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إحضار الكتب المقدسة
عاش النبيل كو في بلدة تونغتايفو كان رجلا طيبا يحب الخير وعرض أن يستضيف سان تسانغ وتلاميذه لفترة طويلة، ولكنهم رفضوا رغم إلحاح عائلة النبيل؛ فلم يجدوا بدا من توديعهم. وما إن غادر سان تسانغ وتلاميذه حتى تعرض بيت النبيل للسرقة، وقتل النبيل كو، فأضمرت زوجته الضغينة لسان تسانغ وتلاميذه لأنهم لم يوافقوا على البقاء رغم الإلحاح عليهم، واتهمت الزوجة سان تسانغ وتلاميذه زورا بارتكاب الجريمة، وقدمت دعوى لمقاضاتهم. وفي طريق اللصوص للفرار، أرادوا سرقة سان تسانغ وتلاميذه أيضا، ولكن وو كونغ قبض عليهم، وحينما التقى سان تسانغ وتلاميذه بالضباط والجنود الذين جاؤوا لملاحقتهم، حدث سوء فهم أدى لاتهام سان تسانغ وتلاميذه.
Book
Quantifying methane emissions from the global scale down to point sources using satellite observations of atmospheric methane
We review the capability of current and scheduled satellite observations of atmospheric methane in the shortwave infrared (SWIR) to quantify methane emissions from the global scale down to point sources. We cover retrieval methods, precision and accuracy requirements, inverse and mass balance methods for inferring emissions, source detection thresholds, and observing system completeness. We classify satellite instruments as area flux mappers and point source imagers, with complementary attributes. Area flux mappers are high-precision (<1 %) instruments with 0.1–10 km pixel size designed to quantify total methane emissions on regional to global scales. Point source imagers are fine-pixel (<60 m) instruments designed to quantify individual point sources by imaging of the plumes. Current area flux mappers include GOSAT (2009–present), which provides a high-quality record for interpretation of long-term methane trends, and TROPOMI (2018–present), which provides global continuous daily mapping to quantify emissions on regional scales. These instruments already provide a powerful resource to quantify national methane emissions in support of the Paris Agreement. Current point source imagers include the GHGSat constellation and several hyperspectral and multispectral land imaging sensors (PRISMA, Sentinel-2, Landsat-8/9, WorldView-3), with detection thresholds in the 100–10 000 kg h−1 range that enable monitoring of large point sources. Future area flux mappers, including MethaneSAT, GOSAT-GW, Sentinel-5, GeoCarb, and CO2M, will increase the capability to quantify emissions at high resolution, and the MERLIN lidar will improve observation of the Arctic. The averaging times required by area flux mappers to quantify regional emissions depend on pixel size, retrieval precision, observation density, fraction of successful retrievals, and return times in a way that varies with the spatial resolution desired. A similar interplay applies to point source imagers between detection threshold, spatial coverage, and return time, defining an observing system completeness. Expanding constellations of point source imagers including GHGSat and Carbon Mapper over the coming years will greatly improve observing system completeness for point sources through dense spatial coverage and frequent return times.
Journal Article
DNMT3A p.R882C driven proliferation and anti-apoptotic effects in pancreatic cancer cells
Pancreatic cancer, one of the most lethal malignancies, is characterized by insidious onset, frequent late-stage diagnosis, rapid progression, and limited surgical opportunities. Pancreatic ductal adenocarcinoma (PDAC), accounting for over 90% of pancreatic cancer cases, remains a therapeutic challenge due to the scarcity of effective targeted therapies. In this study, we collected formalin-fixed paraffin-embedded (FFPE) specimens from three patients with moderately to poorly differentiated PDAC, extracted genomic DNA, and performed whole-exome sequencing. Through bioinformatics analysis, we identified 68 high-risk deleterious variants, including the DNMT3A p.R882C mutation. This mutation exhibits low frequency in public databases (e.g., esp6500si, GnomAD) and is consistently predicted as deleterious by multiple algorithms (SIFT, Polyphen, LRT, CADD). To investigate its functional impact, wild-type and mutant DNMT3A constructs were cloned into p3xflag-CMV-10 plasmids and transfected into the pancreatic cancer cell lines PANC-1 and PaTu 8988t. In vitro cellular experiments demonstrated that the DNMT3A p.R882C mutation does not alter DNMT3A expression at mRNA or protein levels but significantly promotes cancer cell proliferation and migration while inhibiting apoptosis. These findings suggest that the DNMT3A p.R882C mutation may play a critical role in PDAC pathogenesis. This study not only provides essential laboratory evidence for elucidating PDAC development but also offers new insights for potential targeted therapeutic strategies in pancreatic cancer.
Journal Article
Acute fatty liver of pregnancy in the context of normal-dose acetaminophen exposure: a case report
Background
Acute fatty liver of pregnancy (AFLP) is a rare but serious complication in the third trimester, characterized by microvesicular hepatic steatosis and risk of rapid progression to liver failure and multi-organ dysfunction. Despite improved care, maternal and perinatal mortality remain significant. Acetaminophen is commonly used during pregnancy with a good safety profile, but hepatotoxicity can occur. This report highlights the successful treatment of AFLP during therapeutic acetaminophen use, emphasizing the need for timely, multidisciplinary management.
