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.

Synergizing Steric Hindrance and Stacking Interactions to Facilitate the Controlled Assembly of Multiple 41 Metalla-Knots and Pseudo-Solomon Links.

In this work, a noncoplanar terphenyl served as building block to synthesize a novel 3,3'-substituted bipyridyl ligand (L1) which further reacted with binuclear half-sandwich units A/B, giving rise to two aesthetical 41 metalla-knots in high yields via coordination-driven self-assembly strategy. Furthermore, given the inherent compactness of the 41 metalla-knots, it creates favorable conditions for the emergence of steric repulsion. We focused on progressively introducing nitrogen atoms featuring lone pair electrons (LPEs) into ligand L1 to manipulate the balance of H···H/LPEs···LPEs steric repulsion during the assembly process, ultimately achieving controlled assembly from 41 metalla-knots to the pseudo-Solomon link and then to molecular tweezer-like assembly facilitated by stacking interactions. All the assemblies were well characterized by solution-state NMR techniques, ESI-TOF/MS, and single-crystal X-ray diffraction. The evolutionary process of topological architectures is equivalent to visualizing the synergistic effect of steric hindrance and stacking interactions on structural assembly, providing a new avenue for achieving the controlled synthesis of different topologies.

Tailored Supramolecular Interactions in Host-Guest Complexation for Efficient and Stable Perovskite Solar Cells and Modules.

Host-guest complexation offers a promising approach for mitigating surface defects in perovskite solar cells (PSCs). Crown ethers are the most widely used macrocyclic hosts for complexing perovskite surfaces, yet their supramolecular interactions and functional implications require further understanding. Here we show that the dipole moment of crown ethers serves as an indicator of supramolecular interactions with both perovskites and precursor salts. A larger dipole moment, achieved through the substitution of heteroatoms, correlates with enhanced coordination with lead cations. Perovskite films incorporating aza-crown ethers as additives exhibited improved morphology, reduced defect densities, and better energy-level alignment compared to those using native crown ethers. We report power-conversion efficiencies (PCEs) exceeding 25% for PSCs, which show enhanced long-term stability, and a record PCE of 21.5% for host-guest complexation-based perovskite solar modules with an active area of 14.0 cm2.

The Current Position of Postoperative Radiotherapy for Salivary Gland Cancer: A Systematic Review and Meta-Analysis.

BACKGROUND: Because of the rarity, heterogeneous histology, and diverse anatomical sites of salivary gland cancer (SGC), there are a limited number of clinical studies on its management. This study reports the cumulative evidence of postoperative radiotherapy (PORT) for SGC of the head and neck. METHODS: A systematic review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. We searched the PubMed, Embase, Cochrane Library, and Web of Science databases between 7th and 10th November 2023. RESULTS: A total of 2962 patients from 26 studies between 2007 and 2023 were included in this meta-analysis. The median RT dose was 64 Gy (range: 56-66 Gy). The median proportions of high-grade, pathological tumor stage 3 or 4 and pathological lymph node involvement were 42% (0-100%), 40% (0-77%), and 31% (0-75%). The pooled locoregional control rates at 3, 5, and 10 years were 92% (95% confidence interval [CI], 89-94%), 89% (95% CI, 86-93%), and 84% (95% CI, 73-92%), respectively. The pooled disease-free survival (DFS) rates at 3, 5, and 10 years were 77% (95% CI, 70-83%), 67% (95% CI, 60-74%), and 61% (95% CI, 55-67%), respectively. The pooled overall survival rates at 3, 5, and 10 years were 84% (95% CI, 79-88%), 75% (95% CI, 72-79%), and 68% (95% CI, 62-74%), respectively. Severe late toxicity ≥ grade 3 occurred in 7% (95% CI, 3-14%). CONCLUSION: PORT showed favorable long-term efficacy and safety in SGC, especially for patients with high-grade histology. Considering that DFS continued to decrease, further clinical trials exploring treatment intensification are warranted.

