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Abstract Background Myocardial infarction (MI) leads to enhanced activity of cardiac fibroblasts (CFs) and abnormal deposition of extracellular matrix proteins, resulting in cardiac fibrosis. Tartrate-resistant acid phosphatase 5 (ACP5) has been shown to promote cell proliferation and phenotypic transition. However, it remains unclear whether ACP5 is involved in the development of cardiac fibrosis after MI. The present study aimed to investigate the role of ACP5 in post-MI fibrosis and its potential underlying mechanisms. Methods Clinical blood samples were collected to detect ACP5 concentration. Myocardial fibrosis was induced by ligation of the left anterior descending coronary artery. The ACP5 inhibitor, AubipyOMe, was administered by intraperitoneal injection. Cardiac function and morphological changes were observed on Day 28 after injury. Cardiac CFs from neonatal mice were extracted to elucidate the underlying mechanism in vitro. The expression of ACP5 was silenced by small interfering RNA (siRNA) and overexpressed by adeno-associated viruses to evaluate its effect on CF activation. Results The expression of ACP5 was increased in patients with MI, mice with MI, and mice with Ang II-induced fibrosis in vitro. AubipyOMe inhibited cardiac fibrosis and improved cardiac function in mice after MI. ACP5 inhibition reduced cell proliferation, migration, and phenotypic changes in CFs in vitro, while adenovirus-mediated ACP5 overexpression had the opposite effect. Mechanistically, the classical profibrotic pathway of glycogen synthase kinase-3β (GSK3β)/β-catenin was changed with ACP5 modulation, which indicated that ACP5 had a positive regulatory effect. Furthermore, the inhibitory effect of ACP5 deficiency on the GSK3β/β-catenin pathway was counteracted by an ERK activator, which indicated that ACP5 regulated GSK3β activity through ERK-mediated phosphorylation, thereby affecting β-catenin degradation. Conclusion ACP5 may influence the proliferation, migration, and phenotypic transition of CFs, leading to the development of myocardial fibrosis after MI through modulating the ERK/GSK3β/β-catenin signaling pathway.

Abstract Effective representation of molecules is a crucial factor affecting the performance of artificial intelligence models. This study introduces a flexible, fragment-based, multiscale molecular representation framework called t-SMILES (tree-based SMILES) with three code algorithms: TSSA (t-SMILES with shared atom), TSDY (t-SMILES with dummy atom but without ID) and TSID (t-SMILES with ID and dummy atom). It describes molecules using SMILES-type strings obtained by performing a breadth-first search on a full binary tree formed from a fragmented molecular graph. Systematic evaluations using JTVAE, BRICS, MMPA, and Scaffold show the feasibility of constructing a multi-code molecular description system, where various descriptions complement each other, enhancing the overall performance. In addition, it can avoid overfitting and achieve higher novelty scores while maintaining reasonable similarity on labeled low-resource datasets, regardless of whether the model is original, data-augmented, or pre-trained then fine-tuned. Furthermore, it significantly outperforms classical SMILES, DeepSMILES, SELFIES and baseline models in goal-directed tasks. And it surpasses state-of-the-art fragment, graph and SMILES based approaches on ChEMBL, Zinc, and QM9.

Abstract Cities are main carbon emissions generators. Land use changes can not only affect terrestrial ecosystems carbon, but also anthropogenic carbon emissions. However, carbon monitoring at a spatial level is still coarse, and low-carbon land use encounters the challenge of being unable to adjust at the patch scale. This study addresses these limitations by using land-use data and various auxiliary data to explore new methods. The approach involves developing a high-resolution carbon monitoring model and investigating a patch-scale low-carbon land use model by integrating high carbon sink/source images with the Future Land Use Simulation model. Between 2000 and 2020, the results reveal an increasing trend in both carbon emissions and carbon sinks in the Shangyu district. Carbon sinks can only offset approximately 3% of the total carbon emissions. Spatially, the north exhibits net carbon emissions, while the southern region functions more as a carbon sink. A total of 14.5% of the total land area witnessed a change in land-use type, with the transfer-out of cropland constituting the largest area at 96.44 km2, accounting for 50% of the total transferred area. Land-use transfer resulted in an annual increase of 77.72 × 104 t in carbon emissions between 2000 and 2020. Through land-use structure optimisation, carbon emissions are projected to increase by only 7154 t C/year from 2000 to 2030, significantly lower than the amount between 2000 and 2020. Further low-carbon land optimisation at the patch scale can enhance the carbon sink by 129.59 t C/year. The conclusion drawn is that there is considerable potential to reduce carbon emissions through land use control. The new methods developed in our study can effectively contribute to high-resolution carbon monitoring in spatial contexts and support low-carbon land use, promoting the application of low-carbon land use from theory to practice. This will provide technological guidance for land use planning, city planning, and so forth.

Isolation and identification of acid-producing bacteria from environmental samples is still one of important and effective approaches to obtain strains producing lactic acid with high optical purity. In this study, an isolate strain named HL64-1, producing D-lactic acid with high optical purity, was isolated from rotten fruit. And HL64-1 was characterized as Leuconostoc pseudomesenteroides based on morphology, 16S rDNA sequence analysis and sequence similarity Blast analysis. After fermentation for 24 h, 62.18 g/L D-lactic acid was produced with an optical purity of 99.90%(ee) in basic fermentation culture. The acid production rate was 2.59 g/(L·h). Scale-up fermentation of L. pseudomesenteroides HL64-1 in 5-L fermenter for 72 h produced 78.74 g/L D-lactic acid by replenishment of carbon sources, and the average acid production rate was 1.09 g/(L·h). Moreover, L. pseudomesenteroides HL64-1 was found to be capable of using effectively cheap raw materials, such as agricultural by-products peanut cake meal and cottonseed meal, as alternative nitrogen sources, leading a reduction of fermentation cost. In addition, L. pseudomesenteroides HL64-1 could metabolize xylose into D-lactic acid. Co-fermentation of glucose and xylose mixtures showed that glucose significantly enhanced the utilization efficiency of xylose, making L. pseudomesenteroides HL64-1 to be a promising strain for pure D-lactic acid industrial production.

In this study, lotus seed starch was used as the raw material for preparing RS3 resistant starch (EHP-LRS3) through thermoacidophilic type Ⅲ pullulan hydrolase synergistic high-pressure heat treatments. The parameters for this preparation process were optimized using a single-factor experimental design and response surface methodology. The morphological and crystal structures of EHP-LRS3 were observed and analyzed using scanning electron microscopy (SEM) and X-ray diffraction (XRD), respectively, and its pro-proliferative effect on Bifidobacterium longum was investigated. According to the results, the optimal conditions for preparing EHP-LRS3 with TK-PUL enzymatic hydrolysis temperature of 80 ℃ were as follows: Treatment of 35.32% lotus seed starch slurry (pH5.00) with 25.00 U/g (lotus seed starch) TK-PUL at 80 ℃ for 12.70 h, followed by high-pressure heat treatment of the mixture at 121 ℃ for 10 min and retrogradation at 4 ℃ for 24 h. An EHP-LRS3 yield of 58.46% was achieved under these optimal conditions. The SEM analysis revealed that the prepared EHP-LRS3 possessed an irregular ravine-like structure. The XRD analysis showed that the resistant starch had a B-type crystal structure, which differed from the A-type crystal structure of lotus seed starch. The pro-proliferative effect of EHP-LRS3 on B. longum was superior to that of RS3 resistant starch prepared using high-pressure heating alone (HP-LRS3). In summary, a high EHP-LRS3 yield was obtained using both TK-PUL and high-pressure heat treatments. The superior pro-proliferative effect of EHP-LRS3 on B. longum was verified. The results provide a theoretical basis for the high-value utilization of lotus seed starch.

