results: A total of 158 patients were included in this study from January 2018 to December 2022. In BMI < 24 and BMI ≥ 24.0 groups, males had lower ALT flap thickness than females (p < 0.0001 in each subgroup). Similarly, the vascular diameter of the perforators followed the same trend, with females having larger vascular diameters than males in BMI < 24 and BMI ≥ 24.0 groups. In terms of vascular pedicle length, males had longer pedicle length than females in both BMI < 24 and BMI ≥ 24.0 groups (p < 0.05 in each subgroup). Conclusions: Females demonstrate greater ALT flap thickness and larger vascular diameter of the perforators than males, whereas males have a longer length of the vascular pedicle.

Macrophage-Hepatocyte Circuits Mediated by Grancalcin Aggravate the Progression of Metabolic Dysfunction Associated Steatohepatitis.

The dynamic interplay between parenchymal hepatocytes and non-parenchymal cells (NPCs), such as macrophages, is an important mechanism for liver metabolic homeostasis. Although numerous endeavors have been made to identify the mediators of metabolic dysfunction associated steatohepatitis (MASH), the molecular underpinnings of MASH progression remain poorly understood, and therapies to arrest MASH progression remain elusive. Herein, it is revealed that the expression of grancalcin (GCA) is upregulated in the macrophages of patients and rodents with MASH and correlates with MASH progression. Notably, the administration of recombinant GCA aggravates the development of MASH, whereas, Gca deletion in myeloid cells blunts liver steatosis and inflammation in multiple MASH murine models. Mechanistically, GCA activates macrophages via TLR9-NF-κB signaling, and the activated macrophages promote hepatocyte lipid accumulation and apoptosis via secretion of Interleukin-6(IL-6), Tumor Necrosis Factor α (TNFα), and Interleukin-1ß(IL-1ß), thereby leading to hepatic steatosis and inflammation. Finally, the therapeutic administration of antibody blocking GCA effectively halts the progression of MASH. Collectively, these findings implicate GCA as a crucial mediator of MASH and clarify a new metabolic signaling axis between the hepatocytes and macrophages, implying that GCA can emerge as a particularly interesting putative therapeutic target for reversing MASH progression.

Preparation of monoclonal antibody against rhoifolin and its application in enzyme-linked immunosorbent assay of rhoifolin and diosmin.

Both rhoifolin and diosmin belong to flavonoids, which are widely present in citrus. Diosmin is not only used in the medical field in the world, but also used as a dietary supplement in the United States. Rhoifolin has a similar structure to diosmin and also exhibits antioxidant and anti-inflammatory properties. In this study, an anti-rhoifolin monoclonal antibody was prepared and an indirect competitive enzyme-linked immunosorbent assay (icELISA) method was established. The half-maximal inhibitory concentration (IC50) of icELISA was determined to be 4.83 ng/mL, and the detection range was 0.97-33.87 ng/mL. The results of UPLC-MS/MS and icELISA generally demonstrate consistency. Moreover, by exploiting the cross-reactivity of the antibody, diosmin in tablets can be detected by icELISA. The results demonstrate that the developed method has good accuracy, reproducibility, and broad application prospects.

Highly sensitive detection of carbendazim in agricultural products using colorimetric and photothermal lateral flow immunoassay based on plasmonic gold nanostars.

The wide use and high toxicity of carbendazim (CBD) in agriculture pose unprecedented demands for convenient, sensitive, and cost-effective on-site monitoring. Herein, we propose a novel colorimetric and photothermal dual-mode lateral flow immunoassay (LFIA) based on plasmonic gold nanostars (AuNSs) for CBD detection in agricultural products. The AuNSs were synthesized via a rapid seed-mediated growth method (with growth time of ∼5 s). A stable immunoprobe was formed by adsorbing CBD antibodies onto AuNSs. This immunoprobe exhibited high conversion efficiency and sensitivity in photothermal detection with a low limit of detection (LOD) of 0.28 ng mL-1. The LOD of the colorimetric mode was higher (0.48 ng mL-1). The results of CBD detection in various agricultural products aligned well with ultra-performance liquid chromatography tandem mass spectrometry. Overall, our LFIA shows excellent sensitivity, specificity, reproducibility, and rapidness in CBD detection, and thus is a highly potential on-site platform in resource-limited environments.

