UPLC-ESI-MS/MS-based widely targeted metabolomics reveals differences in metabolite composition among four Ganoderma species.

The Chinese name "Lingzhi" refers to Ganoderma genus, which are increasingly used in the food and medical industries. Ganoderma species are often used interchangeably since the differences in their composition are not known. To find compositional metabolite differences among Ganoderma species, we conducted a widely targeted metabolomics analysis of four commonly used edible and medicinal Ganoderma species based on ultra performance liquid chromatography-electrospray ionization-tandem mass spectrometry. Through pairwise comparisons, we identified 575-764 significant differential metabolites among the species, most of which exhibited large fold differences. We screened and analyzed the composition and functionality of the advantageous metabolites in each species. Ganoderma lingzhi advantageous metabolites were mostly related to amino acids and derivatives, as well as terpenes, G. sinense to terpenes, and G. leucocontextum and G. tsugae to nucleotides and derivatives, alkaloids, and lipids. Network pharmacological analysis showed that SRC, GAPDH, TNF, and AKT1 were the key targets of high-degree advantage metabolites among the four Ganoderma species. Analysis of Gene Ontology and Kyoto Encyclopedia of Genes and Genomes demonstrated that the advantage metabolites in the four Ganoderma species may regulate and participate in signaling pathways associated with diverse cancers, Alzheimer's disease, and diabetes. Our findings contribute to more targeted development of Ganoderma products in the food and medical industries.

Clinical observation of extraction-site incisional hernia after laparoscopic colorectal surgery.

BACKGROUND: Laparoscopic colorectal cancer surgery increases the risk of incisional hernia (IH) at the tumor extraction site. AIM: To investigate the incidence of IH at extraction sites following laparoscopic colorectal cancer surgery and identify the risk factors for IH incidence. METHODS: This study retrospectively analyzed the data of 1614 patients who underwent laparoscopic radical colorectal cancer surgery with tumor extraction through the abdominal wall at our center between January 2017 and December 2022. Differences in the incidence of postoperative IH at different extraction sites and the risk factors for IH incidence were investigated. RESULTS: Among the 1614 patients who underwent laparoscopic radical colorectal cancer surgery, 303 (18.8%), 923 (57.2%), 171 (10.6%), and 217 (13.4%) tumors were extracted through supraumbilical midline, infraumbilical midline, umbilical, and off-midline incisions. Of these, 52 patients developed IH in the abdominal wall, with an incidence of 3.2%. The incidence of postoperative IH was significantly higher in the off-midline incision group (8.8%) than in the middle incision groups [the supraumbilical midline (2.6%), infraumbilical midline (2.2%), and umbilical incision (2.9%) groups] (χ2 = 24.985; P < 0.05). Univariate analysis showed that IH occurrence was associated with age, obesity, sex, chronic cough, incision infection, and combined diabetes, anemia, and hypoproteinemia (P < 0.05). Similarly, multivariate analysis showed that off-midline incision, age, sex (female), obesity, incision infection, combined chronic cough, and hypoproteinemia were independent risk factors for IH at the site of laparoscopic colorectal cancer surgery (P < 0.05). CONCLUSION: The incidence of postoperative IH differs between extraction sites for laparoscopic colorectal cancer surgery. The infraumbilical midline incision is associated with a lower hernia rate and is thus a suitable tumor extraction site.

LTBP2 regulates cisplatin resistance in GC cells via activation of the NF-κB2/BCL3 pathway.

Gastric cancer (GC) often develops resistance to cisplatin treatment, but while latent transforming growth factor ß-binding protein (LTBP2) is recognized as a potential regulator in GC, its specific role in cisplatin resistance is not fully understood. This study investigated LTBP2's impact on cisplatin resistance in GC. LTBP2 expression was assessed in various GC cell lines, and its correlation with cisplatin sensitivity was determined through cell viability assays. Lentivirus-mediated LTBP2 silencing in HGC-27 cells demonstrated enhanced cisplatin sensitivity, reduced cell proliferation, and inhibition of the NF-κB2/Bcl-3/cyclin D1 pathway. Additionally, transient transfection overexpressed the NFκB2 gene in LTBP2-silenced HGC-27/DDPR cells, restoring cisplatin sensitivity and upregulating p52/Bcl-3/cyclin D1. In conclusion, silencing LTBP2 could effectively inhibit cell proliferation and mitigate cisplatin resistance via the NFKB noncanonical pathway NFKB2 p52/Bcl-3/cyclin D1. These findings propose LTBP2 as a potential therapeutic target for overcoming cisplatin resistance in GC patients.

