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The Opening of Pandora's Box: An Emerging Role of Long Noncoding RNA in Viral Infections
Emerging evidence has proved that long noncoding RNAs (lncRNAs) participate in various physiological and pathological processes. Recent evidence has demonstrated that lncRNAs are crucial regulators of virus infections and antiviral immune responses. Upon viral infections, significant changes take place at the transcriptional level and the majority of the expression modifications occur in lncRNAs from both the host and viral genomes with dynamic regulatory courses. These lncRNAs exert diverse effects. Some are antiviral either through directly inhibiting viral infections or through stimulating antiviral immune responses, while others are pro-viral through directly promoting virus replication or through influencing cellular status, such as suppressing antiviral mechanisms. Consequently, these dynamic regulations lead to disparate pathophysiological outcomes and clinical manifestations. This review will focus on the roles of lncRNAs in viral infection and antiviral responses, summarize expression patterns of both host- and virally derived lncRNAs, describe their acting stages and modes of action, discuss challenges and novel concepts, and propose solutions and perspectives. Research into lncRNA will help identify novel viral infection-related regulators and design preventative and therapeutic strategies against virus-related diseases and immune disorders.
Journal Article
التخفيف من حدة الفقر في الصين المعاصرة
استنادا إلى نظرة عامة على أوضاع الفقر، يقدم هذا الكتاب مسار التخفيف من حدة الفقر والتنمية في الصين، ويشرح نموذج التنمية والتخفي من حدة الفقر بخصائص صينية والتمسك بمباديء (سيطرة الحكومة ومشاركة المجتمع والاعتماد على الذات والتنمية الموجهة والتنمية الشاملة) كما يقدم الكتاب تلخيصا شاملا لإنجازات الصين العظيمة وخبراتها الهامة وإسهاماتها الرئيسية في قضية التخفيف من حدة الفقر في العالم، ويعرض بإيجاز نظرات وممارسات التخفيف المستهدف من الفقر في العصر الجديد من أجل توفير مراجع لكسب المعركة ضد الفقر في الصين وقضية التخفيف من حدة الفقر في العالم.
Book
An interferon-independent lncRNA promotes viral replication by modulating cellular metabolism
Viruses regulate host metabolic networks to improve their survival. The molecules that are responsive to viral infection and regulate such metabolic changes are hardly known, but are essential for understanding viral infection. Here we identify a long noncoding RNA (lncRNA) that is induced by multiple viruses, but not by type I interferon (IFN-I), and facilitates viral replication in mouse and human cells. In vivo deficiency of lncRNA-ACOD1 (a lncRNA identified by its nearest coding gene Acod1, aconitate decarboxylase 1) significantly attenuates viral infection through IFN-I–IRF3 (interferon regulatory factor 3)–independent pathways. Cytoplasmic lncRNA-ACOD1 directly binds the metabolic enzyme glutamic-oxaloacetic transaminase (GOT2) near the substrate niche, enhancing its catalytic activity. Recombinant GOT2 protein and its metabolites could rescue viral replication upon lncRNA-ACOD1 deficiency and increase lethality. This work reveals a feedback mechanism of virus-induced lncRNA-mediated metabolic promotion of viral infection and a potential target for developing broad-acting antiviral therapeutics.
Journal Article
The status of MATLAB in the Software Development Market
With the continuous development of technology, it is necessary to analyze the applicability of MATLAB in the field of software development according to the mainstream trend of the market. This article aims to outline the design purpose of MATLAB and its applicable user groups, and emphasizes the advantages of MATLAB in scientific computing and engineering applications. By comparing it with other programming languages such as Python, this article further highlights the unique advantages of MATLAB in computing performance and functions, thereby clarifying its importance and application value in related fields. This article concludes that as a programming language specializing in computing, MATLAB is not only loved by professionals in engineering, finance, physics, and other fields but also has a high status in education. Through the experiment of developing small games and comparing the rich functions of Python in software development, it points out the immaturity of MATLAB in UI design, code optimization, data transmission, and other aspects. The subsequent research provides some improvements that MATLAB can make in code performance optimization and loop performance. The significance of this study is to let people who are new to software development choose a more suitable programming language.
