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Abstract Introduction Pyroptosis, inflammatory necrosis of cells, is a programmed cell death involved in the pathological process of diseases. Endoplasmic reticulum stress (ERS), as a protective stress response of cell, decreases the unfold protein concentration to inhibit the unfold protein agglutination. Whereas the relationship between endoplasmic reticulum stress and pyroptosis in pulmonary hypertension (PH) remain unknown. Previous evident indicated that circular RNA (circRNA) can participate in several biological process, including cell pyroptosis. However, the mechanism of circRNA regulate pyroptosis of pulmonary artery smooth muscle cells through endoplasmic reticulum stress still unclear. Here, we proved that circSSR1 was down-regulate expression during hypoxia in pulmonary artery smooth muscle cells, and over-expression of circSSR1 inhibit pyroptosis both in vitro and in vivo under hypoxic. Our experiments have indicated that circSSR1 could promote host gene SSR1 translation via m6A to activate ERS leading to pulmonary artery smooth muscle cell pyroptosis. In addition, our results showed that G3BP1 as upstream regulator mediate the expression of circSSR1 under hypoxia. These results highlight a new regulatory mechanism for pyroptosis and provide a potential therapy target for pulmonary hypertension. Methods RNA-FISH and qRT-PCR were showed the location of circSSR1 and expression change. RNA pull-down and RIP verify the circSSR1 combine with YTHDF1. Western blotting, PI staining and LDH release were used to explore the role of circSSR1 in PASMCs pyroptosis. Results CircSSR1 was markedly downregulated in hypoxic PASMCs. Knockdown CircSSR1 inhibited hypoxia induced PASMCs pyroptosis in vivo and in vitro. Mechanistically, circSSR1 combine with YTHDF1 to promote SSR1 protein translation rely on m6A, activating pyroptosis via endoplasmic reticulum stress. Furthermore, G3BP1 induce circSSR1 degradation under hypoxic. Conclusion Our findings clarify the role of circSSR1 up-regulated parental protein SSR1 expression mediate endoplasmic reticulum stress leading to pyroptosis in PASMCs, ultimately promoting the development of pulmonary hypertension.

Objective This study investigated the effects of Apidaecin Api-PR19 as feed additive on growth performance, intestinal health, and small intestinal microbiota of broilers. Methods A total of 360 1-d-old Arbor Acres broilers were randomly assigned to 3 groups with 6 replicates including control group with basal diet (CON), antibiotic growth promotor group with basal plus 10 mg/kg colistin sulfate and 50 mg/kg roxarsone (AGP), and antibacterial peptide group with basal diet plus 330 mg/kg Apidaecin Api-PR19 (ABP). The trial lasted 35 d. Results Results showed that dietary Api-PR19 addition increased (p

Lipopolysaccharide (LPS) plays an important role in Raw264.7 macrophage ferroptosis and inflammation. Purine-rich element-binding protein B (Purb) influences cellular processes by regulating gene expression as a transcription factor. However, the effect and molecular mechanism of Purb in regulating Raw264.7 macrophage ferroptosis is still unknown. In this study, we used malondialdehyde, glutathione (GSH) assays, Fe2+ fluorescence, reactive oxygen species staining, and western blotting to determine the effect of Purb on LPS-induced Raw264.7 macrophage ferroptosis. Pharmacological inhibitor of ferroptosis was utilized to explore its potential effects for inflammation by reverse transcription-quantitative polymerase chain reaction analysis. Meanwhile, chromatin immunoprecipitation was performed to verify the binding of Purb and the GSH-dependent peroxidase 4 (Gpx4). The results showed that LPS-induced inflammation in Raw264.7 macrophages was inhibited by ferroptosis inhibitor Fer-1 treatment. LPS inhibited the expression of Purb in Raw264.7 macrophages. In addition, Purb overexpression relieved the ferroptosis, and inflammatory response of Raw264.7 macrophages induced by LPS. Mechanistically, the binding of Purb to the Gpx4 promoter was decreased after LPS stimulation. Therefore, we concluded for the first time that Purb played a critical role in LPS-induced ferroptosis and inflammatory response by regulating the transcription of Gpx4. These results provide a theoretical basis for further research on the macrophage ferroptosis and inflammation.

Abstract Genome-scale metabolic models (GEMs) can facilitate metabolism-focused multi-omics integrative analysis. Since Yeast8, the yeast-GEM of Saccharomyces cerevisiae, published in 2019, has been continuously updated by the community. This has increased the quality and scope of the model, culminating now in Yeast9. To evaluate its predictive performance, we generated 163 condition-specific GEMs constrained by single-cell transcriptomics from osmotic pressure or reference conditions. Comparative flux analysis showed that yeast adapting to high osmotic pressure benefits from upregulating fluxes through central carbon metabolism. Furthermore, combining Yeast9 with proteomics revealed metabolic rewiring underlying its preference for nitrogen sources. Lastly, we created strain-specific GEMs (ssGEMs) constrained by transcriptomics for 1229 mutant strains. Well able to predict the strains’ growth rates, fluxomics from those large-scale ssGEMs outperformed transcriptomics in predicting functional categories for all studied genes in machine learning models. Based on those findings we anticipate that Yeast9 will continue to empower systems biology studies of yeast metabolism.

Abstract Background Wild food plants (WFPs) play an important role in the traditional dietary habits of various indigenous communities worldwide, particularly in mountainous regions. To understand the dynamics of food preferences, cross-cultural studies on food plants should be conducted across diverse ethnic groups in a given area. In this context, the current study investigated the use of WFPs by seven different cultural groups in the Kashmir Himalayan Region. In this area, people gather wild plants and their parts for direct consumption, traditional foods, or sale in local markets. Despite this reliance, documentation of the food system, especially concerning WFPs, is notably lacking. Hence, our research aimed to document WFPs, along with associated traditional ecological knowledge, and identify major threats to their long-term sustainability in Division Muzaffarabad. Methods Through a comprehensive approach involving questionnaires, interviews, focus groups, and market surveys, we gathered data from 321 respondents. PCA was performed to analyze threats and plant use using “factoextra” in R software. Origin Pro was used to create a chord diagram, while R software was used to generate a Polar heat map. Additionally, a Venn diagram was created using Bioinformatics software. Results The study included 321 informants, of whom 75.38% were men and 24.61% were women. In total, 113 plant taxa from 74 genera and 41 botanical families were reported. Polygonaceae and Rosaceae accounted for the majority (17 species each), followed by Lamiaceae (7 species). Leaves were the most used part as food sources (41.04%), followed by fruits (33.33%). Most of the species are consumed as cooked (46.46%) and as raw snacks (37.80%). A total of 47 plant species were collected and cooked as wild vegetables, followed by 40 species used as fruits. This study is the first to describe the market potential and ecological distribution of WFPs in the study area. Cross-comparison showed that utilization of WFPs varies significantly across the region and communities, including their edible parts and mode of consumption. Jaccard index (JI) value ranged from 5.81 to 25. Furthermore, the current study describes 29 WFPs and 10 traditional food dishes that have rarely been documented in Pakistan's ethnobotanical literature. Climate change, invasive species, expansion of agriculture, and plant diseases are some of the most significant threats to WFPs in the study area. Conclusions The older age group has more knowledge about WFPs compared to the younger generation, who are not interested in learning about the utilization of WFPs. This lack of interest in information about WFPs among the younger generation can be attributed to their limited access to markets and availability of food plants in the study area. Traditional gathering of food plants has been reduced in younger generations during recent years; therefore, it is crucial to develop effective conservation strategies. These efforts not only safeguard indigenous flora, food knowledge, and cultural heritage, but they also contribute to food security and public health by utilizing local wild foods in the examined area.

