Variants in 3p24.3 predicts the risk of early neurological deterioration in large artery atherosclerotic stroke.

The rate of early neurological deterioration (END) differs in different subtypes of ischaemic stroke. Previous studies showed PLCL2 gene is a novel susceptibility locus for the occurrence of atherosclerosis and thrombotic events. The objective of this research is to examine the efficacy that PLCL2 may have on the risk of END in large artery atherosclerotic (LAA) stroke. Tagged single nucleotide polymorphisms (SNPs) were identified by a strategy of fine-mapping. The genotyping of the selected SNPs was performed by SNPscan. The impact of PLCL2 on indicating the susceptibility of END in LAA patients was evaluated by binary logistic regression. The SNP-SNP interactions of PLCL2 for END was assessed by generalized multifactor dimensionality reduction (GMDR). A total of 1527 LAA stroke patients were recruited, 582 patients (38 %) experienced END. Compared to participants without END, participants experienced END were much older (P = 0.018), more likely to suffer pre-existing diabetes mellitus (P = 0.036), higher frequent in active tobacco users (P = 0.022) and had much higher median NIHSS on admission (P < 0.001). Rs4685423 was identified to be a predictor to the risk of END: the frequency of END in AA genotype patients is lower than that in AC or CC genotype patients (multivariate-adjusted, OR 0.63; 95 % CI 0.49-0.80; P < 0.001). The SNP-SNP interactions analysis indicates rs4685423 has the greatest impacton the risk of END for LAA patients. The time from admission diagnosis to END onset in AA genotype patients is much later than that in CA or CC genotype patients (log-rank, P = 0.005). In summary, the PLCL2 rs4685423 SNP is probably associated with the END risk in LAA stroke patients.

Responsively Degradable Nanoarmor-Assisted Super Resistance and Stable Colonization of Probiotics for Enhanced Inflammation-Targeted Delivery.

Manipulation of the gut microbiota using oral microecological preparations has shown great promise in treating various inflammatory disorders. However, delivering these preparations while maintaining their disease-site specificity, stability, and therapeutic efficacy is highly challenging due to the dynamic changes associated with pathological microenvironments in the gastrointestinal tract. Herein, a superior armored probiotic with an inflammation-targeting capacity is developed to enhance the efficacy and timely action of bacterial therapy against inflammatory bowel disease (IBD). The coating strategy exhibits suitability for diverse probiotic strains and has negligible influence on bacterial viability. This study demonstrates that these armored probiotics have ultraresistance to extreme intraluminal conditions and stable mucoadhesive capacity. Notably, the HA-functionalized nanoarmor equips the probiotics with inflamed-site targetability through multiple interactions, thus enhancing their efficacy in IBD therapy. Moreover, timely "awakening" of ingested probiotics through the responsive transferrin-directed degradation of the nanoarmor at the site of inflammation is highly beneficial for bacterial therapy, which requires the bacterial cells to be fully functional. Given its easy preparation and favorable biocompatibility, the developed single-cell coating approach provides an effective strategy for the advanced delivery of probiotics for biomedical applications at the cellular level.

Self-Report Amphiphilic Polymer-Based Drug Delivery System with ROS-Triggered Drug Release for Osteoarthritis Therapy.

The development of drug delivery systems with real-time cargo release monitoring capabilities is imperative for optimizing nanomedicine performance. Herein, we report an innovative self-reporting drug delivery platform based on a ROS-responsive random copolymer (P1) capable of visualizing cargo release kinetics via the activation of an integrated fluorophore. P1 was synthesized by copolymerization of pinacol boronate, PEG, and naphthalimide monomers to impart ROS-sensitivity, hydrophilicity, and fluorescence signaling, respectively. Detailed characterization verified that P1 self-assembles into 11 nm micelles with 10 µg mL-1 CMC and can encapsulate hydrophobic curcumin with 79% efficiency. Fluorescence assays demonstrated H2O2-triggered disassembly and curcumin release with concurrent polymer fluorescence turn-on. Both in vitro and in vivo studies validated the real-time visualization of drug release and ROS scavenging, as well as the therapeutic effect on osteoarthritis (OA). Overall, this nanotheranostic polymeric micelle system enables quantitative monitoring of drug release kinetics for enhanced treatment optimization across oxidative stress-related diseases.