Journal Article
Reduced-dose radiotherapy for human papillomavirus-associated squamous-cell carcinoma of the oropharynx: a single-arm, phase 2 study
Head and neck cancers positive for human papillomavirus (HPV) are exquisitely radiosensitive. We investigated whether chemoradiotherapy with reduced-dose radiation would maintain survival outcomes while improving tolerability for patients with HPV-positive oropharyngeal carcinoma.
We did a single-arm, phase 2 trial at two academic hospitals in the USA, enrolling patients with newly diagnosed, biopsy-proven stage III or IV squamous-cell carcinoma of the oropharynx, positive for HPV by p16 testing, and with Zubrod performance status scores of 0 or 1. Patients received two cycles of induction chemotherapy with 175 mg/m2 paclitaxel and carboplatin (target area under the curve of 6) given 21 days apart, followed by intensity-modulated radiotherapy with daily image guidance plus 30 mg/m2 paclitaxel per week concomitantly. Complete or partial responders to induction chemotherapy received 54 Gy in 27 fractions, and those with less than partial or no responses received 60 Gy in 30 fractions. The primary endpoint was progression-free survival at 2 years, assessed in all eligible patients who completed protocol treatment. This study is registered with ClinicalTrials.gov, numbers NCT02048020 and NCT01716195.
Between Oct 4, 2012, and March 3, 2015, 45 patients were enrolled with a median age of 60 years (IQR 54–67). One patient did not receive treatment and 44 were included in the analysis. 24 (55%) patients with complete or partial responses to induction chemotherapy received 54 Gy radiation, and 20 (45%) with less than partial responses received 60 Gy. Median follow-up was 30 months (IQR 26–37). Three (7%) patients had locoregional recurrence and one (2%) had distant metastasis; 2-year progression-free survival was 92% (95% CI 77–97). 26 (39%) of 44 patients had grade 3 adverse events, but no grade 4 events were reported. The most common grade 3 events during induction chemotherapy were leucopenia (17 [39%]) and neutropenia (five [11%]), and during chemoradiotherapy were dysphagia (four [9%]) and mucositis (four [9%]). One (2%) of 44 patients was dependent on a gastrostomy tube at 3 months and none was dependent 6 months after treatment.
Chemoradiotherapy with radiation doses reduced by 15–20% was associated with high progression-free survival and an improved toxicity profile compared with historical regimens using standard doses. Radiotherapy de-escalation has the potential to improve the therapeutic ratio and long-term function for these patients.
University of California.
Journal Article
Associations between long-term drought and diarrhea among children under five in low- and middle-income countries
Climate change is projected to intensify drought conditions, which may increase the risk of diarrheal diseases in children. We constructed log-binomial generalized linear mixed models to examine the association between diarrhea risk, ascertained from global-scale nationally representative Demographic and Health Surveys, and drought, represented by the standardized precipitation evapotranspiration index, among children under five in 51 low- and middle-income countries (LMICs). Exposure to 6-month mild or severe drought was associated with an increased diarrhea risk of 5% (95% confidence interval 3–7%) or 8% (5–11%), respectively. The association was stronger among children living in a household that needed longer time to collect water or had no access to water or soap/detergent for handwashing. The association for 24-month drought was strong in dry zones but weak or null in tropical or temperate zones, whereas that for 6-month drought was only observed in tropical or temperate zones. In this work we quantify the associations between exposure to long-term drought and elevated diarrhea risk among children under five in LMICs and suggest that the risk could be reduced through improved water, sanitation, and hygiene practices, made more urgent by the likely increase in drought due to climate change.
Increased droughts are associated with climate change. Here, the authors reveal an association between long-term drought and an elevated risk of diarrhea in children under five in low- and middle income countries, and suggest that improving water quality, sanitation, and hygiene practices might reduce the risk.
