Revisiting the four Hexapoda classes: Protura as the sister group to all other hexapods.

Insects represent the most diverse animal group, yet previous phylogenetic analyses based on morphological and molecular data have failed to agree on the evolutionary relationships of early insects and their six-legged relatives (together constituting the clade Hexapoda). In particular, the phylogenetic positions of the three early-diverging hexapod lineages-the coneheads (Protura), springtails (Collembola), and two-pronged bristletails (Diplura)-have been debated for over a century, with alternative topologies implying drastically different scenarios of the evolution of the insect body plan and hexapod terrestrialization. We addressed this issue by sampling all hexapod orders and experimenting with a broad range of across-site compositional heterogeneous models designed to tackle ancient divergences. Our analyses support Protura as the earliest-diverging hexapod lineage ("Protura-sister") and Collembola as a sister group to Diplura, a clade corresponding to the original composition of Entognatha, and characterized by the shared possession of internal muscles in the antennal flagellum. The previously recognized 'Elliplura' hypothesis is recovered only under the site-homogeneous substitution models with partial supermatrices. Our cross-validation analysis shows that the site-heterogeneous CAT-GTR model, which recovers "Protura-sister," fits significantly better than homogeneous models. Furthermore, the morphologically unusual Protura are also supported as the earliest-diverging hexapod lineage by other lines of evidence, such as mitogenomes, comparative embryology, and sperm morphology, which produced results similar to those in this study. Our backbone phylogeny of hexapods will facilitate the exploration of the underpinnings of hexapod terrestrialization and megadiversity.

Hydrate Technologies for CO2 Capture and Sequestration: Status and Perspectives.

CO2 capture and sequestration based on hydrate technology are considered supplementary approaches for reducing carbon emissions and mitigating the greenhouse effect. Direct CO2 hydrate formation and CH4 gas substitution in natural gas hydrates are two of the main methods used for the sequestration of CO2 in hydrates. In this Review, we introduce the crystal structures of CO2 hydrates and CO2-mixed gas hydrates and summarize the interactions between the CO2 molecules and clathrate hydrate/H2O frames. In particular, we focus on the role of diffraction techniques in analyzing hydrate structures. The kinetic and thermodynamic properties then are introduced from micro/macro perspectives. Furthermore, the replacement of natural gas with CO2/CO2-mixed gas is discussed comprehensively in terms of intermolecular interactions, influencing factors, and displacement efficiency. Based on the analysis of related costs, risks, and policies, the economics of CO2 capture and sequestration based on hydrate technology are explained. Moreover, the difficulties and challenges at this stage and the directions for future research are described. Finally, we investigate the status of recent research related to CO2 capture and sequestration based on hydrate technology, revealing its importance in carbon emission reduction.

Charge Redistribution in Mechanochemical Reactions for Solid Interfaces.

Mechanochemical strategies are widely used in various fields, ranging from friction and wear to mechanosynthesis, yet how the mechanical stress activates the chemical reactions at the electronic level is still open. We used first-principles density functional theory to study the rule of the stress-modified electronic states in transmitting mechanical energy to trigger chemical responses for different mechanochemical systems. The electron density redistribution among initial, transition, and final configurations is defined to correlate the energy evolution during reactions. We found that stress-induced changes in electron density redistribution are linearly related to activation energy and reaction energy, indicating the transition from mechanical work to chemical reactivity. The correlation coefficient is defined as the term "interface reactivity coefficient" to evaluate the susceptibility of chemical reactivity to mechanical action for material interfaces. The study may shed light on the electronic mechanism of the mechanochemical reactions behind the fundamental model as well as the mechanochemical phenomena.

Investigating the causal relationship of gut microbiota with GERD and BE: a bidirectional mendelian randomization.

