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AutoDock Vina is one of the most popular molecular docking tools. In the latest benchmark CASF-2016 for comparative assessment of scoring functions, AutoDock Vina won the best docking power among all the docking tools. Modern drug discovery is facing a common scenario of large virtual screening of drug hits from huge compound databases. Due to the seriality characteristic of the AutoDock Vina algorithm, there is no successful report on its parallel acceleration with GPUs. Current acceleration of AutoDock Vina typically relies on the stack of computing power as well as the allocation of resource and tasks, such as the VirtualFlow platform. The vast resource expenditure and the high access threshold of users will greatly limit the popularity of AutoDock Vina and the flexibility of its usage in modern drug discovery. In this work, we proposed a new method, Vina-GPU, for accelerating AutoDock Vina with GPUs, which is greatly needed for reducing the investment for large virtual screens and also for wider application in large-scale virtual screening on personal computers, station servers or cloud computing, etc. Our proposed method is based on a modified Monte Carlo using simulating annealing AI algorithm. It greatly raises the number of initial random conformations and reduces the search depth of each thread. Moreover, a classic optimizer named BFGS is adopted to optimize the ligand conformations during the docking progress, before a heterogeneous OpenCL implementation was developed to realize its parallel acceleration leveraging thousands of GPU cores. Large benchmark tests show that Vina-GPU reaches an average of 21-fold and a maximum of 50-fold docking acceleration against the original AutoDock Vina while ensuring their comparable docking accuracy, indicating its potential for pushing the popularization of AutoDock Vina in large virtual screens.

Compared with widely established monovalent-ion batteries, aqueous multivalent-ion batteries promise higher capacity release by achieving multiple electron-transfer events per ion intercalation in the host material. Despite plausibility, this high-capacity dream is untenable with the total tolerable redox charge-transfer limit of the host material for all carrier species equally, which is historically assumed to depend on the material rather than the guest carrier itself, and the kinetic hysteresis induced by larger charge/radius ratios induced kinetic hysteresis further enlarges the divide. Herein, we report that copper carrier redox in vanadium sulfide (VS 2 ) exceeds the intrinsic intercalation capacity boundary, with the highest capacity release as 675 mAh g -1 at 0.4 A g -1 among all VS 2 cathodes previously reported. Operando X-ray absorption spectroscopy, operando synchrotron X-ray diffraction and composite ex situ characterization jointly demonstrated that intercalated divalent copper is preferentially involved in redox afforded extra electron transfer to form reversible monovalent copper pillars, thus not only ensuring stable topological de/intercalation with high capacity but also sustaining fast migration kinetic paths through reconfigurable pillar effects. Intercalated carrier redox reported here emphasizes the interlayer variable valence advantage of multivalent ions, providing insights into high-performance multivalent-ion storage chemistry in aqueous batteries. Aqueous batteries with multivalent-ion storage chemistry offer higher theoretical capacity than monovalent-ion. Here, authors report divalent copper intercalation into vanadium disulfide with additional copper redox that provides higher capacity than intercalation transition metal redox alone.

Alternative splicing is a fundamental mechanism that enhances proteomic diversity and modulates gene function, with its dysregulation being a hallmark of numerous diseases. Despite its biological significance, the real‐time monitoring of spliced mRNA isoforms in living cells remains challenging due to limited specificity and sensitivity in existing methods. Herein, we present a Stringent dUPlex‐activated Error‐Robust (SUPER) platform, an in situ, split‐DNAzyme‐based system enabling precise imaging of mRNA splicing events in live cells. SUPER employs an identical parental DNAzyme reassembled via isoform‐specific intron‐exon junctions, providing high‐fidelity discrimination of closely related splicing variants. Its dual‐site‐activated fluorescence design ensures error‐robust, background‐minimized imaging with spatial colocalization as an intrinsic validation mechanism. Beyond dynamic isoform profiling, the programmable nature of SUPER enables its conversion into a spatially confined catalytic antenna, locally activating therapeutic aptamers without affecting off‐target transcripts. This approach further allows for real‐time tracking of variant integrity and decay by monitoring subtle changes in probe colocalization. Our platform offers a powerful tool for dissecting splicing mechanisms and holds promise for therapeutic intervention in splicing‐associated diseases by enabling isoform‐selective gene regulation while mitigating oligonucleotide toxicity. A Stringent dUPlex‐activated Error Robust (SUPER) DNAzyme system enables real‐time imaging of alternative mRNA splicing (e.g., Bcl‐xL/Bcl‐xS) in living cells via target‐triggered split‐DNAzyme reassembly and dual‐color fluorescence. It also achieves mRNA‐selective knockdown through DNAzyme‐based gene regulation, serving as a versatile tool for splicing dynamics research and RNA‐guided precision medicine.