NUP85 alleviates lipid metabolism and inflammation by regulating PI3K/AKT signaling pathway in nonalcoholic fatty liver disease.

Nonalcoholic fatty liver disease (NAFLD) is one of the common causes of chronic liver disease in the world. The problem of NAFLD had become increasingly prominent. However, its pathogenesis is still indistinct. As we all know, NAFLD begins with the accumulation of triglyceride (TG), leading to fatty degeneration, inflammation and other liver tissues damage. Notably, structure of nucleoporin 85 (NUP85) is related to lipid metabolism and inflammation of liver diseases. In this study, the results of researches indicated that NUP85 played a critical role in NAFLD. Firstly, the expression level of NUP85 in methionine-choline-deficient (MCD)-induced mice increased distinctly, as well as the levels of fat disorder and inflammation. On the contrary, knockdown of NUP85 had the opposite effects. In vitro, AML-12 cells were stimulated with 2 mm free fatty acids (FFA) for 24 h. Results also proved that NUP85 significantly increased in model group, and increased lipid accumulation and inflammation level. Besides, NUP85 protein could interact with C-C motif chemokine receptor 2 (CCR2). Furthermore, when NUP85 protein expressed at an extremely low level, the expression level of CCR2 protein also decreased, accompanied with an inhibition of phosphorylation of phosphoinositol-3 kinase (PI3K)-protein kinase B (AKT) signaling pathway. What is more, trans isomer (ISRIB), a targeted inhibitor of NUP85, could alleviate NAFLD. In summary, our findings suggested that NUP85 functions as an important regulator in NAFLD through modulation of CCR2.

Plant-LncPipe: a computational pipeline providing significant improvement in plant lncRNA identification.

Long non-coding RNAs (lncRNAs) play essential roles in various biological processes, such as chromatin remodeling, post-transcriptional regulation, and epigenetic modifications. Despite their critical functions in regulating plant growth, root development, and seed dormancy, the identification of plant lncRNAs remains a challenge due to the scarcity of specific and extensively tested identification methods. Most mainstream machine learning-based methods used for plant lncRNA identification were initially developed using human or other animal datasets, and their accuracy and effectiveness in predicting plant lncRNAs have not been fully evaluated or exploited. To overcome this limitation, we retrained several models, including CPAT, PLEK, and LncFinder, using plant datasets and compared their performance with mainstream lncRNA prediction tools such as CPC2, CNCI, RNAplonc, and LncADeep. Retraining these models significantly improved their performance, and two of the retrained models, LncFinder-plant and CPAT-plant, alongside their ensemble, emerged as the most suitable tools for plant lncRNA identification. This underscores the importance of model retraining in tackling the challenges associated with plant lncRNA identification. Finally, we developed a pipeline (Plant-LncPipe) that incorporates an ensemble of the two best-performing models and covers the entire data analysis process, including reads mapping, transcript assembly, lncRNA identification, classification, and origin, for the efficient identification of lncRNAs in plants. The pipeline, Plant-LncPipe, is available at: https://github.com/xuechantian/Plant-LncRNA-pipline.

The NEDD8 activating enzyme inhibitor MLN4924 mitigates doxorubicin-induced cardiotoxicity in mice.

Doxorubicin (DOX) is a widely utilized chemotherapeutic agent in clinical oncology for treating various cancers. However, its clinical use is constrained by its significant side effects. Among these, the development of cardiomyopathy, characterized by cardiac remodeling and eventual heart failure, stands as a major concern following DOX chemotherapy. In our current investigation, we have showcased the efficacy of MLN4924 in mitigating doxorubicin-induced cardiotoxicity through direct inhibition of the NEDD8-activating enzyme, NAE. MLN4924 demonstrated the ability to stabilize mitochondrial function post-doxorubicin treatment, diminish cardiomyocyte apoptosis, alleviate oxidative stress-induced damage in the myocardium, enhance cardiac contractile function, mitigate cardiac fibrosis, and impede cardiac remodeling associated with heart failure. At the mechanistic level, MLN4924 intervened in the neddylation process by inhibiting the NEDD8 activating enzyme, NAE, within the murine cardiac tissue subsequent to doxorubicin treatment. This intervention resulted in the suppression of NEDD8 protein expression, reduction in neddylation activity, and consequential manifestation of cardioprotective effects. Collectively, our findings posit MLN4924 as a potential therapeutic avenue for mitigating doxorubicin-induced cardiotoxicity by attenuating heightened neddylation activity through NAE inhibition, thereby offering a viable and promising treatment modality for afflicted patients.

