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The limited availability of high-cost nucleotide sugars is a significant constraint on the application of their downstream products (glycosides and prebiotics) in the food or pharmaceutical industry. To better solve the problem, this study presented a one-pot approach for the biosynthesis of UDP-Gal using a thermophilic multienzyme system consisting of GalK, UGPase, and PPase. Under optimal conditions, a 2 h reaction resulted in a UTP conversion rate of 87.4%. In a fed-batch reaction with Gal/ATP = 20 mM:10 mM, UDP-Gal accumulated to 33.76 mM with a space-time yield (STY) of 6.36 g/L·h–1after the second feeding. In repetitive batch synthesis, the average yield of UDP-Gal over 8 cycles reached 10.80 g/L with a very low biocatalyst loading of 0.002 genzymes/gproduct. Interestingly, Galk (Tth0595) could synthesize Gal-1P using ADP as a donor of phosphate groups, which had never been reported before. This approach possessed the benefits of high synthesis efficiency, low cost, and superior reaction system stability, and it provided new insights into the rapid one-pot synthesis of UDP-Gal and high-value glycosidic compounds.

Structural color is a fascinating optical phenomenon arising from intricate light–matter interactions. Biological structural colors from natural polymers are invaluable in biomimetic design and sustainable construction. Here, we report a renewable, abundant, and biodegradable cellulose-derived organic gel that generates stable cholesteric liquid crystal structures with vivid structural colors. We construct the chromatic gel using a 68 wt % hydroxypropyl cellulose (HPC) matrix, incorporating distinct polyethylene glycol (PEG) guest molecules. The PEGs contain peculiar end groups with tailored polarity, allowing for precise positioning on the HPC helical backbone through electrostatic repulsion between the PEG and HPC chains. This preserves the HPC’s chiral nematic phase without being disrupted. We demonstrate that the PEGs’ polarity tunes the HPC gel’s reflective color. Additionally, gels with variable polarities are highly sensitive to temperature, pressure, and stretching, resulting in rapid, continuous, and reversible color changes. These exceptional dynamic traits establish the chiral nematic gel as an outstanding candidate for next-generation applications across displays, wearables, flexible electronics, health monitoring, and multifunctional sensors.

Nuclear receptor receptor-related orphan receptor γ (RORγ) is a ligand-dependent transcription factor and has been established as a key player in castration-resistant prostate cancers (CRPC) by driving androgen receptor (AR) overexpression, representing a potential therapeutical target for advanced prostate cancers. Here, we report the identification of the first-in-class RORγ covalent inhibitor 29via the structure-based drug design approach following structure–activity relationship (SAR) exploration. Mass spectrometry assay validated its covalent inhibition mechanism. Compound 29significantly inhibited RORγ transcriptional activity and remarkably suppressed the expression levels of AR and AR-targeted genes. Compound 29also exhibited much superior activity in inhibiting the proliferation and colony formation and inducing apoptosis of the CRPC cell lines relative to the positive control 2and noncovalent control 33. Importantly, it markedly suppressed the tumor growth in a 22Rv1 mouse tumor xenograft model with good safety. These results clearly demonstrate that 29is a highly potent and selective RORγ covalent inhibitor.

Chlorophyll a (Chl a) concentration, a vital indicator of water quality and crucial for assessing the health of marine ecosystems, presents significant challenges for satellite remote sensing due to various interferences, such as cloud cover, sun-glints, and adjacency effects. These impediments limit our understanding of marine ecosystems and hinder sustainable management practices. This study proposes a novel approach to overcome these challenges: the Fourier transform convolutional long short-term memory (FTC-LSTM) framework. Integrating Fourier transform convolution (FTC) and long short-term memory (LSTM) layers, the FTC-LSTM model aims to estimate cloud-free Chl a, improving the accuracy and robustness of the inpainting process. Evaluation of the FTC-LSTM model across the South China Sea (SCS), along with two other state-of-the-art deep learning models [data-interpolating convolutional auto-encoder (DINCAE) and convolutional long short-term memory neural network (Conv-LSTM)], reveals its consistently superior performance across regions with distinct characteristics. Notably, the FTC-LSTM model achieved the highest scores with impressive values: 0.95 for determination coefficient ( $R^{2}$ ), 47.57 for peak signal-to-noise ratio (PSNR), 0.99 for structural similarity index measure (SSIM), and 0.01 for root mean square error (RMSE). The temporal analysis demonstrates the model’s ability to accurately capture the temporal variability of Chl a in the SCS. Furthermore, a comparison of spatial patterns indicates that the FTC-LSTM model excels in reliably reconstructing Chl a distributions within the SCS, outperforming other models, particularly in tropical and subtropical regions significantly impacted by clouds.

Bi3+and Cl−co–doped Li3V1.97Bi0.03(PO4)3−xClx/C compounds (x= 0.03, 0.05, 0.07, 0.09) were prepared via a simple sol–gel method. The XRD patterns proved that a small amount of Bi3+and Cl−doping does not change the crystal structure of Li3V2(PO4)3. Charge/discharge results displayed that Bi3+and Cl−co–doped samples exhibited higher initial capacities than Li3V2(PO4)3/C. Li3V1.97Bi0.03(PO4)2.95Cl0.05/C demonstrated the highest capacity of 188 mAh / g at 0.1 C. Cycling performance at 1 C showed that the capacity retention of Li3V1.97Bi0.03(PO4)2.95Cl0.05/C reaches 81.31 % after 300 cycles. Electrochemical impedance spectroscopy (EIS) and cyclic voltammetry (CV) testing implied that Li3V1.97Bi0.03(PO4)2.95Cl0.05has the smallest charge transfer resistance and the largest lithium ion diffusion coefficient. The improvement can be assigned to the enhanced kinetics of lithium ions, reduction in polarization and decreased charge transfer resistance of the electrode.

