Corrigendum: Patchouli alcohol improved diarrhea-predominant irritable bowel syndrome by regulating excitatory neurotransmission in the myenteric plexus of rats.

[This corrects the article DOI: 10.3389/fphar.2022.943119.].

Impact of thermal ultrasound on enzyme inactivation and flavor improvement of sea cucumber hydrolysates.

In this study, the effects of the thermal ultrasonic enzyme inactivation process on flavor enhancement in sea cucumber hydrolysates (SCHs) and its impact on the inactivation of neutral proteases (NPs) were investigated. The body wall of the sea cucumber was enzymatically hydrolyzed with NPs. On the one hand, the structure of NPs subjected to different enzyme inactivation methods was analyzed using ζ-potential, particle size, and Fourier transform infrared (FT-IR) spectroscopy. On the other hand, the microstructure and flavor changes of SCHs were examined through scanning electron microscopy, E-nose, and gas chromatography-ion mobility spectrometry (GC-IMS). The results indicated that thermal ultrasound treatment at 60 °C could greatly affect the structure of NPs, thereby achieving enzyme inactivation. Furthermore, this treatment generated more pleasant flavor compounds, such as pentanal and (E)-2-nonenal. Hence, thermal ultrasound treatment could serve as an alternative process to traditional heat inactivation of enzymes for improving the flavor of SCHs.

Hydrogel-based immunoregulation of macrophages for tissue repair and regeneration.

The rational design of hydrogel materials to modulate the immune microenvironment has emerged as a pivotal approach in expediting tissue repair and regeneration. Within the immune microenvironment, an array of immune cells exists, with macrophages gaining prominence in the field of tissue repair and regeneration due to their roles in cytokine regulation to promote regeneration, maintain tissue homeostasis, and facilitate repair. Macrophages can be categorized into two types: classically activated M1 (pro-inflammatory) and alternatively activated M2 (anti-inflammatory and pro-repair). By regulating the physical and chemical properties of hydrogels, the phenotypic transformation and cell behavior of macrophages can be effectively controlled, thereby promoting tissue regeneration and repair. A full understanding of the interaction between hydrogels and macrophages can provide new ideas and methods for future tissue engineering and clinical treatment. Therefore, this paper reviews the effects of hydrogel components, hardness, pore size, and surface morphology on cell behaviors such as macrophage proliferation, migration, and phenotypic polarization, and explores the application of hydrogels based on macrophage immune regulation in skin, bone, cartilage, and nerve tissue repair. Finally, the challenges and future prospects of macrophage-based immunomodulatory hydrogels are discussed.

Identification of osteoporosis ferroptosis-related markers and potential therapeutic compounds based on bioinformatics methods and molecular docking technology.

