Exploring the therapeutic implications of natural compounds modulating apoptosis in vascular dementia.

Vascular dementia (VaD) is a prevalent form of dementia stemming from cerebrovascular disease, manifesting in memory impairment and executive dysfunction, thereby imposing a substantial societal burden. Unfortunately, no drugs have been approved for the treatment of VaD due to its intricate pathogenesis, and the development of innovative and efficacious medications is urgently needed. Apoptosis, a programmed cell death process crucial for eliminating damaged or unwanted cells within an organism, assumes pivotal roles in embryonic development and tissue homeostasis maintenance. An increasing body of evidence indicates that apoptosis may significantly influence the onset and progression of VaD, and numerous natural compounds have demonstrated significant therapeutic potential. Here, we discuss the molecular mechanisms underlying apoptosis and its correlation with VaD. We also provide a crucial reference for developing innovative pharmaceuticals by systematically reviewing the latest research progress concerning the neuroprotective effects of natural compounds on VaD by regulating apoptosis. Further high-quality clinical studies are imperative to firmly ascertain these natural compounds' clinical efficacy and safety profiles in the treatment of VaD.

CAMK2G Promotes Neuronal Differentiation and Inhibits Migration in Neuroblastoma.

PURPOSE: Neuroblastoma (NB) originates from differentiation arrest of sympathoadrenal progenitors in the neural crest. It is necessary to reveal the differentiation mechanism of NB. Previously, we reported that Purkinje cell protein 4 (PCP4) is a well-differentiated marker of NB tissues. Herein, we explored the underlying mechanism of PCP4 induced differentiation in order to find better treatment options for patients. METHODS: We screened the interacting proteins of PCP4 by co-immunoprecipitation (Co-IP) and liquid chromatography-mass spectrometry (LC-MS/MS). Then we investigated the relevance between expression of calmodulin-dependent protein kinase II gamma (CAMK2G) and clinical features using R2 platform. We also explored the function of CAMK2G in NB cells by knockdown and RNA sequencing. RESULTS: Here, we verified the binding of PCP4 and calmodulin (CaM) by Co-IP and identified a target kinase of CaM, CAMK2G, by LC-MS/MS. PCP4 overexpression activates the autophosphorylation of CAMK2G. Patients with high CAMK2G expression had better survival while low CAMK2G was associated with unfavorable clinical features including MYCN-amplification, unfavorable histology, progression and high INSS stage. CAMK2G knockdown inhibited neurite outgrowth and down-regulated neuronal differentiation markers (NF-H, MAP2), yet promoted migration, invasion and proliferation. Gene Ontology (GO) analysis showed that knockdown of CAMK2G downregulated the expression of neuronal differentiation-related genes. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed that knockdown of CAMK2G upregulated the expression of migration-related genes. CONCLUSION: These findings indicate that CAMK2G activated by PCP4/CaM complex promotes differentiation and inhibits migration in NB cells. LEVEL OF EVIDENCE: Not applicable.

Research progress on anti-tumor mechanism of TAOK kinases.

Thousand and one amino-acid protein kinases(TAOKs), as a key member of the mitogen-activated protein kinase (MAPK) cascade, has recently attracted widespread attention in the field of anti-cancer research. There are three members of this subfamily: TAOK1, TAOK2, and TAOK3. Studies have shown that members of the TAOK family participate in regulating cell proliferation, apoptosis, migration, and invasion through various pathways, thereby playing an important role in tumorigenesis and progression. This review summarizes the functions of TAOK kinases in tumor cell signal transduction, cell cycle regulation, and the tumor microenvironment, with a particular emphasis on its potential as a target for anti-cancer drugs. Future research will further elucidate the specific mechanisms of action of TAOK kinase in different types of tumors and explore its clinical application prospects.

Ccrk-Mak/Ick signaling is a ciliary transport regulator essential for retinal photoreceptor survival.

