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The adoption of green chemistry protocols in nanoparticle (NP) synthesis has exhibited substantial potential and is presently a central focus in research for generating versatile NPs applicable across a broad spectrum of applications. In this scientific contribution, we, for the first time, examined the ability of Aconitum Laeve (A. Laeve) crude extract to synthesize silver and gold nanoparticles (AgNPs@AL; AuNP@AL) and explored their potential applications in biological activities and the catalytic degradation of environmental pollutants. The synthesized NPs exhibited a distinctive surface plasmon resonance pattern, a spherical morphology with approximate sizes of 5–10 nm (TEM imaging), a crystalline architecture (XRD analysis), and potential functional groups identified by FTIR spectroscopy. The antibacterial activity was demonstrated by inhibition zones that measured 16 and 14 mm for the AgNPs@AL and AuNP@AL at a concentration of 80 µg/mL against Staphylococcus aureus and 14 and 12 mm against Escherichia coli, respectively. The antioxidant potential of the synthesized NPs was evaluated using 2,2-diphenyl-1-picrylhydrazyl (DPPH), 2-Phenyl-4,4,5,5-tetramethylimidazoline-1-oxyl 3-Oxide (PTIO), and 3-ethylbenzothiazoline-6-sulfonic acid (ABTS) assays. Our findings suggest that the AuNP@AL effectively countered the tested radicals considerably, displaying IC50 values of 115.9, 103.54, and 180.85 µg/mL against DPPH, PTIO, and ABTS, respectively. In contrast, the AgNPs@AL showed IC50 values of 144.9, 116.36, and 95.39 µg/mL against the respective radicals. In addition, both the NPs presented significant effectiveness in the photocatalytic degradation of methylene blue and rhodamine B. The overall observations indicate that A. Laeve possesses a robust capability to synthesize spherical nanoparticles, exhibiting excellent dispersion and showcasing potential applications in both biological activities and environmental remediation. [ABSTRACT FROM AUTHOR]

Traditional Chinese medicine (TCM) serves as a significant adjunct to chemical treatment for chronic diseases. For instance, the administration of Baitouweng decoction (BTWD) has proven effective in the treatment of ulcerative colitis. However, the limited understanding of its pharmacokinetics (PK) has impeded its widespread use. Chinese Bama miniature pigs possess anatomical and physiological similarities to the human body, making them a valuable model for investigating PK properties. Consequently, the identification of PK properties in Bama miniature pigs can provide valuable insights for guiding the clinical application of BTWD in humans. To facilitate this research, a rapid and sensitive UPLC-MS/MS method has been developed for the simultaneous quantification of eleven active ingredients of BTWD in plasma. Chromatographic separation was conducted using an Acquity UPLC HSS T3 C18 column and a gradient mobile phase comprising acetonitrile and water (containing 0.1% acetic acid). The methodology was validated in accordance with the FDA Bioanalytical Method Validation Guidance for Industry. The lower limit of quantitation fell within the range of 0.60–2.01 ng/mL. Pharmacokinetic studies indicated that coptisine chloride, berberine, columbamine, phellodendrine, and obacunone exhibited low C max , while fraxetin, esculin, fraxin, and pulchinenoside B 4 were rapidly absorbed and eliminated from the plasma. These findings have implications for the development of effective components in BTWD and the adjustment of clinical dosage regimens. [ABSTRACT FROM AUTHOR]

Background: Isatropolone A and C, produced by Streptomyces sp. CPCC 204095, belong to an unusual class of non-benzenoid aromatic compounds and contain a rare seven-membered ring structure. Isatropolone A exhibits potent activity against Leishmania donovani, comparable to the only oral drug miltefosine. However, its variably low productivity represents a limitation for this lead compound in the future development of new anti-leishmaniasis drugs to meet unmet clinical needs. Results: Here we first elucidated the regulatory cascade of biosynthesis of isatropolones, which consists of two SARP family regulators, IsaF and IsaJ. Through a series of in vivo and in vitro experiments, IsaF was identified as a pathway-specific activator that orchestrates the transcription of the gene cluster essential for isatropolone biosynthesis. Interestingly, IsaJ was found to only upregulate the expression of the cytochrome P450 monooxygenase IsaS, which is crucial for the yield and proportion of isatropolone A and C. Through targeted gene deletions of isaJ or isaS, we effectively impeded the conversion of isatropolone A to C. Concurrently, the facilitation of isaF overexpression governed by selected promoters, prompted the comprehensive activation of the production of isatropolone A. Furthermore, meticulous optimization of the fermentation parameters was conducted. These strategies culminated in the attainment of an unprecedented maximum yield—980.8 mg/L of isatropolone A—achieved in small-scale solid-state fermentation utilizing the genetically modified strains, thereby establishing the highest reported titer to date. Conclusion: In Streptomyces sp. CPCC 204095, the production of isatropolone A and C is modulated by the SARP regulators IsaF and IsaJ. IsaF serves as a master pathway-specific regulator for the production of isatropolones. IsaJ, on the other hand, only dictates the transcription of IsaS, the enzyme responsible for the conversion of isatropolone A and C. By engineering the expression of these pivotal genes, we have devised a strategy for genetic modification aimed at the selective and high-yield biosynthesis of isatropolone A. This study not only unveils the unique regulatory mechanisms governing isatropolone biosynthesis for the first time, but also establishes an essential engineering framework for the targeted high-level production of isatropolone A. [ABSTRACT FROM AUTHOR]

The relative research on investigating the association between dietary diversity scores and anthropometric status among young children is few and inconsistent. Since understanding this association is quite essential to give more detailed advice about diet to ensure young children's healthy growth, we sought to determine the association between dietary diversity levels and anthropometric status among young children under 24 months. The study included 1408 mother−child pairs from the Tongji Maternal and Child Health Cohort, whose children range in age from 12 to 24 months. Multivariable logistic regressions were used to examine the effect of dietary diversity on children's anthropometric failure and obesity. All obese children aged 12 and 24 months had low‐medium diverse diets in their first year of life. Risks of anthropometric failure for 12‐month young children consumed low‐medium diverse diets in their first year and 24‐month young children consumed low‐medium diverse diets in their second year are, respectively, 1.27 (odds ratio [OR], 95% confidence interval [CI] = [1.06−1.53]) and 1.19 (OR, 95% CI = [1.02−1.40]) times of those who consumed high diverse diets in corresponding year. The risk of anthropometric failure for 24‐month‐old children who consumed low‐medium diverse diets during their first year of life is 4.70 (OR, 95% CI = [1.62−19.91]) times that of young children who consumed highly diverse diets during their first year of life. Introducing more diverse diets to young children under 24 months of age may be an effective strategy to prevent anthropometric failure and obesity in young children in later life. Key messages: Malnutrition can substantially impair a children's physical growth, resulting in anthropometric failure and death.The World Health Organization advises that when introducing supplemental feeding for young children, the diet should be sufficiently variety.Through a cohort study in Wuhan, China, the current study aims to investigate the relationship between DDS of young children under 24 months of age and their anthropometric status.Introducing more diverse diets to young children under 24 months of age may be an effective strategy to prevent anthropometric failure and obesity in young children in later life. [ABSTRACT FROM AUTHOR]

Previous studies have demonstrated the rejuvenating and restorative actions of mesenchymal stem cells (MSCs) in multiple diseases, but their role in reversing chronic atrophic gastritis (CAG) is not well understood owing to their low efficiency in homing to the stomach. In this work, we investigated the therapeutic effect of umbilical cord-derived MSCs (UC-MSCs) on CAG by endoscopic submucosal injection and preliminarily explored possible mechanisms in vitro. MSCs and normal saline (NS) were injected into the submucosa of the stomach in randomly grouped CAG rabbits. Therapeutic effects on serum indices and histopathology of the gastric mucosa were analyzed in vivo at 30 and 60 days after MSCs injection. GES-1 cells were co-cultured with MSCs in vitro using a Transwell system and cell viability, proliferation, and migration ability were detected. Additionally, in view of the potential mechanisms, the relative protein expression levels of apoptosis, autophagy and inflammation in vitro were explored by Western Blotting. We found that submucosal injection of MSCs up-regulated serum indices (G-17, PGI and PGI/PGII) and alleviated histopathological damage to the gastric mucosa in CAG rabbits. Co-culture of GES-1 cells with MSCs improved cell viability, proliferation, and migration ability, while suppressing apoptosis. We also observed a reduction in the expression of apoptosis indicators, including Bax and cleaved caspase-3, in GES-1 cells after co-culture with MSCs in vitro. Our findings suggest that submucosal injection of MSCs is a promising approach for reversing CAG, and attenuating apoptosis plays a potential role in this process. [ABSTRACT FROM AUTHOR]

