Lung microbial and host genomic signatures as predictors of prognosis in early-stage adenocarcinoma.

BACKGROUND: Risk of early-stage lung adenocarcinoma (LUAD) recurrence after surgical resection is significant, and post-recurrence median survival is approximately two years. Currently there are no commercially available biomarkers that predict recurrence. Here, we investigated whether microbial and host genomic signatures in the lung can predict recurrence. METHODS: In 91 early-stage (Stage IA/IB) LUAD-patients with extensive follow-up, we used 16s rRNA gene sequencing and host RNA-sequencing to map the microbial and host transcriptomic landscape in tumor and adjacent unaffected lung samples. RESULTS: 23 out of 91 subjects had tumor recurrence over 5-year period. In tumor samples, LUAD recurrence was associated with enrichment with Dialister, Prevotella, while in unaffected lung, recurrence was associated with enrichment with Sphyngomonas and Alloiococcus. The strengths of the associations between microbial and host genomic signatures with LUAD recurrence were greater in adjacent unaffected lung samples than in the primary tumor. Among microbial-host features in the unaffected lung samples associated with recurrence, enrichment with Stenotrophomonas geniculata and Chryseobacterium were positively correlated with upregulation of IL-2, IL-3, IL-17, EGFR, HIF-1 signaling pathways among the host transcriptome. In tumor samples, enrichment with Veillonellaceae Dialister, Ruminococcacea, Haemophilus Influenza, and Neisseria were positively correlated with upregulation of IL-1, IL-6, IL17, IFN, and Tryptophan metabolism pathways. CONCLUSIONS: Overall, modeling suggested that a combined microbial/transcriptome approach using unaffected lung samples had the best biomarker performance (AUC=0.83). IMPACT: This study suggests that LUAD recurrence is associated with distinct pathophysiological mechanisms of microbial-host interactions in the unaffected lung rather than those present in the resected tumor.

Mechanisms and treatments of methamphetamine and HIV-1 co-induced neurotoxicity: a systematic review.

Combination antiretroviral therapy (cART) has dramatically reduced mortality in people with human immunodeficiency virus (HIV), but it does not completely eradicate the virus from the brain. Patients with long-term HIV-1 infection often show neurocognitive impairment, which severely affects the quality of life of those infected. Methamphetamine (METH) users are at a significantly higher risk of contracting HIV-1 through behaviors such as engaging in high-risk sex or sharing needles, which can lead to transmission of the virus. In addition, HIV-1-infected individuals who abuse METH exhibit higher viral loads and more severe cognitive dysfunction, suggesting that METH exacerbates the neurotoxicity associated with HIV-1. Therefore, this review focuses on various mechanisms underlying METH and HIV-1 infection co-induced neurotoxicity and existing interventions targeting the sigma 1 receptor, dopamine transporter protein, and other relevant targets are explored. The findings of this review are envisaged to systematically establish a theoretical framework for METH abuse and HIV-1 infection co-induced neurotoxicity, and to suggest novel clinical treatment targets.

Dipolar Huygens-Kerker radiation for surface waves.

Exotic dipolar radiation with zero light emission in one direction but maximal light emission in the opposite direction was envisioned by Huygens in 1690, and it could emerge in vacuum if the ratio between the source's electric and magnetic dipole moments fulfills the Kerker condition as revealed by Kerker in 1983. Due to its intricate connection with both the Huygens principle and Kerker condition, this radiation phenomenon is suggested to be termed as dipolar Huygens-Kerker radiation, and at this moment, the ratio is termed as the Huygens-Kerker ratio. However, the dipolar Huygens-Kerker radiation remains underexplored in non-vacuum matters, inside which the source locates, especially for surface waves. Here we find that the dipolar Huygens-Kerker radiation of surface waves in principle could occur in non-vacuum matters and is essentially featured with the same normalized radiation pattern, which is closely related to the inclination factor that appears in the Fresnel-Kirchhoff diffraction theory. Moreover, the corresponding Huygens-Kerker ratio is intrinsically determined by the phase velocity of excited surface waves. To be specific, the Huygens-Kerker ratio is proportional to the phase velocity for transverse-magnetic surface waves but becomes inversely proportional to the phase velocity for transverse-electric surface waves.