Primary cilia are microtubule-based sensory organelles whose dysfunction causes ciliopathies in humans. The formation, function, and maintenance of primary cilia depend crucially on intraflagellar transport (IFT); however, the regulatory mechanisms of IFT at ciliary tips are poorly understood. Here, we identified that the ciliopathy kinase Mak is a ciliary tip-localized IFT regulator that cooperatively acts with the ciliopathy kinase Ick, an IFT regulator. Simultaneous disruption of Mak and Ick resulted in loss of photoreceptor ciliary axonemes and severe retinal degeneration. Gene delivery of Ick and pharmacological inhibition of FGF receptors, Ick negative regulators, ameliorated retinal degeneration in Mak -/- mice. We also identified that Ccrk kinase is an upstream activator of Mak and Ick in retinal photoreceptor cells. Furthermore, the overexpression of Mak, Ick, and Ccrk and pharmacological inhibition of FGF receptors suppressed ciliopathy-related phenotypes caused by cytoplasmic dynein inhibition in cultured cells. Collectively, our results show that the Ccrk-Mak/Ick axis is an IFT regulator essential for retinal photoreceptor maintenance and present activation of Ick as a potential therapeutic approach for retinitis pigmentosa caused by MAK mutations.

Imaging Spin-Orbit Excitation of Yttrium through High-Energy Collisions with Rare Gas Atoms.

The energy required for spin-orbit excitation plays a critical role in understanding translational-to-electronic energy conversion, particularly in chemical reactions involving changes in spin states. This is particularly important for transition metal atoms possessing d-orbitals, which result in multiple spin-orbit split energy levels at low energies. The accurate identification and characterization of spin-orbit transitions in such species require advanced experimental techniques and theoretical support. In this study, the spin-orbit excited collisions of Y(2D3/2) with rare gas atoms Ne, Ar, and Kr leading to Y(2D5/2) were observed using laser-ablated crossed-beam and time-sliced ion velocity mapping imaging techniques. Through a comparison of the forward angular distributions of Y(2D3/2) to the backward and sideway scattering distributions of Y(2D5/2) from elastic and inelastic collisions of Y(2D) with rare gas atoms, this study reveals that the spin-orbit electronic excitation occurs with high collision energy and low impact parameters from backward and sideway collisions. The effectiveness of the spin-orbit excitation process is strongly dependent on the collision energy or temperature, suggesting that energy requirements of the process have to be considered in chemical reactions involving changes in spin states.

Inhibition of cortical synaptic transmission, behavioral nociceptive, and anxiodepressive-like responses by arecoline in adult mice.

Areca nut, the seed of Areca catechu L., is one of the most widely consumed addictive substances in the world after nicotine, ethanol, and caffeine. The major effective constituent of A. catechu, arecoline, has been reported to affect the central nervous system. Less is known if it may affect pain and its related emotional responses. In this study, we found that oral application of arecoline alleviated the inflammatory pain and its induced anxiolytic and anti-depressive-like behavior. Arecoline also increased the mechanical nociceptive threshold and alleviated depression-like behavior in naïve mice. In the anterior cingulate cortex (ACC), which acts as a hinge of nociception and its related anxiety and depression, by using the multi-electrode field potential recording and whole-cell patch-clamp recording, we found that the evoked postsynaptic transmission in the ACC of adult mice has been inhibited by the application of arecoline. The muscarinic receptor is the major receptor of the arecoline in the ACC. Our results suggest that arecoline alleviates pain, anxiety, and depression-like behavior in both physiological and pathological conditions, and this new mechanism may help to treat patients with chronic pain and its related anxiety and disorder in the future.

NiO/RuO2 p-n Heterojunction Nanofoam as a High-Performance Electrocatalyst for Desulfurization and Concurrent Hydrogen Evolution.

The development of bifunctional electrocatalysts with excellent performance in both the hydrogen evolution reaction (HER) and sulfide oxidation reaction (SOR) remains a formidable challenge. Herein, we experimentally synthesize a NiO/RuO2 p-n heterojunction nanofoam that exhibits highly desirable electrocatalytic properties for both the HER and the SOR. We further design an electrolytic cell by pairing alkaline HER with SOR utilizing the NiO/RuO2 heterojunction nanofoam as both the anode and the cathode, which demands a low applied voltage of 0.846 V to achieve a current density of 10 mA cm-2. Density functional theory calculations confirm that the formation of the NiO/RuO2 p-n heterojunction nanofoam effectively regulates the electronic structure, thereby boosting the electrocatalytic performances for both HER and SOR. This work not only provides a novel strategy to prepare an efficient and stable nanofoam electrocatalyst for hydrogen production but also highlights the potential application of oxide heterojunction electrocatalysts in treating sulfur-containing waste liquid.