UBE3A and MCM6 synergistically regulate the proliferation and migration of lung adenocarcinoma cells.

Lung cancer is a leading cause of mortality worldwide and shows substantial clinical and biomolecular heterogeneity. Currently, specific therapeutic strategies are lacking, so effective drug targets are urgently needed. E6AP/UBE3A is a multifaceted ubiquitin ligase that controls various signaling pathways implicated in neurological diseases and various cancers; however, its role in lung cancer is incompletely understood. Here, MCM6 was identified as an interacting partner of E6AP using the yeast two-hybrid assay. MCM2 and MCM4 were then shown to interact with E6AP. E6AP knockout enhanced the ubiquitination of MCM2/4/6, suggesting that E6AP was not the E3 ubiquitin ligase for these three MCM proteins. Ablation of E6AP inhibited proliferation and migration, but had no significant effect on apoptosis in A549 and H1975 cells, and proliferation and migration inhibition was also observed in MCM6 knockdown cells. Furthermore, ablation of MCM6 and E6AP synergistically suppressed the proliferation and migration of A549 and H1975 cells. To verify the above findings in vivo, we established tumor models in nude mice and identified that the tumorigenicity of human lung adenocarcinoma (LUAD) cells was synergistically regulated by MCM6 and E6AP. Moreover, the expression levels of MCM6 and E6AP were higher in LUAD tissues than in adjacent tissues. Furthermore, the expression levels of MCM6 and E6AP were positively correlated in human LUAD samples. Thus, our study suggests that the interaction of E6AP and MCM proteins plays an important role in the progression of LUAD, which might offer potential therapeutic targets for cancer treatment.

Progresses, Challenges, and Prospects of CRISPR/Cas9 Gene-Editing in Glioma Studies.

Glioma refers to a tumor that is derived from brain glial stem cells or progenitor cells and is the most common primary intracranial tumor. Due to its complex cellular components, as well as the aggressiveness and specificity of the pathogenic site of glioma, most patients with malignant glioma have poor prognoses following surgeries, radiotherapies, and chemotherapies. In recent years, an increasing amount of research has focused on the use of CRISPR/Cas9 gene-editing technology in the treatment of glioma. As an emerging gene-editing technology, CRISPR/Cas9 utilizes the expression of certain functional proteins to repair tissues or treat gene-deficient diseases and could be applied to immunotherapies through the expression of antigens, antibodies, or receptors. In addition, some research also utilized CRISPR/Cas9 to establish tumor models so as to study tumor pathogenesis and screen tumor prognostic targets. This paper mainly discusses the roles of CRISPR/Cas9 in the treatment of glioma patients, the exploration of the pathogenesis of neuroglioma, and the screening targets for clinical prognosis. This paper also raises the future research prospects of CRISPR/Cas9 in glioma, as well as the opportunities and challenges that it will face in clinical treatment in the future.

Non-linear correlation between amylase day 2 to day 1 ratio and incidence of severe acute pancreatitis.

