Maintaining moderate levels of hypochlorous acid promotes neural stem cell proliferation and differentiation in the recovery phase of stroke.

JOURNAL/nrgr/04.03/01300535-202503000-00029/figure1/v/2024-06-17T092413Z/r/image-tiff It has been shown clinically that continuous removal of ischemia/reperfusion-induced reactive oxygen species is not conducive to the recovery of late stroke. Indeed, previous studies have shown that excessive increases in hypochlorous acid after stroke can cause severe damage to brain tissue. Our previous studies have found that a small amount of hypochlorous acid still exists in the later stage of stroke, but its specific role and mechanism are currently unclear. To simulate stroke in vivo, a middle cerebral artery occlusion rat model was established, with an oxygen-glucose deprivation/reoxygenation model established in vitro to mimic stroke. We found that in the early stage (within 24 hours) of ischemic stroke, neutrophils produced a large amount of hypochlorous acid, while in the recovery phase (10 days after stroke), microglia were activated and produced a small amount of hypochlorous acid. Further, in acute stroke in rats, hypochlorous acid production was prevented using a hypochlorous acid scavenger, taurine, or myeloperoxidase inhibitor, 4-aminobenzoic acid hydrazide. Our results showed that high levels of hypochlorous acid (200 µM) induced neuronal apoptosis after oxygen/glucose deprivation/reoxygenation. However, in the recovery phase of the middle cerebral artery occlusion model, a moderate level of hypochlorous acid promoted the proliferation and differentiation of neural stem cells into neurons and astrocytes. This suggests that hypochlorous acid plays different roles at different phases of cerebral ischemia/reperfusion injury. Lower levels of hypochlorous acid (5 and 100 µM) promoted nuclear translocation of ß-catenin. By transfection of single-site mutation plasmids, we found that hypochlorous acid induced chlorination of the ß-catenin tyrosine 30 residue, which promoted nuclear translocation. Altogether, our study indicates that maintaining low levels of hypochlorous acid plays a key role in the recovery of neurological function.

Care-resistant Behavior Trajectories during Mouth Care among Nursing Home Residents with Dementia.

BACKGROUND AND OBJECTIVES: This study examined day-to-day variation in care-resistant behaviors (CRBs) exhibited by persons living with dementia during mouth health care and the potential influence of time-of-day on CRB trajectories. RESEARCH DESIGN AND METHODS: A secondary analysis was conducted on a sample of 75 nursing home-dwelling persons living with dementia who exhibited CRBs during mouth care activities. Over 21 days, CRBs were measured using the revised Resistiveness to Care Scale (RTC-r) during morning and afternoon mouth care sessions. Group-based Trajectory Modeling was used to identify trajectory patterns and assess differences between morning and afternoon CRB patterns. RESULTS: Three trajectory patterns were identified: morning CRB trajectory patterns showed 50.6% of persons living with dementia had consistently low RTC-r scores, 37.5% of persons living with dementia exhibited fluctuating, moderate RTC-r scores, and 11.9% exhibited RTC-r scores that started high and then decreased over time. Similarly, CRB trajectory patterns during afternoon mouth care showed a consistently low RTC-r score for 54.5% and a fluctuating moderate RTC-r score for 38.6% of persons living with dementia. However, the third CRB trajectory group followed a high-increasing trajectory, with RTC-r scores starting high and continuing to increase for 6.9% of persons living with dementia. DISCUSSION AND IMPLICATIONS: CRBs are dynamic and vary within days and over time; however, the time of the day is often not considered in interventions to manage CRBs. Thus, it is important to consider the timing of providing mouth care for persons living with dementia. Based on the characteristics of the trajectories, we suggest that morning mouth activities may be more efficient.

Large-scale purification of a deprotected macrocyclic peptide by supercritical fluid chromatography (SFC) integrated with liquid chromatography in discovery chemistry.

A macrocyclic peptide A was successfully purified in large quantities (∼30 g) in >95 % purity by an integrated two-step orthogonal purification process combining supercritical fluid chromatography (SFC) with medium-pressure reverse-phase liquid chromatography (MP-RPLC). MP-RPLC was used to fractionate the crude peptide A, remove unwanted trifluoroacetic acid (TFA) originating from the peptide A cleavage off the resin, and convert the peptide A into ammonium acetate salt form, prior to the final purification by SFC. A co-solvent of methanol/acetonitrile containing ammonium acetate and water in CO2 was developed on a Waters BEH 2-Ethylpyridine column. The developed SFC method was readily scaled up onto a 5 cm diameter column to process multi-gram quantities of the MP-RPLC fraction to reach > 95 % purity with a throughput/productivity of 0.96 g/h. The incorporation of SFC with MP-RPLC has been demonstrated to have a broader application in other large-scale polypeptide purifications.