Four new N-acylated aminoalkanoic acids, namely clonoroseins E−H (1−4), together with three previously identified analogs, clonoroseins A, B, and D (5−7), were identified from the endophytic fungus Clonostachys rosea strain 15020 (CR15020), using Feature-based Molecular Networking (FBMN). The elucidation of their chemical structures, including their absolute configurations, was achieved through spectroscopic analysis combined with quantum chemical calculations. Bioinformatics analyses suggested that an iterative type I HR-PKS (CrsE) generates the polyketide side chain of these clonoroseins. Furthermore, a downstream adenylate-forming enzyme of the PKS (CrsD) was suspected to function as an amide synthetase. CrsD potentially facilitates the transformation of the polyketide moiety into an acyl-AMP intermediate, followed by nucleophilic substitution with either β-alanine or γ-aminobutyric acid to produce amide derivatives. These findings significantly expand our understanding of PKS-related products originating from C. rosea and also underscore the powerful application of FBMN analytical methods in characterization of new compounds.

Parageobacillus thermoglucosidasius is emerging as a highly promising thermophilic organism for metabolic engineering. The utilization of CRISPR-Cas technologies has facilitated programmable genetic manipulation in P. thermoglucosidasius. However, the absence of thermostable NHEJ enzymes limited the capability of the endogenous type I CRISPR-Cas system to generate a variety of extensive genomic deletions. Here, two thermophilic NHEJ enzymes were identified and combined with the endogenous type I CRISPR-Cas system to develop a genetic manipulation tool that can achieve long-range genomic deletion across various lengths. By optimizing this tool—through adjusting the expression level of NHEJ enzymes and leveraging our discovery of a negative correlation between GC content of the guide RNA (gRNA) and deletion efficacy—we streamlined a comprehensive gRNA selection manual for whole-genome editing, achieving a 100 % success rate in randomly selecting gRNAs. Notably, using just one gRNA, we achieved genomic deletions spanning diverse length, exceeding 200 kilobases. This tool will facilitate the genomic manipulation of P. thermoglucosidasius for both fundamental research and applied engineering studies, further unlocking its potential as a thermophilic cell factory.

Abstract Predicting and optimizing the mechanical performance of the helically wound nylon-reinforced rubber fertilizer hose (HWNR hose) is crucial for enhancing the performance of hose pumps. This study aims to enhance the service life of HWNR hoses and the efficiency of liquid fertilizer transport. First, a finite element simulation model and a mathematical model were established to analyze the influence of fiber layer arrangement on the maximum shear strain on the coaxial surface (MSS) and the reaction force on the extrusion roller (RF). For the first time, the Crested Porcupine Optimizer algorithm was used to improve the Generalized Regression Neural Network (CPO-GRNN) method to establish a surrogate model for predicting the mechanical properties of HWNR hoses, and it was compared with Response Surface Methodology (RSM). Results showed CPO-GRNN's superiority in handling complex nonlinear problems. Finally, the Non-dominated Sorting Genetic Algorithm II (NSGA-II) was employed for optimization design. Compared to the original HWNR hose with an MSS of 0.906 and an RF of 30,376N, the optimized design reduced the MSS by 7.99% and increased the RF by 2.46%, significantly enhancing their service life and liquid fertilizer transport capacity. However, further research on fatigue damage is needed.

Fungal bifunctional terpene synthases (BFTSs) catalyze the formation of numerous di-/sester-/tri-terpenes skeletons. However, the mechanism in controlling the cyclization pattern of terpene scaffolds is rarely deciphered for further application of tuning the catalytic promiscuity of terpene synthases for expanding the chemical space. In this study, we expanded the catalytic promiscuity of Fusarium oxysporum fusoxypene synthase (FoFS) by a single mutation at L89, leading to the production of three new sesterterpenes. Further computational analysis revealed that the reconstitution of the hydrogen-bond (H-bond) network of second-shell residues around the active site of FoFS influences the orientation of the aromatic residue W69 within the first-shell catalytic pocket. Thus, the dynamic orientation of W69 alters the carbocation transport, leading to the production of diverse ring system skeletons. These findings enhance our knowledge on understanding the molecular mechanisms, which could be applied on protein engineering terpene synthases on regulating the terpene skeletons.

ABSTRACT: This study aimed to investigate the effects of phosphorylated-ovalbumin (P-OVA) at different concentrations (0.5% and 1.0%) on the gel properties of pork myofibrillar protein (MP). The results showed that the textural properties such as gel hardness, cohesiveness, springiness and chewiness were improved with P-OVA addition at 0.5%. The water holding capacity (up to 75.89%) and gel strength (up to 168.56 g·mm) of MP gel were markedly increased after P-OVA addition. The absolute value of zeta potential reached 13.85 mV and maximum hydrophobicity (15.2 μg) resulted from the addition of 0.5% P-OVA. The storage modulus (G’) and loss modulus (G’’) of MP gel were significantly increased from 50°C, and the G’ and G’’ significantly increased after 1.0% P-OVA addition, evidencing that the cross-linking effect of MP protein gel was enhanced. In addition, the P-OVA addition improved the structure of MP gel protein by reducing the α-helix, while increasing the β-sheet and the r-value (the ratio between two ultraviolet second-derivative peak-to-trough distances), which further promoted the uniform and compact gel network structure. This work demonstrated that P-OVA is a highly effective modifier that significantly improves the quality of MP gel. From a view of practice, 0.5% P-OVA is the optimal addition amount.

Abstract The extracytoplasmic function (ECF) sigma factor AlgU is involved in the regulation of various virulence-related pathways in Pseudomonas syringae, especially alginate biosynthesis and motility, and the role of AlgU differs among P. syringae pathovars. However, to date, the mechanism of its regulation in virulence of P. syringae pv. actinidiae (Psa) is still unclear. ECF sigma factors are a class of alternative sigma factors that typically function with anti-sigma factors as part of cell-surface signaling systems. Under non-inducing conditions, AlgU remains inhibited by anti-sigma factors such as MucA and MucB. To investigate the function of AlgU in Psa, mutant strains lacking algU or lacking algU with mucA and mucB genes, as well as complementary and overexpression strains of algU were generated, respectively. The results showed that AlgU was highly conserved among P. syringae pathovars and positively regulated growth rate, pathogenicity, and resistance to osmotic and oxidative stress of Psa QSY6. While AlgU did not affect the motility and exopolysaccharide production of Psa, its abundant expression enhanced the swimming ability of QSY6 and reduced its production of extracellular polysaccharides. Furthermore, AlgU regulates a number of virulence-related factors, including the Hrp system, the type VI secretion system, and flagellar synthesis. Specifically, AlgU induced the expression of hrpL and hrpRS in vivo, and repressed the transcription of hrpL and tssC in vitro, while promoting the expression of hrpS, fliC, and tssJ. This study contributes to a better understanding of the mechanisms of virulence regulation of AlgU in Psa.

