Elemental diet preventative effects for adverse events during chemotherapy in patients with esophageal cancer - A systematic review and meta-analysis.

The effectiveness of an elemental diet (ED) for preventing adverse events (AEs) during chemotherapy for patients with esophageal cancer (EC) remains unclear. The aim of this meta-analysis was to comprehensively assess the efficacy of ED for preventing AE in EC patients during chemotherapy. Medline (via PubMed), Embase, the Cochrane Library, and Web of Science were searched to retrieve prospective and randomized studies published before April 12, 2023. The odds ratio (OR) of each AE was calculated using Review Manger 5.4.1. The risk of bias was assessed, and a random effect model-based meta-analysis was used to analyze the available data. Four prospective and randomized studies involving 237 patients were identified after a systematic search. Regarding gastrointestinal toxicities, the findings indicated a trend toward a decrease in the risk of mucositis (OM) (OR = 0.54, 95 % CI: 0.25-1.14), constipation (OR = 0.87, 95 % CI: 0.49-1.53), and anorexia (OR = 0.99, 95 % CI: 0.32-3.05), as well as an increasing trend in the risk of diarrhea (OR = 1.48, 95 % CI: 0.79-2.79), among patients treated with ED. However, none of these reached statistical significance. For hematological toxicities, the risk of all-grade neutropenia (OR = 0.28, 95 % CI: 0.14-0.57), grade ≥ 2 leucopenia (OR = 0.43, 95 % CI: 0.22-0.84), grade ≥ 2 neutropenia (OR = 0.34, 95 % CI: 0.17-0.67), and grade ≥ 3 neutropenia (OR = 0.28, 95 % CI: 0.12-0.63) was significantly decreased. There is no firm evidence confirming the preventive effect of an ED against OM or diarrhea. However, an ED may potentially be helpful in preventing neutropenia and leucopenia.

Tunable Magnetism in Atomically Thin Itinerant Antiferromagnet with Room-Temperature Ferromagnetic Order.

Addressing the need for modulated spin configurations is crucial, as they serve as the foundational building blocks for next-generation spintronics, particularly in atomically thin structures and at room temperature. In this work, we realize intrinsic ferromagnetism in monolayer flakes and tunable ferro-/antiferromagnetism in (Fe0.56Co0.44)5GeTe2 antiferromagnets. Remarkably, the ferromagnetic ordering (≥1 L) and antiferromagnetic ordering (≥4 L) remain discernible up to room temperature. The TC (∼310 K) of the monolayer flakes sets a record high for known exfoliated monolayer van der Waals magnets. Within the framework of A-type antiferromagnetism, a notable odd-even layer-number effect at elevated temperatures (T = 150 K) is observed. Of particular interest is the strong ferromagnetic order in even-layer flakes at low temperatures. The intricate interplay among magnetic field strength, layer number, and temperature gives rise to a diverse array of phenomena, holding promise not only for new physics but also for practical applications.

Research on the function of CsMYB36 based on an effective hair root transformation system.

The hairy root induction system was used to efficiently investigate gene expression and function in plant root. Cucumber is a significant vegetable crop worldwide, with shallow roots, few lateral roots, and weak root systems, resulting in low nutrient absorption and utilization efficiency. Identifying essential genes related to root development and nutrient absorption is an effective way to improve the growth and development of cucumbers. However, genetic mechanisms underlying cucumber root development have not been explored. Here, we report a novel, rapid, effective hairy root transformation system. Compared to the in vitro cotyledon transformation method, this method shortened the time needed to obtain transgenic roots by 13 days. Furthermore, we combined this root transformation method with CRISPR/Cas9 technology and validated our system by exploring the expression and function of CsMYB36, a pivotal gene associated with root development and nutrient uptake. The hairy root transformation system established in this study provides a powerful method for rapidly identifying essential genes related to root development in cucumber and other horticultural crop species. This advancement holds promise for expediting research on root biology and molecular breeding strategies, contributing to the broader understanding and improvements crop growth and development.

Transcription factor CsMYB36 regulates fruit neck length via mediating cell expansion in cucumber.