Berberine suppressed the epithelial-mesenchymal transition (EMT) of colon epithelial cells through the TGF-ß1/Smad and NF-κB pathways associated with miRNA-1269a.

Objective: To explore the mechanisms of the TGF-ß1/Smad and NF-κB pathways in the effect of berberine (BBR) on colon cancer epithelial-mesenchymal transition (EMT) and their regulatory relationships with microRNAs (miRNAs). Methods: TGF-ß1 was used to induce EMT in normal colon epithelial HCoEpiC cells and colon cancer HT29 cells in vitro. After BBR intervention, the expression of EMT-related markers and the major molecules involved in the TGF-ß1/Smad and NF-κB pathways were detected via western blotting. Cell migration was detected via wound healing assays. SMAD2 and NF-κB p65 were overexpressed and transfected into cells, and the inhibitors SB431542 and BAY 11-7082 were added to block the TGF-ß1/Smad and NF-κB pathways, respectively. The mRNA expression levels of related microRNA genes were detected by using RT‒PCR. Results: Treatment with 10 ng/ml TGF-ß1 for 72 h significantly induced EMT in HCoEpiC and HT29 cells, which was repressed by BBR. BBR significantly inhibited the TGF-ß1-induced migration of HCoEpiC and HT29 cells and the TGF-ß1-promoted expression of p-Smad2/3, NF-κB p65, and p-IκBα. Compared to those in the group treated with TGF-ß1, the expression of NF-κB p65 and p-Smad2 in the group treated with NF-κB pathway inhibitor BAY 11-7082 was decreased (P < 0.05), and TGF-ß1 signalling inhibitor SB431542 significantly reduced the expression of NF-κB p65 (P < 0.05). Overexpression of NF-κB p65 and SMAD2 in HT29 cells decreased the expression of E-cadherin and caused a relative increase in N-cadherin. BBR mediated the expression profile of microRNAs in TGF-ß1-induced HCoEpiC cells, but this pattern differed from that in HT29 cells. SB431542 and BAY 11-7082 significantly reduced the mRNA level of miR-1269a in HCoEpiC and HT29 cells (P < 0.05). Overexpressed NF-κB p65 and SMAD2 increased the mRNA level of miR-1269a in both cell lines; however, this increase was significantly lower than that in the TGF-ß1 treatment group (P < 0.05). Conclusion: BBR can significantly inhibit TGF-ß1-induced EMT in normal and cancerous colon epithelial cells through the inhibition of the TGF-ß1/Smad and NF-κB p65 pathways. TGF-ß1/Smads can promote the NF-κB p65 pathway, which is a common target of miR-1269a, and can partially regulate the expression of miR-1269a.

Identification of programmed cell death-related genes and diagnostic biomarkers in endometriosis using a machine learning and Mendelian randomization approach.

