ABSTRACT
Inorganic superionic conductors possess high ionic conductivity and excellent thermal stability but their poor interfacial compatibility with lithium metal electrodes precludes application in all-solid-state lithium metal batteries1,2. Here we report a LaCl3-based lithium superionic conductor possessing excellent interfacial compatibility with lithium metal electrodes. In contrast to a Li3MCl6 (M = Y, In, Sc and Ho) electrolyte lattice3-6, the UCl3-type LaCl3 lattice has large, one-dimensional channels for rapid Li+ conduction, interconnected by La vacancies via Ta doping and resulting in a three-dimensional Li+ migration network. The optimized Li0.388Ta0.238La0.475Cl3 electrolyte exhibits Li+ conductivity of 3.02 mS cm-1 at 30 °C and a low activation energy of 0.197 eV. It also generates a gradient interfacial passivation layer to stabilize the Li metal electrode for long-term cycling of a Li-Li symmetric cell (1 mAh cm-2) for more than 5,000 h. When directly coupled with an uncoated LiNi0.5Co0.2Mn0.3O2 cathode and bare Li metal anode, the Li0.388Ta0.238La0.475Cl3 electrolyte enables a solid battery to run for more than 100 cycles with a cutoff voltage of 4.35 V and areal capacity of more than 1 mAh cm-2. We also demonstrate rapid Li+ conduction in lanthanide metal chlorides (LnCl3; Ln = La, Ce, Nd, Sm and Gd), suggesting that the LnCl3 solid electrolyte system could provide further developments in conductivity and utility.
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N6-methyladenosine (m6A) in mRNA and 5-methylcytosine (5mC) in DNA have critical functions for regulating gene expression and modulating plant growth and development. However, the interplay between m6A and 5mC is an elusive territory and remains unclear mechanistically in plants. We reported an occurrence of crosstalk between m6A and 5mC in maize (Zea mays) via the interaction between mRNA adenosine methylase (ZmMTA), the core component of the m6A methyltransferase complex, and decrease in DNA methylation 1 (ZmDDM1), a key chromatin-remodeling factor that regulates DNA methylation. Genes with m6A modification were coordinated with a much higher level of DNA methylation than genes without m6A modification. Dysfunction of ZmMTA caused severe arrest during maize embryogenesis and endosperm development, leading to a significant decrease in CHH methylation in the 5' region of m6A-modified genes. Instead, loss of function of ZmDDM1 had no noteworthy effects on ZmMTA-related activity. This study establishes a direct link between m6A and 5mC during maize kernel development and provides insights into the interplay between RNA modification and DNA methylation.
Subject(s)
DNA Methylation , Zea mays , DNA Methylation/genetics , Zea mays/genetics , Zea mays/metabolism , RNA Methylation , Methyltransferases/genetics , Methyltransferases/metabolism , RNA, Messenger/genetics , RNA, Messenger/metabolism , RNA/metabolismABSTRACT
OBJECTIVES: Data supporting routine infectious diseases (ID) consultation in Gram-negative bloodstream infection (GN-BSI) are limited. We evaluated the association between ID consultation and mortality in patients with GN-BSI in a retrospective population-wide cohort study in Ontario using linked health administrative databases. METHODS: Hospitalized adult patients with GN-BSI between April 2017 and December 2021 were included. The primary outcome was time to all-cause mortality censored at 30 days, analyzed using a mixed effects Cox proportional hazards model with hospital as a random effect. ID consultation 1-10 days after the first positive blood culture was treated as a time-varying exposure. RESULTS: Of 30,159 patients with GN-BSI across 53 hospitals, 11,013 (36.5%) received ID consultation. Median prevalence of ID consultation for patients with GN-BSI across hospitals was 35.0% with wide variability (range 2.7-76.1%, interquartile range 19.6-41.1%). 1041 (9.5%) patients who received ID consultation died within 30 days, compared to 1797 (9.4%) patients without ID consultation. In the fully-adjusted multivariable model, ID consultation was associated with mortality benefit (adjusted HR 0.82, 95% CI 0.77-0.88, p < 0.0001; translating to absolute risk reduction of -3.8% or NNT of 27). Exploratory subgroup analyses of the primary outcome showed that ID consultation could have greater benefit in patients with high-risk features (nosocomial infection, polymicrobial or non-Enterobacterales infection, antimicrobial resistance, or non-urinary tract source). CONCLUSIONS: Early ID consultation was associated with reduced mortality in patients with GN-BSI. If resources permit, routine ID consultation for this patient population should be considered to improve patient outcomes.