Designing a strong tissue adhesive and multifunctional hydrogel dressing for various skin injuries is still a significant challenge. Based on the bioactive activities of rosmarinic acid (RA) and its catechol structure being similar to dopamine, RA-grafted dextran/gelatin hydrogel (ODex−AG−RA) was designed and systemically characterized in this study. The ODex−AG−RA hydrogel exhibited excellent physicochemical properties, including fast gelation time (61.6 ± 2.8 s), strong adhesive strength (27.30 ± 2.02 kPa) and enhanced mechanical properties (1.31 × 104 Pa of G′). The examination of hemolysis and co-culturing with L929 cells showed the strong in vitro biocompatibility of ODex−AG−RA hydrogels. The ODex−AG−RA hydrogels exhibited a 100% mortality rate against S. aureus and at least 89.7% against E. coli in vitro. In vivo evaluation for efficacy in skin wound healing was carried out in a rat model of full-thickness skindefect. The amount of collagen deposition and CD31 on wounds in the two ODex−AG−RA−1 groups on day 14 was 4.3 times and 2.3 times of that in the control group, respectively. Furthermore, the mechanism of ODex−AG−RA−1 for promoting wound healing was proved to be related to its anti-inflammatory properties by adjusting the expression of inflammatory cytokines (TNF-α and CD163) and reducing the level of oxidative stress (MDA and H2O2). Overall, this study demonstrated the wound-healing efficacy of RA-grafted hydrogels for the first time. ODex−AG−RA−1 hydrogel, due to its adhesive, anti-inflammatory, antibacterial and antioxidative activities, was a promising candidate as a wound dressing. [ABSTRACT FROM AUTHOR]

This paper provides a detailed evaluation of the photo-piezo-catalytic properties of lead-free Ba 0.85 Ca 0.15 Zr 0.1 (Ti 1-x Co x) 0.9 (BCZT- x Co, x = 0–0.025) ferroelectric ceramics prepared by a solid-state process. By control of the Co doping level, the band gap was reduced to 2.40 eV at the composition x = 0.02, which improved the generation of photo-generated charges and enhanced the photocatalytic activity. When a solution containing BCZT-0.02Co particles was subjected to both ultrasound and illumination, the degree of degradation of Rhodamine B reached 99% within 60 min, which was grater than when subjected to illumination or ultrasound alone. Examination of the dielectric properties, photoelectrochemical measurements and band energy structure of the materials provided new insights into the catalytic mechanism, where a strong coupling between piezoelectricity and photoexcitation was clearly observed. This work therefore highlights the attractive photo-piezo-catalytic properties of BCZT- x Co doped ceramics and is the first demonstration that Co substitution in these lead-free ferroelectric ceramics provides significant potential for photo-piezo-catalysis applications. [ABSTRACT FROM AUTHOR]

Click-through rate (CTR) prediction, whose goal is to predict the probability of the user to click on an item, has become increasingly significant in the recommender systems. Recently, some deep learning models with the ability to automatically extract the user interest from his/her behaviors have achieved great success. In these work, the attention mechanism is used to select the user interested items in historical behaviors, improving the performance of the CTR predictor. Normally, these attentive modules can be jointly trained with the base predictor by using gradient descents. In this paper, we regard user interest modeling as a feature selection problem, which we call user interest selection. For such a problem, we propose a novel approach under the framework of the wrapper method, which is named Meta-Wrapper. More specifically, we use a differentiable module as our wrapping operator and then recast its learning problem as a continuous bilevel optimization. Moreover, we use a meta-learning algorithm to solve the optimization and theoretically prove its convergence. Meanwhile, we also provide theoretical analysis to show that our proposed method 1) efficiencies the wrapper-based feature selection, and 2) achieves better resistance to overfitting. Finally, extensive experiments on three public datasets manifest the superiority of our method in boosting the performance of CTR prediction. [ABSTRACT FROM AUTHOR]

The Area under the ROC curve (AUC) is a well-known ranking metric for problems such as imbalanced learning and recommender systems. The vast majority of existing AUC-optimization-based machine learning methods only focus on binary-class cases, while leaving the multiclass cases unconsidered. In this paper, we start an early trial to consider the problem of learning multiclass scoring functions via optimizing multiclass AUC metrics. Our foundation is based on the M metric, which is a well-known multiclass extension of AUC. We first pay a revisit to this metric, showing that it could eliminate the imbalance issue from the minority class pairs. Motivated by this, we propose an empirical surrogate risk minimization framework to approximately optimize the M metric. Theoretically, we show that: (i) optimizing most of the popular differentiable surrogate losses suffices to reach the Bayes optimal scoring function asymptotically; (ii) the training framework enjoys an imbalance-aware generalization error bound, which pays more attention to the bottleneck samples of minority classes compared with the traditional $O(\sqrt{1/N})$ O (1 / N) result. Practically, to deal with the low scalability of the computational operations, we propose acceleration methods for three popular surrogate loss functions, including the exponential loss, squared loss, and hinge loss, to speed up loss and gradient evaluations. Finally, experimental results on 11 real-world datasets demonstrate the effectiveness of our proposed framework. The code is now available at https://github.com/joshuaas/Learning-with-Multiclass-AUC-Theory-and-Algorithms. [ABSTRACT FROM AUTHOR]

As pairwise ranking becomes broadly employed for elections, sports competitions, recommendation, information retrieval and so on, attackers have strong motivation and incentives to manipulate or disrupt the ranking list. They could inject malicious comparisons into the training data to fool the target ranking algorithm. Such a technique is called “poisoning attack” in regression and classification tasks. In this paper, to the best of our knowledge, we initiate the first systematic investigation of data poisoning attack on the pairwise ranking algorithms, which can be generally formalized as the dynamic and static games between the ranker and the attacker, and can be modeled as certain kinds of integer programming problems mathematically. To break the computational hurdle of the underlying integer programming problems, we reformulate them into the distributionally robust optimization (DRO) problems, which are computational tractable. Based on such DRO formulations, we propose two efficient poisoning attack algorithms and establish the associated theoretical guarantees including the existence of Nash equilibrium and the generalization ability bounds. The effectiveness of the suggested poisoning attack strategies is demonstrated by a series of toy simulations and several real data experiments. These experimental results show that the proposed methods can significantly reduce the performance of the ranker in the sense that the correlation between the true ranking list and the aggregated results with toxic data can be decreased dramatically. [ABSTRACT FROM AUTHOR]

Papillary thyroid carcinoma (PTC) is the most common endocrine malignancy, and its incidence has increased rapidly in recent years. The BRAF inhibitor vemurafenib is effective against BRAFV600E-positive PTC; however, acquired resistance to single agent therapy frequently leads to tumor recurrence and metastasis, underscoring the need to develop tailored treatment strategies. We previously showed that the oncogenic kinase PIM1 was associated with the malignant phenotype and prognosis of PTC. In this study, we showed that sustained expression of the PIM1 protein in PTC was affected by the BRAFV600E mutation. Based on this regulatory mechanism, we tested the synergistic effects of inhibitors of BRAF (BRAFi) and PIM1 in BRAFV600E-positive PTC cell lines and xenograft tumors. LC-MS metabolomics analyses suggested that BRAFi/PIMi therapy acted by restricting the amounts of critical amino acids and nucleotides required by cancer cells as well as modulating DNA methylation. This study elucidates the role of BRAFV600E in the regulation of PIM1 in PTC and demonstrates the synergistic effect of a novel combination, BRAFi/PIMi, for the treatment of PTC. This discovery, along with the pathways that may be involved in the powerful efficacy of BRAFi/PIMi strategy from the perspective of cell metabolism, provides insight into the molecular basis of PTC progression and offers new perspectives for BRAF-resistant PTC treatment. [ABSTRACT FROM AUTHOR]

In this paper, we study the problem of estimating subjective visual properties (SVP) for images, which is an emerging task in Computer Vision. Generally speaking, collecting SVP datasets involves a crowdsourcing process where annotations are obtained from a wide range of online users. Since the process is done without quality control, SVP datasets are known to suffer from noise. This leads to the issue that not all samples are trustworthy. Facing this problem, we need to develop robust models for learning SVP from noisy crowdsourced annotations. In this paper, we construct two general robust learning frameworks for this application. Specifically, in the first framework, we propose a probabilistic framework to explicitly model the sparse unreliable patterns that exist in the dataset. It is noteworthy that we then provide an alternative framework that could reformulate the sparse unreliable patterns as a “contraction” operation over the original loss function. The latter framework leverages not only efficient end-to-end training but also rigorous theoretical analyses. To apply these frameworks, we further provide two models as implementations of the frameworks, where the sparse noise parameters could be interpreted with the HodgeRank theory. Finally, extensive theoretical and empirical studies show the effectiveness of our proposed framework. [ABSTRACT FROM AUTHOR]

