MORN motif-containing protein OsMORN1 and OsMORN2 are crucial for rice pollen viability and cold tolerance.

The pollen viability directly affects the pollination process and the ultimate grain yield of rice. Here, we identified that the MORN motif-containing proteins, OsMORN1 and OsMORN2, had a crucial role in maintaining pollen fertility. Compared with the wild type (WT), the pollen viability of the osmorn1 and osmorn2 mutants was reduced, and pollen germination was abnormal, resulting in significantly lower spikelet fertility, seed-setting rate, and grain yield per plant. Further investigation revealed that OsMORN1 was localized to the Golgi apparatus and lipid droplets. Lipids associated with pollen viability underwent alterations in osmorn mutants, such as the diacylglyceride (18:3_18:3) was 5.1-fold higher and digalactosyldiacylglycerol (18:2_18:2) was 5.2-fold lower in osmorn1, while the triacylglycerol (TG) (16:0_18:2_18:3) was 8.3-fold higher and TG (16:0_18:1_18:3) was 8.5-fold lower in osmorn2 than those in WT. Furthermore, the OsMORN1/2 was found to be associated with rice cold tolerance, as osmorn1 and osmorn2 mutants were more sensitive to chilling stress than WT. The mutants displayed increased hydrogen peroxide accumulation, reduced antioxidant enzyme activities, elevated malondialdehyde content, and a significantly decreased seedling survival rate. Lipidomics analysis revealed distinct alterations in lipids under low temperature, highlighting significant changes in TG (18:2_18:3_18:3) and TG (18:4_18:2_18:2) in osmorn1, TG (16:0_18:2_18:2) and PI (17:2_18:3) in osmorn2 compared to the WT. Therefore, it suggested that OsMORN1 and OsMORN2 regulate both pollen viability and cold tolerance through maintaining lipid homeostasis.

Molecular-Level Insights into the Relationship between Volatility of Organic Aerosol Constituents and PM2.5 Air Pollution Levels: A Study with Ultrahigh-Resolution Mass Spectrometry.

Volatility of organic aerosols (OAs) significantly influences new particle formation and the occurrence of particulate air pollution. However, the relationship between the volatility of OA and the level of particulate air pollution (i.e., particulate matter concentration) is not well understood. In this study, we compared the chemical composition (identified by an ultrahigh-resolution Orbitrap mass spectrometer) and volatility (estimated based on a predeveloped parametrization method) of OAs in urban PM2.5 (particulate matter with aerodynamic diameter ≤ 2.5 µm) samples from seven German and Chinese cities, where the PM2.5 concentration ranged from a light (14 µg m-3) to heavy (319 µg m-3) pollution level. A large fraction (71-98%) of compounds in PM2.5 samples were attributable to intermediate-volatility organic compounds (IVOCs) and semivolatile organic compounds (SVOCs). The fraction of low-volatility organic compounds (LVOCs) and extremely low-volatility organic compounds (ELVOCs) decreased from clean (28%) to heavily polluted urban regions (2%), while that of IVOCs increased from 34 to 62%. We found that the average peak area-weighted volatility of organic compounds in different cities showed a logarithmic correlation with the average PM2.5 concentration, indicating that the volatility of urban OAs increases with the increase of air pollution level. Our results provide new insights into the relationship between OA volatility and PM pollution levels and deepen the understanding of urban air pollutant evolution.

The HN protein of Newcastle disease virus induces cell apoptosis through the induction of lysosomal membrane permeabilization.

Lysosomes are acidic organelles that mediate the degradation and recycling of cellular waste materials. Damage to lysosomes can cause lysosomal membrane permeabilization (LMP) and trigger different types of cell death, including apoptosis. Newcastle disease virus (NDV) can naturally infect most birds. Additionally, it serves as a promising oncolytic virus known for its effective infection of tumor cells and induction of intensive apoptotic responses. However, the involvement of lysosomes in NDV-induced apoptosis remains poorly understood. Here, we demonstrate that NDV infection profoundly triggers LMP, leading to the translocation of cathepsin B and D and subsequent mitochondria-dependent apoptosis in various tumor and avian cells. Notably, the released cathepsin B and D exacerbate NDV-induced LMP by inducing the generation of reactive oxygen species. Additionally, we uncover that the viral Hemagglutinin neuraminidase (HN) protein induces the deglycosylation and degradation of lysosome-associated membrane protein 1 (LAMP1) and LAMP2 dependent on its sialidase activity, which finally contributes to NDV-induced LMP and cellular apoptosis. Overall, our findings elucidate the role of LMP in NDV-induced cell apoptosis and provide novel insights into the function of HN during NDV-induced LMP, which provide innovative approaches for the development of NDV-based oncolytic agents.