Stabilized Hf-doped Ti/Sb-SnO2 electrode for efficient degradation of tetracycline.

The electrochemical advanced oxidation process (EAOP) has shown significant promise in the field of refractory organic wastewater treatment due to its high efficiency and environmentally friendly nature. In this study, Ti/Sb-SnO2 electrodes with varying proportions of Hf were prepared using the sol-gel method. The addition of Hf transformed the original collapsing and broken surface into a flat and regular surface. The results demonstrated that Ti/Sb-SnO2-Hf electrode doped with 6% Hf exhibited a higher oxygen evolution potential (OEP) and excellent stability. The OEP increased from 2.315 V without Hf-doping to 2.482 V, and the corresponding actual life was 321.05% higher than that without Hf. The current density (5-40 mA·cm-2), electrolyte concentration (0.02-0.2 mol·L-1), pH (3-11), and initial pollutant concentration (5-80 mg·L-1) were evaluated to confirm the tetracycline (TC) degradation characterization of Ti/Sb-SnO2-6%Hf electrodes. It was concluded that under the optimal degradation conditions, the removal rate of TC could reach 99.66% within 2 h. The degradation of TC follows first-order reaction kinetics. The oxidative degradation of TC was achieved through indirect oxidation, with ·OH playing a dominant role. TC's electrochemical oxidation degradation pathway has been proposed: Based on LC-MS results, three main pathways are speculated. During the electrocatalytic oxidation process, decarboxylation, deamidation, and ring-opening reactions occur under ·OH attack, producing intermediate compounds with m/z values of 427, 433, 350, 246, 461, 424, 330, 352, 309, 263, and 233. These intermediates are further oxidized to intermediate compounds with an m/z value of 218. This work introduces a new efficient anode electrochemical catalyst for the degradation of TC, providing a strategy for industrial applications.

Emergency rescue of a patient with hemorrhagic shock caused by superior mesenteric artery rupture: A case report.

BACKGROUND: Superior mesenteric artery (SMA) injuries rarely occur during blunt abdominal injuries, with an incidence of < 1%. The clinical manifestations mainly include abdominal hemorrhage and peritoneal irritation, which progress rapidly and are easily misdiagnosed. Quick and accurate diagnosis and timely effective treatment are greatly significant in managing emergent cases. This report describes emergency rescue by a multidisciplinary team of a patient with hemorrhagic shock caused by SMA rupture. CASE SUMMARY: A 55-year-old man with hemorrhagic shock presented with SMA rupture. On admission, he showed extremely unstable vital signs and was unconscious with a laceration on his head, heart rate of 143 beats/min, shallow and fast breathing (frequency > 35 beats/min), and blood pressure as low as 20/10 mmHg (1 mmHg = 0.133 kPa). Computed tomography revealed abdominal and pelvic hematocele effusion, suggesting active bleeding. The patient was suspected of partial rupture of the distal SMA branch. The patient underwent emergency mesenteric artery ligation, scalp suture, and liver laceration closure. In view of conditions with acute onset, rapid progression, and high bleeding volume, key points of nursing were conducted, including activating emergency protocol, opening of the green channel, and arranging relevant examinations with various medical staff for quick diagnosis. The seamless collaboration of the multidisciplinary team helped shorten the preoperative preparation time. Emergency laparotomy exploration and mesenteric artery ligation were performed to mitigate hemorrhagic shock while establishing efficient venous accesses and closely monitoring the patient's condition to ensure hemodynamic stability. Strict measures were taken to avoid intraoperative hypothermia and infection. CONCLUSION: After 3.5 h of emergency rescue and medical care, bleeding was successfully controlled, and the patient's condition was stabilized. Subsequently, the patient was transferred to the intensive care unit for continuous monitoring and treatment. On the sixth day, the patient was weaned off the ventilator, extubated, and relocated to a specialized ward. Through diligent medical intervention and attentive nursing, the patient made a full recovery and was discharged on day 22. The follow-up visit confirmed the patient's successful recovery.