BACKGROUND: Gut microbiota(GM) have been proven associated with lots of gastrointestinal diseases, but its causal relationship with Gastroesophageal reflux disease(GERD) and Barrett's esophagus(BE) hasn't been explored. We aimed to uncover the causal relation between GM and GERD/BE and potential mediators by utilizing Mendelian Randomization(MR) analysis. METHODS: Summary statistics of GM(comprising 301 bacteria taxa and 205 metabolism pathways) were extracted from MiBioGen Consortium(N = 18,340) and Dutch Microbiome Project(N = 7,738), GERD and BE from a multitrait meta-analysis(NGERD=602,604, NBE=56,429). Bidirectional two-sample MR analysis and linkage disequilibrium score regression(LDSC) were used to explore the genetic correlation between GM and GERD/BE. Mediation MR analysis was performed for the risk factors of GERD/BE, including Body mass index(BMI), weight, type 2 diabetes, major depressive disorder(MDD), smoking initiation, alcohol consumption, and dietary intake(including carbohydrate, sugar, fat, protein intake), to detect the potential mediators between GM and GERD/BE. RESULTS: 11 bacterial taxa and 13 metabolism pathways were found associated with GERD, and 18 taxa and 5 pathways exhibited causal relationship with BE. Mediation MR analysis suggested weight and BMI played a crucial role in these relationships. LDSC identified 1 taxon and 4 metabolism pathways related to GERD, and 1 taxon related to BE. Specie Faecalibacterium prausnitzii had a suggestive impact on both GERD(OR = 1.087, 95%CI = 1.01-1.17) and BE(OR = 1.388, 95%CI = 1.03-1.86) and LDSC had determined their correlation. Reverse MR indicated that BE impacted 10 taxa and 4 pathways. CONCLUSIONS: This study established a causal link between gut microbiota and GERD/BE, and identified the probable mediators. It offers new insights into the role of gut microbiota in the development and progression of GERD and BE in the host.

Tuning the Surface Stability and Li/Na Storage of MXenes by Controlling the Surface Termination Coverage.

2D transition metal carbides and/or nitrides, MXenes, are a class of widely studied materials with great potential for energy storage applications. The control of surface chemistry is an effective approach for preparing novel MXenes and modifying their electrochemical properties. However, an in-depth and systematic atomic-scale study of the effect of surface termination on MXene stability and electrochemical performance is scarce and thus is highly desired. Here, through high-throughput first-principles calculations, 28 stable chalcogen-functionalized M2CTz (M = V, Nb, and Ta, T = S, Se, and Te) under different chemical environments are identified. The reduction of termination coverage improves electrical conductivity but weakens in-plane stiffness. Intriguingly, based on charge transfer mechanism, the diffusion barrier of lithium/sodium atoms on the M2CTz exhibits a volcano-like relationship with termination coverage, and the ion diffusion channel formed in half termination coverage greatly accelerates lithium ion diffusion and returns to or exceeds sodium ion diffusion rate at full termination coverage. V2CSe2/Nb2CSz not only displays the large lithium/sodium capacity (592/409-466 mAhg-1) but also exhibits low barrier energy and open-circuit voltage, suggesting a promising candidate anode material for lithium/sodium-ion batteries. These findings provide insights into the design and fabrication of MXenes and tuning the electrochemical performance of MXenes by controlling termination coverage.

Whole-genome-based phylogenetic analyses provide new insights into the evolution of springtails (Hexapoda: Collembola).

