Effect of sanxan as novel natural gel modifier on the physicochemical and structural properties of microbial transglutaminase-induced mung bean protein isolate gels.

Mung bean protein isolate (MBPI) has attracted much attention as an emerging plant protein. However, its application was limited by the poor gelling characteristics. Thus, the effect of sanxan (SAN) on the gelling behavior of MBPI under microbial transglutaminase (MTG)-induced condition were explored in this study. The results demonstrated that SAN remarkably enhanced the storage modulus, water-holding capacity and mechanical strength. Furthermore, SAN changed the microstructure of MBPI gels to become more dense and ordered. The results of zeta potential indicated the electrostatic interactions existed between SAN and MBPI. The incorporation of SAN altered the secondary structure and molecular conformation of MBPI, and hydrophobic interactions and hydrogen bonding were necessary to maintain the network structure. Additionally, in vitro digestion simulation results exhibited that SAN remarkably improved the capability of MBPI gels to deliver bioactive substances. These findings provided a practical strategy to use natural SAN to improve legume protein gels.

The BTB-BACK-TAZ domain protein MdBT2 reduces drought resistance by weakening the positive regulatory effect of MdHDZ27 on apple drought tolerance via ubiquitination.

Drought stress is one of the dominating challenges to the growth and productivity in crop plants. Elucidating the molecular mechanisms of plants responses to drought stress is fundamental to improve fruit quality. However, such molecular mechanisms are poorly understood in apple (Malus domestica Borkh.). In this study, we explored that the BTB-BACK-TAZ protein, MdBT2, negatively modulates the drought tolerance of apple plantlets. Moreover, we identified a novel Homeodomain-leucine zipper (HD-Zip) transcription factor, MdHDZ27, using a yeast two-hybrid (Y2H) screen with MdBT2 as the bait. Overexpression of MdHDZ27 in apple plantlets, calli, and tomato plantlets enhanced their drought tolerance by promoting the expression of drought tolerance-related genes [responsive to dehydration 29A (MdRD29A) and MdRD29B]. Biochemical analyses demonstrated that MdHDZ27 directly binds to and activates the promoters of MdRD29A and MdRD29B. Furthermore, in vitro and in vivo assays indicate that MdBT2 interacts with and ubiquitinates MdHDZ27, via the ubiquitin/26S proteasome pathway. This ubiquitination results in the degradation of MdHDZ27 and weakens the transcriptional activation of MdHDZ27 on MdRD29A and MdRD29B. Finally, a series of transgenic analyses in apple plantlets further clarified the role of the relationship between MdBT2 and MdHDZ27, as well as the effect of their interaction on drought resistance in apple plantlets. Collectively, our findings reveal a novel mechanism by which the MdBT2-MdHDZ27 regulatory module controls drought tolerance, which is of great significance for enhancing the drought resistance of apple and other plants.

Reversal and resumption of anticoagulants in patients with anticoagulant-associated intracerebral hemorrhage.

The use of anticoagulants has become more frequent due to the progressive aging population and increased thromboembolic events. Consequently, the proportion of anticoagulant-associated intracerebral hemorrhage (AAICH) in stroke patients is gradually increasing. Compared with intracerebral hemorrhage (ICH) patients without coagulopathy, patients with AAICH may have larger hematomas, worse prognoses, and higher mortality. Given the need for anticoagulant reversal and resumption, the management of AAICH differs from that of conventional medical or surgical treatments for ICH, and it is more specific. Understanding the pharmacology of anticoagulants and identifying agents that can reverse their effects in the early stages are crucial for treating life-threatening AAICH. When patients transition beyond the acute phase and their vital signs stabilize, it is important to consider resuming anticoagulants at the right time to prevent the occurrence of further thromboembolism. However, the timing and strategy for reversing and resuming anticoagulants are still in a dilemma. Herein, we summarize the important clinical studies, reviews, and related guidelines published in the past few years that focus on the reversal and resumption of anticoagulants in AAICH patients to help implement decisive diagnosis and treatment strategies in the clinical setting.

Artificial Intelligence-Assisted Optimization of Antipigmentation Tyrosinase Inhibitors: De Novo Molecular Generation Based on a Low Activity Lead Compound.

