DOT1L maintains NK cell phenotype and function for optimal tumor control.

Histone methyltransferases (HMTs) are crucial in gene regulation and function, yet their role in natural killer (NK) cell biology within the tumor microenvironment (TME) remains largely unknown. We demonstrate that the HMT DOT1L limits NK cell conversion to CD49a+ CD49b+ intILC1, a subset that can be observed in the TME in response to stimulation with transforming growth factor (TGF)-ß and is correlated with impaired tumor control. Deleting Dot1l in NKp46-expressing cells reveals its pivotal role in maintaining NK cell phenotype and function. Loss of DOT1L skews NK cells toward intILC1s even in the absence of TGF-ß. Transcriptionally, DOT1L-null NK cells closely resemble intILC1s and ILC1s, correlating with altered NK cell responses and impaired solid tumor control. These findings deepen our understanding of NK cell biology and could inform approaches to prevent NK cell conversion to intILC1s in adoptive NK cell therapies for cancer.

Therapeutic implications of quercetin and its derived-products in COVID-19 protection and prophylactic.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a novel human coronavirus, which has triggered a global pandemic of the coronavirus infectious disease 2019 (COVID-19). Outbreaks of emerging infectious diseases continue to challenge human health worldwide. The virus conquers human cells through the angiotensin-converting enzyme 2 receptor-driven pathway by mostly targeting the human respiratory tract. Quercetin is a natural flavonoid widely represented in the plant kingdom. Cumulative evidence has demonstrated that quercetin and its derivatives have various pharmacological properties including anti-cancer, anti-hypertension, anti-hyperlipidemia, anti-hyperglycemia, anti-microbial, antiviral, neuroprotective, and cardio-protective effects, because it is a potential treatment for severe inflammation and acute respiratory distress syndrome. Furthermore, it is the main life-threatening condition in patients with COVID-19. This article provides a comprehensive review of the primary literature on the predictable effectiveness of quercetin and its derivatives docked to multi-target of SARS-CoV-2 and host cells via in silico and some of validation through in vitro, in vivo, and clinically to fight SARS-CoV-2 infections, contribute to the reduction of inflammation, which suggests the preventive and therapeutic latency of quercetin and its derived-products against COVID-19 pandemic, multisystem inflammatory syndromes (MIS), and long-COVID.

IKAROS and AIOLOS directly regulate AP-1 transcriptional complexes and are essential for NK cell development.

Ikaros transcription factors are essential for adaptive lymphocyte function, yet their role in innate lymphopoiesis is unknown. Using conditional genetic inactivation, we show that Ikzf1/Ikaros is essential for normal natural killer (NK) cell lymphopoiesis and IKZF1 directly represses Cish, a negative regulator of interleukin-15 receptor resulting in impaired interleukin-15 receptor signaling. Both Bcl2l11 and BIM levels, and intrinsic apoptosis were increased in Ikzf1-null NK cells, which in part accounts for NK lymphopenia as both were restored to normal levels when Ikzf1 and Bcl2l11 were co-deleted. Ikzf1-null NK cells presented extensive transcriptional alterations with reduced AP-1 transcriptional complex expression and increased expression of Ikzf2/Helios and Ikzf3/Aiolos. IKZF1 and IKZF3 directly bound AP-1 family members and deletion of both Ikzf1 and Ikzf3 in NK cells resulted in further reductions in Jun/Fos expression and complete loss of peripheral NK cells. Collectively, we show that Ikaros family members are important regulators of apoptosis, cytokine responsiveness and AP-1 transcriptional activity.

CD45 limits early Natural Killer cell development.