ABSTRACT
Excessive cadmium in rice grain in agricultural production is an important issue to be addressed in some southern regions of China. In this study, we constructed transgenic rice overexpressing OsVIT1 and OsVIT2 driven by 35S promoter in the cultivar ZH11. Compared with ZH11, OsVIT1 expression in leaves was significantly increased by 3-6.6 times and OsVIT2 expression in leaves was significantly increased by 2-2.5 times. Hydroponic experiments showed that overexpression of OsVIT1 and OsVIT2 increased the tolerance to Fe deficiency, significantly reduced Cd content in shoot and xylem sap, and had no effect on Cd tolerance in rice. Two years of field trials showed that the Fe content in the grain of OsVIT1 and OsVIT2 overexpressed materials was significantly reduced by 20-40% and the straw Fe content was significantly increased by 10-45%, and the grain Fe content distribution ratio was significantly decreased and the straw Fe distribution ratio was significantly increased compared with the wild type. The OsVIT1 and OsVIT2 overexpressed materials significantly reduced the Cd content of grain by 40-80% and the Cd content of straws by 37-77%, and the bioconcentration factor of Cd was significantly reduced in both grains and straw of OsVIT1 and OsVIT2 overexpressed materials. Overexpression of OsVIT1 and OsVIT2 did not affect the concentration of other metal ions in rice straw and grain. qRT-PCR analysis showed that the expression of the low affinity cation transporter OsLCT1 was significantly downregulated in the OsVIT1 and OsVIT2 overexpressed materials. In conclusion, overexpression of OsVIT1 and OsVIT2 reduced Cd accumulation in straw and grains, providing a strategy for Cd reduction in rice.
Subject(s)
Cadmium , Oryza , Plant Leaves , Agriculture , China , Edible Grain , Membrane Transport ProteinsABSTRACT
The mechanism of selenium in the UV photochemical vapor generation (PVG) process was investigated by the use of multiple analytical methods. It was found that the UV-induced photooxidation trapping of the generated volatile SeH2 should be responsible for the previous opinion of relative inertness of Se(VI) in PVG with formic acid. Furthermore, the formation of Se(IV) was found during the PVG process, and the comproportionation of Se(IV) with SeH2 and the photooxidation of Se(IV) into Se(VI) were investigated. Then, a preliminary model was proposed for the PVG process of Se(VI) and Se(IV) with low-molecular-weight organic acids. Then, a novel, simple, and green photocontrolled method without any photocatalyst was thus proposed for the nonchromatographic speciation analysis of Se(IV) and Se(VI), with a limit of detection of 0.2 and 5 ng/mL, respectively.
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Macrophages play an important role in the development and progression of acute rejection after kidney transplantation. The study aims to investigate the biological role and significance of macrophage-associated genes (MAG) in acute rejection after kidney transplantation. We utilized transcriptome sequencing results from public databases related to acute rejection of kidney transplantation for comprehensive analysis and validation in animal experiments. We found that a large number of immune-related signaling pathways are activated in acute rejection. PPI protein interaction networks and machine learning were used to establish a Hub gene consisting of TYROBP and TLR8 for the diagnosis of acute rejection. The single-gene GSEA enrichment analysis and immune cell correlation analysis revealed a close correlation between the expression of Hub genes and immune-related biological pathways as well as the expression of multiple immune cells. In addition, the study of TF, miRNAs, and drugs provided a theoretical basis for regulating and treating the Hub genes in acute rejection. Finally, the animal experiments demonstrated once again that acute rejection can aggravate kidney tissue damage, apoptosis level, and increase the release of inflammatory factors. We established and validated a macrophage-associated diagnostic model for acute rejection after kidney transplantation, which can accurately diagnose the biological alterations in acute rejection after kidney transplantation.
