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Selective synthesis of chiral bridged (hetero)bicyclic scaffolds via asymmetric C–H activation constitutes substantial challenges due to the multiple reactivities of strained bicyclic structures. Herein, we develop the domino transformations through an unprecedented cobalt-catalyzed enantioselective C–H activation/nucleophilic [3 + 2] annulation with symmetrical bicyclic alkenes. The methods offer straightforward access to a wide range of chiral molecules bearing [2.2.1]-bridged bicyclic cores with four and five consecutive stereocenters in a single step. Two elaborate salicyloxazoline (Salox) ligands were synthesized based on the rational design and mechanistic understanding. The well-defined chiral pockets generated from asymmetric coordination around the trivalent cobalt catalyst direct the orientation of bicyclic alkenes, leading to excellent enantioselectivity.

Understanding the molecular pathogenesis of acute myeloid leukemia (AML) with well-defined genomic abnormalities has facilitated the development of targeted therapeutics. Patients with t(8;21) AML frequently harbor a fusion gene RUNX1-RUNX1T1and KITmutations as “secondary hit”, making the disease one of the ideal models for exploring targeted treatment options in AML. In this study we investigated the combination therapy of agents targeting RUNX1-RUNX1T1 and KIT in the treatment of t(8;21) AML with KITmutations. We showed that the combination of eriocalyxin B (EriB) and homoharringtonine (HHT) exerted synergistic therapeutic effects by dual inhibition of RUNX1-RUNX1T1 and KIT proteins in Kasumi-1 and SKNO-1 cells in vitro. In Kasumi-1 cells, the combination of EriB and HHT could perturb the RUNX1-RUNX1T1-responsible transcriptional network by destabilizing RUNX1-RUNX1T1 transcription factor complex (AETFC), forcing RUNX1-RUNX1T1 leaving from the chromatin, triggering cell cycle arrest and apoptosis. Meanwhile, EriB combined with HHT activated JNK signaling, resulting in the eventual degradation of RUNX1-RUNX1T1 by caspase-3. In addition, HHT and EriB inhibited NF-κB pathway through blocking p65 nuclear translocation in two different manners, to synergistically interfere with the transcription of KIT. In mice co-expressing RUNX1-RUNX1T1and KITN822K, co-administration of EriB and HHT significantly prolonged survival of the mice by targeting CD34+CD38−leukemic cells. The synergistic effects of the two drugs were also observed in bone marrow mononuclear cells (BMMCs) of t(8;21) AML patients. Collectively, this study reveals the synergistic mechanism of the combination regimen of EriB and HHT in t(8;21) AML, providing new insight into optimizing targeted treatment of AML.

Electrochemical CO2reduction reaction (CO2RR) in acid can solve alkalinity issues while highly corrosive and reductive acidic electrolytes usually cause catalyst degradation. Inhibiting catalyst degradation is crucial for the stability of acidic CO2RR. Here, we reveal the microenvironment changes of dynamic Bi-based catalysts and develop a pulse chronoamperometry (CA) strategy to improve the stability of acidic CO2RR. In situfluorescence mappings show that the local pH changes from neutral to acid, and the in situRaman spectra reveal the dynamic evolution of interfacial water structures in the microenvironment. We propose that the surface charge properties of dynamic catalysts affect the competitive adsorption of K+and protons, thereby causing the differences in local pH and CO2RR intermediate adsorption. We also develop a pulse CA strategy to reactivate catalysts, and the stability of acidic CO2RR is improved by 2 orders of magnitude for 100 h operation, which is higher than most reports on the stability of acidic CO2RR. This work gives insights on how microenvironment changes affecting the stability of acidic CO2RR, and provides guidance for designing stable catalysts in acidic electrolytes.

The decarboxylation reaction can be accelerated with the assistance of localized surface plasmon resonance under mild conditions, benefiting from the enhanced light utilization and excitation of high-energy hot carriers. However, the reaction rate remains far below the theoretical limit since plasmon-excited hot carriers easily recombine due to their ultrashort lifetime. Herein, we effectively accelerate the decarboxylation reaction of p-mercaptobenzoic acid (PMBA) on the surface of silver nanoparticles (AgNPs) by coadsorbing p-hydroxythiophenol (PHTP) molecules as molecular cocatalysts. More importantly, the period of this coadsorption is crucial to the obtained reaction rate acceleration. Compared with short-period coadsorption, long-period coadsorption could lead to a larger acceleration in reaction rate, due to the further promoted separation of plasmon-generated hot carriers. This work provides a simple, convenient, and effective strategy to boost the decarboxylation reactions on silver surfaces. This strategy holds potential for developing a variety of highly efficient plasmon-based catalysts in the near future.

Microbial-induced carbonate precipitation (MICP) technology has gained significant traction as an eco-friendly, cost-effective, and intelligent self-healing method for concrete cracks. The harsh service environment and high alkalinity of cement matrices have posed a significant challenge to the survival and growth of bacteria, which is crucial for the success of MICP technologies in concrete components. This article aims to present an up-to-date overview of the current research status of self-healing concrete cracks utilizing MICP technology. Specifically, it comprehensively reviews the selection of mineralization repair systems, encompassing repair mechanisms, effects, processes, nutrient addition sequences, and carrier selection. Furthermore, various characterization methods for evaluating the self-healing ability of concrete are explored, accompanied by an in-depth analysis of practical applications of self-healing concrete. Finally, this paper highlights the pressing issues facing this technology while outlining promising directions for future advancement.