RESEARCH BACKGROUND AND PURPOSE: Osteoporosis (OP) is one of the most common bone diseases worldwide, characterized by low bone mineral density and susceptibility to pathological fractures, especially in postmenopausal women and elderly men. Ferroptosis is one of the newly discovered forms of cell death regulated by genes in recent years. Many studies have shown that ferroptosis is closely related to many diseases. However, there are few studies on ferroptosis in osteoporosis, and the mechanism of ferroptosis in osteoporosis is still unclear. This study aims to identify biomarkers related to osteoporosis ferroptosis from the GEO (Gene Expression Omnibus) database through bioinformatics technology, and to mine potential therapeutic small molecule compounds through molecular docking technology, trying to provide a basis for the diagnosis and treatment of osteoporosis in the future. MATERIALS AND METHODS: We downloaded the ferroptosis-related gene set from the FerrDb database ( http://www.zhounan.org/ferrdb/index.html ), downloaded the data sets GSE56815 and GSE7429 from the GEO database, and used the R software "limma" package to screen differentially expressed genes (DEGs) from GSE56815, and intersected with the ferroptosis gene set to obtain ferroptosis-related DEGs. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were performed by the R software "clusterProfiler" package. The random forest model was further screened to obtain essential ferroptosis genes. R software "corrplot" package was used for correlation analysis of essential ferroptosis genes, and the Wilcox test was used for significance analysis. The lncRNA-miRNA-mRNA-TF regulatory network was constructed using Cytoscape software. The least absolute shrinkage and selection operator (LASSO) was used to construct a disease diagnosis model, and a Receiver operating characteristic (ROC) curve was drawn to evaluate the diagnostic performance, and then GSE7429 was used to verify the reliability of the diagnosis model. Molecular docking technology was used to screen potential small molecule compounds from the Drugbank database. Finally, a rat osteoporosis model was constructed, and peripheral blood mononuclear cells were extracted for qRT-PCR detection to verify the mRNA expression levels of crucial ferroptosis genes. RESULT: Six DEGs related to ferroptosis were initially screened out. GO function and KEGG pathway enrichment analysis showed that ferroptosis-related DEGs were mainly enriched in signaling pathways such as maintenance of iron ion homeostasis, copper ion binding function, and ferroptosis. The random forest model identified five key ferroptosis genes, including CP, FLT3, HAMP, HMOX1, and SLC2A3. Gene correlation analysis found a relatively low correlation between these five key ferroptosis genes. The lncRNA-miRNA-mRNA-TF regulatory network shows that BAZ1B and STAT3 may also be potential molecules. The ROC curve of the disease diagnosis model shows that the model has a good diagnostic performance. Molecular docking technology screened out three small molecule compounds, including NADH, Midostaurin, and Nintedanib small molecule compounds. qRT-PCR detection confirmed the differential expression of CP, FLT3, HAMP, HMOX1 and SLC2A3 between OP and normal control group. CONCLUSION: This study identified five key ferroptosis genes (CP, FLT3, HAMP, HMOX1, and SLC2A3), they were most likely related to OP ferroptosis. In addition, we found that the small molecule compounds of NADH, Midostaurin, and Nintedanib had good docking scores with these five key ferroptosis genes. These findings may provide new clues for the early diagnosis and treatment of osteoporosis in the future.

Evaluation and associated factors of public health emergency management among medical college students in a city in Southwest China: a cross-sectional study.

BACKGROUND: Colleges and universities face an increased risk of public health emergencies. Among them, medical colleges and universities deserve more attention as they serve as the play a fundamental role in providing public health emergency services and in cultivating medical professionals. Effectively managing infectious disease prevention and control, as well as responding to public health emergencies in medical colleges and universities, is of great importance for enhancing the capacity of social emergency governance and improving the completeness of the public health system. This study aims to understand the management of public health emergencies in medical colleges in a city in southwest China, explore the factors associated with medical college students' evaluations, and provide recommendations for emergency management mechanisms in colleges and universities. METHODS: In total, 781 medical college students were selected through stratified random sampling and surveyed using a questionnaire. The main factors affecting students' evaluation of emergency management were analyzed using multiple linear regression and structural equation modeling. RESULTS: The overall emergency management situation in medical colleges was relatively complete, with satisfactory results. Medical college students' satisfaction with the timeliness of prevention measures was the highest, while the publicity and education were the lowest. Multiple linear regression analysis showed that grades, emergency education, -simulation training, -information reporting, and dynamic adjustment measures were associated with the evaluation of emergency management by medical students. CONCLUSIONS: Although the evaluation of emergency management in medical colleges was generally positive, certain limitations still existed. To improve the development of the public health system, colleges and universities should constantly reform and innovate emergency management mechanisms according to the important links in the prevention and control processes.

Consolidation chemotherapy after definitive concurrent chemoradiotherapy in patients with inoperable esophageal squamous cell carcinoma: a multicenter non-inferiority phase III randomized clinical trial.

