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Type 2 diabetes (T2D) is a major risk factor for heart failure (HF) and has elevated incidence among individuals with HF. Since genetics and HF can independently influence T2D, collider bias may occur when T2D (i.e., collider) is controlled for by design or analysis. Thus, we conducted a genome-wide association study (GWAS) of diabetes-related HF with correction for collider bias. We first performed a GWAS of HF to identify genetic instrumental variables (GIVs) for HF and to enable bidirectional Mendelian randomization (MR) analysis between T2D and HF. We identified 61 genomic loci, significantly associated with all-cause HF in 114,275 individuals with HF and over 1.5 million controls of European ancestry. Using a two-sample bidirectional MR approach with 59 and 82 GIVs for HF and T2D, respectively, we estimated that T2D increased HF risk (odds ratio [OR] 1.07, 95% confidence interval [CI] 1.04–1.10), while HF also increased T2D risk (OR 1.60, 95% CI 1.36–1.88). Then we performed a GWAS of diabetes-related HF corrected for collider bias due to the study design of index cases. After removing the spurious association of TCF7L2 locus due to collider bias, we identified two genome-wide significant loci close to PITX2 (chromosome 4) and CDKN2B−AS1 (chromosome 9) associated with diabetes-related HF in the Million Veteran Program and replicated the associations in the UK Biobank. Our MR findings provide strong evidence that HF increases T2D risk. As a result, collider bias leads to spurious genetic associations of diabetes-related HF, which can be effectively corrected to identify true positive loci. This study demonstrated the bidirectional relationship between type 2 diabetes and heart failure, addressed the impact of collider bias on the genome-wide association study of diabetes-related heart failure, and identified and replicated two genetic loci. These discoveries offer pivotal insights into the intricate mechanisms and comorbidities associated with heart failure. [ABSTRACT FROM AUTHOR]

Drought stress is a prominent abiotic factor that adversely influences the growth and development of Bupleurum chinense during its seedling stage, negatively impacting biomass and secondary metabolite production, thus affecting yield and quality. To investigate the molecular mechanism underlying the response of B. chinense seedlings under drought stress, this study employed comprehensive physiological, transcriptomic, and metabolomic analyses. The results revealed that under drought stress, the root soluble sugar and free proline content in B. chinense seedlings significantly increased, while the activities of SOD, POD, and CAT increased in the leaves. These findings indicate the presence of distinct response mechanisms in B. chinense to cope with drought stress. Integrated analysis further identified significant correlations between genes and metabolites related to amino acid biosynthesis in the leaves, as well as genes and metabolites associated with acetaldehyde and dicarboxylic acid metabolism. In the roots, genes and metabolites related to plant hormone signaling and the tricarboxylic acid (TCA) cycle showed significant correlations. These findings provide vital views into the molecular-level response mechanisms of B. chinense under drought stress. Moreover, this study establishes the groundwork for identifying drought-tolerant genes and breeding drought-resistant varieties, which could improve the drought tolerance of medicinal plants and have broader implications for agriculture and crop production in water-scarce areas. [ABSTRACT FROM AUTHOR]

Multi beam forward looking sonar plays an important role in underwater detection. However, due to the complex underwater environment, unclear features, and susceptibility to noise interference, most forward looking sonar systems have poor recognition performance. The research on MFLS for underwater target detection faces some challenges. Therefore, this study proposes innovative improvements to the YOLOv5 algorithm to address the above issues. On the basis of maintaining the original YOLOv5 architecture, this improved model introduces transfer learning technology to overcome the limitation of scarce sonar image data. At the same time, by incorporating the concept of coordinate convolution, the improved model can extract features with rich positional information, significantly enhancing the model's detection ability for small underwater targets. Furthermore, in order to solve the problem of feature extraction in forward looking sonar images, this study integrates attention mechanisms. This mechanism expands the receptive field of the model and optimizes the feature learning process by highlighting key details while suppressing irrelevant information. These improvements not only enhance the recognition accuracy of the model for sonar images, but also enhance its applicability and generalization performance in different underwater environments. In response to the common problem of uneven training sample quality in forward looking sonar imaging technology, this study made a key improvement to the classic YOLOv5 algorithm. By adjusting the bounding box loss function of YOLOv5, the model's over sensitivity to low-quality samples was reduced, thereby reducing the punishment on these samples. After a series of comparative experiments, the newly proposed CCW-YOLOv5 algorithm has achieved detection accuracy in object detection mAP@0.5 Reached 85.3%, and the fastest inference speed tested on the local machine was 54 FPS, showing significant improvement and performance improvement compared to existing advanced algorithms. [ABSTRACT FROM AUTHOR]

Cellular senescence is closely related to DNA damage, proteasome inactivity, histone loss, epigenetic alterations, and tumorigenesis. The mammalian proteasome activator PA200 (also referred to as PSME4) or its yeast ortholog Blm10 promotes the acetylation-dependent degradation of the core histones during transcription, DNA repair, and spermatogenesis. According to recent studies, PA200 plays an important role in senescence, probably because of its role in promoting the degradation of the core histones. Loss of PA200 or Blm10 is a major cause of the decrease in proteasome activity during senescence. In this paper, recent research progress on the association of PA200 with cellular senescence is summarized, and the potential of PA200 to serve as a therapeutic target in age-related diseases is discussed. [ABSTRACT FROM AUTHOR]

Expanding gain bandwidth into the L-band for erbium-doped fiber amplifiers (EDFAs) is a crucial strategy to overcome limitations in prevalent C-band focused commercial silica-based EDFAs, significantly boosting optical network transmission capacity. Herein, we synthesized Er3+-doped broadband near-infrared emission tellurite glasses utilizing the melt quenching process, systematically exploring the impact of ZnCl 2 on the glass structure and optical properties. The 82TeO 2 –3Nb 2 O 5 –15ZnCl 2 –3Er 2 O 3 (TNZ15) glass emerged as a standout candidate for broadband amplifiers around wavelength at 1.55 μm. With escalating ZnCl 2 concentration, a discernible red shift in the emission peak wave lines was observed, accompanied by an expansion of the full width at half maximum (FWHM) from 98 nm to 106 nm. Noteworthy characteristics of all samples included exceptional thermal stability and elevated near-infrared (NIR) transmittance. Application of the Judd-Ofelt (J-O) theory facilitated the calculation of J-O parameter intensity, providing deeper insights into the optical behavior of the materials. Finally, the evaluation of TNZ15 planar optical waveguides, employing the vertical top pumping mode of two 980 nm LEDs, encompassed both the C-band (1530–1565 nm) and the L-band (1565–1625 nm). The results underscore the potential of TNZ15 glass as a promising gain material for broadband optical amplifiers and lasers, offering valuable insights into the development of next-generation optical amplification technologies. [ABSTRACT FROM AUTHOR]

In this work, we study the mechanisms of X‐ray induced darkening in the Dy/Al/P co‐doped silica glasses at visible wavelengths and explore the role of P/Al ratio played in the enhancement of irradiation resistance. The absorption, emission spectra and lifetime, Raman, and electron paramagnetic resonance spectra of pristine and irradiated Dy‐silica glasses as a function of P/Al ratio were measured and analyzed. The Si‐related defects (Si‐E′ and non‐bridge oxygen hole center), Al‐related defects (Al‐E′ and Al‐related oxygen hole center), P‐related defects (P‐OHC and P2), and Dy2+ ions were studied and analyzed. Results demonstrate that increasing P/Al is efficient to suppress the photodarkening in Dy‐silica glasses at visible wavelengths. Results imply that Dy‐silica glasses with P/Al > 1 may be a promising candidate for efficient visible fiber lasers operated at around 575 nm wavelength. [ABSTRACT FROM AUTHOR]

Type IV collagen is an integral component of basement membranes. Mutations in COL4A1, one of the key genes encoding Type IV collagen, can result in a variety of diseases. It is clear that a significant proportion of mutations that affect splicing can cause disease directly or contribute to the susceptibility or severity of disease. Here, we analyzed exonic mutations and intronic mutations described in the COL4A1 gene using bioinformatics programs and identified candidate mutations that may alter the normal splicing pattern through a minigene system. We identified seven variants that induce splicing alterations by disrupting normal splice sites, creating new ones, or altering splice regulatory elements. These mutations are predicted to impact protein function. Our results help in the correct molecular characterization of variants in COL4A1 and may help develop more personalized treatment options. [ABSTRACT FROM AUTHOR]