Diabetes Distress and Associated Factors Among Chinese Americans with Type 2 Diabetes in New York City.

Purpose: The purpose of this study is to describe diabetes distress and related factors among Chinese Americans with type 2 diabetes in New York City (NYC). Methods: We conducted a secondary data analysis of the baseline data from three research studies conducted among community-dwelling Chinese American adults with type 2 diabetes. Diabetes Distress Scale (DDS) was used to measure sources of diabetes distress including emotional-, regimen-, interpersonal-, and physician-related distress. A score of 2 or greater indicates moderate diabetes distress or higher. Patient Health Questionnaire-2 (PHQ-2) was used to measure depressive symptoms. Participants' sociodemographic information was also collected. Descriptive statistics were used to describe diabetes distress, and logistic least absolute shrinkage and selection operator (LASSO) regression was used to examine factors associated with diabetes distress level. Results: Data from 178 participants (mean age 63.55±13.56 years) were analyzed. Most participants were married (76.40%), had a high school degree or less (65.73%), had a household annual income < $25,000 (70.25%), and reported limited English proficiency (93.22%). About 25.84% reported moderate or higher overall distress. The most common sources of distress were emotional burden (29.78%), followed by regimen- (28.65%), interpersonal- (18.54%), and physician-related distress (14.04%). Participants who were younger, female, limited English proficient, and had elevated depressive symptoms were more likely to have higher diabetes distress. Conclusion: Diabetes distress is prevalent among Chinese immigrants with type 2 diabetes, especially emotional- and regimen-related distress. Given the known link between diabetes distress and poor glycemic control, it is critical to screen for diabetes distress at primary care clinics and incorporate psychological counseling in diabetes care in this underserved population.

Enhancing the therapeutic potential of P29 protein-targeted monoclonal antibodies in the management of alveolar echinococcosis through CDC-mediated mechanisms.

Alveolar echinococcosis (AE) is a highly lethal helminth infection. Current chemotherapeutic strategies for AE primarily involve the use of benzimidazoles (BZs) such as mebendazole (MDZ) and albendazole (ABZ), which exhibit limited efficacy. In a previous study, the vaccine of recombinant Echinococcus granulosus P29 (rEgP29) showed significant immunoprotection against E. granulosus in both mice and sheep. In the current study, we utilized hybridoma technology to generate five monoclonal antibodies (mAbs) against P29, among which 4G10F4 mAb exhibited the highest antigen-specific binding capacity. This mAb was selected for further investigation of anti-AE therapy, both in vivo and in vitro. In vitro, 4G10F4 inhibited a noteworthy inhibition of E. multilocularis protoscoleces and primary cells viability through complement-dependent cytotoxicity (CDC) mechanism. In vivo, two experiments were conducted. In the first experiment, mice were intraperitoneally injected with Em protoscoleces, and subsequently treated with 4G10F4 mAb (2.5/5/10 mg/kg) at 12 weeks postinfection once per week for 8 times via tail vein injection. Mice that were treated with 4G10F4 mAb only in dosage of 5mg/kg exhibited a significant lower mean parasite burden (0.89±0.97 g) compared to isotype mAb treated control mice (2.21±1.30 g). In the second experiment, mice were infected through hepatic portal vein and treated with 4G10F4 mAb (5mg/kg) at one week after surgery once per week for 8 times. The numbers of hepatic metacestode lesions of the 4G10F4 treatment group were significantly lower in comparison to the isotype control group. Pathological analysis revealed severe disruption of the inner structure of the metacestode in both experiments, particularly affecting the germinal and laminated layers, resulting in the transformation into infertile vesicles after treatment with 4G10F4. In addition, the safety of 4G10F4 for AE treatment was confirmed through assessment of mouse weight and evaluation of liver and kidney function. This study presents antigen-specific monoclonal antibody immunotherapy as a promising therapeutic approach against E. multilocularis induced AE.

BRAF-V600E mutations in plasma and peripheral blood mononuclear cells correlate with prognosis of pediatric Langerhans cell histiocytosis treated with first-line therapy.

