Transcriptome analyses of Acer Truncatum Bunge seeds to delineate the genes involved in fatty acid metabolism.

BACKGROUND: Acer truncatum Bunge is an economic, ecological, oil, and medicinal tree, and its kernel oil is rich in nervonic acid. It is crucial to explore the transcriptional expression patterns of genes affecting fatty acid synthesis to improve the quality of Acer truncatum oil. RESULTS: This study used the seeds from high fatty acid strain YQC and those from low fatty acid strain Y38 as the test materials. Specifically, we performed a comparative transcriptome analysis of Y38 seeds and YQC to identify differentially expressed genes (DEGs) at two time points (seeds 30 days after the blooming period and 90 days after the blooming period). Compared with YQC_1 (YQC seeds at 30 days after the blooming period), a total of 3,618 DEGs were identified, including 2,333 up-regulated and 1,285 downregulated DEGs in Y38_1 (Y38 seeds at 30 days after blooming period). In the Y38_2 (Y38 seeds at 90 days after the blooming period) versus YQC_2 (YQC seeds at 90 days after the blooming period) comparison group, 9,340 genes were differentially expressed, including 5,422 up-regulated and 3,918 down-regulated genes. The number of DEGs in Y38 compared to YQC was significantly higher in the late stages of seed development. Gene functional enrichment analyses showed that the DEGs were mainly involved in the fatty acid biosynthesis pathway. And two fatty acid synthesis-related genes and seven nervonic acid synthesis-related genes were validated by qRT-PCR. CONCLUSIONS: This study provides a basis for further research on biosynthesizing fatty acids and nervonic acidnervonic acids in A. truncatum seeds.

Genes associated with N6-methyladenosine regulators provide insight into the prognosis and immune response to renal clear cell carcinoma.

As one of the most common messenger ribonucleic acid modifications in eukaryotic organisms, N6-methyladenosine (m6A) is involved in a wide variety of biological functions. The imbalance of m6A RNA modification may be linked to cancer and other disorders, according to a growing body of studies. Its effects on clear cell renal cell carcinoma (KIRC) have not been well discussed, though. Here, we acquired the expression patterns of 23 important regulators of m6A RNA modification and assess how they might fare in KIRC. We observed that 17 major m6A RNA modification regulatory factors had a substantial predictive influence on KIRC. Using the "ConsensusCluster" program, we defined two groupings (Cluster 1 and Cluster 2) depending on the expression of the aforementioned 17 key m6A RNA methylation regulators. The Cluster 2 has a less favorable outcome and is strongly related with a lesser immune microenvironment, according to the findings. We also developed a strong risk profile for three m6A RNA modifiers (METTL14, YTHDF1, and LRPPRC) using multivariate Cox regression analysis. According to further research, the aforementioned risk profile could serve as an independent predicting factor for KIRC, and the chemotherapy response sensitivity was analyzed between two risk groups. Moreover, to effectively forecast the future outlook of KIRC clients, we established a novel prognostic approach according to gender, age, histopathological level, clinical stage, and risk score. Finally, the function of hub gene METTL14 was validated by cell proliferation and subcutaneous graft tumor in mice. In conclusion, we discovered that m6A RNA modifiers play an important role in controlling KIRC and created a viable risk profile as a marker of prediction for KIRC clients.

Characteristics of Online Health Care Services From China's Largest Online Medical Platform: Cross-sectional Survey Study.