Subject(s)
Kidney Transplantation , Animals , Kidney Transplantation/adverse effects , Toll-Like Receptor 8 , Gene Expression Profiling , Biomarkers , MacrophagesABSTRACT
BACKGROUND: The SET domain group (SDG) genes encode histone lysine methyltransferases, which regulate gene transcription by altering chromatin structure and play pivotal roles in plant flowering determination. However, few studies have investigated their role in the regulation of flowering in upland cotton. RESULTS: A total of 86 SDG genes were identified through genome-wide analysis in upland cotton (Gossypium hirsutum). These genes were unevenly distributed across 25 chromosomes. Cluster analysis revealed that the 86 GhSDGs were divided into seven main branches. RNA-seq data and qRTâPCR analysis revealed that lysine methyltransferase 3 (KMT3) genes were expressed at high levels in stamens, pistils and other floral organs. Using virus-induced gene silencing (VIGS), functional characterization of GhKMT3;1a and GhKMT3;2a revealed that, compared with those of the controls, the GhKMT3;1a- and GhKMT3;2a-silenced plants exhibited later budding and flowering and lower plant heightwere shorter. In addition, the expression of flowering-related genes (GhAP1, GhSOC1 and GhFT) significantly decreased and the expression level of GhSVP significantly increased in the GhKMT3;1a- and GhKMT3;2a-silenced plants compared with the control plants. CONCLUSION: A total of 86 SDG genes were identified in upland cotton, among which GhKMT3;1a and GhKMT3;2a might regulate flowering by affecting the expression of GhAP1, GhSOC1, GhFT and GhSVP. These findings will provide genetic resources for advanced molecular breeding in the future.
Subject(s)
Flowers , Gene Expression Regulation, Plant , Gossypium , Histone-Lysine N-Methyltransferase , Plant Proteins , Gossypium/genetics , Gossypium/enzymology , Gossypium/physiology , Flowers/genetics , Flowers/growth & development , Plant Proteins/genetics , Plant Proteins/metabolism , Histone-Lysine N-Methyltransferase/genetics , Histone-Lysine N-Methyltransferase/metabolism , Genes, Plant , Gene SilencingABSTRACT
OBJECTIVES: The risk factors and outcomes associated with persistent bacteraemia in Gram-negative bloodstream infection (GN-BSI) are not well described. We conducted a follow-on analysis of a retrospective population-wide cohort to characterize persistent bacteraemia in patients with GN-BSI. METHODS: We included all hospitalized patients >18 years old with GN-BSI between April 2017 and December 2021 in Ontario who received follow-up blood culture (FUBC) 2-5 days after the index positive blood culture. Persistent bacteraemia was defined as having a positive FUBC with the same Gram-negative organism as the index blood culture. We identified variables independently associated with persistent bacteraemia in a multivariable logistic regression model. We evaluated whether persistent bacteraemia was associated with increased odds of 30- and 90-day all-cause mortality using multivariable logistic regression models adjusted for potential confounders. RESULTS: In this study, 8807 patients were included; 600 (6.8%) had persistent bacteraemia. Having a permanent catheter, antimicrobial resistance, nosocomial infection, ICU admission, respiratory or skin and soft tissue source of infection, and infection by a non-fermenter or non-Enterobacterales/anaerobic organism were associated with increased odds of having persistent bacteraemia. The 30-day mortality was 17.2% versus 9.6% in those with and without persistent bacteraemia (aOR 1.65, 95% CI 1.29-2.11), while 90-day mortality was 25.5% versus 16.9%, respectively (aOR 1.53, 95% CI 1.24-1.89). Prevalence and odds of developing persistent bacteraemia varied widely depending on causative organism. CONCLUSIONS: Persistent bacteraemia is uncommon in GN-BSI but is associated with poorer outcomes. A validated risk stratification tool may be useful to identify patients with persistent bacteraemia.