BACKGROUND: The clinical relevance of BRAF-V600E alleles in peripheral blood mononuclear cells (PBMCs) and the prognostic impact of the mutants in cell-free (cf) and PBMC DNAs of Langerhans cell histiocytosis (LCH) have not been fully clarified in pediatric LCH. METHODS: We retrospectively determined the levels of BRAF-V600E mutation in paired plasma and PBMC samples at the time of diagnosis of LCH. Subsequently, we performed a separate or combined analysis of the clinical and prognostic impact of the mutants. RESULTS: We assessed BRAF-V600E mutation in peripheral blood from 94 patients of childhood LCH. Our data showed that cfBRAF-V600E was related to young age, multiple-system (MS) disease, involvements of organs with high risk, increased risk of relapse, and worse progression-free survival (PFS) of patients. We also observed that the presence of BRAF-V600E in PBMCs at baseline was significantly associated with MS LCH with risk organ involvement, younger age, and disease progression or relapse. The coexisting of plasma(+)/PBMC(+) identified 36.2% of the patients with the worst outcome, and the hazard ratio was more significant than either of the two alone or neither, indicating that combined analysis of the mutation in plasma and PBMCs was more accurate to predict relapse than evaluation of either one. CONCLUSIONS: Concurrent assessment of BRAF-V600E mutation in plasma and PBMCs significantly impacted the prognosis of children with LCH. Further prospective studies with larger cohorts need to validate the results of this study.

Multiomics Assessment of the Gut Microbiome in Rare Hyperoxaluric Conditions.

Introduction: Hyperoxaluria is a risk factor for kidney stone formation and chronic kidney disease progression. The microbiome is an important protective factor against oxalate accumulation through the activity of its oxalate-degrading enzymes (ODEs). In this cross-sectional study, we leverage multiomics to characterize the microbial community of participants with primary and enteric hyperoxaluria, as well as idiopathic calcium oxalate kidney stone (CKS) formers, focusing on the relationship between oxalate degrading functions of the microbiome. Methods: Patients diagnosed with type 1 primary hyperoxaluria (PH), enteric hyperoxaluria (EH), and CKS were screened for inclusion in the study. Participants completed a food frequency questionnaire recording their dietary oxalate content while fecal oxalate levels were ascertained. DNA and RNA were extracted from stool samples and sequenced. Metagenomic (MTG) and metatranscriptomic (MTT) data were processed through our bioinformatics pipelines, and microbiome diversity, differential abundance, and networks were subject to statistical analysis in relationship with oxalate levels. Results: A total of 38 subjects were recruited, including 13 healthy participants, 12 patients with recurrent CKS, 8 with PH, and 5 with EH. Urinary and fecal oxalate were significantly higher in the PH and the EH population compared to healthy controls. At the community level, alpha-diversity and beta-diversity indices were similar across all populations. The respective contributions of single bacterial species to the total oxalate degradative potential were similar in healthy and PH subjects. MTT-based network analysis identified the most interactive bacterial network in patients with PH. Patients with EH had a decreased abundance of multiple major oxalate degraders. Conclusion: The composition and inferred activity of oxalate-degrading microbiota were differentially associated with host clinical conditions. Identifying these changes improves our understanding of the relationships between dietary constituents, microbiota, and oxalate homeostasis, and suggests new therapeutic approaches protecting against hyperoxaluria.

The impact of climate policy uncertainty on corporate pollution Emissions--Evidence from China.

Climate change is considered one of the major systemic risks facing the world in the 21st century. To address climate change, China has adopted a series of climate policies, but the uncertainty brought about by frequent climate policy issuance has increased pressure on enterprises, which may not be conducive to enterprises reducing emissions. This paper uses data on 1211 listed companies on the A-share market in China from 2012 to 2022 to study the impact of climate policy uncertainty on enterprise pollutant emissions. The research findings show that climate policy uncertainty increases corporate pollution emissions; climate policy uncertainty mainly generates negative impacts on enterprise environmental regulation, social responsibility, and R&D investment, thereby negatively affecting enterprise emissions reduction. Further heterogeneity analysis shows that climate policy uncertainty in China has a more significant impact on non-state-owned enterprises, technology-intensive enterprises, lightly polluting enterprises, and enterprises in western regions. These findings emphasize the importance of enterprise social responsibility, environmental regulation, and R&D investment in enterprise emissions reduction and provide policy implications for Chinese enterprises to optimize their energy-saving and emission reduction strategies in the face of climate policy uncertainty.

