ABSTRACT
Social capital has long been recognized as a facilitator of socio-economic development. However, the role of social capital in enhancing resilience to multiple shocks in rural China remains insufficiently explored. This study focus on the resilience of households that have recently get rid of poverty and reside in underdeveloped rural areas of China. Unlike previous studies, the article incorporates multiple shocks, social capital, and households' coping strategies into a research framework at the micro level. This study systematically analyses the multiple shocks experienced by households, their coping strategies, and further explores the mediating role of social capital. Utilizing two waves of a rural household panel survey data collected in six underdeveloped counties in 2015 and 2018 in China, we present four key findings. Currently, households primarily contend with drought, illness of family members, and the high costs of agricultural inputs as the main shocks. Their predominant coping strategy is reducing consumption. Importantly, social capital exhibits a mediating effect, accounting for 9.8% of the impact of multiple shocks on households' coping strategies. Notably, natural disasters significantly diminish the informal functions of social capital. While social capital exerts a full mediating effect in non-agricultural households, this effect is not observed among others. This study contributes to a better understanding of the dynamics and specificities of social capital in vulnerable rural areas. Additionally, the findings provide policymakers with practical insights regarding differentiated and preemptive risk governance approaches.
Subject(s)
Adaptation, Psychological , Family Characteristics , Rural Population , Social Capital , Humans , China , Female , Male , Poverty , Adult , Middle Aged , Socioeconomic Factors , Surveys and Questionnaires , Coping SkillsABSTRACT
With the advancement of technology, wastewater treatment has become a significant challenge limiting the clean and sustainable development of chemical and metallurgical industries. Foam extraction, based on interfacial separation and mineral flotation, has garnered considerable attention as a wastewater treatment technology due to its unique physicochemical properties. Although considerable excellent accomplishments were reported, there still lacks a comprehensive summary of process features and contaminant removal mechanisms via foam extraction. According to the latest research progresses, the principles and characteristics of foam extraction technology, the classification and application of flotation reagents are systematically summarized in this work. Then comprehensively commented on the application fields and prospects of iterative flotation technology such as ion flotation, adsorption flotation and floating-extraction. The shortcomings and limitations of the current foam extraction technologies were discussed, and the feasible process intensification techniques were highlighted. This review aims to enchance the understanding of the foam extraction mechanism, and provides guidance for the selection appropriate reagents and foam extraction technologies in wastewater treatment.
ABSTRACT
Ultraviolet radiation (UVR) has various effects on human cells and tissues, which can lead to a variety of skin diseases and cause inconvenience to people's lives. Among them, solar dermatitis is one of the important risk factors for malignant melanoma, so prevention and treatment of solar dermatitis is very necessary. Additionally, liquiritin (LQ) has anti-inflammatory effects. In this study, we aimed to evaluate the anti-inflammatory and pro-wound healing effects of liquiritin carbomer gel cold paste (LQ-CG-CP) in vitro and in vivo. The results of MTT experiments showed no cytotoxicity of LQ at concentrations of 40 µg/mL and below and cell damage at UVB irradiation doses above 60 mJ/cm2. Moreover, LQ can promote cell migration. ELISA results also showed that LQ inhibited the elevation of the inflammatory factors tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), and interleukin-6 (IL-6) after UVB irradiation. In the mouse model of solar dermatitis, 2% LQ-CG-CP showed the best therapeutic efficacy for wound healing and relief of itching compared to MEIBAO moist burn moisturizer (MEBO). What is more, the results of skin histopathological examination show that LQ-CG-CP promotes re-epithelialization, shrinks wounds, and promotes collagen production, thus promoting wound healing. Simultaneously, LQ-CG-CP reduced TNF-α, IL-1ß, and IL-6 expression. In addition, LQ-CG-CP was not observed to cause histopathological changes and blood biochemical abnormalities in mice. Overall, LQ-CG-CP has great potential for the treatment of solar dermatitis.