Radiation nephropathy refers to kidney damage caused by radiation therapy for malignant tumours. Currently, the pathogenesis is unclear and there is a lack of effective treatment methods. With the development of traditional Chinese medicine, the role of traditional Chinese medicine in the protection of radiation nephropathy is receiving increasing attention. Therefore, in this study, we used X-ray intraperitoneal irradiation to construct a mouse model of radiation nephropathy and studied the protective effect of traditional Chinese medicine Keluoxin on radiation nephropathy. We first analysed the potential targets and pathways of Keluoxin in the treatment of radiation nephropathy using network pharmacology methods, combined with in vitroand in vivoexperimental verification, to study its potential mechanism. By searching the database, 136 components of Keluoxin were identified. A total of 333 intersectional targets related to radiation nephropathy were obtained. Among them, key targets include IL-6, TNF-α, HIF-1α, STAT1, STAT3, JAK1, JAK2, etc. In in vivoand in vitroexperiments, we found that as the irradiation dose increased and time prolonged, kidney damage in mice gradually worsened in a time-dependent and dose-dependent manner. As the irradiation dose increases, the expression of pro-inflammatory factors Il-6, TNF-α, TGF-β increased. Compared with the irradiation group, the intervention of Keluoxin can reduce kidney damage caused by X-ray irradiation and reduce the expression of IL-6, TNF-α, TGF-β, STAT1, STAT3, JAK1, JAK2, etc. These results indicated that Keluoxin can alleviate kidney damage caused by X-ray irradiation, possibly by regulating the JAK/STAT signalling pathway, reducing inflammation levels and oxidative stress damage.

The allosteric inhibitor of the mechanistic target of rapamycin (mTOR) everolimus reduces seizures in tuberous sclerosis complex (TSC) patients through partial inhibition of mTOR functions. Due to its limited brain permeability, we sought to develop a catalytic mTOR inhibitor optimized for central nervous system (CNS) indications. We recently reported an mTOR inhibitor (1) that is able to block mTOR functions in the mouse brain and extend the survival of mice with neuronal-specific ablation of the Tsc1 gene. However, 1showed the risk of genotoxicity in vitro. Through structure–activity relationship (SAR) optimization, we identified compounds 9and 11without genotoxicity risk. In neuronal cell-based models of mTOR hyperactivity, both corrected aberrant mTOR activity and significantly improved the survival rate of mice in the Tsc1 gene knockout model. Unfortunately, 9and 11showed limited oral exposures in higher species and dose-limiting toxicities in cynomolgus macaque, respectively. However, they remain optimal tools to explore mTOR hyperactivity in CNS disease models.

The present paper investigates the turbulent cavitating flow around the Clark-Y hydrofoil with special emphasis on the influence of cavitation models by verification and validation (V&V) method. RANS solver coupled with the three major cavitation models (i.e., Zwart-Gerber-Belamri, Schnerr and Sauer and full cavitation model, which are abbreviated to ZGB model, SS model and FC model respectively) is employed in this paper. The results indicate that the three cavitation models can properly reproduce the cavitation evolutions. ZGB model and SS model give better prediction in the overall cavitation patterns. FC model exhibits an obvious under-estimation for the sheet cavity, and the predicted volume fraction is closely related to the turbulent flow. The verification and validation procedure is involved to quantitatively assess the accuracy of these three cavitation models. It is indicated that the V&V procedure is suitable for the unsteady cavitating flow. The errors estimate is robust and conservative within the cavitation region, while gets closer to zero in the no-cavitation region. In addition, ZGB model exhibits the highest overall accuracy among the three models, which further verifies its wide applicability.

Circular RNAs (circRNAs) play important roles in the malignant progression of tumours. Herein, we identified an unreported circRNA (hsa-circ-0072688, also named circADAMTS6) that is specifically upregulated in the hypoxic microenvironment of glioblastoma and closely correlated with poor prognosis of gliblastoma patients. We found that circADAMTS6 promotes the malignant progression of glioblastoma by promoting cell proliferation and inhibiting apoptosis. Mechanistically, the hypoxic tumour microenvironment upregulates circADAMTS6 expression through transcription factor activator protein 1 (AP-1) and RNA-binding protein TAR DNA-binding protein 43 (TDP43). Moreover, circADAMTS6 accelerates glioblastoma progression by recruiting and stabilising annexin A2 (ANXA2) in a proteasomes-dependent manner. Furthermore, we found T-5224 (AP-1 inhibitor) treatment induces downregulation of circADAMTS6 and then inhibits tumour growth. In conclusion, our findings highlight the important role of the circADAMTS6/ANXA2 axis based on hypoxic microenvironment in glioblastoma progression, as well as its regulation in NF-κB pathway. Targeting circADAMTS6 is thus expected to become a novel therapeutic strategy for glioblastoma.

Brominated halonitromethanes (Br-HNMs) are frequently detected when water containing bromide (Br−) is disinfected by UV/chlorine, which are characterized by a higher toxicity to human health than common disinfection byproducts (DBPs) under strict regulation. In this study, tryptophan served as a model precursor to explore Br-HNM generation during UV/chlorine disinfection of bromide-containing water. The results indicated that the Br-HNMs formed were firstly promoted to peak values and then were reduced gradually with time. During the process, dibromonitromethane (DBNM) and tribromonitromethane (TBNM) were the predominant Br-HNM species at first, and the predominant species would be converted to bromonitromethane (BNM) with time. Furthermore, increasing the Br−concentration in the range of 0.36 to 1.80 mM or the free chlorine concentration in the range of 0.2 to 1.8 mM could significantly promote the production of Br-HNMs while increasing the pH in the range of 6.0 to 8.0 could significantly reduce the production of Br-HNMs. Subsequently, it was elaborated that the forms and concentrations of chlorine and nitrogen also changed with time in the disinfection process. Finally, the pathways of Br-HNM production from tryptophan in bromide-containing water disinfected by UV/chlorine were speculated. This study can provide a better understanding of Br-HNM generation during UV/chlorine disinfection of bromide-containing water.

