High Tribocatalytic Performance of FeOOH Nanorods for Degrading Organic Dyes and Antibiotics.

Tribocatalysis is vitally important for electrochemistry, energy conservation, and water treatment. Exploring eco-friendly and low-cost tribocatalysts with high performance is crucial for practical applications. Here, the highly efficient tribocatalytic performance of FeOOH nanorods is reported. The factors related to the tribocatalytic activity such as nanorod diameter, surface area, and surface roughness are investigated, and the diameter of the FeOOH nanorods is found to have a significant effect on their tribocatalytic performance. As a result, under ultrasonic excitation, the optimized FeOOH nanorods exhibit superior tribocatalytic degradation toward rhodamine B (RhB), acid orange 7, methylene blue, methyl orange dyes, and their mixture. The RhB and mixed dyes are effectively degraded within 20 min (k = 0.179 min-1 ) and 35 min (k = 0.089 min-1 ), respectively, with the FeOOH nanorods showing excellent reusability. Moreover, antibiotics, such as tetracycline hydrochloride, phenol, and bisphenol A are efficiently degraded. Investigation of the catalytic mechanism reveals that the friction-generated h+ as well as these yielded •OH and •O2 - active radicals participate in the catalytic reaction. This work not only shed light on the design of high-performance tribocatalyst but also demonstrates that by harvesting mechanical energy, the FeOOH nanorods are promising materials for removing organic contaminants in wastewater.

Bruceine B Displays Potent Antimyeloma Activity by Inducing the Degradation of the Transcription Factor c-Maf.

The oncogenic transcription factor c-Maf has been proposed as an ideal therapeutic target for multiple myeloma (MM), a not-yet-curable malignancy of plasma cells. In the present study, we establish a c-Maf-based luciferase screen system and apply it to screen a homemade library composed of natural products from which bruceine B (BB) is identified to display potent antimyeloma activity. BB is a key ingredient isolated from the Chinese traditional medicinal plant Brucea javanica (L.) Merr. (Simaroubaceae). BB inhibits MM cell proliferation and induces MM cell apoptosis in a caspase-3-dependent manner. The mechanism studies showed that BB inhibits c-Maf transcriptional activity and downregulates the expression of CCND2 and ITGB7, the downstream genes typically modulated by c-Maf. Moreover, BB induces c-Maf degradation via proteasomes by inducing c-Maf for K48-linked polyubiquitination in association with downregulated Otub1 and USP5, two proven deubiquitinases of c-Maf. We also found that c-Maf activates STAT3 and BB suppresses the STAT3 signaling. In the in vivo study, BB displays potent antimyeloma activity and almost suppresses the growth of myeloma xenografts in 7 days but shows no overt toxicity to mice. In conclusion, this study identifies BB as a novel inhibitor of c-Maf by promoting its degradation via the ubiquitin-proteasomal pathway. Given the safety and the successful clinical application of bruceine products in traditional medicine, BB is ensured for further investigation for the treatment of patients with MM.

Seroprevalence of Toxoplasma gondii infection among patients of a tertiary hospital in Guangzhou, Guangdong province, PR China.