Objectives: Elastic band resistance training in elderly individuals can improve physical fitness and promote mental health in addition to other benefits. This systematic review aimed to review, summarize, and evaluate quantitative, qualitative, and mixed methodological studies on the use of elastic band resistance training in elderly individuals, and to investigate the influence of elastic band resistance training on the physical and mental health of elderly individuals, as well as their preferences and obstacles in training. Methods: A convergent separation approach was used to synthesize and integrate the results, specifically the mixed systematic review approach recommended by the Joanna Briggs Institute. The extensive search strategy included electronic database searches in the Cochrane Library, PubMed, Embase, Web of Science, Google Scholar, MEDLINE, and CINAHL. The researchers rigorously screened the literature, extracted and analyzed the data, and evaluated the quality of the included studies using the Mixed Methods Appraisal Tool (MMAT). Results: Twenty-eight studies were included, of which 25 were quantitative studies, 2 were qualitative studies, and 1 was a mixed-methods study. A total of 1,697 subjects were investigated across all studies. Quantitative evidence supports the notion that elastic band resistance training can improve upper and lower limb flexibility, endurance, upper strength, physical balance, and cardiopulmonary function and enhance the mental health of elderly individuals. Participants in the qualitative study reported some preferences and obstacles with band resistance training, but most participants reported physical benefits. Conclusions: Despite the heterogeneity between studies, this review is the first systematic review to comprehensively evaluate the effectiveness of elastic band resistance training in older adults. It not only shows the influence of elastic band resistance training on the physical and mental health of the elderly, but also emphasizes the preference and obstacles of elderly individuals face. [ABSTRACT FROM AUTHOR]

Background: Sleep disorders are a prevalent non-motor symptom of Parkinson's disease (PD), although reliable biological markers are presently lacking. Objectives: To explore the associations between sleep disorders and serum neurofilament light chain (NfL) levels in individuals with prodromal and early PD. Methods: The study contained 1113 participants, including 585 early PD individuals, 353 prodromal PD individuals, and 175 healthy controls (HCs). The correlations between sleep disorders (including rapid eye movement sleep behavior disorder (RBD) and excessive daytime sleepiness (EDS)) and serum NfL levels were researched using multiple linear regression models and linear mixed-effects models. We further investigated the correlations between the rates of changes in daytime sleepiness and serum NfL levels using multiple linear regression models. Results: In baseline analysis, early and prodromal PD individuals who manifested specific behaviors of RBD showed significantly higher levels of serum NfL. Specifically, early PD individuals who experienced nocturnal dream behaviors (β = 0.033; P = 0.042) and movements of arms or legs during sleep (β = 0.027; P = 0.049) showed significantly higher serum NfL levels. For prodromal PD individuals, serum NfL levels were significantly higher in individuals suffering from disturbed sleep (β = 0.038; P = 0.026). Our longitudinal findings support these baseline associations. Serum NfL levels showed an upward trend in early PD individuals who had a higher total RBDSQ score (β = 0.002; P = 0.011) or who were considered as probable RBD (β = 0.012; P = 0.009) or who exhibited behaviors on several sub-items of the RBDSQ. In addition, early PD individuals who had a high total ESS score (β = 0.001; P = 0.012) or who were regarded to have EDS (β = 0.013; P = 0.007) or who exhibited daytime sleepiness in several conditions had a trend toward higher serum NfL levels. Conclusion: Sleep disorders correlate with higher serum NfL, suggesting a link to PD neuronal damage. Early identification of sleep disorders and NfL monitoring are pivotal in detecting at-risk PD patients promptly, allowing for timely intervention. Regular monitoring of NfL levels holds promise for tracking both sleep disorders and disease progression, potentially emerging as a biomarker for evaluating treatment outcomes. [ABSTRACT FROM AUTHOR]

Background: The current nursing procedure after fractional carbon dioxide (fCO2) is complex and needs to be optimized. The present study was conducted to evaluate the assisting effect of filament coating system after fCO2 laser treatment. Methods: Chinese individuals aged from 18 to 65 years diagnosed as photoaging or atrophic acne scar were recruited and each participant was treated with one single pass of fCO2 laser. A split face was randomly assigned as treatment side or control side. For control side, conventional procedure was topically applied respectively, including desonide cream two times for 3 days, fusidic acid cream two times for 7 days, and recombinant human epidermal growth factor (RhEGF) gel four times for 7 days; for treating side, a filament coating system was applied immediately after one application of fusidic acid cream, desonide cream and RhEGF, and removed 3 h later, for 3 days. Erythema, edema, crust, and pain on both sides were scored from 0 to 10 before and 1, 2, 4, and 7 days after fCO2 laser treatment. Stratum corneum hydration (SCH) and sebum of forehead and cheek on both sides were also measured by using Corneometer‐Sebumeter. Results: Twenty photoaging and 11 atrophic acne scar participants finished the observation. All of them complained of erythema, edema, crust, and pain after fCO2 laser treatment, and the scores decreased as time passed by. There were no statistical significances of erythema, edema, crust, pain, SCH, and sebum between treating side and control side at each observation time. Conclusion: Filament coating system was effective, safe, convenient, and economic in assisting recovery of ablative fCO2 laser, which might be a new option for additional nursing procedure. [ABSTRACT FROM AUTHOR]

This document summarizes a study on prenatal screening for copy number variants (CNVs) in the Duchenne muscular dystrophy (DMD) gene using non-invasive prenatal testing (NIPT) data. The study analyzed data from a large population of reproductive-age women in China and identified 33 different pathogenic/likely pathogenic maternal CNVs in the DMD gene. The study found that approximately 40% of offspring inherited true-positive maternal CNVs, and 1.63% of male offspring could potentially be prenatally diagnosed and managed using this method. The study provides important information for genetic counseling and DMD/BMD screening worldwide. [Extracted from the article]

To ensure the safe and stable operation of 5G base stations, it is essential to accurately predict their power load. However, current short‐term prediction methods are rarely applied rationally in pertinent circumstances to the features of base station power load over time. For high accuracy and generalization capabilities, this work proposes a hybrid approach that combines gated recurrent unit (GRU) with particle swarm optimization (PSO) and completes ensemble empirical mode decomposition with adaptive noise (CEEMDAN). The complex load is decomposed into multiple components to improve the fit of the neural network. To deal with the nonlinearity that constrains the modal aliasing and data noise, CEEMDAN is used to reconstruct the trend and noise sequences. The GRU network is utilized to improve the neural network fitness and obtain long‐term features. In addition, PSO is used to optimize the number of neurons and the learning rate of the GRU. Compared with existing neural network GRUs, the RMSE is reduced by 16.6, the mean absolute error is reduced by 11.97, and the coefficient of R2 is improved by 0.13, indicating that the model has a better fitting effect. The comparisons prove that the proposed model has better accuracy than the existing methods. [ABSTRACT FROM AUTHOR]

Moslae Herba (MH) can be used for both medicine and food and has a long history of medicine. MH has the effects of sweating and relieving the exterior, removing dampness and harmonizing, and is mainly used for colds caused by damp heat in summer. It is called "Xiayue Zhi Mahuang" in China. So far, 123 chemical compounds have been isolated and identified from MH, including flavonoids, terpenoids, phenolic acids, phenylpropanoids, and other chemical compounds. Its chemical components have a wide range of pharmacological activities, including antibacterial, antiviral, anti-inflammatory, antioxidant, analgesic sedation, antipyretic, immune regulation, insecticidal, and other effects. In addition, because of its aromatic odor and health care function, MH also has development and utilization value in food, chemical, and other fields. This paper reviewed the research progress of MH in botany, traditional uses, phytochemistry, and pharmacology and provided a possible direction for further research. [ABSTRACT FROM AUTHOR]

This study models a container routing problem using multimodal transportation to improve its economy, timeliness, and reliability. Pickup and delivery time windows are simultaneously formulated in optimization to provide the shipper and the receiver with time-efficient services, in which early pickup and delayed delivery can be avoided, and nonlinear storage periods at the origin and the destination can be minimized. Furthermore, the capacity uncertainty of the multimodal network is incorporated into the advanced routing to enhance its reliability in practical transportation. The LR triangular fuzzy number is adopted to model the capacity uncertainty, in which its spread ratio is defined to measure the uncertainty level of the fuzzy capacity. Due to the nonlinearity introduced by the time windows and the fuzziness from the network capacity, this study establishes a fuzzy nonlinear optimization model for optimization problem. A chance-constrained linear reformulation equivalent to the proposed model is then generated based on the credibility measure, which makes the global optimum solution attainable by using Lingo software. A numerical case verification demonstrates that the proposed model can effectively solve the problem. The case analysis points out that the formulation of pickup and delivery time windows can improve the timeliness of the entire transportation process and help to achieve on-time transportation. Furthermore, improving the confidence level and the uncertainty level increases the total costs of the optimal route. Therefore, the shipper and the receiver must prepare more transportation budget to improve reliability and address the increasing uncertainty level. Further analysis draws some insights to help the shipper, receiver, and multimodal transport operator to organize a reliable and cost-efficient multimodal transportation under capacity uncertainty through confidence level balance and transportation service and transfer service selection. [ABSTRACT FROM AUTHOR]

