Role of Hsa_circ_0000880 in the Regulation of High Glucose-Induced Apoptosis of Retinal Microvascular Endothelial Cells.

Purpose: Circular RNAs (circRNAs) have been verified to participate in multiple biological processes and disease progression. Yet, the role of circRNAs in the pathogenesis of diabetic retinopathy (DR) is still poorly understood and deserves further study. This study aimed to investigate the role of circRNAs in the regulation of high glucose (HG)-induced apoptosis of retinal microvascular endothelial cells (RMECs). Methods: Epiretinal membranes from patients with DR and nondiabetic patients with idiopathic macular epiretinal membrane were collected for this study. The circRNA microarrays were performed using high-throughput sequencing. Hierarchical clustering, functional enrichment, and network regulation analyses were used to analyze the data generated by high-throughput sequencing. Next, RMECs were subjected to HG (25 mM) conditions to induce RMECs apoptosis in vitro. A series of experiments, such as Transwell, the Scratch wound, and tube formation, were conducted to explore the regulatory effect of circRNA on RMECs. Fluorescence in situ hybridization (FISH), immunofluorescence staining, and Western blot were used to study the mechanism underlying circRNA-mediated regulation. Results: A total of 53 differentially expressed circRNAs were found in patients with DR. Among these, hsa_circ_0000880 was significantly upregulated in both the diabetic epiretinal membranes and in an in vitro DR model of HG-treated RMECs. Hsa_circ_0000880 knockout facilitated RMECs vitality and decreased the paracellular permeability of RMECs under hyperglycemia. More importantly, silencing of hsa_circ_0000880 significantly inhibited HG-induced ROS production and RMECs apoptosis. Hsa_circ_0000880 acted as an endogenous sponge for eukaryotic initiation factor 4A-III (EIF4A3). Knockout of hsa_circ_0000880 reversed HG-induced decrease in EIF4A3 protein level. Conclusions: Our findings suggest that hsa_circ_0000880 is a novel circRNA can induce RMECs apoptosis in response to HG conditions by sponging EIF4A3, offering an innovative treatment approach against DR. Translational Relevance: The circRNAs participate in the dysregulation of microvascular endothelial function induced by HG conditions, indicating a promising therapeutic target for DR.

Radiation-induced effects on TGF-ß and PDGF receptor signaling in cancer-associated fibroblasts.

BACKGROUND: Cancer-associated fibroblasts (CAFs) consist of heterogeneous connective tissue cells and are often constituting the most abundant cell type in the tumor stroma. Radiation effects on tumor stromal components like CAFs in the context of radiation treatment is not well-described. AIM: This study explores potential changes induced by ionizing radiation (IR) on platelet-derived growth factor (PDGF)/PDGFRs and transforming growth factor-beta (TGF-ß)/TGFßRs signaling systems in CAFs. METHODS AND RESULTS: Experiments were carried out by employing primary cultures of human CAFs isolated from freshly resected non-small cell lung carcinoma tumor tissues. CAF cultures from nine donors were treated with one high (1 × 18 Gy) or three fractionated (3 × 6 Gy) radiation doses. Alterations in expression levels of TGFßRII and PDGFRα/ß induced by IR were analyzed by western blots and flow cytometry. In the presence or absence of cognate ligands, receptor activation was studied in nonirradiated and irradiated CAFs. Radiation exposure did not exert changes in expression of PDGF or TGF-ß receptors in CAFs. Additionally, IR alone was unable to trigger activation of either receptor. The radiation regimens tested did not affect PDGFRß signaling in the presence of PDGF-BB. In contrast, signaling via pSmad2/3 and pSmad1/5/8 appeared to be down-regulated in irradiated CAFs after stimulation with TGF-ß, as compared with controls. CONCLUSION: Our data demonstrate that IR by itself is insufficient to induce measurable changes in PDGF or TGF-ß receptor expression levels or to induce receptor activation in CAFs. However, in the presence of their respective ligands, exposure to radiation at certain doses appear to interfere with TGF-ß receptor signaling.