The fruit neck is an important agronomic trait of cucumber (Cucumis sativus). However, the underlying genes and regulatory mechanisms involved in fruit neck development are poorly understood. We previously identified a cucumber yellow green peel (ygp) mutant, whose causal gene is MYB DOMAIN PROTEIN 36 (CsMYB36). This study showed that the ygp mutant exhibited a shortened fruit neck and repressed cell expansion in the fruit neck. Further functional analysis showed that CsMYB36 was also a target gene, and its expression was enriched in the fruit neck. Overexpression of CsMYB36 in the ygp mutant rescued shortened fruit necks. Furthermore, transcriptome analysis and reverse transcription quantitative polymerase chain reaction (RT-qPCR) assays revealed that CsMYB36 positively regulates the expression of an expansin-like A3 (CsEXLA3) in the fruit neck, which is essential for cell expansion. Yeast one-hybrid and dual-LUC assays revealed that CsMYB36 regulates fruit neck elongation by directly binding to the promoter of CsEXLA3. Collectively, these findings demonstrate that CsMYB36 is an important gene in the regulation of fruit neck length in cucumber plants.

MSMTSeg: Multi-Stained Multi-Tissue Segmentation of Kidney Histology Images via Generative Self-Supervised Meta-Learning Framework.

Accurately diagnosing chronic kidney disease requires pathologists to assess the structure of multiple tissues under different stains, a process that is timeconsuming and labor-intensive. Current AI-based methods for automatic structure assessment, like segmentation, often demand extensive manual annotation and focus on single stain domain. To address these challenges, we introduce MSMTSeg, a generative self-supervised meta-learning framework for multi-stained multi-tissue segmentation in renal biopsy whole slide images (WSIs). MSMTSeg incorporates multiple stain transform models for style translation of inter-stain domains, a self-supervision module for obtaining pre-trained models with the domain-specific feature representation, and a meta-learning strategy that leverages generated virtual data and pre-trained models to learn the domain-invariant feature representation across multiple stains, thereby enhancing segmentation performance. Experimental results demonstrate that MSMTSeg achieves superior and robust performance, with mDSC of 0.836 and mIoU of 0.718 for multiple tissues under different stains, using only one annotated training sample for each stain. Our ablation study confirms the effectiveness of each component, positioning MSMTSeg ahead of classic advanced segmentation networks, recent few-shot segmentation methods, and unsupervised domain adaptation methods. In conclusion, our proposed few-shot cross-domain technology offers a feasible and cost-effective solution for multi-stained renal histology segmentation, providing convenient assistance to pathologists in clinical practice. The source code and conditionally accessible data are available at https://github.com/SnowRain510/MSMTSeg.

Analysis of heterologous expression of phaCBA promotes the acetoin stress response mechanism in Bacillus subtilis using transcriptomics and metabolomics approaches.

Acetoin, a versatile platform chemical and popular food additive, poses a challenge to the biosafety strain Bacillus subtilis when produced in high concentrations due to its intrinsic toxicity. Incorporating the PHB synthesis pathway into Bacillus subtilis 168 has been shown to significantly enhance the strain's acetoin tolerance. This study aims to elucidate the molecular mechanisms underlying the response of B. subtilis 168-phaCBA to acetoin stress, employing transcriptomic and metabolomic analyses. Acetoin stress induces fatty acid degradation and disrupts amino acid synthesis. In response, B. subtilis 168-phaCBA down-regulates genes associated with flagellum assembly and bacterial chemotaxis, while up-regulating genes related to the ABC transport system encoding amino acid transport proteins. Notably, genes coding for cysteine and D-methionine transport proteins (tcyB, tcyC and metQ) and the biotin transporter protein bioY, are up-regulated, enhancing cellular tolerance. Our findings highlight that the expression of phaCBA significantly increases the ratio of long-chain unsaturated fatty acids and modulates intracellular concentrations of amino acids, including L-tryptophan, L-tyrosine, L-leucine, L-threonine, L-methionine, L-glutamic acid, L-proline, D-phenylalanine, L-arginine, and membrane fatty acids, thereby imparting acetoin tolerance. Furthermore, the supplementation with specific exogenous amino acids (L-alanine, L-proline, L-cysteine, L-arginine, L-glutamic acid, and L-isoleucine) alleviates acetoin's detrimental effects on the bacterium. Simultaneously, the introduction of phaCBA into the acetoin-producing strain BS03 addressed the issue of insufficient intracellular cofactors in the fermentation strain, resulting in the successful production of 70.14 g/L of acetoin through fed-batch fermentation. This study enhances our understanding of Bacillus's cellular response to acetoin-induced stress and provides valuable insights for the development of acetoin-resistant Bacillus strains.