PURPOSE: This study aimed to explore the prevalence of Toxoplasma gondii (T. gondii) among patients in Guangzhou city, South China, and to identify susceptible patient populations and analyze the causes of infection differences. METHODS: From May 2020 to May 2022, a total of 637 sera were collected from patients, and 205 sera were collected from health participants as health control. All sera were examined by colloidal gold kits to detect the positivity of antibodies against T. gondii. And the positivity of antibodies in sera was confirmed with ARCHITECT i2000SR system. RESULTS: The prevalence of T. gondii infection in patients was 7.06% (45/637), which was lower than the prevalence in health participants 4.88% (10/205). Among patients, 34 (5.34%) were positive only for IgG, 10 (1.57%) were only for IgM, and 1 (0.16%) was positive for both IgG and IgM. There was a significant difference in prevalence between male and female patients, but not among different age groups or diseases groups. The prevalence of T. gondii infection in diseases groups varied. The prevalence was relatively high in patients with the disorders of thyroid gland and the malignant neoplasms of digestive organs, which suggests that caution should be taken to avoid T. gondii infection in these patients. Surprisingly, the prevalence was quite low in diffuse Large B-cell Lymphoma (DLBC) patients. This may be due to the overexpression of TNF-α in tumor tissues of DLBC patients and the higher protein level of TNF-α in sera of DLBC patients. CONCLUSION: This study provides a systematic exploration of the prevalence of T. gondii infection in patients in a tertiary hospital. Our data contributes to a better understanding of the epidemic investigation of T. gondii among patients in South China, which can help the prevention and treatment of the disease caused by T. gondii infection.

Identification and Functional Analysis of Transcriptome Profiles, Long Non-Coding RNAs, Single-Nucleotide Polymorphisms, and Alternative Splicing from the Oocyte to the Preimplantation Stage of Sheep by Single-Cell RNA Sequencing.

Numerous dynamic and complicated processes characterize development from the oocyte to the embryo. However, given the importance of functional transcriptome profiles, long non-coding RNAs, single-nucleotide polymorphisms, and alternative splicing during embryonic development, the effect that these features have on the blastomeres of 2-, 4-, 8-, 16-cell, and morula stages of development has not been studied. Here, we carried out experiments to identify and functionally analyze the transcriptome profiles, long non-coding RNAs, single-nucleotide polymorphisms (SNPs), and alternative splicing (AS) of cells from sheep from the oocyte to the blastocyst developmental stages. We found between the oocyte and zygote groups significantly down-regulated genes and the second-largest change in gene expression occurred between the 8- and 16-cell stages. We used various methods to construct a profile to characterize cellular and molecular features and systematically analyze the related GO and KEGG profile of cells of all stages from the oocyte to the blastocyst. This large-scale, single-cell atlas provides key cellular information and will likely assist clinical studies in improving preimplantation genetic diagnosis.

High-Contrast Bidirectional Optoelectronic Synapses based on 2D Molecular Crystal Heterojunctions for Motion Detection.

Light-stimulated optoelectronic synaptic devices are fundamental compositions of the neuromorphic vision system. However, there are still huge challenges to achieving both bidirectional synaptic behaviors under light stimuli and high performance. Herein, a bilayer 2D molecular crystal (2DMC) p-n heterojunction is developed to achieve high-performance bidirectional synaptic behaviors. The 2DMC heterojunction-based field effect transistor (FET) devices exhibit typical ambipolar properties and remarkable responsivity (R) of 3.58×104 A W-1 under weak light as low as 0.008 mW cm-2 . Excitatory and inhibitory synaptic behaviors are successfully realized by the same light stimuli under different gate voltages. Moreover, a superior contrast ratio (CR) of 1.53×103 is demonstrated by the ultrathin and high-quality 2DMC heterojunction, which transcends previous optoelectronic synapses and enables application for the motion detection of the pendulum. Furthermore, a motion detection network based on the device is developed to detect and recognize classic motion vehicles in road traffic with an accuracy exceeding 90%. This work provides an effective strategy for developing high-contrast bidirectional optoelectronic synapses and shows great potential in the intelligent bionic device and future artificial vision.

Inhibition of USP10 induces myeloma cell apoptosis by promoting cyclin D3 degradation.

