Voriconazole plus flucytosine is not superior to amphotericin B deoxycholate plus flucytosine as an induction regimen for cryptococcal meningitis treatment.

BACKGROUND: The efficacy and side effects of voriconazole plus 5-flucytosine (Vori + 5-FC) versus amphotericin B deoxycholate plus 5-flucytosine (AmBd + 5-FC) as an induction treatment for cryptococcal meningitis are unknown. METHODS: Forty-seven patients treated with Vori + 5-FC and 92 patients treated with AmBd + 5-FC were included in the current study after propensity score matching (PSM) at a ratio of 1:2. Two-week laboratory test results and 90-day mortality were compared between the two groups. RESULTS: After 2 weeks of induction treatment, the CSF Cryptococcus sterile culture rate was 57.1% in the Vori + 5-FC group and 76.5% in the AmBd + 5-FC group (p = .026). No difference was found in the normalization of CSF indicators (glucose, total protein, intracranial pressure and India ink sterile rate) between the two groups. Both the Vori + 5FC regimen and AmBd + 5-FC regimen obviously decreased haemoglobin concentrations, platelet counts and serum potassium levels (all p ≤ .010). Notably, the Vori + 5FC regimen did not influence serum creatinine levels (p = .263), while AmBd + 5FC increased serum creatinine levels (p = .019) after 2-week induction treatment. The Vori + 5-FC group and AmBd + 5-FC group had similar 90-day cumulative survival rates (89.9% vs. 87.8%, p = .926). CONCLUSION: The Vori + 5-FC regimen was associated with low 2-week CSF sterile culture and was not superior to AmBd + 5-FC as induction therapy in terms of the 90-day cumulative survival rate of CM patients.

The BACE1-generated C-terminal fragment of the neural cell adhesion molecule 2 (NCAM2) promotes BACE1 targeting to Rab11-positive endosomes.

Beta-site amyloid precursor protein cleaving enzyme 1 (BACE1), also known as ß-secretase, is an aspartic protease. The sorting of this enzyme into Rab11-positive recycling endosomes regulates the BACE1-mediated cleavage of its substrates, however, the mechanisms underlying this targeting remain poorly understood. The neural cell adhesion molecule 2 (NCAM2) is a substrate of BACE1. We show that BACE1 cleaves NCAM2 in cultured hippocampal neurons and NCAM2-transfected CHO cells. The C-terminal fragment of NCAM2 that comprises the intracellular domain and a small portion of NCAM2's extracellular domain, associates with BACE1. This association is not affected in cells with inhibited endocytosis, indicating that the interaction of NCAM2 and BACE1 precedes the targeting of BACE1 from the cell surface to endosomes. In neurons and CHO cells, this fragment and BACE1 co-localize in Rab11-positive endosomes. Overexpression of full-length NCAM2 or a recombinant NCAM2 fragment containing the transmembrane and intracellular domains but lacking the extracellular domain leads to an increase in BACE1 levels in these organelles. In NCAM2-deficient neurons, the levels of BACE1 are increased at the cell surface and reduced in intracellular organelles. These effects are correlated with increased levels of the soluble extracellular domain of BACE1 in the brains of NCAM2-deficient mice, suggesting increased shedding of BACE1 from the cell surface. Of note, shedding of the extracellular domain of Sez6, a protein cleaved exclusively by BACE1, is reduced in NCAM2-deficient animals. These results indicate that the BACE1-generated fragment of NCAM2 regulates BACE1 activity by promoting the targeting of BACE1 to Rab11-positive endosomes.

TRIM16 exerts protective function on myocardial ischemia/reperfusion injury through reducing pyroptosis and inflammation via NLRP3 signaling.

