Longitudinal change of serum AIM2 levels after aneurysmal subarachnoid hemorrhage and its prognostic significance: a two-center prospective cohort study.

Absent in melanoma 2 (AIM2) is implicated in neuroinflammation. Here, we explored the prognostic significance of serum AIM2 in human aneurysmal subarachnoid hemorrhage (aSAH). We conducted a consecutive enrollment of 127 patients, 56 of whom agreed with blood-drawings not only at admission but also at days 1, 2, 3, 5, 7 and 10 days after aSAH. Serum AIM2 levels of patients and 56 healthy controls were measured. Disease severity was assessed using the modified Fisher scale (mFisher) and World Federation of Neurological Surgeons Scale (WFNS). Neurological outcome at poststroke 90 days was evaluated via the modified Rankin Scale (mRS). Univariate analysis and multivariate analysis were sequentially done to ascertain relationship between serum AIM2 levels, severity, delayed cerebral ischemia (DCI) and 90-day poor prognosis (mRS scores of 3-6). Patients, in comparison to controls, had a significant elevation of serum AIM2 levels at admission and at days 1, 2, 3, 5, 7 and 10 days after aSAH, with the highest levels at days 1, 2, 3 and 5. AIM2 levels were independently correlated with WFNS scores and mFisher scores. Significantly higher serum AIM2 levels were detected in patients with a poor prognosis than in those with a good prognosis, as well as in patients with DCI than in those without DCI. Moreover, serum AIM2 levels independently predicted a poor prognosis and DCI, and were linearly correlated with their risks. Using subgroup analysis, there were no significant interactions between serum AIM2 levels and age, gender, hypertension and so on. There were substantially high predictive abilities of serum AIM2 for poor prognosis and DCI under the receiver operating characteristic curve. The combination models of DCI and poor prognosis, in which serum AIM2, WFNS scores and mFisher scores were incorporated, showed higher discriminatory efficiencies than anyone of the preceding three variables. Moreover, the models are delineated using the nomogram, and performed well under the calibration curve and decision curve. Serum AIM2 levels, with a substantial enhancement during early phase after aSAH, are closely related to bleeding severity, poor 90-day prognosis and DCI of patients, substantializing serum AIM2 as a potential prognostic biomarker of aSAH.

M335, a novel small-molecule STING agonist activates the immune response and exerts antitumor effects.

In the context of antitumor immune responses, the activation of the stimulator of interferon genes (STING) assumes a critical role and imparts enhanced immunogenicity. An effective strategy for exogenously activating the immune system involves the utilization of STING agonists, and prior investigations primarily concentrated on modifying endogenous cyclic dinucleotides (CDNs) to achieve this. Nevertheless, the practical utility of CDNs was restricted due to limitations associated with their physicochemical attributes and administration protocols. In this article, we present the discovery of a novel small-molecule agonist denoted as M335, identified through high-throughput screening using surface plasmon resonance (SPR). M335 demonstrates the ability to activate the TBK1-IRF3-IFN axis in a STING-dependent manner in vitro. Through experimentation on mouse models bearing tumors, we observed that the administration of M335 resulted in the activation of immune cells. Notably, significant antitumor effects were achieved with both intratumoral and intraperitoneal administration of M335. These findings suggest the potential of M335 as a promising agent for cancer immunotherapy, which will promote the development of STING agonists in anti-tumor applications.

Effective treatment with Gilteritinib-based regimens for FLT3-mutant extramedullary relapse in acute promyelocytic leukemia.