A tuning fork gyroscope with drive-sense orthogonal thin-walled holes for high sensitivity.

A tuning fork gyroscope (TFG) with orthogonal thin-walled round holes in the driving and sensing directions is proposed to improve sensitivity. The thin walls formed by through holes produce stress concentration, transforming the small displacement of tuning fork vibration into a large concentrated strain. When piezoelectric excitation or detection is carried out here, the driving vibration displacement and detection output voltage can be increased, thereby improving sensitivity. Besides, quadrature coupling can be suppressed because the orthogonal holes make the optimal excitation and detection positions in different planes. The finite element method is used to verify the benefits of the holes, and the parameters are optimized for better performance. The experimental results show that the sensitivity of the prototype gyroscope with a driving frequency of 890.68 Hz is 100.32 mV/(°/s) under open-loop driving and detection, and the rotation rate can be resolved at least 0.016 (°/s)/Hz, which is about 6.7 times better than that of the conventional TFG. In addition, the quadrature error is reduced by 2.7 times. The gyroscope has a simple structure, high reliability, and effectively improves sensitivity, which is helpful to guide the optimization of piezoelectric gyroscopes and derived MEMS gyroscopes.

Spatial-temporal distribution and potential risk of pesticides in ambient air in the North China Plain.

The intensive use of pesticides in the North China Plain (NCP) has resulted in widespread contamination of pesticides in the local atmosphere, posing risks to air quality and human health. However, the occurrence and distribution of atmospheric pesticides in the NCP as well as their risk assessment have not been well investigated. In this study, 300 monthly samples were collected using passive air samplers with polyurethane foam at ten rural sites with different crop systems in Quzhou county, the NCP, from June 2021 to May 2022. The pesticides were quantified using mass-spectrometric techniques. Our results revealed that chlorpyrifos, carbendazim, and atrazine were the most frequently found pesticides in the air samples, with detection frequencies of ≥ 87 % across the samples. The average concentrations of atmospheric pesticides during spring (7.47 pg m-3) and summer (16.05 pg m-3) were significantly higher than those during autumn (2.04 pg m-3) and winter (1.71 pg m-3), attributable to the intensified application of pesticides during the warmer seasons. Additionally, cash crop sites exhibited higher concentrations (10.26 pg m-3) of atmospheric pesticides compared to grain crop (5.59 pg m-3) and greenhouse sites (3.81 pg m-3), primarily due to more frequent pesticides spraying events in cash crop fields. These findings indicate a distinct spatial-temporal distribution pattern of atmospheric pesticides influenced by both seasons and crop systems. Furthermore, the model-based inhalation risk assessment indicates that inhalation exposure to atmospheric pesticides is unlikely to pose a significant public concern.

Sustainable ultrasound-assisted extraction of Polygonatum sibiricum saponins using ionic strength-responsive natural deep eutectic solvents.

The sustainable extraction of saponins was investigated using natural deep eutectic solvents (NADESs) combined with ultrasound-assisted extraction. A novel NADES (butyric acid-urea) that was responsive to ionic strength was designed and used as the extractant. Ultrasound treatment and a catalyst ferric chloride with plant cell wall breaking function were applied to improve the extraction efficiency.Since the solubility of the NADES varied significantly with ionic strength, 95% of NADES was readily separated from the water phase after the addition of sodium chloride, while saponins remained in the water phase for easy collection. The reuse capacity of NADES, the eco-friendliness of the extraction method, and the antioxidant activity of the extract were further evaluated.NADES was continuously recovered and used to extract Polygonatum sibiricum powder: the yield of saponins did not decrease after five cycles of recovery and re-extraction. The penalty point on the "Eco-scale" suggested that the extraction method was "green" (i.e. eco-friendly).Compared with ethanol extracts, the NADES extracts showed a higher saponin concentration and antioxidant activity.The study can contribute to the sustainable and green extraction of hydrophilic active substances in the food and pharmaceutical industries.

Enantioselective Behaviors of Chiral Pesticides and Enantiomeric Signatures in Foods and the Environment.

