Influence of disease course and comprehensive management on blood glucose level in children and adolescents with type 2 diabetes mellitus.

AIMS/INTRODUCTION: The aim of the present study was to evaluate the status of glycemic control, and assess the effects of the disease course and comprehensive management measures on the blood glucose level in children and adolescents with type 2 diabetes mellitus. MATERIALS AND METHODS: The study collected the clinical data of type 2 diabetes patients in Beijing Children's Hospital from January 2015 to September 2020. Patients were grouped based on the disease course to compare their glycated hemoglobin (HbA1c) level, islet ß-cell function, insulin resistance and comprehensive management measures. RESULTS: Of the 170 participants, the median disease course was 2.0 years (interquartile range [IQR] 1.0-4.0 years). The baseline HbA1c was 11.2% (IQR 9.2-12.4%). According to the grouping by the disease course, the median HbA1c was the lowest (5.7% [IQR 5.3-6.1%]) in the half-year course group and the highest in the 4-year course group (9.0 [IQR 6.8%-11.3%]). Compared with the group with a disease duration <2 years, patients in the >4 years group had a lower proportion of patients with HbA1c <7% (29.2% vs 66.2%), a lower homeostasis model assessment of ß-cell function, and a lower proportion with a controlled diet, moderate-intensity exercise, regular follow up and no drug treatment. We deemed HbA1c as the dependent variable, and found that disease duration, homeostasis model assessment of ß-cell function at follow up, continuous moderate-intensity exercise, regular review and treatment regimen were significant influencing factors for glycemic control. CONCLUSIONS: Children and adolescents with type 2 diabetes and a prolonged disease course showed poor glycemic control and decreased islet ß-cell function. A good lifestyle, especially moderate-intensity exercise, can help such cases better control their blood glucose level.

Ordered Perovskite Structure with Functional Units for High Performance and Stable Solar Cells.

Ion migration is one of the most critical challenges that affects the stability of metal-halide perovskite solar cells (PSCs). However, the current arsenal of available strategies for solving this issue is limited. Here, novel perovskite active layers following the concept of ordered structures with functional units (OSFU) to intrinsically suppress ion migration, in which a three-dimensional (3D) perovskite layer is deposited by vapor deposition for light absorption and a 2D layer is deposited by solution process for ion inhibition, are constructed. As a promising result, the activation energy of ion migration increases from 0.36 eV for the conventional perovskite to 0.54 eV for the OSFU perovskite. These devices exhibit substantially enhanced operational stability in comparison with the conventional ones, retaining >85% of their initial efficiencies after 1200 h under ISOS-L-1. Moreover, the OSFU devices show negligible fatigue behavior with a robust performance under light/dark cycling aging test (ISOS-LC-1 protocol), which demonstrates the promising application of functional motif theory in this field.

Primary squamous cell carcinoma of the breast: a case report.

INTRODUCTION: Squamous cell carcinoma (SCC) of the breast is a rare variant of invasive breast cancer that has been classified as metaplastic carcinoma. When a tumor is composed of spindle cells, diagnosis is challenging. CASE REPORT: A 42-year-old woman with a large mass in the right breast underwent modified radical mastectomy. A pathological examination revealed a tumor with central necrosis in it. The tumor had a sarcomatoid growth pattern and the cells were spindle-shaped with severe atypicality. Immunohistochemical staining showed that P63, P53, vimentin, and CKpan were positive, whereas estrogen receptor and C-erbB-2 were negative. Ki-67 proliferation index was as high as 90%. Therefore, a diagnosis of SCC of the right breast was made. The patient received eight cycles of postoperative chemotherapy with paclitaxel and carboplatin, followed by seven cycles of radiotherapy. During follow-up, the patient also had a left thyroid tumor, and postoperative pathology suggested microinvasive follicular carcinoma. Since breast surgery, the patient has remained disease-free for more than four years. CONCLUSION: SCC of the breast with spindle cell and sarcomatoid features is rare. The diagnosis of such tumors requires exclusion of tumors with similar histological morphologies.

