Cooperation of selenium, iron and phosphorus for simultaneously minimizing cadmium and arsenic concentrations in rice grains.

Cadmium (Cd) and arsenic (As), two toxic elements to humans, are ubiquitously coexisting contaminant found in paddy fields. The accumulation of Cd and As in rice, a major food source for many people around the world, can pose a serious threat to food safety and human health. Therefore, it is crucial to be aware of these contaminants and take adequate measures to reduce the accumulation of these two elements in rice. Developing an effective method to simultaneously reduce the accumulation of Cd) and As in rice is challenging. In this study, a pot experiment was conducted to investigate the synergistic effects of selenium (Se), iron (Fe) and phosphorus (P) on the uptake, transport and accumulation of cadmium and arsenic in rice by analyzing the physical and chemical properties of the soil, the elemental concentrations and their interrelationships in the rice tissues, and the composition and morphology of the iron plaque (IP). The results showed that the combined treatments of Se, Fe and P had positive effects on reducing Cd and As accumulation in rice, reducing Cd concentrations in brown rice by 3.86-51.88 % and As concentrations by 25.37-40.81 %. The possible mechanisms for the reduction of As and Cd concentrations in rice grains were: (i) Combined application of Fe, P and Se can effectively reduce the soil available Cd and As concentration. (ii) Combined application significantly improved the formation of IP at the tillering stage and increased the crystalline iron oxides in IP, promoting the deposition of SiO2 in rice roots, thereby effectively inhibiting the uptake of Cd and As by rice roots. (iii) Interplay and interaction between elements facilitated by transporter proteins could contribute to the synergistic mitigation of Cd and As by Se, Fe and P. This study provides a valuable new approach for effective control of Cd and As concentration of rice grown in co-contaminated soil.

Heterologous booster vaccination enhances antibody responses to SARS-CoV-2 by improving Tfh function and increasing B-cell clonotype SHM frequency.

Heterologous prime-boost has broken the protective immune response bottleneck of the COVID-19 vaccines. however, the underlying mechanisms have not been fully elucidated. Here, we investigated antibody responses and explored the response of germinal center (GC) to priming with inactivated vaccines and boosting with heterologous adenoviral-vectored vaccines or homologous inactivated vaccines in mice. Antibody responses were dramatically enhanced by both boosting regimens. Heterologous immunization induced more robust GC activation, characterized by increased Tfh cell populations and enhanced helper function. Additionally, increased B-cell activation and antibody production were observed in a heterologous regimen. Libra-seq was used to compare the differences of S1-, S2- and NTD-specific B cells between homologous and heterologous vaccination, respectively. S2-specific CD19+ B cells presented increased somatic hypermutations (SHMs), which were mainly enriched in plasma cells. Moreover, a heterologous booster dose promoted the clonal expansion of B cells specific to S2 and NTD regions. In conclusion, the functional role of Tfh and B cells following SARS-CoV-2 heterologous vaccination may be important for modulating antibody responses. These findings provide new insights for the development of SARS-CoV-2 vaccines that induce more robust antibody response.

Tracking the hologenome dynamics in aquatic invertebrates by the holo-2bRAD approach.

The "hologenome" concept is an increasingly popular way of thinking about microbiome-host for marine organisms. However, it is challenging to track hologenome dynamics because of the large amount of material, with tracking itself usually resulting in damage or death of the research object. Here we show the simple and efficient holo-2bRAD approach for the tracking of hologenome dynamics in marine invertebrates (i.e., scallop and shrimp) from one holo-2bRAD library. The stable performance of our approach was shown with high genotyping accuracy of 99.91% and a high correlation of r > 0.99 for the species-level profiling of microorganisms. To explore the host-microbe association underlying mass mortality events of bivalve larvae, core microbial species changed with the stages were found, and two potentially associated host SNPs were identified. Overall, our research provides a powerful tool with various advantages (e.g., cost-effective, simple, and applicable for challenging samples) in genetic, ecological, and evolutionary studies.

Natural five-sense experience and positive and negative emotions: the mediating role of nature connectedness.