Dose-Response Study of Norepinephrine Infusion for Maternal Hypotension in Preeclamptic Patients Undergoing Cesarean Delivery Under Spinal Anesthesia.

BACKGROUND AND OBJECTIVE: Spinal anesthesia remains the preferred mode of anesthesia for preeclamptic patients during cesarean delivery. We investigated the incidence of maternal hypotension under spinal anesthesia during cesarean delivery, by comparing different prophylactic infusion rates of norepinephrine with normal saline. METHODS: We randomly allocated 180 preeclamptic patients (45 in each groups) aged 18-45 scheduled for cesarean delivery to receive one of four prophylactic norepinephrine infusions at doses of 0 (normal saline group), 0.025 (0.025 group), 0.05 (0.05 group), or 0.075 (0.075 group) µg/kg/min following spinal anesthesia. The primary endpoint was the incidence of maternal hypotension (systolic blood pressure < 80% of baseline). RESULTS: The incidence of maternal hypotension was reduced with different prophylactic infusion rates of norepinephrine (26.7%, 15.6%, and 6.7%) compared with normal saline (37.8%) with a significant decreasing trend (p = 0.002). As the infusion doses of norepinephrine increased, there is a significant decreasing trend in deviation of systolic blood pressure control (median performance error; median absolute performance error) from baseline (p < 0.001; p < 0.001) and need for rescue norepinephrine boluses (p = 0.020). The effective dose 50 and effective dose 90 of prophylactic norepinephrine infusion were - 0.018 (95% confidence interval - 0.074, 0.002) µg/kg/min and 0.065 (95% confidence interval 0.048, 0.108) µg/kg/min, respectively. CONCLUSIONS: Prophylactic infusion of norepinephrine, as compared to no preventive measures, can effectively reduce the incidence of maternal hypotension in preeclamptic patients under spinal anesthesia during cesarean delivery, without increasing other adverse events for either the mother or neonate. REGISTRATION: Clinical trials.gov identifier number NCT04556370.

Direct Observation of Enhanced Iodine Binding within a Series of Functionalized Metal-Organic Frameworks with Exceptional Irradiation Stability.

Optimization of active sites and stability under irradiation are important targets for sorbent materials that might be used for iodine (I2) storage. Herein, we report the direct observation of I2 binding in a series of Cu(II)-based isostructural metal-organic frameworks, MFM-170, MFM-172, MFM-174, NJU-Bai20, and NJU-Bai21, incorporating various functional groups (-H, -CH3, - NH2, -C≡C-, and -CONH-, respectively). MFM-170 shows a reversible uptake of 3.37 g g-1 and a high packing density of 4.41 g cm-3 for physiosorbed I2. The incorporation of -NH2 and -C≡C- moieties in MFM-174 and NJU-Bai20, respectively, enhances the binding of I2, affording uptakes of up to 3.91 g g-1. In addition, an exceptional I2 packing density of 4.83 g cm-3 is achieved in MFM-174, comparable to that of solid iodine (4.93 g cm-3). In situ crystallographic studies show the formation of a range of supramolecular and chemical interactions [I···N, I···H2N] and [I···C≡C, I-C═C-I] between -NH2, -C≡C- sites, respectively, and adsorbed I2 molecules. These observations have been confirmed via a combination of solid-state nuclear magnetic resonance, X-ray photoelectron, and Raman spectroscopies. Importantly, γ-irradiation confirmed the ultraresistance of MFM-170, MFM-174, and NJU-Bai20 suggesting their potential as efficient sorbents for cleanup of radioactive waste.

Recruitment of cortical silent responses by forskolin in the anterior cingulate cortex of adult mice.