Construction and multicohort validation of a colon cancer prognostic risk score system based on big data of neutrophil-associated differentially expressed genes.

Objective: To investigate the role of neutrophils in colon cancer progression. Methods: Genetic data from 1,273 patients with colon cancer were procured from public databases and categorized based on genes linked to neutrophils through an unsupervised clustering approach. Through univariate Cox regression analysis, differentially expressed genes (DEGs) influencing overall survival (OS) were identified, forming the basis for establishing a prognostic risk score (PRS) system specific to colon cancer. Additionally, the correlation between PRS and patient prognosis, immune cell infiltration, and intratumoral gene mutations were analyzed. Validation of PRS as an indicator for "pan-tumor" immunotherapy was conducted using four distinct immunotherapy cohorts. Results: The research identified two distinct subtypes of colon cancer, namely Cluster A and B, with patients in Cluster B demonstrating remarkably superior prognoses over those in Cluster A. A total of 17 genes affecting OS were screened based on 109 DEGs between the two cluster for constructing the PRS system. Notably, individuals classified under the high-PRS group (PRShigh) exhibited poorer prognoses, significantly linked with immune cell infiltration, an immunosuppressive tumor microenvironment, and increased genomic mutations. Remarkably, analysis of immunotherapy cohorts indicated that patients with PRShigh exhibited enhanced clinical responses, a higher rate of progression-free events, and improved overall survival post-immunotherapy. The PRS system, developed based on tumor typing utilizing neutrophil-associated genes, exhibited a strong correlation with prognostic elements in colon cancer and emerged as a vital predictor of "pan-tumor" immunotherapy efficacy. Conclusions: PRS serves as a prognostic model for patients with colon cancer and holds the potential to act as a "pan-tumor" universal marker for assessing immunotherapy efficacy across different tumor types. The study findings lay a foundation for novel antitumor strategies centered on neutrophil-focused approaches.

Lactiplantibacillus plantarum ZDY2013 Inhibits the Development of Non-Alcoholic Fatty Liver Disease by Regulating the Intestinal Microbiota and Modulating the PI3K/Akt Pathway.

Non-alcoholic fatty liver disease (NAFLD) is a common chronic hepatic condition whose impact on human health is increasingly significant. The imbalance of the gut microbiome, linked to insulin resistance, heightened intestinal permeability, and pro-inflammatory reactions, may be the linchpin in the development of NAFLD. In our research, the impact of Lactiplantibacillus plantarum ZDY2013 administration for 12 weeks on gut microbiota dysbiosis induced by a high-fat, high-fructose, high-cholesterol (FHHC) diet in male C57BL/6n mice was investigated. Research results presented that the intervention of L. plantarum ZDY2013 in mice fed with the FHHC diet could restore their liver function and regulate oxidative stress. Compared to mice in the model group, the intervention of L. plantarum ZDY2013 significantly regulated the gut microbiota, inhibited the LPS/NF-κB pathway, and led to a lower level of colonic inflammation in the mice administered with L. plantarum ZDY2013. It also improved insulin resistance to regulate the PI3K/Akt pathway and lipid metabolism, thereby resulting in reduced fat accumulation in the liver. The above results suggest that the intervention of L. plantarum ZDY2013 can hinder the progression of diet-induced NAFLD by reducing inflammation to regulate the PI3K/Akt pathway and regulating gut microbiota disturbance.

Influence of flavonoids from Sedum aizoon L. on mitochondrial function of Rhizopus nigricans in strawberry.

