A deep learning based multi-model approach for predicting drug-like chemical compound's toxicity.

Ensuring the safety and efficacy of chemical compounds is crucial in small-molecule drug development. In the later stages of drug development, toxic compounds pose a significant challenge, losing valuable resources and time. Early and accurate prediction of compound toxicity using deep learning models offers a promising solution to mitigate these risks during drug discovery. In this study, we present the development of several deep-learning models aimed at evaluating different types of compound toxicity, including acute toxicity, carcinogenicity, hERG_cardiotoxicity (the human ether-a-go-go related gene caused cardiotoxicity), hepatotoxicity, and mutagenicity. To address the inherent variations in data size, label type, and distribution across different types of toxicity, we employed diverse training strategies. Our first approach involved utilizing a graph convolutional network (GCN) regression model to predict acute toxicity, which achieved notable performance with Pearson R 0.76, 0.74, and 0.65 for intraperitoneal, intravenous, and oral administration routes, respectively. Furthermore, we trained multiple GCN binary classification models, each tailored to a specific type of toxicity. These models exhibited high area under the curve (AUC) scores, with an impressive AUC of 0.69, 0.77, 0.88, and 0.79 for predicting carcinogenicity, hERG_cardiotoxicity, mutagenicity, and hepatotoxicity, respectively. Additionally, we have used the approved drug dataset to determine the appropriate threshold value for the prediction score in model usage. We integrated these models into a virtual screening pipeline to assess their effectiveness in identifying potential low-toxicity drug candidates. Our findings indicate that this deep learning approach has the potential to significantly reduce the cost and risk associated with drug development by expediting the selection of compounds with low toxicity profiles. Therefore, the models developed in this study hold promise as critical tools for early drug candidate screening and selection.

Co-circulation of Hantavirus, Pathogenic Leptospira spp., and Bartonella spp. in Rodents in the Wanzhou Section of the Three Gorges Reservoir Region, 2021-2023.

Background: Rodent is a reservoir of various zoonotic pathogens. Wanzhou section of the Three Gorges reservoir region (TGRR) is a superior habitat for rodents, and the situation of rodent-borne zoonotic pathogens in this region has not been surveyed in recent years. Materials and Methods: Rodents were night trapped with mousecage or mousetrap in urban and surrounding towns' indoor or outdoor areas of the Wanzhou section of the TGRR, and nucleic acid was extracted from their lung or a mixture of liver, spleen, and kidney. Commercialized qPCR kits for pathogenic Leptospira spp., Rickettsia typhi, Anaplasma phagocytophilum, Bartonella spp., Orientia tsutsugamushi, and Francisella tularensis and qRT-PCR kits for hantavirus (HV), and severe fever with thrombocytopenia syndrome virus (SFTSV) were used for the detection of associated pathogens in collected rodents. Results: From 2021 to 2023, 604 rodents belonging to 10 species were collected. HV and pathogenic L. spp. were detected positive, with infection rates of 0.66% (4/604) and 1.32% (8/604), respectively. B. spp. were detected positive with an infection rate of 4.73% (19/402) in the rodents trapped in 2022 and 2023. Other five pathogens were all detected negative. Conclusion: This study showed that the Wanzhou section of the TGRR had HV, pathogenic L. spp., and B. spp. co-circulation in rodents. Hence, more attention should be paid to the prevention and control of associated rodent-borne diseases.

Synergistic effects of ceftazidime/avibactam combined with meropenem in a murine model of infection with KPC-producing Klebsiella pneumoniae.