Background: This study aimed to assess whether the amylase day 2/amylase day 1 ratio was associated with severe acute pancreatitis (SAP). Methods: We retrospectively enrolled 464 patients with acute pancreatitis. Serum amylase was measured on admission (day 1) and 24 h later (day 2). Univariable logistic regression with restricted cubic spline analysis, multivariable logistic analysis, and receiver operating characteristic curve analysis was used to evaluate the relationship between the amylase day 2/amylase day 1 ratio and SAP. Results: A non-linear association between the amylase day 2/amylase day 1 ratio and SAP was observed. The multivariable logistic analysis confirmed that a high amylase day 2/amylase day 1 ratio (≥0.3) was independently associated with the development of SAP (OR: 6.62). The area under the receiver operating characteristic curve (AUC) of the amylase day 2/amylase day 1 ratio, as a predictive factor for SAP, was 0.65. When amylase ratio ≥0.3 was counted as 1 point and added to the BISAP score to build a new model named the BISAPA (BISAP plus Amylase ratio) score (AUC = 0.86), it improved the diagnostic power of the original BISAP score (AUC = 0.83) for SAP. With a cut-off value of 3, the BISAPA score achieved a sensitivity of 66.0%, a specificity of 86.7%, and diagnostic accuracy of 84.48%. Conclusions: There is a non-linear correlation between the amylase day 2/amylase day 1 ratio and the incidence of SAP. BISAPA score might also be a useful tool for the same purpose.

Overexpression of Pleckstrin Homology Domain-Containing Family A Member 4 Is Correlated with Poor Prognostic Outcomes and Immune Infiltration in Lower-Grade Glioma.

Introduction: The global incidence of brain tumors, the most common of which is lower grade glioma (LGG), remains high. Pleckstrin homology domain-containing family A member 4 (PLEKHA4) has been reported to be related to tumor invasion and growth. However, its role and correlation with immunity in LGG remain elusive. Methods: We evaluated the expression pattern, prognostic value, biological functions, and immune effects of PLEKHA4 in LGG. We also analyzed the association between PLEKHA4 levels in different tumors, patient prognosis, and its role in tumor immunity. Depending on the type of research data, we used statistical methods such as Student's t-tests, Mann-Whitney U tests one-way ANOVA tests Kruskal-Wallis tests Pearson's or Spearman's correlation analysis Chi-square and Fisher's exact tests in this paper. Results and Conclusions. The results revealed that PLEKHA4 levels were markedly elevated in most tumors (such as LGG). High PLEKHA4 levels are associated with poor overall survival (OS), progression-free interval (PFI) rates, and disease-specific survival (DSS) in LGG patients. Cox regression analysis and nomograms showed that PLEKHA4 levels are independent prognostic factors for LGG patients. According to functional enrichment analysis, PLEKHA4 levels in LGG are associated with immune infiltration and immunotherapy. In conclusion, PLEKHA4 is a potential prognostic marker and immunotherapy target for LGG.

Therapeutic Effects of Retinoic Acid in Lipopolysaccharide-Induced Cardiac Dysfunction: Network Pharmacology and Experimental Validation.

Purpose: Sepsis, which is deemed as a systemic inflammation reaction syndrome in the face of infectious stimuli, is the primary cause of death in ICUs. Sepsis-induced cardiomyopathy (SIC) may derive from systemic inflammation reaction and oxidative stress. Retinoic acid (RA) is recognized by its beneficial roles in terms of the immunoresponse to infections and antioxygen actions. However, the treatment efficacy and potential causal links of RA in SIC are still elusive. Methods: By virtue of the STITCH database, we identified the targets of RA. Differentially expressed genes in SIC were acquired from the GEO database. The PPI network of intersected targets was established. GO and KEGG pathway enrichment analysis was completed. Hub genes were analyzed by cytoHubba plug-in. In the process of experimental validation, a mouse sepsis model was established by lipopolysaccharide (LPS), and the treated mice were intraperitoneally injected with RA or Dexamethasone (DEX) 60 min prior to LPS injections. Survival conditions, cardiac functions and antioxidant levels of the mice were assessed. Cardiac inflammation and injury were detected by HE and TUNEL. The levels of key genes and signal pathway expression were analyzed by RT-PCR and Western blot. Results: PPARA, ITGAM, VCAM-1, IGF-1 and IL-6 were identified as key therapeutic targets of RA by network pharmacology. PI3K-Akt signaling pathway is the main regulatory pathway of RA. In vivo researches unraveled that RA can improve the survival rate and cardiac function of LPS-treated mice, inhibit inflammatory factors and myocardial injury, and regulate the expression of key therapeutic targets and key pathways, which is PI3K-Akt signaling pathway. Conclusion: Network pharmacological method offers a predicative strategy to explore the treatment efficacy and causal links of RA in endotoxemic myocarditis. Through experimental verification, we discover that RA can reduce lipopolysaccharide-induced cardiac dysfunction by regulating the PI3K-Akt signaling pathway and key genes.