Case presentation
We report the case of a 37-year-old primigravida at 36 + 3 weeks’ gestation who presented with nausea, vomiting, abdominal pain, jaundice, and clinical signs of fetal growth restriction. Notably, she had been intermittently taking therapeutic doses of acetaminophen specifically for dental pain. Laboratory investigations revealed marked hepatic dysfunction, coagulopathy, and acute kidney injury. As her clinical condition deteriorated rapidly, an emergency cesarean section was performed, resulting in the birth of a healthy female neonate at 36 weeks of gestation, weighing 2220 g, corresponding to the 7.6th percentile for gestational age according to locally derived reference standards. Postoperatively, her liver failure worsened, requiring plasma exchange, artificial liver support, and intensive care. Multidisciplinary management led to her full recovery, and she was discharged in stable condition. Both the mother and the infant remained in good health during the one‑year follow‑up period.
Conclusion
AFLP is a rare but potentially life threatening complication of late gestation that can rapidly progress to acute hepatic dysfunction with coagulopathy and multiorgan involvement. This case highlights the diagnostic complexity of AFLP in late gestation, particularly when recent therapeutic acetaminophen use may confound clinical assessment despite the absence of overdose. In pregnant patients with acetaminophen exposure, careful differentiation between AFLP and drug induced liver injury is critical. Further studies are warranted to clarify whether therapeutic dose acetaminophen use contributes to AFLP risk in metabolically susceptible patients.
Journal Article
Renal microvascular lesions in lupus nephritis
Renal microvascular lesions, common in lupus nephritis (LN), are associated with long-term poor outcomes. There are mainly five pathological types of renal microvascular lesions in LN: (1) vascular immune complex deposits (ICD), (2) arteriosclerosis (AS), (3) thrombotic microangiopathy (TMA), (4) non-inflammatory necrotizing vasculopathy (NNV), and (5) true renal vasculitis (TRV). The pathogenesis of renal microvascular lesions in LN remains to be elucidated. The activation and dysfunction of endothelial cells, in addition to the contribution of immune system dysfunction, especially the immune complex-induced vascular inflammation and antiphospholipid antibody-associated thrombotic events, are key mechanisms in the development of vascular lesions in LN that need to be further investigated. Alteration of the microvascular environment produces an acute immunological response that recruits immune cells, such as T cells, monocytes, and macrophages, which induces platelet aggregation with microthrombus formation. There is also increased cytotoxicity caused by cytokines produced by immune cells in the kidney. Identifying the mechanism underlying the pathogenesis of renal microvascular lesions in LN might provide potential targets for the development of novel therapies.
Journal Article
Attribution of the accelerating increase in atmospheric methane during 2010–2018 by inverse analysis of GOSAT observations
We conduct a global inverse analysis of 2010–2018 GOSAT observations to better understand the factors controlling atmospheric methane and its accelerating increase over the 2010–2018 period. The inversion optimizes anthropogenic methane emissions and their 2010–2018 trends on a 4∘×5∘ grid, monthly regional wetland emissions, and annual hemispheric concentrations of tropospheric OH (the main sink of methane). We use an analytical solution to the Bayesian optimization problem that provides closed-form estimates of error covariances and information content for the solution. We verify our inversion results with independent methane observations from the TCCON and NOAA networks. Our inversion successfully reproduces the interannual variability of the methane growth rate inferred from NOAA background sites. We find that prior estimates of fuel-related emissions reported by individual countries to the United Nations are too high for China (coal) and Russia (oil and gas) and too low for Venezuela (oil and gas) and the US (oil and gas). We show large 2010–2018 increases in anthropogenic methane emissions over South Asia, tropical Africa, and Brazil, coincident with rapidly growing livestock populations in these regions. We do not find a significant trend in anthropogenic emissions over regions with high rates of production or use of fossil methane, including the US, Russia, and Europe. Our results indicate that the peak methane growth rates in 2014–2015 are driven by low OH concentrations (2014) and high fire emissions (2015), while strong emissions from tropical (Amazon and tropical Africa) and boreal (Eurasia) wetlands combined with increasing anthropogenic emissions drive high growth rates in 2016–2018. Our best estimate is that OH did not contribute significantly to the 2010–2018 methane trend other than the 2014 spike, though error correlation with global anthropogenic emissions limits confidence in this result.
Journal Article
Exposure to volatile organic compounds and sarcopenia risk in US adults based on NHANES
This study investigates the association between volatile organic compounds (VOCs) and sarcopenia in a cohort of 3,391 U.S. participants aged 20–59 years, using NHANES data from 2011 to 2018. Various urinary metabolites of VOCs (mVOCs) were analyzed, and in multivariate logistic regression, CEMA (a metabolite of acrolein), CYMA (a metabolite of acrylonitrile), ATCA (a metabolite of cyanide), and 3,4-MHA (a metabolite of xylene) were found to have significant associations with sarcopenia. Weighted Quantile Sum (WQS) and Bayesian Kernel Machine Regression (BKMR) analyses further supported these findings, identifying ATCA as a key contributor. Subgroup analyses revealed meaningful associations between sarcopenia and mVOCs in both men and women. Additionally, mediation analysis identified high-density lipoprotein (HDL) as a partial mediator, contributing to 3.8% of the effect. These results emphasize the need for future longitudinal studies to establish causality and further explore the underlying biological mechanisms.