Effect of propofol and sevoflurane on postoperative fatigue after laparoscopic hysterectomy.

BACKGROUND: Postoperative fatigue syndrome (POFS) is an important factor in postoperative recovery. However, the effect of anesthetic drugs on postoperative fatigue in female patients has been rarely studied. This study compared the effects of maintaining general anesthesia with propofol or sevoflurane on the incidence of POFS in patients undergoing laparoscopic hysterectomy. METHODS: This prospective, single-blind, randomized controlled trial enrolled patients scheduled for laparoscopic hysterectomy. Eligible patients were randomized into the propofol and sevoflurane groups. The primary outcome was the incidence of POFS within 30 Days, defined by a simplified identity consequence fatigue scale (ICFS-10) scores≥24 or Visual Analogue Scale (VAS) scores of fatigues>6. Secondary outcomes were perioperative grip strength, early ambulation and anal exhaust after surgery, and inpatient days. RESULTS: 32 participants were assigned to the propofol group (P) and 33 to the sevoflurane group (S). Incidence of POFS on postoperative D1 was P (8/32) vs. S (10/33) (p = 0.66, 95% confidence interval [CI]: 16.4-27.00); D3 P (2/32) vs. S (5/33) (p = 0.45,95% CI:5.96-23.76). POFS were not found on postoperative D5 and D30. There were no differences in perioperative grip strength, early ambulation and anal exhaust after surgery, and inpatient days between the two groups. CONCLUSIONS: POFS after scheduled laparoscopic hysterectomy was unaffected by anesthesia with propofol vs. sevoflurane. The incidence of POFS was highest on the first postoperative day, at 27.7%, and declined progressively over the postoperative 30 days. Trial registration Chinese Clinical Trial Registry (No. ChiCTR 2,000,033,861), registered on 14/06/2020).

Novel lignin-based extracellular barrier in glandular trichome.

Successful biochemical reactions in organisms necessitate compartmentalization of the requisite components. Glandular trichomes (GTs) act as compartments for the synthesis and storage of specialized compounds. These compounds not only are crucial for the survival of plants under biotic and abiotic stresses but also have medical and commercial value for humans. However, the mechanisms underlying compartmentalization remain unclear. Here we identified a novel structure that is indispensable for the establishment of compartments in cucumber GTs. Silica, a specialized compound, is deposited on the GTs and is visible on the surface of the fruit as a white powder, known as bloom. This deposition provides resistance against pathogens and prevents water loss from the fruits1. Using the cucumber bloomless mutant2, we discovered that a lignin-based cell wall structure in GTs, named 'neck strip', achieves compartmentalization by acting as an extracellular barrier crucial for the silica polymerization. This structure is present in the GTs of diverse plant species. Our findings will enhance the understanding of the biosynthesis of unique compounds in trichomes and provide a basis for improving the production of compounds beneficial to humans.

Enhanced Superconductivity and Critical Current Density Due to the Interaction of InSe2 Bonded Layer in (InSe2)0.12NbSe2.

Superconductivity was discovered in (InSe2)xNbSe2. The materials are crystallized in a unique layered structure where bonded InSe2 layers are intercalated into the van der Waals gaps of 2H-phase NbSe2. The (InSe2)0.12NbSe2 superconductor exhibits a superconducting transition at 11.6 K and critical current density of 8.2 × 105 A/cm2. Both values are the highest among all transition metal dichalcogenide superconductors at ambient pressure. The present finding provides an ideal material platform for further investigation of superconducting-related phenomena in transition metal dichalcogenides.

CsHLS1-CsSCL28 module regulates compact plant architecture in cucumber.