Artificial intelligence (AI) de novo molecular generation is a highly promising strategy in the drug discovery, with deep reinforcement learning (RL) models emerging as powerful tools. This study introduces a fragment-by-fragment growth RL forward molecular generation and optimization strategy based on a low activity lead compound. This process integrates fragment growth-based reaction templates, while target docking and drug-likeness prediction were simultaneously performed. This comprehensive approach considers molecular similarity, internal diversity, synthesizability, and effectiveness, thereby enhancing the quality and efficiency of molecular generation. Finally, a series of tyrosinase inhibitors were generated and synthesized. Most compounds exhibited more improved activity than lead, with an optimal candidate compound surpassing the effects of kojic acid and demonstrating significant antipigmentation activity in a zebrafish model. Furthermore, metabolic stability studies indicated susceptibility to hepatic metabolism. The proposed AI structural optimization strategies will play a promising role in accelerating the drug discovery and improving traditional efficiency.

RotatedStomataNet: a deep rotated object detection network for directional stomata phenotype analysis.

KEY MESSAGE: Innovatively, we consider stomatal detection as rotated object detection and provide an end-to-end, batch, rotated, real-time stomatal density and aperture size intelligent detection and identification system, RotatedeStomataNet. Stomata acts as a pathway for air and water vapor in the course of respiration, transpiration, and other gas metabolism, so the stomata phenotype is important for plant growth and development. Intelligent detection of high-throughput stoma is a key issue. Nevertheless, currently available methods usually suffer from detection errors or cumbersome operations when facing densely and unevenly arranged stomata. The proposed RotatedStomataNet innovatively regards stomata detection as rotated object detection, enabling an end-to-end, real-time, and intelligent phenotype analysis of stomata and apertures. The system is constructed based on the Arabidopsis and maize stomatal data sets acquired destructively, and the maize stomatal data set acquired in a non-destructive way, enabling the one-stop automatic collection of phenotypic, such as the location, density, length, and width of stomata and apertures without step-by-step operations. The accuracy of this system to acquire stomata and apertures has been well demonstrated in monocotyledon and dicotyledon, such as Arabidopsis, soybean, wheat, and maize. The experimental results that the prediction results of the method are consistent with those of manual labeling. The test sets, the system code, and their usage are also given ( https://github.com/AITAhenu/RotatedStomataNet ).

Assessment of bidirectional relationships between autoimmune diseases and primary ovarian insufficiency: insights from a bidirectional two-sample Mendelian randomization analysis.

PURPOSE: The simultaneous occurrence of primary ovarian insufficiency (POI) and autoimmune diseases has been noted and debated in some epidemiological research. This bidirectional two-sample Mendelian randomization (MR) study aimed to investigate the causal relationships between autoimmune diseases and POI. METHODS: We obtained summary-level data for ten autoimmune diseases and POI from published large-scale genome-wide association studies and the FinnGen consortium of European ancestry. A series of filtering steps was performed to discern independent genetic variants. Causal estimates were mainly calculated by the inverse variance weighting method and verified through multiple sensitivity analyses. RESULTS: Of the ten autoimmune diseases, genetically predicted Addison's disease (odds ratio [OR] = 1.26, 95% confidence interval [CI]: 1.09-1.47, P = 0.003) and systemic lupus erythematosus (OR = 1.12, 95% CI 1.02-1.24, P = 0.021) were associated with an increased risk of POI, and sensitivity analyses confirmed the robustness of the results. In addition, there were weak associations between liability to POI and elevated risks of type 1 diabetes (OR = 1.05, 95% CI 1.00-1.10, P = 0.046) and autoimmune thyroid disease (OR = 1.03, 95% CI 1.01-1.05, P = 0.015). CONCLUSION: This study revealed that Addison's disease and systemic lupus erythematosus are potential risk factors for POI, underscoring the necessity to consider the impact of autoimmune factors in the diagnosis and treatment of POI.

Pharmacokinetics, tissue distribution, and subacute toxicity of oral carrageenan in mice.

