Search

Defective mitophagy is consistently found in postmortem brain and iPSC-derived neurons from Alzheimer disease (AD) patients. However, there is a lack of extensive examination of mitophagy status in serum or cerebrospinal fluid (CSF), and the clinical potential of mitophagy biomarkers has not been tested. We quantified biomarkers of mitophagy/autophagy and lysosomal degradation (PINK1, BNIP3L and TFEB) in CSF and serum from 246 individuals, covering mild cognitive impairment due to AD (MCI-AD, n = 100), dementia due to AD (AD-dementia, n = 100), and cognitively unimpaired individuals (CU, n = 46), recruited from the Czech Brain Aging Study. Cognitive function and brain atrophy were also assessed. Our data show that serum and CSF PINK1 and serum BNIP3L were higher, and serum TFEB was lower in individuals with AD than in corresponding CU individuals. Additionally, the magnitude of mitophagy impairment correlated with the severity of clinical indicators in AD patients. Specifically, levels of PINK1 positively correlated with phosphorylated (p)-MAPT/tau (181), total (t)-MAPT/tau, NEFL (neurofilament light chain), and NRGN (neurogranin) levels in CSF and negatively with memory, executive function, and language domain. Serum TFEB levels negatively correlated with NEFL and positively with executive function and language. This study reveals mitophagy impairment reflected in biofluid biomarkers of individuals with AD and associated with more advanced AD pathology. Abbreviation: Aβ: amyloid beta; AD: Alzheimer disease; AVs: autophagic vacuoles; BNIP3L: BCL2 interacting protein 3 like; CU: cognitively unimpaired; CSF: cerebrospinal fluid; LAMP1: lysosomal-associated membrane protein 1; MAP1LC3/LC3: microtubule associated protein 1 light chain 3; MCI: mild cognitive impairment; NRGN: neurogranin; NEFL: neurofilament light chain; p-MAPT/tau: phosphorylated microtubule associated protein tau; PINK1: PTEN induced kinase 1; t-MAPT/tau: total microtubule associated protein tau; TFEB: transcription factor EB; TMT: Trail Making Test. [ABSTRACT FROM AUTHOR]

Time‐dependent dynamic information encryption technology is a promising approach to enhancing the security and complexity of information transmission. Herein, a time‐dependent information encryption model from a liquid crystalline polymer (LCP) film with a programmable glass transition temperature (Tg) and gradually adjustable fluorescence is demonstrated. The programmable Tg is achieved by adjusting the degree of order of the LC molecules via a configuration interconversion of spiropyran‐based materials (SPBMs), which can convert between a V‐shaped colorless spiro (SP) and a rodlike dark‐colored merocyanine (MC) form. An LCP film obtained by visible light polymerization exhibits a lower Tg than UV light, because the SPBM molecules keep different configurations in the two films. By adjusting the ratio of two isomerization forms of SPBM molecules during the polymerization process, the Tg values of LCP films can change from 11.6 °C to 31.1 °C. Based on the isomerization rate of SPBM in the LCP films with different Tg, time‐dependent information encryption is successfully achieved. [ABSTRACT FROM AUTHOR]

Summary: Therapy‐related acute lymphoblastic leukaemia (tr‐ALL) is a disease entity attributed to previous exposure to chemotherapy and/or radiation for antecedent malignancy. There is observed female predominance for tr‐ALL, likely due to high prevalence and excellent curable rate for non‐metastatic breast cancer as well as the frequent use of carcinogenic agents as part of adjuvant therapy. Here, we reviewed 37 women with diagnosis of ALL following breast cancer treatment with focus on cytogenetic categorization. Philadelphia chromosome positivity (Ph+), KMT2A alterations and other cytogenetic change groups were observed in 32%, 22% and 46% of patients respectively. Median overall survival (OS) and relapse‐free survival (RFS) were 19.4 and 12.9 months, overall while both OS and RFS were superior in tr‐ALL with Ph+ disease compared to KMT2Ar and other cytogenetics respectively. Seventeen (45.9%) patients underwent consolidative allogeneic haematopoietic cell transplantation (alloHCT) in CR1 out of which 4 (24%) relapsed following transplant. Both OS and RFS were superior in the KMT2Ar cytogenetics group following alloHCT. Ph chromosome represents the largest genetic entity of tr‐ALL following breast cancer therapy, and it may be associated with superior survival outcomes while KMT2Ar may be associated with poorer outcomes that can perhaps be mitigated by alloHSCT. [ABSTRACT FROM AUTHOR]

This document presents data on the outcomes and toxicities of a treatment regimen for older adults with newly diagnosed FLT3-mutated acute myeloid leukemia (AML). The study found that the treatment approach, which included induction chemotherapy with the addition of midostaurin, resulted in a high complete remission rate and a median overall survival of 9.3 months. Additionally, a significant number of patients underwent allogeneic hematopoietic stem cell transplantation (allo-HCT) with favorable outcomes. The authors conclude that this treatment approach is feasible and effective for older adults with FLT3-mutated AML. However, the study lacked long-term follow-up and data on minimal residual disease achievement and allo-HCT outcomes. [Extracted from the article]

Introduction The aim of the study was to explore the clinical efficacy and safety of intravenous thrombolysis and bridging artery thrombectomy for hyperacute ischemic stroke with unknown onset time. Material and methods One hundred and twenty-eight patients with hyperacute cerebral infarction and without a clear time of onset were randomly divided into intravenous thrombolysis (n = 66) and bridging artery thrombectomy groups (n = 62). Results In the intravenous thrombolysis group, 37 patients’ vessels had recanalization, 32 patients’ 24-hour National Institute of Health Stroke Scale (NIHSS) score improved, and 42 patients’ 90-day modified Rankin Scale (mRS) score was good. In the bridging artery thrombectomy group, 62 patients’ vessels had recanalization, 28 patients’ 24-hour NIHSS score improved, and 38 patients’ 90-day mRS score was good. Conclusions The benefits and adverse events between intravenous thrombolysis and bridging artery thrombectomy for ischemic stroke with unknown time of onset are similar.