Increased planting densities boost crop yields. A compact plant architecture facilitates dense planting. However, the mechanisms regulating compact plant architecture in cucurbits remain unclear. In this study, we identified a cucumber (Cucumis sativus) compact plant architecture (cpa1) mutant from an ethyl methane sulfonate (EMS)-mutagenized library that exhibited distinctive phenotypic traits, including reduced leaf petiole angle and leaf size. The candidate mutation causes a premature stop codon in CsaV3_1G036420, which shares similarity to Arabidopsis HOOKLESS 1 (HLS1) encoding putative histone N-acetyltransferase (HAT) protein and was named CsHLS1. Consistent with the mutant phenotype, CsHLS1 was predominantly expressed in leaf petiole bases and leaves. Constitutive overexpressing CsHLS1 in cpa1 restored the wild-type plant architecture. Knockout of CsHLS1 resulted in reduces leaf petiole angle and leaf size and as well as decreased acetylation levels. Furthermore, CsHLS1 directly interacted with CsSCL28 and negatively regulated compact plant architecture in cucumber. Importantly, CsHLS1 knockout increased the photosynthesis rate and leaf nitrogen in cucumbers, thereby maintaining cucumber yield at normal density. Overall, our research provides valuable genetic breeding resource and gene target for creating a compact plant architecture for dense cucumber planting.

Study of postoperative laryngopharyngeal discomfort: protocol for a single-centre cohort study.

INTRODUCTION: Postoperative laryngopharyngeal discomfort after extubation can lead to severe throat pain, dysphagia, or postoperative tongue oedema. Possible mechanisms include increased oral pressure, obstruction of venous and lymphatic return in the neck, and increased capillary hydrostatic pressure, which leads to oedema of the tongue and upper airway. However, real-time monitoring indicators of anaesthesia are lacking. Therefore, we designed this study to accurately measure the contact force of the tracheal tube on the tongue in different surgical positions during general anaesthesia. METHODS AND ANALYSIS: This prospective single-centre observational study will enrol 54 patients undergoing elective surgery under general anaesthesia for>2 hours with endotracheal tube application from 1 July 2023 to 30 June 2024. Patients will be divided into the supine (Supine group) and high-risk (Flexion group) groups. Dynamic changes in the contact force between the tracheal tube and tongue will be measured using T-Scan technology. All patients will be followed up for 7 days postoperatively. The primary endpoint is postoperative laryngopharyngeal discomfort. Secondary outcomes include the time to the first successful recovery of oral intake of fluids and solid food, and airway-related events. ETHICS AND DISSEMINATION: Ethical approval was obtained from the Ethics Committee of Clinical Research of China-Japan Friendship Hospital (2023-KY-219, approved on 14 September 2023). Informed consent will be obtained during anaesthesia evaluation. This study aims to explore the characteristics of the contact force on the tongue caused by endotracheal intubation in different surgical positions and to provide a better understanding of the risk factors and prevention of postoperative laryngopharyngeal discomfort. The findings of this study will be presented at our hospital, reported on ClinicalTrials.gov, and published in peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT05987293.

Assessing the Global, Regional, and National Impact of High Body Mass Index on Alzheimer's Disease and Other Dementias Between 1990 and 2019.

BACKGROUND: Obesity significantly increases Alzheimer's disease (AD) and dementia risk. Understanding the link between a high body mass index (BMI) and these conditions is crucial for effective management and prevention. OBJECTIVE: We aimed to estimate the burden of AD and other dementias attributed to high BMI from 1990 to 2019 based on sex, age, and socio-demographic indicators (SDI) at global, regional, and national levels. METHODS: We collected data on deaths, disability-adjusted life years (DALYs), age-standardized mortality rates (ASMR), and age-standardized DALY rates (ASDR) from the 2019 Global Burden of Disease study for AD and dementia attributed to high BMI. We explored the correlation between SDI levels and ASDR. RESULTS: In 2019, there were 198,476.2 deaths (95% UI: 32,695.4-593,366.4) and 3,159,912.4 DALYs (848,330.5-8,042,531) attributed to high BMI. Numbers of deaths, DALYs, ASMR, and ASDR increased since 1990. Females had higher deaths, ASMR, and ASDR than males. Mortality and DALYs rates increased with age. ASMR and ASDR increased across five SDI levels, with the highest rise in Low-middle SDI. High-income North America had the most deaths [30,993.9 (5,101.7-89,912.9)], while North Africa and the Middle East had the highest ASMR [4.61 (0.79-13.64)] and ASDR [72.56 (20.98-181.16)] in 2019. CONCLUSIONS: The burden of AD and other dementias attributed to high BMI increased since 1990 globally and is still heaviest in developed regions. Females accounted predominantly for the burden than males. Timely measures are needed to against high BMI.