AIM: To explore the effect of epidermal growth factor receptor (EGFR) inhibition by erlotinib and EGFR siRNA on epidermal growth factor (EGF)-induced activation of retinal pigment epithelium (RPE) cells. METHODS: Human RPE cell line (ARPE-19 cells) was activated by 100 ng/mL EGF. Erlotinib and EGFR siRNA were used to intervene EGF treatment. Cellular viability, proliferation, and migration were detected by methyl thiazolyl tetrazolium (MTT) assay, bromodeoxyuridine (BrdU) staining assay and wound healing assay, respectively. EGFR/protein kinase B (AKT) pathway proteins and N-cadherin, α-smooth muscle actin (α-SMA), and vimentin were tested by Western blot assay. EGFR was also determined by immunofluorescence staining. RESULTS: EGF treatment for 24h induced a significant increase of ARPE-19 cells' viability, proliferation and migration, phosphorylation of EGFR/AKT proteins, and decreased total EGFR expression. Erlotinib suppressed ARPE-19 cells' viability, proliferation and migration through down regulating total EGFR and AKT protein expressions. Erlotinib also inhibited EGF-induced an increase of proliferative and migrative ability in ARPE-19 cells and clearly suppressed EGF-induced EGFR/AKT proteins phosphorylation and decreased expression of N-cadherin, α-SMA, and vimentin proteins. Similarly, EGFR inhibition by EGFR siRNA significantly affected EGF-induced an increase of cell proliferation, viability, and migration, phosphorylation of EGFR/AKT proteins, and up-regulation of N-cadherin, α-SMA, and vimentin proteins. CONCLUSION: Erlotinib and EGFR-knockdown suppress EGF-induced cell viability, proliferation, and migration via EGFR/AKT pathway in RPE cells. EGFR inhibition may be a possible therapeutic approach for proliferative vitreoretinopathy (PVR).

Abstract Sunlight is closely intertwined with daily life. It remains unclear whether there are associations between sunlight exposure and brain structural markers. General linear regression analysis was used to compare the differences in brain structural markers among different sunlight exposure time groups. Stratification analyses were performed based on sex, age, and diseases (hypertension, stroke, diabetes). Restricted cubic spline was performed to examine the dose–response relationship between natural sunlight exposure and brain structural markers, with further stratification by season. A negative association of sunlight exposure time with brain structural markers was found in the upper tertile compared to the lower tertile. Prolonged natural sunlight exposure was associated with the volumes of total brain (β: − 0.051, P

This study aimed to increase the expression and secretion of type III pullulan hydrolase (TK-PUL) by Brevibacillus choshinensis through the co-expression of molecular chaperone proteins and the optimization of fermentation conditions. By constructing multiple recombinant B. choshinensis co-expressing TK-PUL and molecular chaperone proteins, and screening them using extracellular enzyme activity as an indicator, the most favorable molecular chaperone protein and corresponding recombinant B. choshinensis for TK-PUL secretion and expression were determined. On this basis, single factor experiments and response surface methodology were used to optimize the fermentation conditions of recombinant B. choshinensis. Results showed that, the extracellular enzyme activity of the recombinant B. choshinensis strain co-expressing the molecular chaperone protein PrsABa reached 98.79 U/mL, representing a 0.31-fold increase. The optimal medium for this recombinant B. choshinensis was composed of 19.65 g/L of glucose, 21.46 g/L of yeast extract, 12.01 g/L of MgCl2·6H2O, 9.02 g/L of proline, 0.01 g/L of FeSO4·7H2O, 0.01 g/L of MnSO4·4H2O, and 0.001 g/L of ZnSO4·7H2O. Culturing the optimized recombinant B. choshinensis in the above-mentioned optimized medium for 66 hours at 35 °C and an initial pH of 7.0 increased the extracellular TK-PUL activity to 192.68 U/mL, which represented a 1.56-fold increase. Efficient secretion of TK-PUL in B. choshinensis was achieved through the co-expression of molecular chaperone proteins and the optimization of fermentation conditions. This study provides a foundation for exploring the industrial-scale application of TK-PUL.

AIM: To explore the effects of hepatocyte growth factor (HGF) on retinal pigment epithelium (RPE) cell behaviors. METHODS: The human adult retinal pigment epithelial cell line-19 (ARPE-19) were treated by HGF or mesenchymal-epithelial transition factor (MET) inhibitor SU11274 in vitro. Cell viability was detected by a Cell Counting Kit-8 assay. Cell proliferation and motility was detected by a bromodeoxyuridine incorporation assay and a wound healing assay, respectively. The expression levels of MET, phosphorylated MET, protein kinase B (AKT), and phosphorylated AKT proteins were determined by Western blot assay. The MET and phosphorylated MET proteins were also determined by immunofluorescence assay. RESULTS: HGF increased ARPE-19 cells' viability, proliferation and migration, and induced an increase of phosphorylated MET and phosphorylated AKT proteins. SU11274 significantly reduced cell viability, proliferation, and migration and decreased the expression of MET and AKT proteins. SU11274 suppressed HGF-induced increase of viability, proliferation, and migration in ARPE-19 cells. Additionally, SU11274 also blocked HGF-induced phosphorylation of MET and AKT proteins. CONCLUSION: HGF enhances cellular viability, proliferation, and migration in RPE cells through the MET/AKT signaling pathway, whereas this enhancement is suppressed by the MET inhibitor SU11274. HGF-induced MET/AKT signaling might be a vital contributor of RPE cells survival.

Real-world passive radiative cooling requires highly emissive, selective, and omnidirectional thermal emitters to maintain the radiative cooler at a certain temperature below the ambient temperature while maximizing the net cooling power. Despite various selective thermal emitters have been demonstrated, it is still challenging to achieve these conditions simultaneously because of the extreme difficulty in controlling thermal emission of photonic structures in multidimension. Here we demonstrated hybrid polar dielectric metasurface thermal emitters with machine learning inverse design, enabling a high emissivity of ~0.92 within the atmospheric transparency window 8–13 μm, a large spectral selectivity of ~1.8 and a wide emission angle up to 80 degrees, simultaneously. This selective and omnidirectional thermal emitter has led to a new record of temperature reduction as large as ~15.4 °C under strong solar irradiation of ~800 W/m2, significantly surpassing the state-of-the-art results. The designed structures also show great potential in tackling the urban heat island effect, with modelling results suggesting a large energy saving and deployment area reduction. This research will make significant impact on passive radiative cooling, thermal energy photonics and tackling global climate change.

The hydraulic support is the core of the stability of the ‘surrounding rock and equipm ent’ system in the pitching oblique working face of steeply dipping coal seam. The existing hydraulic support structure can not meet the requirements of spatial stability of pitching oblique mining, which seriously affects the safe and efficient mining of working face under such conditions. Taking the pitching oblique working face of steeply dipping coal seam as the research background, the comprehensive research methods of engineering analogy, structural kinematics analysis and numerical simulation are used to analyze the stability characteristics of ‘support-surrounding rock’ in the pitching oblique working face of steeply dipping coal seam. Based on ZY7000/22/45 hydraulic support, a new parallelogram hydraulic support is invented, the structural rationality design is carried out, and the kinematic response characteristics of key components are analyzed.The research shows that the non-uniform filling of the caving gangue and the crushing, pressing and pushing effect of the gangue on the support are the key factors affecting the stability of the support. The parallelogram top beam and the base are more suitable for the pitching oblique working face. The arrangement of the top beam, base and column of the parallelogram support is parallelogram. The special-shaped shield beam, the rear connecting rod, the oil cylinder connecting rod and the base constitute a flexible four-link structure. The column of the parallelogram support is the main bearing structure, and the cylinder connecting rod is the main motion mechanism. The main influencing factors of its motion characteristics are the distance between the upper and lower column sockets and the distance between the front and rear connecting rods and the hinged position of the shield beam. The shield beam and the rear connecting rod are the key to the position and posture control of the support, and there is no double torsion line during the movement of the support. The research results provide a type selection for the support of this kind of working face, which ensures the safe production of this kind of coal seam to a certain extent.

Abstract Background We aimed to explore the application value of various machine learning (ML) algorithms based on multicenter CT radiomics in identifying peripheral nerve invasion (PNI) of colorectal cancer (CRC). Methods A total of 268 patients with colorectal cancer who underwent CT examination in two hospitals from January 2016 to December 2022 were considered. Imaging and clinicopathological data were collected through the Picture Archiving and Communication System (PACS). The Feature Explorer software (FAE) was used to identify the peripheral nerve invasion of colorectal patients in center 1, and the best feature selection and classification channels were selected. Finally, the best feature selection and classifier pipeline were verified in center 2. Results The six-feature models using RFE feature selection and GP classifier had the highest AUC values, which were 0.610, 0.699, and 0.640, respectively. FAE generated a more concise model based on one feature (wavelet-HLL-glszm-LargeAreaHighGrayLevelEmphasis) and achieved AUC values of 0.614 and 0.663 on the validation and test sets, respectively, using the “one standard error” rule. Using ANOVA feature selection, the GP classifier had the best AUC value in a one-feature model, with AUC values of 0.611, 0.663, and 0.643 on the validation, internal test, and external test sets, respectively. Similarly, when using the “one standard error” rule, the model based on one feature (wave-let-HLL-glszm-LargeAreaHighGrayLevelEmphasis) achieved AUC values of 0.614 and 0.663 on the validation and test sets, respectively. Conclusions Combining artificial intelligence and radiomics features is a promising approach for identifying peripheral nerve invasion in colorectal cancer. This innovative technique holds significant potential for clinical medicine, offering broader application prospects in the field. Critical relevance statement The multi-channel ML method based on CT radiomics has a simple operation process and can be used to assist in the clinical screening of patients with CRC accompanied by PNI. Key points • Multi-channel ML in the identification of peripheral nerve invasion in CRC. • Multi-channel ML method based on CT-radiomics can detect the PNI of CRC. • Early preoperative identification of PNI in CRC is helpful to improve the formulation of treatment strategies and the prognosis of patients. Graphical Abstract