Recent studies using different experimental approaches demonstrate that silent synapses may exist in the adult cortex including the sensory cortex and anterior cingulate cortex (ACC). The postsynaptic form of long-term potentiation (LTP) in the ACC recruits some of these silent synapses and the activity of calcium-stimulated adenylyl cyclases (ACs) is required for such recruitment. It is unknown if the chemical activation of ACs may recruit silent synapses. In this study, we found that activation of ACs contributed to synaptic potentiation in the ACC of adult mice. Forskolin, a selective activator of ACs, recruited silent responses in the ACC of adult mice. The recruitment was long-lasting. Interestingly, the effect of forskolin was not universal, some silent synapses did not undergo potentiation or recruitment. These findings suggest that these adult cortical synapses are not homogenous. The application of a selective calcium-permeable AMPA receptor inhibitor 1-naphthyl acetyl spermine (NASPM) reversed the potentiation and the recruitment of silent responses, indicating that the AMPA receptor is required. Our results strongly suggest that the AC-dependent postsynaptic AMPA receptor contributes to the recruitment of silent responses at cortical LTP.

The Pathway-Selective Dependence of Nitric Oxide for Long-Term Potentiation in the Anterior Cingulate Cortex of Adult Mice.

Nitric oxide (NO) is a key diffusible messenger in the mammalian brain. It has been proposed that NO may diffuse in retrograde into presynaptic terminals, contributing to the induction of hippocampal long-term potentiation (LTP). Here, we present novel evidence that NO is selectively required for the synaptic potentiation of the interhemispheric projection in the anterior cingulate cortex (ACC). Unilateral low-frequency stimulation (LFS) induced a short-term synaptic potentiation on the contralateral ACC through the corpus callosum (CC). The use of the antagonists of the NMDA receptor (NMDAR), or the inhibitor of the L-type voltage-dependent Ca2+ channels (L-VDCCs), blocked the induction of this ACC-ACC potentiation. In addition, the inhibitor of NO synthase, or inhibitors for its downstream signaling pathway, also blocked this ACC-ACC potentiation. However, the application of the NOS inhibitor blocked neither the local electric stimulation-induced LTP nor the stimulation-induced recruitment of silent responses. Our results present strong evidence for the pathway-selective roles of NO in the LTP of the ACC.

Study on Nutrient Carrier of Mulch Based on Hydrogel @SiO2.

Soil conservation is one of the best methods to improve soil fertility and enhance crop growth efficiency. Replacing plastic mulch with biomass is an environmentally friendly strategy. Innovative encapsulated soil granules (ESGs) were developed using PVA/PC film as the wall material and rural soil as the core. The PVA/PC was synthesized using 60% protein polypeptide (PC) from leather waste scrap and 35% poly (vinyl alcohol) (PVA), which was optimized for water absorption expansion and water retention performance. The ESG-10 granulated with 10% PVA/PC exhibited good water absorption, moisture retention, and resistance to water solubility. As an auxiliary material for soil improvement, the amount of ESGs mixed with the topsoil at ratios of 0 g/m2, 200 g/m2, and 400 g/m2 was proportional to the soil insulation and moisture retention. In rapeseed cultivation, the experimental results indicated that the soil mulched with ESG-10 can maintain seedling vitality for a long time under low water content conditions.

Patient-reported outcomes after oral cancer reconstructions with radial and ulnar forearm-free flaps.

OBJECTIVES: This study aimed to evaluate patient-reported quality of life and incidence of decision regret in patients undergoing radial (RFFF) and ulnar forearm-free flaps (UFFF) reconstruction. MATERIALS AND METHODS: Patients undergoing either RFFF or UFFF were assessed with the University of Washington Quality of Life (UW-QOL) and Oral Health Impact Profile (OHIP-14) questionnaires, and the Decision Regret Scale (DRS), both before and at least 12 months post-reconstruction. RESULTS: In total, 40 RFFF and 40 UFFF were included. Harvesting time was longer in RFFF (p = 0.043), and the donor-site defect was significantly larger in RFFF than in UFFF (p = 0.044). Patients with UFFF scored better UW-QOL in the appearance, pain, activity, mood, and social functioning domains (p < 0.05). However, the RFFF group excelled in swallowing and chewing domains. The DRS score revealed a significant difference between RFFF and UFFF, with scores of 36.26 versus 27.36, respectively. Moreover, the mean DRS score reduced at 12 months compared with 6 months, significantly superior for UFFF. CONCLUSION: Oral cancer patients reconstructed with UFFF exhibited a better appearance, social domain, and mild decision regret compared with RFFF, indicating that the UFFF may contribute to improving postoperative quality of life in oral cancer patients.

