Landscape and Dynamics of Single Immune Cells in Hepatocellular Carcinoma.

The immune microenvironment of hepatocellular carcinoma (HCC) is poorly characterized. Combining two single-cell RNA sequencing technologies, we produced transcriptomes of CD45+ immune cells for HCC patients from five immune-relevant sites: tumor, adjacent liver, hepatic lymph node (LN), blood, and ascites. A cluster of LAMP3+ dendritic cells (DCs) appeared to be the mature form of conventional DCs and possessed the potential to migrate from tumors to LNs. LAMP3+ DCs also expressed diverse immune-relevant ligands and exhibited potential to regulate multiple subtypes of lymphocytes. Of the macrophages in tumors that exhibited distinct transcriptional states, tumor-associated macrophages (TAMs) were associated with poor prognosis, and we established the inflammatory role of SLC40A1 and GPNMB in these cells. Further, myeloid and lymphoid cells in ascites were predominantly linked to tumor and blood origins, respectively. The dynamic properties of diverse CD45+ cell types revealed by this study add new dimensions to the immune landscape of HCC.

Recent progress in the advanced strategies, rational design, and engineering of electrocatalysts for nitrate reduction toward ammonia.

Ammonia is a valuable feedstock for most chemicals, pharmaceuticals, and fertilizer products. It is a promising carbon-free energy source. Under severe experimental circumstances (high temperature and high pressure), ammonia is manufactured industrially using the standard Haber-Bosch process. This process uses a lot of energy and emits a huge amount of CO2 into the environment. One method that is seen to be promising and could eventually replace the Haber-Bosch process is the electrocatalytic production of ammonia. However, in ambient conditions, the cleavage of the nitrogen molecule is exceedingly difficult. As a result, the yield of ammonia remains modest and the study's scope is still restricted to the lab. When the catalytic performance is significantly increased, nitrate and nitrite contaminations in water systems can be effectively removed and simultaneously transformed into energy sources if nitrites or nitrates are employed as nitrogen sources instead of nitrogen gas. This may become a new substitute for the synthesis of ammonia, but nitrate and nitrite reduction are not getting enough attention. In this review, we discuss the performance of the electrocatalytic nitrate reduction reaction, which includes cycling stability, reactivity, selectivity, and faradaic efficiency. Following this summary, we look into the crucial elements, the rate-determining step, and the reaction mechanisms that govern the performance of the nitrate reduction reaction. In order to support the practical use of the electrocatalytic nitrate reduction reaction, we finally provided a summary of the challenges and future directions guiding the design of efficient catalyst and reaction systems.

Angiotensin II type-2 receptor signaling facilitates liver injury repair and regeneration via inactivation of Hippo pathway.

The angiotensin II type 2 receptor (AT2R) is a well-established component of the renin-angiotensin system and is known to counteract classical activation of this system and protect against organ damage. Pharmacological activation of the AT2R has significant therapeutic benefits, including vasodilation, natriuresis, anti-inflammatory activity, and improved insulin sensitivity. However, the precise biological functions of the AT2R in maintaining homeostasis in liver tissue remain largely unexplored. In this study, we found that the AT2R facilitates liver repair and regeneration following acute injury by deactivating Hippo signaling and that interleukin-6 transcriptionally upregulates expression of the AT2R in hepatocytes through STAT3 acting as a transcription activator binding to promoter regions of the AT2R. Subsequently, elevated AT2R levels activate downstream signaling via heterotrimeric G protein Gα12/13-coupled signals to induce Yap activity, thereby contributing to repair and regeneration processes in the liver. Conversely, a deficiency in the AT2R attenuates regeneration of the liver while increasing susceptibility to acetaminophen-induced liver injury. Administration of an AT2R agonist significantly enhances the repair and regeneration capacity of injured liver tissue. Our findings suggest that the AT2R acts as an upstream regulator in the Hippo pathway and is a potential target in the treatment of liver damage.

Methylthiophenyl- and Methylthiobiphenyl-Substituted A2B CoIIIcorroles: Modulating Electrocatalyzed Hydrogen Evolution Reactions on Surface-Modified Gold Electrodes.