Biodegradable Ferroelectric Molecular Plastic Crystal HOCH2(CF2)7CH2OH Structurally Inspired by Polyvinylidene Fluoride.

Ferroelectric materials, traditionally comprising inorganic ceramics and polymers, are commonly used in medical implantable devices. However, their nondegradable nature often necessitates secondary surgeries for removal. In contrast, ferroelectric molecular crystals have the advantages of easy solution processing, lightweight, and good biocompatibility, which are promising candidates for transient (short-term) implantable devices. Despite these benefits, the discovered biodegradable ferroelectric materials remain limited due to the absence of efficient design strategies. Here, inspired by the polar structure of polyvinylidene fluoride (PVDF), a ferroelectric molecular crystal 1H,1H,9H,9H-perfluoro-1,9-nonanediol (PFND), which undergoes a cubic-to-monoclinic ferroelectric plastic phase transition at 339 K, is discovered. This transition is facilitated by a 2D hydrogen bond network formed through O-H···O interactions among the oriented PFND molecules, which is crucial for the manifestation of ferroelectric properties. In this sense, by reducing the number of -CF2- groups from ≈5 000 in PVDF to seven in PFND, it is demonstrated that this ferroelectric compound only needs simple solution processing while maintaining excellent biosafety, biocompatibility, and biodegradability. This work illuminates the path toward the development of new biodegradable ferroelectric molecular crystals, offering promising avenues for biomedical applications.

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.

Composing recurrent spiking neural networks using locally-recurrent motifs and risk-mitigating architectural optimization.

In neural circuits, recurrent connectivity plays a crucial role in network function and stability. However, existing recurrent spiking neural networks (RSNNs) are often constructed by random connections without optimization. While RSNNs can produce rich dynamics that are critical for memory formation and learning, systemic architectural optimization of RSNNs is still an open challenge. We aim to enable systematic design of large RSNNs via a new scalable RSNN architecture and automated architectural optimization. We compose RSNNs based on a layer architecture called Sparsely-Connected Recurrent Motif Layer (SC-ML) that consists of multiple small recurrent motifs wired together by sparse lateral connections. The small size of the motifs and sparse inter-motif connectivity leads to an RSNN architecture scalable to large network sizes. We further propose a method called Hybrid Risk-Mitigating Architectural Search (HRMAS) to systematically optimize the topology of the proposed recurrent motifs and SC-ML layer architecture. HRMAS is an alternating two-step optimization process by which we mitigate the risk of network instability and performance degradation caused by architectural change by introducing a novel biologically-inspired "self-repairing" mechanism through intrinsic plasticity. The intrinsic plasticity is introduced to the second step of each HRMAS iteration and acts as unsupervised fast self-adaptation to structural and synaptic weight modifications introduced by the first step during the RSNN architectural "evolution." We demonstrate that the proposed automatic architecture optimization leads to significant performance gains over existing manually designed RSNNs: we achieve 96.44% on TI46-Alpha, 94.66% on N-TIDIGITS, 90.28% on DVS-Gesture, and 98.72% on N-MNIST. To the best of the authors' knowledge, this is the first work to perform systematic architecture optimization on RSNNs.

Mediastinal hematoma after trans-radial cerebral angiography: a case report.