Advanced flexible electronic devices make urgent demand for wearing comfort and data accuracy. Piezoelectric composites exhibit great potential, but mutually constrained mechanical strength and electrical output limit their further applications. Here, we design a gradient PMN-PT/PVDF nanocomposite viaa non-equilibrium process integrated with a modified electrospinning and hot-pressing process to modulate the piezoelectric output and mechanical strength. The enhanced piezoelectric output together with the mechanical strength of the gradient structure are verified from both the experimental and simulation results. Ascribed to a unique three-dimensional gradient distribution, the prepared PMN-PT/PVDF nanocomposite exhibits an excellent mechanical strength (830 MPa) and piezoelectric performance (1.08 V), which are substantially higher than those of a randomly dispersed nanocomposite. The enhancement mechanism is revealed in terms of polarization, stress and crystallinity. These results of the gradient structure offer new opportunities to understand the structure-related mechanical and electrical behaviors of a nanocomposite, and support the design of a nanocomposite with overall performance.

Objective: Patients undergoing hematopoietic stem cell transplant (HSCT) need frequent transfusions, until their red blood cells (RBCs) and platelets start to recover. The safe transfusion for patients who receive ABO-incompatible HSCT is essential to the transplant process. To date, there is no user-friendly tool to choose the right blood product for transfusion treatment, despite the number of guidelines and expert advice on the subject. Methods: R/shiny is a powerful programming language for clinical data analysis and visualization. It can create interactive web applications that work in real-time. The web application named TSR was built using R programming, simplifying blood transfusion practice for ABO-incompatible HSCT with a one-click solution. Results: The TSR is divided into four main tabs. The home tab provides an overview of the application, while RBC, plasma and platelet transfusion tabs offer tailored suggestions for blood product selection in each category. Unlike traditional methods that rely on treatment guidelines and specialist consensus, TSR leverages the power of the R/Shiny interface to extract critical content based on user-specified parameters, providing an innovative approach to improve transfusion support. Conclusion: The present study highlights that the TSR enables real-time analysis, and promotes transfusion practice by offering a unique and efficient one-key output for blood product selection to ABO-incompatible HSCT. TSR has the potential to become a widely-utilized tool for transfusion services, providing a reliable and user-friendly solution that enhances transfusion safety in clinical practice.

Spaceborne observations of primary production (PP) are essential for understanding the role of phytoplankton in the biogeochemical cycles on a global or regional scale. In this study, the vertically generalized production model (VGPM) and two size-fractionated PP algorithms (namely, U10 and B17) were evaluated in the South China Sea (SCS). Comparison between estimated and in situ measured total PP showed the best performance of U10 with an $R^{2}$ of 0.65 and mean absolute percentage deviation (MAPD) of 31.11%. B17 produced better accuracy than U10 for PP from picophytoplankton (PPpico) and microphytoplankton (PPmicro), whereas U10-derived PP from nanophytoplankton (PPnano) agreed better with in situ measurements than B17-derived PPnano. Sensitivity analysis showed that PP estimation was most sensitive to chlorophyll-a (Chla), followed by euphotic zone depth ( $Z_{\mathrm {eu}}$ ), photosynthetically available radiation (PAR), and physiological parameters. With regional optimization of $Z_{\mathrm {eu}}$ , phytoplankton size class (PSC), photosynthesis-irradiance curve parameters, and Chla profile modeling, B17 was tuned for the SCS. Its accuracy was greatly improved, as indicated by slopes close to 1, $R^{2}\text{s} >$ 0.55, and MAPD < 145%, for all size classes and total PP. Application of the tuned algorithm to satellite produced data demonstrated a decreasing trend for the total PP, PPpico, and PPnano while no apparent trend for PPmicro. This study represents the feasibility of improving PP estimation from satellite observation for regional applications through retuning to local data. Our findings are useful for understanding the ecological response to climate change in the region and unveil the role of size-fractionated phytoplankton in biogeochemical and carbon cycles on a basin scale.

SH2 domains have been recognized as promising targets for various human diseases. However, targeting SH2 domains with phosphopeptides or small-molecule inhibitors derived from bioisosteres of the phosphate group is still challenging. Identifying novel bioisosteres of the phosphate group to achieve favorable in vivopotency is urgently needed. Here, we report the feasibility of targeting the STAT3-SH2 domain with a boronic acid group and the identification of a highly potent inhibitor compound 7by replacing the carboxylic acid of compound 4with a boronic acid. Compound 7shows higher binding affinity, better cellular potency, more favorable PK profiles, and higher in vivoantitumor activity than 4. The stronger anticancer effect of 7partially stems from its covalent binding mode with the SH2 domain, verified by the washout experiments. The relatively high level of sequence conservation among SH2 domains makes the results presented here of general significance.

Despite their multifaceted advantages, inverted perovskite solar cells (PSCs) still suffer from lower power conversion efficiencies (PCEs) than their regular counterparts, which is largely due to recombination energy losses (Eloss) that arise from the chemical, physical, and energy level mismatches, especially at the interfaces between perovskites and fullerene electron transport layers (ETLs). To address this problem, we herein introduce an aminium iodide derivative of a buckybowl (aminocorannulene) that is molecularly layered at the perovskite–ETL interface. Strikingly, besides passivating the PbI2-rich perovskite surface, the aminocorannulene enforces a vertical dipole and enhances the surface n-type character that is more compatible with the ETL, thus boosting the electron extraction and transport dynamics and suppressing interfacial Eloss. As a result, the champion PSC achieves an excellent PCE of over 22%, which is superior compared to that of the control device (∼20%). Furthermore, the device stability is significantly enhanced, owing to a lock-and-key-like grip on the mobile iodides by the buckybowls and the resultant increase of the interfacial ion-migration barrier. This work highlights the potential of buckybowls for the multifunctional surface engineering of perovskite toward high-performance and stable PSCs.

ZnO is a typical piezoelectric semiconductor, and enhancing the piezoelectric output of ZnO-based devices is essential for their efficient applications. Surface engineering is an effective strategy to improve the piezoelectric output of ZnO-based devices, but its unclear regulation mechanism leads to a lack of reasonable guidance for device design. In this work, the regulation effect of the barrier layer in ZnO-based piezoelectric devices is systematically investigated from the carrier perspective through surface engineering, resulting in a significant improvement (nearly 10-fold) in the output performance of piezoelectric devices. The regulation mechanism of the ZnO–Cu2O p–n heterojunction devices on piezoelectric output is revealed in terms of built-in electric field, depletion layer width, and junction capacitance. These findings facilitate further insight into the enhancement mechanism of the piezoelectric output of ZnO-based devices and provide reasonable ideas for efficient device design.

