Dechlorination of 1,2,3,4-Tetrachlorobenzene in organic matter- and mineral-dominated soils and effects of Typha latifolia roots

A variety of environments are contaminated with chlorinated benzenes. Therefore, investigating the biodegradation of chlorobenzenes in different types of soils is useful in assessing the feasibility of bioremediation. One mineral-dominated soil: PPI (Petro Processors Inc. site) soil, and three organic matter-dominated soils (natural wetland soil, constructed wetland soil (a mixture of peat, compost and sand), and river sediment) were used to investigate anaerobic biodegradation of 1,2,3,4-Tetrachlorobenzene (1,2,3,4-TeCB) using laboratory microcosms. To determine whether methanogens were directly responsible for dechlorination, a comparative study using 2-bromoethanesulfonic acid (BES) for inhibition of methanogenesis was conducted. Hydrogen and methane concentrations, and microbial diversities were analyzed. The results of the present study showed that 1,2,3,4-TeCB was completely biodegraded in all test soils with different microbial communities. The most dominant dechlorination pathway was: 1,2,3,4-TeCB à 1,2,3-TCB à 1,2-DCB + 1,4-DCB + 1,3-DCB à monochlorobenezene + benzene. The test chemical was biodegraded at rates ranging from 0.023 day-1 (half-life time of 30.5 days) to 1.108 day-1 (half-life time of 0.6 days), with lag periods varied between 1 and 72 days. Dechlorination kinetics of chlorobenzenes was found to depend on many factors other than organic carbon content. DGGE banding profile, methane concentration and dechlorination activities suggest that BES probably changed the compositions of bacteria consortia, and partly inhibited methanogenesis and chlorobenzene dechlorination. Moreover, methanogens were probably not directly responsible for dechlorination of chlorobenzenes. Rhizosphere of some plants can enhance rhizodegradation of organic contaminants. Thus, the present study also investigated the effects of Typha latifolia L. roots on anaerobic degradation of 1,2,3,4-TeCB. Biodegradation rate constant of 1,2,3,4-TeCB was observed to increase with increasing amounts of roots, indicating that Typha, a native wetland plant, could be a very promising vegetation for application in phytoremediation. Due to root matter, higher concentrations of organic acids and hydrogen were observed in treatments with roots compared with the treatment without roots, which probably caused higher dechlorination activities in root-amended microcosms

Development and validation of a model based on immunogenic cell death related genes to predict the prognosis and immune response to bladder urothelial carcinoma

BackgroundImmunogenic cell death (ICD) has been categorized as a variant of regulated cell death that is capable of inducing an adaptive immune response. A growing body of evidence has indicated that ICD can modify the tumor immune microenvironment by releasing danger signals or damage-associated molecular patterns (DAMPs), potentially enhancing the efficacy of immunotherapy. Consequently, the identification of biomarkers associated with ICD that can classify patients based on their potential response to ICD immunotherapy would be highly advantageous. Therefore the goal of the study is to better understand and identify what patients with bladder urothelial carcinoma (BLCA) will respond to immunotherapy by analyzing ICD signatures and investigate ICD-related prognostic factors in the context of BLCA.MethodsThe data obtained from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases regarding BLCA and normal samples was categorized based on ICD-related genes (IRGs). Specifically, we conducted an immunohistochemical (IHC) experiment to validate the expression levels of Calreticulin (CALR) in both tumor and adjacent tissues, and evaluated its prognostic significance using the Kaplan-Meier (KM) curve. Subsequently, the samples from TCGA were divided into two subtypes using consensus clustering. To obtain a more comprehensive comprehension of the biological functions, we utilized Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene Set Enrichment Analysis (GSEA). The calculation of immune landscape between two subtypes was performed through ESTIMATE and CIBERSORT. Risk models were constructed using Cox and Lasso regression and their prognosis predictive ability was evaluated using nomogram, receiver operating characteristic (ROC), and calibration curves. Finally, Tumor Immune Dysfunction and Exclusion (TIDE) algorithms was utilized to predict the response to immunotherapy.ResultsA total of 34 IRGs were identified, with most of them exhibiting upregulation in BLCA samples. The expression of CALR was notably higher in BLCA compared to the adjacent tissue, and this increase was associated with an unfavorable prognosis. The differentially expressed genes (DEGs) associated with ICD were linked to various immune-related pathways. The ICD-high subtypes exhibited an immune-activated tumor microenvironment (TME) compared to the ICD-low subtypes. Utilizing three IRGs including CALR, IFNB1, and IFNG, a risk model was developed to categorize BLCA patients into high- and low-risk groups. The overall survival (OS) was considerably greater in the low-risk group compared to the high-risk group, as evidenced by both the TCGA and GEO cohorts. The risk score was identified as an independent prognostic parameter (all p < 0.001). Our model demonstrated good predictive ability (The area under the ROC curve (AUC), AUC1-year= 0.632, AUC3-year= 0.637, and AUC5-year =0.653). Ultimately, the lower risk score was associated with a more responsive immunotherapy group.ConclusionThe potential of the ICD-based risk signature to function as a marker for evaluating the prognosis and immune landscape in BLCA suggests its usefulness in identifying the suitable population for effective immunotherapy against BLCA