OBJECTIVES: The emergence and expansion of carbapenem-resistant Klebsiella pneumoniae infections is a concern due to the lack of 'first-line' antibiotic treatment options. The ceftazidime/avibactam is an important clinical treatment for carbapenem-resistant K. pneumoniae infections but there is an increasing number of cases of treatment failure and drug resistance. Therefore, a potential solution is combination therapies that result in synergistic activity against K. pneumoniae carbapenemase: producing K. pneumoniae (KPC-Kp) isolates and preventing the emergence of KPC mutants resistant to ceftazidime/avibactam are needed in lieu of novel antibiotics. METHODS: To evaluate their synergistic activity, antibiotic combinations were tested against 26 KPC-Kp strains. Antibiotic resistance profiles, molecular characteristics and virulence genes were investigated by susceptibility testing and whole-genome sequencing. Antibiotic synergy was evaluated by in vitro chequerboard experiments, time-killing curves and dose-response assays. The mouse thigh model was used to confirm antibiotic combination activities in vivo. Additionally, antibiotic combinations were evaluated for their ability to prevent the emergence of ceftazidime/avibactam resistant mutations of blaKPC. RESULTS: The combination of ceftazidime/avibactam plus meropenem showed remarkable synergistic activity against 26 strains and restored susceptibility to both the partnering antibiotics. The significant therapeutic effect of ceftazidime/avibactam combined with meropenem was also confirmed in the mouse model and bacterial loads in the thigh muscle of the combination groups were significantly reduced. Furthermore, ceftazidime/avibactam plus meropenem showed significant activity in preventing the occurrence of resistance mutations. CONCLUSIONS: Our results indicated that the combination of ceftazidime/avibactam plus meropenem offers viable therapeutic alternatives in treating serious infections due to KPC-Kp.

SARS-CoV-2 NSP12 utilizes various host splicing factors for replication and splicing regulation.

The RNA-dependent RNA polymerase (RdRp) is a crucial element in the replication and transcription of RNA viruses. Although the RdRps of lethal human coronaviruses severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), SARS-CoV, and Middle East respiratory syndrome coronavirus (MERS-CoV) have been extensively studied, the molecular mechanism of the catalytic subunit NSP12, which is involved in pathogenesis, remains unclear. In this study, the biochemical and cell biological results demonstrate the interactions between SARS-CoV-2 NSP12 and seven host proteins, including three splicing factors (SLU7, PPIL3, and AKAP8). The entry efficacy of SARS-CoV-2 considerably decreased when SLU7 or PPIL3 was knocked out, indicating that abnormal splicing of the host genome was responsible for this occurrence. Furthermore, the polymerase activity and stability of SARS-CoV-2 RdRp were affected by the three splicing factors to varying degrees. In addition, NSP12 and its homologues from SARS-CoV and MERS-CoV suppressed the alternative splicing of cellular genes, which were influenced by the three splicing factors. Overall, our research illustrates that SARS-CoV-2 NSP12 can engage with various splicing factors, thereby impacting virus entry, replication, and gene splicing. This not only improves our understanding of how viruses cause diseases but also lays the foundation for the development of antiviral therapies.

Circ ubiquitin-like-containing plant homeodomain and RING finger domains protein 1 increases the stability of G9a and ubiquitin-like-containing plant homeodomain and RING finger domains protein 1 messenger RNA through recruiting eukaryotic translation initiation factor 4A3, transcriptionally inhibiting PDZ and homeobox protein domain protein 1, and promotes the metastasis of hepatocellular carcinoma.

BACKGROUND AND AIM: Circular ubiquitin-like, containing PHD and ring finger domains 1 (circUHRF1) is aberrantly upregulated in human hepatocellular carcinoma (HCC) tissues. However, the underlying molecular mechanisms remain obscure. The present study aimed at elucidating the interactive function of circUHRF1-G9a-ubiquitin-like, containing PHD and ring finger domains 1 (UHRF1) mRNA-eukaryotic translation initiation factor 4A3 (EIF4A3)-PDZ and LIM domain 1 (PDLIM1) network in HCC. METHODS: Expression of circUHRF1, mRNAs of G9a, UHRF1, PDLIM1, epithelial-mesenchymal transition (EMT)-related proteins, and Hippo-Yap pathway components was determined by quantitative polymerase chain reaction (Q-PCR), immunofluorescence, or Western blot analysis. Tumorigenic and metastatic capacities of HCC cells were examined by cellular assays including Cell Counting Kit-8, colony formation, wound healing, and transwell assays. Molecular interactions between EIF4A3 and UHRF1 mRNA were detected by RNA pull-down experiment. Complex formation between UHRF1 and PDLIM1 promoter was detected by chromatin immunoprecipitation assay. Co-immunoprecipitation was performed to examine the binding between UHRF1 and G9a. RESULTS: Circular ubiquitin-like, containing PHD and ring finger domains 1, G9a, and UHRF1 were upregulated, while PDLIM1 was downregulated in HCC tissue samples and cell lines. Cellular silencing of circUHRF1 repressed HCC proliferation, invasion, migration, and EMT. G9a formed a complex with UHRF1 and inhibited PDLIM1 transcription. CONCLUSION: Eukaryotic translation initiation factor 4A3 regulated circUHRF1 expression by binding to UHRF1 mRNA promoter. circUHRF1 increased the stability of G9a and UHRF1 mRNAs through recruiting EIF4A3. Overexpression of circUHRF1 aggravated HCC progression through Hippo-Yap pathway and PDLIM1 inhibition. By elucidating the molecular function of circUHRF1-G9a-UHRF1 mRNA-EIF4A3-PDLIM1 network, our data shed light on the HCC pathogenesis and suggest a novel therapeutic strategy for future HCC treatment.