Unreasonable application of pesticides may result in residues in the environment and foods. Chiral pesticides consist of two or more enantiomers, which may exhibit different behaviors. This Review intends to provide progress on the enantioselective residues of chiral pesticides in foods. Among the main chiral analytical methods, high performance liquid chromatography (HPLC) is the most frequently utilized. Most chiral pesticides are utilized as racemates; however, due to enantioselective dissipation, bioaccumulation, biodegradation, and chiral conversion, enantiospecific residues have been found in the environment and foods. Some chiral pesticides exhibit strong enantioselectivity, highlighting the importance of evaluation on an enantiomeric level. However, the occurrence characteristics of chiral pesticides in foods and specific enzymes or transport proteins involved in enantioselectivity needs to be further investigated. This Review could help the production of some chiral pesticides to single-enantiomer formulations, thereby reducing pesticide consumption as well as increasing food production and finally reducing human health risks.

Moxibustion treatment for Parkinson's disease: study protocol for a randomized controlled trial.

BACKGROUND: Parkinson's disease (PD) is the second most common neurodegenerative disorder and seriously affects quality of life globally. Moxibustion is widely used to treat neurodegenerative diseases in the clinic and has achieved a beneficial clinical effect. However, strict control and high-quality randomized controlled trials are still lacking. Therefore, this trial aims to evaluate the clinical efficacy and safety of moxibustion in patients with PD and preliminarily explore the underlying mechanism. METHODS: This is a randomized, single-blind and placebo-controlled trial design in which 70 eligible participants will be randomly divided into a moxibustion group and a sham moxibustion group. Baihui (DU20) and Sishenchong (EX-HN1) are selected for both groups. The treatment will be performed for 30 min per session, two sessions a week for 8 weeks. The mean change in MDS-UPDRS scores (including MDS-UPDRS II, III subscale scores and total scores) from baseline to the observation points will be the primary outcome. The secondary outcomes will include scores on the Parkinson's Disease Questionnaire-39 (PDQ-39), Fatigue Severity Scale (FSS), Parkinson Disease Sleep Scale (PDSS), Montreal Cognitive Assessment (MoCA), and Self-Rating Depression Scale (SDS) as well as the Wexner constipation score. All the above outcomes will be assessed at 4 and 8 weeks. Laboratory blood biochemical analysis and functional magnetic resonance imaging (fMRI) will be conducted at baseline and at the end of treatment to explore the potential mechanisms of moxibustion in regulating PD. DISCUSSION: In conclusion, the results of this trial will reveal whether moxibustion is effective for treating motor and nonmotor symptoms in PD. This trial will also preliminarily explore the underlying mechanism of the regulatory effect of moxibustion in PD, which will contribute to providing a theoretical basis for the treatment of PD. TRIAL REGISTRATION: ClinicalTrials.gov ChiCTR2000029745. Registered on 9 August 2021.