A decline in atmospheric oxygen concentration is projected in the 21st century given the background of global warming. The Qinghai-Tibetan Plateau is located at a high altitude, and thus, it faces a hypoxia challenge; however, knowledge of the factors contributing to its atmospheric oxygen concentration is still lacking. Here, we conducted joint observations of ecosystem oxygen production and carbon sinks and near-surface atmospheric oxygen concentrations on the Qinghai-Tibetan Plateau and meteorological elements at Beijing Fangshan Station. Using seasonal differences and statistical methods, we calculated the relative contribution rates of vegetation to changes in atmospheric oxygen concentration. Our results indicate that solar radiation, atmospheric humidity, and ecosystem oxygen consumption and production have a significant impact on the atmospheric oxygen concentration, and the impact shows temporal and spatial differences. Vegetation significantly impacts the oxygen concentration, with a contribution rate of 16.7%–24.5%, which is underestimated in existing research. Our findings provide important insights into the factors that influence atmospheric oxygen concentration and highlight the contribution of vegetation. To better understand the oxygen dynamics of the Qinghai-Tibetan Plateau, we recommend further field observations of soil respiration and vegetation photosynthesis to clarify the contributions of carbon storage, carbon sinks and other factors to the near-surface atmospheric oxygen concentration.

On 6 February 2023, two 7.8 magnitude earthquakes consecutively hit south-central Türkiye, causing great concern from all governments, the United Nations, academia, and all sectors of society. Analyses indicate that there is also a high possibility of strong earthquakes with a magnitude of 7.8 or above occurring in the western region of China in the coming years. China is a country that is highly susceptible to catastrophic disasters such as earthquakes, floods, and other natural calamities, which can cause significant damages to both human life and property, as well as widespread impacts on the society. Currently, China’s capacity for disaster prevention and control is still limited. In order to effectively reduce the impact of catastrophic disasters, ensure the safety of people’s lives and property to the greatest extent possible, maintain social stability in high-risk areas, and ensure high-quality and sustainable regional development, it is urgent to improve the seismic resistance level of houses and critical infrastructure in high earthquake risk zones and increase the earthquake-resistant design level of houses in high-risk fault areas with frequent seismic activities; significantly enhance the ability to defend against extreme weather and ocean disasters in economically developed areas along the southeastern coast, as well as the level of fortification in response to extreme meteorological and hydrological disasters of coastal towns/cities and key infrastructure; vigorously enhance the emergency response capacity and disaster risk prevention level in western and ethnic minority regions; comprehensively improve the defense level of residential areas and major infrastructure in high geological hazard risk zones with flash floods, landslides, and mudslides; systematically promote national disaster prevention and mitigation education; and greatly enhance the societal disaster risk reduction ability, including catastrophic insurance.

Good toilet hygiene can reduce the risk of pathogenic transmission. During flushing, pathogenic bacteria can be spread by the water droplets, especially in the toilet seat. Escherichia coli(E. coli) is one of the frequently occurring Gram-negative bacterial pathogens found in the toilet seats. In this study, we investigated the potential anti-E. coliactivity of some azobenzene compounds. Among them, compound 2, with the heterocyclic nitrogen in both phenyl rings, showed the strongest antibacterial effect on E. coli, with the minimum inhibitory concentration of 80 µg/mL and the minimum bactericidal concentration of 320 µg/mL Compound 2displayed a comparative zone of clearance [(14.50±2.29) mm] to that of ampicillin [(13.17±1.76) mm]. The reactive oxygen species (ROS) assay suggested that compound 2might induce the loss of bacteria viathe oxidative stress by eliciting the generation of intracellular ROS. We further examined the potential cytotoxicity of compound 2to the human skin HaCaT cells. Compound 2-treated skin cells showed a good maintenance of cellular morphology and a clear definition of cell nuclei, with a satisfactory cell viability (ca.90%) at 80 µg/mL Overall, compound 2would be a possible antibacterial coating agent for the surface sanitizer of the toilet seats to inhibit the growth of E. coli.

Electrocatalytic hydrogen evolution reaction (HER) is receiving increasing attention as an effective process to produce clean energy. The commonly used precious metal catalysts can be hybridized with semiconductors to form heterostructures for the improvement of catalytic efficiency and reduction of cost. It will be promising to further improve the efficiency of heterostructure-based nanocatalysts in electrocatalytic and photocatalytic HER using a simple and effective method. Herein, we improve the efficiency of Au/TiO2in electrocatalytic and photo-electrocatalytic HER by selectively adsorbing p-aminothiophenol (PATP) molecules. The PATP molecules are adsorbed on the gold surface by using a simple solution-based method and favor the charge separation at the Au–TiO2interface. We also compare the PATP molecules with other thiophenol molecules in the enhancement of electrocatalytic HER. The PATP-induced enhancement in electrocatalysis is then further investigated by density functional theory (DFT) calculations, and this enhancement is attributed to a reduction in Gibbs energy of adsorbed hydrogen after surface adsorption of PATP molecules. This work provides a simple, cost-effective, and highly efficient approach to improve the electrocatalytic and photo-electrocatalytic efficiency of Au/TiO2, and this approach could be easily extended to other heterostructure-based nanocatalysts for performance enhancement and may be used in many other catalytic reactions.

Intestinal failure-associated liver disease (IFALD) is a common hepatobiliary complication resulting from long-term parenteral nutrition (PN) in patients with intestinal failure. The spectrum of IFALD ranges from cholestasis, steatosis, portal fibrosis, to cirrhosis. Development of IFALD is a multifactorial process, in which gut dysbiosis plays a critical role in its initiation and progression in conjunction with increased intestinal permeability, activation of hepatic immune responses, and administration of lipid emulsion. Gut microbiota manipulation including pre/probiotics, fecal microbiota transplantation, and antibiotics has been studied in IFALD with varying success. In this review, we summarize current knowledge on the taxonomic and functional changes of gut microbiota in preclinical and clinical studies of IFALD. We also review the function of microbial metabolites and associated signalings in the context of IFALD. By providing microbiota-targeted interventions aiming to optimize PN-induced liver injury, our review provides perspectives for future basic and translational investigations in the field.