Identification of Potential Biomarkers for Ryanodine Receptor 1 (RYR1) Mutation-Associated Myopathies Using Bioinformatics Approach.

Background: Myopathies related to Ryanodine receptor 1 (RYR1) mutation are the most common nondystrophy muscle disorder in humans. Early detection and diagnosis of RYR1 mutation-associated myopathies may lead to more timely treatment of patients, which contributes to the management and preparation for malignant hyperthermia. However, diagnosis of RYR1 mutation-associated myopathies is delayed and challenging. The absence of diagnostic morphological features in muscle biopsy does not rule out the possibility of pathogenic variations in RYR1. Accordingly, it is helpful to seek biomarkers to diagnose RYR1 mutation-associated myopathies. Methods: Skeletal muscle tissue microarray datasets of RYR1 mutation-associated myopathies or healthy persons were built in accordance with the gene expression synthesis (GEO) database. Differentially expressed genes (DEGs) were identified on the basis of R software. Genes specific to tissue/organ were identified through BioGPS. An enrichment analysis of DEGs was conducted in accordance with the Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO). We also built protein-protein interaction (PPI) networks to explore the function and enrichment pathway of DEGs and the identification of hub genes. Lastly, the ROC curve was drawn for hub genes achieving specific expressions within skeletal muscle. Moreover, the area under the curve (AUC) was obtained to calculate the predictive value of key genes. The transcription factors of hub genes achieving specific expressions within skeletal muscle were predicted with the use of the iRegulon plugin. Results: We identified 170 DEGs among 11 muscle biopsy samples of healthy subjects and 17 muscle biopsy samples of RYR1 mutation-associated myopathy patients in the dataset. Among the above DEGs, 30 genes achieving specific expressions within tissues/organs were found. GO and KEGG enrichment analysis of DEGs mainly focused on muscle contraction, actin-mediated cell contraction, actin filament-based movement, and muscular sliding. 12 hub genes were identified with the use of Cytoscape. Four hub genes were specifically expressed in skeletal muscle tissue, including MYH1 (AUC: 0.856), TNNT3 (AUC: 0.840), MYLPF (AUC: 0.786), and ATP2A1 (AUC: 0.765). The iRegulon predicted results suggested that the transcription factor MYF6 was found with the highest reliability. Conclusions: Four skeletal muscle tissue-specific genes were identified, including MYH1, TNNT3, MYLPF, and ATP2A1, as the potential biomarkers for diagnosing and treating RYR1 mutation-associated myopathies, which provided insights into the transcriptome-level development mechanism. The transcription factor MYF6 may be a vital upstream regulator of the above biomarkers.

A Novel Prognostic Signature Based on Ferroptosis-Related Genes Predicts the Prognosis of Patients With Advanced Bladder Urothelial Carcinoma.

Bladder Urothelial Carcinoma (BLCA) is the major subtype of bladder cancer, and the prognosis prediction of BLCA is difficult. Ferroptosis is a newly discovered iron-dependent cell death pathway. However, the clinical value of ferroptosis-related genes (FRGs) on the prediction of BLCA prognosis is still uncertain. In this study, we aimed to construct a novel prognostic signature to improve the prognosis prediction of advanced BLCA based on FRGs. In the TCGA cohort, we identified 23 differentially expressed genes (DEGs) associated with overall survival (OS) via univariate Cox analysis (all P < 0.05). 8 optimal DEGs were finally screened to generate the prognostic risk signature through LASSO regression analysis. Patients were divided into two risk groups based on the median risk score. Survival analyses revealed that the OS rate in the high-risk group was significantly lower than that in the low-risk group. Moreover, the risk score was determined as an independent predictor of OS by the multivariate Cox regression analysis (Hazard ratio > 1, 95% CI = 1.724-2.943, P < 0.05). Many potential ferroptosis-related pathways were identified in the enrichment analysis in BLCA. With the aid of an external FAHWMU cohort (n = 180), the clinical predication value of the signature was further verified. In conclusion, the prognosis of advanced BLCA could be accurately predicted by this novel FRG-signature.

