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Giant heterometallic polyoxometalate (POM) clusters with precise atom structures, flexibly adjustable and abundant active sites are promising for constructing functional nanodrugs. However, current POM drugs are almost vacant in orthotopic brain tumor therapy due to the inability to effectively penetrate the blood–brain barrier (BBB) and low drug activity. Here, we designed the largest (3.0 nm × 6.0 nm) transition‐metal–lanthanide co‐encapsulated POM cluster {[Ce10Ag6(DMEA)(H2O)27W22O70][B‐α‐TeW9O33]9}288− featuring 238 metal centers via synergistic coordination between two geometry‐unrestricted Ce3+ and Ag+ linkers with tungsten‐oxo cluster fragments. This POM was combined with brain‐targeted peptide to prepare a brain‐targeted nanodrug that could efficiently traverse BBB and target glioma cells. The Ag+ active centers in the nanodrug specifically activate reactive oxygen species to regulate the apoptosis pathway of glioma cells with a low half‐maximal inhibitory concentration (5.66 μM). As the first brain‐targeted POM drug, it efficiently prolongs the survival of orthotopic glioma‐bearing mice. [ABSTRACT FROM AUTHOR]

This manuscript reviews some recent and popular error control methods for tree structured hypothesis testing. We review a common setting/definition for hypotheses arranged in a tree structure and we discuss two common Type I errors present in multiple testing: family wise error rates (FWERs) and false discovery rate (FDR). We also contrast these methods with a recent development designed to control the false selection rate (FSR). We discuss the algorithms used to implement these error controls and the strategies used to navigate tree structures in light of these errors. We highlight the assumptions necessary in these strategies, summarize the available R software packages to implement these approaches, and show them at work on an example. This article is categorized under:Data: Types and Structure > Image and Spatial DataApplications of Computational Statistics > Genomics/Proteomics/GeneticsData: Types and Structure > Microarrays [ABSTRACT FROM AUTHOR]

Near‐infrared‐II (NIR‐II) ferroptosis activators offer promising potentials in in vivo theranostics of deep tumors, such as glioma. However, most cases are nonvisual iron‐based systems that are blind for in vivo precise theranostic study. Additionally, the iron species and their associated nonspecific activations might trigger undesired detrimental effects on normal cells. Considering gold (Au) is an essential cofactor for life and it can specifically bind to tumor cells, Au(I)‐based NIR‐II ferroptosis nanoparticles (TBTP‐Au NPs) for brain‐targeted orthotopic glioblastoma theranostics are innovatively constructed. It achieves the real‐time visual monitoring of both the BBB penetration and the glioblastoma targeting processes. Moreover, it is first validated that the released TBTP‐Au specifically activates the effective heme oxygenase‐1‐regulated ferroptosis of glioma cells to greatly extend the survival time of glioma‐bearing mice. This new ferroptosis mechanism based on Au(I) may open a new way for the fabrication of advanced and high‐specificity visual anticancer drugs for clinical trials. [ABSTRACT FROM AUTHOR]

Optimized theranostic strategies for Alzheimer's disease (AD) remain almost absent from bench to clinic. Current probes and drugs attempting to prevent β‐amyloid (Aβ) fibrosis encounter failures due to the blood–brain barrier (BBB) penetration challenge and blind intervention time window. Herein, we design a near‐infrared (NIR) aggregation‐induced emission (AIE) probe, DNTPH, via balanced hydrophobicity‐hydrophilicity strategy. DNTPH binds selectively to Aβ fibrils with a high signal‐to‐noise ratio. In vivo imaging revealed its excellent BBB permeability and long‐term tracking ability with high‐performance AD diagnosis. Remarkably, DNTPH exhibits a strong inhibitory effect on Aβ fibrosis and promotes fibril disassembly, thereby attenuating Aβ‐induced neurotoxicity. DNTPH treatment significantly reduced Aβ plaques and rescued learning deficits in AD mice. Thus, DNTPH serves as the first AIE in vivo theranostic agent for real‐time NIR imaging of Aβ plaques and AD therapy simultaneously. [ABSTRACT FROM AUTHOR]