High-Entropy Metal Oxide-Coated Carbon Cloth as Catalysts for Long-Life Li-S Batteries.

Lithium-sulfur (Li-S) batteries with high specific energy density, low cost, and environmental friendliness of sulfur have been regarded as a competitive alternative to replace lithium-ion batteries. However, the shuttle effect and the sluggish conversion rate of lithium polysulfides (LiPSs) have seriously limited the practical application of Li-S batteries. Herein, high-entropy oxides grown on the carbon cloth (CC/HEO) are synthesized by a simple and ultrafast solution combustion method for the sulfur cathode. The as-prepared composites possess abundant HEO active sites for strong interaction with LiPSs, which can significantly promote redox kinetics. Besides, the carbon fiber substrate not only ensures high electrical conductivity but also accommodates large volume change, leading to a stable sulfur electrochemistry. Benefiting from the rational design, the Li-S batteries with CC/HEO as cathode skeleton exhibits good cyclability with a capacity decay rate of 0.057% per cycle after 1000 cycles at 2 C. More importantly, the Li-S batteries with 4.3 mg cm-2 high sulfur loading can still retain a high capacity retention of 78.2% after 100 cycles.

High adsorption of ammonia in a titanium-based metal-organic framework.

We report the high adsorption of NH3 in a titanium-based metal-organic framework, MFM-300(Ti), comprising extended [TiO6]∞ chains linked by biphenyl-3,3',5,5'-tetracarboxylate ligands. At 273 K and 1 bar, MFM-300(Ti) shows an exceptional NH3 uptake of 23.4 mmol g-1 with a record-high packing density of 0.84 g cm-3. Dynamic breakthrough experiments confirm the excellent uptake and separation of NH3 at low concentration (1000 ppm). The combination of in situ neutron powder diffraction and spectroscopic studies reveal strong, yet reversible binding interactions of NH3 to the framework oxygen sites.

Imaging Rovibrational Excitation of Scattered YO Molecules in Inelastic Collisions with Kr and Ne.

Energy transfer between atoms and molecules is fundamental to many physical and chemical processes, and understanding the mechanisms and outcomes of energy transfer is crucial for various applications in physics and chemistry. Here, the rovibrational excitation of YO(X 2Σ+) molecules with the collision of Kr and Ne has been studied in the laser-ablation crossed beam and time-sliced ion velocity map imaging setup in combination with the resonance enhanced multiphoton ionization scheme. Significant changes in the angular distribution for different rovibrational excitations of YO molecules are observed with the collision of Kr. The sharp forward distribution for low rovibrational excitation of YO(v' = 0, 1) molecules suggest that the weak attractive potential between Kr and YO is dominant at large impact parameters. Comparatively, the strong sideway distribution for highly rovibrationally excited YO(v' = 1, 2, 3, and 5) is due to rainbow scattering from the stronger attractive potential of Kr···YO at relatively small impact parameters. The more isotropic angular distribution in the highly rovibrationally excited YO(v' = 11) indicates the formation of a short-lived complex. A change in the angular distribution of scattered YO with different rovibrational excitations was also observed in the collisions of Ne. For YO as a heteronuclear diatomic molecule, collisions of the Y- and the O-end of YO with rare gases would affect the contribution of inelastic processes at different impact parameters.

Study on energy evolution and fractal characteristics of sandstone with different fracture dip angles under uniaxial compression.

In order to investigate the failure modes and instability mechanism of fractured rock. Uniaxial compression tests were conducted on sandstone specimens with different dip angles. Based on rock energy dissipation theory and fractal theory, the energy evolution characteristics and fragmentation fractal characteristics in the process of deformation and failure of specimens were analyzed. The results show that the peak strength and elastic modulus of fractured rock mass are lower than those of intact samples, and both show an exponential increase with the increase of fracture dip angle. The energy evolution laws of different fracture specimens are roughly similar and can be classified into four stages based on the stress-strain curve: pressure-tight, elastic, plastic, and post-destructive. The total strain energy, elastic strain energy, and dissipated strain energy of the specimen at the peak stress point increased exponentially with crack inclination, and the dissipated strain energy and compressive strength conformed to a power function growth relationship. The distribution of the fragments after the failure of the fracture sample has fractal characteristics, and the fractal dimension increases with the increase of the fracture dip angle. In addition, the higher the compressive strength of the specimen, the greater the energy dissipation, the more serious the degree of fragmentation, and the greater the fractal dimension. The data fitting further shows that there is a power function relationship between the dissipated strain energy and the fractal dimension. The research results can provide a theoretical basis for the stability of rock mass engineering and structural deformation control.