Sphingopyxis sp. USTB-05, which we previously identified and examined, is a well-known bacterial strain for biodegrading cyanobacterial hepatotoxins of both nodularins (NODs) and microcystins (MCs). Although the pathways for biodegrading the different types of [D-Asp1] NOD, MC-YR, MC-LR and MC-RR by Sphingopyxis sp. USTB-05 were suggested, and several biodegradation genes were successfully cloned and expressed, the comprehensive genomic analysis of Sphingopyxis sp. USTB-05 was not reported. Here, based on second and third generation sequencing technology, we analyzed the whole genome of Sphingopyxis sp. USTB-05, which is 4,679,489 bp and contains 4,312 protein coding genes. There are 88 protein-coding genes related to the NODs and MCs biodegradation, of which 16 genes (bioA, hmgL, hypdh, speE, nspC, phy, spuC, murD, glsA, ansA, ocd, crnA, ald, gdhA, murC and murI) are unique. These genes for the transformation of phenylacetic acid CoA (PA-CoA) to CO2 were also found in Sphingopyxis sp. USTB-05. This study expands the understanding of the pathway for complete biodegradation of cyanobacterial hepatotoxins by Sphingopyxis sp. USTB-05. [ABSTRACT FROM AUTHOR]

Brain tumors are the deadliest and most difficult to treat of all forms of cancer. Preoperative classification of brain tumors is conducive to the development of corresponding treatment plan. Take pituitary tumors as an example. Precisely judging the image data of pituitary tumor texture before surgery can provide a basis for the selection of surgical plan and prognosis. However, the existing methods require manual intervention, and the efficiency and accuracy are not high. In this paper, we proposed an automatic brain tumor texture diagnosis method for uneven sequence image data. First, for the small sample of pituitary tumor MRI image data, the T1 and T2 sequence data are uneven or missing; we used the CycleGAN model to perform data conversion between different domains to obtain a completely sampled MRI spatial sequence. Then, we used texture analysis+pseudo-label learning to label pituitary tumor data of some unknown labels. After that, we used the improved U-Net model based on CBAM to optimize feature extraction for pituitary tumor image data. Finally, we used the CRNN model to classify the degree of pituitary tumor texture based on the advantages of sequence data. The entire process only needs to provide labels for the entire sequence data, and the efficiency is greatly improved, with an accuracy rate of 94.23%. [ABSTRACT FROM AUTHOR]

Fully supervised learning (FSL) and weakly supervised learning based on multiple instance learning (WSLMIL) have become two mainstream paradigms for performing computer-aided pathological diagnosis (CAPD). It is well known that the high-intensity annotation burden of FSL and the performance degradation due to poor training constraints of WSLMIL are stumbling blocks for clinical translation. Even more unfortunate is the lack of comprehensive experimental analysis to help researchers make content-specific trade-offs between FSL and WSLMIL. In this work, we systematically compare the performances of FSL and WSLMIL on lymph node metastasis in breast cancer using a publicly available dataset. By analyzing the results of 16 backbone networks in the FSL paradigm, we find that emerging networks based on transformer (PVTv2-B2) and multi-layer perceptron (CycleMLP-B3) are more advantageous for performing patch-level classification task than convolution-based structure (ResNet50); combining their output with morphological feature extraction can be better used to universally perform slide-level classification task. However, the slight improvement brought by the evolution of the backbone network may be overshadowed by the aggregation operation in 6 WSLMIL algorithms, whereas relying on the in-domain backbone network can achieve a stable and excellent prediction performance in both quantitative analysis and interpretability comparisons. All the experimental results ultimately illustrate that the combination of in-domain backbone network and emergent aggregation operation becomes an economical and efficient technical tool for CAPD, which can be regarded as a compromise between FSL and WSLMIL. [ABSTRACT FROM AUTHOR]

As an effective learning paradigm against insufficient training samples, multi-task learning (MTL) encourages knowledge sharing across multiple related tasks so as to improve the overall performance. In MTL, a major challenge springs from the phenomenon that sharing the knowledge with dissimilar and hard tasks, known as negative transfer, often results in a worsened performance. Though a substantial amount of studies have been carried out against the negative transfer, most of the existing methods only model the transfer relationship as task correlations, with the transfer across features and tasks left unconsidered. Different from the existing methods, our goal is to alleviate negative transfer collaboratively across features and tasks. To this end, we propose a novel multi-task learning method called task-feature collaborative learning (TFCL). Specifically, we first propose a base model with a heterogeneous block-diagonal structure regularizer to leverage the collaborative grouping of features and tasks and suppressing inter-group knowledge sharing. We then propose an optimization method for the model. Extensive theoretical analysis shows that our proposed method has the following benefits: (a) it enjoys the global convergence property and (b) it provides a block-diagonal structure recovery guarantee. As a practical extension, we extend the base model by allowing overlapping features and differentiating the hard tasks. We further apply it to the personalized attribute prediction problem with fine-grained modeling of user behaviors. Finally, experimental results on both simulated dataset and real-world datasets demonstrate the effectiveness of our proposed method. [ABSTRACT FROM AUTHOR]

Nowadays, how to effectively evaluate visual properties has become a popular topic for fine-grained visual comprehension. In this paper we study the problem of how to estimate such visual properties from a ranking perspective with the help of the annotators from online crowdsourcing platforms. The main challenges of our task are two-fold. On one hand, the annotations often contain contaminated information, where a small fraction of label flips might ruin the global ranking of the whole dataset. On the other hand, considering the large data capacity, the annotations are often far from being complete. What is worse, there might even exist imbalanced annotations where a small subset of samples are frequently annotated. Facing such challenges, we propose a robust ranking framework based on the principle of Hodge decomposition of imbalanced and incomplete ranking data. According to the HodgeRank theory, we find that the major source of the contamination comes from the cyclic ranking component of the Hodge decomposition. This leads us to an outlier detection formulation as sparse approximations of the cyclic ranking projection. Taking a step further, it facilitates a novel outlier detection model as Huber's LASSO in robust statistics. Moreover, simple yet scalable algorithms are developed based on Linearized Bregman Iteration to achieve an even less biased estimator. Statistical consistency of outlier detection is established in both cases under nearly the same conditions. Our studies are supported by experiments with both simulated examples and real-world data. The proposed framework provides us a promising tool for robust ranking with large scale crowdsourcing data arising from computer vision. [ABSTRACT FROM AUTHOR]

Background: Vascular dementia (VD) is a brain disease featured by cognitive impairment and cerebrovascular pathologies. Idebenone can treat neurodegenerative diseases. This study evaluated the mechanism of Idebenone in VD. Methods: The VD rat model was established by permanent occlusion of bilateral common carotid arteries, followed by intragastrical administration of Idebenone. The learning and spatial memory abilities, and the levels of MDA, SOD, IL-6 and TNF-α were measured. Histological staining was adopted to observe the damage of neurons in the hippocampal cortex and to quantitatively analyze the neuronal damage in CA1 area of hippocampus. Microarray analysis was performed to find out the effect of Idebenone treatment on microRNA (miR) expression in hippocampus of rats. The potential target genes of miR and the pathways regulated by target genes were searched by bioinformatics analysis, and verified by experiments. The mechanism of action behind Idebenone in VD rats was proved by rescue experiment. Results: Idebenone treatment improved the learning and spatial memory abilities of VD rats, inhibited neuroinflammation and oxidative stress, and prevented neuronal apoptosis. Idebenone treatment elevated miR-216a expression in hippocampus of rats, but the therapeutic effect of Idebenone was averted by lentivirus inhibition of miR-216a. miR-216a targeted RSK2. Overexpression of RSK2 annulled the therapeutic effect of Idebenone on VD rats by activating the IκBα/NF-κB axis. Conclusion: Idebenone inhibits the activation of RSK2/IκBα/NF-κB axis by increasing miR-216a, thus alleviating oxidative stress and neuroinflammation in VD rats. [ABSTRACT FROM AUTHOR]