BACKGROUND: Definitive concurrent chemoradiotherapy (dCCRT) is the gold standard for the treatment of locally advanced esophageal squamous cell carcinoma (ESCC). However, the potential benefits of consolidation chemotherapy after dCCRT in patients with esophageal cancer remain debatable. Prospective randomized controlled trials comparing the outcomes of dCCRT with or without consolidation chemotherapy in patients with ESCC are lacking. In this study, we aim to generate evidence regarding consolidation chemotherapy efficacy in patients with locally advanced, inoperable ESCC. METHODS: This is a multicenter, prospective, open-label, phase-III randomized controlled trial comparing non-inferiority of dCCRT alone to consolidation chemotherapy following dCCRT. In total, 600 patients will be enrolled and randomly assigned in a 1:1 ratio to receive either consolidation chemotherapy after dCCRT (Arm A) or dCCRT alone (Arm B). Overall survival will be the primary endpoint, whereas progression-free survival, locoregional progression-free survival, distant metastasis-free survival, and treatment-related toxicity will be the secondary endpoints. DISCUSSION: This study aid in further understanding the effects of consolidation chemotherapy after dCCRT in patients with locally advanced, inoperable ESCC. TRIAL REGISTRATION: ChiCTR1800017646.

Decreased snow depth inhibits litter decomposition via changes in litter microbial biomass and enzyme activity.

Decreased snow depth resulting from global warming has the potential to significantly impact biogeochemical cycles in cold forests. However, the specific mechanisms of how snow reduction affects litter decomposition and the underlying microbial processes remain unclear, this knowledge gap limits our ability to precisely predict ecological processes within cold forest ecosystems under climate change. Hence, a field experiment was conducted in a subalpine forest in southwestern China, involving a gradient of snow reduction levels (control, 50 %, 100 %) to investigate the effects of decreased snow on litter decomposition, as well as microbial biomass and activity, specifically focused on two common species: red birch (Betula albosinensis) and masters larch (Larix mastersiana). After one year of incubation, the decomposition rate (k-value) of the two types of litter ranged from 0.12 to 0.24 across three snow treatments. A significant lower litter mass loss, microbial biomass and enzyme activity were observed under decreased snow depth in winter. Furthermore, a hysteresis inhibitory effect of snow reduction on hydrolase activity was observed in the following growing season. Additionally, the high initial quality (lower C/N ratio) of red birch litter facilitated the colonization by a greater quantity of microorganisms, making it more susceptible to snow reduction compared to the low-quality masters larch litter. Structural equation models indicated that decreased snow depth hindered litter decomposition by altering the biological characterization of litter (e.g., microbial biomass and enzyme activity) and environmental variables (e.g., mean temperature and moisture content). The findings suggest that the potential decline in snow depth could inhibit litter decomposition by reducing microbial biomass and activity, implying that the future climate change may alter the material cycling processes in subalpine forest ecosystems.

Spatiotemporal dynamics and influencing factors of human brucellosis in Mainland China from 2005-2021.

BACKGROUND: Brucellosis poses a significant public health concern. This study explores the spatial and temporal dynamic evolution of human brucellosis in China and analyses the spatial heterogeneity of the influencing factors related to the incidence of human brucellosis at the provincial level. METHODS: The Join-point model, centre of gravity migration model and spatial autocorrelation analysis were employed to evaluate potential changes in the spatial and temporal distribution of human brucellosis in mainland China from 2005 to 2021. Ordinary Least Squares (OLS), Geographically Weighted Regression (GWR), and Multi-scale Geographically Weighted Regression (MGWR) models were constructed to analyze the spatial and temporal correlation between the incidence rate of human brucellosis and meteorological and social factors. RESULTS: From 2005 to 2021, human brucellosis in China showed a consistent upward trend. The incidence rate rose more rapidly in South, Central, and Southwest China, leading to a shift in the center of gravity from the North to the Southwest, as illustrated in the migration trajectory diagram. Strong spatial aggregation was observed. The MGWR model outperformed others. Spatio-temporal plots indicated that lower mean annual temperatures and increased beef, mutton, and milk production significantly correlated with higher brucellosis incidence. Cities like Guangxi and Guangdong were more affected by low temperatures, while Xinjiang and Tibet were influenced more by beef and milk production. Inner Mongolia and Heilongjiang were more affected by mutton production. Importantly, an increase in regional GDP and health expenditure exerted a notable protective effect against human brucellosis incidence. CONCLUSIONS: Human brucellosis remains a pervasive challenge. Meteorological and social factors significantly influence its incidence in a spatiotemporally specific manner. Tailored prevention strategies should be region-specific, providing valuable insights for effective brucellosis control measures.