Nature experience is a relatively easy and beneficial measure for improving emotions. Individuals experience nature through proximal senses (tactile, gustatory, and olfactory) and distal senses (vision and audition). This study examined the relationships between diverse natural senses experience and individuals' positive and negative emotions, along with the mediating role of nature connectedness. We recruited 978 college students (Mage = 20.09 ± 1.09 years old) from Beijing, China. The results showed that tactile experience (e.g. touching trees and water) was negatively related to negative emotions, while gustatory experience (e.g. tasting fresh fruits) was positively correlated with positive emotions. Furthermore, nature connectedness mediated the relationship between other natural sensory experiences and positive and negative emotions, except for the insignificant mediation between olfactory experiences and negative emotions. Therefore, individuals should emphasize the role of the proximal senses (especially tactile and gustatory experiences) during nature experiences and increase nature connectedness to maintain positive emotions.

Establishment and verification of novel TNM staging system for lung mucinous adenocarcinoma.

BACKGROUND: Lung adenocarcinoma is a high-mortality rate cancer. Within this category, Lung mucinous adenocarcinoma (LMAC) is a rare and distinct subtype of lung adenocarcinoma necessitating further investigation. The study was launched to compare the difference of survival features between LMAC and lung non-mucinous adenocarcinoma (LNMAC) and to investigate the significance and demand for developing a new staging system tailored to LMAC. METHODS: This retrospective study assessed the suitableness of the current staging system for LMAC. It compared the overall survival (OS) between LMAC and LNMAC from 2004 to 2020 (LNMAC: 160,387; LMAC: 6,341) and instituted a novel classification framework for LMAC based on US population. Verification group consisting of patients from two Chinese medical centers from 2010 to 2018 (n = 392) was set to ascertain the applicability of this novel system. The primary endpoint was OS. To minimize the bias, propensity score match (PSM) was employed. Survival analysis and Log-rank test were executed to explore the survival features of LMAC. RESULTS: The results indicated that the existed staging system was not suitable for LMAC. Patients diagnosed with LMAC exhibited a superior OS compared to those with LNMAC in stage IA2 (P < 0.0001), IA3 (P < 0.0001), IB (P = 0.0062), IIA (P = 0.0090), IIB (P = 0.0005). In contrast, a worse OS in stage IVA (P = 0.0103) was found in LMAC patients. The novel classification system proposed for LMAC proved to be highly applicable and demonstrated substantial efficacy, as confirmed by the verification group. CONCLUSION: The newly established classification system was more effective for LMAC, but it necessitates large-scale verification to confirm its applicability and reliability.

Multi-functional adhesive hydrogel as bio-interface for wireless transient pacemaker.

Traditional temporary cardiac pacemakers (TCPs), which employ transcutaneous leads and external wired power systems are battery-dependent and generally non-absorbable with rigidity, thereby necessitating surgical retrieval after therapy and resulting in potentially severe complications. Wireless and bioresorbable transient pacemakers have, hence, emerged recently, though hitting a bottleneck of unfavorable tissue-device bonding interface subject to mismatched mechanical modulus, low adhesive strength, inferior electrical performances, and infection risks. Here, to address such crux, we develop a multifunctional interface hydrogel (MIH) with superior electrical performance to facilitate efficient electrical exchange, comparable mechanical strength to natural heart tissue, robust adhesion property to enable stable device-tissue fixation (tensile strength: ∼30 kPa, shear strength of ∼30 kPa, and peel-off strength: ∼85 kPa), and good bactericidal effect to suppress bacterial growth. Through delicate integration of this versatile MIH with a leadless, battery-free, wireless, and transient pacemaker, the entire system exhibits stable and conformal adhesion to the beating heart while enabling precise and constant electrical stimulation to modulate the cardiac rhythm. It is envisioned that this versatile MIH and the proposed integration framework will have immense potential in overcoming key limitations of traditional TCPs, and may inspire the design of novel bioelectronic-tissue interfaces for next-generation implantable medical devices.

Transformation of As and Cd associated with Fe-Mn-modified biochar during simultaneous remediation on the contaminated soil.