Abstract Background Intestinal barrier is a dynamic interface between the body and the ingested food components, however, dietary components or xenobiotics could compromise intestinal integrity, causing health risks to the host. Gossypol, a toxic component in cottonseed meal (CSM), caused intestinal injury in fish or other monogastric animals. It has been demonstrated that probiotics administration benefits the intestinal barrier integrity, but the efficacy of probiotics in maintaining intestinal health when the host is exposed to gossypol remains unclear. Here, a strain (YC) affiliated to Pediococcus pentosaceus was isolated from the gut of Nile tilapia (Oreochromis niloticus) and its potential to repair gossypol-induced intestinal damage was evaluated. Results A total of 270 Nile tilapia (2.20 ± 0.02 g) were allotted in 3 groups with 3 tanks each and fed with 3 diets including CON (control diet), GOS (control diet containing 300 mg/kg gossypol) and GP (control diet containing 300 mg/kg gossypol and 108 colony-forming unit (CFU)/g P. pentosaceus YC), respectively. After 10 weeks, addition of P. pentosaceus YC restored growth retardation and intestinal injury induced by gossypol in Nile tilapia. Transcriptome analysis and siRNA interference experiments demonstrated that NOD-like receptors (NLR) family caspase recruitment domain (CARD) domain containing 3 (Nlrc3) inhibition might promote intestinal stem cell (ISC) proliferation, as well as maintaining gut barrier integrity. 16S rRNA sequencing and gas chromatography-mass spectrometry (GC-MS) revealed that addition of P. pentosaceus YC altered the composition of gut microbiota and increased the content of propionate in fish gut. In vitro studies on propionate’s function demonstrated that it suppressed nlrc3 expression and promoted wound healing in Caco-2 cell model. Conclusions The present study reveals that P. pentosaceus YC has the capacity to ameliorate intestinal barrier injury by modulating gut microbiota composition and elevating propionate level. This finding offers a promising strategy for the feed industry to incorporate cottonseed meal into fish feed formulations. Graphical Abstract

To address the lack of theoretical guidance for sponge city construction (SCC) in China, this study introduces a method to evaluate the available water volume (AWV) in urban watersheds. This evaluation is based on the water balance relationship, water volume, and ecological water demand (EWD). The Xi'an urban area was selected as a case study due to its water shortage and flooding issues. Results show monthly surface and subsurface AWV ranging between 53.06 and 53.98 million m3 and between 8,701.89 and 8,898.14 million m3, respectively. By maximizing the potential for surface AWV, an annual water supply of 527.75 million m3 could be provided, surpassing the annual artificial water consumption of 394.20 million m3, effectively addressing water scarcity. During the rainy season, implementing measures such as employing permeable paving materials, establishing wetlands and rainwater gardens, and constructing lakes and reservoirs can mitigate flooding caused by rainfall exceeding 32.8 mm. While the subsurface space in Xi'an holds significant potential for subsurface AWV utilization, revitalizing the ecological environment of subsurface water is crucial. Overall, the AWV theoretical framework offers a comprehensive solution to water shortage and flooding issues in the Xi'an urban area, serving as a vital theory for SCC. HIGHLIGHTS Available water volume (AWV) is a novel index to guide sponge city construction.; Water volume refers to the maximum volume to store water resources.; EWD refers to the minimum water resources to meet the ecological environment.; AWV refers to the total dynamic water volume to store water and used by humans.; Water shortage problem in Xi'an urban area can be solved by using AWV.;

In this study, the extruded Mg-Zn-Mn-Ce-Ca alloy tube with a low compression anisotropy along the ED, 45ED and TD was prepared. The effect of the second phases, initial texture and deformation behavior on this low mechanical anisotropy was investigated. The results revealed that the alloy tube contains the high content (Mg1-xZnx)11Ce phase and the low content of Mg12Ce phase. These second phases are respectively incoherent and coherent with the Mg matrix, and their influence can be ignored. Additionally, the alloy tube exhibited a weak basal fiber texture, where the c-axis was aligned along the 0° ∼ 30° tilt from TD to ED. Such a texture made the initial deformation (at 1.0% ∼ 1.6% strain) of the three samples controlled by comparable basal slip. As deformation progressed (1.6∼9.0% strain), larger amounts of ETWs nucleated and gradually approached saturation in the three samples, re-orienting the c-axis to a 0°∼±30° deviation with respect to the loading directions. Meanwhile, the prismatic 〈a〉 and pyramidal slips replaced the dominant deformation progressively until fracture. Eventually, the similar deformation mechanisms determined by the weak initial texture in the three samples contribute to the comparable strain hardening rates, resulting in the low compressive anisotropy of the alloy tube.

Abstract In the realm of photovoltaics, organometallic hybridized perovskite solar cells (PSCs) stand out as promising contenders for achieving high‐efficiency photoelectric conversion, owing to their remarkable performance attributes. Nevertheless, defects within the perovskite layer, especially at the perovskite grain boundaries and surface, have a substantial impact on both the overall photoelectric performance and long‐term operational stability of PSCs. To mitigate this challenge, we propose a method for water‐induced condensation polymerization of small molecules involving the incorporation of 1,3‐phenylene diisocyanate (1,3‐PDI) into the perovskite film using an antisolvent technique. Subsequent to this step, the introduction of water triggers the polymerization of [P(1,3‐PDI)], thereby facilitating the in situ passivation of uncoordinated lead defects inherent in the perovskite film. This passivation process demonstrates a notable enhancement in both the efficiency and stability of PSCs. This approach has led to the attainment of a noteworthy power conversion efficiency (PCE) of 24.66% in inverted PSCs. Furthermore, based on the P(1,3‐PDI) modification, these devices maintain 90.15% of their initial efficiency after 5000 h of storage under ambient conditions of 25°C and 50 ± 5% relative humidity. Additionally, even after maximum power point tracking for 1000 h, the PSCs modified with P(1,3‐PDI) sustain 82.05% of the initial PCE. Small molecules can rationally manipulate water and turn harm into benefit, providing new directions and methods for improving the efficiency and stability of PSCs.

Abstract The radiator with heat transfer capability is able to guarantee the stable operation of hydro generator set, while the long-term and continuous scouring on radiator pipes by cooling medium will lead to thinning or even perforation of pipe wall, which triggers wall failure. This paper analyzes and predicts the failure mechanism of radiator’s pipe wall, and investigates the effects of water flow velocity, sand content and sand particle size on erosion damage of radiator pipe by establishing a test bench for pipe erosion. The results show that the increase of above parameters will lead to the increasing erosion rate, especially when the sand content is 1%, the velocity is 8 m/s and the sand particle size is 0.85 mm, the erosion damage will be particularly serious. Based on experimental data, BP and LSSVM models are employed to predict the pipe wall failure, and PSO algorithm is used to optimize the two models. The optimized PSO-BP has the highest accuracy with the mean absolute error (MAE) of 0.2070 and the mean absolute percentage error (MAPE) of 4.702%. The findings provide a reference for wall failure analysis of radiator, which is of great significance for unit's safe operation.

Abstract A compact Archimedean spiral antenna with high gain for electrostatic discharge (ESD) detection is investigated. A frustum‐shaped cavity proposed in this work is formed to optimise the maximum antenna gain. Additionally, a helix arm is loaded to enhance antenna gain in lower band. The measured results demonstrate that the proposed antenna, which employs a unidirectional radiation mode, exhibits a maximum antenna gain ranging from −0.74 dBi to 9.46 dBi and a voltage standing wave ratio less than 3 across a frequency range of 0.65–5 GHz. A test system consisted of proposed antenna and a commercial ESD detection antenna is established. The verified results indicate that the proposed antenna has a performance close to the commercial antenna, so that proposed antenna with compact size is preferred to be utilised for ESD detection.