Tiaogan Jiejiu Tongluo Formula attenuated alcohol-induced chronic liver injury by regulating lipid metabolism in rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Tiaogan Jiejiu Tongluo Formula (TJTF), a traditional Chinese medicine formula, is modified from the well-known ancient prescription Danzhi-Xiaoyao Powder (DXP). Owing to its ability to regulate liver, strengthen spleen, detoxicating, and dredge collaterals in Chinese medicine, TJTF is usually used to treat anxiety, hypertension, alcoholic fatty liver disease in clinical application. However, the protective effect and potential molecular mechanism of TJTF on alcoholic liver injury has not fully been clarified. AIM OF THE STUDY: To explore the effect of TJTF on chronic alcoholic liver injury and figure out whether its effects were due to the regulation of lipid metabolism. MATERIAL AND METHODS: 75 male SD rats were divided into the following five groups, control group, EtOH group, TJTF high dose group, TJTF low dose group and silybin group. Then a chronic alcoholic liver injury model was established by increasing concentration of 56% ethanol in rats. The rats in each TJTF group were given the corresponding dose of TJTF, the rats in the silybin group were given silybin, the rats in the control group and the EtOH group were given distilled water by gavage, once a day for 8 consecutive weeks. The components of TJTF were analyzed by UPLC-Q-TOF-MS. Hematoxylin and Eosin (H&E) was used to assess the severity of liver injury. in the pathological examination. Periodic acid-Schiff (PAS) and oil red O staining were used to evaluate the degree of the liver glycogen accumulation and lipid deposition, respectively. The serum ALT, AST, T-CHO, TG, LDL-C, ADH, HDL-C, and ALDH levels as well as liver tissue GSH, MDA, and SOD levels were analyzed in rats. Immunohistochemistry and western blotting were used to detect lipid metabolism-related proteins expressed in rat liver. RESULTS: TJTF significantly alleviated the chronic liver injury caused by alcohol in rats, and enhanced liver function. TJTF significantly decreased AST, ALT, ADH levels and increased ALDH level of serum, and increased GSH, SOD levels and decreased MDA level of liver tissue. In addition, TJTF significantly decreased the serum T-CHO, TG and LDL-C levels and increased HDL-C level in chronic alcoholic liver injury rats by regulating the expression of lipid metabolism associated proteins including p-LKB1, p-AMPKα, p-ACC, FAS, HMGCR, SREBP-1c, PPARα and CPT-1A. The results of western blot and immunohistochemical staining confirmed that TJTF can inhibit lipid production and promote fatty acid oxidation in the liver tissue of chronic alcoholic liver injury rats by activating the LKB1-AMPKα axis and then downregulating the protein expressions of p-ACC, FAS, HMGCR and SREBP-1c, as well as promoting the protein expressions of PPARα and CPT-1A. Meanwhile, TJTF also increased the glycogen content of liver and alleviated the liver damage. CONCLUSION: According to current research, TJTF is effective in treating chronic liver damage induced by alcohol in rats. Additionally, TJTF exhibits the protective benefits by modulating LKB1-AMPKα signal axis, which in turn inhibits the synthesis of lipids and promotes the oxidation of fatty acids.

Staplers versus energy devices for the intersegmental plane separation in thoracoscopic segmentectomy: a comparative study.

BACKGROUND: In segmentectomy, in addition to the anatomy of the segmental hilum, the identification and separation of the intersegmental plane is also an important step of the operation. Because of its simplicity and high efficiency, most thoracic surgeons choose the staplers. But the energy devices also have its unique advantages in the separation of the intersegmental plane. This study compared the clinical efficacy of staplers and energy devices in the separation of the intersegmental planes during the uniport thoracoscopic segmentectomy through the clinical data. METHODS: Clinical data of 89 patients undergoing uniport VATS lung segmentectomy from January 2019 to October 2020 at the First Affiliated Hospital of Soochow University were analyzed retrospectively. According to the different treatment methods of intersegmental plane, the patients were divided into two groups, 55 in the stapler group and 34 in the energy device group. The clinical data of the two groups were compared and analyzed statistically. And the univariate and multivariate logistic regression were also used to explore the influencing factors of postoperative complications. RESULTS: Lung segmentectomy was successfully operated in both groups. There were statistically significant differences in operative duration, number of staplers used, surgical expenses and postoperative complications (P < 0.05). In terms of general data, including tumor location, operative hemorrhage, drainage volume on the first postoperative day, total postoperative drainage volume, postoperative chest tube retention duration, postoperative hospital stay, postoperative blood routine indexes, and postoperative pulmonary function indexes after 3 months, no significant differences were observed (P > 0.05). Smoking history (OR 5.08, 95% CI 1.05-24.56, P = 0.043) and intersegmental plane treatment (OR 3.18, 95% CI 1.11-9.14, P = 0.031) were risk factors for postoperative complications. Patients of the energy device group had a higher incidence of postoperative complications. CONCLUSIONS: In uniport thoracoscopic segmentectomy, the use of energy devices to treat the intersegmental plane will result in longer operative duration and higher postoperative complication rate, but it does not affect postoperative recovery and can help reduce surgical expenses. Both methods are safe and reliable. Clinically, the two methods can be reasonably selected according to the specific situation.

Transcriptional multiomics reveals the mechanism of seed deterioration in Nicotiana tabacum L. and Oryza sativa L.