The Establishment of a precise intelligent evaluation system for sports events: Diving.

The introduction of action quality assessment technology in sports events to achieve precise intelligent evaluation can greatly enhance the objectivity and effectiveness of competition results. Taking diving as the specific application background, this study proposes a novel Multi-granularity Extraction Approach for Temporal-spatial features in judge scoring prediction (MEAT) under the conditions of action quality assessment. On the one hand, it uses dual-modal inflated 3D ConvNet to extract the temporal and spatial features of each modal diving video at the video granularity parallelly and to merge them to form a global feature. On the other hand, the human body pose is modeled, and the simulated athlete's three-dimensional splash state is taken as local characteristics at the object granularity. Finally, the global and local features are concatenated into the fully connected layer, and heuristic method inspired by competition rules using labeled distribution learning are employed to output the probability distribution of the average score of all referees. The maximum probability score is selected and multiplied by the difficulty coefficient to obtain the final diving score. Through comprehensive experiments, comparing the Spearman's rank correlation (SRC) evaluation results of existing methods on the UNIV-Dive dataset, this framework reflects the greater accuracy advantage and further lays the foundation for the actual implementation of the technology.

Cognitive Reappraisal and Expressive Suppression Evoke Distinct Neural Connections during Interpersonal Emotion Regulation.

Interpersonal emotion regulation is the dynamic process where the regulator aims to change the target's emotional state, which is presumed to engage three neural systems: cognitive control (i.e., dorsal and ventral lateral PFC, etc.), empathy/social cognition (i.e., dorsal premotor regions, temporal-parietal junction, etc.), and affective response (i.e., insula, amygdala, etc.). This study aimed to identify the underlying neural correlate (especially the interpersonal one), of interpersonal emotion regulation based on two typical strategies (cognitive appraisal, expressive suppression). Thirty-four female dyads (friends) were randomly assigned into two strategy groups, with one assigned as the target and the other as the regulator to downregulate the target's negative emotions using two strategies. A functional near-infrared spectroscopy system was used to simultaneously measure participants' neural activity. Results showed that these two strategies could successfully downregulate the targets' negative emotions. Both strategies evoked intrapersonal and interpersonal neural couplings between the cognitive control, social cognition, and mirror neuron systems (e.g., PFC, temporal-parietal junction, premotor cortex, etc.), whereas cognitive reappraisal (vs expressive suppression) evoked a broader pattern. Further, cognitive reappraisal involved increased interpersonal brain synchronization between the prefrontal and temporal areas at the sharing stage, whereas expressive suppression evoked increased interpersonal brain synchronization associated with the PFC at the regulation stage. These findings indicate that intrapersonal and interpersonal neural couplings associated with regions within the abovementioned systems, possibly involving mental processes, such as cognitive control, mentalizing, and observing, underlie interpersonal emotion regulation based on cognitive reappraisal or expressive suppression.SIGNIFICANCE STATEMENT As significant as intrapersonal emotion regulation, interpersonal emotion regulation subserves parent-child, couple, and leader-follower relationships. Despite enormous growth in research on intrapersonal emotion regulation, the field lacks insight into the neural correlates underpinning interpersonal emotion regulation. This study aimed to probe the underlying neural correlates of interpersonal emotion regulation using a multibrain neuroimaging (i.e., hyperscanning) based on functional near-infrared spectroscopy. Results showed that both cognitive reappraisal and expressive suppression strategies successfully downregulated the target's negative emotions. More importantly, they evoked intrapersonal and interpersonal neural couplings associated with regions within the cognitive control, social cognition, and mirror neuron systems, possibly involving mental processes, such as cognitive control, mentalizing, and observing. These findings deepen our understanding of the neural correlates underpinning interpersonal emotion regulation.

Similarities and Distinctions between Cortical Neural Substrates That Underlie Generation of Malevolent Creative Ideas.