Subject(s)
Acrylic Resins , Dermatitis , Flavanones , Glucosides , Sunburn , Animals , Mice , Humans , Ultraviolet Rays , Interleukin-6 , Tumor Necrosis Factor-alpha , Wound Healing , Interleukin-1beta , Anti-Inflammatory AgentsABSTRACT
Objective: This article analyzes the relationship between intrahousehold empowerment gaps and food and nutrition security using quantitative data collected through a household survey organized by the Agricultural Information Institute, Chinese Academy of Agricultural Sciences (CAAS-AII), in 2023. Methods: Based on empowerment theory, this study measured the relative empowerment of spouses from the Abbreviated Women's Empowerment in Agriculture Index (A-WEAI). Results: From the micro-level evidence of 468 rural households, this study found that intrahousehold empowerment gaps harm the diversity of household diets. In particular, reducing gender gaps in access to resources, leadership, and income can help diversify household diets. However, data on the impact of shortening the difference in working hours between wives and husbands for the benefit of food safety are yet to be conclusive. Additionally, gender gaps in the group of non-coresident mothers-in-law and non-migrants hurt household food security. Conclusion: The paper also provides further justification for policies and interventions that aim to improve women's bargaining position in the household.
ABSTRACT
Given the 'subsistence' character of smallholder production, agricultural production diversification is often seen as an effective strategy for smallholders to improve their diets' diversity and nutritional status, yet the existing evidence remains inadequate. The study applies bibliometric data from the "Web of Science" database to synthesize 46 papers from developing countries to explore the relationship between production diversity, dietary diversity, and nutrition in smallholder households. The study identifies the most influential journals, authors, organizations, and countries and reveals research themes related to agricultural production and food security. This data analysis can help researchers target potential collaborators and access influential literature in agricultural production diversity and dietary diversity research. In addition, the results showed that agricultural production diversity potentially influences households' dietary diversity, with mixed results: Agricultural production diversification is the primary way to improve food and nutritional security among smallholder families with low socio-economic status, inaccessible transportation, and poverty; market access and trade have more potential to improve dietary diversity among smallholder households with well-developed markets and higher income levels; the significant measures of agricultural production diversity include Crop Counts, FGPD, SI, and SWDI; the significant measures of dietary diversity include HDDS and IDDS. This paper provides a roadmap for agricultural production and food security researchers by conducting a systematic review of the literature, summarizing some research methods and perspectives applicable to local socio-economic development.
ABSTRACT
Ion precipitation flotation technology was demonstrated to be an efficient method for the separation of valuable metals from low-concentration solution. However, the selective separation of three metals from mixing solution is a great challenge, and highly selective reagents are the key to polymetallic separation. In this work, stepwise separation of Co and Zn from the simulated zinc hydrometallurgy wastewater containing ternary Co-Zn-Mn metals by ion precipitation flotation process was proposed. It's demonstrated that organic reagents of 1-nitroso-2-naphthol (NN) and sodium dimethyldithiocarbamate (SDDC) had excellent selectivity for the capture of Co and Zn to form respective precipitate from wastewaters via the chelation reactions. After precipitation, dodecylpyridinium chloride (DPC) and tetradecyltrimethylammonium bromide (TTAB) were chosen as surfactants for the separation of Co and Zn sediments from the solution via the flotation process. The effects of solution pH, molar ratio, reaction temperature, and reaction time on the selective precipitation efficiencies of Co and Zn as well as the effects of surfactant dosage and flotation gas velocity on the flotation separation efficiencies were systematically investigated. It's demonstrated that the comprehensive recovery rates of Co, Mn, and Zn reach 98%, 90%, and 99%, respectively. After separation, oxidation calcination of the foam products was conducted to prepare high-purity Co3O4 and ZnO nanoparticles in which the organic matters were burnt out with gas emissions. The stepwise chelation capture mechanisms of Co and Zn by highly selective precipitation reagents were minutely discussed. It's demonstrated that the proposed selective stepwise precipitation and flotation method is suitable for recovery of critical metal ions from low-concentration polymetallic wastewaters.