The clinical development of Natural Killer (NK) cell-mediated immunotherapy marks a milestone in the development of new cancer therapies and has gained traction due to the intrinsic ability of the NK cell to target and kill tumor cells. To fully harness the tumor killing ability of NK cells, we need to improve NK cell persistence and to overcome suppression of NK cell activation in the tumor microenvironment. The trans-membrane, protein tyrosine phosphatase CD45, regulates NK cell homeostasis, with the genetic loss of CD45 in mice resulting in increased numbers of mature NK cells. This suggests that CD45-deficient NK cells might display enhanced persistence following adoptive transfer. However, we demonstrate here that adoptive transfer of CD45-deficiency did not enhance NK cell persistence in mice, and instead, the homeostatic disturbance of NK cells in CD45-deficient mice stemmed from a developmental defect in the progenitor population. The enhanced maturation within the CD45-deficient NK cell compartment was intrinsic to the NK cell lineage, and independent of the developmental defect. CD45 is not a conventional immune checkpoint candidate, as systemic loss is detrimental to T and B cell development, compromising the adaptive immune system. Nonetheless, this study suggests that inhibition of CD45 in progenitor or stem cell populations may improve the yield of in vitro generated NK cells for adoptive therapy.

O2-Independent H2O2 Production via Water-Polymer Contact Electrification.

Hydrogen peroxide (H2O2), as a critical green chemical, has received immense attention in energy and environmental fields. The ability to produce H2O2 in earth-abundant water without relying on low solubility oxygen would be a sustainable and potentially economic process, applicable even to anaerobic microenvironments, such as groundwater treatment. However, the direct water to H2O2 process is currently hindered by low selectivity and low production rates. Herein, we report that poly(tetrafluoroethylene) (PTFE), a commonly used inert polymer, can act as an efficient triboelectric catalyst for H2O2 generation. For example, a high H2O2 production rate of 24.8 mmol gcat-1 h-1 at a dosage of 0.01 g/L PTFE was achieved under the condition of pure water, ambient atmosphere, and no sacrificial agents, which exceeds the performance of state-of-the-art aqueous H2O2 powder catalysts. Electron spin resonance and isotope experiments provide strong evidence that water-PTFE tribocatalysis can directly oxidize water to produce H2O2 under both anaerobic and aerobic conditions, albeit with different synthetic pathways. This study demonstrates a potential strategy for green and effective tribocatalytic H2O2 production that may be particularly useful toward environmental applications.

Gas-phase synthesis of Ti2CCl2 enables an efficient catalyst for lithium-sulfur batteries.

MXenes have aroused intensive enthusiasm because of their exotic properties and promising applications. However, to date, they are usually synthesized by etching technologies. Developing synthetic technologies provides more opportunities for innovation and may extend unexplored applications. Here, we report a bottom-up gas-phase synthesis of Cl-terminated MXene (Ti2CCl2). The gas-phase synthesis endows Ti2CCl2 with unique surface chemistry, high phase purity, and excellent metallic conductivity, which can be used to accelerate polysulfide conversion kinetics and dramatically prolong the cyclability of Li-S batteries. In-depth mechanistic analysis deciphers the origin of the formation of Ti2CCl2 and offers a paradigm for tuning MXene chemical vapor deposition. In brief, the gas-phase synthesis transforms the synthesis of MXenes and unlocks the hardly achieved potentials of MXenes.

Efficacy and safety of the integration of traditional Chinese medicine and western medicine in the treatment of diabetes-associated cognitive decline: a systematic review and meta-analysis.