ABSTRACT In this work, the effect of physical properties of recycled coarse aggregate (RCA) on the workability and mechanical properties of recycled aggregate thermal insulation concrete (RATIC) was studied. Two [...]

MD simulations have been accomplished to study the transport properties of molten CaO-Si[O.sub.2]-[P.sub.2][O.sub.5]-FeO system. The self-diffusion coefficients of Ca, Si, P, Fe and O ions increase with increasing slag basicity and FeO content, while decrease with increasing [P.sub.2][O.sub.5] content. The diffusivities of these ions in the quaternary melts follow the sequence of Ca>Fe>O>P>Si. The calculated viscosities are in good agreement with the experimental ones. It is obvious that increasing the amount of network formers (e. g., Si and P ions) leads to larger viscosity and degree of slag polymerization, while adding network modifiers (e. g., Fe and Ca ions) causes viscosity and slag polymerization to decrease. Except for the calculation, the FT-IR analysis also confirmed the relationship between structural properties of the slag and composition. The viscosity of the slag increases linearly with increasing the parameter of Q(Si + P). Keywords: MD simulations, transport properties, self-diffusion coefficient, viscosity PACS[R] (2010). 61.20.Ja, 61.20.Qg, 66.20.Cy, Introduction The transport properties (including diffusion coefficient, viscosity, electrical, and thermal conductivity, etc.) of liquids or melts are important for most physical, chemical and biotechnological processes. In engineering practices, such [...]

In this paper, a thiacalix[4]arene complex [Zn2(TIT4A)L2]·4DMF·2CH3OH (H2L = 4,4′-oxybisbenzoic acid) (Zn-TIT4A-L) was synthesized by a solvothermal method. The composites were prepared by combining Zn-TIT4A-L with reduced graphene oxide (RGO), mesoporous carbon (MC), and multi-walled carbon nanotubes (MWCNTs), respectively. Three representative composites are Zn-TIT4A-L@RGO(1:1), Zn-TIT4A-L@MC(1:2), and Zn-TIT4A-L@MWCNT(1:2). X-ray diffraction and scanning electron microscopy characterized their structures and morphologies. The results showed that three composites were successfully prepared, and the crystals of the complex remained in the composites. The electrochemical properties of the composites were characterized by electrochemical impedance spectroscopy and cyclic voltammetry. The results indicated that they had good electrocatalytic activity and conductivity. Among them, Zn-TIT4A-L@RGO(1:1) had the best performance and was used for the quantitative detection of flutamide (FTA). The linear range of detection is 0.1–200 μM, and the limit of detection is 0.015 μM. At the same time, the sensor also had good reproducibility, anti-interference, and stability. The sensor was also used for the detection of FTA in lake water, human urine, and serum with a satisfactory recovery rate. The possible mechanism of electrochemical detection of FTA was also discussed.

A novel hybrid alloy, designed for plastic injection dies, was fabricated by depositing M789 steel on wrought N709 steel through laser powder bed fusion (LPBF). The M789–N709 interface (with a thickness of about 300 μm) is characterized by the variation of titanium content from 0 wt% in the N709 section to about 1 wt% near the M789 region. A thermodynamic and kinetic simulation after aging treatment was performed to reveal the precipitation behavior in the M789–N709 interface. Different sizes and amounts of ETA-Ni3(Ti,Al) strengthening precipitates exist, with a maximum volume fraction and radius of about 5% and 5 nm, respectively (near the M789 region). Moreover, the volume fraction of precipitates significantly increases with Ti additions of up to 0.6 wt% (i.e., 100 μm from the N709 region); however, beyond this threshold, the increase in the amount of precipitation becomes gradual. The thermodynamic and kinetic simulations performed in the interface are validated by electron diffraction spectroscopy (EDS), electron probe microanalyzer (EPMA) and atomic probe tomography (APT) results; the measured precipitate size from the APT analysis is consistent with the simulation results. Two morphologies of precipitates were detected: elongated and spherical; both contribute to the robustness of the interface. The robust M789–N709 interface formed during the process shows good compatibility between the alloys, which is critical for extended tool life. These new insights about the precipitation at the interface of M789–N709 alloy are crucial in assessing the feasibility of N709 as a cost-effective base material to minimize the use of M789 when printing plastic injection dies.

New pollutants in remote regions have become a global issue of concern. This study collected soil, lichen, moss, and air samples from the high mountain area of southeastern Tibet to analyze the altitude pollution distribution of 16 polycyclic aromatic hydrocarbons(PAHs) and the related influencing factors. The results revealed that the average levels of Σ6PAH in soil, moss, lichen, and air samples were 46.8 ng/g dry weight(dw), 140.6 ng/g dw, 712.0 ng/g dw, and 60.1 ng/m3, respectively. Naphthalene and phenanthrene were the most abundant individual isomers, and 2–4 rings PAHs accounted for approximately 90% of the total ΣPAH concentration in the samples. Source apportionment analysis highlighted the impact of atmospheric PAH inputs on this region. Octanol/air distribution factor(Koa), altitude, plant coverage, and soil organic matter were the key determinants of PAH concentration along the altitudinal gradient. Across all the soil sampling sites, the average contribution of the forest filter effect (FFE) was greater than that of the mountain cold trapping effect based on the principal component analysis and multiple linear regression. The findings of this study strengthened the reasons for the preferential accumulation of organic pollutants in the high-altitude mountainous area, and provided important insights for effective environmental strategies of new pollutants.