Research Progress on the Ability of Astragaloside IV to Protect the Brain Against Ischemia-Reperfusion Injury.

Stroke, a disease with a sudden onset and high morbidity and mortality rates, is difficult to treat in the clinic. Traditional Chinese medicine has become increasingly widely used in clinical practice. Modern pharmacological studies have found that Radix Astragali has a variety of medicinal properties, i.e., immunoregulatory, antioxidative, anti-cancer, anti-diabetes, myocardial protective, hepatoprotective, and antiviral functions. This article reviews the protective effect and mechanism of astragaloside IV, which is extracted from Radix Astragali, on stroke, discusses the cerebroprotective effect of astragaloside IV against ischemia-reperfusion-related complications, offers insight into research prospects, and expands the idea of integrating traditional Chinese and Western medicine treatment strategies and drugs to provide a theoretical reference for the clinical treatment of cerebral ischemia-reperfusion injury and the improvement of stroke prognosis.

Secondary Structure-Dominated Layer-by-Layer Growth Mode of Protein Coatings.

Benefiting from the luxury functions of proteins, protein coatings have been extended to various applications, including tissue engineering scaffolds, drug delivery, antimicrobials, sensing and diagnostic equipment, food packaging, etc. Fast construction of protein coatings is always interesting to materials science and significant to industrialization. Here, we report a layer-by-layer (LbL) multilayer-constructed coating of tannic acid (TA) and lysozyme (Lyz), in which the secondary conformations of Lyz dominate the growth rate of the TA/Lyz coating. As well characterized by various techniques (quartz crystal microbalance with dissipation (QCM-D), circular dichroism (CD) spectra, Fourier transform infrared (FTIR) spectroscopy, atomic force microscopy (AFM), contact angle, etc.), TA-induced conformational transition of Lyz to α-helices occurs at pH 8 from other secondary structures (ß-sheets, ß-turns, and random coils), which leads to the very fast growth of TA/Lyz with a number of deposited bilayers, with thicknesses of more than 90 nm for six bilayers. In contrast to the leading conformation of α-helices at pH 8, Lyz displayed multiple conformations (α-helices, ß-sheets, ß-turns, and random coils) at pH 6, which resulted in coating thicknesses of less than 30 nm for six bilayers. By the addition of NaCl, Tween 20, and urea, we further confirmed that the secondary conformations of Lyz relied greatly on the interactions between TA and Lyz and dominated the growth rate of the multilayers. We believe that these findings will help to understand the transformation of secondary conformations by TA or other polyphenols and inspire a new route to quickly build protein coatings.

Efficient Delivery of Antibodies Intracellularly by Co-Assembly with Hexahistidine-Metal Assemblies (HmA).