Hybrid surgery management challenges of a Behcet's disease patient with recurrence of aortic aneurysms: a case report.

Background: Behcet's disease is a vasculitis of unknown origin that can involve multiple organs or tissues. Aneurysm or pseudoaneurysm, also one of the complications of Behcet's disease, is usually accompanied by a poor prognosis. Surgery is usually accompanied by a high risk of complications, such as the recurrence of anastomotic pseudoaneurysms and blockage of the target vessel. Using hybrid surgery, we successfully treated a complex and recurrent abdominal aortic pseudoaneurysm in a patient with BD. Methods: We report a 32-year-old female diagnosed with Behcet's disease with recurrent thoracoabdominal aortic aneurysm. Adequate immunotherapy was given during the perioperative period. The splanchnic artery branches were reconstructed, and the aneurysm was sequestered with endovascular repair. The patient recovered uneventfully and was discharged from the hospital 8 days after hybrid surgery. At the 60-month follow-up, no aneurysm was observed, the stent had no displacement or internal leakage, and the reconstructed blood vessels were unobstructed. Conclusion: Hybrid surgery could be a feasible and effective strategy for BD aneurysms. Adequate preoperative and postoperative immunotherapy with arterial anastomosis away from the diseased artery may be the key to success.

Comparative Study on Tuberculosis Drug Resistance and Molecular Detection Methods Among Different Mycobacterium Tuberculosis Lineages.

Purpose: This study aims to compare drug resistance and detection efficacy across different Mycobacterium tuberculosis lineages, offering insights for precise treatment and molecular diagnosis. Methods: 161 strains of Mycobacterium tuberculosis (M.tb) were tested for drug resistance using Phenotypic Drug Susceptibility Testing (pDST), High-Resolution Melting analysis (HRM), and Whole Genome Sequencing (WGS) methods. The main focus was on evaluating the accuracy of different methods for detecting resistance to rifampicin (RIF), isoniazid (INH), and streptomycin (SM). Results: Among the 161 strains of M.tb, 83.85% (135/161) were fully sensitive to RIF, INH, and SM according to pDST, and the rate of multidrug resistance was 4.35% (7/161). The drug resistance rates of lineage 2 M.tb to the three drugs (26/219, 11.87%) were significantly higher than those of non-lineage 2 M.tb (12/264, 4.45%) (P<0.05). Compared with pDST, WGS had a sensitivity of 100%, 94.12%, and 92.31% and a specificity of 100%, 99.31%, and 98.65% for RIF, INH, and SM, respectively, with no significant difference. The sensitivity of HRM for RIF, INH, and SM was 87.50%, 52.94%, and 76.92%, respectively, while the specificity was 96.08%, 99.31%, and 99.32%, respectively. The sensitivity of HRM for detecting INH resistance was significantly lower than that of pDST (P=0.039). Compared with HRM, WGS increased the sensitivity of RIF, INH, and SM by 12.50%, 41.18%, and 15.38%, respectively. Conclusion: There are significant differences in drug resistance rates among different lineages of M.tb, with lineage 2 having higher rates of RIF, INH, and SM resistance than lineages 3 and 4. The sensitivity of HRM is far lower than that of pDST, and currently, the accuracy of HRM is not sufficient to replace pDST. WGS has no significant difference in detecting drug resistance compared with pDST but can identify new anti-tuberculosis drug-resistant mutations, providing effective guidance for clinical decision-making.

New Interpretation of Neonatal Outcomes by Phenotypically Classified Preterm Syndrome: A Retrospective Cohort Study.