Modulation of DOM-Induced Head-Twitch Response by mGluR2 Agonist/Inverse Agonist is Associated with 5-HT2AR-Mediated Gs Signaling Pathway.

Hallucinogenic 5-HT2A receptor (5-HT2AR) agonists-induced head-twitch response (HTR) is regulated by Gs signaling pathway. Formation of heterodimers between 5-HT2AR and metabotropic glutamate mGlu2 receptor (mGluR2) is essential for the hallucinogenic 5-HT2AR agonist-induced HTR. In order to investigate the effects of mGluR2 agonists and inverse agonists on hallucinogenic 5-HT2AR agonists DOM-induced HTR, C57BL/6 mice were pretreated with mGluR2 agonists (LY379268, LY354740, LY404039) or the inverse agonist LY341495, and the HTR was manually counted after administering DOM immediately. IP-One (IP1) HTRF assay and cAMP assay were performed to evaluate the effect of LY341495 or LY354740 on DOM-induced Gq and Gs activation in Human Embryonic Kidney-293 (HEK-293) T-type cells co-expressing 5-HT2AR and mGluR2. The results showed that DOM-induced HTR in mice was dose-dependently inhibited by LY379268, LY354740, and LY404039, while it was dose-dependently enhanced by LY341495. Moreover, LY341495 reversed the inhibitory effect of LY354740 on DOM-induced HTR. In HEK-293T cells co-expressing 5-HT2AR and mGluR2, DOM-induced cAMP level was decreased by LY354740 and increased by LY341495, but DOM-induced IP1 level was not regulated by LY354740 or LY341495. The regulation of DOM-induced HTR by mGluR2 agonists and inverse agonists is closely related to 5-HT2AR-mediated Gs signaling pathway. In HEK-293T cells co-expressing 5-HT2AR and mGluR2 A677S/A681P/A685G mutant (mGluR2 3 A mutant), DOM-induced cAMP level was not regulated by LY354740, but was significantly enhanced by LY341495. The 5-HT2AR/mGluR2 heterodimers is critical for DOM-induced HTR and cAMP level, both of which are inhibited by mGluR2 agonists and enhanced by mGluR2 inverse agonists.

Identification of novel SHANK2 variants in two Chinese families via exome and RNA sequencing.

Background: SHANK2 encodes a postsynaptic scaffolding protein involved in synapse formation, stabilization and homeostasis. Variations or microdeletions in the SHANK2 gene have been linked to a variety of neurodevelopmental disorders, including autism spectrum disorders (ASD) and mild to moderate intellectual disability (ID) in human. However, the number of reported cases with SHANK2 defects remains limited, with only 14 unrelated patients documented worldwide. Methods: In this study, we investigated four patients from three families with ID. Whole-exome sequencing (WES) was performed to explore the genetic causes, while Sanger sequencing was used to confirm the identified variants. Furthermore, RNA sequencing and functional enrichment analysis were performed on patients with likely pathogenic variants to gain further insights into the molecular landscape associated with these variants. Results: Two novel variants in the SHANK2 gene: a heterozygous splicing substitution (NM_012309.5:c.2198-1G>A p.Pro734Glyfs*22) in Family 1, and a heterozygous nonsense variant [NM_012309.5:c.2310dupT p.(Lys771*)] in Family 2 were identified by WES and confirmed by Sanger sequencing. RNA sequencing and cohort analysis identified a total of 1,196 genes exhibiting aberrant expression in three patients. Functional enrichment analysis revealed the involvement of these genes in protein binding and synaptic functions. Conclusion: We identified two novel loss of function variants that broadens the spectrum of SHANK2 variants. Furthermore, this study enhances our understanding of the molecular mechanisms underlying SHANK2-related disorders.

Influence of HIV/AIDS knowledge on HIV testing behavior among young students (14-27 years) with a history of sexual activity: chain mediation analysis of social discrimination, self-efficacy, and sexual behavior characteristics.