Springtails (Collembola) stand as one of the most abundant, widespread, and ancient terrestrial arthropods on earth. However, their evolutionary history and deep phylogenetic relationships remain elusive. In this study, we employed phylogenomic approaches to elucidate the basal relationships among Collembola. We sampled whole-genome data representing all major collembolan lineages in proportion to their known diversity. To account for potential phylogenomic biases, we implemented various data extraction, locus sampling, and signal filtering strategies to generate matrices. Subsequently, we applied a diverse array of tree-searching and rate-modelling methods to reconstruct the phylogeny. Our analyses, utilizing different matrices and methods, converged on the same unrooted relationships among collembolan ingroups, supporting the current ordinal classification and challenging the monophyly of Arthropleona and Symphypleona s.l. However, discrepancies across analyses existed in the root of Collembola. Among various root positions, those based on more informative matrices and biologically realistic models, favoring a basal topology of Entomobryomorpha + (Symphypleona s.s. + (Neelipleona + Poduromorpha)), were supported by subsequent methodological assessment, topology tests, and rooting analyses. This optimal topology suggests multiple independent reduction of the pronotum in non-poduromorph orders and aligns with the plesiomorphic status of neuroendocrine organs and epicuticular structure of Entomobryomorpha. Fossil-calibrated dating analyses based on the optimal topology indicated late-Paleozoic to mid-Mesozoic origins of the crown Collembola and four orders. In addition, our results questioned the monophyly of Isotomidae and Neanuridae, underscoring the need for further attention to the systematics of these families. Overall, this study provides novel insights into the phylogenetic backbone of Collembola, which will inform future studies on the systematics, ecology, and evolution of this significant arthropod lineage.

Prospective, multicenter, self-controlled clinical trial on the effectiveness and safety of a cable-transmission magnetically controlled capsule endoscopy system for the examination of upper GI diseases.

BACKGROUND AND AIMS: Many GI disorders and precancerous conditions often present asymptomatically, leading to delayed patient diagnoses and treatment interventions. In this study, we developed a novel cable-transmission magnetically controlled capsule endoscopy (CT-MCCE) system for detecting GI diseases and assessed its safety and feasibility through clinical trials. METHODS: This prospective, multicenter trial compared CT-MCCE with conventional gastroscopy in patients aged 18 to 75 years with upper GI tract diseases between October 2022 and July 2023. The primary endpoints were the evaluation of sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) in the detection of focal lesions within the esophagus, stomach, and duodenal bulb using CT-MCCE. RESULTS: One hundred eighty individuals (mean age, 43.1 years; 52.22% women) were recruited from 3 hospitals in China. CT-MCCE detected lesions in the esophagus with a sensitivity of 97.22%, specificity of 100%, PPV of 100%, NPV of 98.18%, and accuracy of 98.89%; detected gastric focal lesions in the entire stomach with a sensitivity of 96.81%, specificity of 98.84%, PPV of 98.91%, NPV of 96.59%, and accuracy of 97.78%; and detected lesions in the duodenal bulb with a sensitivity of 100%, specificity of 100%, PPV of 100%, NPV of 100%, and accuracy of 100%. There were no significant differences between CT-MCCE and EGD regarding the cleanliness of the upper GI tract and visibility of the upper GI mucosa. However, CT-MCCE was associated with a lower incidence of discomfort than EGD (P < .001). CONCLUSIONS: The diagnostic performance of CT-MCCE is comparable with that of EGD in the completion of upper GI tract examinations and lesion detection. Furthermore, the improved tolerance of CT-MCCE in detecting upper GI diseases was noted without any observed adverse events. (Clinical trial registration number: ChiCTR2200063630.).

Electrochromic Smart Window Based on Transition-Metal Phthalocyanine Derivatives.

Phthalocyanines have been widely investigated as electrochromic materials because of their large conjugated structure. However, they have shown limited applicability due to their complex electrochromism mechanism and low solubility in common organic solvents. Replacement of central metal ions in phthalocyanines affects their stability and is responsible for various electrochromic phenomena, such as color change. Herein, the relationship between the electron d-orbital arrangement in the outermost layer of transition metals and the electrochromic stability of phthalocyanine derivatives has been investigated. An enhanced solubility of phthalocyanines in organic solvents was obtained through the introduction of quaternary tert-butyl substitution. Electrochromic devices fabricated with transition-metal phthalocyanine derivatives showed high response speeds and good stability. The fast color-switching feature between blue/green and blue/purple makes it a promising candidate for smart windows and adaptive camouflage applications.