Carrageenan (CGN) is a typical sulfated polysaccharide widely applied in the food and pharmaceutical industries. Its in vivo behavior plays vital roles in understanding structural and biological functional relationships. The lack of UV chromophores in highly sulfated polysaccharides presents a challenge for their in vivo behavior studies. Therefore, this study aimed to develop a fast and effective quantitative fluorescence method for investigating the pharmacokinetics and tissue distribution of CGN. Fluorescence isothiocyanate labeling of CGN (FCGN) and microplate reader-based measurements were developed and validated to study its pharmacokinetics. These results showed that the FCGN concentration peaked at 3 h, the mean residence time was 36.6 h, and the clearance rate was 0.1 L/h/kg. Most of the FCGN was excreted in the feces, while 9.2 % was excreted in the urine, suggesting absorption and metabolism. The pharmacokinetic parameters indicated that the FCGN was absorbed quickly, eliminated slowly, and could remain in the body for a sustained profile. Moreover, ex vivo imaging and quantification of FCGN in tissues revealed that FCGN accumulated in the liver and kidney. Furthermore, oral administration of CGN or KOs for 14 days led to changes in liver and kidney indices. Histological analysis of significant organs revealed hepatocyte necrosis in the liver, renal tubular vacuolization in the kidney, and incomplete colonic epithelial cells. The KOs had a more significant effect on inflammatory cell infiltration than did CGNs. These in vivo findings laid the foundation for the study and application of CGN in food and pharmaceutical applications.

Directionally Illuminated Autostereoscopy with Seamless Viewpoints for Multi-Viewers.

Autostereoscopy is usually perceived at finite viewpoints that result from the separated pixel array of a display system. With directionally illuminated autostereoscopy, the separation of the illumination channel from the image channel provides extra flexibility in optimizing the performance of autostereoscopy. This work demonstrates that by taking advantage of illumination freedom, seamless viewpoints in the sweet viewing region, where the ghosting does not cause significant discomfort, are realized. This realization is based on illuminating the screen with a polyline array of light emitting diodes (LEDs), and continuous viewpoints are generated through independent variation in the radiance of each individual LED column. This new method is implemented in the directionally illuminated display for both single and multiple viewers, proving its effectiveness as a valuable technique for achieving a high-quality and high-resolution autostereoscopic display with seamless viewpoints.

Eudragit S100 coated nanodiamond-based nanoparticles as an oral chemo-photothermal delivery system for local treatment of colon cancer.

Oral colonic nano-drug delivery system has received more and more attention in the treatment of colon cancer due to local precision treatment and reduction of drug system distribution. However, the complex and harsh gastrointestinal environment and the retention of nanoparticles in the colon limit its development. To this end, we designed Eudragit S100 (ES) coated nanoparticles (ES@PND-PEG-TPP/DOX). Polydopamine coated nanodiamond (PND) was modified with amino-functionalized polyethylene glycol (NH2-PEG-NH2) and triphenylphosphine (TPP) successively. Due to the high specific surface area of PND, it can efficiently load the model drug doxorubicin hydrochloride (DOX). In addition, PND also has high photothermal conversion efficiency, generating heat to kill cancer cells under near infrared (NIR) laser, realizing the combination of chemotherapy and photothermal therapy (CT-PTT). TPP modification enhanced nanoparticle uptake by colon cancer cells and prolonged preparations retention time at the colon. ES shell protected the drug from being destroyed and prevented the nanoparticles from sticking to the small intestine. Ex vitro fluorescence imaging showed that TPP modification can enhance the residence time of nanoparticles in the colon. In vivo pharmacodynamics demonstrated that CT-PTT group has the greatest inhibitory effect on tumor growth, which means that the nanocarrier has potential clinical value in the in-situ treatment of colon cancer.

Two sex pheromone receptors for sexual communication in the American cockroach.

Volatile sex pheromones are vital for sexual communication between males and females. Females of the American cockroach, Periplaneta americana, produce and emit two sex pheromone components, periplanone-A (PA) and periplanone-B (PB). Although PB is the major sex attractant and can attract males, how it interacts with PA in regulating sexual behaviors is still unknown. In this study, we found that in male cockroaches, PA counteracted PB attraction. We identified two odorant receptors (ORs), OR53 and OR100, as PB/PA and PA receptors, respectively. OR53 and OR100 were predominantly expressed in the antennae of sexually mature males, and their expression levels were regulated by the sex differentiation pathway and nutrition-responsive signals. Cellular localization of OR53 and OR100 in male antennae further revealed that two types of sensilla coordinate a complex two-pheromone-two-receptor pathway in regulating cockroach sexual behaviors. These findings indicate distinct functions of the two sex pheromone components, identify their receptors and possible regulatory mechanisms underlying the male-specific and age-dependent sexual behaviors, and can guide novel strategies for pest management.

A Review of Capacity Decay Studies of All-vanadium Redox Flow Batteries: Mechanism and State Estimation.