Four A2B-type CoIIIcorroles (2a-2d) with electron-donating/withdrawing substituents at the A2 meso-aryl substituents and a 4-(methylthio)phenyl ring at the B position have been synthesized and characterized, along with a series of meso-extended CoIIIcorroles (4a-4c) with 4'-(methylthio)biphenyl moieties. The electronic structures and structure-property relationships of the dyes have been analyzed by comparing their redox and optical properties to trends predicted in density functional theory calculations. Au electrodes surface-modified with 2a-2d and 4a-4c are highly efficient catalysts for electrocatalyzed hydrogen evolution reactions, and the electrocatalytic properties can be readily modulated by fine-tuning the electronic structure of the CoIIIcorrole and the distance between the "Au-S" bond and CoIII center.

Single silicon-doped CNT as a metal-free electrode for robust nitric oxide reduction utilizing a Lewis base site: an ingenious electronic "Reflux-Feedback" mechanism.

The electrocatalytic reduction of nitric oxide (NO) has become the most charming approach for the sustainable synthesis of ammonia (NH3), however, the development of a valid catalyst endowed with low cost, high efficiency, and long-term endurance still faces an enormous challenge. In view of the famous concept of "donate and accept", various transition metal-based electrodes have been predicted and brought into production for electrocatalysis, but metal-free materials or novel activation mechanisms are rarely reported. Here, metal-free electrocatalysts, namely individual silicon (Si) atom-embedded single-walled carbon nanotubes (CNTs), for the NO reduction reaction (NORR) were put forward by performing first-principles calculations. The results disclose that the discarded NO can be converted into value-added NH3 on Si-CNT(10, 0) with a limiting potential of -0.25 V. Importantly, the doped Si atom acts as a Lewis base site that drives some of the p-orbital electrons to return to the surrounding carbon atoms and then feed adequate electron back to intermediates, rendering it more flat for the electroreduction progress. In summary, the designed carbon-based electrode holds great promise for experimental trial and offers a certain degree of theoretical guidance.

Theoretical insight into the essential role of charged surface for ammonia synthesis: Si-decorated carbon nitride electrode.

We report a new Si-decorated carbon nitride (C5N2H2) electrode for the sustainable generation of a hydrogen storage medium, ammonia (NH3), which not only possesses sound electrical conductivity, dynamic stability, and electrochemical activity for the nitric oxide/nitrogen reduction reaction (NORR/NRR), but also provides an option for designing metal-free electrodes. Most importantly, it is found that the charged surface is of great significance to the improved catalytic performance compared to the neutral condition, but this has always been overlooked. Herein, by means of DFT computations, the stubborn chemical bonds of NO and N2 can be entirely activated under an electron density of -2.15 × 10-2 e Å-2 on the Si-C5N2H2 material with an inconsiderable kinetic energy barrier (0.28 eV) along the protonation path. In brief, this finding paves a way for understanding false results by theoretical calculations compared to experiments.

Renal hemodynamic evaluation protocol based on the pathophysiological mechanism of acute kidney injury: Critical Care UltraSound Guided-A(KI)BCDE.

The multiple etiological characteristics of acute kidney injury (AKI) have brought great challenges to its clinical diagnosis and treatment. Renal injury in critically ill patients always indicates hemodynamic injury. The Critical Care UltraSound Guided (CCUSG)-A(KI)BCDE protocol developed by the Chinese Critical Ultrasound Study Group (CCUSG), respectively, includes A(KI) diagnosis and risk assessment and uses B-mode ultrasound, Color doppler ultrasound, spectral Doppler ultrasound, and contrast Enhanced ultrasound to obtain the hemodynamic characteristics of the kidney so that the pathophysiological mechanism of the occurrence and progression of AKI can be captured and the prognosis of AKI can be predicted combined with other clinical information; therefore, the corresponding intervention and treatment strategies can be formulated to achieve targeted, protocolized, and individualized therapy.

Effects of Nanoparticle Size on the Thermal Decomposition Mechanisms of 3,5-Diamino-6-hydroxy-2-oxide-4-nitropyrimidone through ReaxFF Large-Scale Molecular Dynamics Simulations.