Leaf senescence is the terminal stage of leaf development, and its initiation and progression are closely controlled by the integration of a myriad of endogenous signals and environmental stimuli. It has been documented that WRKY transcription factors (TFs) play essential roles in regulating leaf senescence, yet the molecular mechanism of WRKY-mediated leaf senescence still lacks detailed elucidation in crop plants. In this study, we cloned and identified a tobacco WRKY TF gene, designated NtWRKY70b, acting as a positive regulator of natural leaf senescence. The expression profile analysis showed that NtWRKY70b transcript levels were induced by aging and hydrogen peroxide (H2O2) and downregulated upon hydrogen sulfide (H2S) treatment. The physiological and biochemical assays revealed that overexpression of NtWRKY70b (OE) clearly promoted leaf senescence, triggering increased levels of reactive oxygen species (ROS) and decreased H2S content, while disruption of NtWRKY70b by chimeric repressor silencing technology (SRDX) significantly delayed the onset of leaf senescence, leading to a decreased accumulation of ROS and elevated concentration of H2S. The quantitative real-time PCR analysis showed that the expression levels of various senescence-associated genes and ROS biosynthesis-related genes (NtRbohD and NtRbohE) were upregulated in OE lines, while the expression of H2S biosynthesis-related genes (NtDCD and NtCYSC1) were inhibited in OE lines. Furthermore, the Yeast one-hybrid analysis (Y1H) and dual luciferase assays showed that NtWRKY70b could directly upregulate the expression of an ROS biosynthesis-related gene (NtRbohD) and a chlorophyll degradation-related gene (NtPPH) by binding to their promoter sequences. Accordingly, these results indicated that NtWYKY70b directly activated the transcript levels of NtRbohD and NtPPH and repressed the expression of NtDCD and NtCYCS1, thereby promoting ROS accumulation and impairing the endogenous H2S production, and subsequently accelerating leaf aging. These observations improve our knowledge of the regulatory mechanisms of WRKY TFs controlling leaf senescence and provide a novel method for ensuring high agricultural crop productivity via genetic manipulation of leaf senescence in crops. [ABSTRACT FROM AUTHOR]

Phytophthora root and stem rot of soybean (Glycine max), caused by the oomycete Phytophthora sojae, is an extremely destructive disease worldwide. In this study, we identified GmEIL1, which encodes an ethylene‐insensitive3 (EIN3) transcription factor. GmEIL1 was significantly induced following P. sojae infection of soybean plants. Compared to wild‐type soybean plants, transgenic soybean plants overexpressing GmEIL1 showed enhanced resistance to P. sojae and GmEIL1‐silenced RNA‐interference lines showed more severe symptoms when infected with P. sojae. We screened for target genes of GmEIL1 and confirmed that GmEIL1 bound directly to the GmERF113 promoter and regulated GmERF113 expression. Moreover, GmEIL1 positively regulated the expression of the pathogenesis‐related gene GmPR1. The GmEIL1‐regulated defence response to P. sojae involved both ethylene biosynthesis and the ethylene signalling pathway. These findings suggest that the GmEIL1‐GmERF113 module plays an important role in P. sojae resistance via the ethylene signalling pathway. [ABSTRACT FROM AUTHOR]

Background: Posterior cortical atrophy (PCA) is a form of dementia that frequently displays significant visual dysfunction and relatively preserved cognitive and executive functions, thus hindering early diagnosis and treatment. This study aimed to investigate possible fundus markers in PCA patients and compare them with those of typical Alzheimer's disease (AD) patients to seek potential diagnostic patterns. Methods: Age-matched PCA and AD patients and healthy controls (HC) completed optometry, intraocular pressure measurement, neuropsychologic assessments, optical coherence tomography (OCT), and optical coherence tomography angiography (OCTA) examination in one visit. Overall, six outcomes of thicknesses of various retinal layers and seven outcomes of the retinal microvascular network were calculated. After adjusting for age, sex, and years of education, the OCT and OCTA results were analyzed using analysis of covariance and generalized linear models. Correlation analyses were performed using Spearman correlation, and ROC curves were plotted. Results: Twelve PCA patients, nineteen AD patients, and thirty HC, aged 45–80 years were included. Fifty HC, thirty AD, and twenty PCA eyes were available for foveal avascular zone (FAZ) area analysis; forty-nine HC, thirty-four AD, and eighteen PCA eyes were available for OCT and OCTA assessments. PCA patients had thinner retinal nerve fiber layer and ganglion cell layer + inner plexiform layer than HC in the 0–3 mm circle and 1–3 mm ring. Few structural differences were observed between the AD group and the other two groups. The flow area of the superficial capillary plexus and the intermediate capillary plexus was smaller in the PCA group than in the HC group in the 0–1 mm circle, 0–3 mm circle. MMSE performed better than any combination of optical parameters in identifying AD and PCA from HC (AUC = 1), while the combination of MoCA, retinal thickness and vascular density of ICP in the 1-3 mm ring, with flow area of ICP in the 0-1 mm circle showed the strongest ability to distinguish PCA from AD (AUC = 0.944). Conclusions: PCA patients exhibited similar impairment patterns to AD patients in the fundus structure and microvascular network. OCTA may aid in the non-invasive detection of AD and PCA, but still remains to be substantiated. [ABSTRACT FROM AUTHOR]

The fractional Fourier transform (FRFT) is a generalized form of the Fourier transform (FT), it is another important class of time–frequency analysis tool in signal processing. In this paper, we study the two-dimensional (2D) FRFT in the polar coordinates setting. First, Parseval theorem of the 2D FRFT in the polar coordinates is obtained. Then, according to the relationship between 2D FRFT and fractional Hankel transform (FRHT), the convolution theorem for the 2D FRFT in polar coordinates is obtained. It shows that the FRFT of the convolution of two functions is the product of their respective FRFTs. Moreover, the fast algorithm for the convolution theorem of the 2D FRFT is discussed. Finally, the sampling theorem for signal is explored. [ABSTRACT FROM AUTHOR]

Motivation Drug–target interaction (DTI) prediction aims to identify interactions between drugs and protein targets. Deep learning can automatically learn discriminative features from drug and protein target representations for DTI prediction, but challenges remain, making it an open question. Existing approaches encode drugs and targets into features using deep learning models, but they often lack explanations for underlying interactions. Moreover, limited labeled DTIs in the chemical space can hinder model generalization. Results We propose an interpretable nested graph neural network for DTI prediction (iNGNN-DTI) using pre-trained molecule and protein models. The analysis is conducted on graph data representing drugs and targets by using a specific type of nested graph neural network, in which the target graphs are created based on 3D structures using Alphafold2. This architecture is highly expressive in capturing substructures of the graph data. We use a cross-attention module to capture interaction information between the substructures of drugs and targets. To improve feature representations, we integrate features learned by models that are pre-trained on large unlabeled small molecule and protein datasets, respectively. We evaluate our model on three benchmark datasets, and it shows a consistent improvement on all baseline models in all datasets. We also run an experiment with previously unseen drugs or targets in the test set, and our model outperforms all of the baselines. Furthermore, the iNGNN-DTI can provide more insights into the interaction by visualizing the weights learned by the cross-attention module. Availability and implementation The source code of the algorithm is available at https://github.com/syan1992/iNGNN-DTI. [ABSTRACT FROM AUTHOR]

This study investigates a green multimodal routing problem with soft time window. The objective of routing is to minimize the total costs of accomplishing the multimodal transportation of a batch of goods. To improve the feasibility of optimization, this study formulates the routing problem in an uncertain environment where the capacities and carbon emission factors of the travel process and the transfer process in the multimodal network are considered fuzzy. Taking triangular fuzzy numbers to describe the uncertainty, this study proposes a fuzzy nonlinear programming model to deal with the specific routing problem. To make the problem solvable, this study adopts the fuzzy chance-constrained programming approach based on the possibility measure to remove the fuzziness of the proposed model. Furthermore, we use linear inequality constraints to reformulate the nonlinear equality constraints represented by the continuous piecewise linear functions and realize the linearization of the nonlinear programming model to improve the computational efficiency of problem solving. After model processing, we can utilize mathematical programming software to run exact solution algorithms to solve the specific routing problem. A numerical experiment is given to show the feasibility of the proposed model. The sensitivity analysis of the numerical experiment further clarifies how improving the confidence level of the chance constraints to enhance the possibility that the multimodal route planned in advance satisfies the real-time capacity constraint in the actual transportation, i.e., the reliability of the routing, increases both the total costs and carbon emissions of the route. The numerical experiment also finds that charging carbon emissions is not absolutely effective in emission reduction. In this condition, bi-objective analysis indicates the conflicting relationship between lowering transportation activity costs and reducing carbon emissions in routing optimization. The sensitivity of the Pareto solutions concerning the confidence level reveals that reliability, economy, and environmental sustainability are in conflict with each other. Based on the findings of this study, the customer and the multimodal transport operator can organize efficient multimodal transportation, balancing the above objectives using the proposed model. [ABSTRACT FROM AUTHOR]

Angelicae sinensis radix is commonly used in Chinese medicine and is also widely used as a spice and condiment in many countries. Due to the different geographical sources and processing methods, the contents of chemical components are different and affect the quality of Angelica sinensis radix. A simple and efficient method was established to comprehensively evaluate the quality of Angelica sinensis radix by combining HPLC fingerprint and single-standard multi-component quantitative analysis. With ferulic acid as a single marker, the contents of eight main active ingredients, including ferulic acid, senkyunolide I, senkyunolide H, coniferyl ferulate, E-ligustilide, E-butylidenephthalide, Z-ligustilide, and Z-butylidenephthalide, were simultaneously determined in 30 min by reliable relative correction factor. The overall chemical profiles of Angelica sinensis radix were compared by fingerprint similarity evaluation, the specific content level of each component was compared by simultaneous content determination of multiple components of a single standard, and the specific different components of Angelica sinensis radix before and after processing were analyzed by chemometrics. The established method was successfully applied to the quality evaluation of 44 batches of Angelica sinensis radix from 4 different origins and 45 batches of Angelica sinensis radix with different processing methods. This study proposed a simple, rapid, low-cost, and reliable quality comprehensive evaluation method for ASR from different origins and processing methods, which may be readily transferred and applied to other industries. [ABSTRACT FROM AUTHOR]