Background: Endometriosis (EM) is a prevalent gynecological disorder frequently associated with irregular menstruation and infertility. Programmed cell death (PCD) is pivotal in the pathophysiological mechanisms underlying EM. Despite this, the precise pathogenesis of EM remains poorly understood, leading to diagnostic delays. Consequently, identifying biomarkers associated with PCD is critical for advancing the diagnosis and treatment of EM. Methods: This study used datasets from the Gene Expression Omnibus (GEO) to identify differentially expressed genes (DEGs) following preprocessing. By cross-referencing these DEGs with genes associated with PCD, differentially expressed PCD-related genes (DPGs) were identified. Enrichment analyses for KEGG and GO pathways were conducted on these DPGs. Additionally, Mendelian randomization and machine learning techniques were applied to identify biomarkers strongly associated with EM. Results: The study identified three pivotal biomarkers: TNFSF12, AP3M1, and PDK2, and established a diagnostic model for EM based on these genes. The results revealed a marked upregulation of TNFSF12 and PDK2 in EM samples, coupled with a significant downregulation of AP3M1. Single-cell analysis further underscored the potential of TNFSF12, AP3M1, and PDK2 as biomarkers for EM. Additionally, molecular docking studies demonstrated that these genes exhibit significant binding affinities with drugs currently utilized in clinical practice. Conclusion: This study systematically elucidated the molecular characteristics of PCD in EM and identified TNFSF12, AP3M1, and PDK2 as key biomarkers. These findings provide new directions for the early diagnosis and personalized treatment of EM.

Abnormal Degree Centrality in Zoster-Associated Pain with or Without Psychiatric Comorbidities: A Resting-State Functional MRI Study.

Purpose: Zoster-associated pain (ZAP) is frequently concomitant with psychiatric comorbidities. However, the underlying neuropathological mechanisms of ZAP with psychiatric comorbidities remain poorly understood. Patients and Methods: Rest-stating functional MRI (rs-fMRI) data from 41 ZAP patients without anxiety or depression (noA/D-ZAP), 11 ZAP patients with anxiety or depression (A/D-ZAP) and 29 healthy controls (HCs) were acquired. Degree centrality (DC) based on rs-fMRI was used to explore the node changes in the brain functional network in these subjects. Moreover, correlations and receiver operating characteristic curve analysis were performed. Results: One-way analysis of variance revealed abnormal DC values in the right middle frontal gyrus (MFG) and bilateral precuneus among the three groups. Compared with HCs, A/D-ZAP showed increased DC values in the bilateral pons, while noA/D-ZAP showed increased DC values in the right pons, left brainstem and rectal gyrus and decreased DC values in the right cingulate gyrus and bilateral precuneus. A/D-ZAP showed increased DC values in the left MFG and precentral gyrus (PG) compared with noA/D-ZAP. The DC value of the left pons in A/D-ZAP was positively correlated with the self-rating anxiety scale score. Areas under the curve of DC values in the left PG and MFG for distinguishing A/D-ZAP from the noA/D-ZAP group were 0.907 and 1.000, respectively. Conclusion: This study revealed the node differences in the brain functional network of ZAP patients with or without psychiatric comorbidities. In particular, abnormal DC values of the left MFG and PG may play an important role in the neuropathologic mechanism of the disease.

Development and validation of an integrated system for lung cancer screening and post-screening pulmonary nodules management: a proof-of-concept study (ASCEND-LUNG).