OBJECTIVE: The global aim to lower preterm birth rates has been hampered by the insufficient and incomplete understanding of its etiology, classification, and diagnosis. This study was designed to evaluate the association of phenotypically classified preterm syndromes with neonatal outcomes; to what extent would these outcomes be modified after the obstetric interventions, including use of glucocorticoid, magnesium sulfate, and progesterone. METHODS: This was a retrospective cohort study conducted at Tongji Hospital (composed of Main Branch, Optical Valley Branch and Sino-French New City Branch) in Wuhan. A total of 900 pregnant women and 1064 neonates were retrospectively enrolled. The outcomes were the distribution of different phenotypes among parturition signs and pathway to delivery, the association of phenotypically classified clusters with short-term unfavorable neonatal outcomes, and to what extent these outcomes could be modified by obstetric interventions. RESULTS: Eight clusters were identified using two-step cluster analysis, including premature rupture of fetal membranes (PPROM) phenotype, abnormal amniotic fluid (AF) phenotype, placenta previa phenotype, mixed condition phenotype, fetal distress phenotype, preeclampsia-eclampsia & hemolysis, elevated liver enzymes, and low platelets syndrome (PE-E&HELLP) phenotype, multiple fetus phenotype, and no main condition phenotype. Except for no main condition phenotype, the other phenotypes were associated with one or more complications, which conforms to the clinical practice. Compared with no main condition phenotype, some phenotypes were significantly associated with short-term adverse neonatal outcomes. Abnormal AF phenotype, mixed condition phenotype, PE-E&HELLP phenotype, and multiple fetus phenotype were risk factors for neonatal small-for gestation age (SGA); placenta previa phenotype was not associated with adverse outcomes except low APGAR score being 0-7 at one min; mixed condition phenotype was associated with low APGAR scores, SGA, mechanical ventilation, and grade HI-W intraventricular hemorrhage (IVH); fetal distress phenotype was frequently associated with neonatal SGA and mechanical ventilation; PE-E&HELLP phenotype was correlated with low APGAR score being 0-7 at one min, SGA and neonatal intensive care unit (NICU) admission; multiple fetus phenotype was not a risk factor for the outcomes included except for SGA. Not all neonates benefited from obstetric interventions included in this study. CONCLUSION: Our research disclosed the independent risk of different preterm phenotypes for adverse pregnancy outcomes. This study is devoted to putting forward the paradigm of classifying preterm birth phenotypically, with the ultimate purpose of defining preterm phenotypes based on multi-center studies and diving into the underlying mechanisms.

Gap junction is essential for the antidepressant effects of fluoxetine.

OBJECTIVES: Fluoxetine has been used as the first line for the therapy of depression. However, lack of therapeutic efficacy and time lag still limit the application of fluoxetine. Gap junction dysfunction is a potentially novel pathogenic mechanism for depression. To clarify the mechanism underlying these limitations, we investigated whether gap junction was related to the antidepressant effects of fluoxetine. METHODS AND KEY FINDINGS: After chronic unpredictable stress (CUS), animals showed decreases in gap junction intracellular communication (GJIC). Treatment with fluoxetine 10 mg/kg significantly improved GJIC and anhedonia of rats until six days. These results indicated that fluoxetine improved gap junction indirectly. Furthermore, to test the role of gap junction on antidepressant effects of fluoxetine, we blocked gap junction using carbenoxolone (CBX) infusion in the prefrontal cortex. CBX dampened fluoxetine-induced decrease in immobility time of mice in tail suspension test (TST). CONCLUSIONS: Our study suggested that gap junction dysfunction blocks antidepressant effects of fluoxetine, contributing to understanding the mechanism underlying the time lag of fluoxetine.

Simultaneous stabilization of Pb, Cd, and As in soil by rhamnolipid coated sulfidated nano zero-valent iron: Effects and mechanisms.