Objective: In order to offer possible therapeutic treatment evidence for diabetes-associated cognitive decline (DACD), we thoroughly evaluated the effectiveness and safety of combining Traditional Chinese Medicine (TCM) and Western Medicine (WM) in the current study. Methods: The present study employed a comprehensive search strategy across multiple databases, namely, PubMed, EMBASE, Web of Science, the Cochrane Library, China National Knowledge Infrastructure (CNKI), Wanfang Data, Chinese Scientific Journals Database (VIP), and Chinese Biomedical Literature Database (CBM), to identify relevant articles published until July 2023. Subsequently, a systematic review and meta-analysis of randomized controlled trials (RCTs) were conducted to assess the efficacy and safety of integrating TCM with WM for the treatment of DACD. The literature included in this study was assessed using the GRADE criteria and the Cochrane Handbook for Systematic Reviews of Interventions. Statistical analysis was conducted using RevMan 5.4 software. Results: A total of 20 RCTs involving 1,570 patients were ultimately included in this meta-analysis. The pooled results demonstrated that the integration of TCM and WM therapy significantly enhanced the overall effectiveness rate compared to WM therapy alone [OR = 4.94, 95% CI (3.56, 6.85), p < 0.00001]. Additionally, the combination therapy resulted in reductions in fasting blood glucose [MD = -0.30, 95% CI (-0.49, -0.10), p = 0.003], HbA1c [MD = -0.71, 95%CI (-1.03, -0.40), p < 0.00001], TNF-α levels [MD = -8.28, 95%CI (-13.12, -3.44), p = 0.0008], and TCM Syndrome Score [MD = -5.97, 95%CI (-9.06, -2.88), p = 0.0002]. Meanwhile, the combination therapy had a positive effect on MoCA Score [MD = 2.52, 95% CI (1.75, 3.30), p < 0.00001], and MMSE Score [MD = 2.31, 95% CI (1.33, 3.29), p < 0.00001]. In addition, the safety of the combination therapy was comparable to that of the WM alone [OR = 0.40, 95% CI (0.12, 1.31), p = 0.13]. Conclusion: The integration of TCM and WM therapy outperformed WM alone in DACD treatment. Simultaneously, the combination therapy could improve the therapeutic effect on blood glucose, cognitive function, and inflammation to a certain extent with few adverse effects. However, given the constraints imposed by the quality limitations of the incorporated studies, as well as the potential presence of reporting bias, it is imperative that our findings be substantiated through rigorous, large-scale, randomized controlled trials of superior quality in the future.

Functional near-infrared spectroscopy approach to the emotional regulation effect of drawing: Venting versus distraction.

BACKGROUND: Drawing can regulate emotions through venting or distraction. Distraction is more helpful for short-term emotion recovery; however, the sustainability of this difference is yet to be clarified. This study used functional near-infrared spectroscopy (fNIRS) to explore potential differences between venting and distraction. METHODS: A total of 44 college students participated in the experiment. After inducing fear by video, they were divided into two groups: The venting group drew their emotional experience, and the distraction group drew a house. Subsequently, the participants were instructed to relax by a brief video. RESULTS: Although the distraction group had a higher valence than the venting group at the end of the drawing activity, there was no difference between the two groups after a relaxation period. Additionally, the activation pattern of the prefrontal cortex differed between the two groups. Compared to the distraction group, the venting group had fewer channels with elevated prefrontal activity during drawing, suggesting less cognitive control, and had more channels with reduced prefrontal activity during relaxation, suggesting a higher level of relaxation. Drawing coding and fNIRS data were both associated with variations in valence. CONCLUSION: The less the cognitive control over emotion and the more free the expression of emotion during drawing, the higher the increase in valence; inversely, the more the cognitive control over emotion and the less free the expression of emotion, the lower the increase in valence.

Vanadium Intercalation into Niobium Disulfide to Enhance the Catalytic Activity for Lithium-Sulfur Batteries.

Despite their high specific energy and great promise for next-generation energy storage, lithium-sulfur (Li-S) batteries suffer from polysulfide shuttling, slow redox kinetics, and poor cyclability. Catalysts are needed to accelerate polysulfide conversion and suppress the shuttling effect. However, a lack of structure-activity relationships hinders the rational development of efficient catalysts. Herein, we studied the Nb-V-S system and proposed a V-intercalated NbS2 (Nb3VS6) catalyst for high-efficiency Li-S batteries. Structural analysis and modeling revealed that undercoordinated sulfur anions of [VS6] octahedra on the surface of Nb3VS6 may break the catalytic inertness of the basal planes, which are usually the primary exposed surfaces of many 2D layered disulfides. Using Nb3VS6 as the catalyst, the resultant Li-S batteries delivered high capacities of 1541 mAh g-1 at 0.1 C and 1037 mAh g-1 at 2 C and could retain 73.2% of the initial capacity after 1000 cycles. Such an intercalation-induced high activity offers an alternative approach to building better Li-S catalysts.

Rational engineering yolk-shell In2S3@void@carbon hybrid as polysulfide-absorbable sulfur host for high-performance lithium-sulfur batteries.