BACKGROUND: Internet hospitals in China are in great demand due to limited and unevenly distributed health care resources, lack of family doctors, increased burdens of chronic diseases, and rapid growth of the aged population. The COVID-19 epidemic catalyzed the expansion of online health care services. In recent years, internet hospitals have been rapidly developed. Ping An Good Doctor is the largest, national online medical entry point in China and is a widely used platform providing online health care services. OBJECTIVE: This study aims to give a comprehensive description of the characteristics of the online consultations and inquisitions in Ping An Good Doctor. The analyses tried to answer the following questions: (1) What are the characteristics of the consultations in Ping An Good Doctor in terms of department and disease profiles? (2) Who uses the online health services most frequently? and (3) How is the user experience of the online consultations of Ping An Good Doctor? METHODS: A total of 35.3 million consultations and inquisitions over the course of 1 year were analyzed with respect to the distributions of departments and diseases, user profiles, and consulting behaviors. RESULTS: The geographical distribution of the usage of Ping An Good Doctor showed that Shandong (18.4%), Yunnan (15.6%), Shaanxi (7.2%), and Guangdong (5.5%) were the provinces that used it the most; they accounted for 46.6% of the total consultations and inquisitions. In terms of department distribution, we found that gynecology and obstetrics (19.2%), dermatology (17.0%), and pediatrics (14.4%) were the top three departments in Ping An Good Doctor. The disease distribution analysis showed that, except for nondisease-specific consultations, acute upper respiratory infection (AURI) (4.1%), pregnancy (2.8%), and dermatitis (2.4%) were the most frequently consulted diseases. In terms of user profiles, females (60.4%) from 19 to 35 years of age were most likely to seek consultations online, in general. The user behavior analyses showed that the peak times of day for online consultations occurred at 10 AM, 3 PM, and 9 PM. Regarding user experience, 93.0% of users gave full marks following their consultations. For some disease-related health problems, such as AURI, dermatitis, and eczema, the feedback scores were above average. CONCLUSIONS: The prevalence of internet hospitals, such as Ping An Good Doctor, illustrated the great demand for online health care services that can go beyond geographical limitations. Our analyses showed that nondisease-specific issues and moderate health problems were much more frequently consulted about than severe clinical conditions. This indicated that internet hospitals played the role of the family doctor, which helped to relieve the stress placed on offline hospitals and facilitated people's lives. In addition, good user experiences, especially regarding disease-related inquisitions, suggested that online health services can help solve health problems. With support from the government and acceptance by the public, online health care services could develop at a fast pace and greatly benefit people's daily lives.

Correction to: Identification of ALDH3A2 as a novel prognostic biomarker in gastric adenocarcinoma using integrated bioinformatics analysis.

An amendment to this paper has been published and can be accessed via the original article.

Identification of ALDH3A2 as a novel prognostic biomarker in gastric adenocarcinoma using integrated bioinformatics analysis.

BACKGROUND: Extensive research has revealed that genes play a pivotal role in tumor development and growth. However, the underlying involvement of gene expression in gastric carcinoma (GC) remains to be investigated further. METHODS: In this study, we identified overlapping differentially expressed genes (DEGs) by comparing tumor tissue with adjacent normal tissue using the Gene Expression Omnibus (GEO) and the Cancer Genome Atlas (TCGA) database. RESULTS: Our analysis identified 79 up-regulated and ten down-regulated genes. Functional enrichment analysis and prognosis analysis were conducted on the identified genes, and the fatty aldehyde dehydrogenase (FALDH) gene, ALDH3A2, was chosen for more detailed analysis. We performed Gene Set Enrichment Analysis (GSEA) and immunocorrelation analysis (infiltration, copy number alterations, and checkpoints) to elucidate the mechanisms of action of ALDH3A2 in depth. The immunohistochemical (IHC) result based on 140 paraffin-embedded human GC samples indicated that ALDH3A2 was over-expressed in low-grade GC cases and the OS of patients with low expression of ALDH3A2 was significantly shorter than those with high ALDH3A2 expression. In vitro results indicated that the expression of ALDH3A2 was negatively correlated with PDCD1, PDCD1LG2, and CTLA-4. CONCLUSION: We conclude that ALDH3A2 might be useful as a potential reference value for the relief and immunotherapy of GC, and also as an independent predictive marker for the prognosis of GC.

[Efficacy of Lactated Ringer's versus Normal Saline in Treating Patients with Septic Shock].