Acute pancreatitis (AP) is a severe inflammatory condition characterized by the activation of pancreatic enzymes within acinar cells, leading to tissue damage and inflammation. Interleukin (IL)-22 is a potential therapeutic agent for AP owing to its anti-inflammatory properties and ability to promote tissue repair. The present study evaluated the differentially expressed proteins in arginine-induced pancreatic acinar cell injury following treatment with IL-22, and the possible mechanisms involved in IL-22-mediated alleviation of AP. AR42J cells were stimulated using L-arginine to establish an acinar cell injury model in vitro and the damaged cells were subsequently treated with IL-22. The characteristics of the model and the potential therapeutic effects of IL-22 were examined by CCK-8 assay, flow cytometry, TUNEL assay, transmission electron microscopy and ELISA. Differentially expressed proteins in cells induced by arginine and treated with IL-22 were assessed using liquid chromatography-mass spectrometry. The identified proteins were further subjected to Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analysis to elucidate their functional roles. The present study demonstrated that arginine-stimulated cells showed significant pathological changes resembling those in AP, which were alleviated after IL-22 treatment. Proteomic analysis then demonstrated that in IL-22-treated cells, proteins related to the formation and fusion of autophagosomes with lysosomes were significantly downregulated, whereas endocytosis related proteins were enriched in the upregulated proteins. After IL-22 treatment, western blotting demonstrated reduced expression of autophagy-associated proteins. In conclusion, by inhibiting the formation and fusion of autophagosomes with lysosomes, IL-22 may have mitigated premature trypsinogen activation, subsequently minimizing acinar cell injury induced by L-arginine. This was accompanied by concurrent upregulation of endocytosis, which serves a pivotal role in sustaining regular cellular material transport and signal propagation. This research underscored the potential of IL-22 in mitigating arginine-induced AR42J injury, which could be valuable in refining treatment strategies for AP. [ABSTRACT FROM AUTHOR]

The effects of chitooligosaccharide (COS) supplementation in laying hen diets on egg production, egg quality, blood biochemistry, antioxidant capacity and immunity during the late laying period were investigated in this 10-week trial. A total of 3000 Fengda No.1 laying hens, 52 weeks of age, were randomly allocated to three treatment groups, each of which included five replicates of 200 hens. Treatments consisted of the basal diet only or the basal diet supplemented with COS at 75 or 125 mg/kg. Hens fed with both COS supplemented diets had improved hen-day egg production, egg mass and feed conversion ratio than control birds. The higher level of COS supplementation exerted positive effects on eggshell strength and eggshell thickness, but significantly decreased yolk colour. Addition of 125 mg/kg COS was also found to significantly increase serum albumin content and significantly decrease serum cholesterol level. Dietary supplementation with COS significantly decreased serum triglyceride level compared with birds fed the control diet. Moreover, COS significantly increased total antioxidative capacity and significantly decreased malondialdehyde level in serum, but had no significance on the activities of antioxidant enzymes. The only change in blood immune response compounds observed in this study was a significantly increased concentration of C3 when laying hens were fed COS supplemented diets. In conclusion, COS could improve laying performance and egg quality in hens during the late laying period. Inclusion of COS in the diet might be beneficial to hens' health by lowering serum lipids, enhancing antioxidant activity and slightly enhancing immune ability. COS improved laying performance and egg quality in hens during the late laying period. Inclusion of COS in the diet might be beneficial to hens' health by lowering serum lipids, enhancing the antioxidant activity and slightly enhancing immune ability. The optimum concentration of COS is 75 mg/kg in the basal diet in order to achieve an increased egg production, egg quality and health condition. [ABSTRACT FROM AUTHOR]

Aberrant signal transducer and activator of transcription 3 (STAT3) signaling promotes the initiation and progression of cancer in humans by either inhibiting apoptosis or inducing cell proliferation, angiogenesis, invasion, and metastasis. The role of resveratrol（RES）in inhibiting the STAT3 signaling pathway in vivo, particularly in cervical cancer is still unknown. This study aims to investigate the role of STAT3 and its phosphorylation in RES‐mediated suppression of cervical cancer. The effects of RES on cervical cancer were determined by examining tumor tissues, their histological changes, and the volume and weight of tumor tissues grown from HeLa cells injected in female athymic BALB/C nude mice. The structure and target interaction of RES were virtually screened using the molecular docking program Autodock Vina. The status of phosphorylated STAT3, protein levels of epithelial‐mesenchymal transition molecular markers and extracellular matrix degradation enzymes were determined through Western blot. We demonstrated that RES could suppress the proliferation and metastatic potential of cervical cancer cells by inactivating phosphorylation of STAT3 at Tyr705 but not Ser727. This effect was intensified by inhibition of the STAT3 signal pathway. [ABSTRACT FROM AUTHOR]

This study aimed to evaluate the anti-post-weaning diarrhoea effect of a low dose coated-ZnO in weaned piglets in relation to intestinal permeability. A total of 72 cross-bred piglets, weaned at 27 d, were allocated to three dietary treatments as follows: basal diet without supplemental ZnO (control group); basal diet supplemented with 2250 mg/kg ZnO (ZnO group); basal diet supplemented with 562.5 mg/kg coated-ZnO (C-ZnO group). The trial lasted 21 days. Compared with control group, supplementation with coated-ZnO reduced (P <.05) diarrhoea index, plasma D-lactate level, and improved (P <.05) jejunal villus height and the expression of occludin and zonula occludens protein-1 in jejunal mucosa. In the C-ZnO group, intestinal total antioxidant capacity was enhanced (P <.05), and levels of malondialdehyde were decreased (P <.05) compared with the control group. The apoptotic index of intestinal epithelial cell was decreased (P <.05). Furthermore, the effects of the low dose coated-ZnO were similar to the high dose ZnO on the aforementioned parameters. Our results indicated that the low dose of coated-ZnO can alleviate diarrhoea by decreasing intestinal permeability as does a pharmacological dose of ZnO. [ABSTRACT FROM AUTHOR]

According to the performance degradation problem of feature extraction from higher-order statistics in the context of alpha-stable noise, a new feature extraction method is proposed. Firstly, the nonstationary vibration signal of rolling bearings is decomposed into several product functions by LMD to realize signal stability. Then, the distribution properties of product functions in the time domain are discussed by the comparison of heavy tails and characteristic exponent estimation. Fractional lower-order p-function optimization is obtained by the calculation of the distance ratio based on K-means algorithms. Finally, a fault feature dataset is established by the optimal FLOS and lower-dimensional mapping matrix of covariation to accurately and intuitively describe various bearing faults. Since the alpha-stable noise is effectively suppressed and state described precisely, the presented method has shown better performance than the traditional methods in bearing experiments via fractional lower-order feature extraction. [ABSTRACT FROM AUTHOR]

Abstract Stable 2D/2D reduced graphene oxide-bismuth tungstate (rGO-BWO) compounds were synthesized via a facile hydrothermal process. The synthesized rGO-BWO compounds show high photocatalytic activity on aqueous tetracycline degradation, better than that of pure 2D BWO and rGO. rGO not only acts as the acceptor, transporter, and mediator to promote the photogenerated electrons transfer, also plays an important role in the blue shift of Fermi level, leading to the more negative conduction band potential, and benefitting the generation of O 2 −. Graphical abstract Unlabelled Image Highlights • Stable 2D/2D nano-structured rGO-BWO compounds were successfully synthesized. • rGO act as the acceptor, transporter, and mediator to promote the carriers transfer. • O 2 – and holes play the main roles in the photocatalytic degradation over rGO-BWO. [ABSTRACT FROM AUTHOR]

In crowdsourced preference aggregation, it is often assumed that all the annotators are subject to a common preference or social utility function which generates their comparison behaviors in experiments. However, in reality, annotators are subject to variations due to multi-criteria, abnormal, or a mixture of such behaviors. In this paper, we propose a parsimonious mixed-effects model, which takes into account both the fixed effect that the majority of annotators follows a common linear utility model, and the random effect that some annotators might deviate from the common significantly and exhibit strongly personalized preferences. The key algorithm in this paper establishes a dynamic path from the social utility to individual variations, with different levels of sparsity on personalization. The algorithm is based on the Linearized Bregman Iterations, which leads to easy parallel implementations to meet the need of large-scale data analysis. In this unified framework, three kinds of random utility models are presented, including the basic linear model with $L_2$ loss, Bradley-Terry model, and Thurstone-Mosteller model. The validity of these multi-level models are supported by experiments with both simulated and real-world datasets, which shows that the parsimonious multi-level models exhibit improvements in both interpretability and predictive precision compared with traditional HodgeRank. [ABSTRACT FROM AUTHOR]

Hepatotoxic microcystins (MCs) are produced and released by the harmful bloom-forming cyanobacteria, which severely threaten drinking water safety and human health due to their high toxicity, widespread distribution, and structural stability. The linearized microcystinase (MlrB) further hydrolyses the poisonous linearized MCs produced by the microcystinase-catalysed MCs to form tetrapeptides. Here, the purification and activity of MlrB were investigated. The results showed that the linearized products generated by 12.5 mg/L MC-LR and MC-RR were removed by purified recombinant MlrB at a protein concentration of 1 mg/L within 30 min. The high catalytic activity of MlrB can be obtained via heterologous expression and affinity purification, which lays the foundation for further studies on the properties and mechanism of MCs biodegradation enzymes. [ABSTRACT FROM AUTHOR]