Subject(s)
Bacteremia , Gram-Negative Bacterial Infections , Humans , Bacteremia/epidemiology , Bacteremia/microbiology , Bacteremia/mortality , Retrospective Studies , Male , Female , Middle Aged , Aged , Ontario/epidemiology , Gram-Negative Bacterial Infections/epidemiology , Gram-Negative Bacterial Infections/mortality , Gram-Negative Bacterial Infections/microbiology , Risk Factors , Gram-Negative Bacteria/isolation & purification , Adult , Blood Culture , Cross Infection/epidemiology , Cross Infection/microbiology , Cross Infection/mortality , Aged, 80 and over , Anti-Bacterial Agents/therapeutic use , Clinical RelevanceABSTRACT
The vacuole is an important organelle for nitrate storage, and the reuse of vacuolar nitrate under nitrate starvation helps plants adapt to low-nitrate environments. CHLORIDE CHANNEL-b (CLC-b) in the vacuolar membrane is a nitrate transporter; however, its regulation and effects on nitrate efflux have not been established. Here, we evaluated CLC-b expression and its effects on physiological parameters under low nitrate conditions. CLC-b expression increased significantly in the roots of wild-type Arabidopsis (Arabidopsis thaliana) Col-0 under nitrate starvation. Under low nitrate, clcb mutants showed reductions in chlorophyll content and xylem sap nitrate concentration, shoot/root nitrate ratios, shoot/root total N ratios, and biomass. CLC-b-overexpression yielded opposite phenotypes and increased nitrogen use efficiency. CLC-b mutants showed elevated chlorate tolerance and an increased proportion of vacuolar nitrate relative to the total protoplast nitrate content as compared to the wild type. Yeast 1-hybrid, EMSA, and chromatin immunoprecipitation (ChIP) experiments showed that HRS1 HOMOLOG2 (HHO2), the expression of which is downregulated under low nitrate, binds directly to the promoter of CLC-b. clcb/hho2 double mutants and HHO2-overexpressing clcb plants had similar phenotypes under low nitrate to those of clcb single mutants. Thus, CLC-b mediates vacuolar nitrate efflux and is negatively regulated by HHO2, providing a theoretical basis for improving plant adaptability to low nitrate.
Subject(s)
Arabidopsis Proteins , Arabidopsis , Arabidopsis/metabolism , Nitrates/metabolism , Nitrogen/metabolism , Vacuoles/metabolism , Chloride Channels/genetics , Chloride Channels/metabolism , Arabidopsis Proteins/genetics , Arabidopsis Proteins/metabolism , Plants/metabolism , Plant Roots/genetics , Plant Roots/metabolismABSTRACT
The toxicity of aluminum (Al) in acidic soil inhibits plant root development and reduces crop yields. In the plant response to Al toxicity, the initiation of programmed cell death (PCD) appears to be an important mechanism for the elimination of Al-damaged cells to ensure plant survival. In a previous study, the type I metacaspase AhMC1 was found to regulate the Al stress response and to be essential for Al-induced PCD. However, the mechanism by which AhMC1 is altered in the peanut response to Al stress remained unclear. Here, we show that a nuclear protein, mutator-like transposable element 9A (AhMULE9A), directly interacts with AhMC1 in vitro and in vivo. This interaction occurs in the nucleus in peanut and is weakened during Al stress. Furthermore, a conserved C2HC zinc finger domain of AhMULE9A (residues 735-751) was shown to be required for its interaction with AhMC1. Overexpression of AhMULE9A in Arabidopsis and peanut strongly inhibited root growth with a loss of root cell viability under Al treatment. Conversely, knock down of AhMULE9A in peanut significantly reduced Al uptake and Al inhibition of root growth, and alleviated the occurrence of typical hallmarks of Al-induced PCD. These findings provide novel insight into the regulation of Al-induced PCD.