[Potential Ecological Risk Assessment of Soil Heavy Metals in Fengdong New District Based on Information Diffution Model].

The large-scale construction of new districts has led to severe soil heavy metal pollution. Therefore, taking Fengdong New District as the target research area, the descriptive statistics of heavy metal content characteristics and Kriging interpolation analysis have been conducted, and the potential ecological risk index and information diffusion theory were further combined to create an information diffusion model based on risk assessment. Finally, the pollution degree, ecological risk, and risk occurrence probability of Pb, Cu, Cd, and Hg were discussed. The findings revealed that the average concentrations of the four heavy metals far exceeded the background value of soil heavy metals by a factor of 1.943 (Pb), 1.419 (Cu), 3.074 (Cd), and 3.567 (Hg), respectively. Moreover, the distribution of soil heavy metals showed strong variability(CV>65%)owing to human interference. The distribution of Pb and Cu pollution were predominantly influenced by industrial production and land development for construction purposes, whereas industrial activities, agricultural practices, and transportation served as the primary sources of Cd contamination. On the other hand, industrial construction emerged as the major factor contributing to Hg pollution. The average values of individual potential ecological risk index for heavy metals of 9.716 (Pb), 7.095 (Cu), 92.292 (Cd), and 142.469 (Hg), coupled with the regional comprehensive potential ecological risk index (RI) average of 251.573, signified that the region was overall characterized by a relatively high potential ecological risk status. The overall potential ecological risk for Pb and Cu in the region were mild, whereas Cd and Hg posed moderate to high risks, indicating that Cd and Hg were the dominant driving factors behind regional heavy metal pollution. The evaluation results of the information diffusion model based on the potential ecological risk indicated that the probability ranking of different levels of comprehensive potential ecological risk was as follows:slightly high (38.98%) > moderate (38.55%) > high (5.89%) > slight (5.15%) > extremely high (3.56%). The exceeding probabilities of potential ecological risk levels for Cd and Hg were significantly higher than those for Pb and Cu. The exceeding probability of different pollution levels of Hg were slight (94.89%), moderate (66.85%), slightly high (23.62%), high (3.9%), and extremely high (2%), of which only the surpassing probability of the slight level was lower than that of Cd. The prediction error of pollution probability of each potential ecological risk level was less than 5%, demonstrating the reliability of the information diffusion model based on the risk assessment. This research will provide technical reference and support for the monitoring and management of potential ecological risks from soil heavy metals in limited sample data regions.

A toxicological review of alkaloids.

Alkaloids are naturally occurring compounds with complex structures found in natural plants. To further improve the understanding of plant alkaloids, this review focuses on the classification, toxicity and mechanisms of action, providing insight into the occurrence of alkaloid-poisoning events and guiding the safe use of alkaloids in food, supplements and clinical applications. Based on their chemical structure, alkaloids can be divided into organic amines, diterpenoids, pyridines, isoquinolines, indoles, pyrrolidines, steroids, imidazoles and purines. The mechanisms of toxicity of alkaloids, including neurotoxicity, hepatoxicity, nephrotoxicity, cardiotoxicity and cytotoxicity, have also been reviewed. Some cases of alkaloid poisoning have been introduced when used as food or clinically, including accidental food poisoning, excessive consumption, and poisoning caused by the improper use of alkaloids in a clinical setting, and the importance of safety evaluation was illustrated. This review summarizes the toxicity and mechanism of action of alkaloids and provides evidence for the need for the safe use of alkaloids in food, supplements and clinical applications.

Longitudinal faster anxiety progression of GBA variant carriers in the early Parkinson's disease cohort.