BACKGROUND: Trans-radial (TRA) access has become increasingly prevalent in neurointervention. Nonetheless, mediastinal hematoma after TRA is an infrequent yet grave complication associated with a notably elevated mortality rate. While our review found no reported mediastinal hematoma cases managed conservatively within neuro-interventional literature, similar complications are documented in cardiac and vascular interventional radiology, indicating its potential occurrence across disciplines. CASE PRESENTATION: Carotid computed tomography angiography (CTA) showed calcified plaques with stenosis (Left: Severe, Right: Moderate) in the bilateral internal carotid arteries (ICAs) of an 81-year-old male presented with paroxysmal weakness in the right upper limb. Dual antiplatelet therapy with aspirin and clopidogrel was administered. On day 7, DSA of the bilateral ICAs was performed via TRA. Post-DSA, the patient experienced transient loss of consciousness, chest tightness, and other symptoms without ECG or MRI abnormalities. Hemoglobin level decreased from 110 g/L to 92 g/L. Iodinated contrast-induced laryngeal edema was suspected, and the patient was treated with intravenous methylprednisolone. Neck CT indicated a possible mediastinal hemorrhage, which chest CTA confirmed. The patient's treatment plan involved discontinuing antiplatelet medication as a precautionary measure against the potential occurrence of an ischemic stroke instead of the utilization of a covered stent graft and surgical intervention. Serial CTs revealed hematoma absorption. Discharge CT showed a reduced hematoma volume of 35 × 45 mm. CONCLUSIONS: This case underscores the need for timely identification and precise manipulation of guidewires and guide-catheters through trans-radial access. The critical components of successful neuro-interventional techniques include timely examination, rapid identification, proper therapy, and diligent monitoring.

Assessment of Posttransplant Bacteremia Caused by Extended-Spectrum Beta-Lactamase-Producing Gram-Negative Bacteria Among Kidney Transplant Recipients.

BACKGROUND: Extended-spectrum beta-lactamase-producing gram-negative rods (ESBL-GNR) are a rising cause of bacteremia in kidney transplant recipients (KT). The study purpose was to examine patient mortality, allograft survival, estimated glomerular filtration rate (eGFR) at the end of 1 year, and readmission rates while looking at treatment strategies among KTs with ESBL-GNR and non-ESBL-GNR bacteremia at our institution. METHODS: This study was a retrospective, cohort analysis of KTs with gram-negative bacteremia from January 1, 2020, to December 31, 2021. The primary outcome of the study was mortality. Patient outcomes were assessed for 365 days after positive blood cultures. RESULTS: The study included 63 patients. Of these, 18 (29%) patients had bacteremia caused by an ESBL-GNR and 45 (71%) patients had bacteremia caused by a non-ESBL-GNR. Patient survival at 90 days was 94% in the ESBL-GNR group and 96% in the non-ESBL-GNR group. Ciprofloxacin was the most common antimicrobial therapy at discharge (68.9%) in the non-ESBL-GNR group whereas ertapenem was the most common in the ESBL-GNR group (44.5%). Median eGFR at discharge was 41 mL/min/1.73 m2 in the ESBL-GNR group and 48 mL/min/1.73 m2 in the non-ESBL-GNR group. Ninety-day readmission occurred in 9 (50%) ESBL-GNR patients and 14 (32%) non-ESBL-GNR patients. None of the above comparisons are statistically significant (p > 0.05). Eleven (61%) ESBL-GNR and 2 (4%) non-ESBL-GNR patients used outpatient parenteral antimicrobial therapy (p < 0.001). CONCLUSIONS: Among KTs with ESBL-GNR bacteremia, no significant difference was detected in mortality or allograft function compared to non-ESBL-GNR bacteremia.

Mutation of mpv17 results in loss of iridophores due to mitochondrial dysfunction in tilapia.

Mpv17 (mitochondrial inner membrane protein MPV17) deficiency causes severe mitochondrial DNA depletion syndrome in mammals and loss of pigmentation of iridophores and a significant decrease of melanophores in zebrafish. The reasons for this are still unclear. In this study, we established an mpv17 homozygous mutant line in Nile tilapia. The developing mutants are transparent due to loss of iridophores and aggregation of pigment granules in the melanophores and disappearance of the vertical pigment bars on the side of the fish. Transcriptome analysis using skin of fish at 30 dpf (days post fertilization) revealed that the genes related to purine (especially pnp4a) and melanin synthesis were significantly downregulated. However, administration of guanine diets failed to rescue the phenotype of the mutants. In addition, no obvious apoptosis signals were observed in the iris of the mutants by TUNEL staining. Significant downregulation of genes related to iridophore differentiation was detected by qPCR. Insufficient ATP, as revealed by ATP assay, α-MSH treatment and adcy5 mutational analysis, might account for the defects of melanophores in mpv17 mutants. Several tissues displayed less mtDNA and decreased ATP levels. Taken together, these results indicated that mutation of mpv17 led to mitochondrial dTMP deficiency, followed by impaired mtDNA content and mitochondrial function, which in turn, led to loss of iridophores and a transparent body color in tilapia.

Mass spectrometry detection of organophosphorus pesticide adducts on butyrylcholinesterase and albumin.