INTRODUCTION: Mature seeds deteriorate gradually and die eventually during long-term storage. Controlled deterioration is often used to accelerate the seed deterioration rate to assess the seed vigor and physiological quality of seed lots. OBJECTIVES: Although it is well known that the process of seed deterioration produced by controlled deterioration is distinct from that caused by long-term storage, the differences in transcriptional levels have not been reported. Clarifying the mechanism of seed deterioration is critical for identifying, conserving and utilizing germplasm resources. METHODS: Tobacco (Nicotiana tabacum L.) seeds were studied thoroughly using transcriptome, small RNA, and degradome sequencing after long-term storage (LS) and controlled deterioration (CD). Co-expression trend analysis identified transcripts involved in tobacco seed deterioration, while phylogenetic analysis helped to uncover comparable targets in rice (Oryza sativa L.) for further verification and utilization. RESULTS: In LS and CD, a total of 2,112 genes and 164 miRNAs were differentially expressed, including 20 interaction miRNA-mRNA pairs with contrasting expression. Transcriptional multiomics found that the main causes of LS were plant hormone signal transduction and protein processing in the endoplasmic reticulum, whereas the primary cause of CD was nucleotide excision repair dysfunction. The homeostatic balance of RNA degradation and the spliceosome occurred in both modes of seed deterioration. Additionally, co-expression trend analysis identified two coherent pairs, nta-miR160b-NtARF18 and nta-miR396c-NtMBD10, as being significant in LS and CD, respectively. For utilization, rice homologous targets OsARF18 and OsMBD707 were verified to play similar roles in LS and CD, respectively. CONCLUSION: This study demonstrated the transcriptional mechanism of tobacco and key genes in seed deterioration. And the application of key genes in rice also verified the feasibility of the multiomics method, guiding the identification of candidate genes to precisely delay seed deterioration in other species of seed research.

The AMPK pathway in fatty liver disease.

Lipid metabolism disorders are the primary causes for the occurrence and progression of various liver diseases, including non-alcoholic fatty liver disease (NAFLD) and alcoholic fatty liver disease (AFLD) caused by a high-fat diet and ethanol. AMPK signaling pathway plays an important role in ameliorating lipid metabolism disorders. Progressive research has clarified that AMPK signal axes are involved in the prevention and reduction of liver injury. Upregulation of AMK can alleviate FLD in mice induced by alcohol or insulin resistance, type 2 diabetes, and obesity, and most natural AMPK agonists can regulate lipid metabolism, inflammation, and oxidative stress in hepatocytes, consequently regulating FLD in mice. In NAFLD and AFLD, increasing the activity of AMPK can inhibit the synthesis of fatty acids and cholesterol by down-regulating the expression of adipogenesis gene (FAS, SREBP-1c, ACC and HMGCR); Simultaneously, by increasing the expression of fatty acid oxidation and lipid decomposition genes (CPT1, PGC1, and HSL, ATGL) involved in fatty acid oxidation and lipid decomposition, the body's natural lipid balance can be maintained. At present, some AMPK activators are thought to be beneficial during therapeutic treatment. Therefore, activation of AMPK signaling pathway is a potential therapeutic target for disorders of the liver. We summarized the most recent research on the role of the AMPK pathway in FLD in this review. Simultaneously, we performed a detailed description of each signaling axis of the AMPK pathway, as well as a discussion of its mechanism of action and therapeutic significance.

Feasibility and applicability of pulmonary nodule day surgery in thoracic surgery.

Background: More patients with lung diseases were identified with low-dose computed tomography (CT) popularization and increasing physical examination awareness. Day surgery was routinely conducted in many departments as a relatively mature diagnosis and treatment mode. Thus, this study aimed to assess the feasibility of day surgery in thoracic surgery for pulmonary surgery and provide guidance for selecting suitable patients. Methods: This study retrospectively analyzed the clinical data of patients with pulmonary nodule surgeries. Patients were divided into the day and routine surgery groups following chest tube removal within 48 h postoperatively and the discharge criteria. Each group was further divided into the wedge and anatomic lung resection groups. The feasibility and applicability of day surgery in thoracic surgery was evaluated by calculating the percentage of the day surgery group and comparing the clinical data of the two groups, and corresponding guidance was given for selecting suitable patients for day surgery. Results: The day surgery group accounted for 53.4% of the total number of patients in both groups. Data comparison revealed differences in age, hypertension, coronary heart disease, pulmonary function index, nodule localization, pleural adhesion, total postoperative drainage, and complications in the wedge resection and age, gender, smoking history, pulmonary function indexes, intraoperative adhesions, operative duration, total postoperative drainage volume, and complications in the anatomic lung resection (P < 0.05). There were no significant differences in the rates of re-hospitalization (1/172 ratio 1/150) and re-drainage (0/172 ratio 1/150) (P > 0.05). Conclusion: This study concluded that more than half of the pulmonary surgery can be applied to the treatment mode of day surgery, and day surgery can be applied to the screened patients. It conforms to the concept of accelerated rehabilitation and can speed up bed turnover so that more patients can receive high-level medical treatment promptly.