Rhizopus nigricans (R. nigricans), one of the fungi that grows the fastest, is frequently discovered in postharvest fruits, it's the main pathogen of strawberry root rot. Flavonoids in Sedum aizoon L. (FSAL) is a kind of green and safe natural substance extracted from Sedum aizoon L. which has antifungal activity. In this study, the minimum inhibitory concentration (MIC) of FSAL on R. nigricans and cell apoptosis tests were studied to explore the inhibitory effect of FSAL on R. nigricans. The effects of FSAL on mitochondria of R. nigricans were investigated through the changes of mitochondrial permeability transition pore(mPTP), mitochondrial membrane potential(MMP), Ca2+ content, H2O2 content, cytochrome c (Cyt c) content, the related enzyme activity and related genes of mitochondria. The results showed that the MIC of FSAL on R. nigricans was 1.800 mg/mL, with the addition of FSAL (1.800 mg/mL), the mPTP openness of R. nigricans increased and the MMP reduced. Resulting in an increase in Ca2+ content, accumulation of H2O2 content and decrease of Cyt c content, the activity of related enzymes was inhibited and related genes were up-regulated (VDAC1, ANT) or down-regulated (SDHA, NOX2). This suggests that FSAL may achieve the inhibitory effect of fungi by damaging mitochondria, thereby realizing the postharvest freshness preservation of strawberries. This lays the foundation for the development of a new plant-derived antimicrobial agent.

Applying machine-learning models to differentiate benign and malignant thyroid nodules classified as C-TIRADS 4 based on 2D-ultrasound combined with five contrast-enhanced ultrasound key frames.

Objectives: To apply machine learning to extract radiomics features from thyroid two-dimensional ultrasound (2D-US) combined with contrast-enhanced ultrasound (CEUS) images to classify and predict benign and malignant thyroid nodules, classified according to the Chinese version of the thyroid imaging reporting and data system (C-TIRADS) as category 4. Materials and methods: This retrospective study included 313 pathologically diagnosed thyroid nodules (203 malignant and 110 benign). Two 2D-US images and five CEUS key frames ("2nd second after the arrival time" frame, "time to peak" frame, "2nd second after peak" frame, "first-flash" frame, and "second-flash" frame) were selected to manually label the region of interest using the "Labelme" tool. A total of 7 images of each nodule and their annotates were imported into the Darwin Research Platform for radiomics analysis. The datasets were randomly split into training and test cohorts in a 9:1 ratio. Six classifiers, namely, support vector machine, logistic regression, decision tree, random forest (RF), gradient boosting decision tree and extreme gradient boosting, were used to construct and test the models. Performance was evaluated using a receiver operating characteristic curve analysis. The area under the curve (AUC), sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), accuracy (ACC), and F1-score were calculated. One junior radiologist and one senior radiologist reviewed the 2D-US image and CEUS videos of each nodule and made a diagnosis. We then compared their AUC and ACC with those of our best model. Results: The AUC of the diagnosis of US, CEUS and US combined CEUS by junior radiologist and senior radiologist were 0.755, 0.750, 0.784, 0.800, 0.873, 0.890, respectively. The RF classifier performed better than the other five, with an AUC of 1 for the training cohort and 0.94 (95% confidence interval 0.88-1) for the test cohort. The sensitivity, specificity, accuracy, PPV, NPV, and F1-score of the RF model in the test cohort were 0.82, 0.93, 0.90, 0.85, 0.92, and 0.84, respectively. The RF model with 2D-US combined with CEUS key frames achieved equivalent performance as the senior radiologist (AUC: 0.94 vs. 0.92, P = 0.798; ACC: 0.90 vs. 0.92) and outperformed the junior radiologist (AUC: 0.94 vs. 0.80, P = 0.039, ACC: 0.90 vs. 0.81) in the test cohort. Conclusions: Our model, based on 2D-US and CEUS key frames radiomics features, had good diagnostic efficacy for thyroid nodules, which are classified as C-TIRADS 4. It shows promising potential in assisting less experienced junior radiologists.

Pharmacokinetics and safety of a new generic lurasidone: a phase I bioequivalence study in healthy Chinese subjects.