Subject(s)
Wastewater , Zinc , Metals , Indicators and Reagents , Surface-Active Agents , IonsABSTRACT
High-temperature rechargeable batteries are essential for energy storage in elevated-temperature situations. Due to the resource abundance of potassium, high-temperature K-ion batteries are drawing increasing research interest. However, raising the working temperature would aggravate the chemical and mechanical instability of the KIB anode, resulting in very fast capacity fading, especially when high capacity is pursued. Here, we demonstrated that a porous conductive metal-organic framework (MOF), which is constructed by N-rich aromatic molecules and CuO4 units via π-d conjugation, could provide multiple accessible redox-active sites and promised robust structure stability for efficient potassium storage at high temperatures. Even working at 60 °C, this MOF anode could deliver high initial capacity (455 mAh g-1), impressive rate, and extraordinary cyclability (96.7% capacity retention for 1600 cycles), which is much better than those of reported high-temperature KIB anodes. The mechanistic study revealed that CâN groups and CuO4 units contributed abundant redox-active sites; the synergistic effect of π-d conjugated character and reticular porous architecture facilitated the K+/e- transport and ensured an insoluble electrode with small volume deformation, thus achieving stable high-capacity potassium storage.
ABSTRACT
Clean and efficient extraction and separation of precious metals from discarded Pb-Sn alloy is critical to the sustainable utilization of solid waste resources. Dense oxide layer and compact alloy texture in the waste Pb-Sn alloy pose challenges to the effective leaching process. Ultrasonic waves are demonstrated to improve separation efficiency via the favorable physical and chemical effects in solution system. In this study, ultrasound-assisted leaching technology is attempted to rapidly and selectively extract Pb from the waste Pb-Sn alloy, and gives emphasis on ultrasonic electrochemical behaviors. The Eh-pH diagrams of Sn-H2O and Pb-H2O systems were firstly analyzed to lay the selective dissolution foundation. It's indicated that oxidizing HNO3 lixiviant is suitable to realize the selective separation of Pb. Both Sn and Pb can be dissolved to ionic Sn2+ and Pb2+ in the HNO3 solution. However, Sn2+ rapidly oxidizes to Sn4+ and Sn4+ further hydrolyzes to insoluble SnO2, which will agglomerate on unreacted materials to limit internal metal leaching in conventional leaching process. Due to the vibratory stripping of oxide layer by physical effect of ultrasound, the conventional acid leaching time for Pb extraction can be halved with the ultrasound assistance. About 99.12 % Pb and only 0.1 % Sn are dissolved in ultrasound-assisted leaching under the following optimal parameters: 0.5 mol/L HNO3, leaching temperature of 80 °C, time of 30 min, liquid-to-solid ratio of 20 mL/g, and ultrasound intensity of 0.52 W/cm2. Leaching kinetics of Pb, phase transition, microstructure evolution, Pb-Sn galvanic corrosion and dissolution polarization curve were studied to determine the ultrasonic enhanced dissolution mechanism. Notably, Pb and Sn form a microcorrosion galvanic cell in which Sn acts as a cathode and is protected while the Pb undergoes intensifying corrosion as the anode giving rise to the higher Pb dissolution efficiency. Eventually, it's suggested that Pb can be rapidly extracted and separated from the waste Pb-Sn alloy during the ultrasound-assisted HNO3 leaching process via the ultrasound physical and chemical effects, especially the sonochemistry aspect of intensified spot corrosion and galvanic corrosion. The proposed ultrasonic electrochemical corrosion in this work were applicable to the extraction of valuable metals from various waste alloys through leaching method.