Abstract Background Pseudomonas syringae pv. actinidiae (Psa) is an important bacterial plant pathogen that causes severe damage to the kiwifruit industry worldwide. Three Psa strains were recently obtained from different kiwifruit orchards in Anhui Province, China. The present study mainly focused on the variations in virulence and genome characteristics of these strains based on the pathogenicity assays and comparative genomic analyses. Results Three strains were identified as biovar 3 (Psa3), along with strain QSY6 showing higher virulence than JZY2 and YXH1 in pathogenicity assays. The whole genome assembly revealed that each of the three strains had a circular chromosome and a complete plasmid. The chromosome sizes ranged from 6.5 to 6.6 Mb with a GC content of approximately 58.39 to 58.46%, and a predicted number of protein-coding sequences ranging from 5,884 to 6,019. The three strains clustered tightly with 8 Psa3 reference strains in terms of average nucleotide identity (ANI), whole-genome-based phylogenetic analysis, and pangenome analysis, while they were evolutionarily distinct from other biovars (Psa1 and Psa5). Variations were observed in the repertoire of effectors of the type III secretion system among all 15 strains. Moreover, synteny analysis of the three sequenced strains revealed eight genomic regions containing 308 genes exclusively present in the highly virulent strain QSY6. Further investigation of these genes showed that 16 virulence-related genes highlight several key factors, such as effector delivery systems (type III secretion systems) and adherence (type IV pilus), which might be crucial for the virulence of QSY6. Conclusion Three Psa strains were identified and showed variant virulence in kiwifruit plant. Complete genome sequences and comparative genomic analyses further provided a theoretical basis for the potential pathogenic factors responsible for kiwifruit bacterial canker.

Summary: The abnormal expression of circular RNAs (circRNAs) is emerging as a critical cause in regulation of pathological changes of hypoxic pulmonary hypertension (PH), in which ferroptosis is a new pathological change reported recently. However, how circRNAs regulate ferroptosis remains unclear. Here, we proved a significant decrease in circMyst4 expression in hypoxia. In vitro assays revealed that circMyst4 alleviated hypoxic pulmonary artery smooth muscle cell (PASMC) ferroptosis through directly combing with DDX5 in the nucleus to promote GPX4 mRNA processing and inhibiting the formation of the Eef1a1/ACSL4 complex in the cytoplasm. Additionally, superenhancer (SE) was verified to drive the generation of circMyst4. In vivo assays revealed that circMyst4 inhibited the progression of hypoxic PH. Overall, SE-driven circMyst4 may be a new potential therapeutic target for mediating PASMC ferroptosis through promoting DDX5-regulated GPX4 mRNA processing and inhibiting the binding between Eef1a1 and ACSL4.

Background Pulmonary hypertension is a rare, progressive disorder that can lead to right ventricular hypertrophy, right heart failure, and even sudden death. N6‐methyladenosine modification and the main methyltransferase that mediates it, methyltransferase‐like (METTL) 3, exert important effects on many biological and pathophysiological processes. However, the role of METTL3 in pyroptosis remains unclear. Methods and Results Here, we characterized the role of METTL3 and the underlying cellular and molecular mechanisms of pyroptosis, which is involved in pulmonary hypertension. METTL3 was downregulated in a pulmonary hypertension mouse model and in hypoxia‐exposed pulmonary artery smooth muscle cell. The small interfering RNA–induced silencing of METTL3 decreased the m6A methylation levels and promoted pulmonary artery smooth muscle cell pyroptosis, mimicking the effects of hypoxia. In contrast, overexpression of METTL3 suppressed hypoxia‐induced pulmonary artery smooth muscle cell pyroptosis. Mechanistically, we identified the phosphate and tension homology deleted on chromosome 10 (PTEN) gene as a target of METTL3‐mediated m6A modification, and methylated phosphate and tension homology deleted on chromosome 10 mRNA was subsequently recognized by the m6A “reader” protein insulin‐like growth factor 2 mRNA‐binding protein 2, which directly bound to the m6A site on phosphate and tension homology deleted on chromosome 10 mRNA and enhanced its stability. Conclusions These results identify a new signaling pathway, the METTL3/phosphate and tension homology deleted on chromosome 10/insulin‐like growth factor 2 mRNA‐binding protein 2 axis, that participates in the regulation of hypoxia‐induced pyroptosis.

Accurate parameter identification of photovoltaic (PV) models is essential for the optimal operation and control of PV systems. However, PV cell modeling exhibits nonlinearity and involves numerous challenging-to-solve unknown parameters, thereby reducing the utilization efficiency of solar energy in PV systems. Therefore, this paper proposes an enhanced Snake algorithm (ISASO) that integrates Subtraction Average-Based Optimization (SABO) to address the shortcomings of traditional PV model parameter identification methods, such as low accuracy, slow convergence, and susceptibility to local optima. The SABO algorithm, which updates the positions of search agents using a consistent arithmetic mean position throughout the optimization process, demonstrates high convergence. By integrating SABO's global search strategy into the exploration phase of SO, the global search capability of SO is further enhanced, mitigating the risk of early local optima in the original SO. Additionally, the Tent chaotic map initialization method is incorporated into standard SO to improve the quality of the initial population and enhance population diversity. A dynamic learning factor and adaptive inertia weight strategy are also employed to accelerate the convergence speed of the SO algorithm, balancing its exploration and exploitation capabilities. To validate the performance of ISASO, it is applied to the CEC2005 benchmark functions and employed to identify the optimal parameters of various PV models. Statistical and analytical results reveal that ISASO markedly outperforms existing methods in parameter identification accuracy and reliability, achieving the lowest Root Mean Square Error (RMSE) values between standard and simulated data. Additionally, the superior performance of ISASO is further verified by comparative analysis with existing meta-heuristic algorithms and the Friedman mean ranking statistical method. Therefore, ISASO can be considered as a reliable and effective method to accurately estimate solar PV model parameters.

Abstract Background Effective stroke rehabilitation requires high-dose, repetitive-task training, especially during the early recovery phase. However, the usability of upper-limb rehabilitation technology in acute and subacute stroke survivors remains relatively unexplored. In this study, we introduce subacute stroke survivors to MyoGuide, a mobile training platform that employs surface electromyography (sEMG)-guided neurofeedback training that specifically targets wrist extension. Notably, the study emphasizes evaluating the platform’s usability within clinical contexts. Methods Seven subacute post-stroke patients (1 female, mean age 53.7 years, mean time post-stroke 58.9 days, mean duration per training session 48.9 min) and three therapists (one for eligibility screening, two for conducting training) participated in the study. Participants underwent ten days of supervised one-on-one wrist extension training with MyoGuide, which encompassed calibration, stability assessment, and dynamic tasks. All training records including the Level of Difficulty (LoD) and Stability Assessment Scores were recorded within the application. Usability was assessed through the System Usability Scale (SUS) and participants’ willingness to continue home-based training was gauged through a self-developed survey post-training. Therapists also documented the daily performance of participants and the extent of support required. Results The usability analysis yielded positive results, with a median SUS score of 82.5. Compared to the first session, participants significantly improved their performance at the final session as indicated by both the Stability Assessment Scores (p = 0.010, mean = 229.43, CI = [25.74–433.11]) and the LoD (p

Abstract Solar power is a renewable energy source, and its efficient development and utilization are important for achieving global carbon neutrality. However, partial shading conditions cause the output of PV systems to exhibit nonlinear and multipeak characteristics, resulting in a loss of output power. In this paper, we propose a novel Maximum Power Point Tracking (MPPT) technique for PV systems based on the Dung Beetle Optimization Algorithm (DBO) to maximize the output power of PV systems under various weather conditions. We performed a performance comparison analysis of the DBO technique with existing renowned MPPT techniques such as Squirrel Search Algorithm, Cuckoo search Optimization, Horse Herd Optimization Algorithm, Particle Swarm Optimization, Adaptive Factorized Particle Swarm Algorithm and Gray Wolf Optimization Hybrid Nelder-mead. The experimental validation is carried out on the HIL + RCP physical platform, which fully demonstrates the advantages of the DBO technique in terms of tracking speed and accuracy. The results show that the proposed DBO achieves 99.99% global maximum power point (GMPP) tracking efficiency, as well as a maximum improvement of 80% in convergence rate stabilization rate, and a maximum improvement of 8% in average power. A faster, more efficient and robust GMPP tracking performance is a significant contribution of the DBO controller.