Latuda® is a novel antipsychotic drug for schizophrenia and bipolar depression. A bioequivalence trial was performed to investigate the bioequivalence of Latuda® and its generic drug lurasidone. Two independent trials were carried out, each involving 28 subjects. In the fasting trial, subjects were randomly assigned to two groups (1:1 ratio), receiving either 40 mg of generic lurasidone or Latuda®. After a 7-day washout period, subjects entered the second period with a crossover administration of 40 mg of generic lurasidone or Latuda®. The postprandial study design was similar to that of the fasting study. In the fasting study, the pharmacokinetic (PK) parameter values of generic lurasidone and Latuda® were as follows: the Cmax was 28.84 ± 19.34 ng/ml and 28.22 ± 21.19 ng/ml, respectively; the AUC0-t was 121.39 ± 58.47 h*ng/ml and 118.35 ± 52.24 h*ng/ml, respectively; and the AUC0-∞ was 129.63 ± 63.26 h*ng/ml and 126.59 ± 57.99 h*ng/ml, respectively. The primary pharmacokinetic parameter, Cmax, was assessed for equivalence using reference-scaled average bioequivalence (RSABE), while other parameters (AUC0-t, AUC0-∞) were evaluated using average bioequivalence (ABE). The results indicate that both Cmax and AUC meet the equivalence criteria. In the postprandial study, the PK values of generic lurasidone and Latuda® were as follows: the Cmax was 74.89 ± 32.06 ng/ml and 83.51 ± 33.52 ng/ml, respectively; the AUC0-t was 274.77 ± 103.05 h*ng/ml and 289.26 ± 95.25 h*ng/ml, respectively; and the AUC0-∞ was 302.44 ± 121.60 h*ng/ml and 316.32 ± 109.04 h*ng/ml, respectively. The primary pharmacokinetic parameters (Cmax, AUC0-t, AUC0-∞) were assessed for equivalence using ABE, and both met the equivalence criteria. In the study, lurasidone and Latuda® both exhibited acceptable safety and tolerability. The results displayed that lurasidone and Latuda® were bioequivalent and safe in healthy Chinese participants. Clinical Trial Registry: This trial is registered at chinadrugtrials.org.cn (no.: CTR20191717, date: 2019.08.29).

Poly(ADP-ribose) polymerase (PARP)-targeted PET imaging in non-oncology application: a pilot study in preclinical models of nonalcoholic steatohepatitis.

Poly(ADP-ribose) polymerase (PARP) activation often indicates a disruptive signal to lipid metabolism, the physiological alteration of which may be implicated in the development of non-alcoholic fatty liver disease. The objective of this study was to evaluate the capability of [68Ga]DOTA-PARPi PET to detect hepatic PARP expression in a non-alcoholic steatohepatitis (NASH) mouse model. In this study, male C57BL/6 mice were subjected to a choline-deficient, L-amino acid-defined, high-fat diet (CDAHFD) for a 12-week period to establish preclinical NASH models. [68Ga]DOTA-PARPi PET imaging of the liver was conducted at the 12-week mark after CDAHFD feeding. Comprehensive histopathological analysis, covering hepatic steatosis, inflammation, fibrosis, along with blood biochemistry, was performed in both NASH models and control groups. Despite the induction of severe inflammation, steatosis and fibrosis in the liver of mice with the CDAHFD-NASH model, PET imaging of NASH with [68Ga]-DOTA-PARPi did not reveal a significantly higher uptake in NASH models compared to the control. This underscores the necessity for further development of new chelator-based PARP1 tracers with high binding affinity to enable the visualization of PARP1 changes in NASH pathology.

The Performance of Niobium-Microalloying Ultra-High-Strength Bridge Cable Steel during Hot Rolling.

This study focuses on exploring the effects of niobium (Nb)-microalloying on the properties of steel for ultra-high-strength bridge cables during hot-rolling processes. We employed a combination of dual-pass compression tests, stress-strain curve analysis, and Electron Backscatter Diffraction (EBSD) techniques to investigate the influence of Nb-microalloying on the static recrystallization behavior and grain size of the steel. The key findings reveal that Nb-microalloying effectively inhibits static recrystallization, particularly at higher temperatures, significantly reducing the volume fraction of recrystallized grains, resulting in a finer grain size and enhanced deformation resistance. Secondly, at a deformation temperature of 975 °C, Nb-containing steel exhibited finer grain sizes compared to Nb-free steel when held for 10 to 50 s; however, the grain size growth accelerated when the hold time exceeded 50 s, likely linked to the increased deformation resistance induced by Nb. Lastly, this research proposes optimal hot-rolling process parameters for new bridge cable steel, recommending specific finishing rolling temperatures and inter-pass times for both Nb-containing and Nb-free steels during the roughing and finishing stages. This study suggests optimal hot-rolling parameters for both Nb-containing and Nb-free steels, providing essential insights for improving hot-rolling and microalloying processes in high-carbon steels for bridge cables.