Glacier-retreated areas are ideal areas to study soil biogeochemical processes during vegetation succession, because of the limited effect of other environmental and climatic factors. In this study, the changes of soil dissolved organic matter (DOM) and its relationship with microbial communities along the Hailuogou Glacier forefield chronosequence were investigated. Both microbial diversity and DOM molecular chemodiversity recovered rapidly at the initial stage, indicating the pioneering role of microorganisms in soil formation and development. The chemical stability of soil organic matter enhanced with vegetation succession due to the retaining of compounds with high oxidation state and aromaticity. The molecular composition of DOM affected microbial communities, while microorganisms tended to utilize labile components to form refractory components. This complex relationship network between microorganisms and DOM components played an important role in the development of soil organic matter as well as the formation of stable soil carbon pool in glacier-retreated areas.

137Cs and other radionuclides in the wastewater of nuclear energy have caused great harm to the environment and human body. Removed of these radionuclides has become one of focuses of research. Prussian blue (PB), as an excellent adsorbent for cesium ion, faces the difficulty in recovery from water after adsorption. In this article, PB powder was packed in tube-in-tube hollow fiber membranes to eliminate the problems of recovery and secondary pollution. The effects of one pass-through adsorption and cyclic adsorption in the adsorption of cesium ion were explored. In the one pass-through adsorption, the solution contacts with the adsorbent layer for a short time, resulting in a low adsorption capacity. For the cyclic adsorption, the adsorption capacity can reach 36.26 mg g–1. With the increase of PES inner hollow fiber membranes, the flux increases while the adsorption capacity decreases. The permeation of solution through the PB layer favors the mass transfer of ion to the adsorbent. The tube-in-tube adsorption can solve the recovery problem of PB powder and also improve the adsorption efficiency.

Stable operation of the sintering process is critical to ensuring the final quality of ternary cathode materials. However, the strong nonlinearity and dynamics, resulting from the process feedback control, coupled temperature zones, and the unstable external environment, often lead to the traditional process-monitoring methods monitoring poor performance. To this end, this article proposes a recurrent variational autoencoder (RVAE)-based industrial process-monitoring method. First, the variational autoencoder-based nonlinear dynamic system (NDS) model of the sintering process is learned, which can fully extract the process nonlinearity. Then, the autoregressive equation among the latent variables (LVs) is established according to a recurrent neural network (RNN), and the weights to samples at various times are assigned by the weighted moving average method. On this basis, the dynamic characteristics among the LVs can be excavated effectively. Subsequently, some appropriate monitoring statistics are designed based on principal component analysis (PCA), which are more sensitive to faults than indicators based on reconstruction errors. Correspondingly, the RVAE-based process-monitoring strategy is proposed. Finally, the proposed method has been verified to be effective and superior by the industrial application of the sintering process.

Image captioning aims at automatically describing images by sentences. It often requires lots of paired image-sentence data for training. However, trained captioning models can hardly be applied to new domains in which some novel words exist. In this paper, we introduce the zero-shot novel object captioning task, where the machine generates descriptions about novel objects without extra training sentences. To tackle the challenging task, we mimic the way that babies talk about something unknown, i.e., using the word of a similar known object. Following this motivation, we build a key-value object memory by detection models, containing visual information and corresponding words for objects in the image. For those novel objects, we use words of most similar seen objects as proxy visual words to solve the out-of-vocabulary issue. We then propose a Switchable LSTM that incorporates knowledge from the object memory into sentence generation. The model has two switchable working modes, i.e., 1) generating the sentences like standard LSTMs and 2) retrieving proper nouns from the key-value memory. Thus our model is learned to fully disentangle language generation from training objects, and requires zero training sentence in describing novel objects. Experiments on three large-scale datasets demonstrate the ability of our method to describe novel concepts.

Accurate and effective detection of hydrogen peroxide (H2O2) is of great significance in physiological functions as well as industrial applications. In this paper, the rod-like NiO–Co3O4nanomaterials were synthesized by a simple hydrothermal method for electrochemical detection of H2O2. The characterization results indicated that the nanomaterials possess high porosity and excellent conductivity, and displayed good electrocatalysis activity at the same time. Under alkaline conditions, the as-prepared nanomaterials can catalyze the reduction of H2O2and realize the electron transfer between H2O2and the electrode. The H2O2electrochemical sensor based on NiO–Co3O4nanomaterials exhibited a wide linear response (1–250 and 250–1200 μmol/L), a low detection limit (0.1 μmol/L) and a high sensitivity (5305.59 μA/ (mmol/L·cm2) (S/N= 3)). In addition, the fabricated sensor showed high selectivity, good repeatability and high stability. The applications of the proposed sensor for H2O2detection in food samples were demonstrated and satisfactory results were obtained.

The marine environment is regarded as a crucial “sink” of numerous land-origin pollutants. As typical boundary regions, the coastal and offshore areas are used to evaluate the dominating transfer process and land–ocean exchange mechanism of semivolatile organic compounds. In air samples collected from a coastal area in North China over a whole year, chlorinated paraffins (CPs), including short-chain CPs and medium-chain CPs, and prior control 16 polycyclic aromatic hydrocarbons (PAHs) were determined, with mean concentrations of 25.8 and 94.7 ng/m3, respectively. Results of different gas–particle partitioning models indicated that the steady-state hypothesis provides a better description of the possible land–ocean exchange molecular mechanism. The source–sink influences for CPs and PAHs were affected by the predominant atmospheric motion, which alternated between gaseous diffusion and particulate sedimentation in different seasons. Source apportionment results indicated that different transfer characteristics contributed to the source divergence of ambient CPs and PAHs within 12 nautical miles in the same area. Coal/biomass combustion and diesel/natural gas combustion were the main PAH sources in the coast site (43.1%) and sea site (35.3%), respectively. Similar industrial sources CP-52 and CP-42 were the main CP sources in the coast site (41.4%) and sea site (40.8%), respectively.