Abstract Microbial interactions can lead to different colonization outcomes of exogenous species, be they pathogenic or beneficial in nature. Predicting the colonization of exogenous species in complex communities remains a fundamental challenge in microbial ecology, mainly due to our limited knowledge of the diverse mechanisms governing microbial dynamics. Here, we propose a data-driven approach independent of any dynamics model to predict colonization outcomes of exogenous species from the baseline compositions of microbial communities. We systematically validate this approach using synthetic data, finding that machine learning models can predict not only the binary colonization outcome but also the post-invasion steady-state abundance of the invading species. Then we conduct colonization experiments for commensal gut bacteria species Enterococcus faecium and Akkermansia muciniphila in hundreds of human stool-derived in vitro microbial communities, confirming that the data-driven approaches can predict the colonization outcomes in experiments. Furthermore, we find that while most resident species are predicted to have a weak negative impact on the colonization of exogenous species, strongly interacting species could significantly alter the colonization outcomes, e.g., Enterococcus faecalis inhibits the invasion of E. faecium invasion. The presented results suggest that the data-driven approaches are powerful tools to inform the ecology and management of microbial communities.

Abstract Artificial Intelligence (AI) is currently experiencing a bloom driven by deep learning (DL) techniques, which rely on networks of connected simple computing units operating in parallel. The low communication bandwidth between memory and processing units in conventional von Neumann machines does not support the requirements of emerging applications that rely extensively on large sets of data. More recent computing paradigms, such as high parallelization and near-memory computing, help alleviate the data communication bottleneck to some extent, but paradigm- shifting concepts are required. Memristors, a novel beyond-complementary metal-oxide-semiconductor (CMOS) technology, are a promising choice for memory devices due to their unique intrinsic device-level properties, enabling both storing and computing with a small, massively-parallel footprint at low power. Theoretically, this directly translates to a major boost in energy efficiency and computational throughput, but various practical challenges remain. In this work we review the latest efforts for achieving hardware-based memristive artificial neural networks (ANNs), describing with detail the working principia of each block and the different design alternatives with their own advantages and disadvantages, as well as the tools required for accurate estimation of performance metrics. Ultimately, we aim to provide a comprehensive protocol of the materials and methods involved in memristive neural networks to those aiming to start working in this field and the experts looking for a holistic approach.

Traditional hot-dip galvanized coatings, typically single-silver in color, present increasing aesthetic challenges in diverse applications, while prevailing organic coating methods involve complex processes with high energy consumption and pollution emissions. In this study, a novel hot-dip process for in-situ synthesis of color coating on steel was proposed, capable of producing various uniform color coating. The microstructure of color coatings on steel was systematically examined, and an assessment of their corrosion and weather resistance was conducted. The results demonstrate the sequence of typical color variation is gold, purple, blue, cyan, red, green, and grey. By controlling the immersion temperature range, and regulating the final stable color of the oxide film. The coloration mechanism mainly is attributed to the light interference on the Mn oxide film. The cyan and brown coatings mainly consist of the dense rod-like ζ-FeZn13 phases which provide a structural foundation for corrosion resistance. Furthermore, the brown coating exhibited excellent weather resistance.

Abstract Background Yaks (Bos grunniens), prized for their ability to thrive in high-altitude environments, are indispensable livestock in the plateau region. Modifying their feeding systems holds significant promise for improving their growth and meat quality. Tenderness, a key determinant of yak meat quality and consumer appeal, is demonstrably influenced by dietary regimen. Indoor feeding regimes have been shown to enhance tenderness by lowering shear stress and optimizing pH values. CircRNAs, well-known modulators of circulatory function, also play a crucial role in skeletal muscle development across various animal species. However, their functional significance in yak skeletal muscle remains largely unexplored. Results In this study, we identified a total of 5,534 circRNAs within the longissimus dorsi muscle, and we found 51 differentially expressed circRNAs (20 up-regulated and 31 down-regulated) between the two feeding groups. Constructing a comprehensive ceRNA network illuminated intricate regulatory mechanisms, with PGP and circRNA_0617 converging on bta-miR-2285q, mirrored by KLF15/circRNA_0345/bta-miR-20b and CTSF/circRNA_0348/bta-miR-146a. These findings shed light on the potential of circRNAs to influence yak muscle development and meat quality, offering valuable insights for future research. Conclusions This investigation unraveled a complex interaction network between circRNAs、mRNAs and miRNAs in yak skeletal muscle. We further elucidated the target genes regulated by these target genes within the network, offering valuable insights into the potential regulatory mechanisms governing muscle development and meat quality-related traits in yaks.

Background: The Klebsiella oxytoca complex is an opportunistic pathogen that has been recently identified as an actual complex. However, the characteristics of each species remain largely unknown. We aimed to study the clinical prevalence, antimicrobial profiles, genetic differences, and interaction with the host of each species of this complex. Methods: One hundred and three clinical isolates of the K. oxytoca complex were collected from 33 hospitals belonging to 19 areas in China from 2020 to 2021. Species were identified using whole genome sequencing based on average nucleotide identity. Clinical infection characteristics of the species were analyzed. Comparative genomics and pan-genome analyses were performed on these isolates and an augmented dataset, including 622 assemblies from the National Center for Biotechnology Information. In vitro assays evaluating the adhesion ability of human respiratory epithelial cells and survivability against macrophages were performed on randomly selected isolates. Results: Klebsiella michiganensis (46.6%, 48/103) and K. oxytoca (35.92%, 37/103) were the major species of the complex causing human infections. K. michiganensis had a higher genomic diversity and larger pan-genome size than did K. oxytoca. K. michiganensis isolates with blaoxy-5 had a higher resistance rate to various antibiotics, antimicrobial gene carriage rate, adhesion ability to human respiratory epithelial cells, and survival rate against macrophages than isolates of other species. Conclusion: Our study revealed the genetic diversity of K. michiganensis and firstly identified the highly antimicrobial-resistant profile of K. michiganensis carrying blaoxy-5.

Soil copper (Cu) pollution is a serious environmental risk in the Panax notoginseng planting area. However, the effect of Cu on soil microbial metabolism and nutrient cycling in this area remains unknown. Therefore, Biolog ECO-plate and enzyme stoichiometry methods were utilized in this study to investigate the impact of exogenous Cu (control: 0 mg·kg−1; Cu100: 100 mg·kg−1; Cu400: 400 mg·kg−1; and Cu600: 600 mg·kg−1) on the metabolic function of soil microbial and nutrient limitation in the P. notoginseng soil. The results indicated that Cu100 significantly increased soil organic carbon (SOC), total phosphorus (TP), soil C:N, microbial biomass carbon (MBC), and microbial biomass nitrogen (MBN) 9.89%, 15.65%, 17.91%, 61.87%, and 90.56% higher than the control, respectively. Moreover, the carbon source utilization ratio of carbohydrates, amino acids, and amphiphilic compounds of Cu100 also increased by 7.16%, 25.47%, and 84.68%, respectively, compared with the control. The activities of β-1,4-glucosidase, cellobiohyrolase, leucine amino peptidase, β-1,4-N-acetylglucosaminidase, and phosphatase significantly decreased with increasing Cu concentration. Soil enzyme stoichiometry showed that all treatments were limited by nitrogen (vector angle < 45°; 19.045–22.081). Cu600 led to the lowest carbon limitation (1.798) and highest carbon use efficiency (CUE:0.267). The PLS-SEM model also showed that MBC, MBN, MBP, and microbial diversity positively affected carbon and nitrogen limitation (0.654 and 0.424). Soil carbon, nitrogen, phosphorus, stoichiometric ratio, MBC, MBN, and MBP positively affected CUE (0.527 and 0.589). The microbial diversity index significantly negatively affected CUE (−1.490). Multiple linear stepwise regression analyses showed that CUE was mainly influenced by MBC, AP, C:P, and LAP. Thus, P. notoginseng soil can benefit soil microbial carbon and nitrogen limitations at low Cu concentrations. Clarifying the metabolic activity and nutritional status of microorganisms under Cu stress can provide some theoretical basis for realizing China's comprehensive and effective management and control policies for environmental risks from metals by 2035.

