Nickel ferrite decorated noble metal containing nitrogen-doped carbon nanotubes as potential magnetic separable catalyst for dinitrotoluene hydrogenation.

The 2,4-toluenediamine (TDA) is one of the most important chemicals in the polyurethane industry, produced by the catalytic hydrogenation of 2,4-dinitrotoluene (DNT). The development of novel catalysts that can be easily recovered from the reaction mixture is of paramount importance. In our work, a NiFe2O4/N-BCNT supported magnetic catalyst was prepared by a modified coprecipitation method. The catalyst support alone also showed activity in the synthesis of TDA. Platinum nanoparticles were deposited on the catalyst support surface by a fast, relatively simple, and efficient sonochemical method, resulting in a readily applicable catalytically active system. The prepared catalyst exhibited high activity in hydrogenation tests, which was proved by the exceptionally high DNT conversion (100% for 120 min at 333 K) and TDA yield (99%). Furthermore, the magnetic catalyst can be easily recovered from the reaction medium by the action of an external magnetic field, which can greatly reduce catalyst loss during separation.

Enhancing neuronal reticulophagy: a strategy for combating aging and APP toxicity.

Reticulophagy, which directs the endoplasmic reticulum (ER) to the phagophore for sequestration within an autophagosome and subsequent lysosomal degradation via specific receptors, is essential for ER quality control and is implicated in various diseases. This study utilizes Drosophila to establish an in vivo model for reticulophagy. Starvation-induced reticulophagy is detected across multiple tissues in Drosophila. Whole-body upregulation or downregulation of the expression of reticulophagy receptors, atl and Rtnl1, negatively affects fly health. Notably, moderate upregulation of reticulophagy in neuronal tissues by overexpressing these receptors reduces age-related degeneration. In a Drosophila Alzheimer model expressing human APP (amyloid beta precursor protein), reticulophagy is compromised. Correcting reticulophagy by enhancing atl and Rtnl1 expression in the neurons promotes APP degradation, significantly reducing neurodegenerative symptoms. However, overexpression of mutated atl and Rtnl1, which disrupts the interaction of the corresponding proteins with Atg8, does not alleviate these symptoms, emphasizing the importance of receptor functionality. These findings support modulating reticulophagy as a therapeutic strategy for aging and neurodegenerative diseases associated with ER protein accumulation.

High-intensity interval training stimulates remyelination via the Wnt/ß-catenin pathway in cuprizone-induced demyelination mouse model.

OBJECTIVES: This study aims to investigate the role of high-intensity interval training (HIIT) in promoting myelin sheath recovery during the remyelination phase in cuprizone (CPZ)-induced demyelination mice and elucidate the mechanisms involving the Wnt/ß-catenin pathway. METHODS: After 5 weeks of a 0.2% CPZ diet to induce demyelination, a 4-week recovery phase with a normal diet was followed by HIIT intervention. Mice body weight was monitored. Morris water maze (MWM) gauged spatial cognition and memory, while the open field test (OFT) assessed anxiety levels. Luxol fast blue (LFB) staining measured demyelination, and immunofluorescence examined myelin basic protein (MBP) and platelet-derived growth factor receptor-alpha (PDGFR-α). Western blotting analyzed protein expression, including MBP, PDGFR-α, glycogen synthase kinase-3ß (GSK3ß), ß-catenin, and p-ß-catenin. Real-time PCR detected mRNA expression levels of CGT and CST. RESULTS: HIIT promoted remyelination in demyelinating mice, enhancing spatial cognition, memory, and reducing anxiety. LFB staining indicated decreased demyelination in HIIT-treated mice. Immunofluorescence demonstrated increased MBP fluorescence intensity and PDGFR-α+ cell numbers with HIIT. Western blotting revealed HIIT reduced ß-catenin levels while increasing p-ß-catenin and GSK3ß levels. Real-time PCR demonstrated that HIIT promoted the generation of new myelin sheaths. Additionally, the Wnt/ß-catenin pathway agonist, SKL2001, decreased MBP expression but increased PDGFR-α expression. DISCUSSION: HIIT promotes remyelination by inhibiting the Wnt/ß-catenin pathway and is a promising rehabilitation training for demyelinating diseases. It provides a new theoretical basis for clinical rehabilitation and care programs.