PAHs as environmental pollutants and their neurotoxic effects.

Polycyclic aromatic hydrocarbons (PAHs), which are widely present in incompletely combusted air particulate matter <2.5 µm (PM2.5), tobacco and other organic materials, can enter the human body through various routes and are a class of environmental pollutants with neurotoxic effects. PAHs exposure can lead to abnormal development of the nervous system and neurobehavioral abnormalities in animals, including adverse effects on the nervous system of children and adults, such as a reduced learning ability, intellectual decline, and neural tube defects. After PAHs enter cells of the nervous system, they eventually lead to nervous system damage through mechanisms such as oxidative stress, DNA methylation and demethylation, and mitochondrial autophagy, potentially leading to a series of nervous system diseases, such as Alzheimer's disease. Therefore, preventing and treating neurological diseases caused by PAHs exposure are particularly important. From the perspective of the in vitro and in vivo effects of PAHs exposure, as well as its effects on human neurodevelopment, this paper reviews the toxic mechanisms of action of PAHs and the corresponding prevention and treatment methods to provide a relevant theoretical basis for preventing the neurotoxicity caused by PAHs, thereby reducing the incidence of diseases related to the nervous system and protecting human health.

Utilizing machine learning for early screening of thyroid nodules: a dual-center cross-sectional study in China.

Background: Thyroid nodules, increasingly prevalent globally, pose a risk of malignant transformation. Early screening is crucial for management, yet current models focus mainly on ultrasound features. This study explores machine learning for screening using demographic and biochemical indicators. Methods: Analyzing data from 6,102 individuals and 61 variables, we identified 17 key variables to construct models using six machine learning classifiers: Logistic Regression, SVM, Multilayer Perceptron, Random Forest, XGBoost, and LightGBM. Performance was evaluated by accuracy, precision, recall, F1 score, specificity, kappa statistic, and AUC, with internal and external validations assessing generalizability. Shapley values determined feature importance, and Decision Curve Analysis evaluated clinical benefits. Results: Random Forest showed the highest internal validation accuracy (78.3%) and AUC (89.1%). LightGBM demonstrated robust external validation performance. Key factors included age, gender, and urinary iodine levels, with significant clinical benefits at various thresholds. Clinical benefits were observed across various risk thresholds, particularly in ensemble models. Conclusion: Machine learning, particularly ensemble methods, accurately predicts thyroid nodule presence using demographic and biochemical data. This cost-effective strategy offers valuable insights for thyroid health management, aiding in early detection and potentially improving clinical outcomes. These findings enhance our understanding of the key predictors of thyroid nodules and underscore the potential of machine learning in public health applications for early disease screening and prevention.

Investigation of the quality of life, mental status in patients with gynecological cancer and its influencing factors.

BACKGROUND: Having a gynecological tumor or undergoing treatment can be a traumatic experience for women, as it affects their self-image and sexual relationships and can lead to psychological reactions. Psychological adjustment following cancer occurrence remains a key issue among the survivors. AIM: To examine the current status of quality of life (QoL), anxiety, and depression in patients with gynecological cancer and to analyze the factors associated with it. METHODS: Data for 160 patients with gynecological malignancies treated at Shanxi Bethune Hospital from June 2020 to June 2023 were collected and analyzed retrospectively. Patients' QoL was assessed using the European Organization for Research on Treatment of Cancer Quality of Life Questionnaire Core 30 and the Functional Assessment of Cancer Therapy-General Questionnaire. Their emotional status was evaluated using the Self-Rating Anxiety/Depression Scale. The associated factors of anxiety and depression were analyzed. RESULTS: The overall QoL score of the patients 6 months after surgery was 76.39 ± 3.63 points. This included low levels of social and emotional function and severe fatigue and pain. The scores for physiological, functional, emotional, social, and family well-being exhibited an upward trend following surgery compared with those before surgery. One month after surgery, some patients experienced anxiety and depression, with an incidence of 18.75% and 18.13%, respectively. Logistic analysis revealed that good sleep was a protective factor against anxiety and depression in patients with gynecological tumors, whereas physical pain was a risk factor. CONCLUSION: Patients with gynecological malignancies often experience anxiety and depression. By analyzing the factors that affect patients' QoL, effective nursing measures can be administered.