Enhanced Theranostic Efficacy of 89Zr and 177Lu-Labeled Aflibercept in Renal Cancer: A Viable Option for Clinical Practice.

Vascular endothelial growth factor (VEGF) targeted therapy serves as an important therapeutic approach for renal cancer, but its clinical effectiveness is unsatisfactory. Moreover, there is a lack of reliable biomarkers for preoperative assessment of tumor VEGF expression. This study aimed to explore the potential for further applications of 177Lu/89Zr-labeled aflibercept (Abe), a VEGF-binding agent, in imaging visualization of VEGF expression and therapy for renal cancer. To determine specificity uptake in renal cancer, BALB/c mice with VEGF-expressing Renca tumor were intravenously injected with [89Zr]Zr-Abe, [177Lu]Lu-Abe, or Cy5.5-Abe and the blocking group was designed as a control group. PET, SPECT, and fluorescence images were acquired, and the biodistribution of [89Zr]Zr-Abe and [177Lu]Lu-Abe was performed. Additionally, the [177Lu]Lu-Abe, [177Lu]Lu-Abe-block, 177Lu only, Abe only, and PBS groups were compared for evaluation of the therapeutic effect. To assess the safety, we monitored and evaluated the body weight, blood biochemistry analysis, and whole blood analysis and major organs were stained with hematoxylin and eosin after [177Lu]Lu-Abe treatment. DOTA-Abe was successfully labeled with 177Lu and Df-Abe with 89Zr in our study. The uptake in tumor of [89Zr]Zr-Abe was significantly higher than that of [89Zr]Zr-Abe-block (P < 0.05) and provided excellent tumor contrast in PET images. [177Lu]Lu-Abe demonstrated promising tumor-specific targeting capability with a high and persistent tumor uptake. The standardized tumor volume of [177Lu]Lu-Abe was significantly smaller than those of other treatment groups (P < 0.05). [177Lu]Lu-Abe also had smaller tumor volumes and reduced expression of VEGF and CD31 compared to those of the control groups. Fluorescence images demonstrate higher tumor uptake in the Cy5.5-Abe group compared to the Cy5.5-Abe-block group (P < 0.05). In conclusion, [89Zr]Zr-Abe enables noninvasive analysis of VEGF expression, serving as a valuable tool for assessing the VEGF-targeted therapy effect. Additionally, all of the findings support the enhanced therapeutic efficacy and safety of [177Lu]Lu-Abe, making it a viable option for clinical practice in renal cancer.

Plasmonic nanosensor and pressure-induced transparency based on coupled resonator in a nanoscale system.

Plasmonic nanosensors and the dynamic control of light fields are of the utmost significance in the field of micro- and nano-optics. Here, our study successfully demonstrates a plasmonic nanosensor in a compact coupled resonator system and obtains the pressure-induced transparency phenomenon for the first time to our knowledge. The proposed structure consists of a groove and slot cavity coupled in the metal-insulator-metal waveguide, whose mechanical and optical characteristics are investigated in detail using the finite element method. Simulation results show that we construct a quantitative relationship among the resonator deformation quantity, the applied pressure variation, and the resonant wavelength offset by combining the mechanical and optical properties of the proposed system. The physical features contribute to highly efficient plasmonic nanosensors for refractive index and optical pressure sensing with sensitivity of 1800 nm/RIU and 7.4 nm/MPa, respectively. Furthermore, the light waves are coupled to each other in the resonators, which are detuned due to the presence of pressure, resulting in the pressure-induced transparency phenomenon. It is noteworthy to emphasize that, unlike previously published works, our numerical results take structural deformation-induced changes in optical properties into account, making them trustworthy and practical. The proposed structure introduces a novel, to the best of our knowledge, approach for the dynamic control of light fields and has special properties that can be utilized for the realization of various integrated components.

Process management program to prevent falls in hospitalized patients with neuropsychiatric disorders: a quality improvement program.