Objective To compare the clinical efficacy of lactated Ringer's (LR) and normal saline (NS) in treating patients with septic shock. Methods The clinical data of 198 patients with septic shock who received fluid resuscitation in the Intensive Care Unit of Quzhou People's Hospital from January 2014 to January 2016 were retrospectively analyzed. These patients were divided into NS group (n=100) and LR group (n=98) according to fluids used. The amounts of trial fluid,other liquids,and blood products and the average total fluid volume were recorded. The oxygenation index (PO2/FiO2),mean artery pressure (MAP),central venous pressure (CVP),and B-type natriuretic peptide (BNP) before and after treatment as well as the early goal-directed therapy (EGDT) 8 h (EGDT8),EGDT 24 h recovery rate,EGDT recovery time,28-day mortality rate were compared. Other secondary outcomes including bleeding,allergic reaction,acute kidney injury (AKI),venous blood filtration (RRT) rate,hyperkalemia,and ICU stay were also recorded. The 28-day survival rate was calculated using the Kaplan-Maier method,and the difference in survival rate was compared by log-rank test. Results The two groups showed no significant difference in gender,age,body weight,source of admission to ICU,procalcitonin level,source of sepsis,Acute Physiology and Chronic Health Evaluation Ⅱ score,number of AKI patients,amount of white blood cells,and C-reactive protein level (all P>0.05). The amount of blood products on the first day [(782±357)ml vs.(606±273)ml;t=2.044,P=0.046] and the average total amount of liquid on the first three days [(5470±1078)ml vs.(5092±929) ml;t=2.640,P=0.009] were significantly higher in NS group than in LR group. The amount of trial fluid and the volumes of other fluids were not significantly different (both P>0.05). The PO2/FiO2,MAP,CVP,and BNP levels significantly increased after treatment in both groups (all P<0.05);however,they were not significantly different between LR group and NS group at different time points before and after treatment (all P>0.05). The incidences of hyperlactacidemia (86.0% vs.71.4%,OR:2.457,95%CI:1.202-5.023,P=0.012) and hyperchloremia (25.0% vs.13.2%,OR:2.179,95%CI:1.041-4.562,P=0.036) were significantly higher in NS group than in LR group. These two groups showed no significant difference in EGDT8,24 h recovery rate,EGDT recovery time,28-day mortality rate,AKI,RRT rate,hyperkalemia,and ICU stay (all P>0.05). Kaplan-Meier survival analysis showed that the 28-day survival rate was not significantly different (χ2 log-rank=0.012,P=0.911). Conclusion When liquid resuscitation is applied in patients with septic shock,the use of LR can lower blood transfusion requirement on the first day and total liquid dosage on the first three days (compared with NR), along with lower incidences of hyperlactacidemia and hyperchloremia,although there was no significant difference in the 28-day mortality rate.

[Diagnosing Low Health and Wood Borer Attacked Trees of Chinese Arborvitae by Using Thermography].

Water and energy metabolism of plants is very important actions in their lives. Although the studies about these actions by using thermography were often reported, seldom were found in detecting the health status of forest trees. In this study, we increase the measurement accuracy and comparability of thermo-images by creating the difference indices. Based on it, we exam the water and energy status in stem of Chinese arborvitae (Platycladus orientalis (L.) Franco) by detecting the variance of far infrared spectrum between sap-wood and heart-wood of the cross-section of felling trees and the cores from an increment borer using thermography. The results indicate that the sap rate between sapwood and heartwood is different as the variance of the vigor of forest trees. Meanwhile, the image temperature of scale leaves from Chinese arborvitae trees with different vigor is also dissimilar. The far infrared spectrum more responds the sap status not the wood percentage in comparing to the area rate between sapwood and heartwood. The image temperature rate can be used in early determining the health status of Chinese arborvitae trees. The wood borers such as Phloeosinus aubei Perris and Semanotus bifasciatus Motschulsky are the pests which usually attack the low health trees, dying trees, wilted trees, felled trees and new cultivated trees. This measuring technique may be an important index to diagnose the health and vigor status after a large number of measurements for Chinese arborvitae trees. Therefore, there is potential to be an important index to check the tree vigor and pest damage status by using this technique. It will be a key in the tending and management of ecological and public Chinese arborvitae forest.

TIMM17A overexpression in lung adenocarcinoma and its association with prognosis.

Lung adenocarcinoma (LUAD), a leading cause of cancer-related mortality worldwide, demands a deeper understanding of its molecular mechanisms and the identification of reliable biomarkers for better diagnosis and targeted therapy. Leveraging data from the Cancer Genome Atlas (TCGA), the Clinical Proteomic Tumor Analysis Consortium (CPTAC), and the Human Protein Atlas (HPA), we investigated the mRNA and protein expression profiles of TIMM17A and assessed its prognostic significance through Kaplan-Meier survival curves and Cox regression analysis. Through Gene Set Enrichment Analysis, we explored the regulatory mechanisms of TIMM17A in LUAD progression and demonstrated its role in modulating the proliferative capacity of A549 cells, a type of LUAD cell, via in vitro experiments. Our results indicate that TIMM17A is significantly upregulated in LUAD tissues, correlating with clinical staging, lymph node metastasis, overall survival, and progression-free survival, thereby establishing it as a critical independent prognostic factor. The construction of a nomogram model further enhances our ability to predict patient outcomes. Knockdown of TIMM17A inhibited the growth of LUAD cells. The potential of TIMM17A as a biomarker and therapeutic target for LUAD presents a promising pathway for improving patient diagnosis and treatment strategies.

Antiferroptosis therapy alleviated the development of atherosclerosis.