Identification and exploration of a new M2 macrophage marker MTLN in alveolar echinococcosis.

The pathogen of alveolar echinococcosis (AE) is Echinococcus multilocularis (E. multilocularis), which has the characteristics of diffuse infiltration and growth and has a high mortality rate. At present, the role of macrophages in AE infection has attracted more and more attention, but the new biomarkers and polarization mechanisms of macrophages are rarely studied. In this study, CIBERSORT and WGCNA algorithms were used to establish a weighted gene co-expression network, and MTLN was identified as a biological marker of M2-type macrophages, which participated in energy metabolism of macrophages and mediated inflammatory response, but the role of MTLN in AE was not studied. In this study, liver tissue samples from AE patients were collected and immunofluorescence co-localization showed the relationship between MTLN and macrophage distribution. E. multilocularis infected mouse model was established to analyze the expression of MTLN, liver fibrosis, and inflammatory reaction after E. multilocularis infection. The cell experiment simulated the liver microenvironment of E. multilocularis infected human body and analyzed the expression of MTLN by QRT-PCR and western blot in vitro. The data showed that liver fibrosis occurred in AE patients, and MTLN was activated near the focus. After E. multilocularis infected mice, the expression of MTLN increased with time. In the cell experiment, after the antigen of E. multilocularis protoscolex stimulated normal liver cells, the expression of MTLN increased 48 h, at this time, M2 was up-regulated and M1 was down-regulated. Therefore, MTLN may be the key gene to regulate the polarization of M2 macrophages and cause fibrosis.

Dredging wastewater discharge from shrimp ponds affects mangrove soil physical-chemical properties and enzyme activities.

Dredging wastewater discharge is a significant environmental concern for mariculture near mangrove ecosystems. However, little attention has been paid to its effects on the soil physical-chemical properties and enzyme activities in mangrove habitats. This study compared the soil physical-chemical properties and enzyme activities in the polluted area that received dredging wastewater from a shrimp pond with those in the control area without wastewater to explore the effects of wastewater discharge on the soil physical-chemical properties and enzyme activities. Variations in soil physical-chemical properties and enzyme activities across different tidal flat areas and depths were also examined. The polluted area exhibited lower soil salinity (10.47 ± 0.58 vs. 15.64 ± 0.54) and moisture content (41.85 ± 1.03 % vs. 45.81 ± 1.06 %) than the control area. Wastewater discharge increased soil enzyme activities, (acid phosphatase, protease, and catalase), resulting in higher inorganic nitrogen (13.20 ± 0.00 µg g-1 vs. 11.60 ± 0.03 µg g-1) but lower total nitrogen (0.93 ± 0.01 mg g-1 vs. 1.62 ± 0.11 mg g-1) in the contaminated zone. From the control to polluted area, there was an approximate increase of 0.43 and 0.83 mg g-1 in soil total phosphorus and soluble phosphate, driven by increased acid phosphatase. However, soil humus and organic matter decreased by 0.04 and 1.22 %, respectively, because of wastewater discharge. The impact of wastewater discharge on the soil physical-chemical properties and enzyme activities was most pronounced in the landward and surface soil layers (0-5 cm). The results showed that wastewater discharge altered soil physical-chemical properties and enzyme activities, accumulating soil bioavailable nutrients (inorganic nitrogen and soluble phosphate), but at the cost of reduced soil quality, especially organic matter, further adversely affecting the overall health of mangrove ecosystems. Prioritizing the management of wastewater discharged from mariculture adjacent to mangrove forests is crucial for mangrove conservation.