Here, Fe- and Mn-modified biochar (BC-Fe-Mn) was applied to simultaneously stabilize As and Cd in the contaminated soil. The removal efficiencies for NaHCO3-extractable As and DTPA-extractable Cd by BC-Fe-Mn were 60.8% and 49.6%, respectively. The speciation analyses showed that the transformation to low-crystallinity Fe-bound (F3) As, Fe-Mn oxide-bound (OX) of Cd, and residual As and Cd was primarily attributed to stabilizing the two metal(loid)s. Moreover, the correlation analyses showed that the increase of As in F3 fraction was significantly and positively associated with the increase of OX fraction Mn (r = 0.64). Similarly, OX fraction Cd was increased notably with increasing OX fraction Fe (r = 0.91) and OX fraction Mn (r = 0.76). In addition, a novel dialysis experiment was performed to separate the reacted BC-Fe-Mn from the soil for intensively investigating the stabilization mechanisms for As and Cd by BC-Fe-Mn. The characteristic crystalline compounds of (Fe0.67Mn0.33)OOH and Fe2O3 on the surface of BC-Fe-Mn were revealed by SEM-EDS and XRD. And FTIR analyses showed that α-FeOOH, R-COOFe/Mn+, and O-H on BC-Fe-Mn potentially served as the reaction sites for As and Cd. A crystalline compound of MnAsO4 was found in the soil treated by BC-Fe-Mn in the dialysis experiment. Thus, our results are beneficial to deeper understand the mechanisms of simultaneous stabilization of As and Cd by BC-Fe-Mn in soil and support the application of the materials on a large scale.

Molecular response to the influences of Cu(II) and Fe(III) on forming biogenic manganese oxides by Pseudomonas putida MnB1.

The biogeochemical cycle of biogenic manganese oxides (BioMnOx) is closely associated with the environmental behavior and fate of various pollutants. It is significantly interfered by many metals, such as Cu and Fe. However, the bacterial molecular responses are not clear. Here, the effects of Cu(II) and Fe(III) on oxidation of manganese by Pseudomonas putida MnB1 and the bacterial molecular response mechanisms have been studied. The bacterial oxidation of manganese were promoted by both Fe(III) and Cu(II) and the final manganese oxidation rate of the Cu(II) group exceeded 16 % that of the Fe(III) group. The results of transcriptome indicated that Cu(II) promoted manganese oxidation by up-regulating the expression levels of multicopper oxidase (MCO) and peroxidase(POD), and by stimulating electron transfer, while Fe(III) promoted this process by accelerating the electron transfer and nitrogen cycling, and activating POD. The protein-protein interaction (PPI) network indicated that the MCO genes (mnxG and mcoA) were directly linked to the copper homeostasis proteins (cusA, cusB, czcC and cusF). Cytochrome c was closely related to the genes related to nitrogen cycling (glnA, glnL, and putA) and electrons transfer (cycO, cycD, nuoA, nuoK, and nuoL), which also promoted manganese oxidation. This study provides a molecular level insight into the oxidation of Mn(II) by Pseudomonas putida MnB1 with Cu(II) and/or Fe(III) ions.

Gtie-Rt: A comprehensive graph learning model for predicting drugs targeting metabolic pathways in human.

Drugs often target specific metabolic pathways to produce a therapeutic effect. However, these pathways are complex and interconnected, making it challenging to predict a drug's potential effects on an organism's overall metabolism. The mapping of drugs with targeting metabolic pathways in the organisms can provide a more complete understanding of the metabolic effects of a drug and help to identify potential drug-drug interactions. In this study, we proposed a machine learning hybrid model Graph Transformer Integrated Encoder (GTIE-RT) for mapping drugs to target metabolic pathways in human. The proposed model is a composite of a Graph Convolution Network (GCN) and transformer encoder for graph embedding and attention mechanism. The output of the transformer encoder is then fed into the Extremely Randomized Trees Classifier to predict target metabolic pathways. The evaluation of the GTIE-RT on drugs dataset demonstrates excellent performance metrics, including accuracy (>95%), recall (>92%), precision (>93%) and F1-score (>92%). Compared to other variants and machine learning methods, GTIE-RT consistently shows more reliable results.

Simultaneously inhibit cadmium and arsenic uptake in rice (Oryza sativa L.) by Selenium enhanced iron plaque: Performance and mechanism.