[Quality control method for phenolic acid components in abandoned stems and leaves of Artemisia selengensis based on UPLC fingerprint combined with quantitative analysis of multi-components by single marker (QAMS)].

This study established an ultra-performance liquid chromatography(UPLC) fingerprint of abandoned stems and leaves of Artemisia selengensis and quantitative analysis of multi-components by single marker(QAMS) for five phenolic acid components. Waters Acquity UPLC BEH C_(18) chromatography column(2.1 mm×100 mm, 1.7 µm) was used. The gradient elution was carried out with the mobile phase composed of 0.1% phosphoric acid water and acetonitrile at a flow rate of 0.3 mL·min~(-1) and a column temperature at 30 ℃. The detection wavelength was 330 nm, and the injection volume was 2 µL. Similarity evaluation and cluster analysis were conducted on the fingerprint data, and 15 common components in 13 batches of abandoned stems and leaves of A. selengensis were identified. The relative correction factors of ferulic acid, isochlorogenic acid A, isochlorogenic acid B, and isochlorogenic acid C were calculated using chlorogenic acid as the internal reference. The QAMS for determining five components in the abandoned stems and leaves of A. selengensis was established. At the same time, the content of these five components was determined using the external standard method(ESM), and the results showed that there were no significant differences in their content determined by the QAMS and the ESM. The results indicated that the content of phenolic acid components in the abandoned stems and leaves of A. selengensis from different varieties and different origins had obvious differences. In addition, the content of phenolic acid components in the abandoned stems and leaves of lignified A. selengensis was significantly higher than that of non-lignified A. selengensis. In summary, QAMS established in this study can be quickly, accurately, and economically used to determine the content of five phenolic acid components in abandoned stems and leaves of A. selengensis, laying a foundation for the resource development and utilization of abandoned stems and leaves of A. selengensis.

Thermochemical Properties of High Pressure Neodymium Monoxide.

Neodymium monoxide (NdO) is a metastable rare earth oxide material with a unique electronic structure, which has potential applications across various fields such as semiconductors, energy, catalysis, laser technology, and advanced communications. Despite its promising attributes, the thermodynamic properties of NdO remain unexplored. In this study, high pressure, high temperature phases of neodymium monoxide (NdO, with a rocksalt structure) and body-centered cubic (bcc) Nd metal were synthesized at 5 GPa and 1473 K. X-ray photoelectron spectroscopy (XPS) measurements indicate that the Nd 3d peak shifts to higher energy in NdO relative to Nd2O3, suggesting the possibility of complex electronic states in NdO. Formation enthalpies for the reaction 1/3Nd2O3 + 1/3bcc Nd = NdO obtained from high temperature solution calorimetry in molten sodium molybdate and for the reaction dhcp Nd (metal) = bcc Nd (metal) from differential scanning calorimetry are 25.98 ± 8.65 and 5.2 kJ/mol, respectively. Utilizing these enthalpy values, we calculated the pressure-temperature boundary for the reaction 1/3 bcc Nd + 1/3Nd2O3 = NdO, which has a negative P-T slope of -1.68× 10-4 GPa/K. These insights reveal the high pressure behavior of NdO and neodymium metal, underscoring their potential utility in technological applications.

PKMYT1 knockdown inhibits cholesterol biosynthesis and promotes the drug sensitivity of triple-negative breast cancer cells to atorvastatin.

