Background To comprehensively analyze the risk factors, clinical characteristics, outcomes, and prognostic factors of Cytomegalovirus (CMV) enteritis. Methods This retrospective cohort study enrolled ...patients who had undergone pathological examinations for CMV enteritis. They were divided into CMV and non-CMV groups according to immunohistochemistry staining results. The risk factors, clinical presentations, endoscopic features, treatments, outcomes, and prognostic factors of CMV enteritis were then analyzed. Results Forty-two patients (18 CMV, 24 non-CMV group) were included in the study. Major clinical presentations in the CMV group included gastrointestinal bleeding (72.2%), abdominal pain (55.6%), and fever (33.3%); ulcers (72.2%) were the most common endoscopic findings. In-hospital and overall mortality rates were 27.8% and 38.9%, respectively; and longer hospital stays and higher overall mortality rates were observed. Radiotherapy and C-reactive protein levels were prognostic factors for in-hospital mortality. The risk factors for CMV enteritis included immunocompromised status (p = 0.013), steroid use (p = 0.014), shock (p = 0.031), concurrent pneumonia (p = 0.01), antibiotic exposure (p < 0.001), radiotherapy (p = 0.027), chronic kidney disease (p = 0.041), and CMV colitis (p = 0.031). Conclusions Physicians should pay attention to the characteristics of CMV enteritis in high-risk patients to make an early diagnosis and potentially improve the clinical outcome. Keywords: Cytomegalovirus enteritis, Endoscopy, Risk factor, Prognostic factor, Immunohistochemistry staining
The HfNbTaTiZr refractory high-entropy alloy was investigated on the grain growth kinetics and tensile properties. Grain growth at 1200–1350°C is rather slow. The activation energy is 389kJ/mol and ...the growth exponent is 3.5. The HfNbTaTiZr alloy has high strength, small work hardening and high ductility. Grain refining is found to enhance the tensile strength and ductility simultaneously.
•The HfNbTaTiZr alloy exhibits low rate and high activation energy of grain growth.•The slow grain boundary migration is a result of the solute-drag mechanism.•Grain refinement simultaneously increases tensile strength and ductility•The alloy with a small grain size has excellent tensile yield strength and ductility.
Background and aims
Although methamphetamine use is a serious public health problem, large‐scale cohort studies assessing methamphetamine‐related mortality are scant. This study investigated ...all‐cause mortality and suicide methods in people with methamphetamine use disorder.
Design
A cohort record‐linkage study using data from Taiwan's National Health Research Institute Database (NHIRD) linked to Taiwan's National Death Certification System.
Setting
Taiwan.
Participants
A total of 23 248 individuals with methamphetamine use disorder between 1 January 2001 and 31 December 2005.
Measurements
The outcome variables included mortality rates and standardized mortality ratios (SMRs) for all causes of death and for each suicide method.
Findings
Compared with the general population, the current cohort had an increased all‐cause mortality (SMR = 5.4), with the SMR for unnatural causes (14.8) higher than that for natural causes (7.5). Among all causes of death, suicide had the highest SMR (16.3), followed by neurological diseases (9.7). Among the methods of choice for suicide, drug overdose had the highest SMR (24.9). The incidence of charcoal burning and hanging was significantly higher in men and that of jumping from a high place was significantly higher in women.
Conclusion
People in Taiwan with methamphetamine use disorder appear to have a significantly increased all‐cause mortality rate compared with the general population, with suicide having the highest contribution, particularly suicide via drug overdose. The methods of choice for suicide revealed distinct patterns between men and women.
Osteoclasts are multinuclear giant cells responsible for bone resorption in lytic bone diseases such as osteoporosis, arthritis, periodontitis, and bone tumors. Due to the severe side‐effects caused ...by the currently available drugs, a continuous search for novel bone‐protective therapies is essential. Artesunate (Art), the water‐soluble derivative of artemisinin has been investigated owing to its anti‐malarial properties. However, its effects in osteoclastogenesis have not yet been reported. In this study, Art was shown to inhibit the nuclear factor‐κB ligand (RANKL)‐induced osteoclastogenesis, the mRNA expression of osteoclastic‐specific genes, and resorption pit formation in a dose‐dependent manner in primary bone marrow‐derived macrophages cells (BMMs). Furthermore, Art markedly blocked the RANKL‐induced osteoclastogenesis by attenuating the degradation of IκB and phosphorylation of NF‐κB p65. Consistent with the in vitro results, Art inhibited lipopolysaccharide (LPS)‐induced bone resorption by suppressing the osteoclastogenesis. Together our data demonstrated that Art inhibits RANKL‐induced osteoclastogenesis by suppressing the NF‐κB signaling pathway and that it is a promising agent for the treatment of osteolytic diseases.