Sulfidation effectively improves the electron transfer efficiency of nanoscale zero-valent iron (nZVI), but decreases the specific surface area of nZVI. In this study, sulfidated nZVI (S-nZVI) coated with rhamnolipid (RL-S-nZVI) was synthesized and used to stabilize Pb, Cd, and As in combined polluted soil. The stabilization efficiency of 0.3% (wt) RL-S-nZVI to water soluble Pb, Cd, and As in soil reached 88.76%, 72%, and 63%, respectively. Rhamnolipid coating inhibited the reduction of specific surface area and successfully encapsulated nZVI, thus reducing the oxidation of Fe0. The types of iron oxides in RL-S-nZVI were reduced compared to S-nZVI, but the content and strength of Fe0 iron were obviously enhanced. Furthermore, rhamnolipid functional groups (-COOH and -COO-) were also involved in the stabilization process. In addition, the stabilization efficiency of RL-S-nZVI to the bioavailable Pb, Cd, and As in soil increased by 41%, 41%, and 50%, respectively, compared with nZVI. The presence of organic acids, especially citric acid, improved the stabilization efficiency of RL-S-nZVI to the three metals. The result of BCR sequential extraction indicated that RL-S-nZVI increased the residual state of Pb, Cd, and As and reduced the acid-soluble and reducible state after 28 days of soil incubation. XRD and XPS analyses showed that the stabilization mechanisms of RL-S-nZVI on heavy metals involved in ion exchange, surface complexation, adsorption, co-precipitation, chemisorption, and redox.

The association of dietary resistance starch intake with all-cause and cause-specific mortality.

Background: Several studies have estimated daily intake of resistant starch (RS), but no studies have investigated the relationship of RS intake with mortality. Objective: We aimed to examine associations between RS intake and all-cause and cause-specific mortality. Methods: Data from US National Health and Nutrition Examination Survey (NHANES) from 1999 to 2018 with 24-h dietary recall data was used in current study. The main exposure in this study was RS intake, and the main outcome was the mortality status of participants until December 31, 2019. The multivariable Cox proportional hazards regression models were developed to evaluate the hazard ratios (HRs) and 95% confidence interval (95% CI) of cardiovascular disease (CVD), cancer, and all-cause mortality associated with RS intake. Results: A total of 42,586 US adults [mean (SD) age, 46.91 (16.88) years; 22,328 (52.43%) female] were included in the present analysis. During the 454,252 person-years of follow-up, 7,043 all-cause deaths occurred, including 1,809 deaths from CVD and 1,574 deaths from cancer. The multivariable-adjusted HRs for CVD, cancer, and all-cause mortality per quintile increase in RS intake were 1 (95%CI, 0.97-1.04), 0.96 (95%CI, 0.93-1), and 0.96 (95%CI, 0.95-0.98), respectively. The associations remained similar in the subgroup and sensitivity analyses. Conclusion: Higher RS intake is significantly associated with lower cancer and all-cause mortality, but not significantly with CVD mortality. Future studies focusing on other populations with different food sources of RS and RS subtypes are needed to access the dose-response relationship and to improve global dietary recommendations.

Tumor necrosis factor-α inhibition restores matrix formation by human adipose-derived stem cells in the late stage of chondrogenic differentiation.

BACKGROUND: Cartilage tissue engineering is a promising strategy for treating cartilage damage. Matrix formation by adipose-derived stem cells (ADSCs), which are one type of seed cell used for cartilage tissue engineering, decreases in the late stage of induced chondrogenic differentiation in vitro, which seriously limits research on ADSCs and their application. AIM: To improve the chondrogenic differentiation efficiency of ADSCs in vitro, and optimize the existing chondrogenic induction protocol. METHODS: Tumor necrosis factor-alpha (TNF-α) inhibitor was added to chondrogenic culture medium, and then Western blotting, enzyme linked immunosorbent assay, immunofluorescence and toluidine blue staining were used to detect the cartilage matrix secretion and the expression of key proteins of nuclear factor kappa-B (NF-κB) signaling pathway. RESULTS: In this study, we found that the levels of TNF-α and matrix metalloproteinase 3 were increased during the chondrogenic differentiation of ADSCs. TNF-α then bound to its receptor and activated the NF-κB pathway, leading to a decrease in cartilage matrix synthesis and secretion. Blocking TNF-α with its inhibitors etanercept (1 µg/mL) or infliximab (10 µg/mL) significantly restored matrix formation. CONCLUSION: Therefore, this study developed a combination of ADSC therapy and targeted anti-inflammatory drugs to optimize the chondrogenesis of ADSCs, and this approach could be very beneficial for translating ADSC-based approaches to treat cartilage damage.