ABSTRACT
BACKGROUND: The quality of life of patients with advanced gastrointestinal cancer is seriously impaired, and socioeconomic deprivation often has a serious impact on their quality of life. However, little is known about the relative contribution of non-socioeconomic factors to the quality of life of patients with advanced gastrointestinal cancer with socioeconomic deprivation. AIM: This study aims to investigate the situation and predictors of quality of life of patients with socioeconomic deprivation and evaluate the independent effects of some non-socioeconomic factors. DESIGN: A retrospective study based on cross-sectional design. METHODS: Data were obtained from 1075 patients with advanced gastrointestinal cancer who received family palliative treatment in the hospice ward of Zhongnan Hospital of Wuhan University from March 2010 to October 2020, including demographic and clinical questionnaires, Karnofsky Performance Status scale and Cancer Pain and Quality of Life Questionnaire of Chinese Cancer Patients. RESULTS: The quality of life of patients with advanced gastrointestinal cancer with socioeconomic deprivation is impaired and is affected by gait, self-care ability, abdominal distension, nutritional status, weight loss, constipation and posture. Improvement in six of these factors-gait, self-care ability, abdominal distension, nutritional status, weight loss and posture-has an independent positive impact on the development of a healthy quality of life for patients. CONCLUSIONS: Gait, self-care ability, abdominal distension, nutritional status, weight loss and posture are important determinants of healthy quality of life in patients with advanced gastrointestinal cancer with socioeconomic deprivation, and early identification and strength management of these non-socioeconomic factors may neutralize the negative impact of socioeconomic factors on the quality of life. IMPLICATIONS FOR PRACTICE: This study provides new ideas and intervention entry points for global nurses in practice innovations to improve the quality of life of socioeconomically deprived patients with advanced gastrointestinal cancer. It enables them to focus on the effectiveness of non-socioeconomic factors in the development and implementation of targeted care plans for patients with advanced gastrointestinal cancer experiencing socioeconomic deprivation globally. REPORTING METHOD: This study was reported in strict compliance with the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guideline. PATIENT OR PUBLIC CONTRIBUTION: No patient or public contribution.
Subject(s)
Gastrointestinal Neoplasms , Quality of Life , Humans , Cross-Sectional Studies , Retrospective Studies , Weight Loss , Socioeconomic FactorsABSTRACT
Clean and fast extraction of tin from the surface of tinplate scraps is of great significance for the efficient utilization of waste resources. However, the dense tin layer causes the low efficiency of conventional leaching process. To improve Sn leaching efficiency, the ultrasound technique was adopted to extract Sn from tinplate scraps by alkaline leaching in this study. In the NaOH-H2O2 leaching system, metallic tin and alloyed tin in Fe-Sn alloy located on the surface of tinplate scraps can be oxidized and transferred to soluble Na2SnO3, while the iron in Fe-Sn alloy was oxidized to oxides which were chemically inert in alkaline solution. The differences in chemical solubility of Sn and Fe, and solubleness of stannate and iron oxides gave rise to the selective separation of Sn from the tinplate scraps. The effects of the leaching parameters on the Sn leaching behaviors in conventional and ultrasound-assisted leaching processes were compared. The conventional leaching temperature and time were significantly reduced during the ultrasound-assisted leaching process. Almost all of Sn can be extracted after conventional leaching at 1 mol/L NaOH, temperature of 80 â and time of 60 min, however the same Sn leaching effect can be achieved by ultrasound-assisted leaching at 60 â for 30 min with ultrasound power of 60% (360 W). Sn leaching kinetics based on the plate model demonstrated the reaction rate constant of the ultrasound-assisted leaching was 70% higher than that of the conventional leaching. A novel acoustoelectric synergy effect underlying intensifying mechanism by ultrasound irradiation was proposed in this study. Eventually, this work provided a rapid and clean tin extraction method from tinplate scraps via the ultrasound-assisted alkaline leaching treatment.
ABSTRACT
This study analyzed the role of women's empowerment in diversifying the diet of households through their own production. Developed from empowerment and food security theories, this study constructed measures from the household dietary diversity score (HDDS) and Women's Empowerment Index (WEI). The study focused on poverty-stricken regions in China and conducted a thematic questionnaire-based household survey on gender and food consumption in 2021. Based on micro-level evidence from 1199 rural households, this research found a low score of women's empowerment and an average WEI of 0.689; the status of diet diversity, measured by the HDDS, varied by income and social class; and the average rate was low. Agricultural production diversity and women's empowerment are positively associated with diet diversity. There is strong evidence that women's employment mitigates the side effects of decreasing production diversity on households' diet security. As a result, women's empowerment can potentially mitigate the adverse consequences of low agricultural diversification in household diet quality in less developed areas. This study provides evidence for repurposing food and agricultural policies toward healthy diets and gender-responsive agrifood systems.