The slow redox kinetics and shuttling behavior of the intermediate lithium polysulfides constrain the further development of lithium-sulfur (Li-S) electrochemistry. A yolk-shell In2S3@void@carbon hybrid engineered to host the sulfur for Li-S batteries is prepared by using a multi-layered assembly method. The In2S3/electrolyte interface acted as powerful adsorption and activation sites for soluble polysulfides, which is demonstrated using density functional theory (DFT) calculations. Moreover, the carbon shell provides redundancy for volume-changes during the cycles. The results indicate that yolk-shell In2S3@S@C hybrid cathode shows good reversibility and rate capability, which preserves 563.6 mA h g-1 after 500 cycles at 0.5 C, indicating the potential for developing high-performance battery systems.

Fe/Cu diatomic catalysts for electrochemical nitrate reduction to ammonia.

Electrochemical conversion of nitrate to ammonia offers an efficient approach to reducing nitrate pollutants and a potential technology for low-temperature and low-pressure ammonia synthesis. However, the process is limited by multiple competing reactions and NO3- adsorption on cathode surfaces. Here, we report a Fe/Cu diatomic catalyst on holey nitrogen-doped graphene which exhibits high catalytic activities and selectivity for ammonia production. The catalyst enables a maximum ammonia Faradaic efficiency of 92.51% (-0.3 V(RHE)) and a high NH3 yield rate of 1.08 mmol h-1 mg-1 (at - 0.5 V(RHE)). Computational and theoretical analysis reveals that a relatively strong interaction between NO3- and Fe/Cu promotes the adsorption and discharge of NO3- anions. Nitrogen-oxygen bonds are also shown to be weakened due to the existence of hetero-atomic dual sites which lowers the overall reaction barriers. The dual-site and hetero-atom strategy in this work provides a flexible design for further catalyst development and expands the electrocatalytic techniques for nitrate reduction and ammonia synthesis.

Pharmacokinetics, Bioequivalence, and Safety Evaluation of 2 Formulations of 10-mg Rivaroxaban Tablets: A 4-Period Crossover Trial.

This study compared the safety, bioequivalence, and pharmacokinetic properties of 2 formulations of 10-mg rivaroxaban tablets in healthy Chinese participants in fasting and fed arms. The trial was an open, randomized, 4-period, replicated crossover scheme, and 36 volunteers were recruited separately for the fasting and fed arms. Volunteers were randomly administered a single dose of the test or reference formulation (10 mg) orally, followed by a 5-day washout period. Rivaroxaban concentrations in the plasma were determined using liquid chromatography-tandem mass spectrometry, and pharmacokinetic parameters were obtained from the concentration-time profiles. The mean values of the test and the reference product for the area under the plasma concentration-time curve from time 0 to the last measurable concentration, area under the plasma concentration-time curve from time 0 to infinity, and maximum plasma concentration were 996 and 1014 ng • h/mL, 1024 and 1055 ng • h/mL, and 150 and 152 ng/mL in the fasting arm, respectively; the values were 1155 and 1167 ng • h/mL, 1160 and 1172 ng • h/mL, and 202 and 193 ng/mL in the fed arm, respectively. All the parameters were within acceptable limits in terms of bioequivalence. No serious adverse events were observed. This study demonstrated that the 2 rivaroxaban tablets were bioequivalent in healthy Chinese participants under fasting and fed conditions.

CrP Nanocatalyst within Porous MOF Architecture to Accelerate Polysulfide Conversion in Lithium-Sulfur Batteries.

Lithium-sulfur (Li-S) batteries demonstrate great potential for next-generation electrochemical energy storage systems because of their high specific energy and low-cost materials. However, the shuttling behavior and slow kinetics of intermediate polysulfide (PS) conversion pose a major obstacle to the practical application of Li-S batteries. Herein, CrP within a porous nanopolyhedron architecture derived from a metal-organic framework (CrP@MOF) is developed as a highly efficient nanocatalyst and S host to address these issues. Theoretical and experimental analyses demonstrate that CrP@MOF has a remarkable binding strength to trap soluble PS species. In addition, CrP@MOF shows abundant active sites to catalyze the PS conversion, accelerate Li-ion diffusion, and induce the precipitation/decomposition of Li2S. As a result, the CrP@MOF-containing Li-S batteries demonstrate over 67% capacity retention over 1000 cycles at 1 C, ∼100% Coulombic efficiency, and high rate capability (674.6 mAh g-1 at 4 C). In brief, CrP nanocatalysts accelerate the PS conversion and improve the overall performance of Li-S batteries.