Current landscape of CD3 bispecific antibodies in hematologic malignancies.

Over the past 30 years the incorporation of monoclonal antibody (mAb) treatments into the management of hematologic malignancies has led to significant improvements in patient outcomes. The key limitation of mAb treatments is the necessity for target antigen presentation on major histocompatibility complex (MHC) and costimulatory molecules to elicit a cytotoxic immune response. With the advent of bispecific antibodies (BsAbs), these limitations can be overcome through direct stimulation of cytotoxic T cells, thus limiting tumor cell evasion. BsAbs are rapidly being incorporated into treatment regimens for hematologic malignancies, and there are now seven FDA-approved treatments in this class, six of which have been approved in the past year. In this review we describe the function, complications, and clinical trial data available for CD3 BsAbs in the treatment of lymphoma, myeloma, and leukemia.

Modulating Hydrogen Adsorption by Unconventional p-d Orbital Hybridization over Porous High-entropy Alloy Metallene for Efficient Electrosynthesis of Nylon-6 Precursor.

Renewable electricity driven electrosynthesis of cyclohexanone oxime (C6H11NO) from cyclohexanone (C6H10O) and nitrogen oxide (NOx) is a promising alternative to traditional environment-unfriendly industrial technologies for green synthesis of C6H11NO. Precisely controlling the reaction pathway of the C6H10O/NOx-involved electrochemical reductive coupling reaction is crucial for selectively producing C6H11NO, which is yet still challenging. Herein, we report a porous high-entropy alloy PdCuAgBiIn metallene (HEA-PdCuAgBiInene) to boost the electrosynthesis of C6H11NO from C6H10O and nitrite, achieving a high Faradaic efficiency (47.6%) and almost 100% yield under ambient conditions. In situ Fourier transform infrared spectroscopy and theoretical calculations demonstrate that unconventional orbital hybridization between d-block metals and p-block metals could regulate the local electronic structure of active sites and induce electron localization of electron-rich Pd sites, which tunes the active hydrogen supply and facilitates the generation and enrichment of key intermediates NH2OH* and C6H10O*, and efficiently promotes their C-N coupling to selectively produce C6H11NO.

Chitosan/PLGA-based tissue engineered nerve grafts with SKP-SC-EVs enhance sciatic nerve regeneration in dogs through miR-30b-5p-mediated regulation of axon growth.

Extracellular vesicles from skin-derived precursor Schwann cells (SKP-SC-EVs) promote neurite outgrowth in culture and enhance peripheral nerve regeneration in rats. This study aimed at expanding the application of SKP-SC-EVs in nerve grafting by creating a chitosan/PLGA-based, SKP-SC-EVs-containing tissue engineered nerve graft (TENG) to bridge a 40-mm long sciatic nerve defect in dogs. SKP-SC-EVs contained in TENGs significantly accelerated the recovery of hind limb motor and electrophysiological functions, supported the outgrowth and myelination of regenerated axons, and alleviated the denervation-induced atrophy of target muscles in dogs. To clarify the underlying molecular mechanism, we observed that SKP-SC-EVs were rich in a variety of miRNAs linked to the axon growth of neurons, and miR-30b-5p was the most important among others. We further noted that miR-30b-5p contained within SKP-SC-EVs exerted nerve regeneration-promoting effects by targeting the Sin3a/HDAC complex and activating the phosphorylation of ERK, STAT3 or CREB. Our findings suggested that SKP-SC-EVs-incorporating TENGs represent a novel type of bioactive material with potential application for peripheral nerve repair in the clinic.

Electron-induced ligand loss from iron tetracarbonyl methyl acrylate.

We probe the separation of ligands from iron tetracarbonyl methyl acrylate (Fe(CO)4(C4H6O2) or Fe(CO)4MA) induced by the interaction with free electrons. The motivation comes from the possible use of this molecule as a nanofabrication precursor and from the corresponding need to understand its elementary reactions fundamental to the electron-induced deposition. We utilize two complementary electron collision setups and support the interpretation of data by quantum chemical calculations. This way, both the dissociative ionization and dissociative electron attachment fragmentation channels are characterized. Considerable differences in the degree of precursor fragmentation in these two channels are observed. Interesting differences also appear when this precursor is compared to structurally similar iron pentacarbonyl. The present findings shed light on the recent electron-induced chemistry of Fe(CO)4MA on a surface under ultrahigh vacuum.