ReaxFF-lg molecular dynamics method was employed to simulate the decomposition processes of IHEM-1 nanoparticles at high temperatures. The findings indicate that the initial decomposition paths of the nanoparticles with different sizes at varying temperatures are similar, where the bimolecular polymerization reaction occurred first. Particle size has little effect on the initial decomposition pathway, whereas there are differences in the numbers of the species during the decomposition and their evolution trends. The formation of the hydroxyl radicals is the dominant decomposition mechanism with the highest reaction frequency. The degradation rate of the IHEM-1 molecules gradually increases with the increasing temperature. The IHEM-1 nanoparticles with smaller sizes exhibit greater decomposition rate constants. The activation energies for the decomposition are lower than the reported experimental values of bulk explosives, which suggests a higher sensitivity.

Near-infrared plasmonic sensing and digital metasurface via double Fano resonances.

Plasmonic sensing that enables the detection of minute events, when the incident light field interacts with the nanostructure interface, has been widely applied to optical and biological detection. Implementation of the controllable plasmonic double Fano resonances (DFRs) offers a flexible and efficient way for plasmonic sensing. However, plasmonic sensing and digital metasurface induced by tailorable plasmonic DFRs require further study. In this work, we numerically and theoretically investigate the near-infrared plasmonic DFRs for plasmonic sensing and digital metasurface in a hybrid metasurface with concentric ϕ-shaped-hole and circular-ring-aperture unit cells. We show that a plasmonic Fano resonance, resulting from the interaction between a narrow and a wide effective dipolar modes, can be realized in the ϕ-shaped hybrid metasurface. In particular, we demonstrate that the tailoring plasmonic DFRs with distinct mechanisms of actions can be accomplished in three different ϕ-shaped hybrid metasurfaces. Moreover, the resonance mode-broadening and mode-shifting plasmonic sensing can be fulfilled by modulating the polarization orientation and the related geometric parameters of the unit cells in the near-infrared waveband, respectively. In addition, the plasmonic switch with a high ON/OFF ratio can not only be achieved but also be exploited to establish a single-bit digital metasurface, even empower to implement two- and three-bit digital metasurface characterized by the plasmonic DFRs in the telecom L-band. Our results offer a new perspective toward realizing polarization-sensitive optical sensing, passive optical switches, and programmable metasurface devices, which also broaden the landscape of subwavelength nanostructures for biosensors and optical communications.

Strongly Coupled Nitrogen-Doped Mo2C@CoNi Alloy Hybrid Architecture toward Efficient Hydrogen Evolution Reaction.

Development of high-efficiency electrocatalysts for water splitting is a promising channel to produce clean hydrogen energy. Herein, we demonstrate that the combination of nitrogen-doped Mo2C and CoNi alloy to form a hybrid architecture is an effective way to produce hydrogen from electrochemical water splitting. Benefiting from a combination of mechanisms, the optimized N-Mo2C@CoNi-650 shows remarkable hydrogen evolution reaction (HER) activity with small overpotentials of 35, 123, and 220 mV to reach the current density of 10, 50, and 100 mA cm-2 in alkaline media, respectively, outperforming most previously reported HER electrocatalysts. The efficient electrocatalytic performance is ascribed to the highly exposed active sites, fast reaction kinetics, and improved charge-transfer steaming from the synergistic effect between each component. This work presents a new insight into designing and preparing highly efficient electrocatalysts toward the HER.

Subtotal gastrectomy pancreaticoduodenectomy versus conventional pancreaticoduodenectomy in the incidence of delayed gastric emptying: single-center retrospective cohort study.