IntroductionIntra-tumoral B cells mediate a plethora of immune effector mechanisms with key roles in anti-tumor immunity and serve as positive prognostic indicators in a variety of solid tumor types, including epithelial ovarian cancer (EOC). Several aspects of intra-tumoral B cells remain unclear, such as their state of activation, antigenic repertoires, and capacity to mature into plasma cells.MethodsB lymphocytes were isolated from primary EOC tissue and malignant ascites and were maintained in cell culture medium. The stably maintained cell lines were profiled with flow cytometry and B cell receptor sequencing. Secreted antibodies were tested with a human proteome array comprising more than 21,000 proteins, followed by ELISA for validation. Originating tumor samples were used for spatial profiling with chip cytometry.ResultsAntibody-secreting B lymphocytes were isolated from the ovarian tumor microenvironment (TME) of four different EOC patients. The highly clonal cell populations underwent spontaneous immortalization in vitro, were stably maintained in an antibody-secreting state, and showed presence of Epstein-Barr viral (EBV) proteins. All originating tumors had high frequency of tumor-infiltrating B cells, present as lymphoid aggregates, or tertiary lymphoid structures. The antigens recognized by three of the four cell lines are coil-coil domain containing protein 155 (CCDC155), growth factor receptor-bound protein 2 (GRB2), and pyruvate dehydrogenase phosphatase2 (PDP2), respectively. Anti-CCDC155 circulating IgG antibodies were detected in 9 of 20 (45%) of EOC patients’ sera. Tissue analyses with multiparameter chip cytometry shows that the antibodies secreted by these novel human B cell lines engage their cognate antigens on tumor cells.DiscussionThese studies demonstrate that within the tumor-infiltrating lymphocyte population in EOC resides a low frequency population of antibody-secreting B cells that have been naturally exposed to EBV. Once stably maintained, these novel cell lines offer unique opportunities for future studies on intratumor B cell biology and new target antigen recognition, and for studies on EBV latency and/or viral reactivation in the TME of non-EBV related solid tumors such as the EOC.

The gut microbiota in cattle is essential for protein, energy, and vitamin production and hence, microbiota perturbations can affect cattle performance. This study evaluated the effect of intramammary (IMM) ceftiofur treatment and lactation stage on the functional gut microbiome and metabolome. Forty dairy cows were enrolled at dry-off. Half received IMM ceftiofur and a non-antibiotic teat sealant containing bismuth subnitrate (cases), while the other half received the teat sealant (controls). Fecal samples were collected before treatment at dry off, during the dry period (weeks 1 and 5) and the first week after calving (week 9). Shotgun metagenomic sequencing was applied to predict microbial metabolic pathways whereas untargeted metabolomics was used identify polar and nonpolar metabolites. Compared to controls, long-term changes were observed in the cows given ceftiofur, including a lower abundance of microbial pathways linked to energy production, amino acid biosynthesis, and other vital molecules. The metabolome of treated cows had elevated levels of stachyose, phosphatidylethanolamine diacylglycerol (PE-DAG), and inosine a week after the IMM ceftiofur application, indicating alterations in microbial fermentation, lipid metabolism, energy, and cellular signaling. Differences were also observed by sampling, with cows in late lactation having more diverse metabolic pathways and a unique metabolome containing higher levels of histamine and histamine-producing bacteria. These data illustrate how IMM ceftiofur treatment can alter the functionality of the hindgut metabolome and microbiome. Understanding how antibiotics and lactation stages, which are each characterized by unique diets and physiology, impact the function of resident microbes is critical to define normal gut function in dairy cattle.

Abstract The prevalence of myopia (nearsightedness) is increasing to alarming levels, but its etiology remains poorly understood. Because both laboratory and clinical findings suggest an etiologic role for circadian rhythms in myopia development, we assayed gene expression by RNA-Seq in retina and choroid at the onset of unilateral experimental myopia in chick, isolating tissues every 4 h during a single 24-h period from myopic and contralateral control eyes. Occluded versus open eye gene expression differences varied considerably over the 24-h sampling period, with some occurring at multiple times of day but with others showing differences at only a single investigated timepoint. Some of the genes identified in retina or choroid of chick myopia were previously identified as candidate genes for common human myopia. Like differentially expressed genes, pathways identified by Gene Set Enrichment Analysis also varied dramatically by sampling time. Considered with other laboratory data, human genetic and epidemiology data, these findings further implicate circadian events in myopia pathogenesis. The present results emphasize a need to include time of day in mechanistic studies of myopia and to assess circadian biology directly in trying to understand better the origin of myopia and to develop more effective therapies.

In this study, the impacts of egg consumption on mice model of metabolic syndrome (MetS) were comparatively investigated. Mice were divided into five groups (n=8): normal diet group (ND), high-fat diet group (HFD), HFD with whole egg group (WE), HFD with free-yolk egg substitute group (YFES), and HFD with lovastatin group (Lov). Main biochemical indexes and a non-targeted lipidomic analysis were employed to insight the lipid profile changes in serum. It was revealed that WE could significantly improve serum biochemical indexes by reducing body weight, low-density lipoprotein cholesterol (LDL-C) and total cholesterol (TC), while increasing high-density lipoprotein cholesterol. YFES exhibited remarkably better performance in increasing phosphatidylglycerol and phosphatidic acids, while decreasing phosphatidylinositol than WE. A total of 50 differential lipids biomarkers tightly related to glycerophospholipids metabolism were screened out. Carnitine C18:2 and C12:1, SM (d18:0/12:0), and SM (d18:1/14:1) were significantly upregulated in YFES compared to WE. YFES reduced expression of SREBP-1c and Cpt1a, while did not affect the expression of PPAR-α. Sphingomyelin biomarkers were positively related to the TC (|r| > 0.6), while PPAR-α was negatively correlated with triglyceride and LDL-C levels. To sum up, YFES attenuated HFD-induced MetS by improving the serum phospholipids, which account for its modulation of glycerophospholipid metabolism.

Abstract Background Intramammary (IMM) ceftiofur treatment is commonly used in dairy farms to prevent mastitis, though its impact on the cattle gut microbiome and selection of antibiotic-resistant bacteria has not been elucidated. Herein, we enrolled 40 dairy (Holstein) cows at the end of the lactation phase for dry-cow therapy: 20 were treated with IMM ceftiofur (Spectramast®DC) and a non-antibiotic internal teat sealant (bismuth subnitrate) and 20 (controls) received only bismuth subnitrate. Fecal grab samples were collected before and after treatment (weeks 1, 2, 3, 5, 7, and 9) for bacterial quantification and metagenomic next-generation sequencing. Results Overall, 90% and 24% of the 278 samples had Gram-negative bacteria with resistance to ampicillin and ceftiofur, respectively. Most of the cows treated with ceftiofur did not have an increase in the number of resistant bacteria; however, a subset (25%) shed higher levels of ceftiofur-resistant bacteria for up to 2 weeks post-treatment. At week 5, the antibiotic-treated cows had lower microbiota abundance and richness, whereas a greater abundance of genes encoding extended-spectrum β-lactamases (ESBLs), CfxA, ACI-1, and CMY, was observed at weeks 1, 5 and 9. Moreover, the contig and network analyses detected associations between β-lactam resistance genes and phages, mobile genetic elements, and specific genera. Commensal bacterial populations belonging to Bacteroidetes most commonly possessed ESBL genes followed by members of Enterobacteriaceae. Conclusion This study highlights variable, persistent effects of IMM ceftiofur treatment on the gut microbiome and resistome in dairy cattle. Antibiotic-treated cattle had an increased abundance of specific taxa and genes encoding ESBL production that persisted for 9 weeks. Fecal shedding of ESBL-producing Enterobacteriaceae, which was classified as a serious public health threat, varied across animals. Together, these findings highlight the need for additional studies aimed at identifying factors associated with shedding levels and the dissemination and persistence of antibiotic resistance determinants on dairy farms across geographic locations.