Efficacy of Donor-Recipient-Matched Faecal Microbiota Transplantation in Patients with IBS-D: A Single-Centre, Randomized, Double-Blind Placebo-Controlled Study.

INTRODUCTION: The imbalance in gut microbiota is contributing to the development and progression of IBS. FMT can improve the gut microbiota, and donor-recipient-matched FMT can help develop individualized treatment plans according to different enterotypes. This study aimed to explore the efficacy of donor-recipient-matched FMT in IBS with predominant diarrhoea (IBS-D) and evaluate its effects on gut microbiota. METHODS: Twenty-seven patients with IBS-D were randomly divided into donor-recipient-matched FMT group (group P), random-donor FMT group (group R), and placebo group (group B). All participants received corresponding FMT treatment after filling in IBS-S, IBS-QoL, GSRS, and HADS questionnaires and having their stool samples collected at 4, 8, and 12 weeks after treatment. The improvement in the symptoms and the changes in the bacterial flora were analysed for three groups. RESULTS: The IBS-SSS, IBS-QoL, GSRS, and anxiety scores of group P were significantly lower after treatment (p < 0.05). The IBS-QoL scores of group R were significantly lower after treatment (p < 0.05). Beta diversity analysis showed that the gut microbiota of group P had an obvious trend of classification after treatment. Seven bacterial genera were related to the differences in the IBS-SSS scores before and after treatment. CONCLUSION: Donor-recipient-matched FMT significantly improved the clinical symptoms, quality of life, and anxiety scores of the patients with IBS-D than random-donor FMT.

A Rare Case of Benign Recurrent Intrahepatic Cholestasis Initially Diagnosed in Middle-age.

Background: Repeated episodes of jaundice and pruritus are common in a group of autosomal recessive liver diseases known as benign recurrent intrahepatic cholestasis. Benign recurrent intrahepatic cholestasis (BRIC) is divided into two types, type 1 and type 2, and is caused by mutations in the ATP8B1 and ABCB11 genes. Here, we report a rare case of BRIC type 2 mutation. Case presentation: A 45-year-old Chinese man had three frequent episodes of jaundice marked by extensive excoriation and severe pruritis, although he had no prior history of jaundice. Laboratory investigations showed no evidence of liver damage caused by viral, autoimmune, or acquired metabolic etiologies. The CT scan revealed an enlarged gallbladder with numerous punctate high-density shadows, while no wall thickening was observed. Endoscopic ultrasonography showed no evidence of dilation of the intrahepatic and extrahepatic bile duct, as well as the absence of gallstone. Diagnostic evaluation: Immunohistochemical examinations of liver biopsy samples showed cytokeratin-7 positive hepatocytes, suggesting chronic intrahepatic cholestasis. The reticulin fiberstaining demonstrated that the portions of the hepatic plate in the center of the lobule were asymmetrically organized,and somewhat enlarged, with collapsed areas indicating intralobular inflammation. Moreover, there were areas of collapse that indicated the presence of intralobular inflammation. Whole exome sequencing revealed mutations in the ABCB11 gene; c.3084A>G, p.A1028A homozygous mutation (chr2-169789016), and c.2594C>T, p.A865V heterozygous mutation (chr2-169801131). Based on these findings, the final diagnosis of the patient was metabolism-related jaundice. Treatment: Apart from receiving tapering dosage of prednisone to lower bilirubin levels, the patient received no extra care. Conclusion: The comprehensive diagnosis of a middle-aged male patient with BRIC-2, which involved extensive radiological, hematological, and genetic investigations, informed a tailored tapering prednisone regimen, highlighting the importance of personalized medicine in managing atypical presentations of this rare cholestatic disorder.

Charge Density Evolution Governing Interfacial Friction.