Synthesis of Hybrid Tin-Based Perovskite Microcrystals for LED Applications.

Considerable focus on tin-based perovskites lies on substitution to leadhalide perovskites for the fabrication of eco-friendly optoelectronic devices.The major concern related to tin-based perovskite devices are mainly thestability and the efficiency. However, thinking on the final commercializationscope, other considerations such as precursor stability and cost are majorfactors to carry about. In this regard, this work presents a robust and facilesynthesis of 2D A2SnX4 (A = 4-fluorophenethylammonium(4-FPEA); X = I, Br, I/Br) and 3D FASnI3 perovskite microcrystals followinga developed synthesis strategy with low-cost starting materials. In thisdeveloped methodology, acetic acid is used as a solvent, which helps to protectfrom water by making a hydrophobic network over the perovskite surface, andhence provides sufficient ambient and long-term inert atmosphere stability ofthe microcrystals. Further, the microcrystals are recrystallized in thin filmsfor LED application, allowing the fabrication of orange, near-infrared and purered emitting LEDs. The two-step recrystallized devices show better performanceand stability in comparison to the reference devices made by using commercialprecursors. Importantly, the developed synthesis methodology is defined as ageneric method for the preparation of varieties of hybrid tin-based perovskitesmicrocrystals and application in optoelectronic devices.

Heparosan biosynthesis in recombinant Bacillus megaterium: Influence of N-acetylglucosamine supplementation and kinetic modeling.

Heparosan, an unsulfated polysaccharide, plays a pivotal role as a primary precursor in the biosynthesis of heparin-an influential anticoagulant with diverse therapeutic applications. To enhance heparosan production, the utilization of metabolic engineering in nonpathogenic microbial strains is emerging as a secure and promising strategy. In the investigation of heparosan production by recombinant Bacillus megaterium, a kinetic modeling approach was employed to explore the impact of initial substrate concentration and the supplementation of precursor sugars. The adapted logistic model was utilized to thoroughly analyze three vital parameters: the B. megaterium growth dynamics, sucrose utilization, and heparosan formation. It was noted that at an initial sucrose concentration of 30 g L-1 (S1), it caused an inhibitory effect on both cell growth and substrate utilization. Intriguingly, the inclusion of N-acetylglucosamine (S2) resulted in a significant 1.6-fold enhancement in heparosan concentration. In addressing the complexities of the dual substrate system involving S1 and S2, a multi-substrate kinetic models, specifically the double Andrew's model was employed. This approach not only delved into the intricacies of dual substrate kinetics but also effectively described the relationships among the primary state variables. Consequently, these models not only provide a nuanced understanding of the system's behavior but also serve as a roadmap for optimizing the design and management of the heparosan production method.

Rhei Undulati Rhizoma attenuates memory decline and reduces amyloid-ß induced neuritic dystrophy in 5xFAD mouse.

BACKGROUND: Alzheimer's disease (AD) is a common type of dementia characterized by amyloid-ß (Aß) accumulation, lysosomal dysfunction, and tau hyperphosphorylation, leading to neurite dystrophy and memory loss. This study aimed to investigate whether Rhei Undulati Rhizoma (RUR), which has been reported to have anti-neuroinflammatory effect, attenuates Aß-induced memory impairment, neuritic dystrophy, and tau hyperphosphorylation, and to reveal its mode of action. METHODS: Five-month-old 5xFAD mice received RUR (50 mg/kg) orally for 2 months. The Y-maze test was used to assess working memory. After behavioral testing, brain tissue was analyzed using thioflavin S staining, western blotting, and immunofluorescence staining to investigate the mode of action of RUR. To confirm whether RUR directly reduces Aß aggregation, a thioflavin T assay and dot blot were performed after incubating Aß with RUR. RESULTS: RUR administration attenuated the Aß-induced memory impairment in 5xFAD mice. Furthermore, decreased accumulation of Aß was observed in the hippocampus of the RUR-treated 5xFAD group compare to the vehicle-treated 5xFAD group. Moreover, RUR reduced the dystrophic neurites (DNs) that accumulate impaired endolysosomal organelles around Aß. In particular, RUR treatment downregulated the expression of ß-site amyloid precursor protein cleaving enzyme 1 and the hyperphosphorylation of tau within DNs. Additionally, RUR directly suppressed the aggregation of Aß, and eliminated Aß oligomers in vitro. CONCLUSIONS: This study showed that RUR could attenuate Aß-induced pathology and directly regulate the aggregation of Aß. These results suggest that RUR could be an efficient material for AD treatment through Aß regulation.