Establishment and validation of an individualized nomogram for survival prediction of primary mediastinal germ cell tumors based on the SEER database.

Background: Primary mediastinal germ cell tumors (PMGCT) represent a rare but sometimes highly aggressive type of mediastinal tumors. The current prognostic models for PMGCT are insufficient. This study was undertaken to establish and validate an individualized nomogram for predicting the overall survival (OS) of patients with PMGCT. Methods: We conducted a retrospective analysis of patients with PMGCT diagnosed between 2000 and 2018 in the Surveillance, Epidemiology, and End Results (SEER) database in the United States. Clinical variables included surgery subtype, gender, treatment regimens, age, histology, tumor size, stage, chemotherapy, radiation, race, and survival-related information. The main outcome measure was survival duration. The Kaplan-Meier method along with the log-rank test were utilized to estimate the OS. Independent prognostic factors were identified by performing the univariate and multivariate Cox proportional hazards regression analyses, from which an individualized nomogram was constructed to predict 3-, 5-, and 10-year OS of patients with PMGCT. The concordance index (C-index) and calibration curve were used to verify the discrimination and accuracy of the nomogram. Results: A total of 845 patients with PMGCT were recruited from the SEER database and further randomly assigned to a training set (n=635) and a validation set (n=210) at a ratio of 7:3. The 3-, 5-, and 10-year OS for overall PMGCT was 70.0%, 67.1%, and 63.9%, respectively. Cox regression analysis indicated that age, tumor size, stage, chemotherapy, radiation, histology, and surgery type were as independent factors for OS in patients with PMGCT (P<0.05). An individualized nomogram for OS was constructed utilizing these variables, with the C-index of 0.714 [95% confidence interval (CI): 0.695 to 0.743] and 0.756 (95% CI: 0.735 to 0.787) in the training and validation groups. Moreover, good levels of agreement were observed according to the calibration curve between the predicted and actual 3-, 5-, and 10-year survival rates both in the training and validated cohorts, showing that the model could accurately predict patient prognosis. Conclusions: This study documented the first attempt at establishing and validating a novel nomogram for predicting the 3-, 5-, and 10-year OS probabilities of PMGCT. The prognostic nomogram was demonstrated to have good performance for predicting individualized OS of patients with PMGCT.

Assessment of videos related to lung nodules in China.

Background: With the popularization of mobile phones and the development of the Internet, many patients use social media platforms to seek health information. Currently, TikTok, iQiyi, Bilibili, and Weibo are the most popular video platforms in China. Therefore, based on the above facts, this study estimated the quality of lung nodule videos taken in China using these platforms. Methods: The term "lung nodule" was searched on these platforms. Then, the first 30 videos were selected. Subsequently, some videos were excluded after they had been reviewed and analyzed, after which information on the features and sources of these videos was finally assessed using DISCERN, the Journal of the American Medical Association (JAMA) Benchmark Criteria, and the Hexagonal Radar Schema. Analysis was performed according to different groups. Results: 101 videos were included in this study. According to the different sources, although most videos were from physicians (71.3%), comprising those with shorter durations; faster updates; and more likes, comments, and shares; no significant difference in the scores were obtained. Moreover, regarding the different platforms, while Weibo had the highest update, TikTok had more likes, comments, and shares. Investigations also revealed that while score differences were recorded, most videos were rated "very poor" and "poor." Besides, hexagonal radar charts showed a severe deficiency of video information. Conclusions: Although the quality of most videos on the understudied social media platforms was poor, these platforms have huge potential. Therefore, caution should be exercised when using the platforms as information sources about lung nodules, and a better review and push system is needed.

Synthetical effect of microplastics and chiral drug amphetamine on a primary food source algae Chlorella pyrenoids.