Objective: Anxiety symptoms are prevalent neuropsychiatric manifestations in Parkinson's disease (PD) and impact the development of motor complications. Our aim was to evaluate the association of GBA variants with the anxiety development in early PD cohort. Methods: This cohort study used data from the Parkinson Progression Marker Initiative. The primary outcome anxiety was assessed by State-Trait Anxiety Inventory (STAI). The association between GBA and longitudinal change in the STAI total score was examined using linear mixed-effects model, and the association between GBA and anxiety progression was examined using Cox survival analysis. Results: A total of 385 patients with PD were included in this study, 39 of them were GBA variant carriers and 346 were idiopathic PD without GBA variants. Patients with GBA variants had faster annual increase in anxiety score (ß = 0.44; 95% CI, 0.18 to 0.71; p < 0.001) and were at higher risk of anxiety progression (HR 1.87; 95% CI, 1.03 to 3.41; p = 0.03,). Higher baseline scores for Scales for Outcomes in Parkinson's Disease-Autonomic (SCOPA-AUT), which indicated the autonomic dysfunction, also independently predicted faster increase in anxiety score (ß = 0.48; 95%CI, 0.19 to 0.69; p < 0.001) and higher incidence of anxiety development (HR = 1.05; 95% CI, 1.01 to 1.08; p = 0.008). Interpretation: These findings suggest that longitudinal anxiety symptoms worsening was faster in PD patients who were GBA variant carriers and have dysautonomia, and this association was enhanced if they have both.

Neurotoxicity study of ethyl acetate extract of Zanthoxylum armatum DC. on SH-SY5Y based on ROS mediated mitochondrial apoptosis pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Zanthoxylum armatum DC. (ZADC) is a traditional medicinal plant with various pharmacological activities and is widely used in China, Japan, India, and other regions. Previous studies have revealed that the methanol extract of ZADC can cause neurotoxicity symptoms in rats, such as drooling, decreased appetite, decreased movement, and increased respiratory rate. However, the basis of these toxic substances and the mechanism of neurotoxicity remain unclear. AIM OF THE STUDY: To evaluate the effects of ZADC on nerve cells and their damage mechanisms and discuss the possible toxic substance basis. MATERIALS AND METHODS: The ethyl acetate extract of ZADC is obtained by extracting the methanol extract of ZADC with ethyl acetate. The Q-Orbitrap LC-MS/MS method was employed to analyze the chemical composition of the EA extract of ZADC. SH-SY5Y cells were incubated with different concentrations of the ethyl acetate extract of ZADC. The cytotoxicity of the extract was evaluated using CCK-8, LDH, and ROS assays, and the oxidative stress status of cells was assessed using MDA, GSH, and SOD. Cell apoptosis was detected using flow cytometry. Damage to mitochondrial function was evaluated by labeling mitochondria, ATP, and MMP with fluorescence. Cyto-C, Caspase-3, Caspase-9, Apaf-1, Bax, and reduced Bcl2 expression were measured to evaluate the activation of the mitochondrial apoptosis pathway. Finally, NAC intervention was used to detect changes in the relevant indicators. The activation of mitochondrial apoptosis pathway was evaluated by measuring Cyto-C, Caspase-3, Caspase-9, Apaf-1, and Bax and Bcl2 expression. Finally, NAC intervention was utilized to detect changes in the relevant indicators. RESULTS: After treating SY-SY5Y cells with EA extract from ZADC, cell viability decreased significantly, and the intracellular ROS level increased in a dose-dependent manner. Meanwhile, ZADC can cause cellular oxidative stress and increase MDA and SOD concentrations while decreasing GSH concentrations. It can also shorten the mitochondrial cristae and decrease the number of mitochondria. In contrast, it can reduce ATP synthesis in the mitochondria and mitochondrial membrane potential (MMP). Furthermore, it increased the apoptosis rate and the expression of Cyto-C, Caspase-3, Caspase-9, Apaf-1, and Bax and reduced Bcl2 expression. NAC intervention alleviated the reduction in SH-SY5Y cell survival and the accumulation of reactive oxygen species induced by the EA extract in ZADC. It also inhibits signaling pathways dominated by proteins, such as Cyto-C, reducing cell apoptosis and cytotoxicity. A total of 46 compounds were identified in the extracts. CONCLUSIONS: The results suggest that EA extract of ZADC can induce the mitochondrial apoptotic pathway by accumulating ROS in cells, leading to apoptosis. Antioxidants had a good inhibitory and protective effect against cell damage caused by the EA extract of ZADC. The neurotoxic components of ZADC may be organic acids and compounds containing amino groups.