OBJECTIVE: Extramedullary relapse (EMR) is rare in acute promyelocytic leukemia (APL) and, there is a lack of information on its management. Current practices for EMR in APL are always to adopt strategies from other subtypes of Acute lymphoblastic leukemia (ALL) and Acute myeloid leukemia (AML). Gilteritinib, a highly selective FLT3 inhibitor, has demonstrated a remarkable effect on EMR in FLT3-mutant AML. Therefore, it is worthwhile exploring if FLT3 mutation can be a therapeutic target and assessing the efficacy of Gilteritinib on FLT3-mutant EMR in APL. METHODS: We described three cases of FLT3-mutant EMR in APL, comprising two isolated EMR cases and one systemic relapse. The patients underwent treatment with Gilteritinib-based regimens based on FLT3 mutation. RESULTS: All three patients achieved complete regression of EMR, and no signs of tumor lysis syndrome during Gilteritinib-based therapy, only patient 1 showed mild granulocytopenia. They all maintained molecular complete remission (mCR) during the follow-up period. CONCLUSIONS: The Gilteritinib-based regimen shows a high and sustained therapeutic effect with minimal adverse effects, and provides a valuable experience for further evaluation in EMR APL patients.

Temporal change of serum xanthine oxidase levels and its relation to clinical outcome of severe traumatic brain injury: a prospective cohort study.

Xanthine oxidase (XO) may be involved in the induction of oxidative stress and inflammation. We measured serum XO levels at multiple days to determine whether it is associated with the severity and prognosis of severe traumatic brain injury (sTBI). In this prospective cohort study, we quantified serum XO levels in 112 sTBI patients and 112 controls. Serum XO levels of patients were measured at admission and at days 1, 3, 5, 7, and 10 after sTBI. Extended Glasgow outcome scale scores of 1-4 at post-trauma 180 days were defined as a poor prognosis. Multivariate analysis was employed to determine the relationship between poor prognosis and serum XO levels at multiple days. Serum XO levels were significantly increased at admission among patients, afterwards elevated gradually, peaked at day 3, and then diminished gradually until day 10, and were substantially higher during 10 days in patients than in controls. Serum XO levels at 6 different days were all correlated with admission Rotterdam computed tomography (CT) scores and Glasgow coma scale (GCS) scores. Serum XO levels at 6 different days were all substantially higher in patients with poor prognosis than in those with good prognosis. Serum XO levels at days 7 and 10, but not at days 1, 3, and 5, had significantly lower area under receiver operating characteristic (AUC) than those at admission. Serum XO levels at admission and at days 1 and 3, but not at day 5, were independently associated with 180-day poor prognosis. Prognostic prediction model containing GCS scores, Rotterdam CT scores, and serum XO levels at admission (or at days 1 and 3) showed substantially higher AUC than GCS scores and Rotterdam CT scores alone. The models were visually described using nomograms, which were comparatively stable under calibration curve and were relatively of clinical benefit under decision curve. Elevated serum XO levels during early period of sTBI are more closely associated with trauma severity and clinical adverse outcomes, assuming that serum XO may serve as a potential prognostic biomarker in sTBI.

Noncanonical autophagy is a new strategy to inhibit HSV-1 through STING1 activation.