Myocardial infarction is still a leading cause of morbidity and mortality worldwide, but its pathogenesis has not been fully understood. In the study, we attempted to explore the effects of E3 ligase tripartite motif 16 (TRIM16) on myocardial ischemia-reperfusion (MI/R) injury in vivo and in vitro, and the underlying mechanisms. We identified that TRIM16 was indeed a potent regulator during MI/R progression in murine models and surprisingly showed a negative correlation with the concentrations of cardiac pro-inflammatory cytokines. Adenoviral vectors encoding GFP or TRIM16 (Ad-TRIM16) were subjected to mice through direct injection into the left ventricular (LV). We found that Ad-TRIM16 significantly reduced the infarct size, and improved the cardiac function and structure compared with the Ad-GFP mice after MI/R operation. More studies indicated that TRIM16 over-expression strongly meliorated nucleotide-binding oligomerization domain-like receptor family pyrin domain containing 3 (NLRP3) inflammasome and associated inflammatory response in hearts of MI/R-induced mice, which were validated in hypoxia/reoxygenation (H/R)-exposed primary cardiomyocytes in vitro. In particular, MI/R operation led to cardiac pyroptosis by increasing the cleavage of Caspase-1 and Gasdermin D (GSDMD), while being considerably abrogated upon TRIM16 over-expression. Mechanistically, TRIM16 interacted with NLRP3 and promoted the K48-linked polyubiquitination of NLRP3, ultimately promoted its degradation. Together, we identified TRIM16 as a novel E3 ubiquitin ligase for NLRP3, which played an essential role in modulating its expression, and subsequently influenced inflammatory response and pyroptosis in MI/R murine model, confirming that TRIM16 may be a potential therapeutic target for myocardial infarction.

Disseminated talaromycosis complicated by recurrent gastrointestinal bleeding and hemorrhagic shock: a case report.

BACKGROUND: Gastrointestinal involvement is not uncommon in patients with disseminated talaromycosis, but successful management of massive gastrointestinal bleeding and hemorrhagic shock secondary to talaromycosis is rarely reported. Clinical management strategies for these patients have not been well documented. CASE PRESENTATION: Here, we reported a case of disseminated talaromycosis with recurrent gastrointestinal bleeding and hemorrhagic shock who was successfully alleviated solely with medical treatment. CONCLUSIONS: Early diagnosis and treatment for Talaromyces marneffei, intravenous fluid resuscitation, hemostatic therapy and blood transfusion are all essential for talaromycosis complicated with gastrointestinal bleeding and hemorrhagic shock. It is also necessary to warn about the possibility of bleeding induced or aggravated by endoscopic biopsy trauma.

Anti-arrhythmic and anti-heart failure effects of low-level electrical stimulation on aortic root ventricular ganglionated plexi.

BACKGROUND: It remains uncertain whether low-level electrical stimulation (LL-ES) of the ventricular ganglionated plexi (GP) improves heart function. This study investigated the anti-arrhythmic and anti-heart failure effects of LL-ES of the aortic root ventricular GP (ARVGP). METHODS: Thirty dogs were divided randomly into control, drug, and LL-ES groups after performing rapid right ventricular pacing to establish a heart failure (HF) model. The inducing rate of arrhythmia; levels of bioactive factors influencing HF, including angiotensin II type I receptor (AT-1R), transforming growth factor-beta (TGF-ß), matrix metalloproteinase (MMP), and phosphorylated extracellular signal-regulated kinase (p-ERK1/2); left ventricular stroke volume (LVSV), and left ventricular ejection fraction (LVEF)were measured after treatment with placebo, drugs, and LL-ES. RESULTS: The inducing rate of atrial arrhythmia decreased from 60% in the control group to 50% in the drug group and 10% in the LL-ES group (p = .033 vs. drug group) after 1 week of treatment. The ventricular effective refractory period was prolonged from 139 ± 8 ms in the drug group to 166 ± 13 ms in the LL-ES group (p = .001). Compared to the drug group, the expressions of AT-1R, TGF-ß, and MMP proteins were down-regulated in the LL-ES group, whereas that of p-ERK1/2 was significantly increased (all p = .001). Moreover, in the LL-ES group, LVSV increased markedly from 13.16 ± 0.22 to 16.86 ± 0.27 mL, relative to that in the drug group (p = .001), and LVEF increased significantly from 38.48% ± 0.53% to 48.94% ± 0.57% during the same time frame (p = .001). CONCLUSION: Short-term LL-ES of ARVGP had both anti-arrhythmic and anti-inflammatory effects and contributed to the treatment of tachycardia-induced HF and its associated arrhythmia.

Epidemiological features and viral shedding in children with SARS-CoV-2 infection.