Case Report: Clinical benefit from multi-target tyrosine kinase inhibitor and PARP inhibitor in a patient with cancer of unknown primary with BRCA1 large genomic rearrangement

Background: Cancer of unknown primary (CUP), which accounts for 3%–5% of new cancer cases every year, involves the presence of a type of histologically confirmed metastatic tumors whose primary site cannot be confirmed by conventional diagnostic methods. This difficulty in identifying the primary site means that CUP patients fail to receive precisely targeted therapy. Most patients are treated with empiric chemotherapy, with a median survival of 6 months and even poorer prognosis within an unfavorable subset of CUP.Case report: An 80-year-old woman presented with masses in the abdomen. Following comprehensive imagological and immunohistochemical examinations, she was diagnosed with CUP. She emphatically declined chemotherapy; thus, anlotinib has been administered with patient consent since 02/07/2019, and stable disease (SD) was observed for 2 years. During subsequent treatment, a large genomic rearrangement in BRCA1 was identified in the patient via NGS, and SD was observed for a further 6 months following olaparib treatment. The type of LGR identified in this patient was discovered to be BRCA1 exon 17-18 inversion (inv), which has never been previously reported.Conclusion: For CUP patients, a chemo-free regimen seems to be acceptable as a first-line treatment, and NGS-guided targeted treatment could improve patient outcomes

Sex Differences in Primary and Secondary Prevention of Cardiovascular Disease in China

Background: Despite improvements in diagnostic and therapeutic interventions to combat cardiovascular disease (CVD) in recent decades, there are significant ongoing access gaps and sex disparities in prevention that have not been adequately quantified in China. Methods: A representative, cross-sectional, community-based survey of adults (aged ≥45 years) was conducted in 7 geographic regions of China between 2014 and 2016. Logistic regression models were used to determine sex differences in primary and secondary CVD prevention, and any interaction by age, education level, and area of residence. Data are presented as adjusted odds ratios (ORs) and 95% CIs. Results: Of 47 841 participants (61.3% women), 5454 (57.2% women) had established CVD and 9532 (70.5% women) had a high estimated 10-year CVD risk (≥10%). Only 48.5% and 48.6% of women and 39.3% and 59.8% of men were on any kind of blood pressure (BP)-lowering medication, lipid-lowering medication, or antiplatelet therapy for primary and secondary prevention, respectively. Women with established CVD were significantly less likely than men to receive BP-lowering medications (OR, 0.79 [95% CI, 0.65-0.95]), lipid-lowering medications (OR, 0.69 [95% CI, 0.56-0.84]), antiplatelets (OR, 0.53 [95% CI, 0.45-0.62]), or any CVD prevention medication (OR, 0.62 [95% CI, 0.52-0.73]). Women with established CVD, however, had better BP control (OR, 1.31 [95% CI, 1.14-1.50]) but less well-controlled low-density lipoprotein cholesterol (OR, 0.66 [95% CI, 0.57-0.76]), and were less likely to smoke (OR, 13.89 [95% CI, 11.24-17.15]) and achieve physical activity targets (OR, 1.92 [95% CI, 1.61-2.29]). Conversely, women with high CVD risk were less likely than men to have their BP, low-density lipoprotein cholesterol, and bodyweight controlled (OR, 0.46 [95% CI, 0.38-0.55]; OR, 0.60 [95% CI, 0.52-0.69]; OR, 0.55 [95% CI, 0.48-0.63], respectively), despite a higher use of BP-lowering medications (OR, 1.21 [95% CI, 1.01-1.45]). Younger patients (<65 years) with established CVD were less likely to be taking CVD preventive medications, but there were no sex differences by area of residence or education level. Conclusions: Large and variable gaps in primary and secondary CVD prevention exist in China, particularly for women. Effective CVD prevention requires an improved overall nationwide strategy and a special emphasis on women with established CVD, who have the greatest disparity and the most to benefit

Isl1Cre reveals a common Bmp pathway in heart and limb development.