BACKGROUND: Delayed gastric emptying (DGE) is one of the most common complications after pancreaticoduodenectomy (PD). There is currently no widely accepted procedure for PD to reduce the incidence of DGE. Our institution attempts to perform subtotal gastrectomy in patients undergoing PD to reduce DGE. Here we aimed to evaluate the effectiveness and safety of PD with subtotal gastric resection. METHODS: Patients who underwent PD between January 2014 and December 2021 were reviewed. They were stratified by extent of gastrectomy into a conventional PD group (PD that resected approximately 1/3 of the distal stomach) and a subtotal gastrectomy PD group (PD that resected approximately 3/4 of the distal stomach), which were compared in terms of intraoperative and postoperative parameters. RESULT: From January 2014 to December 2021, a total of 512 patients underwent PD in the Department of Hepatobiliary Surgery, Peking University People's Hospital. Nineteen patients were excluded from this study due to benign disease. A total of 493 patients were included, with 378 in the conventional PD group and 115 in the subtotal gastrectomy PD group. Compared with the conventional PD group, the subtotal gastrectomy PD group had a lower incidence of DGE (8.7% vs. 17.7%, p = 0.019), and a shorter hospital stay. Multivariate analysis showed that conventional PD and higher body mass index were independent risk factors for grade B/C DGE. CONCLUSION: This study showed that, compared with conventional PD, subtotal gastrectomy PD can reduce the incidence of DGE and shorten the length of hospital stay. At the same time, subtotal gastrectomy PD is comparable to conventional PD in terms of surgical safety. Furthermore, high BMI is an independent risk factor for postoperative DGE.

Effects of Cocrystallization on the Structure and Properties of Melt-Cast Explosive 2,4-Dinitroanisole: A Computational Study.

Melt-cast explosive 2,4-dinitroanisole (DNAN) crystal and its cocrystals DNAN/1,3-dinitrobenzene (DNB) and DNAN/2-nitroaniline (NA) were used to identify the effects of cocrystallization on the crystal structure, non-covalent interactions, and melting points of the DNAN crystal through density functional theory and molecular dynamics. The components DNB and NA with subtle structure variations between the nitro group and amino group can significantly affect the non-covalent interactions, especially the π-π stacking and H-bonds, which can lead to different crystal stacking styles. The melting points of the DNAN crystal are decreased through the cocrystallization, which expands the utilization of the DNAN-based melt cast explosives. Our study deciphers the effects caused by the cocrystallization on the structure and properties of melt cast explosives and may help to design and optimize novel melt-cast explosives.

Using a Thin ZnO Film as an Intermediate Layer to Tune the Performance of Mg-Based Nanolaminates: A First-Principles Study.

Recently, an interface engineering method using a thin ZnO film as an intermediate layer was employed to tune the performance of nanothermites. The deposition-related surface chemistry of nanolaminates dominates the ignition and combustion performances of the nanothermites. We performed first-principles calculations and ab initio molecular dynamics simulations to study the chemical mechanisms of adsorption and penetration for Mg on the ZnO polar surface during the early stage of interface formation. The results show that the Mg adatom tends to be adsorbed on the fcc and hcp sites of the surface. The formation of an initial mixed interface is spontaneous at room temperature. The subsurface layer of Zn migrates above the surface, that is, the segregation of Zn on the ZnO surface. The thin ZnO film can act as a barrier layer to avoid the diffusion contact of Mg and Zn atoms with CuO. Our work provides some theoretical insights for tuning the performance of the nanolaminates through interface engineering at atomic and electronic levels.

Controllable magnetization precession dynamics and damping anisotropy in Co2FeAl Heusler-alloy films.

Magnetization dynamics of the epitaxially-grown Co2FeAl (CFA) thin films have been systematically investigated by the time-resolved magneto-optical Kerr effect (TR-MOKE). The dependences of precession frequency f, relaxation time τ and magnetic damping factor α upon the orientation of applied magnetic field are found to have a strong four-fold symmetry. Two series of samples with various substrate temperatures (Ts) and thickness (tCFA) were prepared and a large Gilbert damping difference between the hard and easy axes is extracted to be 3.3 × 10-3 after subtracting the extrinsic contributions of spin pumping, two-magnon scattering and magnetic inhomogeneities. The four-fold variation of Gilbert damping relates closely to the in-plane magnetocrystalline anisotropy and can be attributed to the anisotropic distribution of spin-orbit coupling. Our findings provide new insights into the anisotropic properties of magnetization and damping, which is very helpful for designing and optimizing advanced spintronic devices on different demands.

Cis-Trans Isomerization and Thermal Decomposition Mechanisms of a Series of Nx (x = 4, 8, 10, 11) Chain-Catenated Energetic Crystals.