Background: Hypertrophic scar (HS) is a common fibrotic skin disease that occurs secondary to burns or injuries. The activation of the TGF-β signaling pathway contributes immensely to HS formation. Isorhamnetin (ISO) is a type of flavonoid compound that exerts an antifibrotic effect via TGF-β signaling suppression. However, whether ISO can inhibit HS formation via TGF-β signaling is yet to be elucidated. This study aimed to examine the influence of ISO on HS pathogenesis and TGF-β signaling, especially the downstream molecules and networks of TGF-β signaling that facilitate HS formation. Methods: Hypertrophic scar fibroblasts (HSFBs) were isolated from human HS tissues. The in vitro proliferation, migration, contractile ability, cell cycle, and apoptosis of HSFBs after ISO treatment were determined using cell viability assay, EdU staining, wound healing assay, collagen gel contraction assay, and flow cytometry. The expressions of genes and proteins involved in TGF-β signaling and its downstream molecules in ISO-treated HSFBs were determined using quantitative PCR (qPCR), immunofluorescence, and western blotting. In vivo, a rabbit HS model was established, and the effects of ISO on rabbit HS formation were investigated using histological analysis, immunohistochemical staining, and qPCR. Results: In vitro studies indicated that ISO treatment suppressed the proliferation, migration, and contractile ability of HSFBs; attenuated the expressions of COL Ⅰ, COL Ⅲ, and α-SMA; and inhibited TGF-β1 signaling-induced activation of HSFBs by decreasing the levels of phosphorylated Smad2/3 and cleaved CREB3L1 in a dose-dependent manner. Furthermore, ISO augmented apoptosis and G2 phase cell cycle arrest of HSFBs by upregulating the expressions of the proapoptotic proteins Bax and cleaved caspase-3 and downregulating the expression of the antiapoptotic protein Bcl-2. In vivo studies revealed that ISO ameliorated HS formation in the rabbit ear by lowering the scar elevation index, attenuating the collagen density, facilitating the regular arrangement of collagen fibers, and downregulating the expressions of TGF-β1, CREB3L1, COL Ⅰ, COL Ⅲ, and α-SMA. Conclusions: ISO suppressed HS pathogenesis by dampening TGF-β1/Smad and TGF-β1/CREB3L1 signaling pathways, which suggests that it may serve as a candidate inhibitor of TGF-β1 signaling and a promising anti-HS drug with a high therapeutic potential.

Background: Pay-it-forward is when an individual receives a gift and is offered the opportunity to donate a gift to another person. This prosocial behavior has been used to develop health interventions, including strategies to increase sexually transmitted disease (STD) testing among men who have sex with men (MSM). Although pay-it-forward has improved service uptake across several settings, the underlying mechanism is unclear. This study aims to assess the participant experience to provide a theoretical basis for how pay-it-forward works among MSM in China. Methods: MSM participants of a pay-it-forward intervention were recruited from two STD clinics in Guangzhou, China, and underwent semi-structured interviews. Responses were translated verbatim into English. Transcripts were analyzed thematically. Results: Twenty-four MSM were interviewed. Despite many men feeling detached from other MSM, pay-it-forward engendered hope and solidarity among many participants. From an emotional perspective, reading handwritten postcards from other MSM induced gratitude, warmth, and support. From the perspective of the collective, receiving a free test and donating to other MSM solidified men's connection with the MSM community, even among men not yet out. Donation gave men an opportunity to pass on their gratitude and provide for MSM in need. Conclusions: Our data suggest that upstream reciprocity and warm glow explained pay-it-forward for some men, but this pathway was often complemented by a pathway aligned with principles of mutual aid. Further qualitative and mixed-methods research is needed to understand the basis for MSM decision-making about donating to support others.

Polyvinylidene fluoride (PVDF) membranes, widely used for their stability, face limitations due to the hardly adjustable pore size in nanoscale and inherent hydrophobicity. To address this, we proposed a co-deposition method incorporating dopamine (DA), polyethyleneimine (PEI), and silicon dioxide (SiO2) nanoparticles with glutaraldehyde cross-linking for precise regulation of pore size and hydrophilicity in PVDF hollow fiber membranes. Notably, the pore diameter reduced from 119.0 ± 3.55 nm to 18.4 ± 0.36 nm, while the contact angle decreased from 107.7° to 40.9°. This simultaneous regulation led to a high-performance PDA/PEI/SiO2-PVDF hydrophilic ultrafiltration membrane with a rejection rate exceeding 99% for 20 nm nanoparticles in a long-term simulated separation experiment while achieving a significant protein permeability of 97% in BSA permeation experiments. Additionally, the membrane demonstrated exceptional long-term stability, offering a novel approach for tuning the performance of ultrafiltration/microfiltration membranes.

Abstract Forest plantations most likely promote exotic plant invasion. Using an in situ monitoring method, this study investigated the traits correlated with growth and reproduction of an understory invader, Phytolacca americana L., and ecological factors including understory irradiance, soil stoichiometry and microbial patterns associated with these traits in different exotic plantations of Robinia pseudoacacia L. and Pinus thunbergii Parl. at Mount Lao, Qingdao, China. We found that the traits of P. americana underneath the R. pseudoacacia stand might be situated at the fast side of the trait economic spectrum. The R. pseudoacacia stand appeared to “nurse” P. americana. Furthermore, we intended to explain the nurse effects of R. pseudoacacia stands by examining their ecological factors. First, the R. pseudoacacia stand created understory light attenuation, which matched the sciophilous feature of P. americana. Second, the soil beneath the R. pseudoacacia stand might benefit P. americana more since the soil has greater resource availability. Third, a higher microbial diversity was found in the soil derived from P. americana underneath the R. pseudoacacia stand. A greater abundance of plant pathogens was detected in the soil derived from P. americana in the R. pseudoacacia stand, while more abundant mycorrhizal fungi were detected in the P. thunbergii stand. We speculate that plant pathogens can defend P. americana from aggression from other understory competitors. The mycorrhizal fungi in the P. thunbergii stand might benefit P. americana while simultaneously benefiting other understory plants. Intensive competition from other plants might interfere with P. americana. The potential relationships between plant performance and ecological factors may explain the invasion mechanism of P. americana. The present study provides a novel insight on the facilitative effects of exotic tree plantation on an exotic herb through the modification of soil biota, with implications for the biocontrol of invasive species and forest management and conservation.

BackgroundFrailty correlates with adverse outcomes in many cardiovascular diseases and is prevalent in individuals with heart failure (HF). The Hospital Frailty Risk Score (HFRS) offers an integrated, validated solution for frailty assessment in acute care settings, but its application in critically ill patients with congestive HF lacks exploration. This study aimed to identify the association between frailty assessed by the HFRS and in-hospital mortality in critically ill patients with congestive HF.MethodsThis observational study retrospectively enrolled 12,179 critically ill patients with congestive HF. Data from the Medical Information Mart for Intensive Care IV database was used. The HFRS was calculated to assess frailty. Patients were categorized into three groups: non-frailty (HFRS

Traditional environmental epidemiology has consistently focused on studying the impact of single exposures on specific health outcomes, considering concurrent exposures as variables to be controlled. However, with the continuous changes in environment, humans are increasingly facing more complex exposures to multi-pollutant mixtures. In this context, accurately assessing the impact of multi-pollutant mixtures on health has become a central concern in current environmental research. Simultaneously, the continuous development and optimization of statistical methods offer robust support for handling large datasets, strengthening the capability to conduct in-depth research on the effects of multiple exposures on health. In order to examine complicated exposure mixtures, we introduce commonly used statistical methods and their developments, such as weighted quantile sum, bayesian kernel machine regression, toxic equivalency analysis, and others. Delineating their applications, advantages, weaknesses, and interpretability of results. It also provides guidance for researchers involved in studying multi-pollutant mixtures, aiding them in selecting appropriate statistical methods and utilizing R software for more accurate and comprehensive assessments of the impact of multi-pollutant mixtures on human health.

BackgroundWith increased life expectancy, cognitive decline has emerged as a prevalent neurodegenerative disorder.ObjectiveThis study aimed to examine the correlation between concentrations of Plasma long-chain n-3 polyunsaturated fatty acids (LCPUFAs) and cognitive performance in elderly Americans.MethodsData were analyzed from older adults enrolled in two NHANES cycles. Participants completed four cognitive assessments, including the Immediate Recall Test (IRT), Delayed Recall Test (DRT), Animal Fluency Test (AFT), and Digit Symbol Substitution Test (DSST). Linear regression and restricted cubic spline modeling examined associations between plasma LCPUFAs levels and cognitive test outcomes.ResultsThe cohort included 610 adults aged 69 years on average, 300 (49.2%) males and 310 (50.8%) females. The median LCPUFAs concentration was 309.4 μmol/L, with an interquartile range of 244.7–418.9 μmol/L. In unadjusted and adjusted generalized linear regression model analyses, circulating LCPUFAs exhibited significant positive correlations with DRT performance. No relationships were detected among those with chronic conditions (chronic heart failure, stroke, diabetes). A significant association between LCPUFAs levels and DRT scores was evident in males but not females.ConclusionPlasma LCPUFAs concentrations were significantly associated with DRT performance in males free of chronic illnesses, including heart failure, stroke, and diabetes.