Triple negative breast cancer (TNBC) as the most aggressive molecular subtype of breast cancer is characterized by high cancer cell proliferation and poor patient prognosis. Abnormal lipid metabolism contributes to the malignant process of cancers. Study observed significantly enhanced cholesterol biosynthesis in TNBC. However, the mechanisms underlying the abnormal increase of cholesterol biosynthesis in TNBC are still unclear. Hence, we identified a member of the serine/threonine protein kinase family PKMYT1 as a key driver of cholesterol synthesis in TNBC cells. Aberrantly high-expressed PKMYT1 in TNBC was indicative of unfavorable prognostic outcomes. In addition, PKMYT1 promoted sterol regulatory element-binding protein 2 (SREBP2)-mediated expression of enzymes related to cholesterol biosynthesis through activating the TNF/ TNF receptor-associated factor 1 (TRAF1)/AKT pathway. Notably, downregulation of PKMYT1 significantly inhibited the feedback upregulation of statin-mediated cholesterol biosynthesis, whereas knockdown of PKMYT1 promoted the drug sensitivity of atorvastatin in TNBC cells. Overall, our study revealed a novel function of PKMYT1 in TNBC cholesterol biosynthesis, providing a new target for targeting tumor metabolic reprogramming in the cancer.

Circular RNA oligonucleotides: enzymatic synthesis and scaffolding for nanoconstruction.

We report the efficient synthesis of monomeric circular RNAs (circRNAs) in the size range of 16-44 nt with a novel DNA dumbbell splinting plus T4 DNA ligation strategy. Such a DNA dumbbell splinting strategy was developed by one group among ours recently for near-quantitative conversion of short linear DNAs into monomeric circular ones. Furthermore, using the 44 nt circRNA as scaffold strands, we constructed hybrid RNA:DNA and pure RNA:RNA double crossover tiles and their assemblies of nucleic acid nanotubes and flat arrays.

A Propeller-Like Ligand-Directed Construction of a Tetranuclear Cerium-Organic Framework for Single-Step Ethylene Purification from Ternary C2 Mixtures.

The efficient single-step purification of ethylene from ternary C2 mixtures containing ethane and acetylene is challenging and demanding. Herein, we introduce a novel cerium-based metal-organic framework (MOF) of Ce-NTB-rtk synthesized via a ligand-conformer strategy. The Ce-NTB-rtk features a rare tetranuclear cerium cluster and 2D kgd layers pillared by a 3D rtl framework concomitant with an extraordinary (3,3,12)-c network. The compound encompasses microporous cavities replete with a nonpolar microenvironment. Gas sorption and breakthrough experiments demonstrate its superior affinity for C2H6 and C2H2 over C2H4, enabling effective single-step ethylene purification. Computational simulations reveal that preferential adsorptions are facilitated by different interaction strengths of C-H···O hydrogen bonds. The performance of Ce-NTB-rtk in separation selectivity and regeneration capacity makes it a promising candidate for sustainable and cost-effective ethylene purification, showcasing the potential of MOFs in advanced gas separation applications.

Spore germination and lactic acid combined treatment: A new processing strategy for the shelf-life extension of instant wet noodles.

Bacillus amyloliquefaciens (BAM) was identified as the predominant spoilage bacteria in instant wet noodles (IWNs). The utilization of industrial acid treatment as a long shelf-life strategy resulted in reduced consumer acceptance due to the acidic taste of the products. This study proposed a processing strategy that integrated spore germination (SG) and lactic acid (LA) treatment to effectively reduce the spore survival rate and extend the shelf life of IWNs. L-histidine, d-glucose, and sodium chloride were highly efficient and safe germinants for BAM spores. In IWNs, compound germinants (1.0 % L-histidine, 0.5 % d-glucose, and 1.0 % sodium chloride) boosted the SG rate by 3.61 times. With synergistic LA treatment, the spore lethality increased by 34.41 % -41.68 %. Under the SG and reduced acid-heat conditions of pH 2.30-2.50, the mortality of spores could reach 92.00 %-93.17 %, which was 14.11 %-15.28 % higher than the industrial acid-heat condition of pH 2.10. DPA, ATP, and membrane potential showed that germinants reduced the spore membrane permeability and promoted the occurrence of spore membrane damage under acid-heat conditions. Moreover, this strategy significantly extended the shelf-life of IWNs by 3.00-5.50 times and controlled the pH ≥ 5.50. Additionally, it improved color, texture, and overall sensory evaluation. Accordingly, this strategy solved the contradiction between the long shelf-life of IWNs and the unacceptable acidification in industrial production.