The Fe‐doped LiVPO4F/C cathode material was synthesized by a one‐step solid‐state reaction method. The effects of Fe doping content on the structure and electrochemical performance of LiVPO4F/C were investigated. X‐ray diffraction (XRD) analyses demonstrated that the appropriate addition of Fe3+did not destroy the lattice structure of LiVPO4F/C. Scanning electron microscopy (SEM) showed that the surface of LiVPO4F/C is covered by a carbon film. The decreased grain size of the Fe‐doped LiVPO4F/C could shorten the ion transport path and thus improve the migration rate of lithium ions. X‐ray photoelectron spectroscopy (XPS) showed that the Fe ion exists in the Fe‐doped LiVPO4F/C as Fe3+ion. At the discharge rate of 1 C, the initial discharge capacity and capacity retention rate of the LiV0.98Fe0.02PO4F/C after 500 cycles were 123.5 mAh/g and 88.6%, respectively. Fe‐doped LiVPO4F/C as the cathode material for Li‐ion batteries were prepared by the one‐step solid‐state method. At 1C, the capacity retention rates after 500 cycles of LiVPO4F/C and LiV0.98Fe0.02PO4F/C samples were 59.4% and 88.6%, respectively.

Hyperactive signal transducer and activator of transcription 3 (STAT3) signaling is frequently detected in human triple-negative breast cancer (TNBC) and gastric cancer, leading to uncontrolled tumor growth, resistance to chemotherapy, and poor prognosis. Thus, inhibition of STAT3 signaling is a promising therapeutic approach for both TNBC and gastric cancer, which have high incidences and mortality and limited effective therapeutic approaches. Here, we report a small molecule, WZ-2-033, capable of inhibiting STAT3 activation and dimerization and STAT3-related malignant transformation. We present in vitro evidence from surface plasmon resonance analysis that WZ-2-033 interacts with the STAT3 protein and from confocal imaging that WZ-2-033 disrupts HA-STAT3 and Flag-STAT3 dimerization in intact cells. WZ-2-033 suppresses STAT3-DNA-binding activity but has no effect on STAT5-DNA binding. WZ-2-033 inhibits the phosphorylation and nuclear accumulation of pY705-STAT3 and consequently suppresses STAT3-dependent transcriptional activity and the expression of STAT3 downstream genes. Moreover, WZ-2-033 significantly inhibited the proliferation, colony survival, migration, and invasion of TNBC cells and gastric cancer cells with aberrant STAT3 activation. Furthermore, administration of WZ-2-033 in vivo induced a significant antitumor response in mouse models of TNBC and gastric cancer that correlated with the inhibition of constitutively active STAT3 and the suppression of known STAT3 downstream genes. Thus, our study provides a novel STAT3 inhibitor with significant antitumor activity in human TNBC and gastric cancer harboring persistently active STAT3.

Residues of chloroquine phosphate (CQP) in the aquatic environment pose a potential hazard to aquatic organisms and human health. Herein, the degradation kinetics and pathways of CQP during ultraviolet/hydrogen peroxide (UV/H2O2) process were investigated. Results demonstrated that UV/H2O2process exhibited the highest performance for CQP degradation compared to the single UV or H2O2process. The second-order rate constants of CQP with hydroxyl radicals were determined as 8.9×109–1.2×1010M–1s–1at pH 4.8–10.8. With the increase of H2O2dosage from 0.2 to 3.0 mM, the degradation rate constant of CQP firstly improved from 0.0164 to 0.1267 min–1and then slightly reduced to 0.1104 min–1at 6.0 mM. The degradation efficiency of CQP by UV/H2O2was significantly promoted at pH 4.8. Cl–and HCO3–showed the unobvious effects on the CQP degradation. Meanwhile, a kinetic model was established to simulate the evolution of CQP and various reactive species during UV/H2O2process. The trend of predicted values of CQP degradation obtained from model simulation were well compared with experimental values. According to the identified intermediates of CQP degradation, the possible degradation pathways of CQP were proposed, which mainly involved N-deethylation, C–N bond cleavage, hydrogen abstraction, and N-oxidation. The aquatic toxicity of CQP degradation products was reduced relative to CQP, while the developmental and mutagenic toxicities of some intermediates were higher than CQP. Moreover, the economic consumption of UV/H2O2treatment of CQP was determined under varied H2O2concentrations. In general, UV/H2O2process may constitute an effective option for treating CQP-contaminated water.

In this study, the mechanism of enhanced coagulation was elucidated by oxidizing various components of the algae-laden water with a moderate oxidant, peroxyacetic acid (PAA), based on the optimization of the contents and species of coagulants and oxidants. It was shown that the combination of PAA (10 mg/L) and polymeric aluminosilicate iron (PSAF) (12 mg/L) was the optimal strategy for the treatment of algae-laden water due to its high removal rate of algae and the generation of larger flocs. Moreover, the synergistic and individual oxidation test of algae-laden water proved the moderate oxidation mechanism of PAA to enhance coagulation and algae removal through two pathways: the degradation of dissolved extracellular organic matter (dEOM) and the shedding of bound extracellular organic matter (bEOM) from the algae surface, which led to the aggregation and sedimentation of algae cells. Algae cells did not cause visible rupture and intracellular organic matter release in the presence of PAA and were not considered to be an unfavorable factor for PAA-enhanced coagulation treatment. In general, PAA enhanced the zeta potential of the algae-laden water, degraded humic acids, polysaccharides, proteins, and other organic matter, thus easier to remove the algae cells and pollutants through the coagulation process. This study provides a new insight for the mechanism of oxidation-enhanced coagulation technology.