Chronic non-healing of diabetic wound (DW) remains a critical clinical challenge worldwide. Sustained oxidative stress and prolonged inflammatory responses disrupt the wound microenvironment, while bacterial colonization and biofilm formation on the wound bed compromise drug penetration, consequently leading to suboptimal outcomes with conventional approaches. Here, we developed a core-shell structured microneedle (MN) patch system, designated as MN@Ple/Exo Q10 , to precisely regulate the DW microenvironment through sequential drug release. The photothermal-responsive microneedle patch MN@Ple/Exo Q10 features a dual-phase release: the outer shell’s antimicrobial peptide (Pleurocidin) addresses initial infection, while the core’s engineered exosomes (Exos Q10 ) mitigate oxidative stress and subsequently regulate immune responses. When combined with near-infrared (NIR)-triggered photothermal therapy, this system effectively promotes the healing of DW. This study details that the sustained release of Exos Q10 effectively inhibits high glucose (HG)-induced ferroptosis in vitro, demonstrating potent antioxidant activity and anti-inflammatory capacity. Furthermore, in a S. aureus -infected diabetic mouse wound model, MN@Ple/Exo Q10 demonstrates potent antibacterial activity while mitigating oxidative stress, suppressing inflammation and promoting angiogenesis, thereby accelerating wound healing. Collectively, the developed spatiotemporally controlled MN system overcomes bacterial barriers and stabilizes exosomal delivery, enabling comprehensive regulation of the microenvironment in DWs. This breakthrough approach presents a novel and translational strategy for DW therapy. Graphical abstract

Gesture recognition is critical in the field of Human-Computer Interaction, especially in healthcare, rehabilitation, sign language translation, etc. Conventionally, the gesture recognition data collected by the inertial measurement unit (IMU) sensors is relayed to the cloud or a remote device with higher computing power to train models. However, it is not convenient for remote follow-up treatment of movement rehabilitation training. In this paper, based on a field-programmable gate array (FPGA) accelerator and the Cortex-M0 IP core, we propose a wearable deep learning system that is capable of locally processing data on the end device. With a pre-stage processing module and serial-parallel hybrid method, the device is of low-power and low-latency at the micro control unit (MCU) level, however, it meets or exceeds the performance of single board computers (SBC). For example, its performance is more than twice as much of Cortex-A53 (which is usually used in Raspberry Pi). Moreover, a convolutional neural network (CNN) and a multilayer perceptron neural network (NN) is used in the recognition model to extract features and classify gestures, which helps achieve a high recognition accuracy at 97%. Finally, this paper offers a software-hardware co-design method that is worth referencing for the design of edge devices in other scenarios.

• AGD aims for a green environment, sustainable agriculture and clean water. • Presenting examples of the impact of agriculture on water quality. • Presenting examples of solutions for sustainable agriculture and improved water quality. • Integration of livestock and cropping systems is possible on a farm or among farms. • Providing recommendations for further development of sustainable agriculture. Crop and livestock production are essential to maintain food security. In China, crop and livestock production were integrated in the past. Today, small backyard systems are still integrated but the larger livestock farms are landless and largely geographically separated from crop production systems. As a result, there is less recycling of animal manures and there are lower nutrient use efficiencies in the Chinese food production systems. This, in turn, results in considerable losses of nutrients, causing water pollution and harmful algal blooms in Chinese lakes, rivers and seas. To turn the tide, there is a need for agricultural “green” development for food production through reintegrating crop and livestock production. An additional wish is to turn the Chinese water systems “blue” to secure clean water for current and future generations. In this paper, current knowledge is summarized to identify promising interventions for reintegrating crop and livestock production toward clean water. Technical, social, economic, policy and environmental interventions are addressed and examples are given. The paper highlights recommended next steps to achieve “green” agriculture and “blue” water in China.

Meeting the United Nations’ (UN’s) 17 Sustainable Development Goals (SDGs) has become a worldwide mission. How these SDGs interrelate, however, is not well known. We assess the interactions between SDGs for the case of water pollution by nutrients in China. The results show 319 interactions between SDGs for clean water (SDGs 6 and 14) and other SDGs, of which 286 are positive (synergies) and 33 are negative (tradeoffs) interactions. We analyze six scenarios in China accounting for the cobenefits of water pollution control using a large-scale water quality model. We consider scenarios that benefit from synergies and avoid tradeoffs. Our results show that effective pollution control requires accounting for the interactions between SDGs. For instance, combining improved nutrient management, efficient food consumption, and climate mitigation is effective for simultaneously meeting SDGs 6 and 14 as well as other SDGs for food, cities and climate. Our study serves as an example of assessing SDG interactions in environmental policies in China as well as in other regions of the world. The UN’s 17 Sustainable Development Goals (SDGs) are highly interrelated. This study finds 319 interactions between SDGs for the case of water pollution in China. Results show that effective pollution control requires accounting for these interactions.