This study used a self-administered questionnaire to investigate the relationship between HIV/AIDS knowledge, social discrimination, HIV self-efficacy, sexual behavioral characteristics and HIV testing behavior among young students with a history of sexual activity in Chongqing. Propensity score matching was used to construct a control group with similar demographic characteristics to the HIV testing group, only without HIV testing behaviors. Structural equation modeling was used to conduct chain-mediated effect analysis. The HIV testing rate among young students with a history of sexual behavior was 17.16%. Young students with HIV testing behavior had higher levels of HIV/AIDS knowledge, lower social discrimination, better self-efficacy, and no difference in sexual behavior characteristic scores between the two groups (P = 0.062). The mediated effect values of social discrimination and self-efficacy were 0.022 and 0.063, respectively, while their chain mediated effect value was 0.007. There was no mediated effect of sexual behavior characteristics. The level of young students' HIV/AIDS knowledge does not directly influence their HIV testing behavior but plays a complete chain mediating effect on HIV testing behavior through social discrimination and self-efficacy. HIV testing behavior should be promoted through the perspectives of enhancing HIV/AIDS knowledge level, reducing social discrimination, and improving self-efficacy.

Preparation and Road Performance Study of Rubber-Diatomite Composite-Modified Asphalt Mixture.

To examine the effect mechanism of rubber and diatomite on asphalt as well as the performance of asphalt mixtures for road applications, various composite-modified asphalts are prepared using rubber and diatomite. The performance of modified asphalts with various proportions is analyzed, and the optimal dosage ratio of modifiers is determined via the response surface approach. The microstructure of rubber-diatomite composite-modified asphalt is methodically examined using Fourier transform infrared spectroscopy and scanning electron microscopy. The road performance, aging resistance, and long-term stability of asphalt mixtures are evaluated through Marshall tests, wheel tracking tests, aging wheel tracking tests, freeze-thaw splitting tests, and cyclic freeze-thaw drying aging splitting tests. The obtained results reveal that asphalt with 22% rubber and 4% diatomite exhibits the best overall performance. The composite-modified asphalt essentially demonstrates the physical blending between rubber powder, diatomite, and base asphalt. The asphalt built from them formed a uniform and stable overall structure. Compared with rubber asphalt and rubber-SBS composite-modified asphalt, rubber-diatomite composite-modified asphalt exhibits superior road performance, including better aging resistance and long-term water stability in asphalt mixtures. This study can promote the further extensive application of rubber-diatomite-modified asphalt in road engineering, while providing new ideas for cost-saving and environmentally friendly asphalt modification.

Network Pharmacology and Experimental Validation of the Anti-Inflammatory Effect of Tingli Dazao Xiefei Decoction in Acute Lung Injury Treatment.

Purpose: Tingli Dazao Xiefei Decoction (TDXD) is a Traditional Chinese Medicine (TCM) formula used to treat acute lung injury (ALI). However, the precise mechanism of TDXD in treating ALI remains unclear. We investigated the therapeutic mechanism of TDXD against ALI using a complementary approach combining network pharmacology, molecular docking, and in vitro and in vivo experiments. Material and Methods: Potential drug targets of TDXD and relevant target genes associated with ALI were retrieved from Chinese medicines and disease genes databases. Bioinformatics technology was employed to screen potential active ingredients and core targets. Validation experiments were conducted using a lipopolysaccharide (LPS)-induced ALI mouse (C57BL/6J) model, LPS-induced inflammatory RAW264.7 cells, and molecular docking between active compounds of TDXD and potential targets. Results: Network pharmacology suggested that the mechanism of TDXD against ALI involved phosphoinositide 3-kinase (PI3K) / protein kinase B (AKT) / phosphatase and tensin homolog (PTEN) and Janus kinase 2 (JAK2) / signal transducer and activator of transcription 3 (STAT3) pathways. Quercetin, ß-sitosterol, kaempferol, isorhamnetin, and L-stepholidine were identified as the main active compounds of TDXD that exerted anti-ALI effects. Molecular docking indicated that these compounds exhibited good binding capabilities (≤ -5kcal/mol) to key targets in PI3K/AKT/PTEN and JAK2/STAT3 signaling pathways. In the animal model, TDXD alleviated injuries and inflammatory responses in lung tissues, accompanied by inhibition of expression of tumor necrosis factor-α (TNF-α), Interleukin-6 (IL-6), STAT3, and Suppressor of Cytokine Signaling 3 (SOCS3) mRNA, and key proteins in PI3K/AKT/PTEN and JAK2/STAT3 pathways (all P values < 0.05). Cell based experiments showed that TDXD dose-dependently inhibited the expression of essential proteins in PI3K/AKT/PTEN and JAK2/STAT3 pathways (P < 0.05). Conclusion: This study revealed that the mechanism of TDXD in ALI treatment might involve simultaneous regulation of PI3K/AKT/PTEN and JAK2/STAT3 pathways.