Accurate forecasting of atmospheric rivers (ARs) holds significance in preventing losses from extreme precipitation. However, traditional numerical weather prediction (NWP) models are computationally expensive and can be limited in accuracy due to inaccurate physical parameter settings. To overcome these limitations, we propose a deep learning (DL) model, called GAN‐UNet, to forecast the AR occurrence, position, and intensity in East Asia. GAN‐UNet can capture the complex nonlinear relationship between the inputs at the past moment, including the vertically integrated water vapor transport (IVT), zonal wind at 850 hPa (U850), and meridional wind at 850 hPa (V850), and the forecast output (IVT, U850, or V850), whose results are comparable to NWP models. In addition, the average model (AM) by integrating the results generated by GAN‐UNet and European Centre for Medium‐Range Weather Forecasts (ECMWF) outperforms all the NWP models selected in this study, demonstrating its potential to improve the performance of NWP through the DL method. Specifically, the 5‐day average F1 scores of the AM are 0.777 and 0.845, whose values are significantly better than those obtained by ECMWF (0.712 and 0.794) in the two key regions of East Asia; The AM 5‐day average intersection over unions are 0.706 and 0.688 while the values of ECMWF are 0.675 and 0.64; in terms of intensity forecast, GAN‐UNet and AM exhibited lower differences in most of the intensity bins, except for the final bin with IVT more than 825 kg m−1s−1. With this thorough analysis, GAN‐UNet is shown as an effective model to forecast ARs. This work presents a deep learning (DL) model (called GAN‐UNet) for the spatio‐temporal atmospheric rivers (ARs) forecast. Our goal is to perform long lead‐time AR event forecasts accurately and efficiently. The data from 1959 to 2022 over 40°E−180°E, 20°S−60°N are used for training, validation, and testing. The results show that the proposed GAN‐UNet can forecast the AR occurrence, position, and intensity accurately and its performance is comparable with the state‐of‐the‐art numerical weather prediction (NWP) model. In addition, the ensemble of GAN‐UNet and the NWP model outperform all the NWP models selected in this study. However, The DL model still has certain limitation. Specifically, while GAN‐UNet and the ensemble model demonstrate superior forecast capabilities for most intensity bins in AR events compared to NWP models, they are severely underestimated for the grids of the final bin. The results show that the DL model can effectively forecast AR events in East Asia, and further improve the forecast accuracy of NWP by combining it with NWP model, which holds significance in extreme precipitation forecast. A deep learning model (GAN‐UNet) is developed for efficient and accurate atmospheric river forecastGAN‐UNet achieves comparable performance to ECMWF and NCEP on atmospheric river forecastThe outcomes obtained from the average of GAN‐UNet and NWP exhibit superior performance compared to all the individual NWP models selected in this study A deep learning model (GAN‐UNet) is developed for efficient and accurate atmospheric river forecast GAN‐UNet achieves comparable performance to ECMWF and NCEP on atmospheric river forecast The outcomes obtained from the average of GAN‐UNet and NWP exhibit superior performance compared to all the individual NWP models selected in this study

Hundreds of C60derivatives stand out as electrontransporting materials(ETMs), for example, in perovskite solar cells(PSCs), due to their properties on electron extraction or defect passivation. However, it still lacks of guidelines to update C60-based ETMs with excellent photoelectric properties. In this work, crystallographic data of eight C60-based ETMs, including pristine C60and the well-known PCBM as well as six newly synthesized fullerenes, are analyzed to establish the connections between derivatized structures and photoelectric properties for the typical carbon cluster of C60. In terms of packing centroid-centroid distance between neighboring carbon cages, the crystallographic data are useful for probing photoelectric properties, such as electrochemical properties, electron mobility and photovoltaic performances, and therefore facilitate to design novel C60-based ETMs for PSCs with high performances.

This study investigated the effectiveness of peroxymonosulfate (PMS) as an oxidative agent in micro-contaminant removal with activation viasimulated solar irradiation (Xe-lamp, emission spectrum ranging from 300 to 800 nm). During solar/PMS treatment, the abatement of nitrobenzene (NB), flunixin meglumine (FMME), aspirin (ASA), and benzoic acid (BA) followed pseudo-first order kinetics, with degradation at pH 8.5 faster (1.28–1.78 times) than that at pH 5.5. The removal of NB (1.22 mg L−1), FMME (4.92 mg L−1), ASA (1.80 mg L−1), and BA (1.23 mg L−1) reached 51.2%, 68.0%, 66.6%, and 90.7% in 15 min at pH 8.5, respectively, with corresponding pseudo-first order rate constants (kobs) of 5.1 × 10−2, 7.7 × 10−2, 7.4 × 10−2, and 1.6 × 10−1min−1, respectively. Production of hydroxyl radicals, sulfate radicals (SO4−), and other reactive oxygen species (ROS) was determined by using NB and BA as probe compounds in the solar/PMS system. At pH of 5.5–8.5, SO4−made a dominant contribution (45.7% and 52.0%, respectively) to the overall removal of ASA and FMME. Compared with treatment of chlorination alone, solar/PMS pretreatment followed by post-chlorination resulted in a significant increase in disinfection by-product (DBP) formation (by 176% for trihalomethanes and 273% for haloacetic acids) in the Yangtze River water samples, as well as inhibition of algae growth (by 35.6%) due to higher toxic effects of residual PMS or potential oxidation intermediates in the system. The lowest EE/Ototalconsumed in the solar/PMS system was estimated to be 72–110 kW h m−3order−1with the optimal PMS dosages of 0.36–0.68 mM. This work identified ROS generated during solar/PMS treatment and evaluated their contributions to the efficient depletion of organic micro-pollutants. The potential risk of increased DBP production and bio-toxicity was also investigated when applying the system to actual water treatment.

In metazoans the endoplasmic reticulum (ER) undergoes extensive remodeling during the cell cycle. The endosomal sorting complexes required for transport (ESCRT) protein CHMP7 coordinates ESCRT-III dependent nuclear envelope reformation during mitotic exit. However, potential roles of ER-associated CHMP7 at non-mitotic stages remain unclear. Here we discovered a new role of CHMP7 in mediating three-way ER and ER-mitochondrial membrane contact sites (MCSs). We showed that CHMP7 localizes to multiple cellular membranes including the ER, mitochondrial-associated membranes (MAMs) and the outer mitochondrial membrane (OMM) via its N-terminal membrane-binding domain. CHMP7 undergoes dynamic assembly at three-way ER junctions and ER-mitochondrial MCSs through hydrophobic interactions among α helix-1 and α helix-2 of the C-terminal CHMP-like domain, which was required for tethering different organelles in vivo. Furthermore, CHMP7 mediates the formation of three-way ER junctions in parallel with Atlastins (ATLs). Importantly, CHMP7 also regulates ER-mitochondrial interactions and its depletion affects mitochondrial division independently of ESCRT complex. Taken together, our results suggest a direct role of CHMP7 in the formation of the ER contacts in interphase.