Study on the causal relationship between educational attainment and delirium: A two-sample Mendelian randomization study.

This study aimed to investigate whether there is a causal relationship between educational attainment and delirium at the genetic level using the Mendelian randomization method, and provide new evidence for studies in this field. We found a causal relationship between educational attainment and delirium at the genetic level after excluding confounders using Mendelian randomization. The inverse variance weighting method of random effects was the main analysis method. The weighted median and Mendelian Randomization-Egger methods, as well as simple, and weighted modes were used as supplementary analysis methods. Additionally, horizontal pleiotropy tests were conducted, including the Mendelian Randomization-Egger intercept test and Mendelian Randomization Pleiotropy RESidual Sum and Outlier. Cochran's Q statistic was used to assess the size of heterogeneity. We retrieved all second single nucleotide polymorphism features and performed multivariate Mendelian randomization to adjust for the effect of potential confounders on our results. The inverse variance weighting suggested a negative correlation between genetically predicted educational attainment and delirium (0.67[0.49-0.92], p = 0.013); Mendelian Randomization Pleiotropy RESidual Sum and Outlier (0.67[0.49-0.92], p = 0.013) and multivariate Mendelian randomization (0.52[0.33-0.82], p = 0.005) results were generally consistent with the inverse variance weighting method. The Mendelian Randomization-Egger, simple, and weighted mode results were consistent with the inverse variance weighting results. Our results were not affected by pleiotropy or heterogeneity (p > 0.05, for both pleiotropy and heterogeneity). In addition, the "leave-one-out" analysis showed that the results of our Mendelian randomization analysis were not influenced by individual single nucleotide polymorphisms. Studies have found a causal relationship between educational attainment and delirium at the genetic level; higher educational attainment may be a protective factor against delirium. Clinically, more attention should be paid to patients at a high risk of delirium with low educational attainment.

Clinical characteristics and assessment of risk factors in patients with influenza A-induced severe pneumonia after the prevalence of SARS-CoV-2.

Purpose: The aim of this study is to describe the novel epidemiological and clinical characteristics of influenza A-induced severe pneumonia occurring after the prevalence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and to further assess its potential risk factors for mortality. Methods: We retrospectively studied the consecutive case series of 30 patients with confirmed influenza A-induced severe pneumonia treated in the intensive care unit at Dazhou Central Hospital in Sichuan, China, from March 1 to April 30, 2023. Logistic regression was used to analyze the independent risk factors, and receiver operating characteristic (ROC) curves were applied to evaluate the predictive efficacy of associated risk factors for mortality. Results: The mortality rate was 33.3% in this study. Independent risk factors for mortality of patients were acute respiratory distress syndrome (ARDS) (p = 0.044) and septic shock (p = 0.012). ROC statistics for ARDS and septic shock to predict mortality in patients with influenza A-induced severe pneumonia demonstrated an area under the curve of 0.800 (sensitivity 80.0%, specificity 80.0%) and 0.825 (sensitivity 70.0%, specificity 95.0%), respectively. Conclusion: ARDS and septic shock were the independent risk factors for mortality in patients with influenza A-induced severe pneumonia following the end of the SARS-CoV-2 pandemic. But high level of next generation sequencing reads Aspergillus coinfection, and comorbidities did not increase death risk of the study population.

Skeletal Transformations of Terpenoid Forskolin Employing an Oxidative Rearrangement Strategy.

The skeletal transformations of diterpenoid forskolin were achieved by employing an oxidative rearrangement strategy. A library of 36 forskolin analogues with structural diversity was effectively generated. Computational analysis shows that 12 CTD compounds with unique scaffolds and ring systems were produced during the course of this work.