Selenium (Se) fortification is witnessed to simultaneously inhibit absorbing Cadmium (Cd) and Arsenic (As) by rice plants, but the mechanism is unclear. Here, the effects of Se on the root morphology, iron plaque (IP) content, soil Fe2+ content, radial oxygen loss (ROL), and enzyme activities of the rice plants in the soil contaminated by Cd and As were intensively investigated through the hydroponic and soil experiments. Se effectively alleviated the toxic effects of Cd and As on the plants and the dry weight, root length, and root width were increased by 203.18%, 33.41%, and 52.81%, respectively. It also elucidated that ROL was one of the key factors to elevate IP formation by Se and the specific pathways of Se enhancing ROL were identified. ROL of the plants in the experiment group treated by Se was increased 36.76%, and correspondingly IP was magnified 50.37%, compared to the groups with Cd and As. It was owing to Se significantly increased the root porosity (62.11%), facilitating O2 transport to the roots. Additionally, Se enhanced the activities of catalase (CAT) and superoxide dismutase (SOD) to promote the catalytic degradation of ROS induced by Cd and As stress. It indirectly increased O2 release in the rhizosphere, which benefit to form more robust IP serve as stronger barrier to Cd and As. The results of our study provide a novel molecular level insight for Se promoting root IP to block Cd and As uptake by the rice plants.

eIF6 Promotes Gastric Cancer Proliferation and Invasion by Regulating Cell Cycle.

OBJECTIVE: To investigate the role and function of eIF6 in gastric cancer (GC). METHODS: The expression level of eIF6 in GC tissues and normal tissues was detected in different high-throughput sequencing cohorts. Survival analysis, gene differential analysis, and enrichment analysis were performed in the TCGA cohort. Biological networks centered on eIF6 were constructed through two different databases. Immunohistochemistry (IHC) and Western blot were used to detect protein expression of eIF6, and qRT-PCR was used to detect eIF6 mRNA expression. The correlation between the expression of eIF6 in GC tissues and clinicopathological parameters of GC was analyzed. siRNA knockout of eIF6 was used to study the proliferation, migration, and invasion. The effects of eIF6 on cell cycle and Cyclin B1 were detected by flow cytometry and Western blot. RESULTS: eIF6 was significantly overexpressed in GC tissues and predicted poor prognosis. In addition, 113 differentially expressed genes were detected in cancer-related biological pathways and functions by differential analysis. Biological networks revealed interactions of genes and proteins with eIF6. The expression intensity of eIF6 in cancer tissues was higher than that in adjacent tissues (P = 0.0001), confirming the up-regulation of eIF6 expression in GC tissues. The expression level of eIF6 was statistically significant with pTNM stage (P = 0.006). siRNA knockout of eIF6 significantly reduced the proliferation, colony formation, migration, and invasion ability of GC cells. Silencing of eIF6 also inhibited the cell cycle of GC cells in G2/M phase and decreased the expression level of CyclinB1. CONCLUSION: Our study suggests that eIF6 is up-regulated in GC and may promote the proliferation, migration, and invasion of GC by regulating cell cycle.

Comparing the efficacy of traditional Chinese exercises and general aerobic exercises in university students with sleep disorders: A systematic review and meta-analysis.

BACKGROUND: The objective of this study was to compare the impact of traditional Chinese exercise (TCEs) and general aerobic exercise (GAEs) on the sleep quality of university students and to determine which exercise is more effective in improving sleep quality in this specific population. METHODS: We utilized Review Manager 5.3 to analyze data from 21 randomized controlled trials (RCTs), which included a total of 1252 participants. Effect sizes of TCEs and GAEs were compared using a random-effects model. Subgroup analyses were conducted on 3 modulating variables: times per session, frequency per week, and period. RESULTS: A Meta-analysis of 14 RCTs showed that both TCEs (standard mean difference [SMD] = -0.89, 95% CI: -1.18 to -0.61; P < .00001) and GAEs (SMD = -1.53, 95% CI: -2.10 to -0.97; P < .00001) can significantly improve the sleep of university students, with a significant difference between TCEs and GAEs (P = .05). Both GAEs and TCEs had positive effects on various aspects of sleep quality, including subjective sleep quality, sleep latency, sleep duration, habitual sleep efficiency, sleep disturbance, use of sleep medication, and daytime dysfunction. A subgroup analysis of aerobic exercise showed that the effect size was larger in the 40 to 60 minutes group compared to the 60 to 90 minutes group (SMD = -1.89; 95% CI: -2.19 to -1.59; P < .00001). Furthermore, the effect size was larger in the 3 to 5 times per week group compared to the 2 times per week group (SMD = -1.56; 95% CI: -2.33 to -0.80; P < .0001). The effect size was also found to be larger in a period of 2 to 4 weeks compared to 6 to 18 weeks (SMD = -1.85; 95% CI: -2.17 to -1.54; P < .00001). CONCLUSION: GAEs is more effective than TCEs in improving the sleep quality of university students. An optimal aerobic exercise regimen for enhancing sleep quality among university students involves engaging in sessions lasting 40~60 minutes, 3~5 times per week, over a duration of 4 weeks.