Nitrogen-rich compounds based on heteroaromatic rings with different lengths of nitrogen chains are at the forefront of the energetic materials field. We studied the decomposition processes and reaction kinetics of a series of Nx (x = 4, 8, 10, 11) chain-catenated energetic crystals at various temperatures (2400-3000 K) based on a combinational strategy based on density functional tight binding molecular dynamics (DFTB-MD) simulations and density functional theory (DFT). The results show that the thermal decomposition and reaction kinetics are dependent on both the temperature and nitrogen chain's length. There are two sequential stages in the initial decomposition process for the crystals N8 and N10: (i) competition between cis-trans isomerization and initial unimolecular decomposition and (ii) subsequent complicated global decomposition reactions. Increasing either the temperature or nitrogen chain's length will accelerate the competition and make initial decomposition dominate. However, cis-trans isomerization does not occur in the crystals N4 and N11. The dominant initiation paths for N4, N8, and N10 occur in the heterocycle and in the bond between the heterocycle and azo group, while that for N11 is ring elimination. The decomposition reactions exhibit a clear first-order kinetics character. The energy paths based on DFT calculations are determined as an addition to the DFTB-MD results. Our findings provide insights into the comprehensive understanding of thermal decomposition behaviors of nitrogen chain-catenated and even all-nitrogen energetic materials.

Computational Design of High Energy RDX-Based Derivatives: Property Prediction, Intermolecular Interactions, and Decomposition Mechanisms.

A series of new high-energy insensitive compounds were designed based on 1,3,5-trinitro-1,3,5-triazinane (RDX) skeleton through incorporating -N(NO2)-CH2-N(NO2)-, -N(NH2)-, -N(NO2)-, and -O- linkages. Then, their electronic structures, heats of formation, detonation properties, and impact sensitivities were analyzed and predicted using DFT. The types of intermolecular interactions between their bimolecular assemble were analyzed. The thermal decomposition of one compound with excellent performance was studied through ab initio molecular dynamics simulations. All the designed compounds exhibit excellent detonation properties superior to 2,4,6,8,10,12-hexanitro-2,4,6,8,10,12-hexaazaisowurtzitane (CL-20), and lower impact sensitivity than CL-20. Thus, they may be viewed as promising candidates for high energy density compounds. Overall, our design strategy that the construction of bicyclic or cage compounds based on the RDX framework through incorporating the intermolecular linkages is very beneficial for developing novel energetic compounds with excellent detonation performance and low sensitivity.

Interference femtosecond laser stamping of micro-grating structures and time-resolved observation of its dynamics.

Selective slicing on a 100 nm thick ZnO film deposited on a Si substrate is achieved by an interference femtosecond (fs) laser stamping. A micro-grating structure with a period of ∼5 µm is completely ablated by an energy-optimized single pulse in one step. The elemental mappings demonstrate complete slice removals of the irradiated areas from the substrate without impurities mixed into the thin film. A calculation of the energy transmitted to the substrate and the characterization of the ablated Si channels infer that the irradiated slices are detached from the substrate by the selective ablation of the thin film and the counterforce of the Si substrate. The temporal and spatial evolution of the grating formation is investigated through a pump-probe microscope using the white light continuum (WLC) as the illumination probe. It is found that the extinctive constructive fringes occur at a delay of 8 picosecond (ps) caused by the increase of electron density. The irradiated slices initially bulge at the delay of 10-12 ps, then subsequently swell until strong material ejections at 800 ps. This study provides an opportunity to advance the understanding of micro-grating fabrications and thin film removals on heterostructures using fs lasers.

Transcriptional analysis of deoxynivalenol-induced apoptosis of sow ovarian granulosa cell.