Background: Amomum villosum is an important medicinal and edible plant owing to itsvaluable compositions of volatile and non-volatile compounds. Objective: The study was conducted to reveal the chemical constituents and medicinal values of A. villosumagainst various diseases. Methods: A critical and comprehensive data mining from 2004 to 2021 was performed based onCNKI, PubMed, and Google. Results: 120 Compounds have been reported collectively in seeds, peels, and rhizomes of A. villosum,10 compounds were common however the content of bornyl acetate was maximum inseeds and peels. Similarly, Amomi fructus of China and Vietnam showed 59 different types ofvolatile compounds while 13 were common, the round large black fruits (1.56% bornyl acetateand 4.05% volatile oil) and long small red fruits type (1.64% bornyl acetate and 3.04% volatileoil) from China showed good quality and high medicinal values. In addition, Amomi fructus manifested30-40 kinds of nonvolatile compounds, i.e., phenolic, polysaccharides, saponins, flavonoid,vanillic acid, catechin, epicatechin, polydatin, isoquercitrin, quercitrin, glycosides, inorganic andorganic acids. Conclusion: A. villosum is widely used as anti-inflammatory, gastrointestinal protection, antiobesity,anticancer, antioxidant, analgesic, bacteriostasis, antidiabetic and anti-COVID-19, etc. So,it is manifested that the fruit, flowers, roots, stems, and leaves of A. villosum can be used as amedicine, especially fruit (Amomi fructus=Sharen), as the best functional food for the COVID-19treatment and gastrointestinal protection as well as prevention of other diseases.

We describe the discovery of histone deacetylase (HDACs) 1, 2, and 3 inhibitors with ethyl ketone as the zinc-binding group. These HDACs 1, 2, and 3 inhibitors have good enzymatic and cellular activity. Their serum shift in cellular potency has been minimized, and selectivity against hERG has been improved. They are also highly selective over HDACs 6 and 8. These inhibitors contain a variety of substituted heterocycles on the imidazole or oxazole scaffold. Compounds 31and 48stand out due to their good potency, high selectivity over HDACs 6 and 8, reduced hERG activity, optimized serum shift in cellular potency, and good rat and dog PK profiles.

On-chip metasurfaces play a crucial role in bridging the guided mode and free-space light, enabling full control over the wavefront of scattered free-space light in an optimally compact manner. Recently, researchers have introduced various methods and on-chip metasurfaces to engineer the radiation of guided modes, but the total functions that a single metasurface can achieve are still relatively limited. In this work, we propose a novel on-chip metasurface design that can multiplex up to four distinct functions. We can efficiently control the polarization state, phase, angular momentum, and beam profile of the radiated waves by tailoring the geometry of V-shaped nanoantennas integrated on a slab waveguide. We demonstrate several innovative on-chip metasurfaces for switchable focusing/defocusing and for multifunctional generators of orbital angular momentum beams. Our on-chip metasurface design is expected to advance modern integrated photonics, offering applications in optical data storage, optical interconnection, augmented reality, and virtual reality.

In this Communication, we develop a two-step acyclic diene metathesis in situpolymerization/cross-linking method to synthesize uniaxially aligned main-chain liquid crystal elastomers with chemically bonded near-infrared absorbing four-alkenyl-tailed croconaine-core cross-linkers. Because of the extraordinary photothermal conversion property, such a soft actuator material can raise its local temperature from 18 to 260 °C in 8 s, and lift up burdens 5600 times heavier than its own weight, under 808 nm near-infrared irradiation.

The molecular clock model is fundamental for inferring species divergence times from molecular sequences. However, its direct application may introduce significant biases due to sequencing errors, recombination events, and inaccurately labeled sampling times. Improving accuracy necessitates rigorous quality control measures to identify and remove potentially erroneous sequences. Furthermore, while not all branches of a phylogenetic tree may exhibit a clear temporal signal, specific branches may still adhere to the assumptions, with varying evolutionary rates. Supporting a relaxed molecular clock model better aligns with the complexities of evolution. The root-to-tip regression method has been widely used to analyze the temporal signal in phylogenetic studies and can be generalized for detecting other phylogenetic signals. Despite its utility, there remains a lack of corresponding software implementations for broader applications. To address this gap, we present shinyTempSignal, an interactive web application implemented with the shiny framework, available as an R package and publicly accessible at https://github.com/YuLab-SMU/shinyTempSignal. This tool facilitates the analysis of temporal and other phylogenetic signals under both strict and relaxed models. By extending the root-to-tip regression method to diverse signals, shinyTempSignal helps in the detection of evolving features or traits, thereby laying the foundation for deeper insights and subsequent analyses.

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Light emitting diode (LED-UV)/chlorine disinfection can replace UV/chlorine disinfection in wastewater treatment plants and water supply plants. Halonitromethanes (HNMs) are a class of novel nitrogenous disinfection by-products, which are characterized by higher cytotoxicity and genotoxicity than regulated disinfection by-products. Herein, the impact factors and pathways of HNMs formation from aspartic acid (ASP) were investigated during LED-UV265/chlorine disinfection. The results showed that three types of chlorinated-HNMs (Cl-HNMs) were found during LED-UV265/chlorine disinfection, and their concentrations increased first and then declined as the reaction progressed. Cl-HNMs yields increased with increasing LED-UV265intensity, free chlorine dosage, and ASP concentration, which declined with increasing pH (6.0–8.0). Meantime, the important impact of the coexisting ions contained in water matrices on HNMs formation from ASP was observed during LED-UV265/chlorine disinfection. It was found that copper ions (Cu2+) promoted Cl-HNMs formation. Furthermore, when bromide (Br−) appeared during LED-UV265/chlorine disinfection, nine types of HNMs were detected simultaneously. Moreover, Br−not only converted Cl-HNMs toward brominated (chlorinated)-HNMs and brominated-HNMs but also showed a marked effect on HNMs concentrations and species. Subsequently, the possible pathways of HNMs formation from ASP were proposed during LED-UV265/chlorine disinfection. At last, it was proved that the formation trends of HNMs obtained in the real waters were similar to those in simulated waters. This work elaborated on the influence factors and pathways of HNMs formation, which is conducive to controlling the HNMs produced during LED-UV265/chlorine disinfection.