Subject(s)
Diet , Food Supply , Humans , Female , Poverty , Income , Food SecurityABSTRACT
OBJECTIVES: Currently, it is difficult to assess the expression status of hormone receptor (HR) in breast malignant tumors with human epidermal growth factor receptor 2 (HER-2)-positive in the early preoperative stage, and it is difficult to predict whether it is non-invasively. This study aims to explore the value of MRI on the different HR expression status (HR+/HR-) in HER-2 positive breast cancer. METHODS: Thirty patients with HR+ HER-2-positive breast cancer (HR+ group) and 23 patients with HR-HER-2-positive breast cancer (HR- group) from the First Hospital of Hunan University of Traditional Chinese Medicine between January 7, 2015 and November 26, 2021 were selected as subjects, and all the patients were examined by MRI and all were confirmed by surgery or pathological biopsy puncture. The immunohistochemical staining results were used as the gold standard to analyze the basic clinical conditions, peri-lesion conditions and MRI sign characteristics in the 2 groups. RESULTS: There were all significant differences in terms of mass margins, internal reinforcement features, and apparent diffusion coefficient (ADC) values between the HR+ group and the HR- group (all P<0.05). The logistic multivariate regression model showed that: when the lesion presented as a mass-type breast cancer on MRI, the internal enhancement features of the lesion were an independent predictor for differentiation in the 2 types of breast cancer [odds ratio (OR)=5.95, 95% CI: 1.223 to 28.951, P<0.05], and the mass margin (OR=0.386, 95% CI: 0.137 to 1.082, P>0.05) and ADC value (OR=0.234, 95% CI: 0.001 to 105.293, P>0.05) were not the independent predictors in distinguishing the 2 types of breast cancer. CONCLUSIONS: Multiparametric MRI has good diagnostic value for HR expression status in HER-2-positive breast cancer. Combined logistic regression analysis to construct a predictive model may be helpful to the identical diagnosis.
Subject(s)
Breast Neoplasms , Humans , Female , Breast Neoplasms/surgery , Magnetic Resonance Imaging/methods , Diffusion Magnetic Resonance Imaging/methods , Breast , Magnetic Resonance Spectroscopy , Retrospective StudiesABSTRACT
Pegylated interferon alfa-2b (Peg-IFN α-2b), a first-line treatment for hepatitis B virus (HBV) infection, can significantly achieve HBsAg clearance in clinic. However, only 30-40% of patients had achieved HBsAg clearance after Peg-IFN α-2b administration. The biological targets and the underline mechanisms that distinguish sensitive and insensitive populations to interferon therapy are still unclear. In the present study, only 33.33% of patients achieved HBsAg loss after 48 weeks of Peg-IFN α-2b therapy. Thirty-six exosomal-microRNAs (miRNAs) in the sensitive group were identified that might induce sensitivity specifically, whereas 32 exosomal-miRNAs in the insensitive group were identified that might induce insensitive specifically. Among these miRNAs, five miRNAs (miR-425-5p, miR-8485, miR-619-5p, miR-181a-5p, and miR-484) might increase the sensitivity to Peg-IFN α-2b therapy by regulating key genes GSK3B, KRAS, FLT1, or GRB2, whereas, 13 miRNAs (miR-195-5p, miR-215-5p, miR-9-5p, miR-130a-3p, miR-214-3p, miR-149-5p, miR-429, miR-200b-3p, miR-200c-3p, miR-16-2-3p, miR-141-3p, miR-200a-3p, and miR-218-5p) might decrease the sensitivity to Peg-IFN α-2b therapy by regulating key genes, FGF2, GSK3B, PDGFRA, FGFR1, KRAS, FLT1, MYC, TGFB2, EFNA1, MAPK9, or GRB2. Furthermore, seven novel miRNAs, namely Novel_352, Novel_459, Novel_527, Novel_677, Novel_717, Novel_749, and Novel_801 were found to be downregulated specifically in the sensitive group, whereas, Novel_142 and Novel_664 were found to be downregulated specifically in the insensitive group. Our data indicate that the serum exosomal-miRNAs could be involved in regulating the sensitivity of chronic HBV (CHB) patients to Peg-IFN α-2b therapy, which might suggest potential novel therapeutic biomarkers and standard options for CHB patients. Clinical Trials.gov ID: NCT04035837.