BACKGROUND: Falls were among the most common adverse nursing events. The incidence of falls in patients with neuropsychiatric disorders was high, and the occurrence of falls not only caused physical and psychological harm to patients but also led to medical disputes. Therefore, interventions for falls prevention were essential, but evaluations of the intervention process were lacking. METHODS: In this study, a process management program to prevent falls based on the "structure-process-outcome" quality evaluation model was designed and applied to the clinical practice of falls prevention in hospitalized patients with neuropsychiatric disorders. The process quality evaluation checklist to prevent falls was used to supervise the implementation effect of intervention measures to prevent falls, identify the problems in the intervention measures, and make continuous improvements, to reduce the incidence of falls in such hospitalized patients as the final index. RESULTS: The incidence of inpatient falls decreased from 0.199‰ (0.199 per 1000 patient-days) to 0.101‰ (0.101 per 1000 patient-days) before and after the implementation of the process management program for 12 months, 24 months, and 36 months, respectively, and the difference was statistically significant (P<0.05). The probability of falls was reduced by 49% after 36 months of monitoring. Furthermore, the proportion of patients at high risk of falls exhibited a downward trend. CONCLUSION: This quality improvement program was feasible and effective at reducing falls in hospitalized patients with neuropsychiatric disorders. Therefore, attention should be given to monitoring process quality in the management of falls.

Detachable string magnetically controlled capsule endoscopy for the noninvasive diagnosis of esophageal diseases: A prospective, blind clinical study.

BACKGROUND: Traditional esophagogastroduodenoscopy (EGD), an invasive examination method, can cause discomfort and pain in patients. In contrast, magnetically controlled capsule endoscopy (MCE), a noninvasive method, is being applied for the detection of stomach and small intestinal diseases, but its application in treating esophageal diseases is not widespread. AIM: To evaluate the safety and efficacy of detachable string MCE (ds-MCE) for the diagnosis of esophageal diseases. METHODS: Fifty patients who had been diagnosed with esophageal diseases were prospectively recruited for this clinical study and underwent ds-MCE and conventional EGD. The primary endpoints included the sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic accuracy of ds-MCE for patients with esophageal diseases. The secondary endpoints consisted of visualizing the esophageal and dentate lines, as well as the subjects' tolerance of the procedure. RESULTS: Using EGD as the gold standard, the sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic accuracy of ds-MCE for esophageal disease detection were 85.71%, 86.21%, 81.82%, 89.29%, and 86%, respectively. ds-MCE was more comfortable and convenient than EGD was, with 80% of patients feeling that ds-MCE examination was very comfortable or comfortable and 50% of patients believing that detachable string v examination was very convenient. CONCLUSION: This study revealed that ds-MCE has the same diagnostic effects as traditional EGD for esophageal diseases and is more comfortable and convenient than EGD, providing a novel noninvasive method for treating esophageal diseases.

SBRT-SG-01: final results of a prospective multicenter study on stereotactic body radiotherapy for liver metastases.

OBJECTIVE: This study aimed to assess the efficacy and tolerability of stereotactic body radiation therapy (SBRT) for the treatment of liver metastases. METHODS: Patients with up to 5 liver metastases were enrolled in this prospective multicenter study and underwent SBRT. Efficacy outcomes included in-field local control (LC), progression-free survival (PFS), and overall survival (OS). Acute and late toxicities were evaluated using CTCAE v.4.0. RESULTS: A total of 52 patients with 105 liver metastases were treated between 2015 and 2018. The most common primary tumor was colorectal cancer (72% of cases). Liver metastases were synchronous with the primary tumor diagnosis in 24 patients (46.2%), and 21 patients (40.4%) presented with other extrahepatic oligometastases. All patients underwent intensity-modulated radiation therapy (IMRT)/volumetric-modulated arc therapy (VMAT) with image-guided radiation therapy (IGRT) and respiratory gating, and a minimum biologically effective dose (BED10Gy) of 100 Gy was delivered to all lesions. With a median follow-up of 23.1 months (range: 13.4-30.9 months) since liver SBRT, the median actuarial local progression-free survival (local-PFS) was not reached. The actuarial in-field LC rates were 84.9% and 78.4% at 24 and 48 months, respectively. The median actuarial liver-PFS and distant-PFS were 11 and 10.8 months, respectively. The actuarial median overall survival (OS) was 27.7 months from SBRT and 52.5 months from metastases diagnosis. Patients with lesion diameter ≤ 5 cm had significantly better median liver-PFS (p = 0.006) and OS (p = 0.018). No acute or late toxicities of grade ≥ 3 were observed. CONCLUSIONS: This prospective multicenter study confirms that liver SBRT is an effective alternative for the treatment of liver metastases, demonstrating high rates of local control and survival while maintaining a low toxicity profile.