A pandemic of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection broke out all over the world; however, epidemiological data and viral shedding in pediatric patients are limited. We conducted a retrospective, multicenter study, and followed-up with all children from the families with SARS-CoV-2 infected members in Zhejiang Province, China. All infections were confirmed by testing the SARS-CoV-2 RNA with real-time reverse transcription PCR method, and epidemiological data between children and adults in the same families were compared. Effect of antiviral therapy was evaluated observationally and fecal-viral excretion times among groups with different antiviral regiments were compared with Kaplan-Meier plot. By 29 February 2020, 1298 cases from 883 families were confirmed with SARS-CoV-2 infection and 314 of which were families with children. Incidence of infection in child close contacts was significantly lower than that in adult contacts (13.2% vs 21.2%). The mean age of 43 pediatric cases was 8.2 years and mean incubation period was 9.1 days. Forty (93.0%) were family clustering. Thirty-three children had coronavirus disease 2019 (20 pneumonia) with mild symptoms and 10 were asymptomatic. Fecal SARS-CoV-2 RNA detection was positive in 91.4% (32/35) cases and some children had viral excretion time over 70 days. Viral clearance time was not different among the groups treated with different antiviral regiments. No subsequent infection was observed in family contacts of fecal-viral-excreting children. Children have lower susceptibility of SARS-CoV-2 infection, longer incubation, and fecal-viral excretion time. Positive results of fecal SARS-CoV-2 RNA detection were not used as indication for hospitalization or quarantine.

Study on Structure Activity Relationship of Natural Flavonoids against Thrombin by Molecular Docking Virtual Screening Combined with Activity Evaluation In Vitro.

Thrombin, a key enzyme of the serine protease superfamily, plays an integral role in the blood coagulation cascade and thrombotic diseases. In view of this, it is worthwhile to establish a method to screen thrombin inhibitors (such as natural flavonoid-type inhibitors) as well as investigate their structure activity relationships. Virtual screening using molecular docking technique was used to screen 103 flavonoids. Out of this number, 42 target compounds were selected, and their inhibitory effects on thrombin assayed by chromogenic substrate method. The results indicated that the carbon-carbon double bond group at the C2, C3 sites and the carbonyl group at the C4 sites of flavones were essential for thrombin inhibition, whereas the methoxy and O-glycosyl groups reduced thrombin inhibition. Noteworthy, introduction of OH groups at different positions on flavonoids either decreased or increased anti-thrombin potential. Myricetin exhibited the highest inhibitory potential against thrombin with an IC50 value of 56 µM. Purposively, the established molecular docking virtual screening method is not limited to exploring flavonoid structure activity relationships to anti-thrombin activity but also usefully discovering other natural active constituents.

Luminescence Tuning of Layered Rare-Earth Hydroxides (LRHs, R = Tb, Y) Composites with 3-Hydroxy-2-naphthoic Acid and Application to the Fluorescent Detection of Al3.

Tunable luminescence (quenching or blue shift) of HNA/OS-LRH composites (HNA is 3-hydroxy-2-naphthoic acid; OS is the anionic surfactant of 1-octanesulfonic acid sodium; LRHs are layered rare-earth hydroxides, R = Tb3+, Y3+) in the solid state and delaminated state is reported, which is utilized as an effective fluorescent probe for detecting metal ions. HNA/OS species are intercalated into LRH layers to generate composites of HNA xOS1- x-LTbH ( x = 0.10, 0.15, 0.20 , 0.25) and HNA yOS1- y-LYH ( y = 0.05, 0.10, 0.15, 0.20, 0.25, 0.30). In the solid state, LYH composites exhibit green emissions (from 493 to 504 nm) with a large blue shift in comparison to the 542 nm emission of free HNA- anions, while in the delaminated state in formamide (FM), the composites display blue emission (480 nm) relative to the green emission (512 nm) of an HNA soltuion in FM. However, LTbH composites display coquenched luminescence in both the solid state and delaminated state. Also, HNA0.25OS0.75-1:1-LYH, HNA0.25OS0.75-1:2-LYH, and HNA0.05OS0.95-1:1-LYH (1:1 and 1:2 are HNA:NaOH molar ratios) show significantly elongated fluorescence lifetimes of 15.35, 14.37, and 12.72 ns, respectively, in comparison with free HNA-Na (6.44 ns), and their quantum yields of 23.40%, 21.97%, and 22.31%, respectively, are much larger than that of free HNA-Na (4.86%). The LTbH composite (HNA0.25OS0.75-1:1-LTbH) has also a relatively higher quantum yield of 12.46%. The HNA0.25OS0.75-1:1-LYH colloid exhibits excellent recognition selectivity for Al3+ over other metal ions (Mg2+, Co2+, Ni2+, Cu2+, Zn2+, Pb2+, Cd2+, and Hg2+) with distinct fluorescence sensitization. It shows an intense change in its fluorescence emission when it is bound to Al3+ ions, giving a lower detection limit of 6.32 × 10-6 M. This is novel research on the fluorescence chemosensing of LRH composites.