The cell cycle regulator cyclin D3 (CCND3) is highly expressed in multiple myeloma (MM) and it promotes MM cell proliferation. After a certain phase of cell cycle, CCND3 is rapidly degraded, which is essential for the strict control of MM cell cycle progress and proliferation. In the present study, we investigated the molecular mechanisms regulating CCND3 degradation in MM cells. By utilizing affinity purification-coupled tandem mass spectrometry, we identified the deubiquitinase USP10 interacting with CCND3 in human MM OPM2 and KMS11 cell lines. Furthermore, USP10 specifically prevented CCND3 from K48-linked polyubiquitination and proteasomal degradation, therefore enhancing its activity. We demonstrated that the N-terminal domain (aa. 1-205) of USP10 was dispensable for binding to and deubiquitinating CCND3. Although Thr283 was important for CCND3 activity, it was dispensable for CCND3 ubiquitination and stability modulated by USP10. By stabilizing CCND3, USP10 activated the CCND3/CDK4/6 signaling pathway, phosphorylated Rb, and upregulated CDK4, CDK6 and E2F-1 in OPM2 and KMS11 cells. Consistent with these findings, inhibition of USP10 by Spautin-1 resulted in accumulation of CCND3 with K48-linked polyubiquitination and degradation that synergized with Palbociclib, a CDK4/6 inhibitor, to induce MM cell apoptosis. In nude mice bearing myeloma xenografts with OPM2 and KMS11 cells, combined administration of Spautin-l and Palbociclib almost suppressed tumor growth within 30 days. This study thus identifies USP10 as the first deubiquitinase of CCND3 and also finds that targeting the USP10/CCND3/CDK4/6 axis may be a novel modality for the treatment of myeloma.

B-lymphoid tyrosine kinase-mediated FAM83A phosphorylation elevates pancreatic tumorigenesis through interacting with ß-catenin.

Abnormal activation of Wnt/ß-catenin-mediated transcription is closely associated with the malignancy of pancreatic cancer. Family with sequence similarity 83 member A (FAM83A) was shown recently to have oncogenic effects in a variety of cancer types, but the biological roles and molecular mechanisms of FAM83A in pancreatic cancer need further investigation. Here, we newly discovered that FAM83A binds directly to ß-catenin and inhibits the assembly of the cytoplasmic destruction complex thus inhibiting the subsequent phosphorylation and degradation. FAM83A is mainly phosphorylated by the SRC non-receptor kinase family member BLK (B-lymphoid tyrosine kinase) at tyrosine 138 residue within the DUF1669 domain that mediates the FAM83A-ß-catenin interaction. Moreover, FAM83A tyrosine 138 phosphorylation enhances oncogenic Wnt/ß-catenin-mediated transcription through promoting ß-catenin-TCF4 interaction and showed an elevated nucleus translocation, which inhibits the recruitment of histone deacetylases by TCF4. We also showed that FAM83A is a direct downstream target of Wnt/ß-catenin signaling and correlates with the levels of Wnt target genes in human clinical pancreatic cancer tissues. Notably, the inhibitory peptides that target the FAM83A-ß-catenin interaction significantly suppressed pancreatic cancer growth and metastasis in vitro and in vivo. Our results revealed that blocking the FAM83A cascade signaling defines a therapeutic target in human pancreatic cancer.

Jiedu Yizhi Formula Improves Cognitive Function by Regulating the Gut Dysbiosis and TLR4/NF-κB Signaling Pathway.