Subject(s)
Circulating MicroRNA , Hepatitis B, Chronic , MicroRNAs , Humans , Hepatitis B virus/genetics , Circulating MicroRNA/therapeutic use , Hepatitis B Surface Antigens , Proto-Oncogene Proteins p21(ras)/therapeutic use , MicroRNAs/geneticsABSTRACT
BACKGROUND AND AIMS: Chronic HBV infection evolves through different phases. Interactions between viral replication and the host immune response in the liver underlie the pathogenesis of this disease. The aim of this study was to directly visualize the HBV replication intermediates at a single-cell resolution inscribed on morphological changes corresponding to disease activity. METHODS: A set of archived formalin-fixed paraffin-embedded liver needle biopsies from treatment-naïve patients were collected and categorized into phases according to the American Association for the Study of the Liver Diseases (AASLD) guidelines. HBV RNA and DNA were detected using in situ hybridization assays. RESULTS: The hepatocytes were ubiquitously infected in subjects with immune tolerance, and their percentage was gradually decreased in immune-active and inactive chronic hepatitis B phases. HBV-infected hepatocytes were prone to localize close to fibrous septa. The subcellular distribution of signals was able to distinguish hepatocytes with productive infection from those harboring HBV integrants and transcriptionally inactive covalently closed circular DNAs. A smaller number of hepatocytes with productive infection and more harboring transcriptionally inactive covalently closed circular DNA or HBV integrants became apparent in the inactive chronic hepatitis B phase. CONCLUSION: An atlas of in situ characteristics of viral-host interactions for each phase is described, which sheds light on the nature of viral replication and disease pathogenesis among the phases of chronic HBV infection.
Subject(s)
Hepatitis B, Chronic , Humans , Hepatitis B virus , DNA, Viral/genetics , Virus Replication/genetics , DNA, Circular/geneticsABSTRACT
The androgen receptor (AR) is a crucial coactivator of ELK1 for prostate cancer (PCa) growth, associating with ELK1 through two peptide segments (358-457 and 514-557) within the amino-terminal domain (NTD) of AR. The small-molecule antagonist 5-hydroxy-2-(3-hydroxyphenyl)chromen-4-one (KCI807) binds to AR, blocking ELK1 binding and inhibiting PCa growth. We investigated the mode of interaction of KCI807 with AR using systematic mutagenesis coupled with ELK1 coactivation assays, testing polypeptide binding and Raman spectroscopy. In full-length AR, deletion of neither ELK1 binding segment affected sensitivity of residual ELK1 coactivation to KCI807. Although the NTD is sufficient for association of AR with ELK1, interaction of the isolated NTD with ELK1 was insensitive to KCI807. In contrast, coactivation of ELK1 by the AR-V7 splice variant, comprising the NTD and the DNA binding domain (DBD), was sensitive to KCI807. Deletions and point mutations within DBD segment 558-595, adjacent to the NTD, interfered with coactivation of ELK1, and residual ELK1 coactivation by the mutants was insensitive to KCI807. In a glutathione S-transferase pull-down assay, KCI807 inhibited ELK1 binding to an AR polypeptide that included the two ELK1 binding segments and the DBD but did not affect ELK1 binding to a similar AR segment that lacked the sequence downstream of residue 566. Raman spectroscopy detected KCI807-induced conformational change in the DBD. The data point to a putative KCI807 binding pocket within the crystal structure of the DBD and indicate that either mutations or binding of KCI807 at this site will induce conformational changes that disrupt ELK1 binding to the NTD. SIGNIFICANCE STATEMENT: The small-molecule antagonist KCI807 disrupts association of the androgen receptor (AR) with ELK1, serving as a prototype for the development of small molecules for a novel type of therapeutic intervention in drug-resistant prostate cancer. This study provides basic information needed for rational KCI807-based drug design by identifying a putative binding pocket in the DNA binding domain of AR through which KCI807 modulates the amino-terminal domain to inhibit ELK1 binding.