Artesunate (Art), the water‐soluble derivative of artemisinin has been investigated owing to its anti‐malarial properties. However, its effects on osteoclastogenesis have not yet been reported. In this study, Art was shown to inhibit the nuclear factor‐kB ligand (RANKL)‐induced osteoclastogenesis and lipopolysaccharide (LPS)‐induced bone resorption.
Background and Purpose
Atherosclerosis induced by cyclosporine A (CsA), an inhibitor of the calcineurin/nuclear factor of activated T cells (NFAT) pathway, is a major concern after organ ...transplantation. However, the atherosclerotic mechanisms of CsA remain obscure. We previously demonstrated that calcineurin/NFAT signalling inhibition contributes to atherogenesis via suppressing microRNA‐204 (miR‐204) transcription. We therefore hypothesised that miR‐204 is involved in the development of CsA‐induced atherosclerosis.
Experimental Approach
ApoE−/− mice with macrophage‐miR‐204 overexpression were generated to determine the effects of miR‐204 on CsA‐induced atherosclerosis. Luciferase reporter assays and chromatin immunoprecipitation sequencing were performed to explore the targets mediating miR‐204 effects.
Key Results
CsA alone did not significantly affect atherosclerotic lesions or serum lipid levels. However, it exacerbated high‐fat diet‐induced atherosclerosis and hyperlipidemia in C57BL/6J and ApoE−/− mice, respectively. miR‐204 levels decreased in circulating monocytes and plaque lesions during CsA‐induced atherosclerosis. The upregulation of miR‐204 in macrophages inhibited CsA‐induced atherosclerotic plaque formation but did not affect serum lipid levels. miR‐204 limited the CsA‐induced foam cell formation by reducing the expression of the scavenger receptors SR‐BII and CD36. SR‐BII was post‐transcriptionally regulated by mature miR‐204‐5p via 3′‐UTR targeting. Additionally, nuclear‐localised miR‐204‐3p prevented the CsA‐induced binding of Ago2 to the CD36 promoter, suppressing CD36 transcription. SR‐BII or CD36 expression restoration dampened the beneficial effects of miR‐204 on CsA‐induced atherosclerosis.
Conclusion and Implications
Macrophage miR‐204 ameliorates CsA‐induced atherosclerosis, suggesting that miR‐204 may be a potential target for the prevention and treatment of CsA‐related atherosclerotic side effects.
Danshen has been widely used for the treatment of central nervous system diseases. We investigated the effect of dihydroisotanshinone I (DT), a compound extracted from Danshen, as well as the ...corresponding mechanisms in an in vitro-based 6-OHDA-induced Parkinson's disease (PD) model. SH-SY5Y human neuroblastoma cell lines were pretreated with 6-hydroxydopamine (6-OHDA) and challenged with DT. Subsequently, the cell viability and levels of reactive oxygen species (ROS) and caspase-3 were analyzed. The effect of DT on the 6-OHDA-treated SH-SY5Y cells and the expression of the core circadian clock genes were measured using a real-time quantitative polymerase chain reaction. Our results indicated that DT attenuated the 6-OHDA-induced cell death in the SH-SY5Y cells and suppressed ROS and caspase-3. Moreover, DT reversed both the RNA and protein levels of
and
in the 6-OHDA-treated SH-SY5Y cells. Additionally, the
inhibitor attenuated the effect of DT on
and reduced the cell viability. The DT and
activators activated
and
, and then reduced the death of the SH-SY5Y cells damaged by 6-OHDA. SIRT1 silencing was enhanced by DT and resulted in a BMAL1 downregulation and a reduction in cell viability. In conclusion, our investigation suggested that DT reduces cell apoptosis, including an antioxidative effect due to a reduction in ROS, and regulates the circadian genes by enhancing SIRT1 and suppressing BMAL1. DT may possess novel therapeutic potential for PD in the future, but further in vivo studies are still needed.
A new type of lanthanum‐based high entropy perovskite oxide (HEPO) electrocatalyst for the oxygen evolution reaction is reported. The B‐site lattices in the HEPO consist of five consecutive first‐row ...transition metals, including Cr, Mn, Fe, Co, and Ni. Equimolar and five non‐equimolar HEPO electrocatalysts are studied for their OER electrocatalytic performance. In the five non‐equimolar HEPOs, the concentration of one of the five transition metals is doubled in individual samples. The performances of all the HEPOs outperform the single perovskite oxides. The optimized La(CrMnFeCo2Ni)O3 HEPO exhibits an outstanding OER overpotential of 325 mV at a current density of 10 mA cm−2 and excellent electrochemical stability after 50 h of testing.