The biological effects and fate of the chiral illicit drug amphetamine in the presence and absence of microplastics on freshwater algae (Chlorella pyrenoids), including acute toxicity, growth inhibition, photosynthetic pigment content, oxidative stress, lipid peroxidation, and enantioselective fate were assessed. An agglomeration and the shading effects of microplastics in algae suspension were also determined. Microplastics were observed to increase the toxicity of amphetamine to algae and reduce algae cell growth. Exposed Chlorella pyrenoids exhibited a reduced algae cell counts in an agglomeration test, wherein algae cells decreased between 18% and 56% among treatment groups exposed to 5-50 mg L-1 of microplastics. The agglomeration test suggested that microplastics might significantly increase the adverse effect on algae. Furthermore, our experiments demonstrated enantioselective degradation of amphetamine in algae, and demonstrated that the S-enantiomer was preferably degraded by algae cells. Adding microplastics to the algae suspension significantly reduced the enantioselectivity, with an EF value of 0.41 compared with amphetamine-alone group (0.34) after 21 d exposure. These results demonstrated the first evidence of microplastics acting as a vehicle to enhance amphetamine toxicity to Chlorella pyrenoids, as well as provided new insights into the co-effect of microplastics and organic contaminants on food source.

Chronic Cerebral Hypoperfusion Aggravates Parkinson's Disease Dementia-Like Symptoms and Pathology in 6-OHDA-Lesioned Rat through Interfering with Sphingolipid Metabolism.

Chronic cerebral hypoperfusion (CCH) is a cardinal risk factor for Parkinson's disease dementia (PDD), but this potential causality lacks mechanistic evidence. We selected bilateral common carotid artery occlusion (BCCAO) to simulate chronic cerebral hypoperfusion in the rat model of PD induced by typical neurotoxin 6-hydroxy dopamine (6-OHDA). Four weeks after unilateral injection of 6-OHDA into the medial forebrain bundle, rats underwent BCCAO. Male Sprague-Dawley rats were divided into five groups of ten, including sham, PD+BCCAO 2 weeks, PD+BCCAO 1 week, PD, and BCCAO 2 weeks. Then, open field test (OFT) and Morris water maze test (MWM) were used to assess the PDD-like symptoms in rats. Also, the pathological manifestations and mechanisms of BCCAO impairing cognitive functions have been explored via hematoxylin-eosin staining, Nissl staining, immunohistochemistry, immunofluorescence, RNA sequencing analysis, lipidomics, and quantitative real-time polymerase chain reaction. In this study, we found that CCH could aggravate PDD-like cognitive symptoms (i.e., learning memory and spatial cognition) and PDD-like pathology (higher expression of α-Syn and Aß in prefrontal cortex and striatum). Moreover, a potential relationship between differentially expressed mRNAs and lipid metabolism was revealed by RNA sequencing analysis. Lipidomics showed that CCH could affect the intensity of 5 lipids, including sphingomyelin (SM 9:0;2O/26:2; SM 8:1;2O/25:0; and SM 8:0;2O/28:4), cardiolipin, lysophosphatidylcholine, cholesteryl ester, and triacylglycerol. Interestingly, the KEGG pathway analysis of both RNA sequencing analysis and lipidomics suggested that CCH leaded to learning impairment by affecting sphingolipid metabolism. Finally, we found that CCH disrupts the sphingolipid metabolism by affecting the mRNA expression of SMPD1 and SMS2, leading to the accumulation of sphingomyelin in the prefrontal cortex. In summary, CCH, an independent exacerbating reason for impairment in learning and memory within the pathopoiesis of PD, aggravates Parkinson's disease dementia-like symptoms and pathology in 6-OHDA-lesioned rat through interfering with sphingolipid metabolism.

Screening of rice cultivars for Cr-stress response by using the parameters of seed germination, morpho-physiological and antioxidant analysis.

Rice is the most important crop for the majority of population across the world with sensitive behavior toward heavy metals such as chromium (Cr) in polluted regions. Although, there is no information on the Cr resistance phenotyping in rice. Herein, two different groups of rice cultivars (normal, and hybrid) were used, each group with 14 different rice cultivars. Firstly, seed germination analysis was conducted by evaluating various seed germination indices to identify the rice cultivars with greatest seed germination vigor. Furthermore, exposure of chromium (Cr) toxicity to 28 different rice varieties (NV1-NV14, HV1-HV14) caused noticeable plant biomass reduction. Subsequently, NV2, NV6, NV10, NV12, NV13 (normal type), HV1, HV4, HV8, and HV9 (hybrid types) were pragmatic as moderately sensitive varieties, while NV3, NV4, NV9, and NV14 (normal type), HV3, HV6, HV7, and HV13 were observed as moderately tolerant. Although, NV7, and HV10 were ranked most sensitive cultivars, and NV11, and HV14 were considered as most tolerant varieties as compared to the other rice (both groups) genotypes. Afterward, Cr induced reduction in chlorophyll pigments were significantly lesser in HV14 relative to NV11, NV7, and especially HV10, and as a result HV14 modulated the total soluble sugar level as well as reduced ROS accumulation, and MDA contents production by stimulating the antioxidant defense mechanism conspicuously which further reduced the electrolyte leakage as well. Our outcomes provide support to explore the Cr tolerance mechanism in cereal crops as well as knowledge about rice breeding with increased tolerance against Cr stress.