Subject(s)
Prostatic Neoplasms , Receptors, Androgen , Male , Humans , Receptors, Androgen/genetics , Receptors, Androgen/chemistry , Receptors, Androgen/metabolism , Protein Domains , Peptides/therapeutic use , Prostatic Neoplasms/metabolism , DNA , ets-Domain Protein Elk-1/genetics , ets-Domain Protein Elk-1/metabolism , ets-Domain Protein Elk-1/therapeutic useABSTRACT
BACKGROUND: Chronic hepatitis B is usually treated with nucleos(t)ide analogues (NAs). However, a cure is rarely achieved, even with years of treatment. Here, we investigated whether viral replication is completely halted and how long covalently closed circular DNA (cccDNA) persists in patients successfully treated with NAs. METHODS: A series of longitudinal serum samples and a collection of cross-sectional liver biopsies were obtained from patients successfully treated with NAs. Viral variants in serum HBV RNA were enumerated by deep sequencing. Viral replication intermediates in hepatocytes were directly visualized by in situ hybridization. The apparent half-life of each cccDNA was estimated. RESULTS: Three of 6 successfully treated patients demonstrated clear evidence of a small proportion of virus evolution, although the overwhelming proportion of variants were identical or possessed a similar degree of divergence through time. The apparent half-life of variants was estimated to be from approximately 7.42 weeks to infinite. Hepatocytes remained positive for cytoplasmic nucleocapsids-associated relaxed circular DNA in 4 of 7 liver needle biopsies. CONCLUSIONS: We conclude that even after prolonged treatment, a small proportion of the cccDNA reservoir is constantly replenished by continued low-level HBV replication, whereas a large proportion of the cccDNA reservoir persists over time.
Subject(s)
Hepatitis B, Chronic , Hepatitis B , Humans , Hepatitis B, Chronic/drug therapy , Antiviral Agents/therapeutic use , Cross-Sectional Studies , DNA, Viral/genetics , Hepatitis B virus/genetics , Virus Replication , DNA, Circular , Hepatitis B/drug therapyABSTRACT
In lung adenocarcinoma (LUAD), the appearance of morphologically diverse tumor regions, termed histological patterns, is closely associated with disease progression and lymph node metastasis. However, the molecular characteristics of the histological patterns in LUAD and the underlying molecular evolutionary mechanisms between the histological patterns in primary tumors and lymph node metastases are poorly understood. Here, we re-analyzed the large TCGA-LUAD dataset and depicted a comprehensive profiling of the genome and transcriptome across the histological patterns in LUAD. Tumor phylogenetic trajectory analysis suggested that the complex glands is more apt to metastasize to the lymph node. Further deconvolution of the tumor microenvironment demonstrated that the complex glands had a higher infiltration of cancer-associated fibroblasts (CAFs). Single-cell transcriptome profiling of complex glands pattern identified a novel CAF subtype co-expressing fibroblast activation protein-alpha (FAP) and stimulator of interferon genes (STING). Moreover, our data demonstrated that FAP is an important downstream effector of STING in CAFs. In summary, our results provide the basis for the development of innovative therapeutic guidelines and intervention strategies for LUAD patients.
Subject(s)
Adenocarcinoma of Lung , Lung Neoplasms , Humans , Phylogeny , Gene Expression Regulation, Neoplastic , Biomarkers, Tumor/genetics , Adenocarcinoma of Lung/genetics , Adenocarcinoma of Lung/pathology , Lymphatic Metastasis , Lung Neoplasms/genetics , Lung Neoplasms/pathology , Tumor Microenvironment/geneticsABSTRACT
Prostate cancer (PCa) growth requires tethering of the androgen receptor (AR) to chromatin by the ETS domain transcription factor ELK1 to coactivate critical cell proliferation genes. Disruption of the ELK1-AR complex is a validated potential means of therapeutic intervention in PCa. AR associates with ELK1 by coopting its two ERK docking sites, through the amino-terminal domain (A/B domain) of AR. Using a mammalian two-hybrid assay, we have now functionally mapped amino acids within the peptide segments 358-457 and 514-557 in the A/B domain as required for association with ELK1. The mapping data were validated by GST (glutathione S-transferase)-pulldown and BRET (bioluminescence resonance energy transfer) assays. Comparison of the relative contributions of the interacting motifs/segments in ELK1 and AR to coactivation of ELK1 by AR suggested a parallel mode of binding of AR and ELK1 polypeptides. Growth of PCa cells was partially inhibited by deletion of the upstream segment in AR and nearly fully inhibited by deletion of the downstream segment. Our studies have identified two peptide segments in AR that mediate the functional association of AR with its two docking sites in ELK1. Identification of the ELK1 recognition sites in AR should enable further structural studies of the ELK1-AR interaction and rational design of small molecule drugs to disrupt this interaction.