MicroRNA-24-3p Attenuates Myocardial Ischemia/Reperfusion Injury by Suppressing RIPK1 Expression in Mice.

BACKGROUND/AIMS: This study was developed to investigate a potential therapeutic method for myocardial ischemia/reperfusion injury involving the promotion of miR-24-3p expression. METHODS: Microarray analysis was used to screen differentially expressed genes in a myocardial ischemia/reperfusion (I/R) injury mouse model. Gene set enrichment analysis was utilized to determine vital signaling pathways. Targeting verification was conducted with a luciferase reporter assay. Myocardial I/R injury was developed in mice, and the expression levels of RIPK1 and miR-24-3p were investigated by qRT-PCR and Western blot. Hemodynamic parameters and the activity of serum myocardial enzymes were measured to evaluate cardiac function. Infarct area was observed through HE and TTC staining. Myocardial cell apoptosis was examined by TUNEL staining and caspase-3 activity analysis. RESULTS: RIPK1 was an upregulated mRNA found by microarray analysis and a verified target of the downregulated miRNA miR-24-3p. The upregulation of RIPK1 (1.8-fold) and the downregulation of miR-24-3p (0.3-fold) were confirmed in I/R mice. RIPK1 led to impaired cardiac function indexes, increased infarct area and cell apoptosis, while miR-24-3p could reverse the injury by regulating RIPK1. The TNF signaling pathway was proven to be involved in myocardial I/R injury through the detection of the dysregulation of related proteins. CONCLUSION: In conclusion, RIPK1 was upregulated and miR-24-3p was downregulated in a myocardial I/R injury mouse model. RIPK1 could aggravate myocardial I/R injury via the TNF signaling pathway, while miR-24-3p could suppress RIPK1 and therefore exert cardioprotective effects in myocardial I/R injury.

A case report: a heterozygous deletion (2791_2805 del) in exon 18 of the filamin C gene causing filamin C-related myofibrillar myopathies in a Chinese family.

BACKGROUND: Filamin C-related myofibrillar myopathies (MFM) are progressive skeletal myopathies with an autosomal dominant inheritance pattern. The conditions are caused by mutations of the filamin C gene (FLNC) located in the chromosome 7q32-q35 region. Genetic variations in the FLNC gene result in various clinical phenotypes. CASE PRESENTATION: We describe a 43-year-old woman who suffered filamin C-related MFM, with symptoms first presenting in the proximal muscles of the lower limbs and eventually spreading to the upper limbs and distal muscles. The patient's serum level of creatine kinase was mildly increased. Mildy myopathic changes in the electromyographic exam and moderate lipomatous alterations in lower limb MRI were found. Histopathological examination revealed increased muscle fiber size variability, disturbances in oxidative enzyme activity, and the presence of abnormal protein aggregates and vacuoles in some muscle fibers. Ultrastructural analysis showed inclusions composed of thin filaments and interspersed granular densities. DNA sequencing analysis detected a novel 15-nucleotide deletion (c.2791_2805del, p.931_935del) in the FLNC gene. The patient's father, sister, brother, three paternal aunts, one paternal uncle, and the uncle's son also had slowly progressive muscle weakness, and thus, we detected an autosomal dominant inheritance pattern of the disorder. CONCLUSIONS: A novel heterogeneous 15-nucleotide deletion (c.2791_2805del, p.931_935del) in the Ig-like domain 7 of the FLNC gene was found to cause filamin C-related MFM. This deletion in the FLNC gene causes protein aggregation, abnormalities in muscle structure, and impairment in muscle fiber function, which leads to muscle weakness.