Objective: The objective of this study was to explore the neuroprotective mechanism of JDYZF in treating AD from the perspective of inflammation and intestinal microflora. Methods: A total of 24 APP/PS1 mice were randomly divided into four groups: model (n = 6), JDYZF low-dose (n = 6), JDYZF high-dose (n = 6), and positive drug (n = 6), six C57 mice were used as the control group. The body weights and diets of all mice were examined daily. After 8 weeks of administration, the learning and memory of mice were evaluated by the Morris water maze test. The histopathological changes of hippocampus, liver and kidney in mice were observed by HE staining after being euthanized. The expression of p-tau in hippocampus tissue was detected by immunohistochemistry. After that, 16S rDNA sequencing was used to investigate the relationship between JDYZF and intestinal microbiota. Finally, a comparison of TLR4, p65, p-p65, iκB, p-iκB, and IL-1ß protein expression in the hippocampus tissue of mice in each group was measured by Western blot. Results: The results showed that APP/PS1 mice taking JDYZF orally were generally in good condition. Compared with the control group, JDYZF significantly improved learning and memory ability in ethology. Histology showed that JDYZF improved the hippocampal structure of mice and inhibited the deposition of p-tau. JDYZF treatment could regulate the gut microbiota of APP/PS1 mice by increasing the richness of Lachnospiraceae, Ruminococcaceae, and Actinobacteria and reducing that of Alistipes and Muribaculaceae. It also significantly inhibited the activation of the TLR4/NF-κB signaling pathway in the brain. In addition, no obvious toxic reactions were found in the liver and kidney of APP/PS1 mice after taking JDYZF for 8 weeks. Conclusion: The findings revealed that JDYZF improved cognitive ability and alleviated the TLR4/NF-κB signaling pathway in APP/PS1 mice, and the modulating the gut microbiota presented here may help illuminate its activation mechanism.

Melatonin Suppresses Cyclic GMP-AMP Synthase-Stimulator of Interferon Genes Signaling and Delays the Development of Hearing Loss in the C57BL/6J Presbycusis Mouse Model.

Melatonin supplementation has been shown to delay age-related hearing loss (ARHL) progression. Previously, melatonin was found to inhibit neuronal mitochondrial DNA (mtDNA) release, as well as inhibit cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) signaling, thereby delaying the onset of central nervous system diseases. Therefore, we hypothesized that melatonin may delay the progression of hearing loss in the C57BL/6J presbycusis mouse model by inhibiting cGAS-STING signaling in the auditory pathway. Oral melatonin at 10 mg/kg/d was administered to 3-month-old C57BL/6J mice until 12 months of age. The auditory brainstem response (ABR) threshold was used to assess their hearing ability. By real-time polymerase chain reaction and Western blot analysis, the levels of cytosolic mtDNA, cGAS/STING, and cytokines were examined in the mouse cochlea, inferior colliculus, and auditory cortex. We found that the 12-month-old control mice exhibited significant hearing loss, increased cytosolic mtDNA, increased expression of inflammatory factors TNF-α, IL-6, IFN-ß, Cxcl10, and Ifit3, up-regulated cGAS and STING expression, and enhanced interferon regulatory factor 3 (IRF3) phosphorylation in the C57BL/6J mouse cochlea, inferior colliculus, and auditory cortex. Melatonin treatment significantly improved hearing, decreased cytosolic mtDNA, suppressed the expression of inflammatory cytokines TNF-α, IL-6, IFN-ß, Ifit3, and Cxcl10, down-regulated cGAS and STING expression, and attenuated IRF3 phosphorylation in the C57BL/6J mouse cochlea, inferior colliculus, and auditory cortex. This study suggested that melatonin had a protective effect on auditory function in the C57BL/6J presbycusis mouse model, which may be mediated through reducing mtDNA release, inhibiting the cGAS-STING signaling pathway in the auditory pathway.

Bta-miR-200b promotes endometrial epithelial cell apoptosis by targeting MYB in cattle.

Embryonic mortality is considered to be one of the main reasons for reduced conception rates in the cattle industry. Insufficient endometrial receptivity is a major factor resulting in embryo implantation failure and losses. Apoptosis of endometrial epithelial cells is an important process during establishment of uterine receptivity and embryo implantation. The aim of this study was to explore the role of bta-miR-200b on endometrial epithelial cell apoptosis in cattle. Overexpression of bta-miR-200b upregulated the expression of proapoptotic gene BCL2 associated X, apoptosis regulator (BAX) and endometrial receptivity marker gene osteopontin (OPN) at mRNA and protein level in bovine endometrial epithelial cells. Moreover, overexpression of bta-miR-200b was able to inhibit proliferation and promote apoptosis of bovine endometrial epithelial cells by arresting the cell cycle at the G0/G1 phase. MYB Proto-Oncogene (MYB) was verified to be a target of bta-miR-200b in bovine endometrial epithelial cells using dual-luciferase reporter assay. Transfection of bta-miR-200b mimics decreased the mRNA and protein expression of MYB. Overexpression of MYB decreased the effect of bta-miR-200b on apoptosis of bovine endometrial epithelial cells. Our findings suggest that bta-miR-200b can affect the apoptosis of endometrial epithelial cells in cattle by targeting the MYB gene.