It is well-known that the electron nature of a solid in contact plays a predominant role in determining the many properties of the contact systems, but the general rules of electron coupling that govern interfacial friction remain an open issue for the surface/interface community. Here, density functional theory calculations were used to investigate the physical origins of friction of solid interfaces. It was found that interfacial friction can be inherently traced back to the electronic barrier to the change in the contact configuration of the joints in slip due to the resistance of energy level rearrangement leading to electron transfer, which applies for various interface types ranging from van der Waals, metallic, and ionic to covalent joints. The variation of the electron density accompanying contact conformation changes along the sliding pathways is defined to track the frictional energy dissipation process occurring in slip. The results demonstrate that the frictional energy landscapes evolve synchronously with responding charge density evolution along sliding pathways, yielding an explicitly linear dependence of frictional dissipation on electronic evolution. The correlation coefficient enables us to interpret the fundamental concept of shear strength. The present charge evolution model thereby provides insights into the classic hypothesis that the friction force scales with the real contact area. This may shed light on the intrinsic origin of friction at the electronic level, opening the way to the rational design of nanomechanical devices as well as the understanding of the natural faults.

Field-Gradient-Focusing Ion Guide for Enhanced Transfer Efficiency of Low-Mass Ions.

Efficient transmission of low-mass ions in a rough vacuum pressure region has always been a challenging issue in mass spectrometry (MS). In this study, a novel ion guide, namely, field-gradient-focusing ion guide (FGF-IG), was proposed to improve the transfer efficiency of ions, especially low-mass ions in a rough vacuum region. The FGF-IG has 12 electrodes whose surfaces gradually narrowed and tilted inward, and its electric field gradually varies from dodecapole (or multipole) to quadrupole along the ion transfer route. The field radius was gradually decreased from 6 to 2 mm in the multipole region (65 mm in length) and finally remained unchanged as 2 mm in the quadrupole region (20 mm in length). By integrating into a miniature mass spectrometer (mini-MS) with a continuous atmospheric pressure interface, this ion guide was optimized in terms of inlet capillary position, radio frequency amplitude, and direct current voltage applied on it. Results showed that a reduced low-mass discrimination effect and improved efficiency of simultaneously transferring mid and low m/z ions were achieved for FGF-IG compared with a conventional ion funnel. Under optimized conditions, a limit of detection of 1 ng/mL was obtained for both reserpine (m/z 609) and arginine (m/z 175) ions by integrating FGF-IG into the mini-MS. The sensitivity of smaller arginine ions using FGF-IG was enhanced by ∼10 times than that obtained using the conventional ion funnel (10 ng/mL) in comparative experiments. The idea of smooth transfer from dodecapole to quadrupole fields could be extended to other multipole fields, as well as in lab-scale MS instruments.

Genome-wide meta-analysis identifies susceptibility loci for autoimmune hepatitis type 1.

BACKGROUND AND AIMS: Autoimmune hepatitis (AIH) is a rare and chronic autoimmune liver disease. While genetic factors are believed to play a crucial role in the etiopathogenesis of AIH, our understanding of these genetic risk factors is still limited. In this study, we aimed to identify susceptibility loci to further understand the pathogenesis of this disease. APPROACH AND RESULTS: We conducted a case-control association study of 1,622 Chinese patients with AIH type 1 and 10,466 population controls from two independent cohorts. A meta-analysis was performed to ascertain variants associated with AIH type 1. A single-nucleotide polymorphism within the human leukocyte antigen (HLA) region showed the strongest association with AIH (rs6932730: OR = 2.32; p = 9.21 × 10-73 ). The meta-analysis also identified two non-HLA loci significantly associated with AIH: CD28/CTLA4/ICOS on 2q33.3 (rs72929257: OR = 1.31; p = 2.92 × 10-9 ) and SYNPR on 3p14.2 (rs6809477: OR = 1.25; p = 5.48 × 10-9 ). In silico annotation, reporter gene assays, and CRISPR activation experiments identified a distal enhancer at 2q33.3 that regulated expression of CTLA4. In addition, variants near STAT1/STAT4 (rs11889341: OR = 1.24; p = 1.34 × 10-7 ), LINC00392 (rs9564997: OR = 0.81; p = 2.53 × 10-7 ), IRF8 (rs11117432: OR = 0.72; p = 6.10 × 10-6 ), and LILRA4/LILRA5 (rs11084330: OR = 0.65; p = 5.19 × 10-6 ) had suggestive association signals with AIH. CONCLUSIONS: Our study identifies two novel loci (CD28/CTLA4/ICOS and SYNPR) exceeding genome-wide significance and suggests four loci as potential risk factors. These findings highlight the importance of costimulatory signaling and neuro-immune interaction in the pathogenesis of AIH.