Bioassay-Guided Isolation of New Flavonoid Glycosides from Platanus × acerifolia Leaves and Their Staphylococcus aureus Inhibitory Effects.

Despite the rapid advances in drug R&D, there is still a huge need for antibacterial medications, specifically for the methicillin-resistant Staphylococcus aureus (MRSA). Inspired by the research where a viable class of MRSA inhibitors was found in the species Platanus occidentalis, a S. aureus inhibition screening-guided phytochemical reinvestigation on Platanus × acerifolia (London plane tree) leaves were performed with four flavonoid glycosides garnered, including two new compounds, quercetin-3-O-α-l-(2″-E-p-coumaroyl-3″-Z-p-coumaroyl)-rhamnopyranoside (E,Z-3'-hydroxyplatanoside, 1) and quercetin-3-O-α-l-(2″-Z-p-coumaroyl-3″-E-p-coumaroyl)-rhamnopyranoside (Z,E-3'-hydroxyplatanoside, 2). All of the isolates showed significant S. aureus ATCC 25904 inhibitory activity with MICs ranging from 4 to 64 µg/mL, suggesting the potential of discovering drug leads for the control of S. aureus from such a rich, urban landscaping plant in the Platanus genus.

Association between Mean Corpuscular Hemoglobin and Platelet Distribution Width Ratio and Knee Osteoarthritis Severity.

BACKGROUND: The goal was to simply and efficiently predict the indicators of disease severity in knee osteoarthritis (KOA) patients. METHODS: One hundred eighty-four patients with KOA and 126 healthy subjects were included. WOMAC (Western Ontario and McMaster Universities Osteoarthritis Index) was used as a reference index for disease severity in KOA patients, in which WOMAC < 80 was classified as mild and WOMAC ≥ 80 as moderate and severe. Blood routine parameters of the KOA and the healthy groups were analyzed by the Mann Whitney U test. Receiver operating characteristic curves were used to analyze the sensitivity and specificity of mean corpuscular hemoglobin and platelet distribution width ratio (MPR) and monocyte and hemoglobin ratio (MHR) indicators. The correlation between MPR and MHR and disease severity of KOA was determined by bivariate regression analysis. Independent predictors of disease severity in patients with KOA were assessed by multivariate regression analysis. RESULTS: MPR, MHR, and WOMAC were significantly higher in the KOA group. The ROC curve indicated that the cutoff values of MPR and MHR were 2.09 and 0.0030, respectively, with sensitivity of 86.4% and 68.5% and specificity of 99.2% and 79.4%. Bivariate regression analysis found that MPR was better correlated with disease severity than MHR. The results of multivariate regression analysis demonstrated that the MPR values of moderate and severe patients were more than 19 times that of mild patients, and the OR values were 21.695 and 19.558, respectively. CONCLUSIONS: MPR and MHR demonstrated a good correlation with disease severity in patients with KOA. MPR is a potential independent predictor of disease severity in patients with KOA.

A comparative and modeled approach for three biochar materials in simultaneously preventing the migration and reducing the bioaccessibility of heavy metals in soil: Revealing immobilization mechanisms.

The effectiveness and feasibility of the three biochar materials for remediation of arsenic (As) and lead (Pb) contaminated soil were explored in this study. Significant reduction of bioaccessibility and migration risks of both heavy metals have been explained mechanistically by incubation, column experiments and numerical simulation. Langmuir equation fitted As and Pb sorption isotherms better in the control and biochar (BC) amended soils, while Freundlich model was more suitable for iron modified biochar (Fe-BC) and sulfur/iron modified biochar (S/Fe-BC) amended soils, indicating that modified biochar promoted chemical adsorption process for As and Pb. For the three biochar materials, S/Fe-BC showed the best effects on reducing the bioavailability of As and Pb, with a decrease of 40.42%-64.21%. The reduction in bioaccessibility by metal portioning into available and non-available fractions was better for illustrating the mechanisms including adsorption, precipitation/coprecipitation and As(III) oxidation behind S/Fe-BC efficacy. Moreover, S/Fe-BC can effectively inhibit the leaching behavior of As and Pb under acid rain, which increased by 99.89% and 90.18%, respectively, compared with the control. The HYDRUS-1D modeling indicated that S/Fe-BC could continuously treat As (100 mg/L) and Pb (1000 mg/L) contaminated water for 16.22 years and 40.86 years, respectively, and ensure the groundwater quality criteria being met. Based on these insights, we believe that our study will provide meaningful information about the potentials of biochar derived materials for soil heavy metals' remediation.