The application of pre-hospital first aid mode in patients with acute stroke: meta-analysis.

To systematically evaluate the application effect of pre-hospital and in-hospital emergency mode in patients with acute stroke. The study was conducted by systematic search of Chinese (CNKI, Wanfang and VIP) and English (PubMed, EMBASE and Cochrane Library) databases. The case-control studies comparing the role of pre-hospital and in-hospital emergency mode for patients with acute stroke were included in this study. Outcome indicators included the time from admission to thrombolytic therapy (DNT), the time from calling for help to receiving professional treatment, the first aid effect (effective rate, disability rate and mortality), complications and prognosis. Meta-analysis was performed using RevMan 5.3. Seventeen studies were included in the final analysis. Compared with traditional emergency measures, pre-hospital and in-hospital emergency measures can significantly reduce DNT (mean difference [MD] = -22.63, p < 0.00001), time from call to professional treatment (MD: -13.22, p < 0.00001), disability rate (RR = 0.88, p = 0.004), fatality rate (RR = 0.58, p < 0.00001), central cerebral fever (RR = 0.44, p = 0.0009), and gastrointestinal bleeding (RR = 0.44, p = 0.002). In addition, daily living ability (MD = 16.56, p < 0.00001) and emergency response rate (RR = 1.50, p < 0.00001) were significantly improved. The pre-hospital and in-hospital emergency mode has a significant emergency effect in patients with acute stroke, which is a protective factor. This emergency mode can be widely used in clinical practice.

GPX8 as a Novel Prognostic Factor and Potential Therapeutic Target in Primary Glioma.

One of the most prevalent malignant primary brain tumors is primary glioma. Although glutathione peroxidase 8 (GPX8) is intimately associated with carcinogenesis, its function in primary gliomas has not yet been thoroughly understood. Here, we leveraged Chinese Glioma Genome Atlas (CGGA), The Cancer Genome Atlas (TCGA), and Genotype-Tissue Expression (GTEx) database to investigate the association between GPX8 and overall survival (OS) of patients with primary gliomas, and our results showed that GPX8 expression was negatively correlated with OS. Moreover, the expression of GPX8 is significantly lower in normal tissue when compared to glioma tissue. According to results of univariate and multivariate analysis from CGGA using R studio, GPX8 is a valuable primary glioma prognostic indicator. Interestingly, high GPX8 expression is correlated positively with the hedgehog and kras signaling pathways and negatively with G2 checkpoint, apoptosis, reactive oxygen species (ROS) pathway, and interferon gamma pathway, which could be beneficial for the proliferation of glioma cells. Furthermore, GPX8 knockdown caused G1 cell cycle arrest, increased cell death, and reduced colony formation in U87MG and U118MG cells. In conclusion, GPX8 is a promising therapeutic target and meaningful prognostic biomarker of primary glioma.

Jiedu-Yizhi Formula Alleviates Neuroinflammation in AD Rats by Modulating the Gut Microbiota.