Lanthanum‐based high entropy perovskite oxides (HEPOs) with a B‐site consisting of five consecutive first‐row transition metals are synthesized in both equimolar and non‐equimolar ratios. The HEPO electrocatalysts outperform the single perovskite oxides. The optimized La(CrMnFeCo2Ni)O3 HEPO exhibits an outstanding OER overpotential of 325 mV at 10 mA cm–2 and excellent stability after 50 h of testing.
Magnesium isotopic compositions are reported for twenty‐four international geological reference materials including igneous, metamorphic and sedimentary rocks, as well as phlogopite and serpentine ...minerals. The long‐term reproducibility of Mg isotopic determination, based on 4‐year analyses of olivine and seawater samples, was ≤ 0.07‰ (2s) for δ26Mg and ≤ 0.05‰ (2s) for δ25Mg. Accuracy was tested by analysis of synthetic reference materials down to the quoted long‐term reproducibility. This comprehensive dataset, plus seawater data produced in the same laboratory, serves as a reference for quality assurance and inter‐laboratory comparison of high‐precision Mg isotopic data.
Les compositions isotopiques du magnésium sont fournies pour vingt‐quatre matériaux géologiques de référence internationaux, comprenant des roches ignées, métamorphiques et sédimentaires, ainsi qu'une phlogopite et des serpentines. La reproductibilité à long terme de la détermination isotopique du Mg, basée des analyses sur quatre ans d’échantillons d'olivine et d'eau de mer, était ≤ 0.07% (2s) pour δ26Mg et ≤ 0.05% (2s) pour δ25Mg. La précision a été testée par l'analyse de matériaux de référence synthétiques jusqu’à la reproductibilité à long terme indiquée. Cette base de données complète, ainsi que des données d'eau de mer produites dans le même laboratoire, servent de référence pour l'assurance qualité et la comparaison inter‐laboratoires de haute précision des données isotopiques du Mg.
Large cardiovascular outcome trials have reported favorable effects of sodium-glucose co-transporter 2 (SGLT2) inhibitors on heart failure. To study the potential mechanism of the SGLT2 inhibition in ...heart failure, we used the murine doxorubicin-induced cardiomyopathy model and identified the toll-like receptor 9 (TLR9), NAD-dependent deacetylase sirtuin-3 (SIRT3), and Beclin 1, acting in a complex together in response to empagliflozin treatment. The interactions and implications in mitochondrial function were evaluated with TLR9 deficient, SIRT3 deficient, Beclin 1 haplodeficient, and autophagy reporter mice and confirmed in a patient with SIRT3 point mutation and reduced enzymatic activity. The SGLT2 inhibitor, empagliflozin, protects the heart from doxorubicin cardiomyopathy in mice, by acting through a novel Beclin 1-toll-like receptor (TLR) 9-sirtuin-(SIRT) 3 axis. TLR9 and SIRT3 were both essential for the protective effects of empagliflozin. The dilated cardiomyopathy patient with SIRT3 point mutation and reduced enzymatic activity is associated with reduced TLR9 activation and the absence of mitochondrial responses in the heart after the SGLT2 inhibitor treatment. Our data indicate a dynamic communication between autophagy and Beclin 1-TLR9-SIRT3 complexes in the mitochondria in response to empagliflozin that may serve as a potential treatment strategy for heart failure.
Personalized medical care focuses on prediction of disease risk and response to medications. To build the risk models, access to both large-scale genomic resources and human genetic studies is ...required. The Taiwan Biobank (TWB) has generated high-coverage, whole-genome sequencing data from 1492 individuals and genome-wide SNP data from 103,106 individuals of Han Chinese ancestry using custom SNP arrays. Principal components analysis of the genotyping data showed that the full range of Han Chinese genetic variation was found in the cohort. The arrays also include thousands of known functional variants, allowing for simultaneous ascertainment of Mendelian disease-causing mutations and variants that affect drug metabolism. We found that 21.2% of the population are mutation carriers of autosomal recessive diseases, 3.1% have mutations in cancer-predisposing genes, and 87.3% carry variants that affect drug response. We highlight how TWB data provide insight into both population history and disease burden, while showing how widespread genetic testing can be used to improve clinical care.
PDF