Creativity can be driven by negative intentions, and this is called malevolent creativity (MC). It is a type of creativity that serves antisocial purposes and deliberately leads to harmful or immoral results. A possible classification indicates that there are three kinds of MC in daily life: hurting people, lying, and playing tricks. This study aimed to explore similar and distinct neural substrates underlying these different kinds of MC idea generation. The participants were asked to perform different MC tasks, and their neural responses were recorded using a functional near-infrared spectroscopy device. The findings revealed that most regions within the prefrontal and temporal lobes [e.g., the right dorsolateral prefrontal cortex (rDLPFC), and right angular gyrus] were involved in the three MC tasks. However, the right frontopolar cortex (rFPC) was more activated and less coupled with the rDLPFC and right precuneus during the lying task than during the other tasks. Thus, rFPC may play an important role in constructing novel lies. In the lying task, individuals were more selfish and less compassionate. In the playing tricks and hurting people tasks, there was less neural coupling between the rDLPFC and the left inferior frontal gyrus/right inferior parietal lobule than that in the lying task. This may imply that selfish motivation is released when individuals try to ignore victims' distress or generate aggressive tricks in hurting people or playing tricks tasks. These findings indicate that the three kinds of MC idea generation involve common cortical regions related to creative idea generation and moral judgment, whereas differences in cortical responses exist because of their unique features.

Biodegradability analysis of Dioxins through in silico methods: Model construction and mechanism analysis.

The biodegradation treatment of dioxins has long been of interest due to its good ecological and economic effects. In this study, the biodegradability of polychlorinated dibenzo-p-dioxins (PCDDs) were investigated by constructing machine learning and multiple linear regression models. The maximum chlorine atomic charge (qHirshfeldCl+), which characterizes the biodegradation ability of PCDDs, was used as the response value. The random forest model was used to rank the importance on the 1471 descriptors of PCDDs, and the BCUTp-1 h, QXZ, JGI4, ATSC8c, VE3_Dt, topoShape, and maxwHBa were screened as the important descriptors by Pearson's correlation coefficient method. A quantitative structure-activity relationship (QSAR) model was constructed to predict the biodegradability of PCDDs. In addition, the extreme gradient boosting (XGBoost) and random forest model were also constructed and proved the good predictability of QSAR model. The biodegradability of polychlorinated dibenzofurans (PCDFs) can also be predicted by the constructed three models from a certain level after adjusting some model parameters, which further proved the versatility of the models. Besides, the sensitivity analysis of the QSAR model and a 3D-QSAR model was developed to investigate the biodegradability mechanisms of PCDDs. Results showed that the descriptors BCUTp-1 h, JGI4, and maxwHBa were the key descriptors in the biodegradability effect by the sensitivity analysis of the QSAR model. Coupled with the results of PCDDs biodegradability 3D-QSAR model, BCUTp-1 h, JGI4, and maxwHBa were confirmed as the main descriptors that affect the biodegradability of dioxins. This study provides a novel theoretical perspective for the research of the biodegradation of both PCDDs and PCDFs dioxins.

Mnemonic-trained brain tuning to a regular odd-even pattern subserves digit memory in children.

It is said that our species use mnemonics - that "magic of memorization" - to engrave an enormous amount of information in the brain. Yet, it is unclear how mnemonics affect memory and what the neural underpinnings are. In this electroencephalography study, we examined the hypotheses whether mnemonic training improved processing-efficiency and/or altered encoding-pattern to support memory enhancement. By 22-day training of a digit-image mnemonic (a custom memory technique used by world-class mnemonists), a group of children showed increased short-term memory after training, but with limited gain generalization. This training resulted in regular odd-even neural patterns (i.e., enhanced P200 and theta power during the encoding of digits at even- versus odd- positions in a sequence). Critically, the P200 and theta power effects predicted the training-induced memory improvement. These findings provide evidence of how mnemonics alter encoding pattern, as reflected in functional brain organization, to support memory enhancement.

Modulating endoplasmic reticulum stress in APP/PS1 mice by Gomisin B and Osthole in Bushen-Yizhi formula: Synergistic effects and therapeutic implications for Alzheimer's disease.