Diagnostic study on clinical feasibility of an AI-based diagnostic system as a second reader on mobile CT images: a preliminary result.

Background: Artificial intelligence (AI) has breathed new life into the lung nodules detection and diagnosis. However, whether the output information from AI will translate into benefits for clinical workflow or patient outcomes in a real-world setting remains unknown. This study was to demonstrate the feasibility of an AI-based diagnostic system deployed as a second reader in imaging interpretation for patients screened for pulmonary abnormalities in a clinical setting. Methods: The study included patients from a lung cancer screening program conducted in Sichuan Province, China using a mobile computed tomography (CT) scanner which traveled to medium-size cities between July 10th, 2020 and September 10th, 2020. Cases that were suspected to have malignant nodules by junior radiologists, senior radiologists or AI were labeled a high risk (HR) tag as HR-junior, HR-senior and HR-AI, respectively, and included into final analysis. The diagnosis efficacy of the AI was evaluated by calculating negative predictive value and positive predictive value when referring to the senior readers' final results as the gold standard. Besides, characteristics of the lesions were compared among cases with different HR labels. Results: In total, 251/3,872 patients (6.48%, male/female: 91/160, median age, 66 years) with HR lung nodules were included. The AI algorithm achieved a negative predictive value of 88.2% [95% confidence interval (CI): 62.2-98.0%] and a positive predictive value of 55.6% (95% CI: 49.0-62.0%). The diagnostic duration was significantly reduced when AI was used as a second reader (223±145.6 vs. 270±143.17 s, P<0.001). The information yielded by AI affected the radiologist's decision-making in 35/145 cases. Lesions of HR cases had a higher volume [309.9 (214.9-732.5) vs. 141.3 (79.3-380.8) mm3, P<0.001], lower average CT number [-511.0 (-576.5 to -100.5) vs. -191.5 (-487.3 to 22.5), P=0.010], and pure ground glass opacity rather than solid. Conclusions: The AI algorithm had high negative predictive value but low positive predictive value in diagnosing HR lung lesions in a clinical setting. Deploying AI as a second reader could help avoid missed diagnoses, reduce diagnostic duration, and strengthen diagnostic confidence for radiologists.

[Clinical Application of "Three-Low" Technique Combined with Artificial Intelligence Iterative Reconstruction Algorithm in Aortic CT Angiography].

Objective: To explore the application value of the "three-low" technique (low radiation dose, low contrast agent dosage and low contrast agent flow rate) combined with artificial intelligence iterative reconstruction (AIIR) in aortic CT angiography (CTA). Methods: A total of 33 patients who underwent aortic CTA were prospectively enrolled. Based on the time of their follow-up examinations, the imaging data were divided into Group A and Group B, with Group A being the control group (100 kV, 0.8 mL/kg, 5 mL/s) and Group B being the "three-low" technique group (70 kV, 0.5 mL/kg, 3 mL/s). In group A, the images were reconstructed by Karl iterative algorithm. Group B was divided into B1 and B2 subgroups, with their images being reconstructed by Karl iterative algorithm and AIIR, respectively. The CT and SD values of the ascending aorta, descending aorta, abdominal aorta, left common iliac artery and right common iliac artery were measured, and the signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) were calculated. The subjective scoring of image quality was performed. The radiation dose parameters were documented. Results: Differences in the CT value, SD value, SNR and CNR of the three groups were statistically significant ( P<0.001). The CT value, SNR and CNR of group B2 were significantly higher than those of group B1, while the SD value of group B2 was significantly lower than that of group B1 ( P<0.017). There was no significant difference between the CT values of group A and those of group B2 ( P>0.017). The SD values, SNR and CNR in group B2 were better than those in group A ( P>0.017). There was significant difference in the subjective evaluation of image quality among the three groups ( P<0.05), but there was no significant difference between group A and group B2 ( P>0.017). The radiation dose and contrast medium dosage in group B decreased 84.14% and 37.08%, respectively, compared with those of group A. Conclusion: With the "three-low" technique combined with AIIR algorithm, the image quality of aortic CTA obtained is comparable to that of conventional dose scanning, while the radiation dose, contrast agent dosage and contrast agent flow rate of patients are significantly reduced.