Combined multiple regional anesthesia for microwave ablation of liver Tumors: Initial experience.

OBJECTIVE: This study aims to assess the feasibility and safety of combined multiple regional anesthesia (CMRA) as a potential strategy to decrease pain and reliance on intravenous analgesics during and after ultrasound-guided microwave ablation (US-guided-MWA) of liver tumors. METHODS: A cohort of 75 patients with a total of 99 liver tumors who underwent US-guided-MWA of liver tumors were enrolled. These patients were randomly allocated into three groups: A, B, and C. Prior to the ablation procedure, Group A patients received a combination of hepatic hilar block (HHB), Transversus abdominis plane block (TAPB), and local anesthesia (LA). Patients in Group B were administered HHB in conjunction with LA, while those in Group C received TAPB and LA. Evaluative parameters included the Numerical Rating Scale (NRS) scores, consumption of morphine, incidence of complications, and factors influencing perioperative pain. RESULTS: All patients successfully underwent US-guided-MWA. The peak NRS scores for pain during ablation across the three groups were 2.36 ± 1.19, 3.28 ± 1.59, and 4.24 ± 1.42 respectively (P < 0.01), while the count of patients requiring morphine were 4/25, 8/25, and 13/25 respectively (P < 0.01). Postoperative NRS scores for the three groups at 4, 8, 12, 24, and 36-hour intervals demonstrated a pattern of initial increase followed by a decrease, with the order at each interval being: Group A < Group C < Group B. Factors associated with increased pain included larger tumor size, greater number of tumors, and longer procedure and ablation time (P < 0.05). No major complications were recorded across the three groups. CONCLUSION: CMRA offers an effective and safe modality to manage pain during and after US-guided-MWA of liver tumors.

Amyloid-ß mediates intestinal dysfunction and enteric neurons loss in Alzheimer's disease transgenic mouse.

Alzheimer's disease (AD) is traditionally considered as a brain disorder featured by amyloid-ß (Aß) deposition. The current study on whether pathological changes of AD extend to the enteric nervous system (ENS) is still in its infancy. In this study, we found enteric Aß deposition, intestinal dysfunction, and colonic inflammation in the young APP/PS1 mice. Moreover, these mice exhibited cholinergic and nitrergic signaling pathways damages and enteric neuronal loss. Our data show that Aß42 treatment remarkably affected the gene expression of cultured myenteric neurons and the spontaneous contraction of intestinal smooth muscles. The intra-colon administration of Aß42 induced ENS dysfunction, brain gliosis, and ß-amyloidosis-like changes in the wild-type mice. Our results suggest that ENS mirrors the neuropathology observed in AD brains, and intestinal pathological changes may represent the prodromal events, which contribute to brain pathology in AD. In summary, our findings provide new opportunities for AD early diagnosis and prevention.

Investigation on preventive inerting approach of coal spontaneous combustion in gob considering adsorption effect.

Coal spontaneous combustion in the gob poses a significant threat to coal mining operations. Designing optimal process parameters for nitrogen injection to prevent and control fires efficiently is crucial. To achieve this, a multi-field coupling equation was established, considering the adsorption of coal to gas. The model's accuracy was verified on-site, and the effects of nitrogen injection at different locations and flow rates were simulated. The optimal injection parameters were determined by analyzing temperature and inerting time. The results showed that the coal spontaneous combustion hazardous zone in the gob tested on-site was consistent with the simulation from the perspective of physisorption. Nitrogen injection had three stages: gas expansion, rapid oxygen dilution, and complete inerting. The nitrogen injection effect presented a nonlinear change in injection location and flow rate. The optimal nitrogen injection location for the Tingnan Coal Mine in Shaanxi was determined to be 90 m behind the working face on the inlet side, with an optimal flow rate of 800 m3/min. This study focused on gas adsorption and offered valuable insights for creating high-efficiency fire-fighting techniques that involve inserting in the gob.