Tuning the Local Coordination of CoP1-xSx between NiAs- and MnP-Type Structures to Catalyze Lithium-Sulfur Batteries.

The slow conversion and rapid shuttling of polysulfides remain major challenges that hinder the practical application of lithium-sulfur (Li-S) batteries. Efficient catalysts are needed to accelerate the conversion and suppress the shuttling. However, the lack of a rational understanding of catalysis poses obstacles to the design of catalysts, thereby limiting the rapid development of Li-S batteries. Herein, we theoretically analyze the modulation of the electronic structure of CoP1-xSx caused by the NiAs-to-MnP-type transition and its influence on catalytic activity. We found that the interacting d-orbitals of the active metal sites play a determining role in adsorption and catalysis, and the optimal dz2-, dxz-, and dyz-orbitals in an appropriately distorted five-coordinate pyramid enable higher catalytic activity compared with their parent structures. Finally, rationally designed catalysts and S were electrospun into carbonized nanofibers to form nanoreactor chains for use as cathodes. The resultant Li-S batteries exhibited superior properties over 1000 cycles with only a decay rate of 0.031% per cycle and demonstrated a high capacity of 887.4 mAh g-1 at a high S loading of 10 mg cm-2. The structural modulation and bonding analyses in this study provide a powerful approach for the rational design of Li-S catalysts.

Cu2O/SrTi1-xCrxO3 Heterojunction Photocatalyst for the Efficient Degradation of Isopropanol under Visible Light Irradiation.

A heterojunction of Cu2O and Cr-doped SrTiO3 (SrTi1-xCrxO3) was designed for selective photocatalytic isopropanol (IPA) oxidation under visible light irradiation. The photocatalytic oxidation of IPA was measured in a fixed-bed reactor. Cr dopants can increase the light absorption and improve the activity of the catalyst. The formation of the Cu2O/SrTi1-xCrxO3 heterojunction can further broaden the absorption range of lights and dramatically increase the photocatalytic activity for selective oxidation of IPA. The 3% Cu2O/SrTi0.99Cr0.01O3 catalyst can fully convert ∼1000 ppm IPA under illumination in 2 h. The selectivity of acetone is ∼100%. The yield is 83 and 4 times higher than that using SrTiO3 and SrTi0.99Cr0.01O3 as catalysts, respectively. By measuring the ultraviolet-visible absorption spectra and Mott-Schottky plots, we obtained the band structure of the heterojunction, which shows that the conduction and valence bands of Cu2O are higher than those of SrTi1-xCrxO3, therefore facilitating the separation and transfer of photogenerated electrons and holes. In addition, electron paramagnetic resonance spectroscopy and radical trapping tests reveal that the generation of hydroxyl and superoxide leads to photocatalytic oxidation of IPA by the heterojunction photocatalyst.

Rational engineering of VS4 nanorod array on rose-shaped VS2 nanosheets for high-performance aluminium-ion batteries.

High performance aluminium-ion (Al-ion) batteries are of wide interest owing to the high theoretical capacity, abundance of Al metal and good safety. Here, we develop a hierarchical VS2@VS4 composed of a VS4 nanorod array in situ grown on VS2 rose-shaped nanosheets that displays a good electrochemical performance. The VS2@VS4 cathode displays a high capacity of 162.7 mA h g-1 after 200 cycles at -10 °C, and keeps 116.5 mA h g-1 after 500 cycles at room temperature. Rate-performance at -10 °C shows a capacity retention rate of 90%, which indicates the potential for engineering high-performance energy-storage composites.

GAN-FDSR: GAN-Based Fault Detection and System Reconfiguration Method.

Fault detection and exclusion are essential to ensure the integrity and reliability of the tightly coupled global navigation satellite system (GNSS)/inertial navigation system (INS) integrated navigation system. A fault detection and system reconfiguration scheme based on generative adversarial networks (GAN-FDSR) for tightly coupled systems is proposed in this paper. The chaotic characteristics of pseudo-range data are analyzed, and the raw data are reconstructed in phase space to improve the learning ability of the models for non-linearity. The trained model is used to calculate generation and discrimination scores to construct fault detection functions and detection thresholds while retaining the generated data for subsequent system reconfiguration. The influence of satellites on positioning accuracy of the system under different environments is discussed, and the system reconfiguration scheme is dynamically selected by calculating the relative differential precision of positioning (RDPOP) of the faulty satellites. Simulation experiments are conducted using the field test data to assess fault detection performance and positioning accuracy. The results show that the proposed method greatly improves the detection sensitivity of the system for small-amplitude faults and gradual faults, and effectively reduces the positioning error during faults.