Journal Article
Dynamic Properties of Thermally Treated Granite Subjected to Cyclic Impact Loading
The Earth’s deep rock mass is subjected to various complex temperature and stress perturbations. To study the effect of temperature and dynamic disturbance on the damage mechanical properties of these rocks, a series of laboratory tests was carried out by means of a modified split Hopkinson pressure bar system. Specimens were heat treated from room temperature up to a maximum of 800 °C and then cooled to room temperature. During repeated loading tests, the dynamic incident energy was kept constant in each cycle. For samples under the same treated temperature, the dynamic strength and deformation capacity degraded gradually with increasing impact number. Furthermore, rock strength decreased with increasing treated temperature, with the number of impacts before failure reduced accordingly. Since damage can be initiated by thermal treatment and then aggravated by dynamic disturbance, according to the observed decrease in rock strength and increase in strain rate under the different temperature conditions, a temperature of 400 °C was found be a significant failure threshold. The maximum strain was employed to describe damage evolution during cyclic impact loading, indicating that fatigue damage is gradually accumulated and maintains a three-segment growth with an increase in repeated impacts. Under the coupled effect of temperature and cyclic impact loading, specimens exhibited two different failure modes: split tensile failure and unloading failure. The micro-properties of fracture morphology in granite after different temperature and repeated impact were also discussed in detail.
Journal Article
Association of Socioeconomic Area Deprivation Index with Hospital Readmissions After Colon and Rectal Surgery
Background
Risk adjustment for reimbursement and quality measures omits social risk factors despite adversely affecting health outcomes. Social risk factors are not usually available in electronic health records (EHR) or administrative data. Socioeconomic status can be assessed by using US Census data. Distressed Communities Index (DCI) is based upon zip codes, and the Area Deprivation Index (ADI) provides more granular estimates at the block group level. We examined the association of neighborhood disadvantage using the ADI, DCI, and patient-level insurance status on 30-day readmission risk after colorectal surgery.
Methods
Our 677 patient cohort was derived from the 2013–2017 National Surgical Quality Improvement Program at a safety net hospital augmented with EHR data to determine insurance status and 30-day readmissions. Patients’ home addresses were linked to the ADI and DCI.
Results
Our cohort consisted of 53.9% males and 63.8% Hispanics with a 22.9% 30-day readmission rate from the date of discharge; > 50% lived in highly deprived neighborhoods. Controlling for medical comorbidities and complications, ADI was associated with increased risk of 30 days from the date of discharge readmissions among patients living in medium (OR = 2.15,
p
= .02) or high (OR = 1.88,
p
= .03) deprived areas compared to less-deprived neighborhoods, but not insurance status or DCI.
Conclusions
The ADI identified patients living in deprived communities with increased readmission risk. Our results show that block-group level ADI can potentially be used in risk adjustment, to identify high-risk patients and to design better care pathways that improve health outcomes.
Journal Article
Single cell transcriptomic analyses implicate an immunosuppressive tumor microenvironment in pancreatic cancer liver metastasis
Pancreatic ductal adenocarcinoma (PDAC) is a highly metastatic disease refractory to all targeted and immune therapies. However, our understanding of PDAC microenvironment especially the metastatic microenvironment is very limited partly due to the inaccessibility to metastatic tumor tissues. Here, we present the single-cell transcriptomic landscape of synchronously resected PDAC primary tumors and matched liver metastases. We perform comparative analysis on both cellular composition and functional phenotype between primary and metastatic tumors. Tumor cells exhibit distinct transcriptomic profile in liver metastasis with clearly defined evolutionary routes from cancer cells in primary tumor. We also identify specific subtypes of stromal and immune cells critical to the formation of the pro-tumor microenvironment in metastatic lesions, including RGS5
+
cancer-associated fibroblasts, CCL18
+
lipid-associated macrophages, S100A8
+
neutrophils and FOXP3
+
regulatory T cells. Cellular interactome analysis further reveals that the lack of tumor-immune cell interaction in metastatic tissues contributes to the formation of the immunosuppressive microenvironment. Our study provides a comprehensive characterization of the transcriptional landscape of PDAC liver metastasis.
The metastatic tumour microenvironment in pancreatic ductal adenocarcinoma (PDAC) remains to be explored. Here, the authors perform single cell RNA sequencing analysis for synchronously resected PDAC primary tumours and matched liver metastases and find differences in cellular composition.
Journal Article