In order to investigate the durability of two kinds of fiber-reinforced composite materials, and obtain the degradation mechanism and failure model in a hygrothermal environment, E-glass- fiber-reinforced composite materials, glass fiber-reinforced epoxy vinyl ester and glass fiber-reinforced unsaturated polyester (named GF/VE and GF/UP, respectively) were chosen to suffer rigorous hygrothermal aging. Their mechanical performance was monitored during the aging process to evaluate their durability. The cause of deterioration of the composite was comprehensively analyzed. Based on the analysis results of attenuated total-reflectance-Fourier-transform infrared spectroscopy (ATR-FTIR), thermogravimetric analysis (TGA) and dynamic mechanical analysis (DMA), the change mechanism of chain structure of the resin molecule was proposed. SEM (scanning electron microscopy), X-ray photoelectron spectroscopy (XPS) and X-ray diffraction (XRD) were used to analyze the microstructure and degradation mechanism of the fiber and the interface between fiber and matrix. The degradation mechanism of the composite system, including the resin, the fiber and the interface, was obtained, and it was found that the deterioration of the matrix resin caused by the hygrothermal environment was the main factor leading to the decline in composites performance. [ABSTRACT FROM AUTHOR]

To address the drawbacks of the slow convergence speed and lack of individual information exchange in the cuckoo search (CS) algorithm, this study proposes an improved cuckoo search algorithm based on a sharing mechanism (ICSABOSM). The enhanced algorithm reinforces information sharing among individuals through the utilization of a sharing mechanism. Additionally, new search strategies are introduced in both the global and local searches of the CS. The results from numerical experiments on four standard test functions indicate that the improved algorithm outperforms the original CS in terms of search capability and performance. Building upon the improved algorithm, this paper introduces a numerical solution approach for differential equations involving the coupling of function approximation and intelligent algorithms. By constructing an approximate function using Fourier series to satisfy the conditions of the given differential equation and boundary conditions with minimal error, the proposed method minimizes errors while satisfying the differential equation and boundary conditions. The problem of solving the differential equation is then transformed into an optimization problem with the coefficients of the approximate function as variables. Furthermore, the improved cuckoo search algorithm is employed to solve this optimization problem. The specific steps of applying the improved algorithm to solve differential equations are illustrated through examples. The research outcomes broaden the application scope of the cuckoo optimization algorithm and provide a new perspective for solving differential equations. [ABSTRACT FROM AUTHOR]

Background: The objective of this study is to conduct a systematic review and meta-analysis examining the relationship between the vasoactive-inotropic score (VIS) and patient outcomes in surgical settings. Methods: Two independent reviewers searched PubMed, Web of Science, EMBASE, Scopus, Cochrane Library, Google Scholar, and CNKI databases from November 2010, when the VIS was first published, to December 2022. Additional studies were identified through hand-searching the reference lists of included studies. Eligible studies were those published in English that evaluated the association between the VIS and short- or long-term patient outcomes in both pediatric and adult surgical patients. Meta-analysis was performed using RevMan Manager version 5.3, and quality assessment followed the Joanna Briggs Institute (JBI) Critical Appraisal Checklists. Results: A total of 58 studies comprising 29,920 patients were included in the systematic review, 34 of which were eligible for meta-analysis. Early postoperative VIS was found to be associated with prolonged mechanical ventilation (OR 5.20, 95% CI 3.78–7.16), mortality (OR 1.08, 95% CI 1.05–1.12), acute kidney injury (AKI) (OR 1.26, 95% CI 1.13–1.41), poor outcomes (OR 1.02, 95% CI 1.01–1.04), and length of stay (LOS) in the ICU (OR 3.50, 95% CI 2.25–5.44). The optimal cutoff value for the VIS as an outcome predictor varied between studies, ranging from 10 to 30. Conclusion: Elevated early postoperative VIS is associated with various adverse outcomes, including acute kidney injury (AKI), mechanical ventilation duration, mortality, poor outcomes, and length of stay (LOS) in the ICU. Monitoring the VIS upon return to the Intensive Care Unit (ICU) could assist medical teams in risk stratification, targeted interventions, and parent counseling. Systematic review registration: PROSPERO CRD42022359100. [ABSTRACT FROM AUTHOR]

Multi-axis electrical discharging machining (EDM) is the most commonly used manufacturing method for shrouded blisks. The discharge points and discharge gap distance are time-varying in a multi-axis EDM process. It is difficult to obtain an optimal servo feedrate. In traditional multi-axis EDM servo control systems, servo sensitivity is usually chosen as a smaller constant to avoid arc discharges. Thus, the servo feedrate is lower than the material removal rate in a machining process. The open circuit rate is high and the machining efficiency is decreased. This paper proposes an adaptive servo sensitivity control algorithm for multi-axis EDM of shrouded blisks. Servo sensitivity is adjusted according to discharge status, so as to decrease the open circuit rate and to improve the machining efficiency. Experiment results show that the proposed adaptive servo sensitivity control algorithm can improve the machining efficiency of shrouded blisks by 28.02% without deteriorating surface integrity. [ABSTRACT FROM AUTHOR]

Simple Summary: This investigation delves into the intricate mechanisms of autophagy-dependent cisplatin resistance in bladder cancer. Our primary objective is to unveil the precise role of SIRT1, a deacetylase enzyme, in orchestrating cisplatin resistance through autophagic pathways in the cisplatin-resistant T24/DDP cell line. The findings demonstrate that inhibiting autophagy diminishes drug resistance, while SIRT1 overexpression intensifies this resistance by stimulating autophagy. Significantly, silencing SIRT1 elevates Beclin1 acetylation, suppressing autophagy and attenuating cisplatin resistance. This nuanced understanding of SIRT1-mediated cisplatin resistance not only furthers our theoretical foundation, but also furnishes potential therapeutic targets. Autophagy-dependent cisplatin resistance poses a challenge in bladder cancer treatment. SIRT1, a protein deacetylase, is involved in autophagy regulation. However, the precise mechanism through which SIRT1 mediates cisplatin resistance in bladder cancer via autophagy remains unclear. In this study, we developed a cisplatin-resistant T24/DDP cell line to investigate this mechanism. The apoptosis rate and cell viability were assessed using flow cytometry and the CCK8 method. The expression levels of the relevant RNA and protein were determined using RT-qPCR and a Western blot analysis, respectively. Immunoprecipitation was utilized to validate the interaction between SIRT1 and Beclin1, as well as to determine the acetylation level of Beclin1. The findings indicated the successful construction of the T24/DDP cell line, which exhibited autophagy-dependent cisplatin resistance. Inhibiting autophagy significantly reduced the drug resistance index of these cells. The T24/DDP cell line showed a high SIRT1 expression level. The overexpression of SIRT1 activated autophagy, thereby further promoting cisplatin resistance in the T24/DDP cell line. Conversely, inhibiting autophagy counteracted the cisplatin-resistance-promoting effects of SIRT1. Silencing SIRT1 led to increased acetylation of Beclin1, the inhibition of autophagy, and a reduction in the cisplatin resistance of the T24/DDP cell line. Introducing a double mutation (lysine 430 and 437 to arginine, 2KR) in Beclin-1 inhibited acetylation and activated autophagy, effectively reversing the decreased cisplatin resistance resulting from SIRT1 silencing. In summary, our study elucidated that SIRT1 promotes cisplatin resistance in human bladder cancer T24 cells through Beclin1-deacetylation-mediated autophagy activation. These findings suggest a potential new strategy for reversing cisplatin resistance in bladder cancer. [ABSTRACT FROM AUTHOR]

Purpose: Depressive tendency refers to the early stage of the onset of depression disorder, which can also have a negative impact on individuals' quality of life. However, there are many numerous depression-related scales that are primarily used to evaluate depression disorders with relatively severe symptom severity. And considering the characteristics of the Chinese cultural background, relatively few corresponding scales are currently developed. This study aimed to develop and validate a depressive tendency questionnaire for Chinese middle school students, based on the psychological structure of depressive tendency in the context of Chinese culture.Methods: The initial version of the questionnaire was developed through literature reviews, open surveys, and in-depth interviews. The questionnaire was revised based on the predictions made from 865 middle school students (M=15.84, SD=1.50). Finally, the formal questionnaire was developed through valid administration to 1205 students (M=15.63, SD=1.82), using confirmatory factor analysis, reliability, and validity testing, as well as measurement invariance analysis.Results: The questionnaire consisted of 30 items, including negative self, cognitive function, personal reserve, and social support. The results of confirmatory factor analysis showed that the questionnaire fitted the data with well construct validity. Measurement invariance indicates no gender and grade differences in the questionnaire scores. The questionnaire demonstrates good reliability and validity, meeting the requirements of psychometrics.Conclusion: From a theoretical point of view, we clarified the psychological structure of depressive tendencies among Chinese middle school students, providing a theoretical and empirical basis for subsequent related research. From a practical point of view, the formal questionnaire plays a positive role in the smooth development of mental health counseling, education, and other work in middle schools. [ABSTRACT FROM AUTHOR]