Nano porous silicon (PS) is a strong candidate for thermoelectric application, but it shows low structural stability and is prone to collapse. To enhance the structural stability of PS and offer a new way to improve its electrical conductivity, PS was prepared by electrochemical etching and Bi nanowires were fabricated in the pores of PS by electrodeposition. In addition, for studying the effect of structures on the properties of Bi-filled PS composites, aperiodic single-layer (SL) structure, and periodic rugate (Rgt) structure and Bragg structure PS samples were prepared by changing the etching current waveform and etching time. The results show that the initial Bi deposition position and filling fraction of Bi nanowires in PS templates can be precisely controlled. Since Bi nanowires have significantly different continuity in Rgt and Bragg structures compared with SL structures, we proposed two growth mechanisms of Bi nanowires, including the axis-growth mechanism and transverse-axis-growth mechanism, with the supports of the experimental results of XRD, SEM, and EDS.The room temperature thermal conductivities of pristine and Bi-filled PS layers are in the ranges of 4.5 ∼ 5.0 and 4.2 ∼ 6.0 W･m−1K−1, respectively, about 1/10 of the original unetched silicon wafer. No apparent increase of thermal conductivity was observed in any Bi-filled composites. In addition, the thermal conductivities of PS layers with Bragg structure, including pristine and Bi-filled PS composites, are significantly lower than those of the other two structures.SEM images also demonstrates that Bi greatly improved the mechanical property of PS composites, especially the periodic structures composites. This study firmly demonstrates that Bi-filling in PS with periodic Bragg structure is practical to obtain nanocomposites with low thermal conductivity and improved structural stability. It offers a new dimension to optimize the property of PS for thermoelectric application by pore configuration design and controllable nanowire Bi filling.

The residue remaining after oil extraction from grape seed contain abundant procyanidins. An ultrasonic-assisted enzyme method was performed to achieve a high extraction efficiency of procyanidins when the optimal extraction conditions were 8 U/g of cellulase, ultrasound power of 200 W, ultrasonic temperature of 50 ℃, and ultrasonic reaction time of 40 min. The effects of free procyanidins on both radical scavenging activity and thermal stability at 40, 60, and 80 ℃ of the procyanidins-loaded liposomal systems prepared by the ultrasonic-assisted method were discussed. The presence of procyanidins at concentrations ranging from 0.02 to 0.10 mg/mL was observed to be effective at inhibiting lipid oxidation by 15.15 % to 69.70 % in a linoleic acid model system during reaction for 168 h, as measured using the ferric thiocyanate method. The procyanidins-loaded liposomal systems prepared by the ultrasonic-assisted method were characterized by measuring the mean particle size and encapsulation efficiency. Moreover, the holographic plots showed that the effect–response points of procyanidins combined with α-tocopherol in liposomes were lower than the addition line and 95 % confidence interval limits. At the same time, there were significant differences between the theoretical IC50add value and the experimental IC50mix value. The interaction index (γ) of all combinations was observed to be less than 1. These results indicated that there was a synergistic antioxidant effect between procyanidins combined with α-tocopherol, which will show promising prospects in practical applications. In addition, particle size differentiation and morphology agglomeration were observed at different time points of antioxidant activity determination (0, 48, 96 h).

Abstract Background Renal cell carcinoma (RCC) is one of the most common malignant tumor worldwide. Metastasis is a leading case of cancer-related deaths of RCC. Circular RNAs (circRNAs), a class of noncoding RNAs, have emerged as important regulators in cancer metastasis. However, the functional effects and regulatory mechanisms of circRNAs on RCC metastasis remain largely unknown. Methods High-throughput RNA sequencing techniques were performed to analyze the expression profiles of circRNAs and mRNAs in highly and poorly invasive clear cell renal cell carcinoma (ccRCC) cell lines. Functional experiments were performed to unveil the regulatory role of circPPAP2B in the proliferation and metastatic capabilities of ccRCC cells. RNA pulldown, Mass spectrometry analysis, RNA methylation immunoprecipitation (MeRIP), RNA immunoprecipitation (RIP), co-immunoprecipitation (CoIP), next-generation RNA-sequencing and double luciferase experiments were employed to clarify the molecular mechanisms by which circPPAP2B promotes ccRCC metastasis. Results In this study, we describe a newly identified circular RNA called circPPAP2B, which is overexpressed in highly invasive ccRCC cells, as determined through advanced high-throughput RNA sequencing techniques. Furthermore, we observed elevated circPPAP2B in ccRCC tissues, particularly in metastatic ccRCC tissues, and found it to be associated with poor prognosis. Functional experiments unveiled that circPPAP2B actively stimulates the proliferation and metastatic capabilities of ccRCC cells. Mechanistically, circPPAP2B interacts with HNRNPC in a m6A-dependent manner to facilitate HNRNPC nuclear translocation. Subcellular relocalization was dependent upon nondegradable ubiquitination of HNRNPC and stabilization of an HNRNPC/Vimentin/Importin α7 ternary complex. Moreover, we found that circPPAP2B modulates the interaction between HNRNPC and splicing factors, PTBP1 and HNPNPK, and regulates pre-mRNA alternative splicing. Finally, our studies demonstrate that circPPAP2B functions as a miRNA sponge to directly bind to miR-182-5p and increase CYP1B1 expression in ccRCC. Conclusions Collectively, our study provides comprehensive evidence that circPPAP2B promotes proliferation and metastasis of ccRCC via HNRNPC-dependent alternative splicing and miR-182-5p/CYP1B1 axis and highlights circPPAP2B as a potential therapeutic target for ccRCC intervention.

Abstract Geometric deep learning has been revolutionizing the molecular modeling field. Despite the state-of-the-art neural network models are approaching ab initio accuracy for molecular property prediction, their applications, such as drug discovery and molecular dynamics (MD) simulation, have been hindered by insufficient utilization of geometric information and high computational costs. Here we propose an equivariant geometry-enhanced graph neural network called ViSNet, which elegantly extracts geometric features and efficiently models molecular structures with low computational costs. Our proposed ViSNet outperforms state-of-the-art approaches on multiple MD benchmarks, including MD17, revised MD17 and MD22, and achieves excellent chemical property prediction on QM9 and Molecule3D datasets. Furthermore, through a series of simulations and case studies, ViSNet can efficiently explore the conformational space and provide reasonable interpretability to map geometric representations to molecular structures.

Random phase interference is the main factor leading to uneven optical power distribution, which will affect the positioning accuracy of the four-quadrant detector. This paper uses the power spectrum inversion method to simulate the light spot power distribution affected by random phase interference, and studies the subdivision capability characteristics of the four-quadrant detector under different random phase interference. The simulation experiment results show that when the radius of the light spot received by the detector is 1/2 the radius of the detector, both detection range and positioning accuracy can be taken into account. When the random phase interference is enhanced, the detector's subdivision capability decreases. When the random phase interference is small, the detector can achieve more than 100 subdivisions. When the random phase interference is large, the light spot can only achieve 3 subdivision at the edge of the detector target surface. An experimental system was built to test the subdivision capability of the four-quadrant detector, the experimental test results were basically consistent with the simulation results. The research results provide a technical reference for the application of four-quadrant detector. in free space environments.

Unmanned Aerial Vehicle (UAV)-assisted Mobile Edge Computing (MEC) systems have emerged as promising solutions for enhancing the computational capabilities and reducing latency in next-generation wireless networks. However, the finite energy capacity of UAVs presents a significant challenge. In this study, we formulate a joint user association, computing resource allocation, and task offloading problem, called User Association and Computation Offloading (UACO), to minimize the energy consumption of both mobile devices and UAVs by considering the computational resource limitations of UAVs and the minimum user offloading data rate requirements. The UACO problem is a mixed-integer linear programming (MILP) problem that makes it NP-hard. We transform UACO into an Offload Exact Constrained Potential Game (OFECPG) based on game theory, which facilitates distributed execution. We propose the Best Response dynamics based on Local Decomposition (BR-LD) and Better Response dynamics based on the Local Switch operator (BR-LS) to enhance computational efficiency. We prove the existence of a pure strategy Nash Equilibrium (NE) and the convergence of the proposed algorithms. Extensive simulations demonstrated the effectiveness of the OFECPG, BR-LD, and BR-LS, showing significant improvements in system energy consumption compared to the baseline schemes. Our approach offers valuable insights into the design of efficient association and offloading schemes for multi-UAV MEC networks.