We previously reported that regenerating islet-derived protein 3 alpha (REG3A) exacerbates pancreatic malignancies. The mechanism of this effect has not been clearly elucidated. Here we first identified key differentially expressed genes (DEGs) and signal pathways in the pancreatic cancer cell line SW1990, compared to two control cell lines, by microarray analysis. We then identified key genes and pathways regulated by REG3A or the cytokine IL6 in SW1990 cells. Afterwards, these DEGs induced by REG3A or IL6 were subjected to KEGG pathway enrichment analysis and GO function analysis by the DAVID online tool. Ultimately, we constructed protein–protein interaction networks among the DEGs by Cytoscape. Among the three pancreatic cell lines, SW1990 exhibited highly deterioration with the activation of genes and pathways related to proliferation, survival, angiogenesis, and invasion. As a result, 50 DEGs enriched in 11 pathways were identified in REG3A-treated SW1990 cells, and 28 DEGs enriched in 9 pathways were detected in IL6-treated cells. Overall, results of microarray analysis followed by qRT-PCR and Western blotting suggest that REG3A regulates pancreatic cell growth by increasing the expression of at least 8 genes: JAK1 , STAT3 , IL10 , FOXM1 , KRAS , MYC , CyclinD1 , and c-fos ; and activation of at least 4 signal pathways: TGFβ, PDGF, angiogenesis and RAS. Similar results were obtained with IL6 treatment. Regulation network analysis confirmed the cell growth related DEGs, and further uncovered three transcription factor families with immune functions regulated by REG3A. [ABSTRACT FROM AUTHOR]

The emergence of novel infectious bronchitis viruses (IBVs) has been reported worldwide. Between 2011 and 2014, eight IBV isolates were identified from disease outbreaks in northeast China. In the current study we analysed the S1 gene of these eight IBV isolates in addition to the complete genome of five of them. We confirmed that these isolates emerged through the recombination of LX4 and Taiwan group 1 (TW1) viruses at two switch sites, one was in the Nsp 16 region and the other in the spike protein gene. The S1 gene in these viruses exhibited high nucleotide similarity with TW1-like viruses; the TW1 genotype was found to be present in southern China from 2009. Pathogenicity experiments in chickens using three of the eight virus isolates revealed that they were nephropathogenic and had similar pathogenicity to the parental viruses. The results of our study demonstrate that recombination, coupled with mutations, is responsible for the emergence of novel IBVs. [ABSTRACT FROM PUBLISHER]

The study was aimed to evaluate the morphology and immune function development of the jejunum and ileum in squab pigeons (Columba livia), by determining the villus ultrastructure, secretory IgA, and cytokines. Eight squabs were randomly selected and sampled on the day of hatch (DOH), d 7 (D 7), 14 (D 14), and 21 (D 21) post-hatch, respectively. The results showed that under transmission electron microscope, the enterocyte circumference in jejunum and ileum decreased with age. The tight junction involved in enterocyte circumference of jejunal villi plateaued from D 7, whereas that of ileal villi changed irregularly. The microvilli of jejunal and ileal villi was maximum at D 14. Under scanning electron microscope, the villus morphology of jejunum and ileum appeared finger-shaped at DOH. After D 7, the jejunal villi were still finger-shaped whereas the ileal villi were leaflike. The secretory IgA in jejunum was significantly increased at D 21. The TGF-β decreased linearly in jejunum and ileum. The anti-inflammatory cytokines increased linearly and proinflammatory cytokines decreased linearly in jejunum and ileum with age. In conclusion, the morphological changes of jejunal epithelium were concentrated at DOH–D 7 and ileal epithelium at DOH–D 14 mainly. The changes in mucus layer and immune-related factors of jejunum and ileum persisted for almost the entire period. [ABSTRACT FROM AUTHOR]

Near infrared reflectance spectroscopy (NIRS) and reference data were used to determine the amylose contents of single maize seeds to enable rapid, effective selection of individual seeds with desired traits. To predict the amylose contents of a single seed, a total of 1069 (865 as calibration set, 204 as validation set) single seeds representing 120 maize varieties were analyzed using chemical methods and performed calibration and external validation of the 150 single seeds set in parallel. Compared to various spectral pretreatments, the regression of partial least squares (PLS) with mathematical treatment of Harmonization showed the final optimization. The single-seed amylose contents showed the root mean square error of calibration (RMSEC) of 2.899, coefficient of determination for calibration (R2) of 0.902, and root mean square error of validation (RMSEV) of 2.948. In external validations, the coefficient of determination in cross-validation (r2), root mean square error of the prediction (RMSEP) and ratio of the standard deviation to SEP (RPD) were 0.892, 2.975 and 3.086 in the range of 20–30%, respectively. Therefore, NIRS will be helpful to breeders for determining the amylose contents of single-grain maize. [ABSTRACT FROM AUTHOR]

The use of poly(vinylidene fluoride) (PVDF) microfiltration (MF) membranes to purify oily water has received much attention. However, it is challenging to obtain high-performance PVDF microfiltration membranes due to severe surface fouling and rapid decline of permeability. This study explored a new approach to fabricate high-performance PVDF/silica (SiO2) composite membrane via the use of a polymer solution featuring lower critical solution temperature (LCST) characteristics and the non-solvent thermally induced phase separation method (NTIPS). Coupling with morphological observations, the membrane formation kinetics were analyzed in depth to understand the synergistic effect between the LCST solution properties and fabrication conditions in NTIPS. Utilizing such a synergistic effect, the transition from finger-like macrovoid pores to bi-continuous highly connected pores could be flexibly tuned by increasing the PVDF concentration and the weight ratio of SiO2/PVDF in the dope solution and by raising the coagulation temperature to above the LCST of the solution. The filtration experiments with surfactant-stabilized oil-water emulsion showed that the permeation flux of the PVDF/SiO2 composite membranes was higher than 318 L·m−2·h−1·bar−1 and the rejection above 99.2%. It was also shown that the PVDF/SiO2 composite membranes, especially those fabricated above the LCST, demonstrated better hydrophilicity, which resulted in significant enhancement in the anti-fouling properties for oil/water emulsion separation. Compared to the benchmark pure PVDF membrane in oily water purification, the optimal composite membrane T70 was demonstrated via the 3-cycle filtration experiments with a significantly improved flux recovery ratio (Frr) and minimal reduced irreversible fouling (Rir). Overall, with the developed method in this work, facile procedure to tune the membrane morphology and pore structure was demonstrated, resulting in high performance composite membranes suitable for oil/water emulsion separation. [ABSTRACT FROM AUTHOR]

Cholestasis is an important predisposing factor of liver diseases, such as hepatocyte necrosis, liver fibrosis and primary biliary cirrhosis. In this study, we aimed to investigate the effects of Kinsenoside (KD), a natural active ingredient of Anoectochilus roxburghii, on estrogen-induced cholestatic liver injury in Sprague-Dawley rats and the underlying mechanism. The rats were randomly divided into six groups: control group, model group, low-dose KD group (50 mg/kg body weight, KD-L), medium-dose KD group (100 mg/kg body weight, KD-M), high-dose KD group (200 mg/kg body weight, KD-H) and ursodeoxycholic acid group (40 mg/kg body weight, UDCA). 17α-Ethinylestradiol (EE) was used to establish an experimental animal model of estrogen-induced cholestasis (EIC). The results demonstrated that KD alleviated liver pathologic damage, serum biochemical status and inhibited hepatocellular microstructure disorder and bile duct hyperplasia in EE-induced cholestatic rats. Mechanically, KD alleviated EE-induced cholestatic liver injury by inhibiting inflammatory responses and regulating bile acid homeostasis. Concretely, KD reduced the expression of IL-1β and IL-6 by inhibiting NF-κB p65 to suppress EE-mediated inflammation in rat liver. KD enhanced the expression of FXR and inhibited EE-mediated reduction of FXR in vitro and in vivo. It was the potential mechanism that KD mitigates cholestasis by increasing efflux and inhibiting uptake of bile acids via FXR-mediated induction of bile salt export pump (BSEP) and reduction of Na+-dependent taurocholate cotransport peptide (NTCP) to maintain bile acid homeostasis. Moreover, KD repressed the bile acid synthesis through reducing the expression of synthetic enzyme (CYP7A1), thereby normalizing the expression of metabolic enzyme (SULT2A1) of bile acid. In conclusion, our results revealed that KD may be an effective drug candidate for the treatment of cholestasis. [ABSTRACT FROM AUTHOR]