Subject(s)
Arabidopsis , Arachis , Arachis/genetics , DNA Transposable Elements , Aluminum/metabolism , Incidence , Plant Roots/metabolism , ApoptosisABSTRACT
Two-dimensional double perovskites have experienced rapid development due to their outstanding optoelectronic properties and diverse structural characteristics. However, the synthesis of high-performance multifunctional compounds and the regulation of their properties still lack relevant examples. Herein, we synthesized two multifunctional compounds, (C6H14N)4AgSbBr8 (1) and (F2-C6H12N)4AgSbBr8 (2), which exhibit high solid-state phase transition temperature, bistable dielectric constant switching, second harmonic generation (SHG), and bright emission. Through H/F substitution, the transition temperature increases and achieves a smaller band gap attributed to reduced interlayer spacing. Furthermore, we investigated the broad emission mechanism of the compounds through first-principles calculation and variable-temperature fluorescence, confirming the presence of the STE1 emission. Our work provides insight into the further development of multifunctional compounds and chemical modification that enhances compound properties.
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PURPOSE: To identify the key infection processes and risk factors in Computed Tomography (CT) examination process within the standard prevention and control measures for the COVID-19 epidemic, aiming to mitigate cross-infection occurrences in the hospital. METHOD: The case hospital has assembled a team of 30 experts specialized in CT examination. Based on the CT examination process, the potential failure modes were assessed from the perspective of severity (S), occurrence probability (O), and detectability (D); they were then combined with corresponding risk prevention measures. Finally, key infection processes and risk factors were identified according to the risk priority number (RPN) and expert analysis. RESULTS: Through the application of RPN and further analysis, four key potential infection processes were identified, including "CT request form (A1)," "during the scan of CT patient (B2)," "CT room and objects disposal (C2)," and "medical waste (garbage) disposal (C3)". In addition, eight key risk factors were also identified, including "cleaning personnel does not wear masks normatively (C32)," "nurse does not select the vein well, resulting in extravasation of the peripheral vein for enhanced CT (B25)," "patient cannot find the CT room (A13)," "patient has obtained a CT request form but does not know the procedure (A12)," "patient is too unwell to continue with the CT scan (B24)," "auxiliary staff (or technician) does not have a good grasp of the sterilization and disinfection standards (C21)," "auxiliary staff (or technician) does not sterilize the CT machine thoroughly (C22)," and "cleaning personnel lacks of knowledge of COVID-19 prevention and control (C33)". CONCLUSION: Hospitals can publicize the precautions regarding CT examination through various channels, reducing the incidence of CT examination failure. Hospitals' cleaning services are usually outsourced, and the educational background of the staff employed in these services is generally not high. Therefore, during training and communication, it is more necessary to provide a series of scope and training programs that are aligned with their understanding level. The model developed in this study effectively identifies the key infection prevention process and critical risk factors, enhancing the safety of medical staff and patients. This has significant research implications for the potential epidemic of major infectious diseases.
Subject(s)
COVID-19 , Cross Infection , Humans , Cross Infection/prevention & control , Risk Factors , Tomography, X-Ray Computed , TomographyABSTRACT
Background: Despite the demonstrated efficacy of pembrolizumab in KEYNOTE-024, effectiveness and safety in routine practice remain unclear. Methods: The authors identified first-line pembrolizumab or chemotherapy patients from April 2013 to March 2021. The primary outcome was overall survival; the secondary safety outcomes included rates of hospitalization, emergency department visits, specialist visits, and adverse events. Baseline differences were adjusted using propensity score matching (1:1). Results: The matched cohort included 2284 pairs. Median overall survival for pembrolizumab (13.0 months) was significantly longer than for chemotherapy (9.2 months), with a hazard ratio of 0.81 (95% CI: 0.71-0.92). Pembrolizumab patients reported significantly more adverse events and specialist visits, as well as a higher 1-year cumulative incidence of direct hospitalizations. Conclusion: The survival benefit of first-line pembrolizumab persists in the real world, although with increased toxicity and diminished benefit.
[Box: see text].