[Effects of Combined Stress of High Density Polyethylene Microplastics and Chlorimuron-ethyl on Soybean Growth and Rhizosphere Bacterial Community].

With the vigorous development of agriculture in China， plastic mulch film and pesticides are widely used in agricultural production. However， the accumulation of microplastics （formed by the degradation of plastic mulch film） and pesticides in soil has also caused many environmental problems. At present， the environmental biological effects of microplastics or pesticides have been reported， but there are few studies on the combined effects on crop growth and the rhizosphere soil bacterial community. Therefore， in this study， the high density polyethylene microplastics （HDPE， 500 mesh） were designed to be co-treated with sulfonylurea herbicide chlorimuron-ethyl to study their effects on soybean growth. In addition， the effects of the combined stress of HDPE and chlorimuron-ethyl on soybean rhizosphere soil bacterial community diversity， structure composition， microbial community network， and soil function were investigated using high-throughput sequencing technology， interaction network， and PICRUSt2 function analysis to clarify the combined toxicity of HDPE and chlorimuron-ethyl to soybean. The results showed that the half-life of chlorimuron-ethyl in soil was prolonged by the 1% HDPE treatment （from 11.5 d to 14.3 d）， and the combined stress of HDPE and chlorimuron-ethyl had more obvious inhibition effects on soybean growth than that of the single pollutant or control. The HiSeq 2 500 sequencing showed that the rhizosphere bacterial community of soybean was composed of 20 phyla and 312 genera under combined stress， the number of phyla and genera was significantly less than that of the control and single pollutant treatment， and the relative abundances of bacteria with potential biological control and plant growth-promoting characteristics （such as Nocardioides and Sphingomonas） were reduced. Alpha diversity analysis showed that the combined stress significantly reduced the richness and diversity of the soybean rhizosphere bacterial community， and Beta diversity analysis showed that the combined stress significantly changed the structure of the bacterial community. The dominant flora of the rhizosphere bacterial community were regulated， and the abundances of secondary functional layers such as amino acid metabolism， energy metabolism， and lipid metabolism were reduced under combined stress by the analysis of LEfSe and PICRUSt2. It was inferred from the network analysis that the combined stress of HDPE and chlorimuron-ethyl reduced the total number of connections and network density of soil bacteria， simplified the network structure， and changed the important flora species to maintain the stability of the network. The results above indicated that the combined stress of HDPE and chlorimuron-ethyl significantly affected the growth of soybean and changed the rhizosphere bacterial community structure， soil function， and network structure. Compared with that of the single pollutant treatment， the potential risk of combined stress was greater. The results of this study can provide guidance for evaluating the ecological risks of polyethylene microplastics and chlorimuron-ethyl and for the remediation of contaminated soil.

CO2 Hydrogenation to CH3OH on Metal-Doped TiO2(110): Mechanisms, Strain Effect and a New Thermodynamic-Kinetic Relation.

Surface strain and linear thermodynamic-kinetic relation are interesting topics in catalysis. Development of low temperature methanol catalysts of high activity and selectivity is of particularly importance for conversion of CO2 to methanol. In the present paper CO2 hydrogenation to methanol on Znx@TiO2(110) (x=0-2) was explored using density functional calculations and microkinetic simulations. The reaction mechanisms on the three model systems were determined and it is shown that Zn2@TiO2(110) is the most active. The most favorable pathway on Zn2@TiO2(110) is identified and CO2+H to HCOO is found to be the rate-controlling step. It is demonstrated that there is a linear relation (named AEB relation) between the adsorption energies of the initial states and the barriers for the controlling step on the 18 systems studied. Calculations on strained surfaces show that the AEB relation exists within ±1 % strain. Sr2@TiO2(110) and -1 % strained CaZn and ZnCu doped TiO2(110) are potential good low temperature catalysts and deserve experimental testing.

Development of High-Performance Iron-Based Phosphate Cathodes toward Practical Na-Ion Batteries.