A number of human congenital disorders present with both heart and limb defects, consistent with common genetic pathways. We have recently shown that the LIM homeodomain transcription factor islet 1 (Isl1) marks a subset of cardiac progenitors. Here, we perform lineage studies with an Isl1Cre mouse line to demonstrate that Isl1 also marks a subset of limb progenitors. In both cardiac and limb progenitors, Isl1 expression is downregulated as progenitors migrate in to form either heart or limb. To investigate common heart-limb pathways in Isl1-expressing progenitors, we ablated the Type I Bmp receptor, Bmpr1a utilizing Isl1Cre/+. Analysis of consequent heart and limb phenotypes has revealed novel requirements for Bmp signaling. Additionally, we find that Bmp signaling in Isl1-expressing progenitors is required for expression of T-box transcription factors Tbx2 and Tbx3 in heart and limb. Tbx3 is required for heart and limb formation, and is mutated in ulnar-mammary syndrome. We provide evidence that the Tbx3 promoter is directly regulated by Bmp Smads in vivo

Efficacy and safety of Jianpishengsui for chemotherapy-related fatigue in patients with non-small cell lung cancer : study protocol for a randomized placebo-controlled clinical trial

BACKGROUND: Chemotherapy-related fatigue (CRF) is a common symptom in non-small cell lung cancer (NSCLC) patients. A Chinese herbal formula cream for oral application, called Jianpishengsui (JPSS), is extensively used in the First Affiliated Hospital of Guangzhou University of Chinese Medicine as an internal preparation for CRF and is associated with a promising response. Due to the lack of high-quality clinical evidence, a randomized placebo-controlled trial is required to assess the efficacy and safety of JPSS. METHODS/DESIGN: The efficacy and safety of JPSS herbal formula cream will be evaluated through a prospective, randomized, placebo-controlled trial conducted in the First Affiliated Hospital of Guangzhou University of Chinese Medicine. NSCLC patients with CRF will be randomized into two groups at a ratio of 1:1. Each group will receive either 15 g of the oral JPSS herbal formula cream or placebo twice a day from day 6 to day 20 during two courses of paclitaxel + platinum/docetaxel + platinum/pemetrexed + platinum (TP/DP/AP) chemotherapy. The primary endpoint is the difference in the degree of fatigue between baseline (the day before the start of the intervention) and day 42, which will be assessed by the Revised Piper Fatigue Scale score. The secondary endpoints are quality of life (measured by the 43-item European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Lung Cancer C43), Eastern Cooperative Oncology Group Performance Status, and Traditional Chinese Medicine syndrome score. The toxicity of the treatments will also be evaluated at the same time. All outcomes will be measured at baseline, day 6, day 21, and day 42 of the treatment. DISCUSSION: This randomized trial will investigate the efficacy and safety of JPSS applied for CRF in patients with NSCLC. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR1900023451. Registered on 28 May 2019

Relationships between Fish Communities and Habitat before and after a Typhoon Season in Tropical Mountain Streams

The responses of habitat and fish communities to extreme hydrological and habitat disturbance in typhoon-prone mountain streams are not studied much. Such landscape&ndash;climate settings may provide a unique opportunity for fish to evolve without special habitat adaptation and involve different assembly rules compared to temperate regions. This study aimed to compare fish communities and habitat factors before and after the typhoon season and to test the influences of various aspects of habitat on fish assemblages between seasons. Fish and habitats were surveyed at 30 wadable stream sites in March and December 2010 in tropical southern Taiwan. Habitat variables differed between the pre-typhoon and post-typhoon seasons. Higher species richness and the total number of fish caught in the pre-typhoon season indicated fast recovery. Benthic fish were more vulnerable to typhoon disturbances than sub-benthic fish. Contrary to the original hypothesis, fish communities were more strongly related to physical habitats than water quality and riparian conditions. In addition, consistently high fish variance explained by habitat measures in the dry seasons indicated that environmental filtering predominated. Dominant fish species were related to main habitat gradients, characterized by low species richness but high beta-diversity. Our findings provide implications for fish conservation in typhoon-prone mountain streams