ABSTRACT
Proprotein convertase subtilisin/kexin type 9 (PCSK9) binds to the epidermal growth factor precursor homologous domain A (EGF-A) of low-density lipoprotein receptor (LDLR) in the liver and triggers the degradation of LDLR via the lysosomal pathway, consequently leading to an elevation in plasma LDL-C levels. Inhibiting PCSK9 prolongs the lifespan of LDLR and maintains cholesterol homeostasis in the body. Thus, PCSK9 is an innovative pharmacological target for treating hypercholesterolemia and atherosclerosis. In this study, we discovered that E28362 was a novel small-molecule PCSK9 inhibitor by conducting a virtual screening of a library containing 40,000 compounds. E28362 (5, 10, 20 µM) dose-dependently increased the protein levels of LDLR in both total protein and the membrane fraction in both HepG2 and AML12 cells, and enhanced the uptake of DiI-LDL in AML12 cells. MTT assay showed that E28362 up to 80 µM had no obvious toxicity in HepG2, AML12, and HEK293a cells. The effects of E28362 on hyperlipidemia and atherosclerosis were evaluated in three different animal models. In high-fat diet-fed golden hamsters, administration of E28362 (6.7, 20, 60 mg·kg-1·d-1, i.g.) for 4 weeks significantly reduced plasma total cholesterol (TC), triglyceride (TG), low-density lipoprotein-cholesterol (LDL-C) and PCSK9 levels, and reduced liver TC and TG contents. In Western diet-fed ApoE-/- mice (20, 60 mg·kg-1·d-1, i.g.) and human PCSK9 D374Y overexpression mice (60 mg·kg-1·d-1, i.g.), administration of E28362 for 12 weeks significantly decreased plasma LDL-C levels and the area of atherosclerotic lesions in en face aortas and aortic roots. Moreover, E28362 significantly increased the protein expression level of LDLR in the liver. We revealed that E28362 selectively bound to PCSK9 in HepG2 and AML12 cells, blocked the interaction between LDLR and PCSK9, and induced the degradation of PCSK9 through the ubiquitin-proteasome pathway, which finally resulted in increased LDLR protein levels. In conclusion, E28362 can block the interaction between PCSK9 and LDLR, induce the degradation of PCSK9, increase LDLR protein levels, and alleviate hyperlipidemia and atherosclerosis in three distinct animal models, suggesting that E28362 is a promising lead compound for the treatment of hyperlipidemia and atherosclerosis.
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OBJECTIVES: To investigate the long-term efficacy of ultrasound-guided high-intensity focused ultrasound (USgHIFU) for multiple uterine fibroids and the factors associated with recurrence. MATERIALS AND METHODS: Five hundred and forty-nine patients with multiple uterine fibroids treated with USgHIFU from June 2017 to June 2019 were retrospectively analyzed. The Pictorial Blood Loss Assessment Chart (PBAC) was used to assess menstrual blood loss. The patients were asked to undergo pre- and post-USgHIFU magnetic resonance imaging (MRI) and complete routine follow-up after USgHIFU. Cox regression analysis was used to investigate the risk factors associated with recurrence. RESULTS: The median number of fibroids per patient was 3 (interquartile range: 3-4), and a total of 1371 fibroids were treated. Among them, 446 patients completed 3 years follow-up. Recurrence, defined as PBAC score above or equal to 100 and/or the residual fibroid volume increased by 10%, was detected in 90 patients within 3 years after USgHIFU, with a cumulative recurrence rate of 20.2% (90/446). The multi-factor Cox analysis showed that age was a protective factor for recurrence. Younger patients have a greater chance of recurrence than older patients. Mixed hyperintensity of fibroids on T2WI and treatment intensity were risk factors for recurrence. Patients with hyperintense uterine fibroids and treated with lower treatment intensity were more likely to experience recurrence than other patients after USgHIFU. No major adverse effects occurred. CONCLUSIONS: USgHIFU can be used to treat multiple uterine fibroids safely and effectively. The age, T2WI signal intensity and treatment intensity are factors related to recurrence.