PURPOSE: There has been a substantial global market for antibodies, which are based on extracellular targets. Binding intracellular targets by antibodies will bring new chances in antibody therapeutics and a huge market increase. We aim to evaluate the efficiency of a novel delivery system of His6-metal assembly (HmA) in delivering intracellular antibodies and biofunctions of delivered antibodies. METHODS: In this study, the physicochemical properties of HmA@Antibodies generated through co-assembling with antibodies and HmA were well characterized by dynamic light scatter. The cytotoxicity of HmA@Antibodies was investigated by Cell Counting Kit-8 (CCK-8). The endocytic kinetics and lysosome escape process of HmA@Antibodies were studied by flow cytometry and fluorescent staining imaging, respectively. Compared to the commercialized positive control, the intracellular delivery efficiency by HmA@Antibodies and biofunctions of delivered antibodies were evaluated by fluorescent imaging and CCK-8. RESULTS: Various antibodies (IgG, anti-ß-tubulin and anti-NPC) could co-assemble with HmA under a gentle condition, producing nano-sized (~150 nm) and positively charged (~+30 eV) HmA@Antibodies particles with narrow size distribution (PDI ~ 0.15). HmA displayed very low cytotoxicity to divers cells (DCs, HeLa, HCECs, and HRPE) even after 96 h for the feeding concentration ≤100 µg mL-1, and fast escape from endosomes. In the case of delivery IgG, the delivery efficiency into alive cells of HmA was better than a commercial protein delivery reagent (PULSin). For cases of the anti-ß-tubulin and anti-NPC, HmA showed comparable delivery efficiency to their positive controls, but HmA with ability to deliver these antibodies into alive cells was still superior to positive controls delivering antibodies into dead cells through punching holes. CONCLUSION: Our results indicate that this strategy is a feasible way to deliver various antibodies intracellularly while preserving their functions, which has great potential in various applications and treating many refractory diseases by intracellular antibody delivery.

MK8722, an AMPK activator, inhibiting carcinoma proliferation, invasion and migration in human pancreatic cancer cells.

BACKGROUND: MK8722 is a potent and systemic pan-AMPK activator. It is an effective, direct, allosteric activator of AMPK complex in many mammals. This study tried to explore the underlying anti-cancer molecular mechanism of MK8722 in human pancreatic cancer cells (PCCs). METHODS: The anti-proliferation, invasion and migration functions of MK8722 in human pancreatic cancer analyzed by real time cellular analysis, colony formation assay, cell migration assay, transwell assay and flow cytometery analysis. Moreover, the potential targeted signaling pathway was tested via RNA-seq and pathway enrichment analysis. RESULTS: In the present study, we investigated the anti-PCCs effects of MK8722 on two different human pancreatic cancer cell lines (PANC-1 and Patu8988). The results showed that MK8722 significantly inhibited human tumor cells proliferation and migration/invasion in a dose-dependent manner. Additionally, the influence of MK8722 was examined by analyzing the expression of potential key genes and pathways, which may provide novel insights to the mechanism of MK8722. CONCLUSION: The inhibition of pancreatic cancer by MK8722 through a number of pathways that inhibit carcinoma proliferation, invasion and migration. The potential effect of MK8722 might be determined by regulating the expression of AL162151, IER2, REPIN1, KRT80 to inhibit cycle arrest and migration.

Paeoniflorin improves functional recovery through repressing neuroinflammation and facilitating neurogenesis in rat stroke model.

BACKGROUND: Microglia, neuron, and vascular cells constitute a dynamic functional neurovascular unit, which exerts the crucial role in functional recovery after ischemic stroke. Paeoniflorin, the principal active component of Paeoniae Radix, has been verified to exhibit neuroprotective roles in cerebralischemic injury. However, the mechanisms underlying the regulatory function of Paeoniflorin on neurovascular unit after cerebral ischemia are still unclear. METHODS: In this study, adult male rats were treated with Paeoniflorin following transient middle cerebral artery occlusion (tMCAO), and then the functional behavioral tests (Foot-fault test and modified improved neurological function score, mNSS), microglial activation, neurogenesis and vasculogenesis were assessed. RESULTS: The current study showed that Paeoniflorin treatment exhibited a sensorimotor functional recovery as suggested via the Foot-fault test and the enhancement of spatial learning as suggested by the mNSS in rat stroke model. Paeoniflorin treatment repressed microglial cell proliferation and thus resulted in a significant decrease in proinflammatory cytokines IL-1ß, IL-6 and TNF-α. Compared with control, Paeoniflorin administration facilitated von Willebrand factor (an endothelia cell marker) and doublecortin (a neuroblasts marker) expression, indicating that Paeoniflorin contributed to neurogenesis and vasculogenesis in rat stroke model. Mechanistically, we verified that Paeoniflorin repressed JNK and NF-κB signaling activation. CONCLUSIONS: These results demonstrate that Paeoniflorin represses neuroinflammation and facilitates neurogenesis in rat stroke model and might be a potential drug for the therapy of ischemic stroke.