Completely Free from PAM Limitations: Asymmetric RPA with CRISPR/Cas12a for Nucleic Acid Assays.

Experimentally, Cas12a can recognize multiple protospacer adjacent motif (PAM) sequences and is not restricted to the "TTTN". However, the application of the CRISPR/Cas12a system is still limited by the PAM for double-stranded DNA (dsDNA). Here, we developed asymmetric RPA (Asy-RPA) to completely break the limitations of PAM. Asy-RPA not only achieved efficient amplification but also converted dsDNA to single-stranded DNA (ssDNA) without complicated steps. The ssDNA products activated the trans-cleavage activity of Cas12a, outputting signals. The application of Asy-RPA completely freed Cas12a from the PAM, which can be more widely used in nucleic acid detection, such as lumpy skin disease virus, with an actual detection limit as low as 1.21 × 101 copies·µL-1. More importantly, Cas12a was intolerant to mutations on ssDNA. This provided technical support for the detection and identification of wild-type Mycobacterium tuberculosis (WT-TB) and rifampin-resistant mutant-type M. tuberculosis (MT-TB). The detection limit was as low as 1 fM for 1% mixed samples. The detection and availability of different treatment options for treatment-resistant and WT-TB were significant for the elimination of TB. In summary, the platform consisting of Asy-RPA and CRISPR/Cas12a was suitable for the detection of various viruses and bacteria and was a boon for the detection of dsDNA without recognizable PAM.

Innovative Use of Waste PET-Derived Additive to Enhance Application Potentials of Recycled Concrete Aggregates in Asphalt Rubber.

Polyethylene terephthalate (PET) drinking bottles, rubber tires, and concrete are the very common municipal solid wastes, which are usually disposed of at landfills and stockpiles and cause continuous damage to the environment. Some studies have indicated that waste PET can be chemically converted into an additive for improving the overall properties of asphalt pavement incorporating natural aggregates, especially the moisture-induced damage resistance. However, it is not clear whether this PET additive still works for asphalt rubber containing recycled concrete aggregates (RCA). To well reveal this issue, this study first adopted a similar way to chemically recycle waste PET into the additive for modifying crumb rubber modified asphalt (CRMA) binder and then mixed the binder with the 13 mm maximum aggregate stone matrix asphalt containing 100% coarse RCA for preparing the mixtures. After a series of physicochemical characterizations of the PET additive, the moisture resistance, rutting resistance, low-temperature cracking resistance, and fatigue resistance of the mixture were systematically evaluated. The results showed that the PET additive is capable of improving the resistance to moisture and high-temperature deformation of asphalt rubber and helps greatly reduce the moisture-induced damage to the interfacial bonding layer. To be more detailed, the residual Marshall stability (RMS) value of RCA-CRMAM/1PET after 72 h of immersion is higher than 85% by contrast to that of RCA-CRMAM (77.1%), while the tensile strength ratio (TSR) value of RCA-CRMAM/1PET shows more than 80% compared to that of 65.2%. In addition, only 1% PET additive can enhance the high-temperature resistance of asphalt rubber containing RCA to rut and allow it to maintain higher resistance to rut after moisture-induced damage. 1% PET additive can help improve the bearing capacity of RCA-CRMAM under a low-temperature environment and delay its fatigue life at small stresses. Generally, with the successful introduction of PET additives to asphalt rubber containing RCA, more durable and sustainable highway pavement can be produced and applied in practice to alleviate the negative impacts caused by waste PET, waste tire rubber, and waste concrete.

Inversion of soil heavy metals in metal tailings area based on different spectral transformation and modeling methods.