As a promising large-scale energy storage technology, all-vanadium redox flow battery has garnered considerable attention. However, the issue of capacity decay significantly hinders its further development, and thus the problem remains to be systematically sorted out and further explored. This review provides comprehensive insights into the multiple factors contributing to capacity decay, encompassing vanadium cross-over, self-discharge reactions, water molecules migration, gas evolution reactions, and vanadium precipitation. Subsequently, it analyzes the impact of various battery parameters on capacity. Based on this foundation, the article expounds upon the significance of battery internal state estimation technology. Additionally, the review also summarizes domestic and international mathematical models utilized for simulating capacity decay, serving as a valuable reference for future research endeavors. Finally, through the comparison of traditional experimental methods and mathematical modeling methods, this article offers effective guidance for the future development direction of battery state monitoring. This review generally overview the problems related to the capacity attenuation of all-vanadium flow batteries, which is of great significance for understanding the mechanism behind capacity decay and state monitoring technology of all-vanadium redox flow battery.

An intelligent DNA nanodevice for precision thrombolysis.

Thrombosis is a leading global cause of death, in part due to the low efficacy of thrombolytic therapy. Here, we describe a method for precise delivery and accurate dosing of tissue plasminogen activator (tPA) using an intelligent DNA nanodevice. We use DNA origami to integrate DNA nanosheets with predesigned tPA binding sites and thrombin-responsive DNA fasteners. The fastener is an interlocking DNA triplex structure that acts as a thrombin recognizer, threshold controller and opening switch. When loaded with tPA and intravenously administrated in vivo, these DNA nanodevices rapidly target the site of thrombosis, track the circulating microemboli and expose the active tPA only when the concentration of thrombin exceeds a threshold. We demonstrate their improved therapeutic efficacy in ischaemic stroke and pulmonary embolism models, supporting the potential of these nanodevices to provide accurate tPA dosing for the treatment of different thromboses.

Sequence-dependent material properties of biomolecular condensates and their relation to dilute phase conformations.

Material properties of phase-separated biomolecular condensates, enriched with disordered proteins, dictate many cellular functions. Contrary to the progress made in understanding the sequence-dependent phase separation of proteins, little is known about the sequence determinants of condensate material properties. Using the hydropathy scale and Martini models, we computationally decipher these relationships for charge-rich disordered protein condensates. Our computations yield dynamical, rheological, and interfacial properties of condensates that are quantitatively comparable with experimentally characterized condensates. Interestingly, we find that the material properties of model and natural proteins respond similarly to charge segregation, despite different sequence compositions. Molecular interactions within the condensates closely resemble those within the single-chain ensembles. Consequently, the material properties strongly correlate with molecular contact dynamics and single-chain structural properties. We demonstrate the potential to harness the sequence characteristics of disordered proteins for predicting and engineering the material properties of functional condensates, with insights from the dilute phase properties.

The Flavor Characteristics, Antioxidant Capability, and Storage Year Discrimination Based on Backpropagation Neural Network of Organic Green Tea (Camellia sinensis) during Long-Term Storage.

The storage period of tea is a major factor affecting tea quality. However, the effect of storage years on the non-volatile major functional components and quality of green tea remains largely unknown. In this study, a comparative analysis of organic green teas with varying storage years (1-16 years) was conducted by quantifying 47 functional components, using electronic tongue and chromatic aberration technology, alongside an evaluation of antioxidative capacity. The results indicated a significant negative correlation between the storage years and levels of tea polyphenols, total amino acids, soluble sugars, two phenolic acids, four flavonols, three tea pigments, umami amino acids, and sweet amino acids. The multivariate statistical analysis revealed that 10 functional components were identified as effective in distinguishing organic green teas with different storage years. Electronic tongue technology categorized organic green teas with different storage years into three classes. The backpropagation neural network (BPNN) analysis demonstrated that the classification predictive ability of the model based on the electronic tongue was superior to the one based on color difference values and 10 functional components. The combined analysis of antioxidative activity and functional components suggested that organic green teas with shorter storage periods exhibited stronger abilities to suppress superoxide anion radicals and hydroxyl radicals and reduce iron ions due to the higher content of eight components. Long-term-stored organic green teas, with a higher content of substances like L-serine and theabrownins, demonstrated stronger antioxidative capabilities in clearing both lipid-soluble and water-soluble free radicals. Therefore, this study provided a theoretical basis for the quality assessment of green tea and prediction of green tea storage periods.