Background: The absence of heterozygosity (AOH) is a kind of genomic change characterized by a long contiguous region of homozygous alleles in a chromosome, which may cause human genetic disorders. However, no method of low-pass whole genome sequencing (LP-WGS) has been reported for the detection of AOH in a low-pass setting of less than onefold. We developed a method, termed CNVseq-AOH, for predicting the absence of heterozygosity using LP-WGS with ultra-low sequencing data, which overcomes the sparse nature of typical LP-WGS data by combing population-based haplotype information, adjustable sliding windows, and recurrent neural network (RNN). We tested the feasibility of CNVseq-AOH for the detection of AOH in 409 cases (11 AOH regions for model training and 863 AOH regions for validation) from the 1000 Genomes Project (1KGP). AOH detection using CNVseq-AOH was also performed on 6 clinical cases with previously ascertained AOHs by whole exome sequencing (WES). Results: Using SNP-based microarray results as reference (AOHs detected by CNVseq-AOH with at least a 50% overlap with the AOHs detected by chromosomal microarray analysis), 409 samples (863 AOH regions) in the 1KGP were used for concordant analysis. For 784 AOHs on autosomes and 79 AOHs on the X chromosome, CNVseq-AOH can predict AOHs with a concordant rate of 96.23% and 59.49% respectively based on the analysis of 0.1-fold LP-WGS data, which is far lower than the current standard in the field. Using 0.1-fold LP-WGS data, CNVseq-AOH revealed 5 additional AOHs (larger than 10 Mb in size) in the 409 samples. We further analyzed AOHs larger than 10 Mb, which is recommended for reporting the possibility of UPD. For the 291 AOH regions larger than 10 Mb, CNVseq-AOH can predict AOHs with a concordant rate of 99.66% with only 0.1-fold LP-WGS data. In the 6 clinical cases, CNVseq-AOH revealed all 15 known AOH regions. Conclusions: Here we reported a method for analyzing LP-WGS data to accurately identify regions of AOH, which possesses great potential to improve genetic testing of AOH. [ABSTRACT FROM AUTHOR]

The emergence and increasing prevalence of antibiotic resistance pose a global public risk for human health, and nonantimicrobial pharmaceuticals play an important role in this process. Herein, five nonantimicrobial pharmaceuticals, including acetaminophen (ACT), clofibric acid (CA), carbamazepine (CBZ), caffeine (CF) and nicotine (NCT), tetracycline-resistant strains, five ARGs (sul 1, sul 2, tet G, tet M and tet W) and one integrase gene (intI 1), were detected in 101 wastewater samples during two typical sewage treatment processes including anaerobic-oxic (A/O) and biological aerated filter (BAF) in Harbin, China. The impact of nonantibiotic pharmaceuticals at environmentally relevant concentrations on both the resistance genotypes and resistance phenotypes were explored. The results showed that a significant impact of nonantibiotic pharmaceuticals at environmentally relevant concentrations on tetracycline resistance genes encoding ribosomal protection proteins (RPPs) was found, while no changes in antibiotic phenotypes, such as minimal inhibitory concentrations (MICs), were observed. Machine learning was applied to further sort out the contribution of nonantibiotic pharmaceuticals at environmentally relevant concentrations to different ARG subtypes. The highest contribution and correlation were found at concentrations of 1400–1800 ng/L for NCT, 900–1500 ng/L for ACT and 7000–10,000 ng/L for CF for tetracycline resistance genes encoding RPPs, while no significant correlation was found between the target compounds and ARGs when their concentrations were lower than 500 ng/L for NCT, 100 ng/L for ACT and 1000 ng/L for CF, which were higher than the concentrations detected in effluent samples. Therefore, the removal of nonantibiotic pharmaceuticals in WWTPs can reduce their selection pressure for resistance genes in wastewater. [Display omitted] • Target selection tendency towards tetracycline resistance genes code RPPs. • Significant concentration differences in the impact of different pollutants on ARGs. • Removal of non-antibiotic pharmaceuticals reduce selection stress on ARGs. [ABSTRACT FROM AUTHOR]

Periodic floods and ebb tides driven by seawater affect arsenic (As) behavior in coastal wetlands, which is not fully understood. In this study, we combined DGT, high-throughput sequencing, and real-time quantitative polymerase chain reaction (qPCR) techniques for the first time to investigate the effects of flood and ebb tide on As transformation and mobility in a typical coastal tidal flat wetland by laboratory experiments. In the flood-tide stage, more As was released into the water solution, and As(III) concentration in water solution was notably higher (51 μg/L) than in the ebb-tide stage, especially in SA (sodium acetate addition) treatment. As-methylation also occurred in this stage. The release of As was attributed to the reductive dissolution of amorphous and crystalline Fe oxides bound As induced by microbes. Fusibacter , Sva1033 , Bradyrhizobium , Ralstonia , and Desulfobacter were primarily involved in the reduction of As, Fe, and S. The copy numbers of arsC were 20–148 times higher than arrA , suggesting that the detoxification reduction pathway was the primary mechanism of direct As-reduction in the flood-tide stage. However, 2-D high-resolution DGT techniques revealed that the concentrations of As(III) and total As in pore water of sediments in the ebb-tide stage were higher than those in the flood-tide stage. The detected aioA gene indicated that As was oxidized in the sediment surface, resulting in As stabilization by crystalline iron minerals, whereas more As(III) were accumulated in pore water. The reduction pathway mediated by arrA may play a prominent role in the ebb-tide stage. This study provides new insights into As release processes in coastal wetlands in seawater environments, which further deepens our understanding of As biogeochemical cycling behavior in different natural environments. [Display omitted] • As Reduction and methylation occurred in coastal tidal flat sediments. • As(III) release in water solution was higher in the flood tide stage. • As Detoxification reduction was the primary mechanism in flood tide stage. • As(III) release in pore water of coastal sediments was higher in ebb tide stage. • As Reduction pathway mediated by arrA played a prominent role in the ebb tide stage. [ABSTRACT FROM AUTHOR]

Sepsis, a complex clinical syndrome characterized by an exaggerated host response to infection, often necessitates hospitalization and intensive care unit admission. Delayed or inaccurate diagnosis of sepsis, coupled with suboptimal treatment strategies, can result in unfavorable outcomes, including mortality. Maresins, a newly discovered family of lipid mediators synthesized from docosahexaenoic acid by macrophages, have emerged as key players in promoting inflammation resolution and the termination of inflammatory processes. Extensive evidence has unequivocally demonstrated the beneficial effects of maresins in modulating the inflammatory response associated with sepsis; however, their bioactivity and functions exhibit remarkable diversity and complexity. This article presents a comprehensive review of recent research on the role of maresins in sepsis, aiming to enhance our understanding of their effectiveness and elucidate the specific mechanisms underlying their actions in sepsis treatment. Furthermore, emerging insights into the management of patients with sepsis are also highlighted. [Display omitted] [ABSTRACT FROM AUTHOR]

Establishing an accurate quality prediction model is an essential prerequisite for quality management in diesel engine manufacturing factories. However, the large production scale and non-linear relationship between features and the diesel engine power significantly aggravate the complexity of establishing a power prediction model. The identification of key features can not only improve the prediction performance but also facilitate the control of product quality. The mainstream feature selection methods estimate features on a whole static sampling space, which ignores dynamic correlation among candidate features, selected features, and the label variable. This paper focuses on the relevance between the candidate features and diesel engine quality, the complementary and redundancy between the candidate features and selected features, proposing a conditional mutual information-based dynamic feature selection method for the prediction of diesel engine quality. Then, a high-accuracy AdaBoost model is proposed with support vector regression-partial swarm optimization (SVR-PSO) as weak learners, showing a satisfactory non-linear fitting ability and a convenient parameter optimization process. Finally, several cases are performed to evaluate the effectiveness of the proposed methods. The proposed feature selection method shows a better performance than common feature selection methods on UCI datasets. Results on diesel engine power prediction declare that the proposed AdaBoost-SVR-PSO model is an effective quality prediction method compared with adaptive boosting, multilayer perception, and gradient boosting decision tree. [ABSTRACT FROM AUTHOR]