Litter size is one of the most important economic traits in pig production. Recent studies identified that deoxynivalenol (DON), a widespread toxin in fodder, was associated with animal prolificacy. However, the underlying mechanisms have not yet been completely elucidated. Here, we used porcine ovary granulosa cells (pGCs) as a vector to establish DON concentration-time models and performed cell morphology and transcriptome analysis to identify and analyse the effects of DON on reproductive performance in swine. The results showed that DON can induce morphological changes and apoptosis of pGCs, while inhibiting cell proliferation. Moreover, these effects of DON on pGCs were dose-dependent. After treatment of pGCs with different concentrations of DON, the percentage of cells in S phase and G2/M phase increased. RNA-seq analyses revealed 5,937 differentially expressed genes, of which 1995 were down-regulated and 3,942 were up-regulated after DON treatment. KEGG enrichment analysis indicated important metabolic pathways such as IL-17 signalling pathway, eukaryotic ribosome synthesis pathway, RNA transport pathway and RNA degradation. Based on our results, we speculate that the effects of DON are related to the DNA damage process. Our study provides novel insights and a foundation to further understand the effect of DON on swine prolificacy.

MiR-26a promotes apoptosis of porcine granulosa cells by targeting the 3ß-hydroxysteroid-Δ24-reductase gene.

OBJECTIVE: Apoptosis of ovarian granulosa cells (GCs) affects mammalian follicular development and fecundity. This study aimed to explore the regulatory relationship between microRNA-26a (miR-26a) and the 3ß-hydroxysteroid-Δ24-reductase gene (DHCR24) gene in porcine follicular granular cells (pGCs), and to provide empirical data for the development of methods to improve the reproductive capacity of pigs. METHODS: The pGCs were transfected with miR-26a mimic, miR-26a inhibitor and DHCR24-siRNA in vitro. The cell apoptosis rate of pGCs was detected by the flow cytometry. The secretion levels of estradiol (E2) and progesterone (P) in pGCs were detected by enzymelinked immunosorbent assay. Double luciferase validation system was used to detect the binding sites between miR-26a and DHCR24 3'-UTR region. Qualitative real-time polymerase chain reaction and Western blotting were used to verify the DHCR24 mRNA and protein expression in pGCs, respectively, after transfecting with miR-26a mimic and miR-26a inhibitor. RESULTS: Results showed that enhancement of miR-26a promoted apoptosis, and inhibited E2 and P secretion in pGCs. Meanwhile, inhibition of DHCR24 also upregulated the Caspase-3 expression, reduced the BCL-2 expression, promoted pGCs apoptosis, and inhibited E2 and P secretion in pGCs. There were the binding sites of miR-26a located within DHCR24 3'-UTR. Up-regulation of miR-26a inhibited DHCR24 mRNA and protein expression in pGCs. CONCLUSION: This study demonstrates that miR-26a can promote cell apoptosis and inhibit E2 and P secretion by inhibiting the expression of DHCR24 in pGCs.

Regioselectively Halogenated Expanded Porphyrinoids as Building Blocks for Constructing Porphyrin-Porphyrinoid Heterodyads with Tunable Energy Transfer.

Expanded porphyrins have been attracting increasing attention owing to their unique optical and electrochemical properties as well as switchable aromaticity. Toward material applications, regioselective functionalization of the expanded porphyrins at their periphery is indeed challenging due to the presence of multiple reactive sites. Herein, a set of regioselective halogenated isomers (L5-Br-A/B/C) of neo-confused isosmaragdyrin (L5) are synthesized by a combination of the halogenation reaction of L5 and sequential macrocycle-to-macrocycle transformation reactions of its halogenated isomers. On this basis, the regioselectively functionalized isosmaragdyrins are utilized as building blocks for constructing multichromophoric porphyrinoids, specifically, heterodyads L5-ZnP-A/B/C, in which a common zinc porphyrin is linked at three different pyrrolic positions of isosmaragdyrins, respectively, by Sonogashira coupling reactions. The highly efficient energy cascade from porphyrin to isosmaragdyrin is elucidated using steady-state/time-resolved spectroscopies and theoretical calculations. Notably, the energy transfer processes from the porphyrin to the isosmaragdyrin moieties as well as the excitation energy transfer rates in L5-ZnP-A/B/C are highly dependent on the linking sites by through-bond and Förster-type resonance energy transfer mechanisms. The site-selective functionalization and subsequent construction of a set of heterodyads of the expanded porphyrinoid would provide opportunities for developing new materials for optoelectronic applications.