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An effective rhodium(III) catalysis for the construction of valuable tetracyclic compounds is described herein. This domino process involving the C–H activation/[3 + 2] annulation/intramolecular Friedel–Crafts reaction sequences of simple and readily available N-Boc hydrazones and propargylic monofluoroalkynes afforded fused tetracyclic spiro[cyclobutane-1,9′-indeno[1,2-a]indenes] in moderate to good yields, featuring three C–C bond formation. Moreover, control experiments indicated that the C–H activation might be involved in the rate-determining step.

ABSTRACTDiabetic retinopathy (DR) is one of the most common retinal microvascular diseases in diabetic patients. Therefore, elucidating the underlying molecular mechanism of DR is of great significance for its clinical treatment. This study explores the effects of the upregulated circFTO in DR patients in terms of cell apoptosis and viability. Several molecular assays are employed to explore these molecular mechanistic aspects, such as luciferase reporter, RNA pull-down, RT-qPCR, Western blot, and ELISA assays. miR-148a-3p is downregulated in DR patients. The expression of circFTO promoted ARPE-19 cells apoptosis and inhibited proliferation, reflecting the regulatory effect of circFTO/miR-148a-3p on retinal epithelial cells injury. In addition, the absence of circFTO could reduce ARPE-19 cells injury caused by HG by inhibiting oxidative stress and inflammation. Further, the investigations at the molecular level showed that circFTO could regulate the level of miR-148a-3p and TGFA in vitro. As the molecular sponge of miR-148a-3p, circFTO regulated cell viability and apoptosis and promoted the progression of DR through regulating the expression of TGFA. Together, this study provides new targets and markers for early diagnosis and therapy of DR.

Within the hazard and disaster risk research field, explicitly treating carbon emissions as a hazard remains rather nascent. Applying hazard and disaster risk research perspectives to seek new insights on integrated mitigation and adaptation approaches and policy measures is equally elusive. Since China’s pledge to achieve carbon neutrality by 2060, the “dual carbon” goals of carbon emission peaking and neutrality have stimulated nationwide attention, research, and policies and action plans. How to ensure that the transition pathways are on track and well-contextualized is one of the crucial challenges for policymakers and practitioners. This article examines the “risks” of missing the carbon neutrality goal at a regional scale in China, denoted as Carbon Emission Risk (CER). Carbon emissions (CE) as hazard, combined with the human socioeconomic system as exposure and human living environment, constitute the regional carbon emission environmental risk system. The “risks” of missing (or achieving) the carbon neutrality target for any region at any time, the article argues, is essentially determined by the ratio of CE to carbon absorption (CA, for uptake and removal). These variables are modified by a broadly defined “vulnerability coefficient” (Cv) that embodies both the potential for changes (decreasing CE and increasing CA), and the uncertainties of measuring CE and CA. Thus, the ratio of CE to CA is a measure of reality at any moment of time, whereas Cv indicates the overall propensity or capacity for moving the CE/CA ratio towards 1, that is, realizing carbon neutrality. Based on our calculation, CER at the provincial level in eastern China is higher than in western China. The article also calls for strengthening CER research and summarizes key measures for carbon emission risk governance.

Dry eye is a common ocular disease that results in discomfort and impaired vision, impacting an individual's quality of life. A great number of drugs administered in eye drops to treat dry eye are poorly soluble in water and are rapidly eliminated from the ocular surface, which limits their therapeutic effects. Therefore, it is imperative to design a novel drug delivery system that not only improves the water solubility of the drug but also prolongs its retention time on the ocular surface. Herein, we develop a copolymer from mono-functional POSS, PEG, and PPG (MPOSS-PEG-PPG, MPEP) that exhibits temperature-sensitive sol-gel transition behavior. This thermo-responsive hydrogel improves the water solubility of FK506 and simultaneously provides a mucoadhesive, long-acting ocular delivery system. In addition, the FK506-loaded POSS hydrogel possesses good biocompatibility and significantly improves adhesion to the ocular surface. In comparison with other FK506 formulations and the PEG-PPG-FK506 (F127-FK506) hydrogel, this novel MPOSS-PEG-PPG-FK506 (MPEP-FK506) hydrogel is a more effective treatment of dry eye in the murine dry eye model. Therefore, delivery of FK506 in this POSS hydrogel has the potential to prolong drug retention time on the ocular surface, which will improve its therapeutic efficacy in the management of dry eye.

In an effort to identify novel drugs targeting fusion-oncogene–induced acute myeloid leukemia (AML), we performed high-resolution proteomic analysis. In AML1-ETO (AE)-driven AML, we uncovered a deregulation of phospholipase C (PLC) signaling. We identified PLCgamma 1 (PLCG1) as a specific target of the AE fusion protein that is induced after AE binding to intergenic regulatory DNA elements. Genetic inactivation of PLCG1 in murine and human AML inhibited AML1-ETO dependent self-renewal programs, leukemic proliferation, and leukemia maintenance in vivo. In contrast, PLCG1 was dispensable for normal hematopoietic stem and progenitor cell function. These findings are extended to and confirmed by pharmacologic perturbation of Ca++-signaling in AML1-ETO AML cells, indicating that the PLCG1 pathway poses an important therapeutic target for AML1-ETO+ leukemic stem cells.