STING1 (stimulator of interferon response cGAMP interactor 1) plays an essential role in immune responses for virus inhibition via inducing the production of type I interferon, inflammatory factors and macroautophagy/autophagy. In this study, we found that STING1 activation could induce not only canonical autophagy but also non-canonical autophagy (NCA) which is independent of the ULK1 or BECN1 complexes to form MAP1LC3/LC3-positive structures. Whether STING1-induced NCA has similar characters and physiological functions to canonical autophagy is totally unknown. Different from canonical autophagy, NCA could increase single-membrane structures and failed to degrade long-lived proteins, and could be strongly suppressed by interrupting vacuolar-type H+-translocating ATPase (V-ATPase) activity. Importantly, STING1-induced NCA could effectively inhibit DNA virus HSV-1 in cell model. Moreover, STING1 [1-340], a STING1 mutant lacking immunity and inflammatory response due to deletion of the tail end of STING1, could degrade virus through NCA alone, suggesting that the antiviral effect of activated STING1 could be separately mediated by inherent immunity, canonical autophagy, and NCA. In addition, the translocation and dimerization of STING1 do not rely on its immunity function and autophagy pathway. Similar to canonical autophagy, LC3-positive structures of NCA induced by STING1 could finally fuse with lysosomes, and the degradation of HSV-1 could be reverted by inhibition of lysosome function, suggesting that the elimination of DNA virus via NCA still requires the lysosome pathway. Collectively, we proved that besides its classical immunity function and canonical autophagy pathway, STING1-induced NCA is also an efficient antiviral pathway for the host cell.Abbreviations: ATG: autophagy related; Baf: bafilomycin A1; CASM: conjugation of LC3 to a single membrane; CGAS: cyclic GMP-AMP synthase; cGAMP: cyclic GMP-AMP; CQ: chloroquine; CTD: C-terminal domain; CTT: C-terminal tail; ER: endoplasmic reticulum; ERGIC: ER-Golgi intermediate compartment; HSV-1: herpes simplex virus 1; IRF3: interferon regulatory factor 3; IFNs: interferons; LAMP1: lysosomal associated membrane protein 1; LAP: LC3-associated phagocytosis; MAP1LC3/LC3: microtubule associated protein 1 light chain 3; MOI: multiplicity of infection; RB1CC1/FIP200: RB1 inducible coiled-coil 1; STING1: stimulator of interferon response cGAMP interactor 1; TBK1: TANK binding kinase 1; TGOLN2/TGN46: trans-golgi network protein 2; ULK1: unc-51 like autophagy activating kinase 1; V-ATPase: vacuolar-type H+-translocating ATPase; VSV: vesicular stomatitis virus.

How Do Phosphorus Compounds with Different Valence States Affect the Flame Retardancy of PET?

This work investigated the effect of different valence states of phosphorus-containing compounds on thermal decomposition and flame retardancy of polyethylene terephthalate (PET). Three polyphosphates-PBPP with +3-valence P, PBDP with +5-valence P and PBPDP with both +3/+5-valence P-were synthesized. The combustion behaviors of flame-retardant PET were studied and the structure-property relationships between the phosphorus-based structures with different valence states and flame-retardant properties were further explored. It was found that phosphorus valence states significantly affected the flame-retardant modes of action of polyphosphate in PET. For the phosphorus structures with +3-valence, more phosphorus-containing fragments were released in the gas phase, inhibiting polymer chain decomposition reactions; by contrast, those with +5-valence phosphorus retained more P in the condensed phase, promoting the formation of more P-rich char layers. It is worth noting that the polyphosphate containing both +3/+5-valence phosphorous tended to combine the advantage of phosphorus structures with two valence states and balance the flame-retardant effect in the gas phase and condensed phase. These results contribute to guiding the design of specified phosphorus-based structures of flame-retardant compounds in polymer materials.

Warm and Harsh Parenting, Self-Kindness and Self-Judgment, and Well-Being: An Examination of Developmental Differences in a Large Sample of Adolescents.

Objectives: This study aimed to examine the associations between warm and harsh parenting and adolescent well-being, and the mediating effects of self-kindness and self-judgment, in relationships. Moreover, this study investigated developmental differences across three adolescence stages (early, middle, and late). Methods: In total, 14,776 Chinese adolescents (mean age = 13.53 ± 2.08, 52.3% males), including individuals in early (10-12 years old, N = 5055), middle (13-15 years old, N = 6714), and late adolescence (16-18 years old, N = 3007) participated in this study. All the adolescents rated their levels of warm and harsh parenting, self-kindness and self-judgment, and well-being. Structural equation modeling (SEM) was adopted to examine the mediation model. Multi-group analysis was conducted to investigate differences in the mediation model across the different developmental stages. Results: Both warm and harsh parenting were related to adolescent well-being through the mediating effects of self-kindness and self-judgment. However, warm parenting exerted a more substantial impact on adolescent well-being. Self-kindness had a more robust mediating effect than self-judgment in relationships. Moreover, harsh parenting had a weaker impact on adolescent well-being in late adolescence than in early and middle adolescence. Warm parenting had a more significant impact on adolescent well-being in early adolescence than in middle and late adolescence. Conclusions: Overall, warm parenting had a more substantial effect than harsh parenting on adolescent well-being. The findings also highlighted the crucial mediating effect of self-kindness in the relationships between parenting and well-being. Moreover, this study also indicated the importance of warm parenting in early adolescence. Intervention programs should focus on enhancing the level of warm parenting to promote self-kindness in adolescents, in order to improve their well-being.