Simvastatin Protects Heart from Pressure Overload Injury by Inhibiting Excessive Autophagy.

Cardiac hypertrophy is an independent predictor of cardiovascular morbidity and mortality. To identify the mechanisms by which simvastatin inhibits cardiac hypertrophy induced by pressure overload, we determined effects of simvastatin on 14-3-3 protein expression and autophagic activity. Simvastatin was administered intragastrically to Sprague-Dawley (SD) rats before abdominal aortic banding (AAB). Neonatal rat cardiomyocytes (NRCs) were treated with simvastatin before angiotensin II (AngII) stimulation. 14-3-3, LC3, and p62 protein levels were determined by western blot. Autophagy was also measured by the double-labeled red fluorescent protein-green fluorescent protein autophagy reporter system. Simvastatin alleviated excessive autophagy, characterized by a high LC3II/LC3I ratio and low level of p62, and blunted cardiac hypertrophy while increasing 14-3-3 protein expression in rats that had undergone AAB. In addition, it increased 14-3-3 expression and inhibited excessive autophagy in NRCs exposed to AngII. Our study demonstrated that simvastatin may inhibit excessive autophagy, increase 14-3-3 expression, and finally exert beneficial effects on cardioprotection against pressure overload.

Tetrahydroxystilbene Glycoside Improves Microvascular Endothelial Dysfunction and Ameliorates Obesity-Associated Hypertension in Obese ZDF Rats Via Inhibition of Endothelial Autophagy.

AIMS: Obesity is a major risk for hypertension. Endothelial dysfunction contributes to increased peripheral vascular resistance and subsequent hypertension. Autophagy regulates endothelial function, however, whether autophagy is related to hypertension in obesity remains largely unclear. We wished to ascertain: (i) the role of autophagy in obesity-induced hypertension and the underlying mechanisms; (ii) if tetrahydroxystilbene glycoside (TSG) influences endothelial dysfunction and obesity-associated hypertension. METHODS: (TSG-treated) male Zucker diabetic fatty (ZDF) rats and cultured human umbilical vein endothelial cells (HUVECs) were used. Blood pressure was measured non-invasively with a tail-cuff system. Westernblotting was performed to determine the expression of autophagy-associated proteins. Autophagy flux was assessed by transfection HUVECs with the Ad-mGFP-RFP-LC3. RESULTS: Compared with their lean counterparts, obese ZDF rats exhibited hypertension and endothelial dysfunction, along with impaired Akt/mTOR signaling and upregulated expression of autophagy-associated proteins beclin1, microtubule-associated protein 1 light chain 3 II/I, autophagy protein (ATG)5 and ATG7. Two-week TSG administration restored blood pressure and endothelial function, reactivated Akt/mTOR pathway and decreased endothelial autophagy in ZDF rats. Rapamycin pretreatment blocked the hypotensive effect of TSG in ZDF rats. Suppression of Akt/mTOR expression with siRNA significantly blunted the anti-autophagic effect of TSG in HUVECs as evidenced by abnormal autophagic flux and increased expression of autophagy-associated proteins. CONCLUSION: Endothelial dysfunction in ZDF rats is partially attributable to excessive autophagy. TSG improves endothelial function and exerts hypotensive effects via regulation of endothelial autophagy.

BAG3 regulates contractility and Ca(2+) homeostasis in adult mouse ventricular myocytes.