The regulation of Cytochrome f by mannose treatment in broccoli and its relationship with programmed cell death in tobacco BY-2 cells.

It is well established that programmed cell death (PCD) occurred in broccoli during postharvest senescence, but no studies have been conducted on the regulation of broccoli cytochrome f by mannose treatment and its relationship with PCD. In this study, we treated broccoli buds with mannose to investigate the changes in color, total chlorophyll content, gene expression related to chlorophyll metabolism, chloroplast structure, and cytochrome f determination during postharvest storage. In addition, to investigate the effect of cytochrome f on PCD, we extracted cytochrome f from broccoli and treated Nicotiana tabacum L. cv Bright Yellow 2 (BY-2) cells with extracted cytochrome f from broccoli at various concentrations. The results showed that cytochrome f can induce PCD in tobacco BY-2 cells, as evidenced by altered cell morphology, nuclear chromatin disintegration, DNA degradation, decreased cell viability, and increased caspase-3-like protease production. Taken together, our study indicated that mannose could effectively delay senescence of postharvest broccoli by inhibiting the expression of gene encoding cytochrome f which could induce PCD.

Drug resistance revealed by in silico deep mutational scanning and mutation tracker.

As COVID-19 enters its fifth year, it continues to pose a significant global health threat, with the constantly mutating SARS-CoV-2 virus challenging drug effectiveness. A comprehensive understanding of virus-drug interactions is essential for predicting and improving drug effectiveness, especially in combating drug resistance during the pandemic. In response, the Path Laplacian Transformer-based Prospective Analysis Framework (PLFormer-PAF) has been proposed, integrating historical data analysis and predictive modeling strategies. This dual-strategy approach utilizes path topology to transform protein-ligand complexes into topological sequences, enabling the use of advanced large language models for analyzing protein-ligand interactions and enhancing its reliability with factual insights garnered from historical data. It has shown unparalleled performance in predicting binding affinity tasks across various benchmarks, including specific evaluations related to SARS-CoV-2, and assesses the impact of virus mutations on drug efficacy, offering crucial insights into potential drug resistance. The predictions align with observed mutation patterns in SARS-CoV-2, indicating that the widespread use of the Pfizer drug has lead to viral evolution and reduced drug efficacy. PLFormer-PAF's capabilities extend beyond identifying drug-resistant strains, positioning it as a key tool in drug discovery research and the development of new therapeutic strategies against fast-mutating viruses like COVID-19.

Effects of dredging wastewater input history and aquaculture type on greenhouse gas fluxes from mangrove sediments along the shorelines of the Jiulong River Estuary, China.

Dredging wastewater (DW) from aquaculture ponds is a major disturbance factor in mangrove management, and its effects on the greenhouse gas (GHG) fluxes from mangrove sediment remain controversial. In this study, we investigated GHG (N2O, CH4, and CO2) fluxes from mangrove sediment at typical aquaculture pond-mangrove sites that were stimulated by DW discharged for different input histories and from different farm types. The GHG fluxes exhibited differing cumulative effects with increasing periods of DW input. The N2O and CH4 fluxes from mangrove sediment that received DW inputs for 17 y increased by ∼10 and ∼1.5 times, respectively, whereas the CO2 flux from mangrove sediment that received DW inputs for 11 y increased by ∼1 time. The effect of DW from shrimp ponds on the N2O flux was significantly larger than those of DW from fish/crab ponds and razor clam ponds. Moreover, the total global warming potentials (GWPs) at the field sites with DW inputs increased by 29-129% of which the CO2 flux was the main contributor to the GWP (85-96%). N2O as a proportion of CO2-equivalent flux increased from 2% to 12%, indicating that N2O was an important contributor to the increase in GWP. Overall, DW increased the GHG fluxes from mangrove sediments, indicating that the contribution of mangroves to climate warming was enhanced under DW input. It also implies that the carbon sequestration potential of mangrove sediments may be threatened to some extent. Therefore, future assessments of the carbon sequestration capacity of mangroves at regional or global scales should consider this phenomenon.