The exploitation of mineral resources has seriously polluted the environment around mines, notably in terms of heavy metal contamination of tailings pond soil. Hyperspectral remote sensing, as opposed to conventional on-site sampling and laboratory analysis, offers a potent tool for effective monitoring the content of soil heavy metals. Therefore, we investigated the inversion models of heavy metal content in metal tailings area based on measured hyperspectral and multispectral data. Hyperspectral and its transformation, as well as the simulated Landsat8-OLI multispectral were used for model inversion respectively. Stepwise Multiple Linear Regression (SMLR), Partial Least Squares Regression (PLSR) and Back Propagation Neuron Network (BPNN) were established to study the spectral inversion of eight heavy metals (Cu, Cd, Cr, Ni, Pb, Zn, As, and Hg). The direct inversion models were established on the basis of correlation analysis and the adjust coefficient of determination (Adjust_R2) and Root Mean Square Error (RMSE) were used for model evaluation. Then the best combination of spectral transformation and inversion model were explored. The model inversion results suggested that: (1) Hyperspectral transformation can generally improve the model accuracy, especially the second derivative spectral, based on which the training Adjust_R2 of Hg SMLR and PLSR models are as high as 0.795 and 0.802. (2) The BP neural network inversion based on the denoised hyperspectrum demonstrate that both the training and testing Adjust_R2 of Cd, Ni and Hg models are all greater than 0.5, indicating good applicability in practical extrapolation. (3) Both the training and testing Adjust_R2 of Cu and Hg PLSR models based on simulated R_Landsat8-OLI multispectral are greater than 0.5, and Hg has lower RMSE and lager Adjust_R2 with training and testing Adjust_R2 values of 0.833 and 0.553 respectively. (4) Multispectral remote sensing detection and mapping of Hg contamination were realized by the optimal simulation model of Hg. Hence, it is feasible to simulate the multispectral with hyperspectral data for investigating heavy metal contamination.

Improved quantification of Fusarium pseudograminearum (Fusarium crown rot) using qPCR measurement of infection in multi-species winter cereal experiments.

Fusarium crown rot (FCR) causes significant grain yield loss in winter cereals around the world. Breeding for resistance and/or tolerance to FCR has been slow with relatively limited success. In this study, multi-species experiments were used to demonstrate an improved method to quantify FCR infection levels at plant maturity using quantitative PCR (qPCR), as well as the genotype yield retention using residual regression deviation. Using qPCR to measure FCR infection allowed a higher degree of resolution between genotypes than traditional visual stem basal browning assessments. The results were consistent across three environments with different levels of disease expression. The improved measure of FCR infection along with genotype yield retention allows for partitioning of both tolerance and partial resistance. Together these methods offer new insights into FCR partial resistance and its relative importance to tolerance in bread wheat and barley. This new approach offers a more robust, unbiased way to select for both FCR traits within breeding programs. Key message: Genetic gain for tolerance and partial resistance against Fusarium crown rot (FCR) in winter cereals has been impeded by laborious and variable visual measures of infection severity. This paper presents results of an improved method to quantify FCR infection that are strongly correlated to yield loss and reveal previously unrecognised partial resistance in barley and wheat varieties.

Combined versus sequential penetrating keratoplasty and cataract surgery for herpes simplex keratitis: a retrospective study.

Purpose: To compare the surgical outcomes of combined penetrating keratoplasty (PK) and cataract surgery with those of sequential surgery (cataract surgery after PK) for herpes simplex keratitis (HSK). Methods: The medical records of consecutive patients diagnosed with HSK who underwent combined or sequential PK and cataract surgery in active and stable stages between June 2015 and June 2022 were reviewed retrospectively. Complications, graft survival, endothelial cell density (ECD), and final BCVA were compared and analyzed between both surgical methods in each stage. Results: A total of 171 eyes of 171 patients were enrolled, including active stage (69 combined, 46 sequential) and stable stage (34 combined, 22 sequential). The average follow up was 24.2 ± 15.8 months (range, 3 months - 48 months). The final BCVA had obvious improvement and the postoperative ECD was not different in combined and sequential groups of each stage. In sequential group of active stage, 66.7% of persistent epithelial defects and 50% of HSK recurrence occurred within 3 months after cataract surgery; nevertheless, compared to that in sequential group, capsular rupture (p = 0.021), persistent epithelial defects (p = 0.027), and HSK recurrence (p = 0.035) occurred more frequently in combined group, leading to a lower graft survival rate (p = 0.045); at the last visit, 46.4 and 67.4% of grafts remained clear in combined and sequential groups, respectively. By contrary, 82.4 and 50.0% of grafts remained clear in stable stages of combined and sequential groups at the last visit, respectively, and a higher graft survival rate was observed in combined group (p = 0.030). Conclusion: Although the postoperative ECD is not different between two surgical groups in each stage, sequential surgery in active stage of HSK seems to have advantages in less complications and higher graft survival rate, whereas combined surgery in stable stage has a better outcome than that in sequential surgery.