Alfosbuvir is a novel potent HCV NS5B polymerase inhibitor in development for the treatment of chronic HCV infection. Our previous studies indicated that alfosbuvir monotherapy was well‐tolerated and druggable in healthy subjects and HCV‐infected patients. Here, we evaluate the efficacy and safety of alfosbuvir in combination with daclatasvir in Chinese patients with HCV genotype 1, 2, 3 or 6. In this open‐label study, patients with chronic HCV infection were randomly assigned with a 1:1:1 ratio to receive 12 weeks of daclatasvir 60 mg plus alfosbuvir at a dose of 400, 600 or 800 mg (Cohort A, B or C) daily. Randomization was stratified by HCV genotype and the presence or absence of cirrhosis at screening. The primary endpoint was a sustained virologic response 12 weeks after the end of treatment (SVR12). A total of 124 patients were enrolled in the study, all of whom were available for post‐treatment week 12 assessments. SVR12 was achieved in 92.7% (38/41), 95.2% (40/42) and 100% (41/41) of patients in Cohort A, B and C respectively. The most common adverse events were hepatic steatosis, upper respiratory tract infection, hypercholesterolaemia, hypertriglyceridaemia, blood bilirubin increased, and total bile acids increased. There were no discontinuations due to adverse events, and no treatment‐related serious adverse events were reported. Once‐daily oral administration of alfosbuvir plus daclatasvir were highly effective and safe in Chinese patients infected with HCV genotype 1, 2, 3 or 6, suggesting this regimen could be a promising drug candidate for HCV treatment irrespective of genotype. (ClinicalTrials.gov number, NCT04070235). [ABSTRACT FROM AUTHOR]

Phototheranostic agents have thrived as promising tools for cancer theranostics because of the integration of sensitive in situ fluorescence imaging and effective multi‐model synergistic therapy. However, how to manipulate the intangible photon energy transfer to balance the competitive radiative and nonradiative processes is still challenging. Although numerous phototheranostic molecules are reported, their complicated molecular design and tedious synthesis often stumble further their development. Herein, three simple molecules with electron donating−accepting structures are developed. The electron acceptor engineering on molecules by introducing acridinium unit gives rise to TPEDCAc with aggregation‐induced second near‐infrared emission (AIE NIR‐II), high reactive oxygen species generation capability, and excellent photothermal conversion efficiency (44.8%) due to the drastic intramolecular motion of large acridinium rotor and balanced AIE effect. Experimental analysis and calculation on the controlled molecules suggested that large torsional angle and the strong electron‐withdrawing ability of the acridinium unit are keys for NIR‐II emission and balanced photodynamic/photothermal conversion. Impressively, the positively charged TPEDCAc shows mitochondria‐targeting capability and high performance in in vivo multi‐modal cancer theranostics under NIR laser irradiation. Hence, this work not only provides a single NIR‐II AIE‐based multi‐modal cancer theranostic system but inspires new insights into future development of new theranostic platforms. [ABSTRACT FROM AUTHOR]

Objective: Myocardial injury leads to higher mortality in COVID‐19, but the causes and risk factors are variable. We evaluated the potential risk factors for myocardial injury in COVID‐19 patients to improve treatment strategies and reduce mortality. Methods: This retrospective analysis enrolled 325 COVID‐19 patients in Shanghai, China. Results: The median age in our cohort was 51 [range 15‐88] years, 26 (8%) were critically ill, and 177 patients (19.7%) had myocardial injury. The myocardial injury group comprised older, more critically ill patients with hypertension, other comorbidities, history of angiotensin‐converting enzyme inhibitor/angiotensin receptor blocker use, lower peripheral blood lymphocyte count and higher D‐dimer levels. Binary logistic regression analysis identified only age was an independent risk factor for myocardial injury (odds ratio 1.019; 95% confidence interval 1.003‐1.036; age increase by 1 year = myocardial injury risk increase by 1.9%). Conclusions: Older age was associated with a higher incidence of myocardial injury for COVID‐19 patients. [ABSTRACT FROM AUTHOR]

In an article published in Angewandte Chemie International Edition, researchers Jiefei Wang, Bingyang Shi, Junwei Zhao, and others discuss the development of a giant heterometallic polyoxometalate (POM) cluster for enhanced brain-targeted glioma therapy. The POM cluster, which is the largest of its kind, has adjustable active sites and is designed to overcome the challenge of delivering drugs to the brain. The cluster, co-encapsulated with Ce3+ and Ag+, has been shown to activate the apoptosis pathway of glioma cells and improve the survival of mice with orthotopic glioma. This research represents a significant advancement in the field of brain drug delivery. [Extracted from the article]

In the article titled "A Giant Heterometallic Polyoxometalate Nanocluster for Enhanced Brain-Targeted Glioma Therapy," researchers Jiefei Wang, Bingyang Shi, Junwei Zhao, and others discuss the design of a large polyoxometalate (POM) cluster for drug delivery to the brain. This cluster, which is co-encapsulated with Ce3+ and Ag+, has the ability to cross the blood-brain barrier and target mitochondria, addressing the challenge of delivering drugs to treat glioma. The researchers found that Ag+ activates a pathway that induces apoptosis in glioma cells, leading to improved survival in mice with orthotopic glioma. [Extracted from the article]