To address the issue of spatial resolution limitations in traditional Brillouin optical time-domain analysis systems due to phonon lifetime constraints, we employed pre-pumped pulse technology. Additionally, to mitigate the double-peak phenomenon observed in pre-pumped Brillouin optical time-domain analysis systems, we implemented a two-sided band interference method to reduce the linewidth of the double-peak fitting. We conducted bending measurements on three eccentric cores and intermediate cores spaced 120° apart. Our results demonstrate that the system described in this paper can achieve a spatial resolution of 30 cm, with bimodal linewidths of 23.1 MHz and 16.0 MHz. Using the parallel transmission frame algorithm, we determined the curvature of a seven-core fiber with a curvature diameter of approximately 10 cm to be 20.67 m−1, with an error margin of 3.2%.

PurposeThe purpose of this study was to observe, using Footscan analysis, the effect of electromyographic feedback functional electrical stimulation (FES) on the changes in the plantar pressure of drop foot patients.MethodsThis case–control study enrolled 34 stroke patients with foot drop. There were 17 cases received FES for 20 min per day, 5 days per week for 4 weeks (the FES group) and the other 17 cases only received basic rehabilitations (the control group). Before and after 4 weeks, the walking speed, spatiotemporal parameters and plantar pressure were measured.ResultsAfter 4 weeks treatments, Both the FES and control groups had increased walking speed and single stance phase percentage, decreased step length symmetry index (SI), double stance phase percentage and start time of the heel after 4 weeks (p

Decrease in the cost of acquiring 3D point cloud data coupled with the rapid advancements in GPU computing power have resulted in an increased demand for 3D point cloud semantic segmentation in numerous 3D visual applications, including but not limited to autonomous driving, industrial control, and MR/XR, which further advances the development of deep learning methods in 3D point cloud semantic segmentation. Recently, many novel deep learning network architectures, such as RandLA-Net and Point Transformer, have been proposed and have achieved notable improvements in semantic segmentation accuracy while decreasing the computational load. However, previous research on 3D point cloud semantic segmentation methods has focused primarily on relatively early works, whose approaches have been gradually abandoned over the years and cannot accurately reflect the current research status. Moreover, the existing methods have been categorized based on their input data types, making it difficult to compare the segmentation performance of different techniques and not providing a comprehensive view of the relationship between methods using different network architectures. Therefore, this paper reviews the mainstream 3D semantic segmentation methods developed in the last three years using different deep learning network architectures and is organized into three levels. First, the two principal 3D point cloud data acquisition methods, including their customary datasets and metrics to evaluate model performance, are introduced. Second, a systematic review of 3D semantic segmentation methods based on different network architectures is organized, followed by a statistical analysis of the evaluation of performance between different models on two 3D segmentation datasets—S3DIS and ScanNet. The analysis of model performance on these two commonly used datasets includes model structure relevance, strengths, and limitations. Finally, an insightful discussion of the remaining methodological and application challenges and potential research directions is provided. This paper offers an extensive overview of the recent three-year research progress in 3D point cloud semantic segmentation and summarizes various network architecture pipelines, elucidates their fundamental operations, compares the model performance across multiple architectures, discusses their notable strengths and limitations, most importantly, concludes the current challenges and promising research directions for future investigations. Furthermore, this paper enables researchers to effortlessly identify the relevant research and research hotspots among different 3D point cloud semantic segmentation methods based on the analyses presented and aims to update the reviews on 3D point cloud semantic segmentation methods with a better viewpoint and highlight key properties and contributions of proposed methods, providing promising research directions for the main challenges.

Abstract Background Human umbilical cord mesenchymal stem cells (hUC-MSCs) are widely used in cell therapy due to their robust immunomodulatory and tissue regenerative capabilities. Currently, the predominant method for obtaining hUC-MSCs for clinical use is through planar culture expansion, which presents several limitations. Specifically, continuous cell passaging can lead to cellular aging, susceptibility to contamination, and an absence of process monitoring and control, among other limitations. To overcome these challenges, the technology of microcarrier–bioreactor culture was developed with the aim of ensuring the therapeutic efficacy of cells while enabling large-scale expansion to meet clinical requirements. However, there is still a knowledge gap regarding the comparison of biological differences in cells obtained through different culture methods. Methods We developed a culture process for hUC-MSCs using self-made microcarrier and stirred bioreactor. This study systematically compares the biological properties of hUC-MSCs amplified through planar culture and microcarrier–bioreactor systems. Additionally, RNA-seq was employed to compare the differences in gene expression profiles between the two cultures, facilitating the identification of pathways and genes associated with cell aging. Results The findings revealed that hUC-MSCs expanded on microcarriers exhibited a lower degree of cellular aging compared to those expanded through planar culture. Additionally, these microcarrier-expanded hUC-MSCs showed an enhanced proliferation capacity and a reduced number of cells in the cell cycle retardation period. Moreover, bioreactor-cultured cells differ significantly from planar cultures in the expression of genes associated with the cytoskeleton and extracellular matrix. Conclusions The results of this study demonstrate that our microcarrier–bioreactor culture method enhances the proliferation efficiency of hUC-MSCs. Moreover, this culture method exhibits the potential to delay the process of cell aging while preserving the essential stem cell properties of hUC-MSCs.

Abstract Thermophilic cell factories have remarkably broad potential for industrial applications, but are limited by a lack of genetic manipulation tools and recalcitrance to transformation. Here, we identify a thermophilic type I-B CRISPR-Cas system from Parageobacillus thermoglucosidasius and find it displays highly efficient transcriptional repression or DNA cleavage activity that can be switched by adjusting crRNA length to less than or greater than 26 bp, respectively, without ablating Cas3 nuclease. We then develop an orthogonal tool for genome editing and transcriptional repression using this type I-B system in both thermophile and mesophile hosts. Empowered by this tool, we design a strategy to screen the genome-scale targets involved in transformation efficiency and established dynamically controlled supercompetent P. thermoglucosidasius cells with high efficiency ( ~ 108 CFU/μg DNA) by temporal multiplexed repression. We also demonstrate the construction of thermophilic riboflavin cell factory with hitherto highest titers in high temperature fermentation by genome-scale identification and combinatorial manipulation of multiple targets. This work enables diverse high-efficiency genetic manipulation in P. thermoglucosidasius and facilitates the engineering of thermophilic cell factories.