This study established a method to prepare and detect OPs adducts on butyrylcholinesterase (BChE) and human serum albumin (HSA). OPs (methyl paraoxon, ethyl paraoxon, methyl parathion, parathion) were incubated with BChE or HSA in vitro, and the adducts of OPs-BChE or OPs-HSA were prepared and qualitatively analyzed by ultra-performance liquid chromatography data-dependent high-resolution tandem mass spectrometry (UPLC-ddHRMS/MS). The amounts of BChE and HSA in the incubating systems were varied and the resulting amounts of the adducts were determined using linear regression. OPs-BChE in the blood were isolated by immunomagnetic separation (IMS), and then digested into the OPs-nonapeptide adduct by pepsin. The proteins in the remaining blood plasma were precipitated and digested by pronase to OPs-tyrosines(OPs-Tyr), which were quantified by UPLC-ddHRMS/MS. 4 OPs-nonapeptides and 4 OPs-Tyr adducts were obtained through the process above. The relative mass deviation of incubated adducts between the actual and theoretical exact masses was less than 10 ppm, and further confirmed by fragmentation mass spectra analysis. Calibration curves were linear for all adducts with a coefficient of determination value (R2) ≥0.995. The limits of detection (LOD) and limits of quantification (LOQ) for adducts detected by MS ranged from 0.05 to 1.0 ng/mL, and from 0.1 to 2.0 ng/mL, respectively. The recovery percentages for adducts ranged from 76.1 % to 107.1 %, matrix effects ranged from 83.4 % to 102.1 %. The inter-day and intra-day precision were 6.1-10.1 % and 6.9-12.9 % for adducts. This study provides a new reference method for the detection of organophosphorus pesticide poisoning. In addition, two blood samples with organophosphorus poisoning were tested by the designed method, and the corresponding adducts were detected in both samples.

Role of acupuncture in improving the outcome of sepsis-induced lung injury.

OBJECTIVE: The purpose of this study was to investigate the effect of serum exosomes of mice after acupuncture (acu-exo) on acute lung injury (ALI) in sepsis in vitro and in vivo. METHODS: Serum exosomes (acu-exo) of normal mice were prepared after acupuncture. Lipopolysaccharide (LPS) was used to establish the model of ALI in vivo and in vitro. Immunohistochemistry, western blot, and immunofluorescence were used to evaluate the mechanism of acu-exo on ALI. P2X7 knockout mice and P2X7 siRNA were used to verify the mechanism. RESULTS: Compared with normal mice, serum exosomes were significantly increased in normal mice after acupuncture. The results showed that P2X7 was increased in the lung of septic mice as compared with the WT group. It was also found that the increase in NLRP3 and NF-κB was accompanied by the activation of P2X7. Increased P2X7 led to activation of the P2X7 receptor causing mitochondrial dysfunctions in lung tissue of septic mice. Knockout of P2X7 or silenced P2X7 markedly decreased NLRP3 and NF-κB and led to mitochondrial function recovery in lung tissue of sepsis. At the same time, acu-exo significantly restored the above changes in the lung tissue of septic mice. CONCLUSIONS: Inhibition of P2X7 led to mitochondrial function recovery of lung tissue by inhibiting NLRP3 and NF-κB. At the same time, acu-exo could improve ALI by decreasing NLRP3 and NF-κB activation.

Iridium single-atoms anchored on a TiO2 support as an efficient catalyst for the hydrogen evolution reaction.

Single-atom catalysts (SACs) play a vital role in the hydrogen evolution reaction (HER) owing to the highly desirable atom efficiency and the minimal amount of precious metals. Herein, we use TiO2 nanosheets to anchor stable atomically dispersed iridium (Ir) to be used as a catalyst (Ir@TiO2) for the HER. The atomic dispersion of Ir on the TiO2 substrate is confirmed by aberration-corrected scanning transmission electron microscopy and it is anchored by numerous surface functional groups on abundantly exposed basal planes in TiO2. In acidic media, the Ir@TiO2 catalyst (1.35 wt% Ir) shows a low overpotential (41 mV at 10 mA cm-2), a small Tafel slope of 42 mV dec-1, and a decent durability for 1000 cycles of the HER with the polarization curve having only a 1 mV shift, which are comparable with those of a commercial Pt/C catalyst with 20 wt% Pt. This work paves a way to design Ir atomically anchored catalysts with low cost and high activity.