Design of p-n heterojunction between CoWO4 and Zn-defective Zn0.3Cd0.7S for efficient photocatalytic H2 evolution.

To enhance the efficiency of photocatalytic H2 evolution, numerous methods are employed by increasing the utilization of photogenerated charge carriers (PCCs), including catalyst design, defect regulation, and selection of suitable H+ resources. Using self-assembly method, CoWO4/ZnxCd1-xS with p-n heterojunction was synthesized. Although CoWO4 (CW) cannot produce H2 under visible light irradiation, it can provide photogenerated electrons (e-) to Zn0.3Cd0.7S (ZCS), and largely increase the photocatalytic activity of ZCS. The optimal CW/ZCS composite can reach 15.58 mmol·g-1·h-1, which is 45.8 and 24.3 times higher than the values of the pure CdS and ZCS, respectively. The largely enhanced photocatalytic H2 production is attributed to the Zn vacancies (VZn), p-n heterojunction, and p-chlorobenzyl alcohol (Cl-PhCH2OH) as the H+ source of H2 production. VZn on the ZCS surface as the capture center of photogenerated holes (h+), can regulate the carrier distribution, which results in more photogenerated e- and less generated h+. The combination of p-n heterojunction and VZn can enhance the separation and transfer efficiency of PCCs, and effectively inhibit the recombination of charge carriers. To further improve the utilization rate of PCCs, the photocatalytic H2 evolution is proceeded by Cl-PhCH2OH oxidation in N,N-dimethylformamide solution, with 4-chlorobenzaldehyde (Cl-PhCHO) generated. The separated photogenerated e- and h+ both participated in the redox reaction of H+ reduction and Cl-PhCH2OH oxidation, considering that the amount of H2 and Cl-PhCHO products are close to 1:1. This work not only facilitates the separation and transfer of PCCs, but also provides directions for the design of efficient photocatalysts and H2 evolution in the organic phase.

LOC644656 promotes cisplatin resistance in cervical cancer by recruiting ZNF143 and activating the transcription of E6-AP.

Cisplatin resistance remains a persistent challenge in cervical cancer (CC) treatment. Molecular biomarkers have garnered attention for their association with cisplatin resistance in various diseases. Long non-coding RNAs (lncRNAs) exert significant influence on CC development. This study explores the role of LOC644656 in regulating cisplatin resistance in CC. Parental and cisplatin-resistant CC cells underwent cisplatin treatment. Functional assays assessed cell proliferation and apoptosis under different conditions. RNA pull-down with mass spectrometry, along with literature review, elucidated the interaction between LOC644656, ZNF143, and E6-AP. Mechanistic assays analyzed the relationship between different factors. RT-qPCR and western blot quantified RNA and protein levels, respectively. In vivo models validated E6-AP's function. Results revealed LOC644656 overexpression in cisplatin-resistant CC cells, exacerbating cell growth. LOC644656 recruited ZNF143 to activate E6-AP transcription, promoting cisplatin resistance in CC. In conclusion, LOC644656 positively modulates E6-AP expression via ZNF143-mediated transcriptional activation, contributing to cisplatin resistance in CC.

Neural network establishes co-occurrence links between transformation products of the contaminant and the soil microbiome.

It remains challenging to establish reliable links between transformation products (TPs) of contaminants and corresponding microbes. This challenge arises due to the sophisticated experimental regime required for TP discovery and the compositional nature of 16S rRNA gene amplicon sequencing and mass spectrometry datasets, which can potentially confound statistical inference. In this study, we present a new strategy by combining the use of 2H-labeled Stable Isotope-Assisted Metabolomics (2H-SIAM) with a neural network-based algorithm (i.e., MMvec) to explore links between TPs of pyrene and the soil microbiome. The links established by this novel strategy were further validated using different approaches. Briefly, a metagenomic study provided indirect evidence for the established links, while the identification of pyrene degraders from soils, and a DNA-based stable isotope probing (DNA-SIP) study offered direct evidence. The comparison among different approaches, including Pearson's and Spearman's correlations, further confirmed the superior performance of our strategy. In conclusion, we summarize the unique features of the combined use of 2H-SIAM and MMvec. This study not only addresses the challenges in linking TPs to microbes but also introduces an innovative and effective approach for such investigations. Environmental Implication: Taxonomically diverse bacteria performing successive metabolic steps of the contaminant were firstly depicted in the environmental matrix.