Subject(s)
High-Intensity Focused Ultrasound Ablation , Leiomyoma , Humans , Female , Leiomyoma/therapy , Leiomyoma/diagnostic imaging , Adult , Risk Factors , High-Intensity Focused Ultrasound Ablation/methods , Middle Aged , Retrospective Studies , Uterine Neoplasms/therapy , Uterine Neoplasms/diagnostic imaging , Treatment OutcomeABSTRACT
BACKGROUND: Essential tremor (ET) and Parkinson's disease (PD) are the two most prevalent movement disorders, sharing several overlapping tremor clinical features. Although growing evidence pointed out that changes in similar brain network nodes are associated with these two diseases, the brain network topological properties are still not very clear. OBJECTIVE: The combination of graph theory analysis with machine learning (ML) algorithms provides a promising way to reveal the topological pathogenesis in ET and tremor-dominant PD (tPD). METHODS: Topological metrics were extracted from Resting-state functional images of 86 ET patients, 86 tPD patients, and 86 age- and sex-matched healthy controls (HCs). Three steps were conducted to feature dimensionality reduction and four frequently used classifiers were adopted to discriminate ET, tPD, and HCs. RESULTS: A support vector machine classifier achieved the best classification performance of four classifiers for discriminating ET, tPD, and HCs with 89.0% mean accuracy (mACC) and was used for binary classification. Particularly, the binary classification performances among ET vs. tPD, ET vs. HCs, and tPD vs. HCs were with 94.2% mACC, 86.0% mACC, and 86.3% mACC, respectively. The most power discriminative features were mainly located in the default, frontal-parietal, cingulo-opercular, sensorimotor, and cerebellum networks. Correlation analysis results showed that 2 topological features negatively and 1 positively correlated with clinical characteristics. CONCLUSIONS: These results demonstrated that combining topological metrics with ML algorithms could not only achieve high classification accuracy for discrimination ET, tPD, and HCs but also help to reveal the potential brain topological network pathogenesis in ET and tPD.
Subject(s)
Brain , Essential Tremor , Machine Learning , Magnetic Resonance Imaging , Parkinson Disease , Humans , Essential Tremor/diagnosis , Essential Tremor/diagnostic imaging , Parkinson Disease/diagnostic imaging , Parkinson Disease/diagnosis , Parkinson Disease/physiopathology , Female , Male , Aged , Middle Aged , Brain/diagnostic imaging , Magnetic Resonance Imaging/methods , Support Vector Machine , Diagnosis, DifferentialABSTRACT
Allicin (AL) is one of garlic-derived organosulfides and has a variety of pharmacological effects. Studies have reported that AL has notable inhibitory effects on liver cancer, gastric cancer, breast cancer, and other cancers. However, there are no relevant reports about its role in human nasopharyngeal carcinoma. Ferroptosis is an iron-dependent form of non-apoptotic regulated cell death. Increasing evidence indicates that induction of ferroptosis can inhibit the proliferation, migration, invasion, and survival of various cancer cells, which act as a tumor suppressor in cancer. In this study, we confirmed that AL can inhibit cell proliferation, migration, invasion, and survival in human nasopharyngeal carcinoma cells. Our finding shows that AL can induce the ferroptosis axis by decreasing the level of GSH and GPX4 and promoting the induction of toxic LPO and ROS. AL-mediated cytotoxicity in human nasopharyngeal carcinoma cells is dependent on ferroptosis. Therefore, AL has good anti-cancer properties and is expected to be a potential drug for the treatment of nasopharyngeal carcinoma.