Bcl2-associated athanogene 3 (BAG3) is a 575 amino acid anti-apoptotic protein that is constitutively expressed in the heart. BAG3 mutations, including mutations leading to loss of protein, are associated with familial cardiomyopathy. Furthermore, BAG3 levels have been found to be reduced in end-stage non-familial failing myocardium. In contrast to neonatal myocytes in which BAG3 is found in the cytoplasm and involved in protein quality control and apoptosis, in adult mouse left ventricular (LV) myocytes BAG3 co-localized with Na(+)-K(+)-ATPase and L-type Ca(2+) channels in the sarcolemma and t-tubules. BAG3 co-immunoprecipitated with ß1-adrenergic receptor, L-type Ca(2+) channels and phospholemman. To simulate decreased BAG3 protein levels observed in human heart failure, we targeted BAG3 by shRNA (shBAG3) in adult LV myocytes. Reducing BAG3 by 55% resulted in reduced contraction and [Ca(2+)]i transient amplitudes in LV myocytes stimulated with isoproterenol. L-type Ca(2+) current (ICa) and sarcoplasmic reticulum (SR) Ca(2+) content but not Na(+)/Ca(2+) exchange current (INaCa) or SR Ca(2+) uptake were reduced in isoproterenol-treated shBAG3 myocytes. Forskolin or dibutyryl cAMP restored ICa amplitude in shBAG3 myocytes to that observed in WT myocytes, consistent with BAG3 having effects upstream and at the level of the receptor. Resting membrane potential and action potential amplitude were unaffected but APD50 and APD90 were prolonged in shBAG3 myocytes. Protein levels of Ca(2+) entry molecules and other important excitation-contraction proteins were unchanged in myocytes with lower BAG3. Our findings that BAG3 is localized at the sarcolemma and t-tubules while modulating myocyte contraction and action potential duration through specific interaction with the ß1-adrenergic receptor and L-type Ca(2+) channel provide novel insight into the role of BAG3 in cardiomyopathies and increased arrhythmia risks in heart failure.

Vasonatrin peptide attenuates myocardial ischemia-reperfusion injury in diabetic rats and underlying mechanisms.

Diabetes mellitus increases morbidity/mortality of ischemic heart disease. Although atrial natriuretic peptide and C-type natriuretic peptide reduce the myocardial ischemia-reperfusion damage in nondiabetic rats, whether vasonatrin peptide (VNP), the artificial synthetic chimera of atrial natriuretic peptide and C-type natriuretic peptide, confers cardioprotective effects against ischemia-reperfusion injury, especially in diabetic patients, is still unclear. This study was designed to investigate the effects of VNP on ischemia-reperfusion injury in diabetic rats and to further elucidate its mechanisms. The high-fat diet-fed streptozotocin-induced diabetic Sprague-Dawley rats were subjected to ischemia-reperfusion operation. VNP treatment (100 µg/kg iv, 10 min before reperfusion) significantly improved the instantaneous first derivation of left ventricle pressure (±LV dP/dtmax) and LV systolic pressure and reduced LV end-diastolic pressure, apoptosis index, caspase-3 activity, plasma creatine kinase (CK), and lactate dehydrogenase (LDH) activities. Moreover, VNP inhibited endoplasmic reticulum (ER) stress by suppressing glucose-regulated protein 78 (GRP78) and C/EBP homologous protein (CHOP). These effects were mimicked by 8-bromine-cyclic guanosinemonophosphate (8-Br-cGMP), a cGMP analog, whereas they were inhibited by KT-5823, the selective inhibitor of PKG. In addition, pretreatment with tauroursodeoxycholic acid (TUDCA), a specific inhibitor of ER stress, could not further promote the VNP's cardioprotective effect in diabetic rats. In vitro H9c2 cardiomyocytes were subjected to hypoxia/reoxygenation and incubated with or without VNP (10(-8) mol/l). Gene knockdown of PKG1α with siRNA blunted VNP inhibition of ER stress and apoptosis, while overexpression of PKG1α resulted in significant decreased ER stress and apoptosis. VNP protects the diabetic heart against ischemia-reperfusion injury by inhibiting ER stress via the cGMP-PKG signaling pathway. These results suggest that VNP may have potential therapeutic value for the diabetic patients with ischemic heart disease.

Prevalence and types of drug-resistant variants in Chinese patients with acute hepatitis B.