One-pot, microwave (MW)-assisted production of furfural from almond-, oil-, and wine-derived co-products through biorefinery-based approaches.

This work outlines the first microwave (MW)-assisted protocol for the production of biofuel precursor furfural (FF) from the raw agricultural waste almond hull (AH), olive stone (OS), and the winemaking-derived grape stalk (GS), grape marc (GM) and exhausted grape marc (EGM) through a one-pot synthesis process. To enhance the overall yield, a catalytic process was firstly developed from xylose, major constituent of hemicellulose present in lignocellulosic biomass. This method afforded FF with 100 % selectivity, yielding over 85 % in isolated product when using H2SO4, as opposed to a 37 % yield with AlCl3·6H2O, at 150 °C in only 10 min. For both catalysts, the developed methodology was further validated, proving adaptable and efficient in producing the targeted FF from the aforementioned lignocellulosic raw materials. More specifically, the employment of AlCl3·6H2O resulted in the highest selectivity (up to 89 % from GM) and FF yield (42 % and 39 % molar from OS and AH, respectively), maintaining notable selectivity for the latter (61 and 48 % from AH and OS). At this regard, and considering the environmental factor of sustainability, it is important to point out the role of AlCl3·6H2O in contrast to H2SO4, thus mitigating detrimental substances. This study provides an important management of agricultural waste through sustainable practises for the development of potential bio-based chemicals, aligning with Green Chemistry and process intensification principles.

The Effect of Hematopoietic Stem Cell Transplantation on Treatment Outcome in Children with Acute Lymphoblastic Leukemia.

Purpose: Hematopoietic stem cell transplantation (HSCT) has been an important method of treatment in the advance of pediatric acute lymphoblastic leukemia (ALL). The indications for HSCT are evolving and require updated establishment. In this study, we aimed to investigate the efficacy of HSCT on the treatment outcome of pediatric ALL, considering the indications for HSCT and subgroups. Materials and Methods: A retrospective analysis was conducted on ALL patients diagnosed and treated at a single center. Risk groups were categorized based on age at diagnosis, initial white blood cell count, disease lineage (B/T), and cytogenetic study results. Data on the patients' disease status at HSCT and indications of HSCT were collected. Indications for HSCT were categorized as upfront HSCT at 1st complete remission, relapse, and refractory disease. Results: Among the 549 screened patients, a total of 418 patients were included in the study; B-ALL (n=379) and T-ALL (n=39). HSCT was conducted on a total of 106 patients (25.4%), with a higher frequency as upfront HSCT in higher risk groups and specific cytogenetics. The overall survival (OS) was significantly better when done upfront than in relapsed or refractory state in T-ALL patients (p=0.0016). The KMT2A-rearranged ALL patients showed superior event-free survival (p=0.0023) and OS (p=0.0221) when HSCT was done as upfront treatment. Conclusion: HSCT had a substantial positive effect in a specific subset of pediatric ALL. In particular, frontline HSCT for T-ALL and KMT2A-rearranged ALL offered a better prognosis than when HSCT was conducted in a relapsed or refractory setting.

Myeloid ectopic viral integration site 2 accelerates the progression of Alzheimer's disease.