Background: Hepatic failure is a main cause of death after hepatectomy. Accurate preoperative evaluation of functional liver reserve is the key to ensure safe resection. Studies have found that the spleen would gradually enlarge as chronic liver disease worsened. This study was designed to determine whether preoperative liver-to-spleen ratio (LSR) would be an indicator to evaluate severity of liver disease and predict safety of hepatectomy. Methods: The volumes of liver and spleen were evaluated on computed tomography scan in 67 patients who received partial hepatectomy. Preoperative LSR was calculated. Statistical analysis was conducted to examine the relationship between LSR and the degree of chronic liver disease. Ability of LSR to predict the safety of hepatectomy also was evaluated. Results: LSR had a negative correlation with the degree of chronic liver diseases ( r = −0.606, P < 0.0001). LSR = 3.22 was the cutoff point for predicting posthepatectomy complications and inadequacy. AUC, sensitivity, and specificity for predicting posthepatectomy complications and inadequacy respectively were 0.830 (95 % confidence interval [CI] 0.715-0.950, P < 0.0001), 69.6, 93.2 %, and 0.863 (95 % CI 0.777-0.949, P < 0.0001), 68.8, 84.3 %. Multivariate analysis showed that LSR = 3.22 was the factor that affected both posthepatectomy complications and liver inadequacy. Conclusions: Preoperative LSR score correlated well with the degree of chronic liver diseases, and it probably help us to improve the safety of hepatectomy. [ABSTRACT FROM AUTHOR]

Background & Aims The important pathophysiological role of immune dysfunction, especially innate immune dysfunction in patients with acute-on-chronic liver failure ( ACLF), has been investigated in recent years, but dysregulation of adaptive immunity remains poorly elucidated. The aim of this study was to (i) determine the CD3+ T-lymphocyte count and the balance between CD4+ regulatory T (Tregs) and conventional T cells (Tconv) in hepatitis B virus ( HBV)-related ACLF patients; (ii) analyse the frequencies of Tregs subpopulations; and (iii) assess the suppressive potency of CD4+ Tregs and each fraction. Methods We enrolled 20 HBV- ACLF patients, 10 septic shock subjects, 20 chronic hepatitis B ( CHB) patients and 20 healthy volunteers ( HC). Based on flow cytometry, we performed the absolute counting of circulating T lymphocytes and phenotyping of CD4+ Tregs and quantified the effects of Tregs and each subpopulation on Tconv proliferation by CFSE staining. Results Compared with CHB patients and HC, we observed an equal reduction in peripheral T subsets in HBV- ACLF and septic shock subjects; the number of CD4+ Tregs remained unchanged and the Tconv count declined, promoting elevation of the Treg-to-Tconv ratio. The frequencies of Treg-II and -III were elevated in HBV- ACLF. Functional studies showed that the suppressive capacity of Tregs was preserved in the HBV- ACLF group and Treg-II came first. Conclusions Similar to septic shock subjects, in HBV- ACLF patients there exists a reduction in CD4+ T lymphocytes, predominantly CD4+ Tconv, and the development of suppressive CD4+ Tregs greatly prevails over Tconv, constituting important characteristics of adaptive immune dysfunction of HBV- ACLF. [ABSTRACT FROM AUTHOR]

Background & Aims: The important pathophysiological role of immune dysfunction, especially innate immune dysfunction in patients with acute-on-chronic liver failure (ACLF), has been investigated in recent years, but dysregulation of adaptive immunity remains poorly elucidated. The aim of this study was to (i) determine the CD3(+) T-lymphocyte count and the balance between CD4(+) regulatory T (Tregs) and conventional T cells (Tconv) in hepatitis B virus (HBV)-related ACLF patients; (ii) analyse the frequencies of Tregs subpopulations; and (iii) assess the suppressive potency of CD4(+) Tregs and each fraction., Methods: We enrolled 20 HBV-ACLF patients, 10 septic shock subjects, 20 chronic hepatitis B (CHB) patients and 20 healthy volunteers (HC). Based on flow cytometry, we performed the absolute counting of circulating T lymphocytes and phenotyping of CD4(+) Tregs and quantified the effects of Tregs and each subpopulation on Tconv proliferation by CFSE staining., Results: Compared with CHB patients and HC, we observed an equal reduction in peripheral T subsets in HBV-ACLF and septic shock subjects; the number of CD4(+) Tregs remained unchanged and the Tconv count declined, promoting elevation of the Treg-to-Tconv ratio. The frequencies of Treg-II and -III were elevated in HBV-ACLF. Functional studies showed that the suppressive capacity of Tregs was preserved in the HBV-ACLF group and Treg-II came first., Conclusions: Similar to septic shock subjects, in HBV-ACLF patients there exists a reduction in CD4(+) T lymphocytes, predominantly CD4(+) Tconv, and the development of suppressive CD4(+) Tregs greatly prevails over Tconv, constituting important characteristics of adaptive immune dysfunction of HBV-ACLF., (© 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)