• Research the solubility of bezafibrate in pure and mixed solvents; • Solubility data was correlated by Jouyban-Acree model and van't Hoff-Jouyban-Acree model; • Discuss the influence of solvent properties on solubility. By using the saturation shake-flask method, the saturated solubility of bezafibrate in neat water, methanol, ethanol, n-propanol and isopropanol and aqueous co-solvent mixtures of methanol (1) + water (2), ethanol (1) + water (2), isopropanol (1) + water (2) and n-propanol (1) + water (2) was experimentally acquired at temperatures from 283.15 Kto 323.15 K and local atmospheric pressure. The maximum solubility magnitudes in mole fraction were recorded in the neat solvents of methanol/ethanol/ n -propanol/isopropanol for corresponding solutions. The mole fraction solubility was described mathematically by using the van't Hoff-Jouyban-Acree and Jouyban-Acree models. The largest value of relative average deviations was 6.23%; and, root-mean-square deviations, 8.92 × 10−5. The local mole fractions of water and co-solvent (methanol, ethanol, n -propanol or isopropanol) around the drug bezafibrate were quantitatively investigated by the use of Inverse Kirkwood–Buff integrals method. Results indicated that the bezafibrate was preferentially solvated by methanol (ethanol, n -propanol or isopropanol) in alcohol-rich and intermediate compositions in the alcohol mixtures; while in water-rich compositions, bezafibrate was preferentially solvated by water. The main factors relating to solvent effect were inspected through Kamlet and Taft linear solvation energy relationships, demonstrating that the cavity formation energy and dipolarity-polarizability in methanol solutions, cavity formation energy and basicity in ethanol solutions, and cavity formation energy in n -propanol (isopropanol) solutions played the principal role upon the bezafibrate solubility variation. [ABSTRACT FROM AUTHOR]

Severe acute pancreatitis (SAP) begins with premature activation of enzymes, promoted by the immune system, triggering a potential systemic inflammatory response that leads to organ failure with increased mortality and a bleak prognosis. Interleukin-22 (IL-22) is a cytokine that may have a significant role in SAP. IL-22, a member of the IL-10 cytokine family, has garnered growing interest owing to its potential tissue-protective properties. Recently, emerging research has revealed its specific effects on pancreatic diseases, particularly SAP. This paper provides a review of the latest knowledge on the role of IL-22 and its viability as a therapeutic target in SAP. Highlights: 1. Interleukin-22 (IL-22) is a member of the IL-10 family of cytokines. 2. IL-22 is a potential indicator for monitoring organ dysfunction and severity of severe acute pancreatitis (SAP). 3. IL-22 acts as a protective factor against acinar cell damage by suppressing autophagy and reducing the infiltration of inflammatory cells. 4. IL-22 alleviate SAP-induced multiorgan injury. 5. IL-22 protect SAP-induced intestinal barrier damage. [ABSTRACT FROM AUTHOR]

Transparent heat mirrors have been attracting a great deal of interest in the last few decades due to their broad applications, which range from solar thermal convection to energy-saving. Here, we present a flexible Polyethylene terephthalate/Ag-doped Indium tin oxide/Polydimethylsiloxane (PAIP) thin film that exhibits high transmittance in visible range and low emissivity in the thermal infrared region. Experimental results show that the temperature of the sample can be as high as 108 °C, which is ~23 °C higher than that of a blackbody control sample under the same solar radiation. Without solar radiation, the temperature of the PAIP thin film is ~6 °C higher than that of ordinary fabric. The versatility of the large-area, low-radiation-loss, highly-transparent and flexible hydrophobic PAIP thin film suggest great potential for practical applications in thermal energy harvesting and manipulation. [ABSTRACT FROM AUTHOR]

Simple Summary: Research on antioxidant status and lipid metabolism in pigeon squabs as meat type poultry is limited. The objective of this study was to explore the age-related changes in the antioxidant status and lipid metabolism of pigeon squabs (Columba livia). Ten squabs were randomly selected, out of 400 hatched squabs, on the following days: day of hatching (DOH) and days 7 (D7), 14 (D14), 21 (D21) post-hatch, respectively. BW, serum lipid levels, antioxidant capacity indices, lipid metabolism-related enzyme activities, lipid metabolism-related gene expression, and liver morphology were determined. Results indicated that the phase from DOH to D14 was a growth spurt, especially in the first seven days. The antioxidant capacity of squabs had a continuous decline from DOH to D14. Besides, changes regarding lipid metabolism mainly occurred in the phase from DOH to D14. The first seven days mainly showed less lipid breakdown, while the second seven days displayed more complicated lipid metabolism. The results obtained from this study suggested that, in the pigeon industry, it is better to take nutritional manipulation in squabs before D14. The objective of this study was to evaluate the age-related changes in antioxidant status and the lipid metabolism of pigeon squabs (Columba livia), by determining the BW, antioxidant indices, serum lipid levels, lipid metabolism-related enzyme activities, lipid metabolism-related gene expression, and liver morphology in squabs. Ten squabs were randomly selected and sampled on the day of hatching (DOH), days 7 (D7), 14 (D14) and 21 (D21) post-hatch, respectively. The results showed that BW of squabs increased linearly from DOH to D21. The minimum fold of BW gain was observed in the phase from D14 to D21. Serum triglyceride and free fatty acid levels displayed linear and quadratic trends as age increased, with these maximum responses in D14. Serum low-density lipoprotein cholesterol level responded to age linearly and quadratically with the minimum in D14. Serum high-density lipoprotein cholesterol level and the ratio of high-density lipoprotein cholesterol to low-density lipoprotein cholesterol increased linearly with age, whereas the very low-density lipoprotein cholesterol level decreased linearly. The activities of glutathione peroxidase, catalase, and superoxide dismutase in liver displayed linear and quadratic trends as age increased, with these minimum responses in D14. Hepatic malondialdehyde concentration responded to age linearly and quadratically, with the maximum in D14. Activities of lipoprotein lipase, hepatic lipase, and 3-hydroxy-3-methyl glutaryl coenzyme A reductase in liver responded to age linearly and quadratically, with these minimum responses in D14. Hepatic hormone-sensitive lipase activity displayed linear and quadratic trends as age increased with the maximum in D14. Hepatic acetyl CoA carboxylase activity on D14 was significantly lower than squabs on DOH and D7. Hepatic carnitine palmitoyltransferase 1 mRNA expression responded to age linearly and quadratically, with minimum response in D14. Hepatic mRNA expression of acetyl CoA carboxylase and fatty acid synthetase increased linearly with age. Hepatic Oil-Red-O staining area displayed a quadratic trend as age increased, with the maximum response in D14. In conclusion, the phase from DOH to D14 was a crucial development stage for growth, antioxidant status and lipid metabolism in pigeon squabs. The results suggest it is better to take nutritional manipulation in squabs before D14. [ABSTRACT FROM AUTHOR]

In this paper, low Ni-doped Co 3 O 4 (Ni: 2 wt%, 4 wt%, 6 wt% and 8 wt%) porous nanoplates are synthesized by hydrothermal method and annealing treatment. For the low Ni-doped Co 3 O 4 , X-ray diffraction (XRD) and Raman data show that the Ni ions are successfully incorporated into the Co 3 O 4 lattices. Electrochemical measurements indicate that Co 3 O 4 with low amount of Ni doping possesses remarkably enhanced activity for oxygen evolution reaction (OER) and hydrogen evolution reaction (HER) in alkaline media. And especially, 4 wt% Ni-doped Co 3 O 4 possesses the most efficient activity with an overpotential of 240 mV at the current density of 10 mA cm−2 for OER and 120 mV for HER in 1 M KOH than the pure Co 3 O 4 and other Ni-doped Co 3 O 4 samples. Our study suggests that the low doping would have a great potential in rational design of spinel oxides toward highly efficient electrocatalysis. • The Ni-doped Co 3 O 4 porous nanoplates are successfully synthesized by hydrothermal method and annealing treatment. • This is the first report of low-doped Ni-doped Co 3 O 4 porous nanoplates for both OER and HER in alkaline media. • The 4 wt % Ni-doped Co 3 O 4 possesses the most efficient activity than the pure Co 3 O 4 and other Ni-doped Co 3 O 4 samples. [ABSTRACT FROM AUTHOR]

To investigate the structure and immunomodulatory activity of polysaccharide from Solanum muricatum, a novel acid polysaccharide named SMP-3a was purified from Solanum muricatum pulp through DEAE-52 cellulose column and Sephadex G-200 chromatography. Monosaccharide composition analysis showed that SMP-3a was mainly composed of rhamnose, arabinose, galactose, and galacturonic acid with the molar ratio of 1.09:2.64:1.54:1. The average molecular weight was found to be 227 kDa by high performance gel permeation chromatography (HPGPC). Thermal studies revealed the SMP-3a was a thermally stable polymer. Based on the results of methylation and NMR analysis, the backbone chain of SMP-3a was composed of →2)-α-l-Rhap-(1→, →4)-α-d-GalpA-(1→ and →4)-α-d-Galp-(1→. The side chain was consisted of α-l-Araf-(1→ and →5)-α-l-Araf-(1→. Immunomodulatory assay indicated that SMP-3a could significantly promote the proliferation of macrophages and stimulate the secretion of cytokines, including TNF-α, IL-1β, and IL-6. Our results suggested that SMP-3a could be used as a novel potential immunomodulatory agent in functional food. [ABSTRACT FROM AUTHOR]