Development and validation of nomogram for predicting the risk of transferring to the ICU for children with influenza.

OBJECTIVE: Development of a nomogram model for predicting the magnitude of risk of transferring hospitalized children with influenza to the ICU. METHODS: In a single-center retrospective study, 318 children with influenza who were hospitalized in our hospital from January 2018 to August 2023 were collected as study subjects. Children with influenza were randomly assigned to the training set and validation set in a ratio of 4:1. In the training set, risk factors were identified using univariate and multivariate logistic regression analyses, and a nomogram model was created on this basis. The validation set was used to evaluate the predictive power of the model. RESULTS: Multifactorial logistic regression analysis revealed six independent risk factors for transfer to the ICU in hospitalized children with influenza, including elevated peripheral white blood cell counts, elevated large platelet ratios, reduced mean platelet width, reduced complement C3, elevated serum globulin levels, and reduced total immunoglobulin M levels. Using these six metrics as predictors to construct a nomogram graphical model, the C-index was 0.970 (95% Cl: 0.953-0.988). The areas under the curve for the training and validation sets were 0.966 (95%Cl 0.947-0.985) and 0.919 (95%Cl 0.851-0.986), respectively. CONCLUSION: A nomogram for predicting the risk of transferring to the ICU for children with influenza was developed and validated, which demonstrates good calibration and clinical benefits.

Lnc PVT1 facilitates TGF-ß1-induced human cardiac fibroblast activation in vitro and ISO-induced myocardial fibrosis in vivo through regulating MYC.

Cardiac fibrosis is a commonly seen pathophysiological process in various cardiovascular disorders, such as coronary heart disorder, hypertension, and cardiomyopathy. Cardiac fibroblast trans-differentiation into myofibroblasts (MFs) is a key link in myocardial fibrosis. LncRNA PVT1 participates in fibrotic diseases in multiple organs; however, its role and mechanism in cardiac fibrosis remain largely unknown. Human cardiac fibroblasts (HCFs) were stimulated with TGF-ß1 to induce myofibroblast; Immunofluorescent staining, Immunoblotting, and fluorescence in situ hybridization were used to detect the myofibroblasts phenotypes and lnc PVT1 expression. Cell biological phenotypes induced by lnc PVT1 knockdown or overexpression were detected by CCK-8, flow cytometry, and Immunoblotting. A mouse model of myocardial fibrosis was induced using isoproterenol (ISO), and the cardiac functions were examined by echocardiography measurements, cardiac tissues by H&E, and Masson trichrome staining. In this study, TGF-ß1 induced HCF transformation into myofibroblasts, as manifested as significantly increased levels of α-SMA, vimentin, collagen I, and collagen III; the expression level of lnc PVT1 expression showed to be significantly increased by TGF-ß1 stimulation. The protein levels of TGF-ß1, TGFBR1, and TGFBR2 were also decreased by lnc PVT1 knockdown. Under TGF-ß1 stimulation, lnc PVT1 knockdown decreased FN1, α-SMA, collagen I, and collagen III protein contents, inhibited HCF cell viability and enhanced cell apoptosis, and inhibited Smad2/3 phosphorylation. Lnc PVT1 positively regulated MYC expression with or without TGF-ß1 stimulation; MYC overexpression in TGF-ß1-stimulated HCFs significantly attenuated the effects of lnc PVT1 knockdown on HCF proliferation and trans-differentiation to MFs. In the ISO-induced myocardial fibrosis model, lnc PVT1 knockdown partially reduced fibrotic area, improved cardiac functions, and decreased the levels of fibrotic markers. In addition, lnc PVT1 knockdown decreased MYC and CDK4 levels but increased E-cadherin in mice heart tissues. lnc PVT1 is up-regulated in cardiac fibrosis and TGF-ß1-stimulated HCFs. Lnc PVT1 knockdown partially ameliorates TGF-ß1-induced HCF activation and trans-differentiation into MFs in vitro and ISO-induced myocardial fibrosis in vivo, potentially through interacting with MYC and up-regulating MYC.

High body mass index is associated with elevated risk of perioperative ischemic stroke in patients who underwent noncardiac surgery: A retrospective cohort study.