Background: The Jiedu-Yizhi formula (JDYZF) is a Chinese herbal prescription used to treat Alzheimer's disease (AD). It was previously confirmed that JDYZF can inhibit the expression of pyroptosis-related proteins in the hippocampus of AD rats and inhibit gut inflammation in AD rats. Therefore, it is hypothesized that JDYZF has a regulatory effect on the gut microbiota. Methods: In this study, an AD rat model was prepared by bilateral hippocampal injection of Aß 25-35 and AD rats received high, medium, and low doses of JDYZF orally for 8 weeks. The body weights of the AD rats were observed to assess the effect of JDYZF. The 16S rRNA sequencing technique was used to study the regulation of the gut microbiota by JDYZF in AD rats. Immunohistochemical staining was used to observe the expression levels of Caspase-1 and Caspase-11 in the hippocampus. Results: JDYZF reduced body weight in AD rats, and this effect may be related to JDYZF regulating body-weight-related gut microbes. The 16S rRNA analysis showed that JDYZF increased the diversity of the gut microbiota in AD rats. At the phylum level, JDYZF increased the abundances of Bacteroidota and Actinobacteriota and decreased the abundances of Firmicutes, Campilobacterota, and Desulfobacterota. At the genus level, the abundances of Lactobacillus, Prevotella, Bacteroides, Christensenellaceae_R-7_group, Rikenellaceae_RC9_gut_group, and Blautia were increased and the abundances of Lachnospiraceae-NK4A136-group, Anaerobiospirillum, Turicibacter, Oscillibacter, Desulfovibrio, Helicobacter, and Intestinimonas were decreased. At the species level, the abundances of Lactobacillus johnsonii, Lactobacillus reuteri, and Lactobacillus faecis were increased and the abundances of Helicobacter rodentium and Ruminococcus_sp_N15.MGS-57 were decreased. Immunohistochemistry showed that JDYZF reduced the levels of Caspase-1- and Caspase-11-positive staining. Conclusion: JDYZF has a regulatory effect on the gut microbiota of AD rats, which may represent the basis for the anti-inflammatory effect of JDYZF.

A druggable addiction to de novo pyrimidine biosynthesis in diffuse midline glioma.

Diffuse midline glioma (DMG) is a uniformly fatal pediatric cancer driven by oncohistones that do not readily lend themselves to drug development. To identify druggable targets for DMG, we conducted a genome-wide CRISPR screen that reveals a DMG selective dependency on the de novo pathway for pyrimidine biosynthesis. This metabolic vulnerability reflects an elevated rate of uridine/uracil degradation that depletes DMG cells of substrates for the alternate salvage pyrimidine biosynthesis pathway. A clinical stage inhibitor of DHODH (rate-limiting enzyme in the de novo pathway) diminishes uridine-5'-phosphate (UMP) pools, generates DNA damage, and induces apoptosis through suppression of replication forks-an "on-target" effect, as shown by uridine rescue. Matrix-assisted laser desorption/ionization (MALDI) mass spectroscopy imaging demonstrates that this DHODH inhibitor (BAY2402234) accumulates in the brain at therapeutically relevant concentrations, suppresses de novo pyrimidine biosynthesis in vivo, and prolongs survival of mice bearing intracranial DMG xenografts, highlighting BAY2402234 as a promising therapy against DMGs.

Ginsenoside Rb1 Improves Metabolic Disorder in High-Fat Diet-Induced Obese Mice Associated With Modulation of Gut Microbiota.