A Janus photocathode of asymmetric wettability with hydrophobic oxygen storage layer and hydrophilic catalyst layer was successfully fabricated by graphite felt (GF) polytetrafluoroethylene (PTFE)-hydrophobization and a subsequent hollow sphere NiFe 2 O 4 @ZnFe 2 O 4 (NF@ZF) Z-scheme photocatalysts coating on the other side of GF. The designed Janus electrode showed significantly higher H 2 O 2 production than hydrophilic (NF@ZF/GF) and hydrophobic (NF@ZF/PTFE/GF) electrodes, and achieved a higher faradaic efficiency of 72%, as well as a record H 2 O 2 production rate of 255.9 mg·L−1∙h−1, while maintaining a stable photoelectrochemical performance for 9 h at 2.8 mA∙cm−2 in Na 2 SO 4 solution. The two-electrode co-photoelectrolysis system by coupling the ORR with inorganic arsenic/organoarsenic oxidation can simultaneously produce H 2 O 2 at Janus photocathode and As (V) at Fe anode under a low energy consumption (a cell voltage of only 0.7 V), respectively, and then the generated As (V) could be rapidly removed (above 93%) by adsorption onto Fe (III) (hydro)oxides. [Display omitted] • Novel architecture of NiFe 2 O 4 @ZnFe 2 O 4 electrode with tunable wettability is proposed. • Designed Janus photoelectrode shows highly H 2 O 2 yield and low energy consumption. • Janus electrode mitigated the O 2 mass transport and adequate ion transport limitation. • Clever build Janus ‖ Fe cell in-situ Fenton achieves arsenic pollution remediation. • Generated low toxic arenates can be simultaneously immobilized on iron (hydro)oxide. [ABSTRACT FROM AUTHOR]

A novel zero carbon emission combined power and hydrogen system is developed in this paper, which integrates power generation, hydrogen production, and energy storage. The novel combined system is composed of solar power tower subsystem, supercritical carbon dioxide recompression Brayton cycle subsystem, hydrogen gas turbine subsystem, hydrogen production subsystem and thermoelectric generator subsystem. Considering the solar instability, three operating modes are set for the combined system: pure hydrogen mode, solar‑hydrogen hybrid mode and pure solar energy mode. Comprehensive energy, exergy and economic analyses are performed for the combined system. The effects of five key parameters on the system performance are investigated. Taking the maximum exergy efficiency and the minimum levelized cost of energy as the objective function, the key parameters are optimized by the genetic algorithm. Results show that in pure hydrogen mode, the thermal and exergy efficiency of the combined system are 44.79% and 45.49%, respectively. Compared with pure hydrogen mode, the levelized cost of energy is reduced by 44.76% and 75.16% in solar‑hydrogen hybrid and pure solar energy mode. There is an optimal compressor pressure ratio to make the combined system have better thermodynamic and economic performance. Parameter optimization results show that for pure solar mode, the levelized cost of energy of the combined system is 75.4% and 56.3% lower than that of pure hydrogen mode, solar‑hydrogen hybrid mode respectively in the levelized cost of energy optimal design. The derived significant contributions of this work highlight strong potentials for combined system based on solar energy‑hydrogen complementary utilization. [Display omitted] • Development of a novel system for production power, hydrogen and energy storage. • Complementary power generation technology of solar energy and hydrogen is proposed. • Three operating modes have been proposed to reduce the impact of solar fluctuation. • Compared with pure hydrogen mode, the LCOE is reduced by 75.16% in pure solar mode. [ABSTRACT FROM AUTHOR]

This study first constructs an evaluation index system based on the pressure state response model, and assigns weights through entropy method and coefficient of variation method, providing theoretical and methodological support for comprehensive measurement and evaluation. Second, the least squares decision model is introduced and the PVAR model is used to analyze the development level of China's marine economy, ecology, and technological and financial innovation. The results indicated that from 2012 to 2022, the marine economic development level, marine ecological development level, and marine technology and financial innovation development level of 9 coastal provinces in China all showed a certain growth trend. However, in terms of the level of marine ecological development, various provinces had shown a downward trend, with Hebei performing the best, with an average of 0.230. Although various regions have achieved significant development in marine economy, ecology, and technological and financial innovation, the level of development varies among regions, and some regions have relatively low levels of technological innovation. The pressure and challenges between the marine economy and ecological environment protection caused by these real environments remain significant. • Integrating safety state response models into marine economic and ecological development assessments. • Analyzing the impact of technological and financial innovation on marine economy and ecological development. • Emphasizing the synergy between promoting marine economic growth and ecological environment protection. [ABSTRACT FROM AUTHOR]

Nowadays, the development of Artificial Intelligence of Things (AIoT) is advancing rapidly, and intelligent devices are increasingly exposed to more security risks on the network. Deep learning‐based intrusion detection is an effective security defence approach. Federated learning (FL) is capable of enabling deep learning models to be trained on local clients without uploading their data to a central server. This paper proposes a novel federated learning aggregation algorithm called fed‐dynamic gravitational search algorithm (Fed‐DGSA), which incorporates the GSA algorithm to optimize the weight updating process of FL local models. During the updating process, the decay rate of the gravity coefficient is optimized and random perturbations and dynamic weights are introduced to ensure a more stable and efficient FL aggregation process. The experimental results show that the detection accuracy of Fed‐DGSA has reached about 97.8%, and it is demonstrated that the model trained using Fed‐DGSA achieves higher accuracy compared to Fed‐Avg. [ABSTRACT FROM AUTHOR]

PETase exhibits a high degradation activity for polyethylene terephthalate (PET) plastic under moderate temperatures. However, the effect of non-active site residues in the second shell of PETase on the catalytic performance remains unclear. Herein, we proposed a crystal structure- and sequence-based strategy to identify the key non-active site residue. D186 in the second shell of PETase was found to be capable of modulating the enzyme activity and stability. The most active PETaseD186N improved both the activity and thermostability with an increase in Tm by 8.89 °C. The PET degradation product concentrations were 1.86 and 3.69 times higher than those obtained with PETaseWT at 30 and 40 °C, respectively. The most stable PETaseD186V showed an increase in Tm of 12.91 °C over PETaseWT. Molecular dynamics (MD) simulations revealed that the D186 mutations could elevate the substrate binding free energy and change substrate binding mode, and/or rigidify the flexible Loop 10, and lock Loop 10 and Helix 6 by hydrogen bonding, leading to the enhanced activity and/or thermostability of PETase variants. This work unraveled the contribution of the key second-shell residue in PETase in influencing the enzyme activity and stability, which would benefit in the rational design of efficient and thermostable PETase. [ABSTRACT FROM AUTHOR]

MiR399 plays an important role in plant growth and development. The objective of the present study was to elucidate the evolutionary characteristics of the MIR399 gene family in grapevine and investigate its role in stress response. To comprehensively investigate the functions of miR399 in grapevine, nine members of the Vvi-MIR399 family were identified based on the genome, using a miRBase database search, located on four chromosomes (Chr 2, Chr 10, Chr 15, and Chr 16). The lengths of the Vvi-miR399 precursor sequences ranged from 82 to 122 nt and they formed stable stem–loop structures, indicating that they could produce microRNAs (miRNAs). Furthermore, our results suggested that the 2 to 20 nt region of miR399 mature sequences were relatively conserved among family members. Phylogenetic analysis revealed that the Vvi-MIR399 members of dicots (Arabidopsis, tomato, and sweet orange) and monocots (rice and grapevine) could be divided into three clades, and most of the Vvi-MIR399s were closely related to sweet orange in dicots. Promoter analysis of Vvi-MIR399s showed that the majority of the predicted cis-elements were related to stress response. A total of 66.7% (6/9) of the Vvi-MIR399 promoters harbored drought, GA, and SA response elements, and 44.4% (4/9) of the Vvi-MIRR399 promoters also presented elements involved in ABA and MeJA response. The expression trend of Vvi-MIR399s was consistent in different tissues, with the lowest expression level in mature and young fruits and the highest expression level in stems and young leaves. However, nine Vvi-MIR399s and four target genes showed different expression patterns when exposed to low light, high light, heat, cold, drought, and salt stress. Interestingly, a putative target of Vvi-MIR399 targeted multiple genes; for example, seven Vvi-MIR399s simultaneously targeted VIT_213s0067g03280.1. Furthermore, overexpression of Vvi_MIR399e and Vvi_MIR399f in Arabidopsis enhanced tolerance to drought compared with wild-type (WT). In contrast, the survival rate of Vvi_MIR399d-overexpressed plants were zero after drought stress. In conclusion, Vvi-MIR399e and Vvi-MIR399f, which are related to drought tolerance in grapevine, provide candidate genes for future drought resistance breeding. [ABSTRACT FROM AUTHOR]