Abstract Enteric pathogens cause widespread foodborne illness and are increasingly resistant to important antibiotics yet their ecological impact on the gut microbiome and resistome is not fully understood. Herein, shotgun metagenome sequencing was applied to stool DNA from 60 patients (cases) during an enteric bacterial infection and after recovery (follow-ups). Overall, the case samples harbored more antimicrobial resistance genes (ARGs) with greater resistome diversity than the follow-up samples (p

Abstract The filler is the core component of the cooling tower, filler performance refers to both its thermal and flow resistance characteristics, which use empirical formulas of tower characteristic N, volumetric mass transfer coefficient βxv, and pressure drop ΔP obtained through experimentation under specific conditions. However, the performance equations for identical countercurrent fillers can vary at different heights or seawater concentrations. Linear interpolation is the conventional method for obtaining the filler performance under different conditions, but its uncertainty limits the application. This paper explores the use of the radial basis function artificial neural network (RBF ANN) to analyze filler performance based on existing performance equations. The data set is generated by the filler performance equations. The results demonstrate that RBF ANN has a preferable prediction effect with high correlation (the determination coefficient R2 > 0.99) and prediction accuracy (the proportion of relative error within 10% N10 > 90%). Furthermore, the predicted results are consistent with the experimental results of the filler performance. Therefore, RBF ANN can accurately predict filler performance at varying heights and seawater concentrations, making it universal and providing a basis for cooling tower design.

The efficient operation of smart farms relies on the precise monitoring of farm environmental information, necessitating the deployment of a large number of wireless sensors. These sensors must be integrated with their specific locations within the fields to ensure data accuracy. Therefore, efficiently and rapidly determining the positions of sensor nodes presents a significant challenge. To address this issue, this paper proposes a hybrid optimization DV-Hop localization algorithm based on the chaotic crested porcupine optimizer. The algorithm leverages the received signal strength indicator, combined with node hierarchical values, to achieve graded processing of the minimum number of hops. Polynomial fitting methods are employed to reduce the estimation distance error from the beacon nodes to unknown nodes. Finally, the chaotic optimization crested porcupine optimizer is designed for intelligent optimization. Simulation experiments verify the proposed algorithm’s localization performance across different monitoring areas, varying beacon node ratios, and assorted communication radii. The simulation results demonstrate that the proposed algorithm effectively enhances node localization accuracy and significantly reduces localization errors compared to the results for other algorithms. In future work, we plan to consider the impact of algorithm complexity on the lifespan of wireless sensor networks and to further evaluate the algorithm in a pH monitoring system for farmland.

The mechanism of the electrochemical CO2 reduction reaction on a Cu(110) surface has yet to be fully revealed. In this work, based on first-principles calculations, we investigate the mechanisms of the CO2 reduction reaction to produce C1 (including one C atom) and C2 (including two C atoms) products on a Cu(110) surface. The results show that CH4 and C2H5OH are the main C1 and C2 products on the Cu(110) surface, respectively. CH4 is produced along the pathway CO2 → COOH* → CO* → CHO* → CH2O* → CH3O* → CH4. C2H5OH is produced via the C-C coupling pathway between CO* and CH2O* intermediates, which is the key reaction step. This is because CO* and CH2O* coupling to CO-CH2O* has the lowest barrier among the CHxO* (x = 0–2) coupling pathways. Therefore, it is the most likely C-C coupling pathway. Further, CO-CH2O* is gradually hydrogenated to C2H5OH along the following pathway: CO-CH2O* → CHO-CH2O* → CHOH-CH2* → CH2OH-CH2* → CH2OH-CH3* → C2H5OH.

Fragment-based drug discovery (FBDD) focuses on small compounds, known as fragments, typically with a molecular weight of less than 300 Da. This study highlights the benefits of employing a pure natural product library for FBDD, contrasting with the predominant use of synthetic libraries. Practical methods for rapidly constructing such libraries from crude extracts were demonstrated across various plant and microbial samples. Twenty-nine (29) natural product fragments, including a new compound (20), were identified. Antimicrobial activities were assessed for a subset of the isolated compounds, revealing potent fragments (MICs 4–8 μg/mL) against Mycobacterium bovis bacille Calmette-Guérin (BCG), Staphylococcus aureus (SA), and methicillin-resistant S. aureus (MRSA). Furthermore, a native mass spectrometry technique was introduced to rapidly identify non-competitive fragments against malarial proteins. As a result, two pairs of non-competitive fragments, lepiotin C (31) and 7-amino deacetoxy cephalosporanic acid (32) binding to dynein light chain 1, methyl gallate (33) and β-santanin (34) binding to dUTPase, were identified, serving as promising starting points for developing potent malarial protein inhibitors.

This paper proposes a conceptual design of an innovative deep-sea aquaculture platform that integrates a steel structural framework and high-density polyethylene (HDPE) floats. It aims to overcome the limitations of prevailing aquaculture equipment, including inadequate resistance to strong wind and waves, complex technologies, and prohibitively high costs. The design scheme and key parameters of the main platform, the netting system, and the mooring systems are presented. Based on the stochastic design wave method, the characteristic load response scenarios and design wave parameters are determined and analyzed. Strength analysis is conducted to assess the structural performance, vulnerabilities, and overall safety of the platform under various characteristic load conditions. The results indicate that the Von Mises stress levels across different sections of the platform conform to the allowable stress thresholds under various characteristic load conditions. However, the stress levels of the platform are notably higher when subjected to characteristic loads associated with vertical shear, vertical bending moments, and torsion about the horizontal axis, which requires further efforts in the design process to enhance the structural safety of the platform. The proposed design methodology and the presented research results can provide a wide range of references for the design and analysis of deep-sea fisheries aquaculture equipment.

As nearshore aquaculture spaces become saturated, the development of fisheries aquaculture for deep sea has become an inevitable trend. This paper proposes an innovative deep-sea aquaculture platform that incorporates a vessel-shaped main structure and a single-point mooring system. The potential flow theory and the Morison equation are utilized to calculate the hydrodynamic loads on the main structure and the netting and mooring systems, respectively. The deformation and force of the netting in current are simulated, and the accuracy of the analytical methods used is validated based on experimental results. The influences of the netting system on the hydrodynamic characteristics of the platform are analyzed. Optimization on the single-point mooring system is conducted under static and dynamic conditions, considering the influences of various mooring parameters, including mooring line length, buoyancy of buoys, and mass of sinkers. The patterns of changes in motion response, mooring line tension, and minimum touchdown length under different mooring parameters are calculated and analyzed. The results indicate that changes in mooring line length have minimal impact on the dynamic response of the platform and mooring system. The addition of appropriate buoys or sinkers can reduce the motion response of the platform and the tension in the mooring lines. Moreover, compared to adding buoys, incorporating sinkers more effectively enhances the overall safety and stability of the platform system.

A new dimeric C-glycoside polyketide chrysomycin F (1), along with four new monomeric compounds, chrysomycins G (2), H (3), I (4), J (5), as well as three known analogues, chrysomycins A (6), B (7), and C (8), were isolated and characterised from a strain of Streptomyces sp. obtained from a sediment sample collected from the South China Sea. Their structures were determined by detailed spectroscopic analysis. Chrysomycin F contains two diastereomers, whose structures were further elucidated by a biomimetic [2 + 2] photodimerisation of chrysomycin A. Chrysomycins B and C showed potent anti-tuberculosis activity against both wild-type Mycobacterium tuberculosis and a number of clinically isolated MDR M. tuberculosis strains.