This study demonstrates the feasibility and effectiveness of utilizing native soils as a resource for inocula to produce n-caproate through the chain elongation (CE) platform, offering new insights into anaerobic soil processes. The results reveal that all five of the tested soil types exhibit CE activity when supplied with high concentrations of ethanol and acetate, highlighting the suitability of soil as an ideal source for n-caproate production. Compared with anaerobic sludge and pit mud, the native soil CE system exhibited higher selectivity (60.53%), specificity (82.32%), carbon distribution (60.00%), electron transfer efficiency (165.00%), and conductivity (0.59 ms∙cm−1). Kinetic analysis further confirmed the superiority of soil in terms of a shorter lag time and higher yield. A microbial community analysis indicated a positive correlation between the relative abundances of Pseudomonas, Azotobacter, and Clostridiumand n-caproate production. Moreover, metagenomics analysis revealed a higher abundance of functional genes in key microbial species, providing direct insights into the pathways involved in n-caproate formation, including in situCO2utilization, ethanol oxidation, fatty acid biosynthesis (FAB), and reverse beta-oxidation (RBO). The numerous functions in FAB and RBO are primarily associated with Pseudomonas, Clostridium, Rhodococcus, Stenotrophomonas, and Geobacter, suggesting that these genera may play roles that are involved or associated with the CE process. Overall, this innovative inoculation strategy offers an efficient microbial source for n-caproate production, underscoring the importance of considering CE activity in anaerobic soil microbial ecology and holding potential for significant economic and environmental benefits through soil consortia exploration.

Objective: Autosomal dominant polycystic kidney disease (ADPKD) is mainly caused by the pathogenic mutation of PKD1or PKD2gene and usually affects bilateral kidneys. Synonymous mutations are generally assumed to be neutral as they do not alter amino acids. Herein, we described an extremely rare ADPKD child caused by a heterozygous synonymous mutation of PKD2gene accompanied by massive proteinuria and congenital solitary kidney. Methods: Clinical characteristics of the patients were summarized. Whole-exome sequencing was performed to screen the disease-causing gene mutation, and reverse transcription polymerase chain reaction (RT-PCR) and Sanger sequencing were applied to analyze the impact of the identified mutation on gene transcription and splicing. Results: Polycystic changes were found in the solitary kidney of a girl initially presented with nephrotic-range proteinuria. Thereafter her mother and 2 other family members were diagnosed to be ADPKD. Whole-exome sequencing of the proband identified a heterozygous synonymous mutation (c.1716G>A, p.Lys572=) located in the splicing site of exon 7 in PKD2gene, which was co-segregated with the PKD phenotype in the family. RT-PCR and direct sequencing of amplified products revealed that this heterozygous synonymous mutation led to exon7 skipping in PKD2gene. Conclusion: We reported an extremely rare child case of ADPKD2in combination with solitary kidney and nephrotic-range proteinuria, and firstly confirmed the pathogenicity of a heterozygous synonymous mutation (c.1716G>A) in PKD2gene. The results indicate that synonymous mutations should not be excluded from disease-causing if they are located in splicing site of an exon.

We report the first fast switchable multiwavelength optical parametric oscillator based on aperiodic optical superlattice technology. The constructed aperiodically poled lithium niobate (APPLN) integrates the functionalities of two quasi-phase-matching devices on a chip to work simultaneously as an electro-optic (EO) switchable notch-like filter and a multiline optical parametric downconverter. When such an APPLN is built in a 1064-nm-pumped optical resonator system, we achieve the oscillation of dual signals at 1540 and 1550 nm, for a single signal at 1540 nm, and a single signal at 1550 nm in the system when the 3-cm-long APPLN is driven by 0 V, 354 V, and 805 V, respectively. The switching among the three signal spectra is operationally simple and electro-optically fast. The electro-optically switched signals also feature enhanced power spectral density due to the unique EO gain-spectrum filtering mechanism employed in this work.

In p-i-nstructure perovskite solar cells (PSCs), the most prevalent electron transport layer (ETL), [6, 6]-phenyl-C61-butyric acid methyl ester (PC61BM), acts as both electron extractor and protective coverage to the underlayer perovskite. Notably, multifunctional mixed fullerene ETLs show great potential in further improving both the power conversion efficiency (PCE) and stability of PSCs compared to the single PC61BM ETL. In this work, we reported the mixed fullerene ETLs comprising of PC61BM and its two analogs with different length of fluorocarbon chains, [6, 6]-phenyl-C61-buryric acid 1H,1H-trifluoro-1-ethyl ester (abbreviated, CF3–PC61BM) and [6, 6]-phenyl-C61-buryric acid 1H, 1H-tridecafluoro-1-heptyl ester (abbreviated, C6F13–PC61BM). We obtained excellent PCEs of 18.37% and 17.71% for 1 wt % CF3–PC61BM- and C6F13–PC61BM-based PSCs (1 wt % addition of PC61BM) with CH3NH3PbI3(MAPbI3) perovskites, respectively. Moreover, champion PCEs of ∼19% were obtained based on the CsFAMAPbIBr perovskites. Subsequent experiments demonstrated that the fluorocarbon chains of CF3–PC61BM and C6F13–PC61BM assembled at the surfaces of ETLs with the formation of thin-layer moisture-resistant protective coverage above perovskite. Results show that it significantly retarded water penetrating down to perovskite layers and led to optimal humidity stability under ambient atmosphere.