A SIMPLE, QUICK, AND ECONOMICAL METHOD FOR IN VITRO CULTIVATION OF ECHINOCOCCUS MULTILOCULARIS METACESTODE AND GENERATION OF PRIMARY CELLS.

Alveolar echinococcosis is considered to be one of the most potentially lethal parasitic zoonotic diseases. However, the molecular mechanisms by which Echinococcus multilocularis interacts with hosts are poorly understood, hindering the prevention and treatment of this disease. Due to the great advantages of cell culture systems for molecular research, numerous attempts have been made to establish primary cell cultures for E. multilocularis. In this study we developed a simple, rapid, and economical method that allows E. multilocularis metacestode tissue blocks to generate daughter vesicles without the continuous presence of host feeder cells in a regular medium. We performed anaerobic, hypoxic (1% O2), normoxic, and semi-anaerobic (in sealed tubes) cultures and found that E. multilocularis metacestode tissues can produce daughter vesicles only in the sealed tubes after 4 wk of incubation. The daughter vesicles cultivated in this system were remarkably enlarged under anaerobic conditions after 8 days of culture, whereas vesicles cultured under hypoxic (1% O2) and normoxic conditions showed only a mild increase in volume. Our in vitro cultivated vesicles showed strong viability and could be used to test antiparasitic drugs, isolate primary cells, and infect animals.

Identification of the circRNA-miRNA-mRNA network for treating methamphetamine-induced relapse and behavioral sensitization with cannabidiol.

AIMS: This study aims to investigate the pharmacological effects and the underlying mechanism of cannabidiol (CBD) on methamphetamine (METH)-induced relapse and behavioral sensitization in male mice. METHODS: The conditioned place preference (CPP) test with a biased paradigm and open-field test were used to assess the effects of CBD on METH-induced relapse and behavioral sensitization in male mice. RNA sequencing and bioinformatics analysis was employed to identify differential expressed (DE) circRNAs, miRNAs, and mRNAs in the nucleus accumbens (NAc) of mice, and the interaction among them was predicted using competing endogenous RNAs (ceRNAs) network analysis. RESULTS: Chronic administration of CBD (40 mg/kg) during the METH withdrawal phase alleviated METH (2 mg/kg)-induced CPP reinstatement and behavioral sensitization in mice, as well as mood and cognitive impairments following behavioral sensitization. Furthermore, 42 DEcircRNAs, 11 DEmiRNAs, and 40 DEmRNAs were identified in the NAc of mice. The circMeis2-miR-183-5p-Kcnj5 network in the NAc of mice is involved in the effects of CBD on METH-induced CPP reinstatement and behavioral sensitization. CONCLUSIONS: This study constructed the ceRNAs network for the first time, revealing the potential mechanism of CBD in treating METH-induced CPP reinstatement and behavioral sensitization, thus advancing the application of CBD in METH use disorders.

LADRC-based grid-connected control strategy for single-phase LCL-type inverters.

To ensure that grid-connected currents are of high quality, it is crucial to optimize the dynamic performance of grid-connected inverters and their control. This study suggests using a combination of reduced-order linear active disturbance rejection control (LADRC) and a Proportional-Integral (PI) controller. By applying this control strategy to a single-phase photovoltaic grid-connected system, the system's ability to suppress grid harmonics is significantly improved. The validity and effectiveness of this control approach have been confirmed through simulations and experiments. The results show that the LADRC-based control system is robust and capable of rejecting disturbances, resulting in a significant reduction in the Total Harmonic Distortion (THD) of grid-connected currents. Comparative analysis with traditional control methods demonstrates the superior performance of the proposed approach.

Forkhead box E1, frequently downregulted by promoter methylation, inhibits colorectal cancer cell growth and migration.