Sesquiterpenoids served as an important source for natural product drug discovery. Although genome mining approaches have revealed numerous novel sesquiterpenoids and biosynthetic enzymes, the comprehensive landscape of fungal sesquiterpene synthases (STSs) remains elusive. In this study, 123 previously reported fungal STSs were subjected to phylogenetic analysis, resulting in the identification of a fungi-specific STS family known as trichodiene synthase-like sesquiterpene synthases (TDTSs). Subsequently, the application of hidden Markov models allowed the discovery of 517 TDTSs from our in-house fungi genome library of over 400 sequenced genomes, and these TDTSs were defined into 79 families based on a sequence similarity network. Based on the novelty of protein sequences and the completeness of their biosynthetic gene clusters, 23 TDTS genes were selected for heterologous expression in Aspergillus oryzae. In total, 10 TDTSs were active and collectively produced 12 mono- and sesquiterpenes, resulting in the identification of the first chamipinene synthase, as well as the first fungi-derived cedrene, sabinene, and camphene synthases. Additionally, with the guidance of functionally characterized TDTSs, we found that TDTSs in Family 1 could produce bridged-cyclic sesquiterpenes, while those in Family 2 could synthesize spiro- and bridged-cyclic sesquiterpenes. Our research presents a new avenue for the genome mining of fungal sesquiterpenoids.

Land-use change is an important factor affecting terrestrial carbon balance, and it is crucial to explore the response of terrestrial carbon stocks to land-use change, especially in the Songnen Plain, which faces a fierce conflict between the rapid growth of production activities and ecosystem degradation. In this study, we measured soil organic carbon and vegetation biocarbon stocks in the Songnen Plain based on IPCC-recommended methodologies, and explored the characteristics of carbon stock changes in land-use trajectories, land-use drivers, and specific land-use change scenarios (cropland cultivation, returning cropland to forests, the expansion of land for construction, deforestation, greening, and land degradation). The results showed that soil organic carbon stock in the Songnen Plain decreased by 1.63 × 105 t, and vegetation biocarbon stock increased by 2.10 × 107 t from 2005 to 2020. Human factors and natural factors jointly contributed to the land-use change, but the extent of the role of human factors was greater than that of natural factors. The increase in land-use trajectory led to the decrease in soil organic carbon stock and the increase in vegetation biocarbon stock. There was no difference in the effects of human-induced and natural-induced land-use changes on vegetation biocarbon stocks, but the effects on soil organic carbon stocks were diametrically opposite, increasing by 43.27 t/km2 and decreasing by 182.02 t/km2, respectively. The reclamation of arable land, returning cropland to forests, and greening led to a net increase in terrestrial carbon stocks (+813,291.84 t), whereas land degradation, deforestation, and land-use expansion led to a decrease in terrestrial carbon stocks (−460,710.2 t). The results of this study can provide a reference for the adjustment of land-use structure and the increase in terrestrial carbon stock in the Songnen Plain.

A crimping and pultruding forming process for truss rods using Carbon Fiber (CF)/Polyether–Ether–Ketone (PEEK) prepreg tape as the raw material is proposed to address the problem of continuous manufacturing of space trusses on orbit. The proposed process provides material rods for continuous truss manufacturing. Through numerical simulation and experimental verification, the effects of relevant parameters on the forming process are determined, an efficient method of rod curl pultrusion, in-rail, equal material forming is proposed, and the structural configuration of the rod curl pultrusion forming mold is determined. The equivalent macroscopic mechanical properties of unidirectional CF/PEEK prepreg strips are considered, and the rod-forming process is investigated. Rod samples with different process parameters are prepared, and several tests are conducted on them. The results show that the forming load pull is negatively correlated with the temperature at the same forming speed, and forming speed is positively correlated with the forming load pull at a certain temperature. Temperature and speed affect the surface quality of the rod, the density of the material filling, and the mechanical properties of the rod. The optimal forming process parameters are determined through numerical simulation and experimental verification. The developed molding technology has the advantages of high efficiency, low energy consumption, and high integration. It reduces manufacturing costs and improves manufacturing efficiency, so it can serve as a new and effective solution for the manufacturing of high-performance truss rods in the aerospace field.

This study aimed to investigate the impact of selenium (Se) treatment on the accumulation of reactive oxygen species (ROS) and the expressions of related genes in broccoli. To achieve this, one group of broccoli heads was treated with a selenite solution of 2 mg L−1, while another group was soaked in distilled water, serving as the control. The effects of these treatments were evaluated by analyzing the browning, hydrogen peroxide (H2O2) and malondialdehyde (MDA) contents, enzyme activity, and gene expression levels of WARK and RBOH. Our results show that the Se treatment effectively inhibited H2O2 accumulation in the broccoli and reduced harmful MDA levels. The inhibition of ROS accumulation following the Se treatment was associated with enhanced activity of the CAT and SOD enzymes, increased expression levels of BoCAT and BoSOD, and decreased expression levels of the WRKY and RBOH transcription factors. Our study provides insights into the mechanism of action of selenium and its potential application in vegetable storage.

Raspberry (Rubus corchorifolius L. f.) is easy to be infected by pathogens after harvesting. The species of pathogens are not only related to the fruit species, but also related to the cultivation environment. In this study, the main pathogens of post-harvest raspberry were isolated and identified from three different producing areas of raspberry in Taiyuan, Yangquan and Changzhi of Shanxi Province and their biological characteristics were studied. The pathogens were isolated and purified to determine their species by combining morphological and molecular biological characteristics, so as to determine the spore production of pathogens in the same period and their growth under different conditions. The results indicated that Trichoderma koningiopsis, Penicillium crustosum, Botrytis sp. and Rhizopus arrhizus were the main pathogens infecting post-harvest raspberry in the three regions. Penicillium crustosum had the highest spore production capacity, followed by Botrytis sp. and Rhizopus arrhizus. The optimum pH for the growth of four pathogens was 7, with Penicillium crustosum growing the fastest. Botrytis sp. and Penicillium crustosum presented faster growing during storage at 0, 4 and 10 ℃, while Trichoderma koningiopsis and Rhizopus arrhizus grew slower at 0 and 4 ℃.

Port-wine stain (PWS) is a congenital capillary malformation that occurs in 0.3%–0.5% of newborns. The pulsed dye laser is the current gold standard treatment for PWS; however, its efficacy is poor. Photosensitizer photodynamic therapy (PDT) is considered a promising treatment for PWS. Here we provide a comprehensive overview of PDT.

Nucleic acid detection plays a key role in diverse diagnosis and disease control. Currently available nucleic acid detection techniques are challenged by trade-offs among speed, simplicity, precision and cost. Here, we described a novel method, designated SENSOR (Sulfur DNA mediated nucleic acid sensing platform), for rapid nucleic acid detection. SENSOR was developed from phosphorothioate (PT)-DNA and sulfur binding domain (SBD) which specifically binds double-stranded PT-modified DNA. SENSOR utilizes PT-DNA oligo and SBD as targeting module, which is linked with split luciferase reporter to generate luminescence signal within 10 min. We tested detection on synthesized nucleic acid and COVID-19 pseudovirus, achieving attomolar sensitivity combined with an amplification procedure. Single nucleotide polymorphisms (SNP) could also be discriminated. Indicating SENSOR a new promising nucleic acid detection technique.

The joining of aluminum alloy and Ti–Ni–Hf shape memory dissimilar metals was realized by cold metal transfer (CMT) welding-brazing with an Al-based filler for the first time. The relationship between heat input, microstructures, and joint strength was studied. The joint consisted of three regions: the Al/SMA brazing interface, weld metal zone and Al-weld metal zone. The interfacial intermetallic compound (IMC) with thin strip or needle-like morphology was identified to be TiAl3. An inhomogeneous morphology of the IMC was observed from top to bottom along the brazing interface. The Ti–Ni–Hf SMA adjacent to the interface still presented reversible martensitic transformation. Moreover, the phase transition temperature increased slightly with the increasing of distance from the interface due to the variation in the Ti + Hf/Ni ratio. This meant that the functional properties of Ti–Ni–Hf SMA were not significantly affected by welding. With increasing heat input, the thickness of the IMC increased, and the joint strength decreased. The maximum tensile strength reached 122 MPa when the heat input was 553.6 J/mm. The fracture originated from the interface between the IMC and Ti–Ni–Hf and then propagated along the interface.