The role of LncRNA-mediated autophagy in cancer progression.

Long non-coding RNAs (lncRNAs) are a sort of transcripts that are more than 200 nucleotides in length. In recent years, many studies have revealed the modulatory role of lncRNAs in cancer. Typically, lncRNAs are linked to a variety of essential events, such as apoptosis, cellular proliferation, and the invasion of malignant cells. Simultaneously, autophagy, an essential intracellular degradation mechanism in eukaryotic cells, is activated to respond to multiple stressful circumstances, for example, nutrient scarcity, accumulation of abnormal proteins, and organelle damage. Autophagy plays both suppressive and promoting roles in cancer. Increasingly, studies have unveiled how dysregulated lncRNAs expression can disrupt autophagic balance, thereby contributing to cancer progression. Consequently, exploring the interplay between lncRNAs and autophagy holds promising implications for clinical research. In this manuscript, we methodically compiled the advances in the molecular mechanisms of lncRNAs and autophagy and briefly summarized the implications of the lncRNA-mediated autophagy axis.

Alternaria solani effectors AsCEP19 and AsCEP20 reveal novel functions in pathogenicity and conidiogenesis.

Previous work identified a pair of specific effectors AsCEP19 and AsCEP20 in Alternaria solani as contributors to the virulence of A. solani. Here, we constructed AsCEP19 and AsCEP20 deletion mutants in A. solani strain HWC168 to further reveal the effects of these genes on the biology and pathogenicity of A. solani. Deletion of AsCEP19 and AsCEP20 did not affect vegetative growth but did affect conidial maturation, with an increase in the percentage of abnormal conidia produced. Furthermore, we determined the expression patterns of genes involved in the conidiogenesis pathway and found that the regulatory gene abaA was significantly upregulated and chsA, a positive regulator for conidiation, was significantly downregulated in the mutant strains compared to the wild-type strain. These results suggest that AsCEP19 and AsCEP20 indirectly affect the conidial development and maturation of A. solani. Pathogenicity assays revealed significantly impaired virulence of ΔAsCEP19, ΔAsCEP20, and ΔAsCEP19 + AsCEP20 mutants on potato and tomato plants. Moreover, we performed localization assays with green fluorescent protein-tagged proteins in chili pepper leaves. We found that AsCEP19 can specifically localize to the chloroplasts of chili pepper epidermal cells, while AsCEP20 can localize to both chloroplasts and the plasma membrane. Weighted gene co-expression network analysis revealed enrichment of genes of this module in the photosynthesis pathway, with many hub genes associated with chloroplast structure and photosynthesis. These results suggest that chloroplasts are the targets for AsCEP19 and AsCEP20. IMPORTANCE: Alternaria solani is an important necrotrophic pathogen causing potato early blight. Previous studies have provide preliminary evidence that specific effectors AsCEP19 and AsCEP20 contribute to virulence, but their respective functions, localization, and pathogenic mechanisms during the infection process of A. solani remain unclear. Here, we have systematically studied the specific effectors AsCEP19 and AsCEP20 for the first time, which are essential for conidial maturation. The deletion of AsCEP19 and AsCEP20 can significantly impair fungal pathogenicity. Additionally, we preliminarily revealed that AsCEP19 and AsCEP20 target the chloroplasts of host cells. Our findings further enhance our understanding of the molecular mechanisms underlying the virulence of necrotrophic pathogens.

Planning biosynthetic pathways of target molecules based on metabolic reaction prediction and AND-OR tree search.

Bioretrosynthesis problem is to predict synthetic routes using substrates for given natural products (NPs). However, the huge number of metabolic reactions leads to a combinatorial explosion of searching space, which is high time-consuming and costly. Here, we propose a framework called BioRetro to predict bioretrosynthesis pathways using a one-step bioretrosynthesis network, termed HybridMLP combined with AND-OR tree heuristic search. The HybridMLP predicts precursors that will produce the target NPs, while the AND-OR tree generates the iterative multi-step biosynthetic pathways. The one-step bioretrosynthesis prediction experiments are conducted on MetaNetX dataset by using HybridMLP, which achieves 46.5%, 74.6%, 81.6% in terms of the top-1, top-5, top-10 accuracies. The great performance demonstrates the effectiveness of HybridMLP in one-step bioretrosynthesis. Besides, the evaluation of two benchmark datasets reveals that BioRetro can significantly improve the speed and success rate in predicting biosynthesis pathways. In addition, the BioRetro is further shown to find the synthetic pathway of compounds, such as ginsenoside F1 with the same substrates as reported but different enzymes, which may be the novel potential enzyme to have better catalytic performance.