The Value of RBP4 in Assessing Coronary Artery Elasticity in Patients with Coronary Heart Disease and Type 2 Diabetes Mellitus.

Background: Existing research has shown that retinol binding protein (RBP4) has an impairing effect on arterial elasticity and induces insulin resistance, but the clinical value of RBP4 in patients with coronary heart disease (CHD) combined with type 2 diabetes mellitus (T2DM) has not been investigated. This study sought to compare the complexity of coronary artery lesions and coronary artery elasticity between patients with CHD combined with T2DM and those with CHD without T2DM, analyze the risk factors affecting coronary artery elasticity, and investigate the value of RBP4 in assessing coronary artery elasticity in patients with CHD and T2DM. Methods: A total of 130 patients with confirmed CHD were consecutively enrolled, including 38 patients with CHD combined with T2DM and 92 patients with CHD without T2DM. Basic clinical data, laboratory findings, coronary angiography and intravascular ultrasound (IVUS) imaging data, and Gensini scores and coronary artery elasticity parameters were calculated in both groups. Elasticity parameters included: stiffness parameter ( ß ), pressure-strain elastic modulus ( E p ), distensibility coefficient (DC), and compliance coefficient (CC). Multiple linear regression equations were established with elasticity parameters as dependent variables to explore the factors influencing coronary artery elasticity parameters in patients within the two groups. Results: Compared with patients in the CHD without T2DM group, patients in the CHD combined with T2DM group had higher RBP4 levels, Gensini scores, ß and E p values, and lower DC and CC values. Linear regression analysis showed that Gensini score increased with higher ß and E p values and decreased with higher DC and CC values. In all patients in the CHD and CHD combined with T2DM groups, RBP4 was an independent risk factor for ß values after correction for confounders by multiple linear regression analysis, whereas in patients in the CHD without T2DM group, the effect of RBP4 on ß values was not statistically different. Conclusions: RBP4 was an independent risk factor of coronary artery elasticity in CHD patients with T2DM and in overall CHD patients, but it did not affect coronary artery elasticity in CHD patients without T2DM.

Specific Loss of ABCA1 (ATP-Binding Cassette Transporter A1) Suppresses TCR (T-Cell Receptor) Signaling and Provides Protection Against Atherosclerosis.