The rapid deployment of large-scale UAV-assisted cellular networks has emerged as an effective solution for delivering high-speed data services to ground users in areas where terrestrial base station (BS) infrastructure is inadequate. In this paper, we address a crucial problem in these networks by aiming to maximize the uplink total rate through joint optimization of Unmanned Aerial Vehicle (UAV) association and Orthogonal Frequency Division Multiple Access (OFDMA) subcarrier assignment. However, due to the mobility of pedestrians, fixed association and subcarrier assignments lack adaptation, and centralized optimization does not scale well, especially in large-scale UAV settings. To overcome these challenges, we formulate the joint optimization problem as an exact Constrained Potential Game, called the Subcarrier Assignment and UAV Association Game (SAUAG), based on game theory. In SAUAG, each user selfishness selects the most appropriate strategy with the objective of maximizing their own utility while still fulfilling the system’s Quality of Service (QoS) constraints. We analyze the conditions under which a Nash Equilibrium (NE) exists and provide rigorous proof of its existence.To mitigate the computational complexity typically associated with Best Response Dynamics (BRD), we introduce the Two-Step Better Response (TS-BR) algorithm, which significantly reduces the computational load while ensuring convergence to an NE. Furthermore, we proposed a distributed algorithm based on sequential play and demonstrated its effectiveness in achieving NE convergence. Through comprehensive simulations, the superiority of the proposed SAUAG and TS-BR algorithms was demonstrated, showing their potential in enhancing network performance and adaptability in UAV-assisted OFDMA networks with mobile ground users.

Enhancing power system resilience against extreme events is becoming increasingly critical. This paper discusses a unified framework for preventive control of power systems to enhance system resilience, which includes three parts: resilience assessment, resilience grading, and resilience enhancement. First, the resilience assessment contains facility-level and system-level resilience assessment. The concept of fragility curve is used in the facility-level resilience assessment. Various resilience indices are developed in system-level resilience assessment to roundly depict the impacts of extreme events on power systems and determine the system resilience. On this basis, the resilience is divided into different levels by resilience grading strategy, which can efficiently quantify the severity of the impact of extreme events and provide decision-making for the resilience enhancement strategies. Then, control strategies for enhancing power system resilience are also divided according to different resilience levels. A controlled islanding based preventive control is proposed to enhance system resilience, which aims to strengthen the first defensive line of power systems to deal with extreme events. Finally, taking the typhoon disaster in extreme events as an example, two tests carried out with two typhoons demonstrate the efficiency of the proposed method.

Abstract We conducted a retrospective study to evaluate the efficacy of immune checkpoint inhibitor (ICI) rechallenge in patients with advanced non-small cell lung cancer (NSCLC). The study included 111 patients who had previously received ICI therapy and experienced disease progression. The primary endpoints assessed were overall survival (OS), progression-free survival (PFS), and objective response rate (ORR). Our findings revealed that the ICI rechallenge showed promising results in improving patient outcomes. OS (r) is the time from rechallenging with immune checkpoint inhibitors to the last follow-up or death from any cause. The median OS (r) was 14.3 months (95% CI 11.3–17.3 months), with a median PFS (r) of 5.9 months (95% CI 4.1–7.7 months). The ORR was 17.1%; the DCR was 82.3%. Subgroup analysis demonstrated that patients without brain or liver metastases had a longer OS (r) compared to those with metastases (21.6 vs. 13.8 months, χ2 = 3.873, P = 0.046; 20.8 vs. 9.1 months, χ2 = 10.733, P = 0.001, respectively). Moreover, patients without driver gene mutations exhibited significantly longer OS than those with mutations or wild-type patients (22.9 vs. 16.1 vs. 7.5 months, χ2 = 10.710, P = 0.005). Notably, patients who switched to a different ICI during the rechallenge had shorter OS than those who did not change medications (10.4 vs. 21.1 months, χ2 = 9.014, P = 0.003). The incidence of immune-related adverse events did not significantly differ between the two treatment phases. These findings suggest that ICI rechallenge may be a viable therapeutic strategy for select NSCLC patients. Further prospective studies are needed to validate these results and guide treatment decisions for advanced NSCLC.

Abstract Emerging evidence reveals associations between metabolic syndrome (MetS) and psychiatric disorders (PDs), although causality remains uncertain. Consequently, we conducted Mendelian randomization (MR) to systematically evaluate the causality between MetS and PDs. Linkage disequilibrium score regression estimated the heritability of PDs and their genetic correlations with MetS. In primary analyses, the main model employed inverse variance weighting method, with sensitivity analyses using various MR models to ensure robustness. Replication MR analyses, involving cohorts distinct from those in the primary analyses, were performed to validate the generalizability of the findings. Multivariable MR analyses were carried out to account for genetically predicted body mass index (BMI). As a result, genetic correlations of MetS with attention-deficit/hyperactivity disorder(ADHD), anorexia nervosa(ANO), major depressive disorder(MDD), and schizophrenia were identified. Causal effects of MetS on ADHD (OR: 1.59 [95% CI:1.45–1.74]), ANO (OR: 1.42 [95% CI:1.25–1.61]), MDD(OR: 1.23 [95% CI: 1.13–1.33]), and the effects of ADHD (OR: 1.03 [95% CI: 1.02–1.04]) and ANO (OR: 1.01 [95% CI: 1.01–1.02]) on MetS were observed in primary analyses. Results from sensitivity analyses and replication analyses were generally consistent with the primary analyses, confirming the robustness and generalizability of the findings. Associations between MetS and ADHD, as well as ANO persisted after adjusting for BMI, whereas the statistical significance of the association between MetS and MDD was no longer observable. These results contribute to a deeper understanding of the mechanisms underlying PDs, suggesting potential modifiable targets for public prevention and clinical intervention in specific PDs related to metabolic pathways.

AIM: To investigate the effects of Sonic hedgehog (Shh) gene-modified bone marrow mesenchymal stem cells (MSCs) on graft-induced retinal gliosis and retinal ganglion cells (RGCs) survival in diabetic mice. METHODS: Bone marrow-derived MSCs were genetically modified with the Shh gene to generate a stably transfected cell line of Shh-modified MSCs (MSC-Shh). Intravitreal injections of MSC-Shh and green fluorescent protein-modified MSCs (MSC-Gfp; control) were administered in diabetic mice. After 4wk, the effects of MSC-Shh on retinal gliosis were evaluated using fundus photography, and markers of gliosis were examined by immunofluorescence and Western blotting. The neurotrophic factors expression and RGCs survival in the host retina were evaluated using Western blotting and immunofluorescence. The mechanisms underlying the effects of MSC-Shh was investigated. RESULTS: A significant reduction of proliferative vitreoretinopathy (PVR) was observed after intravitreal injection of MSC-Shh compared to MSC-Gfp. Significant downregulation of glial fibrillary acidic protein (GFAP) was demonstrated in the host retina after MSC-Shh administration compared to MSC-Gfp. The extracellular signal-regulated kinase 1/2 (ERK1/2), protein kinase B (AKT) and phosphatidylin-ositol-3-kinase (PI3K) pathways were significantly downregulated after MSC-Shh administration compared to MSC-Gfp. Brain-derived neurotrophic factor (BDNF) and ciliary neurotrophic factor (CNTF) levels were significantly increased in the host retina, and RGCs loss was significantly prevented after MSC-Shh administration. CONCLUSION: MSC-Shh administration reduces graft-induced reactive gliosis following intravitreal injection in diabetic mice. The ERK1/2, AKT and PI3K pathways are involved in this process. MSC-Shh also increases the levels of neurotrophic factors in the host retina and promoted RGCs survival in diabetic mice.