Gut microbiota plays an important role in metabolic homeostasis. Previous studies demonstrated that ginsenoside Rb1 might improve obesity-induced metabolic disorders through regulating glucose and lipid metabolism in the liver and adipose tissues. Due to low bioavailability and enrichment in the intestinal tract of Rb1, we hypothesized that modulation of the gut microbiota might account for its pharmacological effects as well. Here, we show that oral administration of Rb1 significantly decreased serum LDL-c, TG, insulin, and insulin resistance index (HOMA-IR) in mice with a high-fat diet (HFD). Dynamic profiling of the gut microbiota showed that this metabolic improvement was accompanied by restoring of relative abundance of some key bacterial genera. In addition, the free fatty acids profiles in feces were significantly different between the HFD-fed mice with or without Rb1. The content of eight long-chain fatty acids (LCFAs) was significantly increased in mice with Rb1, which was positively correlated with the increase of Akkermansia and Parasuttereller, and negatively correlated with the decrease of Oscillibacter and Intestinimonas. Among these eight increased LCFAs, eicosapentaenoic acid (EPA), octadecenoic acids, and myristic acid were positively correlated with metabolic improvement. Furthermore, the colonic expression of the free fatty acid receptors 4 (Ffar4) gene was significantly upregulated after Rb1 treatment, in response to a notable increase of LCFA in feces. These findings suggested that Rb1 likely modulated the gut microbiota and intestinal free fatty acids profiles, which should be beneficial for the improvement of metabolic disorders in HFD-fed mice. This study provides a novel mechanism of Rb1 for the treatment of metabolic disorders induced by obesity, which may provide a therapeutic avenue for the development of new nutraceutical-based remedies for treating metabolic diseases, such as hyperlipidemia, insulin resistance, and type 2 diabetes.

Characteristics of children ≤36 months of age with DIPG: A report from the international DIPG registry.

BACKGROUND: Children ≤36 months with diffuse intrinsic pontine glioma (DIPG) have increased long-term survival (LTS, overall survival (OS) ≥24 months). Understanding distinguishing characteristics in this population is critical to improving outcomes. METHODS: Patients ≤36 months at diagnosis enrolled on the International DIPG Registry (IDIPGR) with central imaging confirmation were included. Presentation, clinical course, imaging, pathology and molecular findings were analyzed. RESULTS: Among 1183 patients in IDIPGR, 40 were eligible (median age: 29 months). Median OS was 15 months. Twelve patients (30%) were LTS, 3 (7.5%) very long-term survivors ≥5 years. Among 8 untreated patients, median OS was 2 months. Patients enrolled in the registry but excluded from our study by central radiology review or tissue diagnosis had median OS of 7 months. All but 1 LTS received radiation. Among 32 treated patients, 1-, 2-, 3-, and 5-year OS rates were 68.8%, 31.2%, 15.6% and 12.5%, respectively. LTS had longer duration of presenting symptoms (P = .018). No imaging features were predictive of outcome. Tissue and genomic data were available in 18 (45%) and 10 patients, respectively. Among 9 with known H3K27M status, 6 had a mutation. CONCLUSIONS: Children ≤36 months demonstrated significantly more LTS, with an improved median OS of 15 months; 92% of LTS received radiation. Median OS in untreated children was 2 months, compared to 17 months for treated children. LTS had longer duration of symptoms. Excluded patients demonstrated a lower OS, contradicting the hypothesis that children ≤36 months with DIPG show improved outcomes due to misdiagnosis.

Production of the 2,5-Furandicarboxylic Acid Bio-Monomer From 5-Hydroxymethylfurfural Over a Molybdenum-Vanadium Oxide Catalyst.

2, 5-Furandicarboxylic acid (FDCA) is an important bio-monomer that can potentially replace terephthalic acid to synthesize degradable polyesters. Efficient selective oxidation of biomass-based 5-hydroxymethylfurfural (HMF) to FDCA has been a significant but challenging work in the past decades. In this study, a novel molybdenum-vanadium oxide (Mo-V-O) catalyst was prepared by a simple method and showed excellent catalytic activity for converting HMF to FDCA. A high FDCA selectivity of 94.5 and 98.2% conversion of HMF were achieved under the optimal conditions with tert-butyl hydroperoxide as the oxidant. FT-IR, SEM, XRD and TG were applied to investigate the properties of Mo-V-O catalyst. After fitting experimental data with the first-order kinetics equation, the evaluated apparent activation energies of HMF oxidation were obtained. The experimental design and study were carried out by response surface methodology (RSM) to test the effects of reaction conditions on the catalytic process.

Negative Phototransistors with Ultrahigh Sensitivity and Weak-Light Detection Based on 1D/2D Molecular Crystal p-n Heterojunctions and their Application in Light Encoders.