Crohn's disease-associated IgA nephropathy may prone to better renal outcome.

BACKGROUND AND AIM: Renal involvement in Crohn's Disease (CD) was rare in the population. Little was known between IgA nephropathy and CD. This study aimed to investigate the differences in clinical and outcome features of CD-associated IgA nephropathy (CD-IgAN) and primary IgA nephropathy (PIgAN). METHODS: Clinical data of patients diagnosed with IgAN by kidney biopsy were collected in the Sixth Affiliated Hospital of Sun Yat-sen University from January 1st, 2016 to June 1st, 2023. 17 patients with CD-IgAN and 87 patients with PIgAN were enrolled in this retrospective study. RESULTS: Compared with PIgAN patients, CD-IgAN patients had lower levels of urinary protein excretion (1.57 g per 24 h vs. 0.33 g per 24 h, p < 0.01), but higher levels of estimated glomerular filtration rate (77.63 ± 40.11 ml per min per 1.73m2 vs. 104.53 ± 32.97 ml per min per 1.73m2, p = 0.008). From the point of renal pathology of PIgAN, patients with CD-IgAN had a less incidence of tubular atrophy or interstitial fibrosis (p = 0.001). CD-IgAN patients had a higher incidence of complete remission of proteinuria (45.8% vs. 81.8%, p = 0.031) or hematuria (10.4% vs. 45.4%, p = 0.019) than PIgAN patients after twelve-month treatments. CONCLUSIONS: CD-IgAN manifests a milder progression of renal function than those PIgAN. After the treatment, proteinuria or hematuria are more prone to remit in patients with CD-IgAN.

Alantolactone enhances the sensitivity of melanoma to MAPK pathway inhibitors by targeting inhibition of STAT3 activation and down-regulating stem cell markers.

Mitogen-activated protein kinase inhibitors (MAPKi) were the first line drugs for advanced melanoma patients with BRAF mutation. Targeted therapies have significant therapeutic effects; however, drug resistance hinders their long-term efficacy. Therefore, the development of new therapeutic strategies against MAPKi resistance is critical. Our previous results showed that MAPKi promote feedback activation of STAT3 signaling in BRAF-mutated cancer cells. Studies have shown that alantolactone inhibited the activation of STAT3 in a variety of tumor cells. Our results confirmed that alantolactone suppressed cell proliferation and promoted apoptosis by inhibiting STAT3 feedback activation induced by MAPKi and downregulating the expression of downstream Oct4 and Sox2. The inhibitory effect of alantolactone combined with a MAPKi on melanoma cells was significantly stronger than that on normal cells. In vivo and in vitro experiments showed that combination treatment was effective against drug-resistant melanomas. Our research indicates a potential novel combination therapy (alantolactone and MAPKi) for patients with BRAF-mutated melanoma.

Unraveling NEK4 as a Potential Drug Target in Schizophrenia and Bipolar I Disorder: A Proteomic and Genomic Approach.

BACKGROUND AND HYPOTHESIS: Investigating the shared brain protein and genetic components of schizophrenia (SCZ) and bipolar I disorder (BD-I) presents a unique opportunity to understand the underlying pathophysiological processes and pinpoint potential drug targets. STUDY DESIGN: To identify overlapping susceptibility brain proteins in SCZ and BD-I, we carried out proteome-wide association studies (PWAS) and Mendelian Randomization (MR) by integrating human brain protein quantitative trait loci with large-scale genome-wide association studies for both disorders. We utilized transcriptome-wide association studies (TWAS) to determine the consistency of mRNA-protein dysregulation in both disorders. We applied pleiotropy-informed conditional false discovery rate (pleioFDR) analysis to identify common risk genetic loci for SCZ and BD-I. Additionally, we performed a cell-type-specific analysis in the human brain to detect risk genes notably enriched in distinct brain cell types. The impact of risk gene overexpression on dendritic arborization and axon length in neurons was also examined. STUDY RESULTS: Our PWAS identified 42 proteins associated with SCZ and 14 with BD-I, among which NEK4, HARS2, SUGP1, and DUS2 were common to both conditions. TWAS and MR analysis verified the significant risk gene NEK4 for both SCZ and BD-I. PleioFDR analysis further supported genetic risk loci associated with NEK4 for both conditions. The cell-type specificity analysis revealed that NEK4 is expressed on the surface of glutamatergic neurons, and its overexpression enhances dendritic arborization and axon length in cultured primary neurons. CONCLUSIONS: These findings underscore a shared genetic origin for SCZ and BD-I, offering novel insights for potential therapeutic target identification.