BACKGROUND: ABCA1 (ATP-binding cassette transporter A1) mediates cholesterol efflux to apo AI to maintain cellular cholesterol homeostasis. The current study aims to investigate whether T-cell-specific deletion of ABCA1 modulates the phenotype/function of T cells and the development of atherosclerosis. METHODS: Mice with T-cell-specific deletion of ABCA1 on low-density lipoprotein receptor knockout (Ldlr-/-) background (Abca1CD4-/CD4-Ldlr-/-) were generated by multiple steps of (cross)-breedings among Abca1flox/flox, CD4-Cre, and Ldlr-/- mice. RESULTS: Deletions of ABCA1 greatly suppressed cholesterol efflux to apo AI but slightly reduced membrane lipid rafts on T cells probably due to the upregulation of ABCG1. Moreover, ABCA1 deficiency impaired TCR (T-cell receptor) signaling and inhibited the survival and proliferation of T cells as well as the formation of effector memory T cells. Despite the comparable levels of plasma total cholesterol after Western-type diet feeding, Abca1CD4-/CD4-Ldlr-/- mice showed significantly attenuated arterial accumulations of T cells and smaller atherosclerotic lesions than Abca1+/+Ldlr-/-controls, which were associated with reduced surface CCR5 (CC motif chemokine receptor 5) and CXCR3 (CXC motif chemokine receptor 3), decreased antiapoptotic Bcl-2 (B-cell lymphoma 2) and Bcl-xL (B-cell lymphoma extra-large), and hampered abilities to produce IL (interleukin)-2 and IFN (interferon)-γ by ABCA1-deficient T cells. CONCLUSIONS: ABCA1 is essential for T-cell cholesterol homeostasis. Deletion of ABCA1 in T cells impairs TCR signaling, suppresses the survival, proliferation, differentiation, and function of T cells, thereby providing atheroprotection in vivo.

AisNet: A Universal Interatomic Potential Neural Network with Encoded Local Environment Features.

This paper proposes a new interatomic potential energy neural network, AisNet, which can efficiently predict atomic energies and forces covering different molecular and crystalline materials by encoding universal local environment features, such as elements and atomic positions. Inspired by the framework of SchNet, AisNet consists of an encoding module combining autoencoder with embedding, the triplet loss function and an atomic central symmetry function (ACSF), an interaction module with a periodic boundary condition (PBC), and a prediction module. In molecules, the prediction accuracy of AisNet is comparabel with SchNet on the MD17 dataset, mainly attributed to the effective capture of chemical functional groups through the interaction module. In selected metal and ceramic material datasets, the introduction of ACSF improves the overall accuracy of AisNet by an average of 16.8% for energy and 28.6% for force. Furthermore, a close relationship is found between the feature ratio (i.e., ACSF and embedding) and the force prediction errors, exhibiting similar spoon-shaped curves in the datasets of Cu and HfO2. AisNet produces highly accurate predictions in single-commponent alloys with little data, suggesting the encoding process reduces dependence on the number and richness of datasets. Especially for force prediction, AisNet exceeds SchNet by 19.8% for Al and even 81.2% higher than DeepMD on a ternary FeCrAl alloy. Capable of processing multivariate features, our model is likely to be applied to a wider range of material systems by incorporating more atomic descriptions.

Multielemental single-atom-thick A layers in nanolaminated V2(Sn, A) C (A = Fe, Co, Ni, Mn) for tailoring magnetic properties.

Tailoring of individual single-atom-thick layers in nanolaminated materials offers atomic-level control over material properties. Nonetheless, multielement alloying in individual atomic layers in nanolaminates is largely unexplored. Here, we report 15 inherently nanolaminated V2(A xSn1-x)C (A = Fe, Co, Ni, Mn, and combinations thereof, with x ∼ 1/3) MAX phases synthesized by an alloy-guided reaction. The simultaneous occupancy of the 4 magnetic elements and Sn in the individual single-atom-thick A layers constitutes high-entropy MAX phase in which multielemental alloying exclusively occurs in the 2-dimensional (2D) A layers. V2(A xSn1-x)C exhibit distinct ferromagnetic behavior that can be compositionally tailored from the multielement A-layer alloying. Density functional theory and phase diagram calculations are performed to understand the structure stability of these MAX phases. This 2D multielemental alloying approach provides a structural design route to discover nanolaminated materials and expand their chemical and physical properties. In fact, the magnetic behavior of these multielemental MAX phases shows strong dependency on the combination of various elements.

Bioorthogonal Reaction-Mediated Tumor-Selective Delivery of CRISPR/Cas9 System for Dual-Targeted Cancer Immunotherapy.