The Incidence of and Risk Factors for Localized Pain at the Epidural Insertion Site After Epidural Anesthesia: A Prospective Survey of More Than 5000 Cases in Nonobstetric Surgery.

BACKGROUND: This prospective research aimed to determine the incidence of and risk factors for localized pain at the epidural insertion site following nonobstetric surgery performed with epidural anesthesia. METHODS: A total of 5083 surgical inpatients at the teaching hospital undergoing epidural anesthesia were included in the study. The characteristics of the patients, preoperative basic diseases, details of the epidural techniques, surgical procedures and complications were recorded pre-anesthesia until the complications resolved. Multivariate logistic regression analysis was performed to identify predictors of localized pain at the epidural insertion site. RESULTS: In our analysis, target complications were reported in 532 (10.5%) patients; localized pain at the epidural insertion site occurred in 460 (9.05%) patients, while other major complications occurred in 72 (1.45%) patients. A total of 334 patients had mild pain, and 126 patients had moderate pain. The incidence of localized pain at the epidural insertion site was highest among all complications, and the identified risk factors in the multivariate analysis were as follows: lumbar insertion (odds ratio, 1.77; 95% CI 1.33-2.35), age less than 50 years old (odds ratio, 1.56; 95% CI 1.29-1.89), multiple block attempts (odds ratio, 3.39; 95% CI 2.68-4.31), and postoperative patient-controlled epidural analgesia (odds ratio, 0.46; 95% CI 0.33-0.63). CONCLUSION: Localized pain at the epidural insertion site is the most common complaint after epidural anesthesia and requires adequate clinical attention. Improving the proficiency of anesthesiologists to avoid repeated punctures is the best way to reduce injuries.

Sheltering proteins from protease-mediated degradation and a de novo strategy for preventing acute liver injury.

Restoring protein functions or supplying proteins is considered one of the most powerful therapeutic strategies for many diseases, but it is mainly limited by the denaturation of proteins during encapsulation and degradation by proteases during in vivo delivery, and limits its delivery. Herein, by encapsulating a protein (catalase, an enzyme) in a hexahistidine-metal assembly (HmA) via a de novo strategy under mild conditions, we demonstrated that HmA could maintain the bioactivity of the enzyme, protect the enzyme from proteinase degradation, and deliver the encapsulated protein for the prevention of disease in an acute liver injury model.

Profiling of gut microbial dysbiosis in adults with myeloid leukemia.

Dysregulation of gut microbiota is implicated in the pathogenesis of various diseases, including metabolic diseases, inflammatory diseases, and cancer. To date, the link between gut microbiota and myeloid leukemia (ML) remains largely unelucidated. Herein, a total of 29 patients with acute myeloid leukemia (AML), 17 patients with chronic myeloid leukemia (CML), and 33 healthy subjects were enrolled, and gut microbiota were profiled via Illumina sequencing of the 16S rRNA. We evaluated the correlation between ML and gut microbiota. The microbial α-diversity and ß-diversity exhibited significant differences between ML patients and healthy controls (HCs). Compared to healthy subjects, we found that at the phylum level, the relative abundance of Actinobacteria, Acidobacteria, and Chloroflexi was increased, while that of Tenericutes was decreased. Correspondingly, at the genus level in ML, Streptococcus were increased, especially in AML patients, while Megamonas (P = 0.02), Lachnospiraceae NC2004 group, and Prevotella 9 (P = 0.007) were decreased. Moreover, ML-enriched species, including Sphingomonas, Lysobacyer, Helicobacter, Lactobacillus, Enterococcus, and Clostridium sensu stricto 1, were identified. Our results indicate that the gut microbiota was altered in ML patients compared to that of healthy subjects, which could contribute to the elucidation of microbiota-related pathogenesis of ML, and the development of novel therapeutic strategies in the treatment of ML.