Background Recently, trimethylamine-N-oxide (TMAO) plasma levels have been proved to be associated with atherosclerosis development. Among the targets aimed to ameliorating atherosclerotic lesions, inducing bile acid synthesis to eliminate excess cholesterol in body is an effective way. Individual bile acid as endogenous ligands for the nuclear receptor has differential effects on regulating bile acid metabolism. It is unclear whether bile acid profiles are mechanistically linked to TMAO-induced development of atherosclerosis. Methods Male apoE −/− mice were fed with control diet containing 0.3% TMAO for 8 weeks. Aortic lesion development and serum lipid profiles were determined. Bile acid profiles in bile, liver and serum were measured by liquid chromatographic separation and mass spectrometric detection (LC-MS). Real-time PCRs were performed to analyze mRNA expression of genes related to hepatic bile acid metabolism. Results The total plaque areas in the aortas strongly increased 2-fold ( P  < 0.001) in TMAO administration mice. The levels of triglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-c) in TMAO group were also significantly increased by 25.5% ( P  = 0.044), 31.2% ( P  = 0.006), 28.3% ( P  = 0.032), respectively. TMAO notably changed bile acid profiles, especially in serum, the most prominent inductions were tauromuricholic acid (TMCA), deoxycholic acid (DCA) and cholic acid (CA). Mechanically, TMAO inhibited hepatic bile acid synthesis by specifically repressing the classical bile acid synthesis pathway, which might be mediated by activation of small heterodimer partner (SHP) and farnesoid X receptor (FXR). Conclusions These findings suggested that TMAO accelerated aortic lesion formation in apoE −/− mice by altering bile acid profiles, further activating nuclear receptor FXR and SHP to inhibit bile acid synthesis by reducing Cyp7a1 expression.

Government subsidies have been instrumental in fostering the development of the China‐Europe Railway Express (CERE), yet the continued implementation without thought has led to significant market distortions and inefficiency, raising a critical policy dilemma: whether to maintain, reduce, or phase out subsidies. To address this question, this paper employs an evolutionary game model to examine the strategic interactions between local governments and railway companies. We analyze their evolutionarily stable strategies (ESS) and evaluate the cumulative utility of local governments under varying subsidy schemes. The key findings indicate: (1) railway companies consistently prefer high‐frequency shift (HFS) operations, irrespective of subsidy schemes; (2) the ESS for the local governments is highly sensitive to human resource costs and opportunity cost; (3) the initial probabilities of HFS and subsidy strategies affect the convergence speed towards ESS but do not alter the final ESS; and (4) the optimal subsidy scheme can maximize local governments’ cumulative utility. By integrating these findings into a multiperiod cumulative‐utility framework, the study provides a basis for determining strategic subsidy levels that improve governmental welfare while reducing long‐term subsidy dependence. These results offer actionable guidance for designing more targeted, transition‐sensitive, and fiscally sustainable CERE subsidy policies.

Objective: The prognosis of patients with advanced melanoma remains poor, particularly in those with brain metastases. To date, no standardized later-line treatment regimen has been established for this patient population. This study aimed to explore prognostic factors in patients with advanced melanoma and brain metastases, with a specific focus on the prognostic significance of baseline lactate dehydrogenase (LDH) levels and cranial radiotherapy. Materials and Methods: This retrospective cohort study consecutively enrolled 145 patients diagnosed with melanoma brain metastases (MBM) between 1 December 2015 and 31 August 2024. Baseline LDH data were available for 139 patients (95.9%), while the remaining six cases were excluded from LDH-stratified analyses. Patients were divided into an elevated LDH group (>250 U/L) and a normal LDH group (≤250 U/L). Collected clinical variables included brain intensity-modulated radiotherapy (IMRT), systemic treatment strategies (immunotherapy, targeted therapy, and chemotherapy), the number of prior treatment lines, and neurological symptoms at diagnosis. The completeness of all other clinical variables reached 100%. Univariate and multivariate Cox regression analyses were performed to identify independent prognostic factors for overall survival (OS) and progression-free survival (PFS). All statistical analyses were conducted using SPSS 21.0. Results: The median OS of the entire cohort was 6.7 months (range: 0.4–101.0 months). Multivariate Cox regression identified three independent protective factors for superior OS and PFS: brain IMRT administration (OS: HR = 0.565, 95% CI: 0.365–0.874, p = 0.010; PFS: HR = 0.623, 95% CI: 0.420–0.924, p = 0.019), normal baseline LDH (OS: HR = 2.091, 95% CI: 1.425–3.069, p < 0.001; PFS: HR = 1.456, 95% CI: 1.023–2.071, p = 0.037), and ≤3 prior lines of systemic therapy before MBM diagnosis (OS: HR = 0.853, p = 0.004; PFS: HR = 1.679, p = 0.015). Moreover, the absence of neurological symptoms at baseline was an independent favorable prognostic factor for OS (HR = 1.919, p = 0.001) but not for PFS. Patients with normal LDH combined with brain IMRT exhibited the best OS and PFS outcomes (p < 0.001). Conclusions: Baseline LDH level and cranial radiotherapy are robust independent prognostic indicators for survival in MBM patients. More prior treatment lines and the presence of neurological symptoms correlate with inferior clinical outcomes. These findings provide evidence for clinical risk stratification and individualized treatment decision-making for this high-risk and challenging population.