Iron-based phosphate cathode of Na4Fe3(PO4)2(P2O7) has been regarded as a low-cost and structurally stable cathode material for Na-ion batteries (NIBs). However, their practical application is greatly hindered by the insufficient electrochemical performance and limited energy density. Here, we report a new iron-based phosphate cathode of Na4.5Fe3.5(PO4)2.5(P2O7) with the intergrown heterostructure of the maricite-type NaFePO4 and orthorhombic Na4Fe3(PO4)2(P2O7) phases at a mole ratio of 0.5:1. Benefited from the increased composition ratio and the spontaneous activation of the maricite-type NaFePO4 phase, the as-prepared Na4.5Fe3.5(PO4)2.5(P2O7) composites deliver a reversible capacity over 130 mA h g-1 and energy density close to 400 W h kg-1, which is far beyond that of the single-phase Na4Fe3(PO4)2(P2O7) cathode (∼120 mA h g-1 and ∼350 W h kg-1). Moreover, the kg-level products from the scale-up synthesis demonstrate a stable cycling performance over 2000 times at 3 C in pouch cells. We believe that our findings could show the way forward the practical application of the iron-based phosphate cathodes for NIBs.

DPP8/9 inhibition attenuates the TGF-ß1-induced excessive deposition of extracellular matrix (ECM) in human mesangial cells via Smad and Akt signaling pathways.

The pathogenesis of glomerular diseases is strongly influenced by abnormal extracellular matrix (ECM) deposition in mesangial cells. Dipeptidyl peptidase IV (DPPIV) enzyme family contains DPP8 and DPP9, which are involved in multiple diseases. However, the pathogenic roles of DPP8 and DPP9 in mesangial cells ECM deposition remain unclear. In this study, we observed that DPP8 and DPP9 were significantly increased in glomerular mesangial cells and podocytes in CKD patients compared with healthy individuals, and DPP9 levels were higher in the urine of IgA nephropathy (IgAN) patients than in control urine. Therefore, we further explored the mechanism of DPP8 and DPP9 in mesangial cells and revealed a significant increase in the expression of DPP8 and DPP9 in human mesangial cells (HMCs) following TGF-ß1 stimulation. Silencing DPP8 and DPP9 by siRNAs alleviated the expression of ECM-related proteins including collagen Ⅲ, collagen Ⅳ, fibronectin, MMP2, in TGF-ß1-treated HMCs. Furthermore, DPP8 siRNA and DPP9 siRNA inhibited TGF-ß1-induced phosphorylation of Smad2 and Smad3, as well as the phosphorylation of Akt in HMCs. The findings suggested the inhibition of DPP8/9 may alleviate HMCs ECM deposition induced by TGF-ß1 via suppressing TGF-ß1/Smad and AKT signaling pathways.

Plant growth-promoting bacteria improve the Cd phytoremediation efficiency of soils contaminated with PE-Cd complex pollution by influencing the rhizosphere microbiome of sorghum.

Composite pollution by microplastics and heavy metals poses a potential threat to the soilplant system and has received increasing attention. Plant growth-promoting bacteria (PGPB) have good application potential for the remediation of combined microplastic and heavy metal pollution, but few related studies exist. The present study employed a pot experiment to investigate the effects of inoculation with the PGPB Bacillus sp. SL-413 and Enterobacter sp. VY-1 on sorghum growth and Cd accumulation under conditions of combined cadmium (Cd) and polyethylene (PE) pollution. Cd+PE composite contamination led to a significant reduction in sorghum length and biomass due to increased toxicity. Inoculation with Bacillus sp. SL-413 and Enterobacter sp. VY-1 alleviated the stress caused by Cd+PE complex pollution, and the dry weight of sorghum increased by 25.7% to 46.1% aboveground and by 12.3% to 45.3% belowground. Bacillus sp. SL-413 and Enterobacter sp. VY-1 inoculation increased the Cd content and accumulation in sorghum and improved the phytoremediation efficiency of Cd. The inoculation treatment effectively alleviated the nutrient stress caused by the reduction in soil mineral nutrients due to Cd+PE composite pollution. The composition of the soil bacterial communities was also affected by the Cd, Cd+PE and bacterial inoculation treatments, which affected the diversity of the soil bacterial communities. Network analyses indicated that bacterial inoculation regulated the interaction of rhizospheric microorganisms and increased the stability of soil bacterial communities. The Mantel test showed that the changes in the soil bacterial community and function due to inoculation with Bacillus sp. SL-413 and Enterobacter sp. VY-1 were important factors influencing sorghum growth and Cd remediation efficiency. The results of this study will provide new evidence for the research on joint plantmicrobe remediation of heavy metal and microplastic composite pollution.