Mitochondrial structure and function: A new direction for the targeted treatment of chronic liver disease with Chinese herbal medicine.

ETHNOPHARMACOLOGICAL RELEVANCE: Excessive fat accumulation, biological clock dysregulation, viral infections, and sustained inflammatory responses can lead to liver inflammation, fibrosis, and cancer, thus promoting the development of chronic liver disease. A comprehensive understanding of the etiological factors leading to chronic liver disease and the intrinsic mechanisms influencing its onset and progression can aid in identifying potential targets for targeted therapy. Mitochondria, as key organelles that maintain the metabolic homeostasis of the liver, provide an important foundation for exploring therapeutic targets for chronic liver disease. Recent studies have shown that active ingredients in herbal medicines and their natural products can modulate chronic liver disease by influencing the structure and function of mitochondria. Therefore, studying how Chinese herbs target mitochondrial structure and function to treat chronic liver diseases is of great significance. AIM OF THE STUDY: Investigating the prospects of herbal medicine the Lens of chronic liver disease based on mitochondrial structure and function. MATERIALS AND METHODS: A computerized search of PubMed was conducted using the keywords "mitochondrial structure", "mitochondrial function", "mitochondria and chronic liver disease", "botanicals, mitochondria and chronic liver disease".Data from the Web of Science and Science Direct databases were also included. The research findings regarding herbal medicines targeting mitochondrial structure and function for the treatment of chronic liver disease are summarized. RESULTS: A computerized search of PubMed using the keywords "mitochondrial structure", "mitochondrial function", "mitochondria and chronic liver disease", "phytopharmaceuticals, mitochondria, and chronic liver disease", as well as the Web of Science and Science Direct databases was conducted to summarize information on studies of mitochondrial structure- and function-based Chinese herbal medicines for the treatment of chronic liver disease and to suggest that the effects of herbal medicines on mitochondrial division and fusion.The study suggested that there is much room for research on the influence of Chinese herbs on mitochondrial division and fusion. CONCLUSIONS: Targeting mitochondrial structure and function is crucial for herbal medicine to combat chronic liver disease.

Preparation and characterization of amphiphilic, biodegradable, waterborne polyurethanes without using organic solvent and catalyst.

Traditionally, waterborne polyurethanes (WPUs) are prepared using toxic organic solvents and catalysts. These WPUs are non-biodegradable and are buried or incinerated after the expiration date. This has adverse effects on the environment and human health, which limits the applications of WPUs. Herein, a special synthetic method was developed for biodegradable waterborne polyurethane (BWPU) by adding hydrophilic prepolymers into WPU prepolymers without using organic solvents and catalysts. Different proportions of polyethylene glycol (PEG) were introduced into polycaprolactone (PCL)-based BWPUs to improve the comprehensive properties. Results showed that as the PEG content was increased from 0 to 16 wt%, the solid content of BWPU increased from 34.8 wt% to 53.1 wt%, while the tensile strength and Young's modulus of BWPU films increased from 21.81 MPa to 56.83 MPa and 8.08 MPa to 19.4 MPa, respectively. However, the elongation at break did not decrease significantly, but still reached 827.17%. With an increase in PEG content, the crystallinity and phase separation decreased, while the hydrophilicity and surface energy increased for BWPU films. In addition, the prepared BWPUs had good biodegradability in PBS/lipase solution. The mass loss of BWPU without PEG reached 6.3 wt% after 4 weeks of degradation, whereas the mass losses of BWPUs with PEG reached 2.3-4.3 wt%. Obviously, the introduction of PEG did not increase biodegradability. Thus, the higher the PCL content, the faster the biodegradation rate. This work would provide an effective method for the preparation of ecofriendly biodegradable BWPU with excellent comprehensive properties.