[Optical genome mapping analysis of a Chinese pedigree with a rare chromosome 17 paracentric inversion insertion].

OBJECTIVE: To carry out optical genome mapping (OGM) for a Chinese pedigree with a rare paracentric reverse insertion of chromosome 17. METHODS: A high-risk pregnant woman identified at the Prenatal Diagnosis Center of Hangzhou Women's Hospital in October 2021 and her family members were selected as the study subjects. Chromosome G banding analysis, fluorescence in situ hybridization (FISH), single nucleotide polymorphism array (SNP array) and OGM were applied to verify the balanced structural abnormality of chromosome 17 in the pedigree. RESULTS: Chromosomal karyotyping analysis and SNP array assay have identified a duplication of 17q23q25 in the fetus. Karyotyping analysis of the pregnant woman showed that the structure of chromosome 17 was abnormal, whilst SNP array has detected no abnormality. OGM revealed that the woman has carried a paracentric reverse insertion, which was confirmed by FISH. The karyotype of her husband was normal. CONCLUSION: The duplication of 17q23q25 in the fetus has derived from a paracentric reverse insertion of chromosome 17 in its mother. OGM has the advantage for delineating balanced chromosome structural abnormalities.

Clinical characterization of polycythemia vera associated with IgA nephropathy in a single Chinese center: A case series.

BACKGROUND: Polycythemia vera (PV) is a myeloproliferative neoplasm which is characterized by excessive production of erythrocytes as well as myeloid and megakaryocytic proliferation. PV associated with IgA nephropathy (IgAN) has rarely been reported in the literature. The long-term renal prognosis of these patients is unknown. METHODS: Clinical and pathological characteristics of 7 patients with renal biopsy-proven IgAN associated with PV were retrospectively analyzed. RESULTS: The 7 patients were all males, with a mean age of 49.1 ±â€…18.8 years when admitted to our hospital. Systemic symptoms include: hypertension in case 2, 3, 5, and 6, splenomegaly in case 2, 4, and 5, and multiple lacunar infarction in case 6. Bone marrow biopsy test revealed relative erythroid hyperplasia and atypical megakaryocyte proliferation which consistent with a chronic myeloproliferative neoplasm. All patients had JAK2V617F and BCR-ABL tested, and JAK2V617F positive in 2 patients. Mild mesangial proliferation was observed in 5 patients and moderate/severe mesangial proliferation in 2patients. Immunofluorescence mainly showed diffuse granular deposition of dominant IgA in mesangium. After follow-up of 56.7 ±â€…44.0 months, hemoglobin level was 144 ±â€…29 g/L and hematocrit lever was 0.470 ±â€…0.03, compared with 187 ±â€…29 g/L and 0.563 ±â€…0.087 respectively when admitted to our hospital. The urine protein was 0.85 ±â€…0.64 g/24 h compared with 3.97 ±â€…4.68 g/24 h. Case 3 progressed to end stage renal disease and had received hemodialysis for 5 years before renal transplantation. CONCLUSIONS: The results of this study showed that PV associated with IgAN mainly occurs in males and is often accompanied by hematuria and mild-to-moderate renal insufficiency. The long-term prognosis was good for most patients, and few progressed relatively quickly to end stage renal disease.

Impact of GBA variants on longitudinal freezing of gait progression in early Parkinson's disease.