Amyloid plaques, a major pathological hallmark of Alzheimer's disease (AD), are caused by an imbalance between the amyloidogenic and non-amyloidogenic pathways of amyloid precursor protein (APP). BACE1 cleavage of APP is the rate-limiting step for amyloid-ß production and plaque formation in AD. Although the alteration of BACE1 expression in AD has been investigated, the underlying mechanisms remain unknown. In this study, we determined MEIS2 was notably elevated in AD models and AD patients. Alterations in the expression of MEIS2 can modulate the levels of BACE1. MEIS2 downregulation improved the learning and memory retention of AD mice and decreased the number of amyloid plaques. MEIS2 binds to the BACE1 promoter, positively regulates BACE1 expression, and accelerates APP amyloid degradation in vitro. Therefore, our findings suggest that MEIS2 might be a critical transcription factor in AD, since it regulates BACE1 expression and accelerates BACE1-mediated APP amyloidogenic cleavage. MEIS2 is a promising early intervention target for AD treatment.

Eta-secretase-like processing of the amyloid precursor protein (APP) by the rhomboid protease RHBDL4.

The amyloid precursor protein (APP) is a key protein in Alzheimer's disease synthesized in the endoplasmic reticulum (ER) and translocated to the plasma membrane where it undergoes proteolytic cleavages by several proteases. Conversely to other known proteases, we previously elucidated rhomboid protease RHBDL4 as a novel APP processing enzyme where several cleavages likely occur already in the ER. Interestingly, the pattern of RHBDL4-derived large APP C-terminal fragments resemble those generated by the η-secretase or MT5-MMP, which was described to generate so called Aη fragments. The similarity in large APP C-terminal fragments between both proteases raised the question whether RHBDL4 may contribute to η-secretase activity and Aη-like fragments. Here, we identified two cleavage sites of RHBDL4 in APP by mass spectrometry, which, intriguingly, lie in close proximity to the MT5-MMP cleavage sites. Indeed, we observed that RHBDL4 generates Aη-like fragments in vitro without contributions of α-, ß-, or γ-secretases. Such Aη-like fragments are likely generated in the ER since RHBDL4-derived APP-C-terminal fragments do not reach the cell surface. Inherited, familial APP mutations appear to not affect this processing pathway. In RHBDL4 knockout mice, we observed increased cerebral full length APP in comparison to wild type (WT) in support of RHBDL4 being a physiologically relevant protease for APP. Furthermore, we found secreted Aη fragments in dissociated mixed cortical cultures from WT mice, however significantly less Aη fragments in RHBDL4 knockout cultures. Our data underscores that RHBDL4 contributes to η-secretease-like processing of APP and that RHBDL4 is a physiologically relevant protease for APP.

Physicochemical and Adsorption Properties of Nanoporous Activated Biocarbons from Thermochemical Treatment of Horsetail Herb.

The adsorption characteristics of novel activated biocarbons prepared from horsetail herb by physical activation (using carbon dioxide) and chemical one (using phosphoric(V) acid) in the process of simultaneous proteins immobilization in multicomponent solutions were examined. The carbon materials were characterized in terms of their porous structure, acidic-basic properties, and surface morphology. The binding mechanisms of such proteins as bovine serum albumin (BSA) and lysozyme (LSZ), differing in internal stability, were determined alone and in their blends. This was done based on the comprehensive analysis of the results of adsorption/desorption, surface, electrokinetic and stability measurements. These experiments were carried out over a wide pH range of 3-11. They included the following issues: (1) determination of the protein adsorbed/desorbed amounts on/from a surface of activated biocarbons; (2) study of the kinetics of these processes; (3) examination of the macromolecules impact on the surface charge density and zeta potential of the carbon materials; and (4) determination of the suspension stability and size of aggregates formed in the examined systems. The analysis of the obtained results indicated the differences in the binding mechanism of both proteins that is of key importance for their simultaneous immobilization on activated biocarbons surface in the soil environment.

Navigating oligodendrocyte precursor cell aging in brain health.