Abstract Undoubtedly, it is important to remain vigilant and manage invasive grasses to prevent their spread and mitigate their negative impact on the environment. However, these aggressive plants can also play a beneficial role in certain contexts. For example, several invasive grasses provide valuable forage for livestock and have disease control potential. Therefore, a research experiment was conducted to explore the pros and cons of this approach, not only for surrounding vegetation but also for human and animal disease control. The study is primarily focused on developing livestock feed, plant-derived herbicides, and an understanding of the phytotoxic effects of invasive species. All plant parts of Cenchrus ciliaris L., Polypogon monspeliansis L., and Dicanthium annulatum (Forssk.) Stapf, were tested for their phyto-chemical screening, proximate, and toxicity analysis which was caused by the methanolic extract of these grass species. Qualitative phytochemical screening tests were performed for proximate composition analysis and toxicity assessment essays. The phytochemical analysis revealed the positive results for alkaloids, flavonoids, coumarins, phenols, saponins, and glycosides, while negative for tannins. Comparison of proximate analysis intimated maximum moisture (10.8%) and crude fat (4.1%) in P. monspeliensis, whereas maximum dry matter (84.1%), crude protein (13.95%), crude fiber (11%), and ash (7.2%) in D. annulatum. Five (10, 100, 500, 100, 10,000 ppm) and three (10, 1000, 10,000 ppm) different concentrations of methanolic extract prepared from C. ciliaris, P. monspeliansis, and D. annulatum were used respectively for root inhibition and seed germination essay. Furthermore, three different concentrations (10, 30, 50 mg) of plant fine powder were used for sandwich method test. There was a significant decline in the growth rate of experimental model radish seeds (P > 0.005), and results from sandwich method tests showed suppressed growth of root hairs, inhibiting the anchoring of the radish seed. In comparison, results manifest that; P. monspeliansis indicated an upsurge of inhibition (66.58% at 10,000 ppm), D. annulatum revealed soar germination (75.86% in controlled conditions), and C. ciliaris exhibited dramatic shoot up of inhibition because of sandwich method test (14.02% at 50 mg). In conclusion, although grasses are toxic, it is important to consider the beneficiary account.

The increasing abundance of extended spectrum β-lactamase (ESBL) genes in E. coli, and other commensal and pathogenic bacteria, endangers the utility of third or more recent generation cephalosporins, which are major tools for fighting deadly infections. The role of domestic animals in the transmission of ESBL carrying bacteria has been recognized, especially in low- and middle-income countries, however the horizontal gene transfer of these genes is difficult to assess. Here we investigate blaCTX-M gene diversity (and flanking nucleotide sequences) in E. coli from chicken and humans, in an Ecuadorian rural community and from chickens in another location in Ecuador. The blaCTX-M associated sequences in isolates from humans and chickens in the same remote community showed greater similarity than those found in E. coli in a chicken industrial operation 200 km away. Our study may provide evidence of blaCTX-M transfer between chickens and humans in the community.

ABSTRACTAntibody-based immune checkpoint blockade (ICB)-based therapeutics have become effective clinical applications for cancers. Applications of monoclonal antibodies (mAbs) to de-activate the PD-1-PD-L1 pathway could effectively reverse the phenotype of depleted activated thymocytes (T cells) to recover their anti-tumoral activities. High-resolution structures of the complexes of the therapeutic monoclonal antibodies with PD-1 or PD-L1 have revealed the key inter-molecular interactions and provided valuable insights into the fundamental mechanisms by which these antibodies inhibit PD-L1-PD-1 binding. Each anti-PD-1 mAb exhibits a unique blockade mechanism, such as interference with large PD-1-PD-L1 contacting interfaces, steric hindrance by overlapping a small area of this site, or binding to an N-glycosylated site. In contrast, all therapeutic anti-PD-L1 mAbs bind to a similar area of PD-L1. Here, we summarized advances in the structural characterization of the complexes of commercial mAbs that target PD-1 or PD-L1. In particular, we focus on the unique characteristics of those mAb structures, epitopes, and blockade mechanisms. It is well known that the use of antibodies as anti-tumor drugs has increased recently and both PD-1 and PD-L1 have attracted substantial attention as target for antibodies derived from new technologies. By focusing on structural characterization, this review aims to aid the development of novel antibodies targeting PD-1 or PD-L1 in the future.

Industrial ammonia production mainly relies on the conventional Haber–Bosch process accompanied by high energy consumption and plentiful carbon dioxide emissions, which triggered the recent interest to explore more energy‐efficient and environmentally benign alternatives. Very recently, electrochemical nitrite reduction in an aqueous medium promises new opportunities for advanced, energy‐efficient, and sustainable ammonia production at ambient conditions. The ammonia formation rate and Faradic efficiency are strongly associated with the adopted electrocatalysts; therefore, striving for high‐efficient electrocatalysts is the key to sustainable ammonia production via the electrochemical nitrite reduction reaction. Herein, a critical overview of recent advances in electrochemical nitrite reduction reaction to ammonia is presented, highlighting the latest innovative heterogenous electrocatalysts including noble metal catalysts, transition‐metal‐based catalysts, and their compounds. Meanwhile, the possible reaction pathway of nitrite electroreduction to ammonia, ammonia detection, and catalytic activity descriptor are briefly summarized. Finally, the perspective and research challenges of electrocatalysts that convert nitrite to ammonia are outlined, increasing their contributions in the route of realizing a neutral carbon footprint.

Abstract This report analyzes the problem of complex soil movement patterns under the action of coupled forces, such as tension and shear, in agricultural processes and aims to improve the accuracy of contact parameters used in discrete element simulation studies of rototiller-soil interactions. This study focuses on the soil of Shihezi cotton field in the 8th division of Xinjiang and investigates the rotating tiller roller as a soil-touching component of tillage machinery. A combination of simulations and physical testing is used. We perform angle of repose tests and use edge detection, fitting, and other image processing methods to automatically, quickly, and accurately detect the soil accumulation and angle calibration of the contact parameters with soil particles. Additionally, soil slip tests are conducted to calibrate the contact parameters between the soil and the rotary blades. Optimization is achieved based on orthogonal simulations and the Box-Behnken response surface method using physically measured values as the target. A regression model of the stacking angle and rolling friction angle is established to determine the optimal combination of simulation contact parameters: between soil and soil, the recovery coefficient is 0.402, static friction coefficient is 0.621, and rolling friction coefficient is 0.078; between soil contact parts and soil, the recovery coefficient is 0.508, static friction coefficient is 0.401, and rolling friction coefficient is 0.2. Furthermore, the calibration parameters are selected as contact parameters for the discrete element simulation. By combining the above two simulation methods to analyze and compare the simulation process of cutting soil from rototiller roller parts to rototiller single blade parts, we obtained the changes in energy, cutting resistance, and soil particle movement at different depths of the soil cutting process. Finally, the average cutting resistance was used as an index for validation in the field tests. The measured value is 0.96 kN and the error of the discrete element simulation is 13%. This demonstrates the validity of the calibrated contact parameters and the accuracy of the simulation, which can provide a theoretical reference and technical support for the study of the interaction mechanisms between of tillage equipment parts and soil, as well as the design and optimization of these interactions in the future.