[Clinical Value of Translocator Protein Gene in Evaluating the Efficacy of FLT3-ITD/DNMT3A R882 Double-Mutated Acute Myeloid Leukemia].

OBJECTIVE: To observe the clinical significance of translocator proteins (TSPO) gene in the treatment of FLT3-ITD/DNMT3A R882 double-mutated acute myeloid leukemia (AML). METHODS: Seventy-six patients with AML hospitalized in the Department of Hematology of the Affiliated People's Hospital of Ningbo University from June 2018 to June 2020 were selected, including 34 patients with FLT3-ITD mutation, 27 patients with DNMT3A R882 mutation, 15 patients with FLT3-ITD/DNMT3A R882 double mutation, as well as 19 patients with immune thrombocytopenia (ITP) hospitalized during the same period as control group. RNA was routinely extracted from 3 ml bone marrow retained during bone puncture, and TSPO gene expression was detected by transcriptome sequencing (using 2-deltadeltaCt calculation). RESULTS: The expression of TSPO gene in FLT3-ITD group and DNMT3A R882 group at first diagnosis was 2.02±1.04 and 1.85±0.76, respectively, which were both higher than 1.00±0.06 in control group, but the differences were not statistically significant (P=0.671, P=0.821). The expression of TSPO gene in the FLT3-ITD/DNMT3A R882 group was 3.98±1.07, wich was significantly higher than that in the FLT3-ITD group and DNMT3A R882 group, the differences were statistically significant (P=0.032, P=0.021). The expression of TSPO gene in patients who achieved complete response after chemotherapy in the FLT3-ITD/DNMT3A R882 group was 1.19±0.87, which was significantly lower than that at first diagnosis, and the difference was statistically significant (P=0.011). CONCLUSION: TSPO gene may be used as an indicator of efficacy in FLT3-ITD /DNMT3A R882 double-mutated AML.

Vicious circle of family dysfunction and adolescent internet addiction: Do only child and non-only child exhibit differences?

The primary aim of the current study was to probe the longitudinal relationships between family dysfunction (FD) and adolescent Internet addiction (IA), as well as the group difference between only child and non-only child. Data were from a three-wave longitudinal data of 1301 Chinese adolescents, collected when adolescents were at Grade 7, Grade 8, and Grade 9. FD and IA were assessed via adolescent self-reported questionaries of Chinese Family Assessment Instrument and Internet Addiction Test. Cross-lagged panel model was constructed to estimate possible associations between FD and adolescent IA after controlling for demographic variables. Our results suggest that adolescents might get stuck in a vicious cycle of dysfunctional family and addictive Internet use: adolescents who lived in a dysfunctional family showed increased risk in IA in the subsequent year; in turn, adolescent IA further increased the possibility of FD. Moreover, multigroup comparison analysis revealed that the vicious cycle between FD and adolescent IA could be applied to both the only child and the non-only child. The findings may enrich the application of the Developmental Contextualism Theory and contribute to the identification of the starting points for intervention strategies of adolescent IA.

A Phosphorous-Based Bi-Functional Flame Retardant Based on Phosphaphenanthrene and Aluminum Hypophosphite for an Epoxy Thermoset.