BACKGROUND: Freezing of gait (FOG) is a common disabling gait disturbance among patients with Parkinson's disease (PD), but the influence of genetic variants on the incidence of FOG has been poorly studied to date. OBJECTIVES: We aimed to evaluate the association of GBA variants with the risk of FOG development in a large early PD cohort. METHODS: This study included 371 early PD patients from the Parkinson's Progression Markers Initiative (PPMI) who were divided into a GBA variant carrier group (GBA-PD group, n = 44) and an idiopathic PD group without GBA variants (iPD group, n = 327). They were followed up for up to 5 years to examine the progression of FOG. The cumulative incidence of FOG and risk factors for FOG were assessed using Kaplan‒Meier and Cox regression analyses. RESULTS: At baseline, the GBA-PD group had lower CSF ß-amyloid 1-42 (Aß42) levels and more severe motor and nonmotor symptoms than the iPD group. During the 5-year follow-up, the GBA-PD group had a higher incidence of FOG than the iPD group, and the FOG progression rate was related to GBA variant severity. In the multivariable Cox model without CSF Aß42, GBA variants were significant predictors of future FOG, and the association remained significant after adding CSF Aß42 to the model. In the subgroup analyses, the effect of GBA variants was not observed in the "low-level" group. However, in the "high-level" group, GBA variants independently increased the risk of FOG, and this association was stronger than the association with CSF Aß42. CONCLUSION: GBA variants are novel genetic risk factors for future FOG development in early PD patients. This association seemed to be mediated by both Aß-dependent pathways and Aß-independent pathways.

Detection rates of abnormalities in over 10,000 amniotic fluid samples at a single laboratory.

BACKGROUND: A growing number of cytogenetic techniques have been used for prenatal diagnosis. This study aimed to demonstrate the usefulness of karyotyping, BACs-on-Beads (BoBs) assay and single nucleotide polymorphism (SNP) array in prenatal diagnosis during the second trimester based on our laboratory experience. METHODS: A total of 10,580 pregnant women with a variety of indications for amniocentesis were enrolled in this retrospective study between January 2015 and December 2020, of whom amniotic fluid samples were analysed in 10,320 women. The main technical indicators of participants in the three different technologies were summarized, and cases of chromosome abnormalities were further evaluated. RESULTS: The overall abnormality detection rate of karyotyping among all the amniotic fluid samples was 15.4%, and trisomy 21 was the most common abnormality (20.9%). The total abnormality detection rate of the BoBs assay was 5.6%, and the diagnosis rate of microdeletion/microduplication syndromes that were not identified by karyotyping was 0.2%. The detection results of the BoBs assay were 100.0% concordant with karyotyping analysis in common aneuploidies. Seventy (87.5%) cases of structural abnormalities were missed by BoBs assay. The total abnormality detection rate of the SNP array was 21.6%. The detection results of common aneuploidies were exactly the same between SNP array and karyotyping. Overall, 60.1% of structural abnormalities were missed by SNP array. The further detection rate of pathogenic significant copy number variations (CNVs) by SNP was 1.4%. CONCLUSIONS: Karyotyping analysis combined with BoBs assay or SNP array for prenatal diagnosis could provide quick and accurate results. Combined use of the technologies, especially with SNP array, improved the diagnostic yield and interpretation of the results, which contributes to genetic counselling. BoBs assay or SNP array could be a useful supplement to karyotyping.

Research progress on components and mechanisms of neurotoxicity induced by traditional Chinese medicine.

Over the years, the safety of traditional Chinese medicine (TCM) has received widespread attention, especially the central nervous system-related adverse reactions. Indeed, the complexity of TCM has limited the widespread application of TCM. The article summarizes the main components associated with neurotoxicity, including alkaloids, terpenes, flavonoids, saponins, proteins, and heavy metals, by reviewing the literature on the neurotoxicity of TCM. It has been established that the neurotoxicity mechanisms mainly include mitochondrial damage, oxidative damage, inhibition of cell proliferation (including transcriptional and DNA damage), changes in cell membrane permeability, and apoptosis. By reviewing the latest literature, this paper provides the foothold for follow-up studies and can assist clinicians in preventing neurotoxicity via rational and safe TCM drug use.

Endoplasmic reticulum stress-mediated cell death in liver injury.