Journal Article
Identification of Serum miRNAs as Effective Diagnostic Biomarkers for Distinguishing Primary Central Nervous System Lymphoma from Glioma
Invasive surgical cerebrum biopsy results in delayed treatment for the definitive diagnosis of primary central nervous system lymphoma (PCNSL). The existent research was aimed at confirming the underlying diagnostic miRNAs of distinguishing PCNSL from glioma. A publicly available miRNA expression profiles (GSE139031) from adult PCNSL as well as glioma specimens were provided by GEO datasets. Differentially expressed miRNAs (DEMs) were filtered between 42 PCNSL patients and 170 glioma patients. Candidate miRNAs were identified through SVM-RFE analysis and LASSO model. ROC assays were operated to determine the diagnostic value of serum miRNAs in distinguishing PCNSL from glioma. StarBase v2.0 was applied to screen the targeting genes of miRNAs, and KEGG analysis was applied using the targeting genes of miRNAs. In this study, we identified 12 dysregulated miRNAs between PCNSL and glioma samples. The ten critical miRNAs (miR-6820-3p, miR-6803-3p, miR-30a-3p, miR-4751, miR-3918, miR-146a-3p, miR-548am-3p, miR-371a-3p, miR-487a-3p, and miR-4756-5p) between these two algorithms were ultimately identified. The results of KEGG revealed that the targeting genes of hsa-miR-3918 were primarily related to MAPK signal pathway, PI3K-Akt signal pathway, and human papillomavirus infection. Overall, bioinformatics analysis revealed that ten miRNAs are potential biomarker for distinguishing PCNSL from glioma.
Journal Article
Unexpected slowdown of US pollutant emission reduction in the past decade
Ground and satellite observations show that air pollution regulations in the United States (US) have resulted in substantial reductions in emissions and corresponding improvements in air quality over the last several decades. However, large uncertainties remain in evaluating how recent regulations affect different emission sectors and pollutant trends. Here we show a significant slowdown in decreasing US emissions of nitrogen oxides (NOₓ) and carbon monoxide (CO) for 2011–2015 using satellite and surface measurements. This observed slowdown in emission reductions is significantly different from the trend expected using US Environmental Protection Agency (EPA) bottom-up inventories and impedes compliance with local and federal agency air-quality goals. We find that the difference between observations and EPA’s NOₓ emission estimates could be explained by: (i) growing relative contributions of industrial, area, and off-road sources, (ii) decreasing relative contributions of on-road gasoline, and (iii) slower than expected decreases in on-road diesel emissions.
Journal Article
Differences in risk of serious infections between patients with secondary versus primary nephropathy following rituximab treatment: a retrospective cohort study
The incidence of severe infections (SIs) in patients with autoimmune nephropathy after rituximab (RTX) treatment varies significantly. Our study aims to identify high-risk populations, specifically by comparing the differences in the risk of SIs between patients with primary nephropathy and those with nephropathy in the context of systemic autoimmune diseases (referred to as secondary nephropathy).
This retrospective cohort study investigated the occurrence of SIs in adult patients with immune-related kidney disease who received RTX treatment at our institution from 2017 to 2022. Multivariable COX regression models were used to analyze the association between the type of nephropathy (primary or secondary) and SIs. Propensity score analyses, subgroup analyses, and E-value calculations were performed to ensure the reliability of the results.
Out of 123 patients, 32 (26%) developed 39 cases of SIs during a mean follow-up period of 19.7 ± 14.6 months post-RTX treatment, resulting in an incidence rate of 18.9/100 patient-years. The multivariable COX regression analysis indicated that patients with secondary nephropathy had a significantly higher risk of SIs compared to those with primary nephropathy (HR = 5.86, 95% CI: 1.05-32.63, P = 0.044), even after accounting for confounding variables including gender, age, BMI, history of prior SIs, baseline eGFR, lymphocyte counts, IgG levels, and the utilization of other immunosuppressive therapies. Various sensitivity analyses consistently supported these findings, with an E-value of 5.99. Furthermore, advanced age (HR: 1.03; 95% CI: 1.01-1.06; P = 0.023), low baseline IgG levels (HR: 0.75; 95% CI: 0.64-0.89; P < 0.001), and recent history of SIs (HR: 5.68; 95% CI: 2.2-14.66; P < 0.001) were identified as independent risk factors.
The incidence of SIs following RTX administration in patients with autoimmune nephropathy is significant. It is crucial to note that there are distinct differences between the subgroups of primary and secondary nephropathy. Patients with secondary nephropathy, particularly those who are elderly, have low baseline IgG levels, and have a recent history of SI, are more susceptible to SIs.
Journal Article