Ferroptosis has been confirmed to be associated with various diseases, but the relationship between ferroptosis and atherosclerosis (AS) remains unclear. Our research detailly clarified the roles of ferroptosis in three continuous and main pathological stages of AS respectively (injury of endothelial cells [ECs], adhesion of monocytes, and formation of foam cells). We confirmed that oxidized low-density lipoprotein (ox-LDL), the key factor in the pathogenesis of AS, strongly induced ferroptosis in ECs. Inhibition of ferroptosis repressed the adhesion of monocytes to ECs by inhibiting inflammation of ECs. Ferroptosis also participated in the formation of foam cells and lipids by regulating the cholesterol efflux of macrophages. Further research confirmed that ox-LDL repressedthe activity of glutathione peroxidase 4 (GPX4), the classic lipid peroxide scavenger. Treatment of a high-fat diet significantly induced ferroptosis in murine aortas and aortic sinuses, which was accompanied by AS lesions and hyperlipidemia. Treatment with ferroptosis inhibitors significantly reduced ferroptosis, hyperlipidemia, and AS lesion development. In conclusion, our research determined that ox-LDL induced ferroptosis by repressing the activity of GPX4. Antiferroptosis treatment showed promising treatment effects in vivo. Ferroptosis-associated indexes also showed promising diagnostic potential in AS patients.

Super-enhancer-driven LIF promotes the mesenchymal transition in glioblastoma by activating ITGB2 signaling feedback in microglia.

BACKGROUND: The mesenchymal (MES) subtype of glioblastoma (GBM) is believed to be influenced by both cancer cell-intrinsic alterations and extrinsic cellular interactions, yet the underlying mechanisms remain unexplored. METHODS: Identification of microglial heterogeneity by bioinformatics analysis. Transwell migration, invasion assays, and tumor models were used to determine gene function and the role of small molecule inhibitors. RNA sequencing, chromatin immunoprecipitation, and dual-luciferase reporter assays were performed to explore the underlying regulatory mechanisms. RESULTS: We identified the inflammatory microglial subtype of tumor-associated microglia (TAM) and found that its specific gene ITGB2 was highly expressed in TAM of MES GBM tissues. Mechanistically, the activation of ITGB2 in microglia promoted the interaction between the SH2 domain of STAT3 and the cytoplasmic domain of ITGB2, thereby stimulating the JAK1/STAT3/IL-6 signaling feedback to promote the MES transition of GBM cells. Additionally, microglia communicated with GBM cells through the interaction between the receptor ITGB2 on microglia and the ligand ICAM-1 on GBM cells, while an increased secretion of ICAM-1 was induced by the proinflammatory cytokine LIF. Further studies demonstrated that inhibition of CDK7 substantially reduced the recruitment of SNW1 to the super-enhancer of LIF, resulting in transcriptional inhibition of LIF. We identified notoginsenoside R1 as a novel LIF inhibitor that exhibited synergistic effects in combination with temozolomide. CONCLUSIONS: Our research reveals that the epigenetic-mediated interaction of GBM cells with TAM drives the MES transition of GBM and provides a novel therapeutic avenue for patients with MES GBM.

Self-Assembled Aza-Boron-Dipyrromethene-Based H2S Prodrug for Synergistic Ferroptosis-Enabled Gas and Sonodynamic Tumor Therapies.

Glioblastoma multiforme (GBM) is the most aggressive and lethal subtype of gliomas of the central nervous system. The efficacy of sonodynamic therapy (SDT) against GBM is significantly reduced by the expression of apoptosis-inhibitory proteins in GBM cells. In this study, an intelligent nanoplatform (denoted as Aza-BD@PC NPs) based on the aza-boron-dipyrromethene dye and phenyl chlorothionocarbonate-modified DSPE-PEG molecules is developed for synergistic ferroptosis-enabled gas therapy (GT) and SDT of GBM. Once internalized by GBM cells, Aza-BD@PC NPs showed effective cysteine (Cys) consumption and Cys-triggered hydrogen sulfide (H2S) release for ferroptosis-enabled GT, thereby disrupting homeostasis in the intracellular environment, affecting GBM cell metabolism, and inhibiting GBM cell proliferation. Additionally, the released Aza-BD generated abundant singlet oxygen (1O2) under ultrasound irradiation for favorable SDT. In vivo and in vitro evaluations demonstrated that the combined functions of Cys consumption, H2S production, and 1O2 production induced significant death of GBM cells and markedly inhibited tumor growth, with an impressive inhibition rate of up to 97.5%. Collectively, this study constructed a cascade nanoreactor with satisfactory Cys depletion performance, excellent H2S release capability, and prominent reactive oxygen species production ability under ultrasound irradiation for the synergistic ferroptosis-enabled GT and SDT of gliomas.