Background: Breast Cancer (BC) is a highly heterogeneous and complex disease. Personalized treatment options require the integration of multi-omic data and consideration of phenotypic variability. Radiogenomics aims to merge medical images with genomic measurements but encounter challenges due to unpaired data consisting of imaging, genomic, or clinical outcome data. In this study, we propose the utilization of a well-trained conditional generative adversarial network (cGAN) to address the unpaired data issue in radiogenomic analysis of BC. The generated images will then be used to predict the mutations status of key driver genes and BC subtypes. Methods: We integrated the paired MRI and multi-omic (mRNA gene expression, DNA methylation, and copy number variation) profiles of 61 BC patients from The Cancer Imaging Archive (TCIA) and The Cancer Genome Atlas (TCGA). To facilitate this integration, we employed a Bayesian Tensor Factorization approach to factorize the multi-omic data into 17 latent features. Subsequently, a cGAN model was trained based on the matched side-view patient MRIs and their corresponding latent features to predict MRIs for BC patients who lack MRIs. Model performance was evaluated by calculating the distance between real and generated images using the Fréchet Inception Distance (FID) metric. BC subtype and mutation status of driver genes were obtained from the cBioPortal platform, where 3 genes were selected based on the number of mutated patients. A convolutional neural network (CNN) was constructed and trained using the generated MRIs for mutation status prediction. Receiver operating characteristic area under curve (ROC-AUC) and precision-recall area under curve (PR-AUC) were used to evaluate the performance of the CNN models for mutation status prediction. Precision, recall and F1 score were used to evaluate the performance of the CNN model in subtype classification. Results: The FID of the images from the well-trained cGAN model based on the test set is 1.31. The CNN for TP53, PIK3CA, and CDH1 mutation prediction yielded ROC-AUC values 0.9508, 0.7515, and 0.8136 and PR-AUC are 0.9009, 0.7184, and 0.5007, respectively for the three genes. Multi-class subtype prediction achieved precision, recall and F1 scores of 0.8444, 0.8435 and 0.8336 respectively. The source code and related data implemented the algorithms can be found in the project GitHub at https://github.com/mattthuang/BC%5fRadiogenomicGAN. Conclusion: Our study establishes cGAN as a viable tool for generating synthetic BC MRIs for mutation status prediction and subtype classification to better characterize the heterogeneity of BC in patients. The synthetic images also have the potential to significantly augment existing MRI data and circumvent issues surrounding data sharing and patient privacy for future BC machine learning studies. [ABSTRACT FROM AUTHOR]

The myometrium, composed of the inner circular muscle (CM) and outer longitudinal muscle (LM), is crucial in establishing and maintaining early pregnancy. However, the molecular mechanisms involved are not well understood. In this study, we identified the transcriptomic features of the CM and LM collected from the mesometrial (M) and anti-mesometrial (AM) sides of the pig uterus on day 18 of pregnancy during the placentation initiation phase. Some genes in the cellular zinc ion level regulatory pathways (MT-1A , MT-1D , MT-2B , SLC30A2 , and SLC39A2) were spatially and highly enriched in uterine CM at the mesometrial side. In addition, the histone modification profiles of H3K27ac and H3K4me3 in uterine CM and LM collected from the mesometrial side were characterized. Genomic regions associated with the expression of genes regulating the cellular zinc ion level were detected. Moreover, six highly linked variants in the H3K27ac-enriched region of the pig SLC30A2 gene were identified and found to be significantly associated with the total number born at the second parity (P < 0.05). In conclusion, the genes in the pathways of cellular zinc homeostasis and their regulatory elements identified have implications for pig reproduction trait improvement and warrant further investigations. • The myometrium includes the circular muscle (CM) and longitudinal muscle (LM) layers. • Genes in the cellular zinc homeostasis pathway were highly enriched in pig uterine CM. • Genomic regions related to gene expression that regulate zinc ion levels were detected. • Six variants in the H3K27ac-enriched region upstream of the SLC30A2 gene were associated with litter size in pigs. [ABSTRACT FROM AUTHOR]

The major histocompatibility complexes of vertebrates play a key role in the immune response. Antigen-presenting cells are loaded on MHC I molecules, which mainly present endogenous antigens; when MHC I presents exogenous antigens, this is called cross-presentation. The discovery of cross-presentation provides an important theoretical basis for the study of exogenous antigens. Cross-presentation is a complex process in which MHC I molecules present antigens to the cell surface to activate CD8+ T lymphocytes. The process of cross-representation includes many components, and this article briefly outlines the origins and development of MHC molecules, gene structures, functions, and their classical presentation pathways. The cross-presentation pathways of MHC I molecules, the cell lines that support cross-presentation, and the mechanisms of MHC I molecular transporting are all reviewed. After more than 40 years of research, the specific mechanism of cross-presentation is still unclear. In this paper, we summarize cross-presentation and anticipate the research and development prospects for cross-presentation. [ABSTRACT FROM AUTHOR]

Regulating nuclear export precisely is essential for maintaining mRNA homeostasis and impacts tumor progression. However, the mechanisms governing nuclear mRNA export remain poorly elucidated. Herein, it is revealed that the enhanced hypoxic long no‐ncoding RNA (lncRNA prostate cancer associated transcript 6 (PCAT6) in breast cancer (BC) promotes the nuclear export of m6A‐modified mRNAs, bolstering breast cancer stem cells (BCSCs) stemness and doxorubicin resistance. Clinically, hypoxic PCAT6 correlates with malignant BC features and poor prognosis. Mechanically, PCAT6 functions as a scaffold between interferon‐stimulated gene 15 (ISG15) and heterogeneous nuclear ribonucleoprotein A2/B1 (hnRNPA2B1), leading to ISGylation of hnRNPA2B1, thus protecting hnRNPA2B1 from ubiquitination‐mediated proteasomal degradation. Interestingly, as an m6A reader, hnRNPA2B1 selectively mediates m6A‐tagged mRNAs nuclear export via the Aly/REF export factor (ALYREF)/ nuclear RNA export factor 1 (NXF1) complex, which promotes stemness‐related genes expression. HnRNPA2B1 knockdown or mRNA export inhibition can result in the retention of nuclear m6A‐tagged mRNA associated with stemness maintenance, which suppresses BCSCs self‐renewal and effectively improves the efficacy of doxorubicin therapy. These findings demonstrate the pivotal role of m6A‐modified mRNA nuclear export in BC progression, highlighting that the inhibition of m6A‐tagged mRNA and its nuclear export is a potential therapeutic strategy for the amelioration of cancer chemotherapy. [ABSTRACT FROM AUTHOR]

The regulation of PD‐L1 is the key question, which largely determines the outcome of the immune checkpoint inhibitors (ICIs) based therapy. However, besides the transcription level, the protein stability of PD‐L1 is closely correlated with its function and has drawn increasing attention. In this study, EZH2 inhibition enhances PD‐L1 expression and protein stability, and the deubiquitinase ubiquitin‐specific peptidase 22 (USP22) is identified as a key mediator in this process. EZH2 inhibition transcriptionally upregulates USP22 expression, and upregulated USP22 further stabilizes PD‐L1. Importantly, a combination of EZH2 inhibitors with anti‐PD‐1 immune checkpoint blockade therapy improves the tumor microenvironment, enhances sensitivity to immunotherapy, and exerts synergistic anticancer effects. In addition, knocking down USP22 can potentially enhance the therapeutic efficacy of EZH2 inhibitors on colon cancer. These findings unveil the novel role of EZH2 inhibitors in tumor immune evasion by upregulating PD‐L1, and this drawback can be compensated by combining ICI immunotherapy. Therefore, these findings provide valuable insights into the EZH2‐USP22‐PD‐L1 regulatory axis, shedding light on the optimization of combining both immune checkpoint blockade and EZH2 inhibitor‐based epigenetic therapies to achieve more efficacies and accuracy in cancer treatment. [ABSTRACT FROM AUTHOR]

DDB1‐Cullin‐4‐associated factor‐2 (DCAF2, also known as DTL or CDT2), a conserved substrate recognition protein of Cullin‐RING E3 ligase 4 (CRL4), recognizes and degrades several substrate proteins during the S phase to maintain cell cycle progression and genome stability. Dcaf2 mainly expressed in germ cells of human and mouse. Our study found that Dcaf2 was expressed in mouse spermatogonia and spermatocyte. The depletion of Dcaf2 in germ cells by crossing Dcaf2fl/fl mice with stimulated by retinoic acid gene 8(Stra8)‐Cre mice caused a reduction in progenitor spermatogonia and differentiating spermatogonia, eventually leading to the failure of meiosis initiation and male infertility. Further studies showed that depletion of Dcaf2 in germ cells caused abnormal accumulation of the substrate proteins, cyclin‐dependent kinase inhibitor 1A (p21) and thymine DNA glycosylase (TDG), decreasing of cell proliferation, increasing of DNA damage and apoptosis. Overexpression of p21 or TDG attenuates proliferation and increases DNA damage and apoptosis in GC‐1 cells, which is exacerbated by co‐overexpression of p21 and TDG. The findings indicate that DCAF2 maintains the proliferation and differentiation of progenitor spermatogonia by targeting the substrate proteins p21 and TDG during the S phase. [ABSTRACT FROM AUTHOR]