Microcystinase (MlrA) catalyzes the first and most important biodegradation step of hepatotoxic microcystin-LR (MC-LR) produced and released from cyanobacterial cells, and the underlying catalytic mechanism is not completely understood yet. MlrA was postulated previously to be a metalloprotease with an active site of H260AIH263NE265, a variant of the common metal-binding motif of HEXXH. Through comparison with representative modes in HEXXH-containing metalloproteases, molecular dynamics simulation, homology modeling, and docking, the active sites of MlrA involved in the MC-LR biodegradation by Sphingomonas sp. USTB-05 were predicted. Site-directed mutants of MlrA were constructed for verification then. The results show that MlrA is likely not a metalloprotease, but a glutamate protease belonging to type II CAAX prenyl endopeptidases. Combined with the biodegradation of MC-LR by MlrA and its mutants, a complete enzymatic mechanism for MC-LR biodegradation by MlrA is proposed: Glu172 and His205 activate a water molecule facilitating a nucleophilic attack on the Adda-Arg peptide bond of MC-LR; Trp176 and Trp201 contact the carboxylate side chain of Glu172and, by raising its p K a potentially, accelerate the reaction rates; His260 and Asn264 (located in the previous postulated active center of H260AIH263NE265) function as an oxyanion hole to stabilize the transition states. This study reveals the enzymatic mechanism of MlrA for catalyzing MC-LR in both the representative modes and the experiments of site-directed mutagenesis. Image 1 • Microcystinase (MlrA) was predicted belonging to type II CAAX prenyl endopeptidases. • E172, H205, H260, and N264 are critical residues responsible for MlrA activity. • Homology modeling of MlrA was verified positively by site-directed mutagenesis. [ABSTRACT FROM AUTHOR]

Biodegradation is efficient for removing cyanobacterial toxins, such as microcystins (MCs) and nodularin (NOD). However, not all the microbial strains with the microcystin-biodegrading enzymes MlrA and MlrC could biodegrade NOD. Studies on genes and enzymes for biodegrading NOD can reveal the function and the biodegradation pathway of NOD. Based on successful cloning and expression of the USTB-05-A and USTB-05-C genes from Sphingopyxis sp. USTB-05, which are responsible for the biodegradation of MCs, the pathway for biodegrading NOD by these two enzymes was investigated in this study. The findings showed that the enzyme USTB-05-A converted cyclic NOD (m/z 825.4516) into its linear type as the first product by hydrolyzing the arginine and Adda peptide bond, and that USTB-05-C cut off the Adda and glutamic acid peptide bond of linearized NOD (m/z 843.4616) and produced dimeric Adda (m/z 663.4377) as the second product. Further, based on the homology modeling of enzyme USTB-05-A, site-directed mutants of USTB-05-A were constructed and seven crucial sites for enzyme USTB-05-A activity were found. A complete enzymatic mechanism for NOD biodegradation by USTB-05-A in the first step was proposed: glutamic acid 172 and histidine 205 activate a water molecule facilitating a nucleophilic attack on the arginine and Adda peptide bond of NOD; tryptophan 176 and tryptophan 201 contact the carboxylate side chain of glutamic acid 172 and accelerate the reaction rates; and histidine 260 and asparagine 264 function as an oxyanion hole to stabilize the transition states. [ABSTRACT FROM AUTHOR]

For the first time, waste-seashell-derived CaO catalysts were used as high-performance solid base catalysts for cyclopentanone self-condensation, which is an important reaction in bio-jet fuel or perfume precursor synthesis. Among the investigated seashell-derived catalysts, Scapharca Broughtonii-derived CaO catalyst (S-shell-750) exhibited the highest dimer yield (92.1%), which was comparable with commercial CaO (88.2%). The activity sequence of different catalysts was consistent with the CaO purity sequence and contact angle sequence. X-ray diffraction (XRD) results showed that CaCO3 in waste shell were completely converted to CaO after calcination at 750 °C or above for 4 h. CO2 temperature-programmed desorption (CO2-TPD) results indicate that both the amount and strength of base sites increase significantly when the calcination temperature climbs to 750 °C. Therefore, we can attribute the excellent performance of S-shell-750/850/950 catalysts to the higher CaO content, relatively low hydrophilicity, and stronger acidity and basicity of this catalyst. This study developed a new route for waste shell utilization in bio-derived ketone aldol condensation. [ABSTRACT FROM AUTHOR]

Simple Summary: Clustered regularly interspaced short palindromic repeats (CRISPR) ribonucleoprotein (RNP)-mediated precise genome editing can modify a specific targeted gene to establish cell models and improve animal traits, thus playing a significant role in animal breeding. However, the efficiency of precise gene editing is low, which limits its widespread use. To overcome this problem in porcine cells, we used small molecules to improve the efficiency of CRISPR RNP-mediated precise genome editing in porcine fetal fibroblasts (PFFs). We demonstrated that a single small molecule including L-189, NU7441, SCR7, L755507, RS-1, and Brefeldin A increased the efficiency of homology-directed repair (HDR) during precise gene editing in PFFs, respectively. These results provided methodological support for the establishment of an efficient and precise gene editing system in pigs. The aim of this study was to verify whether small molecules can improve the efficiency of precision gene editing using clustered regularly interspaced short palindromic repeats (CRISPR) ribonucleoprotein (RNP) in porcine cells. CRISPR associated 9 (Cas9) protein, small guide RNA (sgRNA), phosphorothioate-modified single-stranded oligonucleotides (ssODN), and different small molecules were used to generate precise nucleotide substitutions at the insulin (INS) gene by homology-directed repair (HDR) in porcine fetal fibroblasts (PFFs). These components were introduced into PFFs via electroporation, followed by polymerase chain reaction (PCR) for the target site. All samples were sequenced and analyzed, and the efficiencies of different small molecules at the target site were compared. The results showed that the optimal concentrations of the small molecules, including L-189, NU7441, SCR7, L755507, RS-1, and Brefeldin A, for in vitro-cultured PFFs' viability were determined. Compared with the control group, the single small molecules including L-189, NU7441, SCR7, L755507, RS-1, and Brefeldin A increased the efficiency of HDR-mediated precise gene editing from 1.71-fold to 2.28-fold, respectively. There are no benefits in using the combination of two small molecules, since none of the combinations improved the precise gene editing efficiency compared to single small molecules. In conclusion, these results suggested that a single small molecule can increase the efficiency of CRISPR RNP-mediated precise gene editing in porcine cells. [ABSTRACT FROM AUTHOR]

Background: Fluvoxamine is one of the selective serotonin reuptake inhibitors (SSRIs) that are regarded as the first-line drugs to manage mental disorders. It has been also recognized with the potential to treat inflammatory diseases and viral infection. However, the effect of fluvoxamine on autoimmune diseases, particularly type 1 diabetes (T1D) and the related cellular and molecular mechanisms, are yet to be addressed. Method: Herein in this report, we treated NOD mice with fluvoxamine for 2 weeks starting from 10-week of age to dissect the impact of fluvoxamine on the prevention of type 1 diabetes. We compared the differences of immune cells between 12-week-old control and fluvoxamine-treated mice by flow cytometry analysis. To study the mechanism involved, we extensively examined the characteristics of CD4+ T cells with fluvoxamine stimulation using RNA-seq analysis, real-time PCR, Western blot, and seahorse assay. Furthermore, we investigated the relevance of our data to human autoimmune diabetes. Result: Fluvoxamine not only delayed T1D onset, but also decreased T1D incidence. Moreover, fluvoxamine-treated NOD mice showed significantly attenuated insulitis coupled with well-preserved β cell function, and decreased Th1 and Th17 cells in the peripheral blood, pancreatic lymph nodes (PLNs), and spleen. Mechanistic studies revealed that fluvoxamine downregulated glycolytic process by inhibiting phosphatidylinositol 3-kinase (PI3K)-AKT signaling, by which it restrained effector T (Teff) cell differentiation and production of proinflammatory cytokines. Conclusion: Collectively, our study supports that fluvoxamine could be a viable therapeutic drug against autoimmunity in T1D setting. [ABSTRACT FROM AUTHOR]