Forkhead box E1 (FOXE1), also known as thyroid transcription factor 2 (TTF-2), belongs to a large family of forkhead transcription factors. It plays important roles in embryogenesis, cell growth, and differentiation. Cancer-specific FOXE1 hypermethylation events have been identified in several cancers. However, the expression and function of FOXE1 in the tumorigenesis of colorectal cancer remain still unknown. In this study, we examined FOXE1 expression and methylation in normal colon mucosa, colorectal cancer (CRC) cell lines, and primary tumors by immunohistochemistry, semi-quantitative RT-PCR, methylation-specific PCR, and bisulfite genomic sequencing. We found that FOXE1 was frequently methylated and silenced in CRC cell lines and was downregulated in CRC tissues compared with paired adjacent non-tumor tissues. Meanwhile, low FOXE1 expression was significantly correlated with lymph node metastasis and advanced TNM stages, indicating its potential as a tumor marker. Subsequently, we established colon cancer cell lines with stable FOXE1 expression to observe the biological effect on colorectal cancer, including cell growth, migration, actin cytoskeleton, and growth of human colorectal xenografts in nude mice. Ectopic expression of FOXE1 could suppress tumor cell growth and migration and affect the organization of the actin cytoskeleton together with suppressing tumorigenicity in vivo. FOXE1 methylation was frequently seen in association with a complete absence of or downregulated gene expression, and FOXE1 plays a suppressive role in the development and progression of colorectal cancer.

Genetic Landscape and Its Prognostic Impact in Children With Langerhans Cell Histiocytosis.

CONTEXT.­: Langerhans cell histiocytosis (LCH) is a rare myeloid neoplasm that predominantly affects young children. OBJECTIVE.­: To investigate genetic alterations and their correlation with clinical characteristics and prognosis in pediatric LCH. DESIGN.­: We performed targeted sequencing to detect mutations in LCH lesions from pediatric patients. RESULTS.­: A total of 30 genomic alterations in 5 genes of the MAPK pathway were identified in 187 of 223 patients (83.9%). BRAF V600E (B-Raf proto-oncogene, serine/threonine kinase) was the most common mutation (51.6%), followed by MAP2K1 (mitogen-activated protein kinase kinase 1) alterations (17.0%) and other BRAF mutations (13.0%). ARAF (A-Raf proto-oncogene, serine/threonine kinase) and KRAS (KRAS proto-oncogene, GTPase) mutations were relatively rare (2.2% and 0.9%, respectively). Additionally, FNBP1 (formin-binding protein 1)::BRAF fusion and MAP3K10 (mitogen-activated protein kinase kinase 10) mutations A17T and R823C were identified in 1 case each, with possible constitutive activation of ERK1/2 phosphorylation. BRAF V600E was more frequent in patients with risk organ involvement, while MAP2K1 mutation was more prevalent in patients with single-system LCH (P = .001). BRAF V600E was associated with craniofacial bone, skin, liver, spleen, and ear involvement (all P < .05). Patients with other BRAF mutations had a higher proportion of spinal column involvement (P = .006). Univariate analysis showed a significant difference in progression-free survival among the 4 molecular subgroups for patients treated with first-line therapy (P = .02). According to multivariate analysis, risk organ involvement was the strongest independent adverse prognostic factor (hazard ratio, 8.854; P < .001); BRAF or MAP2K1 mutation was not an independent prognostic factor. CONCLUSIONS.­: Most pediatric patients with LCH carry somatic mutations involving the MAPK pathway, correlating with clinical characteristics and outcomes for first-line chemotherapy.

The plasma-soluble CSF1R level is a promising prognostic indicator for pediatric Langerhans cell histiocytosis.

Langerhans cell histiocytosis (LCH) is a rare hematologic neoplasm characterized by the clonal proliferation of Langerhans-like cells. Colony-stimulating factor 1 receptor (CSF1R) is a membrane-bound receptor that is highly expressed in LCH cells and tumor-associated macrophages. In this study, a soluble form of CSF1R protein (sCSF1R) was identified by plasma proteome profiling, and its role in evaluating LCH prognosis was explored. We prospectively measured plasma sCSF1R levels in 104 LCH patients and 10 healthy children using ELISA. Plasma sCSF1R levels were greater in LCH patients than in healthy controls (p < .001) and significantly differed among the three disease extents, with the highest level in MS RO+ LCH patients (p < .001). Accordingly, immunofluorescence showed the highest level of membrane-bound CSF1R in MS RO+ patients. Furthermore, the plasma sCSF1R concentration at diagnosis could efficiently predict the prognosis of LCH patients treated with standard first-line treatment (AUC = 0.782, p < .001). Notably, dynamic monitoring of sCSF1R levels could predict relapse early in patients receiving BRAF inhibitor treatment. In vitro drug sensitivity data showed that sCSF1R increased resistance to Ara-C in THP-1 cells expressing ectopic BRAF-V600E. Overall, the plasma sCSF1R level at diagnosis and during follow-up is of great clinical importance in pediatric LCH patients.