Hydrogen Sulfide Alleviates Oxidative Damage under Chilling Stress through Mitogen-Activated Protein Kinase in Tomato.

Tomato is the vegetable with the largest greenhouse area in China, and low temperature is one of the main factors affecting tomato growth, yield, and quality. Hydrogen sulfide (H2S) plays an important role in regulating plant chilling tolerance, but its downstream cascade reaction and mechanism remain unclear. Mitogen-activated protein kinases (MAPK/MPKs) are closely related to a variety of signaling substances in stress signal transmission. However, whether H2S is related to the MPK cascade pathway in response to low-temperature stress is rarely reported. In this study, NaHS treatment significantly decreased the electrolyte leakage (EL), superoxide anion (O2-) production rate, and hydrogen peroxide (H2O2) content of seedlings at low temperatures. In addition, the activities of superoxide dismutase (SOD), peroxidase (POD), and catalase (CAT) were obviously increased; and the photochemical efficiency of PSII (Fv/Fm) was enhanced with treatment with NaHS, indicating that NaHS improved the seedlings' cold tolerance by alleviating the degree of membrane lipid peroxidation and oxidative damage. However, H2S scavenger hypotaurine (HT) treatment showed the opposite effect. We found that H2S content, L-cysteine desulfhydrase (LCD) activity, and mRNA expression were increased by chilling stress but reduced by MPK inhibitor PD98059; PD98059 reversed the alleviating effect of H2S via increasing the EL and H2O2 contents. The expression levels of MPK1-MPK7 at low temperatures showed that SlMPK4 was significantly induced by exogenous NaHS and showed a trend of first increasing and then decreasing, while the expression level of SlMPK4 in HT-treated seedlings was lower than that of the control. After SlMPK4 was silenced by virus-induced gene silencing, the H2S-induced upregulation of C-repeat-Binding Factor (CBF1), inducer of CBF expression 1 (ICE1), respiratory burst oxidase homologs (RBOH1, RBOH2) at low temperatures disappeared, and tomato cold tolerance decreased. In conclusion, H2S improves the cold tolerance of tomato plants by increasing the activity of antioxidant enzymes and reducing reactive oxygen species (ROS) accumulation and membrane lipid peroxidation. MPK4 may act as a downstream signaling molecule in this process.

Serum sodium level fluctuations following the resection of childhood-onset craniopharyngioma.

BACKGROUND: Craniopharyngiomas are low-grade malignancies (WHO I) in the sellar region. Most cases of childhood-onset craniopharyngioma are adamantinomatous craniopharyngioma, and neurosurgery is the treatment of choice. Affected patients have postoperative complications, including water and electrolyte disturbances, because these malignancies develop near the hypothalamus and pituitary gland. Determining postoperative serum sodium fluctuation patterns in these patients can reduce postoperative mortality and improve prognosis. OBJECTIVE: To measure changes in serum sodium levels in pediatric patients who underwent craniopharyngioma surgery and identify influencing factors. METHODS: This retrospective study measured the serum sodium levels of 202 patients aged 0-18 years who underwent craniopharyngioma resection in Beijing Tiantan Hospital and Beijing Children's Hospital and identified predictors of severe hyponatremia and hypernatremia. RESULTS: The mean age of the cohort was 8.35 ± 4.35 years. The prevalence of hypernatremia, hyponatremia, and their severe forms (serum Na+  > 150 mmol/L and serum Na+  < 130 mmol/L) within 14 days after surgery was 66.3%, 72.8%, 37.1%, and 40.6%, respectively. The mean postoperative serum sodium level showed a triphasic pattern, characterized by two peaks separated by a nadir. Sodium levels peaked on days 2 (143.6 ± 7.6 mmol/L) and 14 (143.2 ± 6.7 mmol/L) and reached their lowest on day 6 (135.5 ± 7.5 mmol/L). A total of 31 (15.3%) patients met the diagnostic threshold for hyponatremia and hypernatremia of the triphase response, whereas 116 (57.4%) patients presented this pattern, regardless of met the diagnostic criteria or not. The prevalence of severe hyponatremia varied depending on preoperative endocrine hormone deficiency, tumor status (primary or recurrent), and surgical approach. CONCLUSIONS: Serum sodium levels after craniopharyngioma resection in children showed a triphasic pattern in most cases. The risk of postoperative hyponatremia varied depending on preoperative endocrine hormone deficiency, tumor status (primary or recurrent), and surgical approach.