Enhanced Photoemission Performance of InGaN Inclined Nanowire Array.

We propose to improve the solar energy utilization by using InGaN inclined nanowire array photocathodes. We first study vertical nanowire array. On the basis of vertical nanowire array, we study inclined nanowires by changing the inclination angle of nanowires. The inclined nanowires exhibit higher quantum efficiency at larger period and larger inclination angle. However, the infinite expansion of period will cause its performance to degrade. The quantum efficiency of inclined nanowires with a period of 175 nm and an inclination angle of 5.35° is as high as 80.2% when the incident light angle is irradiated at 5°. In addition, applying an electric field can improve the collection efficiency of inclined nanowires and help them maintain a high collection efficiency over a longer wavelength range. The design principles proposed in this work will provide a theoretical reference for the performance improvement of InGaN photocathodes.

Electro-oxidation of ammonia nitrogen using W, Ti-doped IrO2 DSA as a treatment method for mariculture and livestock wastewater.

Animal farming wastewater is one of the most important sources of ammonia nitrogen (NH4+-N) emissions. Electro-oxidation can be a viable solution for removing NH4+-N in wastewater. Compared with other treatment methods, electro-oxidation has the advantages of i) high removal efficiency, ii) smaller size of treatment facilities, and iii) complete removal of contaminant. In this study, a previously prepared DSA (W, Ti-doped IrO2) was used for electro-oxidation of synthetic mariculture and livestock wastewater. The DSA was tested for chlorine evolution reaction (CER) activity, and the reaction kinetics was investigated. CER current efficiency reaches 60-80% in mariculture wastewater and less than 20% in livestock wastewater. In the absence of NH4+-N, the generation of active chlorine follows zero-order kinetics and its consumption follows first-order kinetics, with cathodic reduction being its main consumption pathway, rather than escape or conversion to ClO3-. Cyclic voltammetry experiments show that NH4+-N in the form of NH3 can be oxidized directly on the anode surface. In addition, the generated active chlorine combines with NH4+-N at a fast rate near the anode, rather than in the bulk solution. In electrolysis experiments, the NH4+-N removal rate in synthetic mariculture wastewater (30-40 mg/L NH4+-N) and livestock wastewater (~ 450 mg/L NH4+-N) is 112.9 g NH4+-N/(m2·d) and 186.5 g NH4+-N/(m2·d), respectively, which is much more efficient than biological treatment. The specific energy consumption (SEC) in synthetic mariculture wastewater is 31.5 kWh/kg NH4+-N, comparable to other modified electro-catalysts reported in the literature. However, in synthetic livestock wastewater, the SEC is as high as 260 kWh/kg NH4+-N, mainly due to the suppression of active chlorine generation by HCO3- and the generation of NO3- as a by-product. Therefore, we conclude that electro-oxidation is suitable for mariculture wastewater treatment, but is not recommended for livestock wastewater. Electrolysis prior to urea hydrolysis may enhance the treatment efficiency in livestock wastewater.

Harnessing Holey MXene/Graphene Oxide Heterostructure to Maximize Ion Channels in Lamellar Film for High-Performance Capacitive Deionization.