A phosphorous-based bi-functional compound HPDAl was used as a reactive-type flame retardant (FR) in an epoxy thermoset (EP) aiming to improve the flame retardant efficiency of phosphorus-based compounds. HPDAl, consisting of two different P-groups of aluminum phosphinate (AHP) and phosphophenanthrene (DOPO) with different phosphorous chemical environments and thus exerting different FR actions, exhibited an intramolecular P-P groups synergy and possessed superior flame-retardant efficiency compared with DOPO or AHP alone or the physical combination of DOPO/AHP in EP. Adding 2 wt.% HPDAl made EP composites acquire a LOI value of 32.3%, pass a UL94 V-0 rating with a blowing-out effect, and exhibit a decrease in the heat/smoke release. The flame retardant modes of action of HPDAl were confirmed by the experiments of the scanning electron microscope (SEM), X-ray photoelectron spectroscopy (XPS), and thermogravimetry-Fourier transform infrared spectroscopy-gas chromatograph/mass spectrometer (TG-FTIR-GC/MS). The results indicate that the phosphorous-based FRs show different influences on the flame retardancy of composites, mainly depending on their chemical structures. HPDAl had a flame inhibition effect in the gas phase and a charring effect in the condensed phase, with a well-balanced distribution of P content in the gas/condensed phase. Furthermore, the addition of HPDAl hardly impaired the mechanical properties of the matrix due to the link by chemical bonds between them.

Discovery of an autophagy inducer J3 to lower mutant huntingtin and alleviate Huntington's disease-related phenotype.

Huntington's disease (HD) is a neurodegenerative disorder caused by aggregation of the mutant huntingtin (mHTT) protein encoded from extra tracts of CAG repeats in exon 1 of the HTT gene. mHTT proteins are neurotoxic to render the death of neurons and a series of disease-associated phenotypes. The mHTT is degraded through autophagy pathway and ubiquitin-proteasome system (UPS). This study identified a small molecule, J3, as an autophagy inducer by high-content screening. The results revealed that J3 could inhibit mTOR, thus promoting autophagic flux and long-lived protein degradation. Further, J3 selectively lowered the soluble and insoluble mHTT but not wild type HTT levels in cell models. The HdhQ140 mice showed reduced HD-associated activity and loss of motor functions. However, administration of J3 showed increased activity and a slight improvement in the motor function in the open-field test, balance beam test, and rotarod tests. Furthermore, in vivo studies revealed that J3 decreased T-HTT and misfolded protein levels in the striatum and increased the levels of the medium spiny neuron marker DARPP-32. In addition, J3 showed good permeability across the brain-blood barrier efficiently, suggesting that J3 was a promising candidate for the treatment of HD.

Factors Associated with Treatment Outcome in Patients with Nontuberculous Mycobacterial Pulmonary Disease: A Large Population-Based Retrospective Cohort Study in Shanghai.

Infectious diseases caused by nontuberculous mycobacteria (NTM) are increasingly common. This retrospective cohort study examined factors associated with outcomes in patients from Shanghai who had NTM pulmonary disease (NTMPD) from January 2014 to December 2018. The causative bacterial species, drug susceptibility test results, treatment outcomes, sputum culture conversion rate, and risk factors associated with treatment failure were determined. The most common species were Mycobacterium avium complex (MAC) (50%), M. abscessus (28%), and M. kansasii (15%). Over five years, the proportions of M. kansasii and M. abscessus increased, and that of MAC decreased. The treatment success rate was significantly greater for patients infected with M. kansasii (89.9%) than MAC (65.0%, p < 0.001) and M. abscessus (36.1%, p < 0.001). Multivariate analysis indicated the risk factors for treatment failure were pathogenic NTM species (M. abscessus: aOR = 9.355, p < 0.001; MAC: aOR = 2.970, p < 0.001), elevated ESR (>60 mm/h: aOR = 2.658, p < 0.001), receipt of retreatment (aOR = 2.074, p < 0.001), and being middle-aged or elderly (>60 years-old: aOR = 1.739, p = 0.021; 45-60 years-old: aOR = 1.661, p = 0.034). The main bacterial species responsible for NTMPD were MAC, M. abscessus, and M. kansasii. Patients who were infected by M. abscessus or MAC, with elevated ESR, received retreatment, and were middle-aged or elderly had an increased risk of treatment failure.

Development of Thyroid Hormones and Synthetic Thyromimetics in Non-Alcoholic Fatty Liver Disease.