Correlation between NGS panel-based mutation results and clinical information in colorectal cancer patients.

Early mutation identification guides patients with colorectal cancer (CRC) toward targeted therapies. In the present study, 414 patients with CRC were enrolled, and amplicon-based targeted next-generation sequencing (NGS) was then performed to detect genomic alterations within the 73 cancer-related genes in the OncoAim panel. The overall mutation rate was 91.5 % (379/414). Gene mutations were detected in 38/73 genes tested. The most frequently mutated genes were TP53 (60.9 %), KRAS (46.6 %), APC (30.4 %), PIK3CA (15.9 %), FBXW7 (8.2 %), SMAD4 (6.8 %), BRAF (6.5 %), and NRAS (3.9 %). Compared with the wild type, TP53 mutations were associated with low microsatellite instability/microsatellite stability (MSI-L/MSS) (P = 0.007), tumor location (P = 0.043), and histological grade (P = 0.0009); KRAS mutations were associated with female gender (P = 0.026), distant metastasis (P = 0.023), TNM stage (P = 0.013), and histological grade (P = 0.004); APC mutations were associated with patients <64 years of age at diagnosis (P = 0.04); PIK3CA mutations were associated with tumor location (P = 4.97e-06) and female gender (P = 0.018); SMAD4 mutations were associated with tumor location (P = 0.033); BRAF mutations were associated with high MSI (MSI-H; P = 6.968e-07), tumor location (P = 1.58e-06), and histological grade (P = 0.04). Mutations in 164 individuals were found to be pathogenic or likely pathogenic. A total of 26 patients harbored MSI-H tumors and they all had at least one detected gene mutation. Mutated genes were enriched in signaling pathways associated with CRC. The present findings have important implications for improving the personalized treatment of patients with CRC in China.

Effects of extreme temperatures on public sentiment in 49 Chinese cities.

The rising sentiment challenges of the metropolitan residents may be attributed to the extreme temperatures. However, nationwide real-time empirical studies that examine this claim are rare. In this research, we construct a daily extreme temperature index and sentiment metric using geotagged posts on one of China's largest social media sites, Weibo, to verify this hypothesis. We find that extreme temperatures causally decrease individuals' sentiment, and extremely low temperature may decrease more than extremely high temperature. Heterogeneity analyses reveal that individuals living in high levels of PM2.5, existing new COVID-19 diagnoses and low-disposable income cities on workdays are more vulnerable to the impact of extreme temperatures on sentiment. More importantly, the results also demonstrate that the adverse effects of extremely low temperatures on sentiment are more minor for people living in northern cities with breezes. Finally, we estimate that with a one-standard increase of extremely high (low) temperature, the sentiment decreases by approximately 0.161 (0.272) units. Employing social media to monitor public sentiment can assist policymakers in developing data-driven and evidence-based policies to alleviate the adverse impacts of extreme temperatures.

Impact of KRAS mutation on the tumor microenvironment in colorectal cancer.

Kirsten rat sarcoma viral oncogene homolog (KRAS) is an oncogene implicated in the pathophysiology of many cancers. Increasing evidence shows that KRAS mutation is correlated with poor prognosis in numerous cancers, including colorectal cancer (CRC), breast cancer, and melanoma. KRAS also participates in regulating the CRC microenvironment. However, the direct and indirect therapeutic targets of KRAS in CRC have not been identified; thus, elucidating the mechanisms and interactions between KRAS and the tumor microenvironment (TME) in-depth is paramount. Herein, we present some of the major roles KRAS plays in shaping the heterogeneity of the TME and propose a potential strategy for targeting the downstream components of the KRAS signaling pathway and the TME in CRC.

Development of a 10-litre pilot scale micro-nano bubble (MNB)-enhanced photocatalytic system for wastewater treatment.