A brain-computer interface (BCI) system based on steady-state visual evoked potentials (SSVEP) was developed by four-class phase-coded stimuli. SSVEPs elicited by flickers at 60Hz, which is higher than the critical fusion frequency (CFF), were compared with those at 15Hz and 30Hz. SSVEP components in electroencephalogram (EEG) were detected using task related component analysis (TRCA) method. Offline analysis with 17 subjects indicated that the highest information transfer rate (ITR) was 29.80±4.65bpm with 0.5s data length for 60Hz and the classification accuracy was 70.07±4.15%. The online BCI system reached an averaged classification accuracy of 87.75±3.50% at 60Hz with 4s, resulting in an ITR of 16.73±1.63bpm. In particular, the maximum ITR for a subject was 80bpm with 0.5s at 60Hz. Although the BCI performance of 60Hz was lower than that of 15Hz and 30Hz, the results of the behavioral test indicated that, with no perception of flicker, the BCI system with 60Hz was more comfortable to use than 15Hz and 30Hz. Correlation analysis revealed that SSVEP with higher signal-to-noise ratio (SNR) corresponded to better classification performance and the improvement in comfortableness was accompanied by a decrease in performance. This study demonstrates the feasibility and potential of a user-friendly SSVEP-based BCI using imperceptible flickers.

In order to meet the requirements of multi-degree-of-freedom (multi-DOF) driving units for omnidirectional vehicle wheels, a multi-DOF spherical induction motor (SIM) is proposed with composite rotor through the conversion of design concept of linear induction motor (LIM), which compensates for the insufficiency of traditional multi-DOF driving scheme with structural complexity, control difficulties and poor dynamic performance. The SIM realizes two DOF driving and has the characteristics of direct output on rotor surface. Firstly, the overall design of SIM is drafted, as well as finite element model and control system are established. Subsequently, in order to optimize SIM performance, the multi-objective optimization design of composite rotor structure is proposed by adopting non-dominated sorting genetic algorithm-II (NSGA-II). The results show that the reasonable design of rotor structure can effectively improve output torque and reduce fluctuation. And the proposed design idea based on theory of LIM can provide a reference for SIM design.

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The partial tandem duplication of histone-lysine N-methyltransferase 2A (KMT2A-PTD) is an important genetic alteration in acute myeloid leukemia (AML) and is associated with poor clinical outcome. Accurate and rapid detection of KMT2A-PTD is important for outcome prediction and clinical management, but next-generation sequencing–based quantitative research is still lacking. In this study, we developed a targeted RNA-based next-generation sequencing panel, together with single primer enrichment and unique molecular identifiers, to identify KMT2A-PTD as well as AML-related gene fusions and other driver mutations. Our panel showed high sensitivity, accuracy, and reproducibility in detecting the fusion ratio of KMT2A-PTD. The mutation profile of KMT2A-PTD–positive patients with AML was characterized and different distribution patterns of driver mutations were found according to KMT2A-PTD fusion ratio level. Survival analyses revealed that the fusion ratio of KMT2A-PTD did not affect clinical outcome, but a novel molecular combination, namely, KMT2A-PTD/DNMT3A/FMS-like tyrosine kinase 3–internal tandem duplication, was associated with poor prognosis. Finally, it was shown that the dynamic changes in the KMT2A-PTD fusion ratio were consistent with the overall process of disease progression. In summary, we applied the unique molecular identifier–based RNA panel to quantitatively detect KMT2A-PTD and elucidate its clinical relevance, which complemented the integrative network of various genetic alterations in AML.

Background: Camrelizumab, which was launched in China on May 29, 2019, is a humanized anti-programmed cell death-1 (PD-1) antibody. It is used for the treatment of complicated or refractory classic Hodgkin's lymphoma with at least second-line chemotherapy. On March 4, 2020, camrelizumab was approved as a second-line drug in China for the treatment of advanced hepatocellular carcinoma. Currently, camrelizumab is undergoing clinical research for advanced solid tumors such as liver cancer, gastric cancer, esophageal cancer, and lung cancer, and all have shown clinical efficacy. Objective: This review describes preclinical studies on camrelizumab and its efficacy and safety in clinical studies in various tumors. Methods: A literature search was conducted on basic research and clinical trials of camrelizumab determined its pharmacology, toxicology, pharmacokinetic properties, and current clinical research status. We also analyzed the difference between camrelizumab and other PD-1 antibodies. Results: The results of preclinical studies show that camrelizumab binds to the PD-1 receptor and has stable anti-tumor activity in a dose-dependent manner. Clinical studies show that camrelizumab has therapeutic effects on a variety of tumors. The incidence of adverse reactions with camrelizumab is low, with most being mild, reversible, and predictable. Conclusion: This review summarizes the current status of preclinical and clinical studies on camrelizumab. Current research confirms that camrelizumab alone or in combination with other drugs shows significant anti-cancer activity and a low incidence of adverse reactions. However, further studies are needed to verify the application potential of camrelizumab in a variety of tumors.

ABSTRACTThe objective of the research was to reveal the potential toxicity effects of methyl mercaptan on rat lung tissue. A dynamic exposure device and Sprague-Dawley (SD) rats were adopted. The exposure concentration of methyl mercaptan was 0.5 ± 0.1 ppm. The exposure procedure was 6 h/day, continuing for 30 days. The routine blood levels, oxidative stress levels in serum, immune molecule and cytokine in the serum and lung tissue were tested. Morphology injury of lung tissue was detected by Hematoxylin and Eosin (HE) staining. Apoptosis rate of alveolar epithelial cells were determined by TdT-mediated dUTP Nick End Labeling (TUNEL) assay. Reduction of body weight gain was observed in the male group during the exposure time, while there was no significant reduction of body weight gain in the female group. Pathological findings of terminal bronchiole constriction, alveolar congestion, and erythrocyte exudation confirmed the lung to be the main target organ. An apparent pneumonocyte apoptotic effection was also observed. Oxidative stress with lipid peroxidation, which affect blood antioxidant enzyme levels and induce apoptosis of alveolar epithelial cells, are recognized as a potential mechanism leading to terminal bronchiole constriction, alveoli congestion, and exudates of erythrocyte.Implications: The odor pollutants greatly affect the health of operation workers in the waste treatment plant, and odor complaints are becoming a major problem. The aim of this work is to identify the lung tissue inflammatory response of SD rats with chronic exposure to methyl mercaptan vapor at close to the recommended workplace concentration. In this study, we used a dynamic exposure device and chronic exposure model of rats to evaluate the potential toxicity effects of methyl mercaptan. The results showed that methyl mercaptan may cause lung inflammatory response and extensive lung cell apoptosis. Oxidative damage, with lipid peroxidation and alterations in blood antioxidant enzyme levels, was observed following methyl mercaptan exposure. This is recognized as a potential mechanism for terminal bronchiolar constriction, alveolar congestion, and erythrocyte exudation.