CRISPR system-assisted immunotherapy is an attractive option in cancer therapy. However, its efficacy is still less than expected due to the limitations in delivering the CRISPR system to target cancer cells. Here, we report a new CRISPR/Cas9 tumor-targeting delivery strategy based on bioorthogonal reactions for dual-targeted cancer immunotherapy. First, selective in vivo metabolic labeling of cancer and activation of the cGAS-STING pathway was achieved simultaneously through tumor microenvironment (TME)-biodegradable hollow manganese dioxide (H-MnO2 ) nano-platform. Subsequently, CRISPR/Cas9 system-loaded liposome was accumulated within the modified tumor tissue through in vivo click chemistry, resulting in the loss of protein tyrosine phosphatase N2 (PTPN2) and further sensitizing tumors to immunotherapy. Overall, our strategy provides a modular platform for precise gene editing in vivo and exhibits potent antitumor response by boosting innate and adaptive antitumor immunity.

Clinical efficacy and safety of fluticasone/salmeterol inhalation powder combined with huaiqihuang granules in the treatment of children with cough variant asthma.

This study was to evaluate the clinical efficacy and safety of fluticasone/ salmeterol inhalation powder plus Huaiqihuang Granules for children with cough variant asthma (CVA). From June 2019 to May 2021, 60 children with CVA were hospitalized to the Pediatrics Department of Cangzhou Central Hospital and randomized to the observation (fluticasone/salmeterol inhalation powder plus huaiqihuang granules) and control group (fluticasone/salmeterol inhalation powder) using the random number table method. The outcome measures include clinical efficacy, forced vital capacity (FVC), forced expiratory volume per second (FEV1), peak expiratory flow (PEF), FeNO, high-sensitivity C-reactive protein (hs-CRP), interleukin-17 (IL-17) and IL-23, airway anatomical indicators and T lymphocyte subsets levels. Both groups exhibited remarkable improvements in FVC, FEV1, PEF and FeNO and hs-CRP, IL-17 and IL-23, with higher FVC, FEV1 and PEF and lower FeNO, hs-CRP, IL-17 and IL-23 in the observation group (all P<0.05). Significantly higher levels of CD4+ and CD4+/CD8+ were observed in the observation group versus control group, but lower airway wall thickness, basement membrane thickness, total airway wall area and CD8+ in the observation group (all P<0.05). Fluticasone/salmeterol inhalation powder plus Huaiqihuang Granules improves lung function, FeNO and airway inflammation in children with CVA and boosts cellular and humoral immune function.

Multistage-Responsive Gene Editing to Sensitize Ion-Interference Enhanced Carbon Monoxide Gas Therapy.

As a promising therapeutic modality targeting cancer, gas therapy still faces critical challenges, especially in enhancing therapeutic efficacy and avoiding gas poisoning risks. Here, a pH/glutathione (GSH) dual stimuli-responsive CRISPR/Cas9 gene-editing nanoplatform combined with calcium-enhanced CO gas therapy for precise anticancer therapy, is established. In the tumor microenvironment (TME), the fast biodegradation of the CaCO3 layer via pH-induced hydrolyzation allows glucose oxidase (GOx) to catalyze glucose for H2 O2 production, which further reacts with manganese carbonyl (MnCO) and achieves the precise release of CO gas. Simultaneously, in situ Ca2+ overload from CaCO3 degradation disturbs mitochondrial Ca2+ homeostasis, resulting in Ca2+ -driven reactive oxygen species (ROS) formation and subsequent mitochondrial apoptosis signaling pathway activation. Subsequently, by GSH-induced cleavage of a disulfide bond, the released Cas9/sgRNA (RNP) can achieve nuclear factor E2-related factor 2 (Nrf2) gene ablation to sensitize gas therapy by interfering with ROS signaling. This therapeutic modality endows codelivery of CRISPR, ions, and gas with smart control features, which demonstrates great potential for future clinical applications in precise nanomedicine.