Self-Functionalized Superlattice Nanosensor Enables Glioblastoma Diagnosis Using Liquid Biopsy.

Glioblastoma (GBM), the most aggressive and lethal brain cancer, is detected only in the advanced stage, resulting in a median survival rate of 15 months. Therefore, there is an urgent need to establish GBM diagnosis tools to identify the tumor accurately. The clinical relevance of the current liquid biopsy techniques for GBM diagnosis remains mostly undetermined, owing to the challenges posed by the blood-brain barrier (BBB) that restricts biomarkers entering the circulation, resulting in the unavailability of clinically validated circulating GBM markers. GBM-specific liquid biopsy for diagnosis and prognosis of GBM has not yet been developed. Here, we introduce extracellular vesicles of GBM cancer stem cells (GBM CSC-EVs) as a previously unattempted, stand-alone GBM diagnosis modality. As GBM CSCs are fundamental building blocks of tumor initiation and recurrence, it is desirable to investigate these reliable signals of malignancy in circulation for accurate GBM diagnosis. So far, there are no clinically validated circulating biomarkers available for GBM. Therefore, a marker-free approach was essential since conventional liquid biopsy relying on isolation methodology was not viable. Additionally, a mechanism capable of trace-level detection was crucial to detecting the rare GBM CSC-EVs from the complex environment in circulation. To break these barriers, we applied an ultrasensitive superlattice sensor, self-functionalized for surface-enhanced Raman scattering (SERS), to obtain holistic molecular profiling of GBM CSC-EVs with a marker-free approach. The superlattice sensor exhibited substantial SERS enhancement and ultralow limit of detection (LOD of attomolar 10-18 M concentration) essential for trace-level detection of invisible GBM CSC-EVs directly from patient serum (without isolation). We detected as low as 5 EVs in 5 µL of solution, achieving the lowest LOD compared to existing SERS-based studies. We have experimentally demonstrated the crucial role of the signals of GBM CSC-EVs in the precise detection of glioblastoma. This was evident from the unique molecular profiles of GBM CSC-EVs demonstrating significant variation compared to noncancer EVs and EVs of GBM cancer cells, thus adding more clarity to the current understanding of GBM CSC-EVs. Preliminary validation of our approach was undertaken with a small amount of peripheral blood (5 µL) derived from GBM patients with 100% sensitivity and 97% specificity. Identification of the signals of GBM CSC-EV in clinical sera specimens demonstrated that our technology could be used for accurate GBM detection. Our technology has the potential to improve GBM liquid biopsy, including real-time surveillance of GBM evolution in patients upon clinical validation. This demonstration of liquid biopsy with GBM CSC-EV provides an opportunity to introduce a paradigm potentially impacting the current landscape of GBM diagnosis.

Expanding the mutational and clinical spectrum of Chinese intellectual disability patients with two novel CTCF variants.

CCCTC-Binding Factor (CTCF) is a protein-coding gene involved in transcriptional regulation, insulator activity, and regulation of chromatin structure, and is closely associated with intellectual developmental disorders. In this study, we report two unrelated Chinese patients with intellectual disability (ID). According to variant interpretation results from exome sequencing data and RNA-seq data, we present two novel heterozygous CTCF variants, NM_006565.3:c.1519_2184del (p. Glu507_Arg727delins47) and NM_006565.3:c.1838_1852del (p.Glu613_Pro617del), found in two distinct unrelated patients, respectively. Moreover, RNA-seq data of patient 1 indicated the absence of the mutant transcript, while in patient 2, the RNA-seq data revealed a CTCF mRNA transcript with a deletion of 15 nucleotides. Notably, the RNA sequencing data revealed 507 differentially expressed genes shared between these two patients. Specifically, among them, 194 were down-regulated, and 313 were up-regulated, primarily involved in gene regulation and cellular response. Our study expands the genetic and clinical spectrum of CTCF and advances our understanding of the pathogenesis of CTCF in vivo.