Peripheral T cell lymphoma (PTCL) is a heterogeneous group of non-Hodgkin’s lymphomas varying in clinical, phenotypic, and genetic features. The molecular pathogenesis and the role of the tumor microenvironment in PTCL are poorly understood, with limited biomarkers available for genetic subtyping and targeted therapies. Through an integrated genomic and transcriptomic study of 221 PTCL patients, we delineate the genetic landscape of PTCL, enabling molecular and microenvironment classification. According to the mutational status of RHOA, TET2, histone-modifying, and immune-related genes, PTCL is divided into 4 molecular subtypes with discrete patterns of gene expression, biological aberrations, and vulnerabilities to targeted agents. We also perform an unsupervised clustering on the microenvironment transcriptional signatures and categorize PTCL into 4 lymphoma microenvironment subtypes based on characteristic activation of oncogenic pathways and composition of immune communities. Our findings highlight the potential clinical rationale of future precision medicine strategies that target both molecular and microenvironment alterations in PTCL.

In the field of oral and maxillofacial surgery, extensive oral soft-tissue injuries occur repeatedly in clinical practice; however, effective restorative materials are lacking. In this study, a biodegradable waterborne polyurethane patch featuring a mucosa bionic bilayer structure is presented. This patch consists of a porous scaffold layer that faces the lesion, incorporating a polydopamine coating to achieve sustained release of epidermal growth factors (EGFs) for mucosal defect reconstruction. Additionally, there is a dense barrier layer toward the oral cavity loaded with silver nanoparticles, which prevents bacteria from entering the wound and simultaneously acts as a physical barrier. This patch can sustainably release EGF in vitro for 2 weeks, thereby facilitating the proliferation and migration of HaCaT and L929 cells, while effectively killing common oral cavity bacteria. In a rabbit buccal mucosal full-thickness defect model, the patch demonstrates better efficacy than the clinical benchmark, decellularized extracellular matrix (dECM). It effectively reduces wound inflammation and significantly upregulates gene expression associated with epithelialization by activating the EGF/epidermal growth factor receptor (EGFR) pathway. These mechanisms promote the proliferation, differentiation, and migration of epithelial/keratinocyte cells, ultimately expediting mucosal defect healing and wound closure.

A K–Eu bimetallic ammonium metal-nitrate three-dimensional (3D) framework incorporating R-N-methyl-3-hydroxyquinuclidine, (RM3HQ)2KEu(NO3)6(RM3HQ = R-N-methyl-3-hydroxyquinuclidine, 1), was characterized and reported. Distinguishing from the former hybrid rare-earth double perovskites, 1adopts a mixed corner- and face-sharing K+/Eu3+-centered polyhedral connectivity to form a 3D inorganic framework, showing a rare (6, 6)-connected ion topology with a 66framework. Notably, 1exhibits clear phase transition, and the switchable thermodynamic behavior is confirmed by variable-temperature dielectric measurements and second-harmonic generation response. Moreover, 1also shows photoluminescence properties. The activator Eu3+plays a crucial role in this process, leading to a significant narrow emission at 592 nm with a photoluminescence quantum yield (PLQY) of 20.76%. The fluorescence lifetime (FLT) of 1is 4.32 ms. This finding enriches the bimetallic hybrid system for potential electronic and/or luminescence applications.

Electro-optical synergy has recently been targeted to improve the separation of hot carriers and thereby further improve the efficiency of plasmon-mediated chemical reactions (PMCRs). However, the electro-optical synergy in PMCRs needs to be more deeply understood, and its contribution to bond dissociation and product selectivity needs to be clarified. Herein, the electro-optical synergy in plasmon-mediated reduction of p-bromothiophenol (PBTP) was studied on a plasmonic nanostructured silver electrode using in situ Raman spectroscopy and theoretical calculations. It was found that the electro-optical synergy-induced enhancements in the cleavage of carbon–bromine bonds, reaction rate, and product selectivity (4,4′-biphenyl dithiol vs thiophenol) were largely affected by the applied bias, laser wavelength, and laser power. The theoretical simulation further clarified that the strong electro-optical synergy is attributed to the matching of energy band diagrams of the plasmonic silver with those of the adsorbed PBTP molecules. A deep understanding of the electro-optical synergy in PBTP reduction and the clarification of the mechanism will be highly beneficial for the development of other highly efficient PMCRs.

Plasmon-mediated electrochemistry is an emerging area of interest in which the electrochemical reactions are enhanced by employing metal nanostructures possessing localized surface plasmon resonance (LSPR). However, the reaction efficacy is still far below its theoretical limit due to the ultrafast relaxation of LSPR-generated hot carriers. Herein, we introduce p-hydroxythiophenol (PHTP) as a molecular cocatalyst to significantly improve the reaction efficacy in plasmon-mediated electrochemical oxidation of p-aminothiophenol (PATP) on gold nanoparticles. Using electrochemical techniques, in situ Raman spectroscopy, and theoretical calculations, we elucidate that the presence of PHTP improves the hot hole-mediated electrochemical oxidation of PATP by 2-fold through the trapping of plasmon-mediated hot electrons. In addition, the selectivity of PATP oxidation could also be modulated by the introduction of PHTP cocatalyst. This tactic of employing molecular cocatalyst can be drawn out to endorse various plasmonic electrochemical reactions because of its simple protocol, high efficiency, and high selectivity.