The presence of therapy-associated hepatitis B virus (HBV) variants is the main drawback of antiviral therapy for HBV infection. Moreover, drug-resistant variants are more insensitive to a second agent and more therapy-associated mutations will be present. To apply better nucleos(t)ide analogues (NA) and reduce the occurrence of resistance, the prevalence and types of drug-resistant mutations in acute hepatitis B patients were investigated in this study. One hundred three HBV DNA-positive patients with symptomatic acute hepatitis B that were observed from 2011 to 2013 were enrolled. Direct polymerase chain reaction sequencing was used firstly to screen HBV reverse-transcriptase domain to detect HBV mutants. Five lamivudine-resistant variants were identified. Clonal sequencing was performed for 5 resistance-positive samples and 10 other random samples. Interestingly, all detected samples harbored drug-resistant mutations, although with different percentage. Thirteen harbored lamivudine-related alone (five) or together with other NA related mutations (five with adefovir, one with entecavir, and one with telbivudine), and two of them harbored adefovir-related mutations. Also, mutations associated with four currently used NA were all detected, and the frequency is in accordance with the popularity of NA used in clinical practice. These data suggest that drug-resistant variants are present in patients with acute hepatitis B and NA should be applied more carefully for chronic hepatitis B patients developed from acute hepatitis B.

Efficient and facile synthesis of novel stable monodeuterium labeled ractopamine.

A novel synthetic route to stable deuterium labeled ractopamine was disclosed with 6.49% total yield and 97.7% isotopic abundance. Its structure and the isotope-abundance were confirmed according to (1)H-NMR and high-resolution mass spectrometry.

Understanding Social Media Information Sharing in Individuals with Depression: Insights from the Elaboration Likelihood Model and Schema Activation Theory.

Purpose: How individuals engage with social media can significantly impact their psychological well-being. This study examines the impact of social media interactions on mental health, grounded in the frameworks of the Elaboration Likelihood Model and Schema Activation Theory. It aims to uncover behavioral differences in information sharing between the general population and individuals with depression, while also elucidating the psychological mechanisms underlying these disparities. Methods: A pre-experiment (N=30) and three experiments (Experiment 1a N=200, Experiment 1b N=180, Experiment 2 N=128) were executed online. These experiments investigated the joint effects of information quality, content valence, self-referential processing, and depression level on the intention to share information. The research design incorporated within-subject and between-subject methods, utilizing SPSS and SPSS Process to conduct independent sample t-tests, two-factor ANOVA analyses, mediation analyses, and moderated mediation analyses to test our hypotheses. Results: Information quality and content valence significantly influence sharing intention. In scenarios involving low-quality information, individuals with depression are more inclined to share negative emotional content compared to the general population, and this tendency intensifies with the severity of depression. Moreover, self-referential processing acts as a mediator between emotional content and intention to share, yet this mediation effect weakens as the severity of depression rises. Conclusion: Our study highlights the importance of promoting viewpoint diversity and breaking the echo chamber effect in social media to improve the mental health of individuals with depression. To achieve this goal, tailoring emotional content on social media could be a practical starting point for practice.

Prognostic value of Geriatric Nutritional Risk Index and systemic immune-inflammatory index in elderly patients with acute coronary syndromes.

The objective of this study was to evaluate the predictive value of the Geriatric Nutritional Risk Index (GNRI) combined with the Systemic Immunoinflammatory Index (SII) for the risk of major adverse cardiovascular events (MACE) following percutaneous coronary intervention in elderly patients with acute coronary syndrome (ACS). We retrospectively reviewed the medical records of 1202 elderly patients with acute coronary syndromes divided into MACE and non-MACE groups according to whether they had a MACE. The sensitivity analysis utilized advanced machine learning algorithms to preliminarily identify the critical role of GNRI versus SII in predicting MACE risk. We conducted a detailed analysis using a restricted cubic spline approach to investigate the nonlinear relationship between GNRI, SII, and MACE risk further. We constructed a clinical prediction model based on three key factors: GNRI, SII, and Age. To validate the accuracy and usefulness of this model, we compared it to the widely used GRACE score using subject work and recall curves. Additionally, we compared the predictive value of models and GRACE scores in assessing the risk of MACE using the Integrated Discriminant Improvement Index (IDI) and the Net Reclassification Index (NRI). This study included 827 patients. The GNRI scores were lower in the MACE group than in the non-MACE group, while the SII scores were higher in the MACE group (P < 0.001). The multifactorial analysis revealed a low GNRI (OR = 2.863, 95% CI: 2.026-4.047, P = 0.001), High SII (OR = 3.102, 95% CI: 2.213-4.348, P = 0.001). The area under the curve (AUC) for the predictive model was 0.778 (95% CI: 0.744-0.813, P = 0.001), while the AUC for the GRACE score was 0.744 (95% CI: 0.708-0.779, P = 0.001). NRI was calculated to be 0.5569, with NRI + at 0.1860 and NRI- at 0.3708. The IDI was found to be 0.0571, with a P-value of less than 0.001. These results suggest that the newly developed prediction model is more suitable for use with the population in this study than the GRACE score. The model constructed using GNRI and SII demonstrated good standardization and clinical impact, as evidenced by the standard, DCA, and clinical impact curves. The study shows that combining GNRI and SII can be a simple, cost-effective, and valuable way to predict the risk of MACE within one year in elderly acute coronary syndromes.