Subject(s)
Cell Proliferation , Disulfides , Ferroptosis , Nasopharyngeal Carcinoma , Nasopharyngeal Neoplasms , Reactive Oxygen Species , Sulfinic Acids , Humans , Ferroptosis/drug effects , Disulfides/pharmacology , Nasopharyngeal Carcinoma/drug therapy , Nasopharyngeal Carcinoma/pathology , Cell Proliferation/drug effects , Sulfinic Acids/pharmacology , Nasopharyngeal Neoplasms/drug therapy , Nasopharyngeal Neoplasms/pathology , Cell Line, Tumor , Reactive Oxygen Species/metabolism , Cell Movement/drug effects , Phospholipid Hydroperoxide Glutathione Peroxidase/metabolism , Glutathione/metabolism , Cell Survival/drug effectsABSTRACT
INTRODUCTION: This study aimed to investigate the association between maternal diabetes and the risk of hypospadias in male infants, as the relationship between them remains uncertain. METHODS: To comprehensively evaluate the association between pregestational diabetes mellitus and gestational diabetes mellitus with hypospadias, we conducted a systematic review and meta-analysis. A thorough literature search was conducted, encompassing relevant publications published prior to January 2023. Crude odds ratios (ORs) and their corresponding 95% confidence intervals (CIs) were calculated using a random-effects model. RESULTS: Our meta-analysis comprised a total of 13 studies, 11 of which investigated the relationship between pregestational diabetes mellitus and hypospadias, while 9 studies explored the association between gestational diabetes mellitus and hypospadias. Notably, these investigations yielded compelling evidence of significant positive associations between pregestational diabetes mellitus and hypospadias (OR = 1.51, 95% CI = 1.13-2.03), as well as between gestational diabetes mellitus and hypospadias (OR = 1.18, 95% CI = 1.04-1.35). CONCLUSION: Our findings suggest that both pregestational diabetes mellitus and gestational diabetes mellitus are associated with an increased risk of hypospadias in offspring. Further investigations are needed to explore the optimal range of blood glucose during pregnancy that minimizes the risk of congenital malformation in the fetus, as well as to develop more effective measures for glycemic control in pregnant women.
Subject(s)
Diabetes, Gestational , Hypospadias , Humans , Hypospadias/epidemiology , Female , Pregnancy , Male , Risk Factors , Pregnancy in Diabetics , Risk AssessmentABSTRACT
Lead halide perovskite nanocrystals (LHP NCs) are regarded as promising emitters for next-generation ultrahigh-definition displays due to their high color purity and wide color gamut. Recently, the external quantum efficiency (EQE) of LHP NC based light-emitting diodes (PNC LEDs) has been rapidly improved to a level required by practical applications. However, the poor operational stability of the device, caused by halide ion migration at the grain boundary of LHP NC thin films, remains a great challenge. Herein, we report a resurfacing strategy via pseudohalogen ions to mitigate detrimental halide ion migration, aiming to stabilize PNC LEDs. We employ a thiocyanate solution processed post-treatment method to efficiently resurface CsPbBr3 NCs and demonstrate that the thiocyanate ions can effectively inhibit bromide ion migration in LHP NC thin films. Owing to thiocyanate resurfacing, we fabricated LEDs with a high EQE of 17.3%, a maximum brightness of 48000 cd m-2, and an excellent operation half-life time.
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Annexins (ANNs) are a structurally conserved protein family present in almost all plants. In the present study, 27 GhANNs were identified in cotton and were unevenly distributed across 14 chromosomes. Transcriptome data and RT-qPCR results revealed that multiple GhANNs respond to at least two abiotic stresses. Similarly, the expression levels of GhANN4 and GhANN11 were significantly upregulated under heat, cold, and drought stress. Using virus-induced gene silencing (VIGS), functional characterization of GhANN4 and GhANN11 revealed that, compared with those of the controls, the leaf wilting of GhANN4-silenced plants was more obvious, and the activities of catalase (CAT), peroxidase (POD), and superoxide dismutase (SOD) were lower under NaCl and PEG stress. Moreover, the expression of stress marker genes (GhCBL3, GhDREB2A, GhDREB2C, GhPP2C, GhRD20-2, GhCIPK6, GhNHX1, GhRD20-1, GhSOS1, GhSOS2 and GhSnRK2.6) was significantly downregulated in GhANN4-silenced plants after stress. Under cold stress, the growth of the GHANN11-silenced plants was significantly weaker than that of the control plants, and the activities of POD, SOD, and CAT were also lower. However, compared with those of the control, the elasticity and orthostatic activity of the GhANN11-silenced plants were greater; the POD, SOD, and CAT activities were higher; and the GhDREB2C, GhHSP, and GhSOS2 expression levels were greater under heat stress. These results suggest that different GhANN family members respond differently to different types of abiotic stress.