Synthesis of bridged scaffolds via Type II cyclization constitutes substantial challenges due to the intrinsic ring strain accumulated in reaction transition states. Catalytic enantioselective Type II-cyclization methods are even rarer. Here, we describe a detailed study of developing a Rh(I)-catalyzed enantioselective intramolecular Type II cyclization of alkynes via C–C activation of cyclobutanones. This method offers a rapid approach to access a wide range of functionalized [3.3.1]-bridged bicycles along with an exocyclic olefin and an all-carbon quaternary stereocenter. Excellent enantioselectivity has been achieved using a combination of cationic rhodium(I) and DTBM-segphos. Attributed to the redox neutral and strong acid/base-free reaction conditions, high chemoselectivity has also been observed. For the oxygen-tethered substrates, the reaction can proceed at room temperature. In addition, partial kinetic resolution has been achieved for substrates with existing stereocenters, forging interesting chiral tricyclic scaffolds. The methylalkyne-derived substrates gave unexpected dimeric structures in good yield with excellent enantioselectivity and complete diastereoselectivity. Furthermore, the bridged bicyclic products can be diversely functionalized through simple transformations. Finally, mechanistic studies reveal a surprising reaction pathway that involves forming a metal-stabilized anti-Bredt olefin intermediate.

The structure-dependent thermal stability of fullerene electron transport layers (ETLs) and its impact on device stability have been underrated for years. Based on cocrystallographic understanding, herein, we develop a thermally stable ETL comprising a hybrid layer of [6,6]-phenyl-C61-butyric acid methyl ester (PCBM) and [6,6]-phenyl-C61-propylbenzene (PCPB). By tuning the weight ratios of PCBM and PCPB to influence the noncovalent intermolecular interactions and packing of fullerene derivatives, we obtained a champion device based on the 20PCPB (20 wt % addition of PCPB into the mixture of PCBM/PCPB) ETL and excellent thermal stability of 500 h under 85 °C thermal aging in a N2atmosphere in the dark. The present work exemplifies that cocrystallography can be a precise tool to probe the interaction and aggregation of fullerene derivatives in ETLs, and mixed fullerene derivatives can be sought as promising ETLs to enhance the long-term stability of perovskite solar cells under high-temperature working environments.

C−C bond activation has emerged as an increasingly useful approach for constructing complex molecular scaffolds through unusual bond-disconnection strategies. As a common versatile functional group, ketones provide an excellent handle and platform for C−C bond activation reactions. Utilizing strain-release, carbon-monoxide-extrusion, and directing-group (DG) approaches, diverse transformations of various ketones have been developed in the past few decades through cleavage of their α C−C bonds. This review highlights the development of C−C bond-activation strategies for both strained and less strained ketones with a focus on transition-metal (TM)-catalyzed approaches.

Recent clinical evaluation of everolimus for seizure reduction in patients with tuberous sclerosis complex (TSC), a disease with overactivated mechanistic target of rapamycin (mTOR) signaling, has demonstrated the therapeutic value of mTOR inhibitors for central nervous system (CNS) indications. Given that everolimus is an incomplete inhibitor of the mTOR function, we sought to develop a new mTOR inhibitor that has improved properties and is suitable for CNS disorders. Starting from an in-house purine-based compound, optimization of the physicochemical properties of a thiazolopyrimidine series led to the discovery of the small molecule 7, a potent and selective brain-penetrant ATP-competitive mTOR inhibitor. In neuronal cell-based models of mTOR hyperactivity, 7corrected the mTOR pathway activity and the resulting neuronal overgrowth phenotype. The new mTOR inhibitor 7showed good brain exposure and significantly improved the survival rate of mice with neuronal-specific ablation of the Tsc1 gene. These results demonstrate the potential utility of this tool compound to test therapeutic hypotheses that depend on mTOR hyperactivity in the CNS.

An external magnetic field is applied in resistance spot welding (RSW) of 3 mm thick AA 6061-T6 sheets to improve the weld quality. Under the action of the external magnetic field, an additional circumferential flow is generated, resulting in the reduction of cooling rate and the change of solidification mode, and it finally influences the nugget profiles, microstructural evolutions, and mechanical properties. The profile of the magnetically assisted resistance spot welding (MA-RSW) nugget became more regular and freer of defects, e.g., the internal shrinkage defects and eyelash-like hot cracks. Moreover, a double-layered columnar grain zone and a nearly single-structured equiaxed grain zone were finally obtained. The tensile properties of the MA-RSW welds were significantly improved by increasing nugget diameter, eliminating defects, and complicating the crack propagation path. As a result, the application of the external magnetic field could achieve an energy-saving effect.

Antisolvent-assisted crystallization is adopted widely in the preparation of double-cation [e.g., cesium/formamidinium (Cs/FA), formamidinium/methylammonium (FA/MA)] and triple-cation (e.g., Cs/FA/MA) FA-based perovskite solar cells (PSCs) to enhance their power conversion efficiencies (PCEs) and device stability. Although many antisolvents have been applied to treat various perovskites with different compositions, their crystallization mechanisms have remained unclear. In this study, we investigated the effects of a series of green antisolvents—namely, the ethers diethyl ether, anisole, diisopropyl ether (DIE), and dibutyl ether—on the crystallization of perovskites. We found that the formation of an intermediate phase was heavily determined by the antisolvent's polarity. Indeed, through judicious control of the antisolvent's polarity, it was possible to form a pure intermediate phase, without a PbI2or perovskite phase. Upon thermal annealing, the crystallization of perovskites was improved. Understanding the mechanism of formation of the intermediate phase led us to identify DIE as a green antisolvent with universal perovskite compatibility, achieving champion PCEs of 20.05%, 20.15%, and 21.26% for Cs/FA, FA/MA, and Cs/FA/MA, respectively. The PCE of large-area (1 cm2) PSCs reached 18.51%. Furthermore, the repeatability of these champion PCEs was greatly improved. This work contributes to the understanding of antisolvent's polarity as an important factor affecting the formation of a pure intermediate phase of FA-based perovskites, which also offers a greener approach for the production of PSCs.

Recent studies have indicated that the presence of ground-glass opacity (GGO) components is associated with favorable survival. The purpose of this study was to reveal the prognostic value of GGO components and differences in prognostic factors for part-solid and solid lesions in invasive stage I NSCLC.