The adsorption mechanisms of oriental plane tree biochar toward bisphenol S: A combined thermodynamic evidence, spectroscopic analysis and theoretical calculations.

Garden pruning waste is becoming a problem that intensifies the garbage siege. It is of great significance to purify polluted water using biochar prepared from garden pruning waste. Herein, the interaction mechanism between BPS and oriental plane tree biochar (TBC) with different surface functional groups was investigated by adsorption experiments, spectroscopic analysis and theoretical calculations. Adsorption kinetics and isotherm of BPS on TBC can be satisfactorily fitted into pseudo-second-order kinetic and Langmuir models, respectively. A rapid adsorption kinetic toward BPS was achieved by TBC in 15 min. As compared with TBC prepared at low temperature (300 °C) (LTBC), the maximum adsorption capacity of TBC prepared at high temperature (600 °C) (HTBC) can be significantly improved from 46.7 mg g-1 to 72.9 mg g-1. Besides, the microstructure and surface functional groups of HTBC were characterized using SEM, BET-N2, and XPS analysis. According to density functional theory (DFT) theoretical calculations, the higher adsorption energy of HTBC for BPS was mainly attributed to π-π interaction rather than hydrogen bonding, which was further supported by the analysis of FTIR and Raman spectra as well as the adsorption thermodynamic parameters. These findings suggested that by improving π-π interaction through high pyrolysis temperature, BPS could be removed and adsorbed by biochar with high efficacy, cost-efficiency, easy availability, and carbon-negative in nature, contributing to global carbon neutrality.

A Lamellar Yolk-Shell Lithium-Sulfur Battery Cathode Displaying Ultralong Cycling Life, High Rate Performance, and Temperature Tolerance.

The shuttling behavior and slow conversion kinetics of the intermediate lithium polysulfides are the severe obstacles for the application of lithium-sulfur (Li-S) batteries over a wide temperature range. Here, an engineered lamellar yolk-shell structure of In2 O3 @void@carbon for the Li-S battery cathode is developed for the first time to construct a powerful barrier that effectively inhibits the shuttling of polysulfides. On the basis of the unique nanochannel-containing morphology, the continuous kinetic transformation of sulfur and polysulfides is confined in a stable framework, which is demonstrated by using X-ray nanotomography. The constructed Li-S battery exhibits a high cycling capability over 1000 cycles at 1.0 C with a capacity decay rate as low as 0.038% per cycle, good rate performance, and temperature tolerance at -10, 25, and 50 °C. A nondestructive in situ monitoring method of the interfacial reaction resistance in different cycling stages is proposed, which provides a new analysis perspective for the development of emerging electrochemical energy-storage systems.

In Situ Formation of Polycyclic Aromatic Hydrocarbons as an Artificial Hybrid Layer for Lithium Metal Anodes.

Nonuniform Li deposition causes dendrites and low Coulombic efficiency (CE), seriously hindering the practical applications of Li metal. Herein, we developed an artificial solid-state interphase (SEI) with planar polycyclic aromatic hydrocarbons (PAHs) on the surface of Li metal anodes by a facile in situ formation technology. The resultant dihydroxyviolanthron (DHV) layers serve as the protective layer to stabilize the SEI. In addition, the oxygen-containing functional groups in the soft and conformal SEI film can regulate the diffusion and transport of Li ions to homogenize the deposition of Li metal. The artificial SEI significantly improves the CEs and shows superior cyclability of over 1000 h at 4 mAh cm-2. The LiFePO4/Li cell (2.8 mAh cm-2) enables a long cyclability for 300 cycles and high CEs of 99.8%. This work offers a new strategy to inhibit Li dendrite growth and enlightens the design on stable SEI for metal anodes.