BACKGROUND: Body mass index (BMI) serves as a global metric for assessing obesity and overall health status. However, the impact of BMI, treated as a continuous variable, on the risk of perioperative stroke remains poorly understood. This retrospective cohort study aimed to elucidate the association between BMI and the risk of perioperative ischemic stroke in patients undergoing non-cardiovascular surgery. METHODS: A cohort of 223,415 patients undergoing noncardiac surgery at the First Medical Center of Chinese PLA General Hospital between January 1, 2008 and August 31, 2019 was screened. Preoperative high BMI, defined as BMI >22.64 kg/m2, was the primary exposure, and the outcome of interest was the new diagnosis of perioperative ischemic stroke within 30 days post-surgery. Robust controls for patient and intraoperative factors were implemented to minimize residual confounding. Logistic regression and propensity score matching were employed, and patients were stratified into subgroups for further investigation. RESULTS: The overall incidence of perioperative ischemic stroke was 0.23% (n = 525) in the cohort. After adjusting for patient-related variables (OR 1.283; 95% CI, 1.04-1.594; p < 0.05), surgery-related variables (OR 1.484; 95% CI, 1.2-1.849; p < 0.001), and all confounding variables (OR 1.279; 95% CI, 1.025-1.607; p < 0.05), patients with BMI >22.64 kg/m2 exhibited a significantly increased risk of perioperative ischemic stroke. This association persisted in the propensity score matched cohort (OR 1.577; 95% CI, 1.203-2.073; p < 0.01). Subgroup analyses indicated that preoperative BMI >22.64 kg/m2 correlated with an elevated risk of perioperative ischemic stroke in female patients, those with coronary heart disease, peripheral vascular diseases, and individuals undergoing neurosurgery. CONCLUSION: We first identified BMI >22.64 kg/m2 as a substantial and independent risk factor for perioperative ischemic stroke in Chinese noncardiac surgery patients. Normal BMI may not suffice as a universal preventive standard. Instead, a more stringent perioperative weight management approach is recommended, particularly for specific subgroups such as female patients, those with coronary heart disease and peripheral vascular disease, and individuals scheduled for neurosurgery.

RHOF activation of AKT/ß-catenin signaling pathway drives acute myeloid leukemia progression and chemotherapy resistance.

Acute myeloid leukemia (AML) is a clonal malignancy originating from leukemia stem cells, characterized by a poor prognosis, underscoring the necessity for novel therapeutic targets and treatment methodologies. This study focuses on Ras homolog family member F, filopodia associated (RHOF), a Rho guanosine triphosphatase (GTPase) family member. We found that RHOF is overexpressed in AML, correlating with an adverse prognosis. Our gain- and loss-of-function experiments revealed that RHOF overexpression enhances proliferation and impedes apoptosis in AML cells in vitro. Conversely, genetic suppression of RHOF markedly reduced the leukemia burden in a human AML xenograft mouse model. Furthermore, we investigated the synergistic effect of RHOF downregulation and chemotherapy, demonstrating significant therapeutic efficacy in vivo. Mechanistically, RHOF activates the AKT/ß-catenin signaling pathway, thereby accelerating the progression of AML. Our findings elucidate the pivotal role of RHOF in AML pathogenesis and propose RHOF inhibition as a promising therapeutic approach for AML management.

Ti4+ Ions-Doped Metal-Organic Framework (MOF-74) for Photoreduction of Carbon Dioxide.

The development of efficient and sustainable methods for reducing carbon dioxide (CO2) and converting it into valuable hydrocarbons has gained significant attention. In this study, researchers focused on Ti4+-doped metal-organic framework (MOF-74) photocatalysts. The incorporation of Ti4+ ions into the MOF-74 structure was achieved through a one-pot hydrothermal method. By replacing Zn2+ ions with Ti4+ ions in a substitutional manner, researchers have aimed to enhance the photocatalytic activity of the CO2 reduction. The obtained Ti4+-doped MOF-74 photocatalysts exhibited a significantly improved performance in the reduction of CO2 into carbon monoxide (CO). The doping of Ti4+ ions induced energy bands below the conduction band minimum (CBM) of MOF-74, extending the visible response range and enabling the photocatalysts to utilize a broader spectrum of light for catalytic reactions. This extension of the visible response range enables photocatalysts to utilize a broader spectrum of light for catalytic reactions. The incorporation of Ti4+ ions not only extends the visible response range but also suppresses charge carrier recombination. This work provides valuable insights into the design principles of MOF-based photocatalysts and paves the way for their practical implementation in addressing the energy crisis and reducing greenhouse gas emissions.