Non-alcoholic fatty liver disease (NAFLD) is the fastest-growing liver disease in the world. Despite targeted agents which are needed to provide permanent benefits for patients with NAFLD, no drugs have been approved to treat NASH. Thyroid hormone is an important signaling molecule to maintain normal metabolism, and in vivo and vitro studies have shown that regulation of the 3,5,3'-triiodothyronine (T3)/ thyroid hormone receptor (TR) axis is beneficial not only for metabolic symptoms but also for the improvement of NAFLD and even for the repair of liver injury. However, the non-selective regulation of T3 to TR subtypes (TRα/TRß) could cause unacceptable side effects represented by cardiotoxicity. To avoid deleterious effects, TRß-selective thyromimetics were developed for NASH studies in recent decades. Herein, we will review the development of thyroid hormones and synthetic thyromimetics based on TR selectivity for NAFLD, and analyze the role of TR-targeted drugs for the treatment of NAFLD in the future.

Design of Highly Durable Core-Shell Catalysts by Controlling Shell Distribution Guided by In-Situ Corrosion Study.

Most degradations in electrocatalysis are caused by corrosion in operation, for example the corrosion of the core in a core-shell electrocatalyst during the oxygen reduction reaction (ORR). Herein, according to the in-situ study on nanoscale corrosion kinetics via liquid cell transmission electron microscopy (LC-TEM) in the authors' previous work, they sequentially designed an optimized nanocube with the protection of more layers on the corners by adjusting the Pt atom distribution on corners and terraces. This modified nanocube (MNC) is much more corrosion resistant in the in-situ observation. Furthermore, in the practical electrochemical stability testing, the MNC catalyst also showed the best stability performance with the 0.37% and 9.01% loss in specific and mass activity after 30 000 cycles accelerated durability test (ADT). This work also demonstrates that how an in-situ study can guide the design of desired materials with improved properties and build a bridge between in-situ study and practical application.

Binding Features and Functions of ATG3.

Autophagy is an evolutionarily conserved catabolic process that is essential for maintaining cellular, tissue, and organismal homeostasis. Autophagy-related (ATG) genes are indispensable for autophagosome formation. ATG3 is one of the key genes involved in autophagy, and its homologs are common in eukaryotes. During autophagy, ATG3 acts as an E2 ubiquitin-like conjugating enzyme in the ATG8 conjugation system, contributing to phagophore elongation. ATG3 has also been found to participate in many physiological and pathological processes in an autophagy-dependent manner, such as tumor occurrence and progression, ischemia-reperfusion injury, clearance of pathogens, and maintenance of organelle homeostasis. Intriguingly, a few studies have recently discovered the autophagy-independent functions of ATG3, including cell differentiation and mitosis. Here, we summarize the current knowledge of ATG3 in autophagosome formation, highlight its binding partners and binding sites, review its autophagy-dependent functions, and provide a brief introduction into its autophagy-independent functions.

A living cell-based fluorescent reporter for high-throughput screening of anti-tumor drugs.

Suppression of cellular O-linked ß-N-acetylglucosaminylation (O-GlcNAcylation) can repress proliferation and migration of various cancer cells, which opens a new avenue for cancer therapy. Based on the regulation of insulin gene transcription, we designed a cell-based fluorescent reporter capable of sensing cellular O-GlcNAcylation in HEK293T cells. The fluorescent reporter mainly consists of a reporter (green fluorescent protein (GFP)), an internal reference (red fluorescent protein), and an operator (neuronal differentiation 1), which serves as a "sweet switch" to control GFP expression in response to cellular O-GlcNAcylation changes. The fluorescent reporter can efficiently sense reduced levels of cellular O-GlcNAcylation in several cell lines. Using the fluorescent reporter, we screened 120 natural products and obtained one compound, sesamin, which could markedly inhibit protein O-GlcNAcylation in HeLa and human colorectal carcinoma-116 cells and repress their migration in vitro. Altogether, the present study demonstrated the development of a novel strategy for anti-tumor drug screening, as well as for conducting gene transcription studies.

[Ikaros Family Zinc Finger 1 Mutation Is an Adverse Prognostic Factor for Patients with Adult B-Cell Acute Lymphoblastic Leukemia].