Objective: To further comprehend the phenotype of multiple mitochondrial dysfunction syndrome type 3 (MMDS3:OMIM#615330) caused by IBA57 mutation. We present a case involving a patient who experienced acute neurological regression, and the literature was reviewed. Methods: Clinical data and laboratory test results were collected; early language and development progress were tested; and genetic testing was performed. Bioinformatics analysis was performed using Mutation Taster and PolyPhen‐2, and the literature in databases such as PubMed and CNKI was searched using MMDS3 and IBA57 as keywords. Results: The child, aged 1 year and 2 months, had motor decline, unable to sit alone, limited right arm movement, hypotonia, hyperreflexia of both knees, and Babinski sign positivity on the right side, accompanied by nystagmus. Blood lactate levels were elevated at 2.50 mmol/L. Brain MR indicated slight swelling in the bilateral frontoparietal and occipital white matter areas and the corpus callosum, with extensive abnormal signals on T1 and T2 images, along with the semioval center and occipital lobes bilaterally. The multiple abnormal signals in the brain suggested metabolic leukoencephalopathy. Whole‐exome sequencing analysis revealed that the child had two heterozygous mutations in the IBA57 gene, c.286T>C (p.Y96H) (likely pathogenic, LP) and c.992T>A (p.L331Q) (variant of uncertain significance, VUS). As of March 2023, a literature search showed that 56 cases of MMDS3 caused by IBA57 mutation had been reported worldwide, with 35 cases reported in China. Among the 35 IBA57 mutations listed in the HGMD database, there were 28 missense or nonsense mutations, 2 splicing mutations, 2 small deletions, and 3 small insertions. Conclusion: MMDS3 predominantly manifests in infancy, with primary symptoms including feeding difficulties, neurological functional regression, muscle weakness, with severe cases potentially leading to mortality. Diagnosis is supported by elevated lactate levels, multisystem impairment (including auditory and visual systems), and distinctive MRI findings. Whole‐exome sequencing is crucial for diagnosis. Currently, cocktail therapy offers symptomatic relief. [ABSTRACT FROM AUTHOR]

Background: Fusarium zanthoxyli is a destructive pathogen causing stem canker in prickly ash, an ecologically and economically important forest tree. However, the genome lack of F. zanthoxyli has hindered research on its interaction with prickly ash and the development of precise control strategies for stem canker. Results: In this study, we sequenced and annotated a relatively high-quality genome of F. zanthoxyli with a size of 43.39 Mb, encoding 11,316 putative genes. Pathogenicity-related factors are predicted, comprising 495 CAZymes, 217 effectors, 156 CYP450s, and 202 enzymes associated with secondary metabolism. Besides, a comparative genomics analysis revealed Fusarium and Colletotrichum diverged from a shared ancestor approximately 141.1 ~ 88.4 million years ago (MYA). Additionally, a phylogenomic investigation of 12 different phytopathogens within Fusarium indicated that F. zanthoxyli originated approximately 34.6 ~ 26.9 MYA, and events of gene expansion and contraction within them were also unveiled. Finally, utilizing conserved domain prediction, the results revealed that among the 59 unique genes, the most enriched domains were PnbA and ULP1. Among the 783 expanded genes, the most enriched domains were PKc_like kinases and those belonging to the APH_ChoK_Like family. Conclusion: This study sheds light on the genetic basis of F. zanthoxyli's pathogenicity and evolution which provides valuable information for future research on its molecular interactions with prickly ash and the development of effective strategies to combat stem canker. [ABSTRACT FROM AUTHOR]

Background: Culex pipiens pallens is a well-known mosquito vector for several diseases. Deltamethrin, a commonly used pyrethroid insecticide, has been frequently applied to manage adult Cx. pipiens pallens. However, mosquitoes can develop resistance to these insecticides as a result of insecticide misuse and, therefore, it is crucial to identify novel methods to control insecticide resistance. The relationship between commensal bacteria and vector resistance has been recently recognized. Bacteriophages (= phages) are effective tools by which to control insect commensal bacteria, but there have as yet been no studies using phages on adult mosquitoes. In this study, we isolated an Aeromonas phage vB AhM-LH that specifically targets resistance-associated symbiotic bacteria in mosquitoes. We investigated the impact of Aeromonas phage vB AhM-LH in an abundance of Aeromonas hydrophila in the gut of Cx. pipiens pallens and its effect on the status of deltamethrin resistance. Methods: Phages were isolated on double-layer agar plates and their biological properties analyzed. Phage morphology was observed by transmission electron microscopy (TEM) after negative staining. The phage was then introduced into the mosquito intestines via oral feeding. The inhibitory effect of Aeromonas phage vB AhM-LH on Aeromonas hydrophila in mosquito intestines was assessed through quantitative real-time PCR analysis. Deltamethrin resistance of mosquitoes was assessed using WHO bottle bioassays. Results: An Aeromonas phage vB AhM-LH was isolated from sewage and identified as belonging to the Myoviridae family in the order Caudovirales using TEM. Based on biological characteristics analysis and in vitro antibacterial experiments, Aeromonas phage vB AhM-LH was observed to exhibit excellent stability and effective bactericidal activity. Sequencing revealed that the Aeromonas phage vB AhM-LH genome comprises 43,663 bp (51.6% CG content) with 81 predicted open reading frames. No integrase-related gene was detected in the vB AH-LH genome, which marked it as a potential biological antibacterial. Finally, we found that Aeromonas phage vB AhM-LH could significantly reduce deltamethrin resistance in Cx. pipiens pallens, in both the laboratory and field settings, by decreasing the abundance of Aeromonas hydrophila in their midgut. Conclusions: Our findings demonstrate that Aeromonas phage vB AhM-LH could effectively modulate commensal bacteria Aeromonas hydrophila in adult mosquitoes, thus representing a promising strategy to mitigate mosquito vector resistance. [ABSTRACT FROM AUTHOR]

In the realm of high-tech materials and energy applications, accurately measuring the transient heat flow at media boundaries and the internal thermal conductivity of materials in harsh heat exchange environments poses a significant challenge when using conventional direct measurement methods. Consequently, the study of photothermal parameter reconstruction in translucent media, which relies on indirect measurement techniques, has crucial practical value. Current research on reconstructing photothermal properties within participating media typically focuses on single-objective or time-invariant properties. There is a pressing need to develop effective methods for the simultaneous reconstruction of time-varying thermal flow fields and internal thermal conductivity at the boundaries of participating media. This paper introduces a computational model based on the numerical simulation theory of internal heat transfer systems in participating media, stochastic particle swarm optimization algorithms, and Kalman filter technology. The model aims to enable the simultaneous reconstruction of various thermal parameters within the target medium. Our results demonstrate that under varying levels of measurement noise, the inversion results for different target parameters exhibit slight oscillations around the true values, leading to a reduction in reconstruction accuracy. However, overall, the model demonstrates robustness and accuracy in ideal conditions, validating its effectiveness. [ABSTRACT FROM AUTHOR]

Hydroponic experiments were conducted to investigate the effects of varying particle sizes (5 μm, 0.1 μm, and 0.08 μm) and concentrations (0, 50, 100, 200, 500, 1000, and 2000 mg/L) of polystyrene plastic microspheres (PS-MPs) on the germination and growth of P. sativum seeds in order to investigate the effects of the microplastic environment on crop seed germination and seedling growth. The findings demonstrated that PS-MPs significantly harmed P. sativum seed germination. Specifically, low concentrations or high particle sizes weakened or promoted P. sativum seed germination, indicating varying susceptibilities to PS-MP treatment at different particle sizes. The strongest inhibitory effect on growth was observed under small particle size (0.08 μm) and high concentration (2000 mg/L). Stress had less of an impact on P. sativum in environments with low concentrations of PS-MPs, but in environments with medium and high concentrations, physiological and biochemical indicators like germination rate, stem length, and root length were significantly impacted. Furthermore, the particle size and concentration of PS-MPs had an impact on the growth effect of P. sativum seedlings. The indices of P. sativum seed germination were significantly impacted by the particle size of PS-MPs, despite the fact that PS-MP concentration was low. When the concentration of PS-MPs is low, the effects of varying PS-MP particle sizes on seed germination and root length are as follows: 0.1 μm > 5 μm > 0.08 μm. The concentration of PS-MPs had a significant impact on how it affected the buildup of dry matter and photosynthetic pigment. [ABSTRACT FROM AUTHOR]

Garnet solid-state electrolytes have become one of the most promising electrolyte materials due to their high ionic conductivity, wide electrochemical window, and excellent electrochemical stability. However, the trial-and-error method used to screen high-performance garnet solid-state electrolytes has the disadvantages of a long development cycle and high cost. Machine learning methods based on big data can be independent of the physical mechanism of the material, and improved the efficiency of material development. In this work, the effect of structural factor (t), first ionization energy, and other feature descriptors on ionic conductivity were studied by using the Gradient boosting regression (GBR), Random Forest (RF), eXtreme Gradient Boosting (XGB), and other models. Machine learning models can improve the accuracy of predicting the ionic conductivity of garnet solid-state electrolytes, and have guided the preparation of five garnet-type solid electrolyte materials, the ionic conductivity of Li 6 · 2 La 3 Zr 2 Fe 0 · 25 O 12 is 1.08 × 10−4 S cm−1, while the predicted value is 1.37 × 10−4 S cm−1, the descriptors in the model will provide a reference for other researchers. [Display omitted] • High accuracy of prediction of LLZO ionic conductivity. • The optimized GBR model predicts the LLZO ionic conductivity. • The feature parameters related to ionic conductivity are given. • A database of ionic conductivity for garnet-type SSEs was established. [ABSTRACT FROM AUTHOR]