2D Ti3C2Tx MXene-based film electrodes with metallic conductivity and high pseudo-capacitance are of considerable interest in cutting-edge research of capacitive deionization (CDI). Further advancement in practical use is however impeded by their intrinsic limitations, e.g., tortuous ion diffusion pathway of layered stacking, vulnerable chemical stability, and swelling-prone nature of hydrophilic MXene nanosheet in aqueous environment. Herein, a nanoporous 2D/2D heterostructure strategy is established to leverage both merits of holey MXene (HMX) and holey graphene oxide (HGO) nanosheets, which optimize ion transport shortcuts, alleviate common restacking issues, and improve film's mechanical and chemical stability. In this design, the nanosized in-plane holes in both handpicked building blocks build up ion diffusion shortcuts in the composite laminates to accelerate the transport and storage of ions. As a direct outcome, the HMX/rHGO films exhibit remarkable desalination capacity of 57.91 mg g-1 and long-term stability in 500 mg L-1 NaCl solution at 1.2 V. Moreover, molecular dynamics simulations and ex situ wide angle X-ray scattering jointly demonstrate that the conductive 2D/2D networks and ultra-short ion diffusion channels play critical roles in the ion intercalation/deintercalation process of HMX/rHGO films. The study paves an alternative design concept of freestanding CDI electrodes with superior ion transport efficiency.

African swine fever virus structural protein p17 inhibits IRF3 activation by recruiting host protein PR65A and inducing apoptotic degradation of STING.

African swine fever virus (ASFV) is notoriously known for evolving strategies to modulate IFN signaling. Despite lots of efforts, the underlying mechanisms have remained incompletely understood. This study concerns the regulatory role of viral inner membrane protein p17. We found that the ASFV p17 shows a preferential interaction with cGAS-STING-IRF3 pathway, but not the RIG-I-MAVS-NF-κB signaling, and can inhibit both poly(I:C)- and poly(A:T)-induced activation of IRF3, leading to attenuation of IFN-ß induction. Mechanistically, p17 interacts with STING and IRF3 and recruits host scaffold protein PR65A, a subunit of cellular phosphatase PP2A, to down-regulate the level of p-IRF3. Also, p17 targets STING for partial degradation via induction of cellular apoptosis that consequently inhibits activation of both p-TBK1 and p-IRF3. Thus, our findings reveal novel regulatory mechanisms for p17 modulation of IFN signaling and shed light on the intricate interplay between ASFV proteins and host immunity.

Functional assessment of CYP3A4 and CYP2C19 genetic polymorphisms on the metabolism of clothianidin invitro.

Clothianidin, classified as a second-generation neonicotinoid, has achieved extensive application due to its high efficacy against insect pests. This broad-spectrum usage has resulted in its frequent detection in environmental surveys. CYP2C19 and CYP3A4 are crucial for converting clothianidin to desmethyl-clothianidin (dm-clothianidin). The expression of these CYP450s can be significantly influenced by genetic polymorphisms. The objective of our research was to examine the catalytic effects of 27 CYP3A4 variants and 31 CYP2C19 variants on the metabolism of clothianidin within recombinant insect microsomes. These variants were assessed through a well-established incubation procedure. In addition, the concentration of its metabolite dm-clothianidin was quantified by employing an ultra performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS). Lastly, the kinetic parameters of these CYP3A4 and CYP2C19 variants were calculated by applying Michaelis-Menten kinetic analysis to fit the data. The observed changes in enzyme activity were related to the metabolic transformation of clothianidin to dm-clothianidin. In the CYP2C19 metabolic pathway, one variant (CYP2C19.23) showed no notable change in intrinsic clearance (CLint), four variants (CYP2C19.29, .30, .31 and L16F) demonstrated a marked increase in CLint (110.86-183.46 %), and the remaining 25 variants exhibited a considerable decrease in CLint (26.38-89.79 %), with a maximum decrease of 73.62 % (CYP2C19.6). In the CYP3A4 metabolic pathway, 26 variants demonstrated significantly reduced CLint (10.54-52.52 %), with a maximum decrease of 89.46 % (CYP3A4.20). Our results suggested that most variants of CYP3A4 and CYP2C19 significantly altered the enzymatic activities associated with clothianidin metabolism to various degrees. This study provides new insights into assessing the metabolic behavior of pesticides and delivers crucial data that can guide clinical detoxification strategies.