Anomalous negative phototransistors in which the channel current decreases under light illumination hold potential to generate novel and multifunctional optoelectronic applications. Although a variety of design strategies have been developed to construct such devices, NPTs still suffer from far lower device performance compared to well-developed positive phototransistors (PPTs). In this work, a novel 1D/2D molecular crystal p-n heterojunction, in which p-type 1D molecular crystal (1DMC) arrays are embedded into n-type 2D molecular crystals (2DMCs), is developed to produce ultrasensitive NPTs. The p-type 1DMC arrays act as light-absorbing layers to induce p-doping of n-type 2DMCs through charge transfer under illumination, resulting in ineffective gate control and significant negative photoresponses. As a result, the NPTs show remarkable performances in photoresponsivity (P) (1.9 × 108 ) and detectivity (D*) (1.7 × 1017 Jones), greatly outperforming previously reported NPTs, which are one of the highest values among all organic phototransistors. Moreover, the device exhibits intriguing characteristics undiscovered in PPTs, including precise control of the threshold voltage by controlling light signals and ultrasensitive detection of weak light. As a proof-of-concept, the NTPs are demonstrated as light encoders that can encrypt electrical signals by light. These findings represent a milestone for negative phototransistors, and pave the way for the development of future novel optoelectronic applications.

Jiedu-Yizhi Formula Improves Cognitive Impairment in an Aß 25-35-Induced Rat Model of Alzheimer's Disease by Inhibiting Pyroptosis.

Jiedu-Yizhi formula (JDYZF) is prescribed for the treatment of Alzheimer's disease (AD) and was created by Jixue Ren, a master of traditional Chinese medicine, based on the "marrow deficiency and toxin damage" theory. In our clinic, this formula has been used for the treatment of AD for many years and has achieved good results. However, the mechanism by which JDYZF improves cognitive impairment has not been determined. In this study, we confirmed that orally administered JDYZF reversed the cognitive deficits in an Aß 25-35-induced rat model, increased the number of neurons in the hippocampal CA1 area, improved their structure, decreased the deposition of ß-amyloid (Aß), reduced the expression of proteins related to the NLRP3/Caspase-1/GSDMD and LPS/Caspase-11/GSDMD pyroptosis pathways, and reduced the levels of interleukin 1ß (IL-1ß) and IL-18, thereby inhibiting the inflammatory response. In addition, JDYZF exerted no hepatotoxicity in rats. In short, these results provide scientific support for the clinical use of JDYZF to improve the cognitive function of patients with AD.

Age-related Activation of Cyclic GMP-AMP synthase-Stimulator of Interferon Genes Signaling in the Auditory System is Associated with Presbycusis in C57BL/6J Male Mice.

Presbycusis, or age-related hearing loss (ARHL), is primarily associated with sensory or transduction nerve cell degeneration in the peripheral and/or central auditory systems. During aging, the auditory system shows mitochondrial dysfunction and increased inflammatory responses. Mitochondrial dysfunction promotes leakage of mitochondrial DNA (mtDNA) into the cytosol, which activates the cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathway to induce type I interferon and inflammatory responses. However, whether this pathway is involved in the occurrence and development of ARHL is unknown. This study aimed to determine whether there are age-related changes in the levels of cytosolic mtDNA and cGAS-STING pathway activation in the auditory pathway and to explore their relationship with ARHL. The results showed that cGAS-positive immunoreactive cells were observed in the cochlea, inferior colliculus, and auditory cortex. Levels of cytosolic mtDNA, cGAS, STING, phosphorylated interferon regulatory factor 3, and cytokines were significantly increased in the cochlea, inferior colliculus, and auditory cortex of 6-, 9-, and 12-month-old mice compared with 3-month-old mice. These findings suggested that cytosolic mtDNA may play an important role in the pathogenesis of ARHL by activating cGAS-STING-mediated type I interferon and inflammatory responses.