Intercalation of azamacrocyclic crown ether into layered rare-earth hydroxide (LRH): secondary host-guest reaction and efficient heavy metal removal.

A carboxyethyl substituted azacrown ether (CSAE) derivative was intercalated as a second host into a parent host of layered gadolinium hydroxides (LGdH) by an anion-exchange reaction. The influence of intercalation temperature and starting material ratios of CSAE/LRH on the structures and compositions of CSAE-LRH nanocomposites were investigated. Higher temperature and larger initial CSAE-LGdH weight ratios favor of higher degree of ion exchange at a certain range, while lower temperature gives good morphology for the composites. The adsorptive properties for transition and heavy metal ions were studied using the 20 °C-reacted composite, which showed higher adsorptivity toward transition and heavy metal ions, accompanied by the introduction of nitrate anions. The adsorptive capacity for transition metal ions was in the sequence of Cu(2+) > Zn(2+)∼Ni(2+)∼Co(2+) with a high selectivity to Cu(2+). For the heavy metal ions Ag(+), Hg(2+), Pb(2+), and Cd(2+), the composite showed markedly high selectivity for Ag(+) and Hg(2+). When putting Cu(2+), Ag(+), Hg(2+), Pb(2+), and Cd(2+) together, Ag(+) and Hg(2+) still have higher adsorptive selectivity over Pb(2+) and Cd(2+), and Cu(2+) has also relatively high selectivity but not as high as Ag(+) and Hg(2+). The nanocomposites with a second host in the interlayer are one promising kind of material because of the synergy of the steric effect of the parent host (LRH layer) and the particular characteristics of the secondary host (interlayer crown ether anions).

Resveratrol attenuates efavirenz-induced hepatic steatosis and hypercholesterolemia in mice by inhibiting pregnane X receptor activation and decreasing inflammation.

Efavirenz (EFV), a widely prescribed antiviral medication, has been implicated in dyslipidemia and can activate the pregnane X receptor (PXR), leading to hepatic steatosis and hypercholesterolemia in mice. Resveratrol (RES) can ameliorate hepatic steatosis and functions as a partial PXR agonist, capable of mitigating PXR expression induced by other PXR agonists. Therefore, we hypothesized that RES could attenuate EFV-induced hepatic steatosis and hypercholesterolemia by downregulating PXR expression and suppressing inflammatory cytokine production. Here, we conducted an in vivo study involving 6-week-old male mice, which were divided into 4 groups for a 7-day intervention: control (carrier solution), EFV (80 mg/kg), RES (50 mg/kg), and RES + EFV groups. Serum and hepatic tissue samples were collected to assess cholesterol and triglyceride concentrations. Hepatic lipid accumulation was evaluated through hematoxylin-eosin and oil red O staining. Polymerase chain reaction and western blot were performed to quantify hepatic inflammatory factors, lipogenic gene, and PXR expression. Our results indicated that hepatic lipid droplet accumulation was reduced in the RES + EFV group compared with the EFV group. Similarly, the expressions of hepatic inflammatory factors were attenuated in the RES + EFV group relative to the EFV group. Furthermore, RES counteracted the upregulation of hepatic lipid-metabolizing enzymes induced by EFV at both the transcriptional and protein levels. Importantly, PXR expression was downregulated in the RES + EFV group compared with the EFV group. Conclusively, our findings suggest that RES effectively mitigates EFV-induced hepatic steatosis and hypercholesterolemia by inhibiting PXR activation and decreasing inflammation.