Simple Summary: This study investigated the developmental differences between in vivo-developed (IVV) and in vitro embryos (in vitro fertilization (IVF) and parthenogenetic activation (PA)) in pigs using single-cell RNA sequencing data from the oocyte to the 8-cell stages. Findings show that in vitro embryos have more similar developmental trajectories and lower gene diversity, especially PA, compared to IVV. Significant variations were observed in maternal mRNA, influencing mRNA splicing, energy metabolism, and chromatin remodeling, where key genes like SMARCB1 and HDAC1 (in vivo) and SIRT1 and EZH2 (in vitro) might be playing crucial roles. Despite similar ZGA timings across embryo types, IVV embryos exhibited more upregulated genes, particularly during major ZGA, and global epigenetic modification differences were evident from the oocyte stage and continued to expand during minor ZGA. They also uniquely upregulated genes linked to mitochondrial function, ATP synthesis, and oxidative phosphorylation. A notable difference in mRNA degradation between in vivo and in vitro embryos was observed during major ZGA, and the timely decay of maternal mRna in IVV except in in vitro embryos was related to phosphatase activity and cell junctions. The study also highlighted the higher expression of mitochondrially encoded genes in in vitro embryos, though nucleosome occupancy and ATP8 expression were higher in IVV. In vitro-fertilized (IVF) and parthenogenetically activated (PA) embryos, key to genetic engineering, face more developmental challenges than in vivo-developed embryos (IVV). We analyzed single-cell RNA-seq data from the oocyte to eight-cell stages in IVV, IVF, and PA porcine embryos, focusing on developmental differences during early zygotic genome activation (ZGA), a vital stage for embryonic development. (1) Our findings reveal that in vitro embryos (IVF and PA) exhibit more similar developmental trajectories compared to IVV embryos, with PA embryos showing the least gene diversity at each stage. (2) Significant differences in maternal mRNA, particularly affecting mRNA splicing, energy metabolism, and chromatin remodeling, were observed. Key genes like SMARCB1 (in vivo) and SIRT1 (in vitro) played major roles, with HDAC1 (in vivo) and EZH2 (in vitro) likely central in their complexes. (3) Across different types of embryos, there was minimal overlap in gene upregulation during ZGA, with IVV embryos demonstrating more pronounced upregulation. During minor ZGA, global epigenetic modification patterns diverged and expanded further. Specifically, in IVV, genes, especially those linked to H4 acetylation and H2 ubiquitination, were more actively regulated compared to PA embryos, which showed an increase in H3 methylation. Additionally, both types displayed a distinction in DNA methylation. During major ZGA, IVV distinctively upregulated genes related to mitochondrial regulation, ATP synthesis, and oxidative phosphorylation. (4) Furthermore, disparities in mRNA degradation-related genes between in vivo and in vitro embryos were more pronounced during major ZGA. In IVV, there was significant maternal mRNA degradation. Maternal genes regulating phosphatase activity and cell junctions, highly expressed in both in vivo and in vitro embryos, were degraded in IVV in a timely manner but not in in vitro embryos. (5) Our analysis also highlighted a higher expression of many mitochondrially encoded genes in in vitro embryos, yet their nucleosome occupancy and the ATP8 expression were notably higher in IVV. [ABSTRACT FROM AUTHOR]

Background: Gastric cancer at different locations has distinct prognoses and biological behaviors, but the specific mechanism is unclear. Methods: Non-targeted metabolomics was performed to examine the differential metabolite phenotypes that may be associated with the effects of tumor location on the prognosis of gastric cancer. And silencing of the rate-limiting enzyme to evaluate the effect of abnormal changes in metabolic pathway on the functional biological assays of gastric cancer cells HGC-27 and MKN28. Results: In a retrospective study of 94 gastric cancer patients, the average survival time of patients with gastric cancer in the middle third of the stomach was significantly lower than that of patients with gastric cancer in other locations (p < 0.05). The middle third location was also found to be an independent risk factor for poor prognosis (HR = 2.723, 95%CI 1.334–5.520), which was closely associated with larger tumors in this location. Non-targeted metabolomic analysis showed that the differential metabolites affected 16 signaling pathways including arginine synthesis, retrograde endocannabinoid signaling, arginine biosynthesis, and alanine and aspartate and glutamate metabolism between gastric cancer and normal tissue, as well as between tumors located in the middle third of the stomach and other locations. Argininosuccinate synthetase 1 (ASS1), the rate-limiting enzyme of the arginine biosynthesis pathway, catalyzes the production of argininosuccinic acid. Here, knockdown of ASS1 significantly inhibited the proliferation, colony formation, and migration/invasion of gastric cancer cells, and promoted apoptosis. Conclusions: Our study suggests that abnormal arginine synthesis may lead to larger tumor size and worse prognosis in gastric cancer located in the middle third position of the stomach. These findings may provide the basis for the stratification and targeted treatment of gastric cancer in different locations. [ABSTRACT FROM AUTHOR]

Purpose: Typically, IgA nephropathy is a slowly progressive type of glomerulonephritis. High-grade proteinuria and hypertension are predictors of reduced kidney function. However, we found some normotensive patients with mild proteinuria could exhibit impaired renal function at the time of IgAN diagnosis. We therefore conduct a study to highlight the occurrence of these cases and to define their clinical characteristics and outcomes. Methods: The clinical, laboratory, pathological manifestations and outcomes of these IgAN patients were collected and were compared with normotensive IgA nephropathy patients with mild proteinuria and normal renal function. Patients were analyzed according to different pathological characteristics. Survival curves were constructed according to the Kaplan–Meier method. Results: Of all normotensive IgA nephropathy patients with mild proteinuria, 108 (10.1%) patients had impaired renal function. Ischemic sclerosis (79 patients) and fibrous crescent (25 patients) were the main pathological characteristics. Macroscopic hematuria (1.3%), prodromal infection (13.9%) and high serum IgA (11.4%) were significantly lower prevalences, but only proteinuria (26.6%) was more common in ischemic sclerosis group patients. Only hematuria were not found in ischemic sclerosis group and crescent group patients. The median follow-up were about 5 years. Patients in crescent group had a poor outcome compared with patients in ischemic sclerosis group. Conclusions: Some normotensive IgA nephropathy patients with mild proteinuria had impaired renal function at diagnosis. Ischemic sclerosis and fibrous crescent were the main pathological features in these patients. Patients in the crescent group had a worse outcome than patients in the ischemic sclerosis group. [ABSTRACT FROM AUTHOR]

Both inosine and guanosine are precursors of uric acid that may cause the diseases of hyperuricemia and gout in humans. Here, a promising bacterial strain for efficiently biodegrading both inosine and guanosine was successfully isolated from a healthy human intestine and identified as Bacillus paranthracis YD01 with 16S rRNA analysis. An initial amount of 49.6 mg·L−1 of inosine or 49.9 mg·L−1 of guanosine was completely removed by YD01 within 12 h, which showed that YD01 had a strong ability to biodegrade inosine and guanosine. Furthermore, the initial amount of 49.2 mg·L−1 of inosine or 49.5 mg·L−1 of guanosine was totally catalyzed by the intracellular crude enzymes of YD01 within 6 h, and the initial inosine amount of 49.6 mg·L−1 or guanosine of 49.7 mg·L−1 was biodegraded by the extracellular crude enzymes of YD01 within 9 h. Illumina Hiseq sequencing and database gene annotation were used to elucidate the genomic characteristics of B. paranthracis YD01. Purine nucleoside phosphorylase, encoded by gene 1785, gene 3933, and gene 4403, was found in the KEEG database, which played a crucial role in the biodegradation of inosine and guanosine. The results of this study provide valuable insights into the mechanisms for biodegrading inosine and guanosine using B. paranthracis YD01. [ABSTRACT FROM AUTHOR]

Extensive use of phthalic acid esters (PAEs) as plasticizer causes diffusion into the environment, which posed a great threat to mankind. It was reported that Comamonas sp. was a potentially robust aromatic biodegrader. Although the biodegradation of several PAEs by Comamonas sp. was studies, the comprehensive genomic analysis of Comamonas sp. was few reported. In the present study, one promising bacterial strain for biodegrading diethyl phthalate (DEP) was successfully isolated from activated sludge and characterized as Comamonas sp. USTBZA1 based on the 16S rRNA sequence analysis. The results showed that pH 7.5, 30 °C and inoculum volume ratio of 6% were optimal for biodegradation. Initial DEP of 50 mg/L could be completely biodegrade by strain USTBZA1 within 24 h which conformed to the Gompertz model. Based on the Q-TOF LC/MS analysis, monoethyl phthalate (MEP) and phthalic acid (PA) were identified as the metabolic products of DEP biodegradation by USTBZA1. Furthermore, the whole genome of Comamonas sp. USTBZA1 was analyzed to clarify the molecular mechanism for PAEs biodegradation by USTBZA1. There were 3 and 41 genes encoding esterase/arylesterase and hydrolase, respectively, and two genes regions (pht34512 and pht4253) were responsible for the conversion of PA to protocatechuate (PCA), and two genes regions (ligCBAIKJ) were involved in PCA metabolism in USTBZA1. These results substantiated that Comamonas sp. USTBZA1 has potential application in the DEP bioremediation. [ABSTRACT FROM AUTHOR]