OBJECTIVE: To investigate the prognosis of patients with adult B-cell acute lymphoblastic leukemia (B-ALL) accompanied with Ikaros family zinc finger 1 (IKZF1) mutation, and to explore the role of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in improving the clinical outcome of patients. METHODS: The clinical data of 164 adult B-ALL patients who received IKZF-1 mutation detection by capillary electrophoresis of bone marrow were collected, and the relationship between the IKZF-1 gene mutation and the prognosis of adult B-ALL patients was analyzed. RESULTS: Among 164 adult B-ALL patients, the patients with IKZF-1 mutation (IKZF-1+) were 80 cases, while the patients without IKZF-1 mutation (IKZF-1-) were 84 cases. Among 80 IKZF-1 positive patients, according to the treatment method after complete remission these patients were divided into HSCT group (48 cases) and chemotherapy group (32 cases). Analysis showed that the 3-year overall survival (OS) and leukemia-free survival (LFS) rates in the IKZF1+ group were much lower. The OS and LFS rate in transplantation group were 50.3%±8.3%, 41.6%±8.5%; the OS and LFS rates in the chemotherapy group were 33.7%±12.8%, 31.5%±9.5%, which were lower than those in the IKZF1- group (the transplantation group: 79.5%±7.6%, 64.0%±8.4%; the chemotherapy group: 54.4%±9.9%, 40.6%±9.6% respectirely (P＜0.05). Among 80 B-ALL patients with IKZF-1- mutation, the 3-year OS and LFS rates were significantly higher in the transplantation group (55.3%±7.5%, 48.3%±7.6%) than those in the chemotherapy group (32.9%±11.8%, 28.4%±10.3%) with IKZF1 mutation (P＜0.05). CONCLUSION: IKZF1 mutation is an adverse prognostic factor for adult B-ALL patients, However, allo-HSCT significantly improves the OS and LFS of patients and also their clinical outcomes.

The effects of Astragalus Membranaceus Active Extracts on Autophagy-related Diseases.

Autophagy is an evolutionarily conserved 'self-eating' process that maintains cellular, tissue, and organismal homeostasis. New studies on autophagy, mediated by subsets of autophagy proteins, are emerging in many physiological and pathological processes. Astragalus membranaceus (AM), also named Huangqi, is one of the fundamental herbs in traditional Chinese medicine and its extracts have been proved to possess many biological activities related to autophagy, including anti-oxidation, anti-inflammation, anticancer, anti-photoaging, and improvement of cardiomyocyte function. Evidence suggests that AM extracts can have therapeutic potential in autophagy dysregulation-associated diseases because of their biological positive effects. Here we will review the literature concerning the effects of AM extracts on autophagy dysregulation-associated diseases.

Niclosamide Triggers Non-Canonical LC3 Lipidation.

Autophagy is a highly- evolutionarily-conserved catabolic pathway activated by various cellular stresses. Recently, non-canonical autophagy (NCA), which does not require all of the ATG proteins to form autophagosome or autophagosome-like structures, has been found in various conditions. Moreover, mounting evidence has indicated that non-canonical LC3 lipidation (NCLL) may reflect NCA. We and others have reported that niclosamide (Nic), an anti-helminthic drug approved by the Food and Drug Administration, could induce canonical autophagy via a feedback downregulation of mTOR complex 1. In this study, we found that Nic could also induce NCLL, which is independent of the ULK1 complex and Beclin 1 complex, but dependent on ubiquitin-like conjugation systems. Although bafilomycin A1 and concanamycin A, two known V-ATPase inhibitors, significantly inhibited Nic-induced NCLL, Nic-induced NCLL was demonstrated to be independent of V-ATPase. In addition, the Golgi complex and vimentin were involved in Nic-induced NCLL, which might be a platform or membrane source for Nic-induced LC3-positive structures. These results would be helpful to broaden our understanding of the working mechanisms of Nic and evaluate its pharmacological activities in diseases.