Probing the effects of silicon amendment on combined stressors on rice: Lead pollution and blast fungus (Magnaporthe oryzae) infection.

As agroecology deteriorates, agricultural production is threatened by the combined stressors of exposure to environmental pollutants and pathogenic microbes. Proper agronomic practices for crop growth management and fertilization require understanding plant tolerance strategies. Both rice blast and heavy metals substantially impair rice crops, while silicon (Si) is an effective amendment to alleviate the combined stressors. Herein, this study was conducted to investigate the rice physiology and pathology perspective on the mechanism of Si alleviation against both lead (Pb) toxicity and Magnaporthe oryzae infection, utilizing pot experiments with inoculation of the virulent Magnaporthe oryzae strain. Exogenous Si reduced the phyto-availability and plant absorption of Pb, resulting in a 73.5% reduction in exchangeable Pb concentration in soil and a 40.23% reduction in rice plants. Furthermore, Si addition boosted the plant antioxidant system by increasing the activities of related enzymes, as the activities of catalase, superoxide dismutase, and polyphenol oxidase were significantly improved while the activity of peroxidase in rice panicles decreased. As a result, an improvement in dry matter quantity by 19.19% was observed compared to treatments without Si application, and the panicle blast severity (PBS) was reduced by 0.4-37.52%. Notwithstanding the interaction between the combined stressors, this study revealed that the speciation of Pb formation in the rhizosphere was the primary contributor to the alleviation of abiotic stresses, whereas the regulation of oxidative stress by enzymatic antioxidants played a dominant role in alleviating Magnaporthe oryzae colonization and impairments. The regulation process may reveal the mechanism of siliceous fertilizer functioning in the paddy system. Thereby the role of exogenous Si in anti-fungal, heavy metal toxicology, and plant physiology needs further study to fully elucidate the role of Si amendment, which is proposed to be considered from the perspective of soil chemistry and plant physiology.

ABCF1/CXCL12/CXCR4 Enhances Glioblastoma Cell Proliferation, Migration, and Invasion by Activating the PI3K/AKT Signal Pathway.

Glioblastoma (GBM) is the most prevalent and fatal form of brain tumor, which is associated with a poor prognosis. ATP-binding cassette subfamily F member 1 (ABCF1) is an E2 ubiquitin-conjugating enzyme, which is implicated in regulating immune responses and tumorigenesis. Aberrant E3 ubiquitylation has been evidenced in GBM. However, the role of ABCF1 in GBM needs to be further explored. The expression of ABCF1, CXC chemokine ligand 12 (CXCL12), and CXC chemokine receptor 4 (CXCR4) in GBM tissues was examined by the GEPIA tool, real-time PCR and Western blotting. HMC3, U251MG, and LN-229 cells were cultured and transfected with shRNA targeting ABCF1 and ABCF1 plasmids. The proliferative, migrative, and invasive ability of cells was detected. Western blotting was used to detect the levels of phosphorylated phosphatidylinositol 3-kinase (PI3K) and phosphorylated protein kinase B (AKT). We observed that GBM tissues had higher ABCF1, CXCL12, and CXCR4 expression levels. The expression levels of CXCL12 and CXCR4 were enhanced by ABCF1 overexpression, which were significantly reversed by silence of ABCF1 in GBM cells. Silencing ABCF1 or CXCR4 inhibition weakened the capacity of GBM cell growth, migration, and invasion, while ectopic ABCF1 expression or CXCL12 treatment enhanced the cellular function of GBM cells. Furthermore, p-PI3K and p-AKT protein levels were downregulated by ABCF1 knockdown or CXCR4 blockade, which were prompted by ABCF1 overexpression or CXCL12 supplement. The ABCF1-CXCL12-CXCR4 axis was identified as a key player in GBM cell survival and metastasis by activating the PI3K/AKT signaling pathway in GBM cells.