Abstract Background In 2022, Omicron outbreaks occurred at multiple sites in China. It is of great importance to track the incidence trends and transmission dynamics of coronavirus disease 2019 (COVID-19) to guide further interventions. Methods Given the population size, economic level and transport level similarities, two groups of outbreaks (Shanghai vs. Chengdu and Sanya vs. Beihai) were selected for analysis. We developed the SEAIQRD, ARIMA, and LSTM models to seek optimal modeling techniques for waves associated with the Omicron variant regarding data predictive performance and mechanism transmission dynamics, respectively. In addition, we quantitatively modeled the impacts of different combinations of more stringent interventions on the course of the epidemic through scenario analyses. Results The best-performing LSTM model showed better prediction accuracy than the best-performing SEAIQRD and ARIMA models in most cases studied. The SEAIQRD model had an absolute advantage in exploring the transmission dynamics of the outbreaks. Regardless of the time to inflection point or the time to R t curve below 1.0, Shanghai was later than Chengdu (day 46 vs. day 12/day 54 vs. day 14), and Sanya was later than Beihai (day 16 vs. day 12/day 20 vs. day 16). Regardless of the number of peak cases or the cumulative number of infections, Shanghai was higher than Chengdu (34,350 vs. 188/623,870 vs. 2,181), and Sanya was higher than Beihai (1,105 vs. 203/16,289 vs. 3,184). Scenario analyses suggested that upgrading control level in advance, while increasing the index decline rate and quarantine rate, were of great significance for shortening the time to peak and R t below 1.0, as well as reducing the number of peak cases and final affected population. Conclusions The LSTM model has great potential for predicting the prevalence of Omicron outbreaks, whereas the SEAIQRD model is highly effective in revealing their internal transmission mechanisms. We recommended the use of joint interventions to contain the spread of the virus.

Abstract Background Breast cancer is the leading cause of cancer death for women worldwide. Most of the breast cancer death are due to disease recurrence and metastasis. Increasingly accumulating evidence indicates that mitochondria play key roles in cancer progression and metastasis. Our recent study revealed that transmembrane protein PRRG4 promotes the metastasis of breast cancer. However, it is not clear whether PRRG4 can affect the migration and invasion of breast cancer cells through regulating mitochondria function. Methods RNA-seq analyses were performed on breast cancer cells expressing control and PRRG4 shRNAs. Quantitative PCR analysis and measurements of mitochondrial ATP content and oxygen consumption were carried out to explore the roles of PRRG4 in regulating mitochondrial function. Luciferase reporter plasmids containing different lengths of promoter fragments were constructed. Luciferase activities in breast cancer cells transiently transfected with these reporter plasmids were analyzed to examine the effects of PRRG4 overexpression on promoter activity. Transwell assays were performed to determine the effects of PRRG4-regulated pathway on migratory behaviors of breast cancer cells. Results Analysis of the RNA-seq data revealed that PRRG4 knockdown decreased the transcript levels of all the mitochondrial protein-encoding genes. Subsequently, studies with PRRG4 knockdown and overexpression showed that PRRG4 expression increased mitochondrial DNA (mtDNA) content. Mechanistically, PRRG4 via Src activated STAT3 in breast cancer cells. Activated STAT3 in turn promoted the transcription of mtDNA polymerase POLG through a STAT3 DNA binding site present in the POLG promoter region, and increased mtDNA content as well as mitochondrial ATP production and oxygen consumption. In addition, PRRG4-mediated activation of STAT3 also enhanced filopodia formation, migration, and invasion of breast cancer cells. Moreover, PRRG4 elevated migratory behaviors and mitochondrial function of breast cancer cells through POLG. Conclusion Our results indicate that PRRG4 via the Src-STAT3-POLG axis enhances mitochondrial function and promotes migratory behaviors of breast cancer cells.

Abstract Cultured meat production has emerged as a breakthrough technology for the global food industry with the potential to reduce challenges associated with environmental sustainability, global public health, animal welfare, and competition for food between humans and animals. The muscle stem cell lines currently used for cultured meat cannot be passaged in vitro for extended periods of time. Here, we develop a directional differentiation system of porcine pre-gastrulation epiblast stem cells (pgEpiSCs) with stable cellular features and achieve serum-free myogenic differentiation of the pgEpiSCs. We show that the pgEpiSCs-derived skeletal muscle progenitor cells and skeletal muscle fibers have typical muscle cell characteristics and display skeletal muscle transcriptional features during myogenic differentiation. Importantly, we establish a three-dimensional differentiation system for shaping cultured tissue by screening plant-based edible scaffolds of non-animal origin, followed by the generation of pgEpiSCs-derived cultured meat. These advances provide a technical approach for the development of cultured meat.

The novel weapon hypothesis suggests that allelopathy is an important mechanism for exotic plants to successfully invade native plant communities. Allelochemicals from exotic plants affect both native plants and arbuscular mycorrhizal fungi (AMF) in soil. To explore these effects, we conducted pot experiments using a native plant community comprising of Chenopodium album L., Vitex negundo L., Rhus chinensis Mill., and Acer truncatum Bunge. We incorporated AMF strains (Funneliformis mosseae, Glomus versiforme, and Rhizophagus intraradices in a 1:1:1 volume ratio) into a soil mixture comprising equal volumes of autoclaved field soil and grass ash at five concentrations (0 g L–1, CK; 10 g L–1, LRE; 20 g L–1, NRE; 30 g L–1, MRE; and 40 g L–1, HRE) to investigate the allelopathy of Rhus typhina L. root and its interactions with AMF on the native plant community. Our results indicated that low concentrations of allelochemicals promoted the relative growth rate and leaf nitrogen content in the native plant community, which was attributed to the increased environmental stress that improved the degree of leaf photosynthetic capacity and organic synthesis rate in the native communities. Moreover, allelochemicals with toxicity decreased the colonization rates of AMF. Meanwhile, the presence of allelopathic effects induced a decrease in leaf nitrogen, and allelopathy altered the effects of AMF on the native community. Specifically, the high concentration of allelochemicals altered the positive effect of AMF on the total aboveground biomass of the native plant community to a negative effect, likely by decreasing colonization rates or affecting soil physicochemical properties and the composition of the mycorrhizal communities. Consequently, it is necessary to consider the effects of AMF when testing the roles of allelopathy or the novel weapons hypothesis in biological invasions. Graphical abstract

Abstract Recent advances in next-generation sequencing (NGS) technology have greatly accelerated the need for efficient annotation to accurately interpret clinically relevant genetic variants in human diseases. Therefore, it is crucial to develop appropriate analytical tools to improve the interpretation of disease variants. Given the unique genetic characteristics of mitochondria, including haplogroup, heteroplasmy, and maternal inheritance, we developed a suite of variant analysis toolkits specifically designed for primary mitochondrial diseases: the Mitochondrial Missense Variant Annotation Tool (MmisAT) and the Mitochondrial Missense Variant Pathogenicity Predictor (MmisP). MmisAT can handle protein-coding variants from both nuclear DNA and mtDNA and generate 349 annotation types across six categories. It processes 4.78 million variant data in 76 min, making it a valuable resource for clinical and research applications. Additionally, MmisP provides pathogenicity scores to predict the pathogenicity of genetic variations in mitochondrial disease. It has been validated using cross-validation and external datasets and demonstrated higher overall discriminant accuracy with a receiver operating characteristic (ROC) curve area under the curve (AUC) of 0.94, outperforming existing pathogenicity predictors. In conclusion, the MmisAT is an efficient tool that greatly facilitates the process of variant annotation, expanding the scope of variant annotation information. Furthermore, the development of MmisP provides valuable insights into the creation of disease-specific, phenotype-specific, and even gene-specific predictors of pathogenicity, further advancing our understanding of specific fields.

Chemical fungicides can cause drug resistance of plant pathogenic fungi, environmental pollution, and potential threats to humans and animals. Therefore, developing low-toxicity, high-efficient and environment-friendly biological control products is critical for green prevention, controlling plant fungal diseases, and maintaining ecological balance. Biocontrol research mainly includes the following aspects: antagonistic microorganisms, fungicidal proteins, RNA interference techniques and botanical fungicides. Significantly, natural products extracted from medicinal plants are valuable repertoire for inhibiting plant fungal diseases. This review systematically reviewed the research advances of using natural products from medicinal plants to inhibit plant pathogenic fungi, including the types of natural products, extraction methods, and antifungal mechanisms. The further prospects for the study and application, which provide the reference for botanical fungicide development and practical application in preventing and controlling plant fungal disease, were also discussed.

Abstract Influenza A viruses (IAV) are a prevalent respiratory pathogen that can cause seasonal flu and global pandemics, posing a significant global public health threat. Emerging research suggests that IAV infections may disrupt the balance of gut microbiota, while gut dysbiosis can affect disease progression in IAV patients. Therefore, restoring gut microbiota balance may represent a promising therapeutic target for IAV infections. Traditional Chinese medicine, with its ability to regulate gut microbiota, offers significant potential in preventing and treating IAV. This article provides a comprehensive review of the relationship between IAV and gut microbiota, highlighting the impact of gut microbiota on IAV infections. It also explores the mechanisms and role of traditional Chinese medicine in regulating gut microbiota for the prevention and treatment of IAV, presenting novel research avenues for traditional Chinese medicine-based IAV treatments.