Zinc oxide nanoparticles alleviate cadmium toxicity and promote tolerance by modulating programmed cell death in alfalfa (Medicago sativa L.).

Cadmium (Cd) can induce programmed cell death (PCD) and zinc oxide nanoparticles (ZnO NPs) effectively alleviate Cd stress. However, the mechanisms of ZnO NPs-mediated Cd detoxification in alfalfa (Medicago sativa L.) are limited. The pot experiment was conducted with Cd soil (19.2 mg kg-1) and foliar ZnO NPs (100 mg L-1) on alfalfa. The results showed that Cd reduced shoot height and biomass, and accumulated reactive oxygen species (ROS), resulting in oxidative stress and further PCD (plasmolysis, cytosolic and nuclear condensation, subcellular organelle swelling, and cell death). ZnO NPs positively regulated the antioxidant system, cell membrane stability, ultrastructure, osmotic homeostasis, and reduced PCD, indicating a multi-level coordination for the increased Cd tolerance. ZnO NPs up-regulated the activity and expression of antioxidant enzymes and regulated PCD-related genes to scavenge ROS and mitigate PCD caused by Cd. The genes related to ZnO NPs-mediated Cd detoxification were significantly enriched in cell death and porphyrin and chlorophyll metabolism. Overall, it elucidates the molecular basis of ZnO NPs-mediated Cd-tolerance by promoting redox and osmotic homeostasis, maintaining cellular ultrastructure, reducing Cd content, and attenuating Cd-induced PCD. it provides a promising application of ZnO NPs to mitigate Cd phytotoxicity and the related cellular and biochemical mechanisms. ENVIRONMENTAL IMPLICATION: Cd, one of the most toxic heavy metals, has caused serious environmental pollution. ZnO NPs can effectively alleviate Cd stress on plants and the environment. This study revealed that foliar-applied ZnO NPs alleviate Cd toxicity by mitigating the oxidative damage and regulating Cd-induced PCD via morphological, physiological, and transcriptomic levels. The findings elucidated the molecular basis of ZnO NPs-mediated Cd tolerance by promoting osmotic and redox homeostasis, reducing Cd content and lipid peroxidation, attenuating Cd-induced PCD features, and altering PCD-related genes in alfalfa. The study laid a theoretical foundation for the safe production of alfalfa under Cd pollution.

Insight into the relationship between metabolic enzymes and oxadiazon degradation in Oryza sativa for reducing environmental risks.

Oxadiazon (ODZ) is extensively utilized in agricultural fields for weed control owing to its strong effectiveness. However, excessive loading of ODZ in water bodies and agricultural soils can lead to various environmental concerns. Therefore, it is crucial to understand the ODZ metabolic process and associated mechanisms in crops to assess the likelihood of ODZ contamination in the environment. This study aimed to assess the effects of ODZ on the growth and toxicological responses of rice (Oryza sativa). The growth of rice tissues was notably compromised with the increase in ODZ concentrations. RNA sequencing in combination with liquid chromatography-quadrupole-time-of-flight-high-resolution mass spectrometry/mass spectrometry (LC-Q-TOF-HRMS/MS) analysis allowed for the identification of numerous transcriptional components associated with ODZ metabolism. Four libraries comprising rice roots and shoots exposed to ODZ were RNA-sequenced in triplicate. The application of environmentally realistic ODZ concentrations upregulated the expression of 844 genes in shoots and 1476 genes in roots. Gene enrichment analysis revealed the presence of multiple enzymes involved in ODZ metabolism and detoxification. These enzymes play a critical role in mitigating environmental stress and facilitating xenobiotic metabolism. Notably, among differentially expressed genes, several key enzymes were identified, including cytochrome P450s, protein kinases, aminotransferases, and ATP-binding cassette transporters involved in the metabolic process. Using LC-Q-TOF-HRMS/MS, 3 metabolites and 13 conjugates were identified in multiple metabolic pathways involving oxidation, hydrolysis, glycosylation, acetylation, and methylation. This study successfully established a potential link between the specific metabolic products of ODZ and increased activities of their corresponding enzymes. Moreover, this study considerably elucidates the detailed pathways and mechanisms involved in ODZ metabolism. The study findings provide valuable insights into the development of genotypes for reducing ODZ residues in paddy fields and minimizing their accumulation in rice crops.

The genetic landscape and phenotypic spectrum of GAA-FGF14 ataxia in China: a large cohort study.