Pilot study of a novel nanobody 68 Ga-NODAGA-SNA006 for instant PET imaging of CD8+ T cells.

PURPOSE: Positron emission tomography (PET) with specific diagnostic probes for quantifying CD8+ T cells has emerged as a powerful technique for monitoring the immune response. However, most CD8+ T cell radiotracers are based on antibodies or antibody fragments, which are slowly cleared from circulation. Herein, we aimed to develop and assess 68 Ga-NODAGA-SNA006 for instant PET (iPET) imaging of CD8+ T cells. METHODS: A novel nanobody without a hexahistidine (His6) tag, SNA006-GSC, was designed, site-specifically conjugated with NODAGA-maleimide and radiolabelled with 68 Ga. The PET imaging profiles of 68 Ga-NODAGA-SNA006 were evaluated in BALB/c MC38-CD8+/CD8- tumour models and cynomolgus monkeys. Three volunteers with lung cancer underwent whole-body PET/CT imaging after 68 Ga-NODAGA-SNA006 administration. The biodistribution, pharmacokinetics and dosimetry of patients were also investigated. In addition, combined with immunohistochemistry (IHC), the quantitative performance of the tracer for monitoring CD8 expression was evaluated in BALB/c MC38-CD8+/CD8- and human subjects. RESULTS: 68 Ga-NODAGA-SNA006 was prepared with RCP > 98% and SA > 100 GBq/µmol. 68 Ga-NODAGA-SNA006 exhibited specific uptake in MC38-CD8+ xenografts tumours, CD8-rich tissues (such as the spleen) in monkeys and CD8+ tumour lesions in patients within 1 h. Fast washout from circulation was observed in three volunteers (t1/2 < 20 min). A preliminary quantitative linear relationship (R2 = 0.9668, p < 0.0001 for xenografts and R2 = 0.7924, p = 0.0013 for lung patients) appeared between 68 Ga-NODAGA-SNA006 uptake and CD8 expression. 68 Ga-NODAGA-SNA006 was well tolerated by all patients. CONCLUSION: 68 Ga-NODAGA-SNA006 PET imaging can instantly quantify CD8 expression with an ideal safety profile and is expected to be important for dynamically tracking CD8+ T cells and monitoring immune responses for individualised cancer immunotherapy. TRIAL REGISTRATION: NCT05126927 (19 November 2021, retrospectively registered).

Sorting Nexin 5 Plays an Important Role in Promoting Ferroptosis in Parkinson's Disease.

Parkinson's disease (PD) is a common neurodegenerative disease in the elderly, which is related to brain iron metabolism disorders. Ferroptosis is a newly discovered iron-dependent programmed cell death mode, which has been considered an essential mechanism of PD pathogenesis in recent years. However, its underlying mechanisms have not been fully understood. In the present study, the PD rat model and PD cell model were induced by 6-hydroyxdopamine (6-OHDA). The results showed that the expression of Sorting Nexin 5 (SNX5) and the level of ferroptosis will increase after treatment with 6-OHDA. Consistent with these results, ferroptosis inducer erastin synergistically reduced the expression of glutathione peroxidase 4 (GPX4) and increased the expression of SNX5 in the PD cell model, while ferroptosis inhibitor ferrostatin-1 (Fer-1) inhibited the decrease of GPX4 and the increase of SNX5 in the PD cell model. Knockdown of SNX5 in PC-12 cells could reduce intracellular lipid peroxidation and accumulation of Fe2+ and significantly inhibit the occurrence of ferroptosis. In conclusion, the present study suggested that SNX5 promotes ferroptosis in the PD model, thus providing new insights and potential for research on the pharmacological targets of PD.