The development of transmucosal drug delivery systems is a practical requirement in oral clinical practice, and controlled sequential delivery of multiple drugs is usually required. On the basis of the previous successful construction of monolayer microneedles (MNs) for transmucosal drug delivery, we designed transmucosal double-layer sequential dissolving MNs using hyaluronic acid methacryloyl (HAMA), hyaluronic acid (HA), and polyvinyl pyrrolidone (PVP). MNs have the advantages of small size, easy operation, good strength, rapid dissolution, and one-time delivery of two drugs. Morphological test results showed that the HAMA-HA-PVP MNs were small and intact in structure. The mechanical strength and mucosal insertion test results indicated the HAMA-HA-PVP MNs had appropriate strength and could penetrate the mucosal cuticle quickly to achieve transmucosal drug delivery. The in vitroand in vivoexperiment results of the double-layer fluorescent dyes simulating drug release revealed that MNs had good solubility and achieved stratified release of the model drugs. The results of the in vivoand in vitrobiosafety tests also indicated that the HAMA-HA-PVP MNs were biosafe materials. The therapeutic effect of drug-loaded HAMA-HA-PVP MNs in the rat oral mucosal ulcer model demonstrated that these novel HAMA-HA-PVP MNs quickly penetrated the mucosa, dissolved and effectively released the drug, and achieved sequential drug delivery. Compared to monolayer MNs, these HAMA-HA-PVP MNs can be used as double-layer drug reservoirs for controlled release, effectively releasing the drug in the MN stratification by dissolution in the presence of moisture. The need for secondary or multiple injections can be avoided, thus improving patient compliance. This drug delivery system can serve as an efficient, multipermeable, mucosal, and needle-free alternative for biomedical applications.

Global interest grows in blue foods as part of sustainable diets, but little is known about the potential and environmental performance of blue foods from rice–animal coculture systems. Here, we compiled a large experimental database and conducted a comprehensive life cycle assessment to estimate the impacts of scaling up rice–fish and rice–crayfish systems in China. We find that a large amount of protein can be produced from the coculture systems, equivalent to ∼20% of freshwater aquaculture and ∼70% of marine wild capture projected in 2030. Because of the ecological benefits created by the symbiotic relationships, cocultured fish and crayfish are estimated to be carbon-negative (−9.8 and −4.7 kg of CO2e per 100 g of protein, respectively). When promoted at scale to displace red meat, they can save up to ∼98 million tons of greenhouse gases and up to ∼13 million hectares of farmland, equivalent to ∼44% of China’s total rice acreage. These results suggest that rice–animal coculture systems can be an important source of blue foods and contribute to a sustainable dietary shift, while reducing the environmental footprints of rice production. To harvest these benefits, robust policy supports are required to guide the sustainable development of coculture systems and promote healthy and sustainable dietary change.

The “micro-course” and “flipped classroom” are emerging tools for medical education but little is known about their utility for emergency medicine teaching. The suitability of the micro-course combined with flipped classroom is investigated for delivery of an emergency medicine course in West Anhui Health Vocational College. Students from Class A and Class B of the Clinical Department of West Anhui Health Vocational College, Grade 2000, were assigned to experimental (micro-course plus flipped classroom, n = 102) and control (traditional, didactic teaching, n = 104) groups, respectively. The effectiveness of teaching was assessed by theoretical tests and questionnaires at the end of the course. Theory test results were significantly better for the experimental group than for controls (t = 3.122, P < .01). General satisfaction of students who had participated in the micro-course plus flipped classroom exceeded that of those who had received traditional teaching. Enthusiasm, efficiency, and learning facility was self-reported to be enhanced by students in the experimental group relative to controls. Use of the micro-course combined with flipped classroom successfully increased the outcome of emergency medicine teaching and may be considered as an approach to reform emergency medicine teaching in medical colleges and universities.

Background: Liraglutide can effectively reduce the weight of patients with type 2 diabetes. Nonetheless, its weight loss effect was highly heterogeneous in different patients in the clinical practice.Objective: To identify the factors most associated with the weight loss effect of liraglutide in obese or overweight patients with type 2 diabetes with poorly controlled oral medication in northeast China.Design: A prospective study.Methods: A prospective study was performed in subjects with type 2 diabetes who were taking oral medication and had a body mass index (BMI) of ⩾24 kg/m2. Liraglutide was administered for at least 12 weeks, while the original hypoglycemic regimen was kept unchanged (Phase I). Later, liraglutide treatment was continued or stopped as necessary or as subjects thought fit in the 13–52 weeks that followed (Phase II), and the potential factors affecting the effect of weight loss of liraglutide were analyzed.Results: Of the 127 recruited subjects, 90 had comprehensive follow-up data at week 12. In Phase I, the subjects’ blood sugar levels and weight decreased significantly(P< 0.001). Among all the significant factors, the gastrointestinal adverse reactions score (GARS) was more correlated with BMI change (ΔBMI; r= 0.43) and waist circumference change (ΔWC; r= 0.32) than the baseline BMI (BMI0) and WC (WC0). At week 12, linear regression showed that BMI0independently affected ΔBMI and ΔWC, whereas WC0only affected ΔWC. The GARS was significantly associated with ΔBMI and ΔWC, and this association continued until week 52, even after most subjects had discontinued liraglutide treatment.Conclusion: The degree of obesity and gastrointestinal adverse reactions were the most promising predictors of weight loss in liraglutide treatment.