BACKGROUND: An intronic GAA repeat expansion in FGF14 was recently identified as a cause of GAA-FGF14 ataxia. We aimed to characterise the frequency and phenotypic profile of GAA-FGF14 ataxia in a large Chinese ataxia cohort. METHODS: A total of 1216 patients that included 399 typical late-onset cerebellar ataxia (LOCA), 290 early-onset cerebellar ataxia (EOCA), and 527 multiple system atrophy with predominant cerebellar ataxia (MSA-c) were enrolled. Long-range and repeat-primed PCR were performed to screen for GAA expansions in FGF14. Targeted long-read and whole-genome sequencing were performed to determine repeat size and sequence configuration. A multi-modal study including clinical assessment, MRI, and neurofilament light chain was conducted for disease assessment. FINDINGS: 17 GAA-FGF14 positive patients with a (GAA)≥250 expansion (12 patients with a GAA-pure expansion, five patients with a (GAA)≥250-[(GAA)n (GCA)m]z expansion) and two possible patients with biallelic (GAA)202/222 alleles were identified. The clinical phenotypes of the 19 positive and possible positive cases covered LOCA phenotype, EOCA phenotype and MSA-c phenotype. Five of six patients with EOCA phenotype were found to have another genetic disorder. The NfL levels of patients with EOCA and MSA-c phenotypes were significantly higher than patients with LOCA phenotype and age-matched controls (p < 0.001). NfL levels of pre-ataxic GAA-FGF14 positive individuals were lower than pre-ataxic SCA3 (p < 0.001) and similar to controls. INTERPRETATION: The frequency of GAA-FGF14 expansion in a large Chinese LOCA cohort was low (1.3%). Biallelic (GAA)202/222 alleles and co-occurrence with other acquired or hereditary diseases may contribute to phenotypic variation and different progression. FUNDING: This study was funded by the National Key R&D Program of China (2021YFA0805200 to H.J.), the National Natural Science Foundation of China (81974176 and 82171254 to H.J.; 82371272 to Z.C.; 82301628 to L.W.; 82301438 to Z.L.; 82201411 to L.H.), the Innovation Research Group Project of Natural Science Foundation of Hunan Province (2020JJ1008 to H.J.), the Key Research and Development Program of Hunan Province (2020SK2064 to H.J.), the Innovative Research and Development Program of Development and Reform Commission of Hunan Province to H.J., the Natural Science Foundation of Hunan Province (2024JJ3050 to H.J.; 2022JJ20094 and 2021JJ40974 to Z.C.; 2022JJ40783 to L.H.; 2022JJ40703 to Z.L.), the Project Program of National Clinical Research Center for Geriatric Disorders (Xiangya Hospital, 2020LNJJ12 to H.J.), the Central South University Research Programme of Advanced Interdisciplinary Study (2023QYJC010 to H.J.) and the Science and Technology Innovation Program of Hunan Province (2022RC1027 to Z.C.). D.P. holds a Fellowship award from the Canadian Institutes of Health Research (CIHR).

Expression, purification, and characterization of transmembrane protein homogentisate solanesyltransferase.

Homogentisate solanesyltransferase (HST) is a crucial enzyme in the plastoquinone biosynthetic pathway and has recently emerged as a promising target for herbicides. In this study, we successfully expressed and purified a stable and highly pure form of seven times transmembrane protein Chlamydomonas reinhardtii HST (CrHST). The final yield of CrHST protein obtained was 12.2 mg per liter of M9 medium. We evaluated the inhibitory effect on CrHST using Des-Morpholinocarbony Cyclopyrimorate (DMC) and found its IC50 value to be 3.63 ± 0.53 µM, indicating significant inhibitory potential. Additionally, we investigated the substrate affinity of CrHST with two substrates, determining the Km values as 22.76 ± 1.70 µM for FPP and 48.54 ± 3.89 µM for HGA. Through sequence alignment analyses and three-dimensional structure predictions, we identified conserved amino acid residues forming the active cavity in the enzyme. The results from molecular docking and binding energy calculations indicate that DMC has a greater binding affinity with HST compared to HGA. These findings represent substantial progress in understanding CrHST's properties and potential for herbicide development. KEY POINTS: • First high-yield transmembrane CrHST protein via E. coli system • Preliminarily identified active cavity composition via activity testing • Determined substrate and inhibitor modes via molecular docking.