Preclinical Evaluation of Novel Positron Emission Tomography (PET) Probes for Imaging Leucine-Rich Repeat Kinase 2 (LRRK2).

Parkinson's disease (PD) is one of the most highly debilitating neurodegenerative disorders, which affects millions of people worldwide, and leucine-rich repeat kinase 2 (LRRK2) mutations have been involved in the pathogenesis of PD. Developing a potent LRRK2 positron emission tomography (PET) tracer would allow for in vivo visualization of LRRK2 distribution and expression in PD patients. In this work, we present the facile synthesis of two potent and selective LRRK2 radioligands [11C]3 ([11C]PF-06447475) and [18F]4 ([18F]PF-06455943). Both radioligands exhibited favorable brain uptake and specific bindings in rodent autoradiography and PET imaging studies. More importantly, [18F]4 demonstrated significantly higher brain uptake in the transgenic LRRK2-G2019S mutant and lipopolysaccharide (LPS)-injected mouse models. This work may serve as a roadmap for the future design of potent LRRK2 PET tracers.

Radial nerve palsy in the newborn combined with congenital radial head dislocation: Case report and literature review.

RATIONALE: Radial nerve palsy in the newborn and congenital radial head dislocation (CRHD) are both rare disorders, and early diagnosis is challenging. We reported a case of an infant with concurrent presence of these 2 diseases and provide a comprehensive review of the relevant literature. The purpose of the study is to share diagnostic and treatment experiences and provide potentially valuable insights. PATIENT CONCERNS: A newborn has both radial nerve palsy and CRHD, characterized by limited wrist and fingers extension but normal flexion, normal shoulder and elbow movement on the affected side, characteristic skin lesions around the elbow, and an "audible click" at the radial head. The patient achieved significant improvement solely through physical therapy and observation. DIAGNOSES: The patient was diagnosed with radial nerve palsy in the newborn combined with CRHD. INTERVENTIONS: The patient received regular physical therapy including joint function training, low-frequency pulse electrical therapy, acupuncture, paraffin treatment, as well as overnight splint immobilization. OUTCOMES: The child could actively extend the wrist to a neutral position and extend all fingers. LESSONS: If a neonate exhibits limited extension in the wrist and fingers, but normal flexion, along with normal shoulder and elbow movement, and is accompanied by skin lesions around the elbow, there should be a high suspicion of radial nerve palsy in the newborn.

Label-Free and High-Throughput Removal of Residual Undifferentiated Cells From iPSC-Derived Spinal Cord Progenitor Cells.

The transplantation of spinal cord progenitor cells (SCPCs) derived from human-induced pluripotent stem cells (iPSCs) has beneficial effects in treating spinal cord injury (SCI). However, the presence of residual undifferentiated iPSCs among their differentiated progeny poses a high risk as these cells can develop teratomas or other types of tumors post-transplantation. Despite the need to remove these residual undifferentiated iPSCs, no specific surface markers can identify them for subsequent removal. By profiling the size of SCPCs after a 10-day differentiation process, we found that the large-sized group contains significantly more cells expressing pluripotent markers. In this study, we used a sized-based, label-free separation using an inertial microfluidic-based device to remove tumor-risk cells. The device can reduce the number of undifferentiated cells from an SCPC population with high throughput (ie, >3 million cells/minute) without affecting cell viability and functions. The sorted cells were verified with immunofluorescence staining, flow cytometry analysis, and colony culture assay. We demonstrated the capabilities of our technology to reduce the percentage of OCT4-positive cells. Our technology has great potential for the "downstream processing" of cell manufacturing workflow, ensuring better quality and safety of transplanted cells.