Is biochar a reliable catalyst for activating peroxydisulfate? Damage of biochar during catalytic process.

The unsatisfactory reuse performance of biochar in the catalytic system has become an important factor limiting its application. Damage of biochar in the catalytic systems has been reported, but the mechanism of damage is still unclear. In this study, cotton stalk and walnut shell biochar were used to activate peroxydisulfate (PDS) for sulfamethazine degradation, and multiple characterization methods were used to determine the damage of biochar. The comparative experiments of biochar, recycled biochar, and the biochar treated by PDS in catalytic reaction showed that the performance of biochars decreased by 37.5%-65.3%. After the catalytic reaction, the unstable carbon in biochar was lost, and the biochar surface was oxidized, which reduced its affinity to organic matter. CO2 physisorption showed that the pore structure of biochars barely changed. However, for walnut shell biochar, its adsorption capacity of nitrogen decreased obviously. Moreover, the electrochemical tests showed that the conductivity of walnut shell biochar decreased, which would lead to the reduction of its catalytic performance through the electron transfer path. Overall, the effects of catalytic process on the performance of biochar cannot be ignored. Therefore, more efforts are needed to improve the stability and homogeneity of biochar as an efficient and sustainable PDS activator.

Amniotic membrane for covering high myopic macular hole associated with retinal detachment following failed primary surgery.

AIM: To evaluate the therapeutic effect of amniotic membrane (AM) for covering high myopic macular hole associated with retinal detachment following failed primary surgery. METHODS: Seventeen eyes of 17 patients whose axial length was more than 29 mm suffered from macular hole (MH) or MH associated with retinal detachment (RD), and had previously surgery of pars plana vitrectomy (PPV) with internal limiting membrane (ILM) peeling and silicone oil (SO) tamponade. Half a year after the surgery, optical coherence tomography (OCT) showed that MH did not heal in all 17 eyes and RD was still maintained in 13 eyes of these 17 eyes. We performed SO removal combined with AM covering on macular area and C3F8 tamponade, and phacoemulsification combined with intraocular lens implantation simultaneously cataract eyes. We followed up these patients for one year. RESULTS: In all 17 eyes, SO was removed successfully, MHs were healed and RDs were reattached. One eye (5.89%, 1/17) had AM shifted half a month after surgery and underwent a second surgery to adjust the position of the AM and supplement C3F8. After surgery, the visual acuity (VA) improved in 15 eyes (88.24%, 15/17), no change in two eyes (11.76%, 2/17). No serious complications occurred in all eyes. CONCLUSION: AM covering is helpful to rescue the previous failure surgery of high myopic MH.

HDAC4 promotes the growth and metastasis of gastric cancer via autophagic degradation of MEKK3.

BACKGROUND: Histone deacetylases (HDACs) have been shown to be involved in tumorigenesis, but their precise role and molecular mechanisms in gastric cancer (GC) have not yet been fully elucidated. METHODS: Bioinformatics screening analysis, qRT-PCR, and immunohistochemistry (IHC) were used to identify the expression of HDAC4 in GC. In vitro and in vivo functional assays illustrated the biological function of HDAC4. RNA-seq, GSEA pathway analysis, and western blot revealed that HDAC4 activated p38 MAPK signalling. Immunofluorescence, western blot, and IHC verified the effect of HDAC4 on autophagy. ChIP and dual-luciferase reporter assays demonstrated that the transcriptional regulation mechanism of HDAC4 and ATG4B. RESULTS: HDAC4 is upregulated in GC and correlates with poor prognosis. In vitro and in vivo assays showed that HDAC4 contributes to the malignant phenotype of GC cells. HDAC4 inhibited the MEF2A-driven transcription of ATG4B and prevented MEKK3 from p62-dependent autophagic degradation, thus activating p38 MAPK signalling. Reciprocally, the downstream transcription factor USF1 enhanced HDAC4 expression by regulating HDAC4 promoter activity, forming a positive feedback loop and continuously stimulating HDAC4 expression and p38 MAPK signalling activation. CONCLUSION: HDAC4 plays an oncogenic role in GC, and HDAC4-based targeted therapy would represent a novel strategy for GC treatment.