Subject(s)
Prostatic Neoplasms , Receptors, Androgen , Animals , Cell Line, Tumor , Cell Proliferation , Humans , Male , Mammals/metabolism , Peptides/genetics , Peptides/therapeutic use , Prostatic Neoplasms/genetics , Receptors, Androgen/chemistry , ets-Domain Protein Elk-1/genetics , ets-Domain Protein Elk-1/metabolism , ets-Domain Protein Elk-1/therapeutic useABSTRACT
Recent evidence indicates that cancer stem cells (CSCs) are the origin of cancers. Scientists have identified CSCs in various tumors and have suggested the existence of a variety of states of CSCs. The existence of epithelial-mesenchymal transition (EMT)-like CSCs has been confirmed in vitro, but they have not been identified in vivo. Tumor budding was defined as single cell or clusters of ≤ 5 cells at the invasive front of cancers. Such tumor budding is hypothesized to be closely related to EMT and linked to CSCs, especially to those migrating at the invasive front. Therefore, tumor budding has been proposed to represent EMT-like stem cells. However, this hypothesis has not yet been proven. Thus, we studied the expression of EMT markers, certain CSC markers of tumor budding, and the tumor center of cervical squamous cell carcinoma (CxSCC). We performed tissue chip analyses of 95 primary CxSCCs from patients. Expression of EMT and CSC markers (E-cadherin, ß-catenin, vimentin, Ki67, CD44, SOX2 , and ALDH1A1) in a set of tumor samples on tissue chips (87 cases of tumor budding/the main tumor body) were evaluated by immunohistochemistry. We found that the cell-membranous expression of ß-catenin was stronger in the main tumor body than in tumor buds. Compared with the main tumor body, tumor buds had reduced proliferative activity as measured by Ki67. Moreover, vimentin expression was high and E-cadherin expression was low in tumor buds. Expression of EMT-related markers suggested that tumor buds were correlated with EMT. We noted that CxSCC tumor buds had a CD44negative/low/SOX2high/ALDH1A1high staining pattern, indicating that tumor buds of CxSCC present CSC-like immunophenotypic features. Taken together, our data indicate that tumor buds in CxSCC may represent EMT-like CSCs in vivo.
Subject(s)
Carcinoma, Squamous Cell , Epithelial-Mesenchymal Transition , Uterine Cervical Neoplasms , Female , Humans , beta Catenin/metabolism , Cadherins/metabolism , Carcinoma, Squamous Cell/metabolism , Ki-67 Antigen/metabolism , Neoplastic Stem Cells/metabolism , Vimentin/metabolism , Uterine Cervical Neoplasms/metabolismABSTRACT
Embryo quality determines the success of in vitro fertilization and embryo transfer (IVF-ET) treatment. Biomarkers for the evaluation of embryo quality have some limitations. Apoptosis in cumulus cells (CCs) is important for ovarian function. PTEN (phosphatase and tensin homolog) is a well known tumour suppressor gene that functions as a mediator of apoptosis and is crucial for mammalian reproduction. In the present study, we analyzed the expression level of PTEN in human CCs and aimed to investigate its association with embryo developmental competence in IVF treatment cycles. The PTEN mRNA level in CCs was measured using real-time fluorescence quantitative PCR. The association of the differential expression of PTEN with embryo quality was analyzed. Our data showed that PTEN mRNA levels were significantly decreased in CCs surrounding mature oocytes compared with immature oocytes. Similar changes were found in the analysis of fertilization and blastocyst formation. The speculation that the measurement of PTEN mRNA levels in human CCs would provide a useful tool for selecting oocytes with greater chances to implant into the uterus needs to be further verified through single-embryo transfer in the future. The proapoptotic mechanism of PTEN in human reproduction needs to be further studied.