A 10-litre pilot scale micro-nano bubble (MNB)-enhanced photocatalytic degradation system was developed using ZnO as the photocatalyst and salicylic acid (SA) as the model pollutant. The effectiveness of the MNB/ZnO/UV system was systematically compared with those of MNB, UV, MNB/UV, MNB/ZnO and ZnO/UV degradation systems. The effects of process parameters, including catalyst dosage, pollutant concentration, air-intake rate, pH and salt content on the degradation of SA, were comprehensively investigated. Optimum performance was obtained at neutral conditions with a catalyst dosage of 0.3 g/L and an air-intake rate of 0.1 L/min. For the degradation of SA, a kinetic constant of 0.04126/min was achieved in the MNB/ZnO/UV system, which is 4.5 times greater than that obtained in the conventional ZnO/UV system. The substantial increase in the degradation rate can be attributed to that the air MNB not only enhanced the gas-liquid mass transfer efficiency but also elevated the concentration of dissolved oxygen. A 10-litre pilot scale MNB/ZnO/UV system was successfully applied to the purification of lake water and river water, demonstrating great application potential for wastewater treatment.

Autoantibodes to GP210 are a metric for UDCA responses in primary biliary cholangitis.

Objectives: Antibodies to gp210 and sp100 are specific and unique anti-nuclear autoantibodies (ANAs) associated with primary biliary cholangitis (PBC). Importantly the presence of anti-gp210 and anti-sp100 responses is indicative of poor clinical outcomes. However, the utility of measuring titers of these antibodies remains unclear. Materials and methods: Using the in-house purified gp210 (HSA108-C18) and sp100 (amino acid position 296-386), we quantitatively measured serum autoantibodies to gp210 and sp100 using chemiluminescence immunoassay (CLIA) in a very large cohort of 390 patients with PBC, including 259 cases with no prior ursodesoxycholic acid (UDCA) treatment and 131 cases with UDCA treatment. We also analyzed serial changes in anti-gp210 and anti-sp100 levels in 245 sequential samples from 88 patients. Results: In our cross-sectional analysis, we detected anti-gp210 immunoglobulin G (IgG) and anti-sp100 IgG autoantibodies in 129 out of 390 (33.1%) and 80 out of 390 (20.5%) PBC patients, respectively. Multivariate analysis revealed that serum IgG (st.ß = 0.35, P = 0.003) and gamma-glutamyltransferase (GGT) (st.ß = 0.23, P = 0.042) levels at baseline were independently associated with anti-gp210 concentrations. In serial testing, we observed significant fluctuations in anti-gp210 antibody levels. These fluctuations reflected responsiveness to UDCA therapy, particularly in anti-gp210-positive patients with initially lower concentrations in the stages of disease. Conclusions: Our study reflects that quantitative changes of anti-gp210 antibody are indicative of UDCA responses. There is a great need for newer metrics in PBC and we suggest that a more detailed and longer study of these unique ANAs is warranted.

Relationship between subtype-specific minimal residual disease level and long-term prognosis in children with acute lymphoblastic leukemia.

Minimal residual disease (MRD) based risk stratification criteria for specific genetic subtypes remained unclear in childhood acute lymphoblastic leukemia (ALL). Among 723 children with newly diagnosed ALL treated with the Chinese Children Leukemia Group CCLG-2008 protocol, MRD was assessed at time point 1 (TP1, at the end of induction) and TP2 (before consolidation treatment) and the MRD levels significantly differed in patients with different fusion genes or immunophenotypes (P all < 0.001). Moreover, the prognostic impact of MRD varied by distinct molecular subtypes. We stratified patients in each molecular subtype into two MRD groups based on the results. For patients carrying BCR::ABL1 or KMT2A rearrangements, we classified patients with MRD < 10-2 at both TP1 and TP2 as the low MRD group and the others as the high MRD group. ETV6::RUNX1+ patients with TP1 MRD < 10-3 and TP2 MRD-negative were classified as the low MRD group and the others as the high MRD group. For T-ALL, We defined children with TP1 MRD ≥ 10-3 as the high MRD group and the others as the low MRD group. The 10-year relapse-free survival of low MRD group was significantly better than that of high MRD group. We verified the prognostic impact of the subtype-specific MRD-based stratification in patients treated with the BCH-ALL2003 protocol. In conclusion, the subtype-specific MRD risk stratification may contribute to the precise treatment of childhood ALL.