Background: In order to address the low compliance and dissatisfied specificity of low-dose computed tomography (LDCT), efficient and non-invasive approaches are needed to complement its limitations for lung cancer screening and management. The ASCEND-LUNG study is a prospective two-stage case-control study designed to evaluate the performance of a liquid biopsy-based comprehensive lung cancer screening and post-screening pulmonary nodules management system. Methods: We aimed to develop a comprehensive lung cancer system called Peking University Lung Cancer Screening and Management System (PKU-LCSMS) which comprises a lung cancer screening model to identify specific populations requiring LDCT and an artificial intelligence-aided (AI-aided) pulmonary nodules diagnostic model to classify pulmonary nodules following LDCT. A dataset of 465 participants (216 cancer, 47 benign, 202 non-cancer control) were used for the two models' development phase. For the lung cancer screening model development, cancer participants were randomly split at a ratio of 1:1 into the train and validation cohorts, and then non-cancer controls were age-matched to the cancer cases in a 1:1 ratio. Similarly, for the AI-aided pulmonary nodules model, cancer and benign participants were also randomly divided at a ratio of 2:1 into the train and validation cohorts. Subsequently, during the model validation phase, sensitivity and specificity were validated using an independent validation cohort consisting of 291 participants (140 cancer, 25 benign, 126 non-cancer control). Prospectively collected blood samples were analyzed for multi-omics including cell-free DNA (cfDNA) methylation, mutation, and serum protein. Computerized tomography (CT) images data was also obtained. Paired tissue samples were additionally analyzed for DNA methylation, DNA mutation, and messenger RNA (mRNA) expression to further explore the potential biological mechanisms. This study is registered with ClinicalTrials.gov, NCT04817046. Findings: Baseline blood samples were evaluated for the whole screening and diagnostic process. The cfDNA methylation-based lung cancer screening model exhibited the highest area under the curve (AUC) of 0.910 (95% CI, 0.869-0.950), followed by the protein model (0.891 [95% CI, 0.845-0.938]) and lastly the mutation model (0.577 [95% CI, 0.482-0.672]). Further, the final screening model, which incorporated cfDNA methylation and protein features, achieved an AUC of 0.963 (95% CI, 0.942-0.984). In the independent validation cohort, the multi-omics screening model showed a sensitivity of 99.2% (95% CI, 0.957-1.000) at a specificity of 56.3% (95% CI, 0.472-0.652). For the AI-aided pulmonary nodules diagnostic model, which incorporated cfDNA methylation and CT images features, it yielded a sensitivity of 81.1% (95% CI, 0.732-0.875), a specificity of 76.0% (95% CI, 0.549-0.906) in the independent validation cohort. Furthermore, four differentially methylated regions (DMRs) were shared in the lung cancer screening model and the AI-aided pulmonary nodules diagnostic model. Interpretation: We developed and validated a liquid biopsy-based comprehensive lung cancer screening and management system called PKU-LCSMS which combined a blood multi-omics based lung cancer screening model incorporating cfDNA methylation and protein features and an AI-aided pulmonary nodules diagnostic model integrating CT images and cfDNA methylation features in sequence to streamline the entire process of lung cancer screening and post-screening pulmonary nodules management. It might provide a promising applicable solution for lung cancer screening and management. Funding: This work was supported by Science, Science, Technology & Innovation Project of Xiongan New Area, Beijing Natural Science Foundation, CAMS Innovation Fund for Medical Sciences (CIFMS), Clinical Medicine Plus X-Young Scholars Project of Peking University, the Fundamental Research Funds for the Central Universities, Research Unit of Intelligence Diagnosis and Treatment in Early Non-small Cell Lung Cancer, Chinese Academy of Medical Sciences, National Natural Science Foundation of China, Peking University People's Hospital Research and Development Funds, National Key Research and Development Program of China, and the fundamental research funds for the central universities.

Effective Temporal Graph Learning via Personalized PageRank.

Graph representation learning aims to map nodes or edges within a graph using low-dimensional vectors, while preserving as much topological information as possible. During past decades, numerous algorithms for graph representation learning have emerged. Among them, proximity matrix representation methods have been shown to exhibit excellent performance in experiments and scale to large graphs with millions of nodes. However, with the rapid development of the Internet, information interactions are happening at the scale of billions every moment. Most methods for similarity matrix factorization still focus on static graphs, leading to incomplete similarity descriptions and low embedding quality. To enhance the embedding quality of temporal graph learning, we propose a temporal graph representation learning model based on the matrix factorization of Time-constrained Personalize PageRank (TPPR) matrices. TPPR, an extension of personalized PageRank (PPR) that incorporates temporal information, better captures node similarities in temporal graphs. Based on this, we use Single Value Decomposition or Nonnegative Matrix Factorization to decompose TPPR matrices to obtain embedding vectors for each node. Through experiments on tasks such as link prediction, node classification, and node clustering across multiple temporal graphs, as well as a comparison with various experimental methods, we find that graph representation learning algorithms based on TPPR matrix factorization achieve overall outstanding scores on multiple temporal datasets, highlighting their effectiveness.