BACKGROUND: Alzheimer's disease (AD) is a prevalent neurodegenerative disorder with no effective cure. Targeting endoplasmic reticulum (ER) stress pathway may offer a novel approach to ameliorate cognitive deficits in AD. Bushen-Yizhi formula (BSYZ), a traditional Chinese medicine (TCM) prescription, has shown potential benefits for AD. To facilitate the development of new therapeutic agents for AD, it is important to identify the active components and the underlying mechanisms of BSYZ against AD. PURPOSE: The aim of this study was to systematically screen the active components of BSYZ that could improve learning and memory impairment in AD by modulating ER stress pathway. METHODS: A drug-target (D-T) network was constructed to analyze the herbal components of BSYZ. Network proximity method was used to identify the potential anti-AD components that targeted ER stress and evaluate their synergistic effects. The absorption, distribution, metabolism, excretion, and toxicity (ADMET) properties and the literature evidence were considered to select promising candidates for further validation. The selected components were tested in vitro using an AD cell model (APPswe-SH-SY5Y). In vivo anti-AD effects of the components were assessed in APP/PS1 double-transgenic mice. RESULTS: 58 potential anti-AD components targeting ER stress were detected by network proximity analysis, and 13 out of them were selected based on ADMET properties and literature evidence. In vitro experiments confirmed that 5 components, namely gomisin B, ß-Carotene, imperatorin, chrysophanol, and osthole (OST), exhibited anti-AD effects on the APPswe-SH-SY5Y model. Moreover, network proximity analysis suggested that OST and Gomisin B might have synergistic effects on modulating ER stress. In vivo experiments demonstrated that OST, Gomisin B, OST+Gomisin B, and BSYZ all improved learning and memory function in APP/PS1 mice. Gomisin B and OST also restored cellular morphology and tissue structure in APP/PS1 mice. Thioflavine-S (Th-S) staining revealed that they reduced amyloid plaque deposition in the brain tissue of AD model mice. The qPCR results indicated that BSYZ, OST, and Gomisin B differentially regulated IRE1α, PERK, EIF2α, DDIT3, and Caspase 12 expression levels, while the OST and Gomisin B co-administration group showed better efficacy. This trend was further confirmed by immunofluorescence experiments. CONCLUSION: This study identified the active components of BSYZ that could ameliorate learning and memory impairment in AD by targeting ER stress pathway. OST and Gomisin B exhibited synergistic effects on modulating ER stress and reducing amyloid plaque deposition in vivo. Overall, our study elucidated the molecular mechanisms of BSYZ and its active components in attenuating AD symptoms which suggested the therapeutic potential of TCM for AD.

The COPII subunit CsSEC23 mediates fruit glossiness in cucumber.

To improve our understanding of the mechanism underlying cucumber glossiness regulation, a novel cucumber mutant with a glossy peel (Csgp) was identified. MutMap, genotyping, and gene editing results demonstrated that CsSEC23, which is the core component of COPII vesicles, mediates the glossiness of cucumber fruit peel. CsSEC23 is functionally conserved and located in the Golgi and endoplasmic reticulum. CsSEC23 could interact with CsSEC31, but this interaction was absent in the Csgp mutant, which decreased the efficiency of COPII vesicle transportation. Genes related to wax and cutin transport were upregulated in the Csgp mutant, and the cuticle structure of the Csgp-mutant peel became thinner. Moreover, the wax and cutin contents were also changed due to CsSEC23 mutation. Taken together, the results obtained from this study revealed that CsSEC23 mediates cucumber glossiness, and this mediating might be affected by COPII vesicle transportation.

A multi-framework for bisphenols based on their high performance and environmental friendliness: Design, screening, and recommendations.

Bisphenols (BPs) have gained significant attention due to their extensive use in the production of medical equipment, packaging materials, and everyday commodities. Urgent attention is required for assessing and identifying the risks associated with BP exposure to the environment and human health, as well as developing regulatory strategies. In this paper, 29 common BPs were selected as the research object, high-performance BP substitutes with environmental and human health friendliness characteristics were designed and screened. The above eight BP substitutes were considered as examples, and the first-level evaluation indicators of BPs and their substitutes were predicted using a random forest classification/regression model. Subsequently, the key indicators affecting the first-level evaluation indicators were ranked. The ranking results were environmental friendliness (64.30%) > human health risk (18.00%) > functionality (17.69%), indicating that environmental friendliness was the main influencing factor for the first-level evaluation indicators of BPs and their substitutes. Therefore, the study employed density functional theory (DFT) to simulate the biodegradation pathways of BPs and their substitutes in contaminated soil and landfill leachate, using Derivative-50 as an example. Furthermore, the environmental risk associated with the degradation products was evaluated, and regulatory recommendations based on risk identification were proposed.