The endoplasmic reticulum is an important intracellular organelle that plays an important role in maintaining cellular homeostasis. Endoplasmic reticulum stress (ERS) and unfolded protein response (UPR) are induced when the body is exposed to adverse external stimuli. It has been established that ERS can induce different cell death modes, including autophagy, apoptosis, ferroptosis, and pyroptosis, through three major transmembrane receptors on the ER membrane, including inositol requirement enzyme 1α, protein kinase-like endoplasmic reticulum kinase and activating transcription factor 6. These different modes of cell death play an important role in the occurrence and development of various diseases, such as neurodegenerative diseases, inflammation, metabolic diseases, and liver injury. As the largest metabolic organ, the liver is rich in enzymes, carries out different functions such as metabolism and secretion, and is the body's main site of protein synthesis. Accordingly, a well-developed endoplasmic reticulum system is present in hepatocytes to help the liver perform its physiological functions. Current evidence suggests that ERS is closely related to different stages of liver injury, and the death of hepatocytes caused by ERS may be key in liver injury. In addition, an increasing body of evidence suggests that modulating ERS has great potential for treating the liver injury. This article provided a comprehensive overview of the relationship between ERS and four types of cell death. Moreover, we discussed the mechanism of ERS and UPR in different liver injuries and their potential therapeutic strategies.

Multi-stage resistance to Zymoseptoria tritici revealed by GWAS in an Australian bread wheat diversity panel.

Septoria tritici blotch (STB) has been ranked the third most important wheat disease in the world, threatening a large area of wheat production. Although major genes play an important role in the protection against Zymoseptoria tritici infection, the lifespan of their resistance unfortunately is very short in modern wheat production systems. Combinations of quantitative resistance with minor effects, therefore, are believed to have prolonged and more durable resistance to Z. tritici. In this study, new quantitative trait loci (QTLs) were identified that are responsible for seedling-stage resistance and adult-plant stage resistance (APR). More importantly was the characterisation of a previously unidentified QTL that can provide resistance during different stages of plant growth or multi-stage resistance (MSR). At the seedling stage, we discovered a new isolate-specific QTL, QSt.wai.1A.1. At the adult-plant stage, the new QTL QStb.wai.6A.2 provided stable and consistent APR in multiple sites and years, while the QTL QStb.wai.7A.2 was highlighted to have MSR. The stacking of multiple favourable MSR alleles was found to improve resistance to Z. tritici by up to 40%.

Zanthoxylum armatum DC. extract induces liver injury via autophagy suppression and oxidative damage by activation of mTOR/ULK1 pathway.

Zanthoxylum armatum DC. (ZADC) has anti-inflammatory, antioxidative, and antibacterial effects. The cytotoxicity of methanol extract of Zanthoxylum armatum DC. (MZADC) has been reported for BRL 3 A cell lines. However, whether MZADC can induce liver damage in vivo remains unclear. Therefore, it is essential to explore whether ZADC causes liver injury and, if the results confirm hepatotoxicity, to further study the potential mechanisms for the in-vitro cytotoxicity of the BRL 3 A cell lines. In vivo, different doses (0.346, 0.519, and 1.038 g/kg/day) of MZADC treatment were given by intragastric administration among male Sprague Dawley rats for 28 days. Levels of serum alanine transaminase (ALT), aspartate transaminase (AST), and alkaline phosphatase (ALP) in the high dose group increased. Steatosis and focal necrosis were found in liver cells in rats in the high dose group. In vitro, BRL 3 A cells were cultivated with MZADC at different concentrations (30, 50, and 70 µg/mL) for 24 h. The cell viability, the number of autophagosomes, and the expression levels of LC3 and Beclin-1 were on a decreasing trend. Besides, proportions of p-mTOR/mTOR and p-ULK1/ULK1 increased. Meanwhile, reactive oxygen species (ROS) accumulation and the content of malondialdehyde (MDA) were on the rise while the activity of superoxide dismutase (SOD) and the content of glutathione (GSH) was on the decline. This research suggests that MZADC may cause rats liver injury and inhibit autophagy in BRL 3 A cells by the mTOR/ULK1 pathway, and further induce intracellular oxidative damage.