Oligodendrocyte precursor cells (OPCs) comprise 5-8 % of the adult glial cell population and stand out as the most proliferative cell type in the central nervous system (CNS). OPCs are responsible for generating oligodendrocytes (OLs), the myelinating cells of the CNS. However, OPC functions decline as we age, resulting in impaired differentiation and inadequate remyelination. This review explores the cellular and molecular changes associated with OPC aging, and their impact on OPC differentiation and functionality. Furthermore, it examines the impact of OPC aging within the context of multiple sclerosis and Alzheimer's disease, both neurodegenerative conditions wherein aged OPCs exacerbate disease progression by impeding remyelination. Moreover, various pharmacological interventions targeting pathways related to senescence and differentiation are discussed as potential strategies to rejuvenate aged OPCs. Enhancing our understanding of OPC aging mechanisms holds promise for developing new therapies to improve remyelination and repair in age-related neurodegenerative disorders.

Ductal Carcinoma In Situ.

In breast cancer (BC) pathogenesis models, normal cells acquire somatic mutations and there is a stepwise progression from high-risk lesions and ductal carcinoma in situ to invasive cancer. The precancer biology of mammary tissue warrants better characterization to understand how different BC subtypes emerge. Primary methods for BC prevention or risk reduction include lifestyle changes, surgery, and chemoprevention. Surgical intervention for BC prevention involves risk-reducing prophylactic mastectomy, typically performed either synchronously with the treatment of a primary tumor or as a bilateral procedure in high-risk women. Chemoprevention with endocrine therapy carries adherence-limiting toxicity.

Clinicopathologic Features and Outcomes of Acute Leukemia Harboring PICALM::MLLT10 Fusion.

The PICALM::MLLT10 fusion is a rare but recurrent cytogenetic abnormality in acute leukemia, with limited clinicopathologic and outcome data available. Herein, we analyzed 156 acute leukemia patients with PICALM::MLLT10 fusion, including 12 patients from our institutions and 144 patients from the literature. The PICALM::MLLT10 fusion preferentially manifested in pediatric and young adult patients, with a median age of 24 years. T-lymphoblastic leukemia/lymphoma (T-ALL) constituted 65% of cases, acute myeloid leukemia (AML) 27%, and acute leukemia of ambiguous lineage (ALAL) 8%. About half of T-ALL were classified as an early T-precursor (ETP)-ALL. In our institutions' cohort, mediastinum was the most common extramedullary site of involvement. Eight of 12 patients were diagnosed with T-ALL exhibiting a pro-/pre-T stage phenotype (CD4/CD8-double negative, CD7-positive), and frequent CD79a expression. NGS revealed pathogenic mutations in 5 of 6 tested cases, including NOTCH1, and genes in RAS and JAK-STAT pathways and epigenetic modifiers. Of 138 cases with follow-up, pediatric patients (<18 years) had 5-year overall survival (OS) of 71%, significantly better than adults at 33%. The 5-year OS for AML patients was 25%, notably shorter than T-ALL patients at 54%; this distinction was observed in both pediatric and adult populations. Furthermore, adult but not pediatric ETP-ALL patients demonstrated inferior survival compared to non-ETP-ALL patients. Neither karyotype complexity nor transplant status had a discernible impact on OS. In conclusion, PICALM::MLLT10 fusion is most commonly seen in T-ALL patients, particularly those with an ETP phenotype. AML and adult ETP-ALL patients had adverse prognosis. PICALM::MLTT10 fusion testing should be considered in T-ALL, AML, and ALAL patients.

RNAi-based Boolean gates in the yeast Saccharomyces cerevisiae.

Boolean gates, the fundamental components of digital circuits, have been widely investigated in synthetic biology because they permit the fabrication of biosensors and facilitate biocomputing. This study was conducted to design and construct Boolean gates in the yeast Saccharomyces cerevisiae, the main component of which was the RNA interference pathway (RNAi) that is naturally absent from the budding yeast cells. We tested different expression cassettes for the siRNA precursor (a giant hairpin sequence, a DNA fragment-flanked by one or two introns-between convergent promoters or transcribed separately in the sense and antisense directions) and placed different components under the control of the circuit inputs (i.e., the siRNA precursor or proteins such as the Dicer and the Argonaute). We found that RNAi-based logic gates are highly sensitive to promoter leakage and, for this reason, challenging to implement in vivo. Convergent-promoter architecture turned out to be the most reliable solution, even though the overall best performance was achieved with the most difficult design based on the siRNA precursor as a giant hairpin.