Rapid altitude displacement induce zebrafish appearing acute high altitude illness symptoms.

Rapid ascent to high-altitude areas above 2500 m often leads to acute high altitude illness (AHAI), posing significant health risks. Current models for AHAI research are limited in their ability to accurately simulate the high-altitude environment for drug screening. Addressing this gap, a novel static self-assembled water vacuum transparent chamber was developed to induce AHAI in zebrafish. This study identified 6000 m for 2 h as the optimal condition for AHAI induction in zebrafish. Under these conditions, notable behavioral changes including slow movement, abnormal exploration behavior and static behavior in the Novel tank test. Furthermore, this model demonstrated changes in oxidative stress-related markers included increased levels of malondialdehyde, decreased levels of glutathione, decreased activities of superoxide dismutase and catalase, and increased levels of inflammatory markers IL-6, IL-1ß and TNF-α, and inflammatory cell infiltration and mild edema in the gill tissue, mirroring the clinical pathophysiology observed in AHAI patients. This innovative zebrafish model not only offers a more accurate representation of the high-altitude environment but also provides a high-throughput platform for AHAI drug discovery and pathogenesis research.

Inactivated vaccines reduce the risk of liver function abnormality in NAFLD patients with COVID-19: a multi-center retrospective study.

BACKGROUND: Abnormal liver function was frequently observed in nonalcoholic fatty liver disease (NAFLD) patients infected with SARS-CoV-2. Our aim was to explore the effect of SARS-CoV-2 inactivated vaccines on liver function abnormality among NAFLD patients with COVID-19. METHODS: The multi-center retrospective cohort included 517 NAFLD patients with COVID-19 from 1 April to 30 June 2022. Participants who received 2 doses of the vaccine (n = 274) were propensity score matched (PSM) with 243 unvaccinated controls. The primary outcome was liver function abnormality and the secondary outcome was viral shedding duration. Logistic and Cox regression models were used to calculate the odds ratio (OR) and hazard ratio (HR) for the outcomes. Sensitivity analysis was conducted to assess robustness. FINDINGS: PSM identified 171 pairs of vaccinated and unvaccinated patients. Liver function abnormality was less frequent in the vaccinated group (adjusted OR, 0.556 [95% CI (confidence interval), 0.356-0.869], p = 0.010). Additionally, the vaccinated group demonstrated a lower incidence of abnormal bilirubin levels (total bilirubin: adjusted OR, 0.223 [95% CI, 0.072-0.690], p = 0.009; direct bilirubin: adjusted OR, 0.175 [95% CI, 0.080-0.384], p < 0.001) and shorter viral shedding duration (adjusted HR, 0.798 [95% CI, 0.641-0.994], p = 0.044) than the unvaccinated group. Further subgroup analysis revealed similar results, while the sensitivity analyses indicated consistent findings. INTERPRETATION: SARS-CoV-2 vaccination in patients with NAFLD may reduce the risk of liver dysfunction during COVID-19. Furthermore, vaccination demonstrated beneficial effects on viral shedding in the NAFLD population. FUNDING: 23XD1422700, Tszb2023-01, Zdzk2020-10, Zdxk2020-01, 2308085J27 and JLY20180124.

CircRNA RNA hsa_circ_0008234 Promotes Colon Cancer Progression by Regulating the miR-338-3p/ETS1 Axis and PI3K/AKT/mTOR Signaling.

Circular RNAs (circRNAs) have been shown to play a crucial role in cancer occurrence and progression. This present work investigated the link between hsa_circ_0008234 and colon cancer. Data retrieved from GSE172229 was used to compare the circRNA profiles of colon cancer and surrounding non-tumorous tissues. The amount of RNA and protein in the molecules was determined using quantitative real-time PCR (qRT-PCR) and Western blot analysis, respectively. The cell proliferation ability was assessed using CCK8, EdU, colon formation, and nude mice tumorigenesis tests. Cell invasion and migration abilities were evaluated using transwell wound healing and mice lung metastasis model. Hsa_circ_0008234 piqued our interest because bioinformatics and qRT-PCR analyses revealed that it is upregulated in colon cancer tissue. Cell phenotypic studies suggest that hsa_circ_0008234 may significantly increase colon cancer cell aggressiveness. Mice experiments revealed that inhibiting hsa_circ_0008234 significantly reduced tumor growth and metastasis. Moreover, the fluorescence in situ hybridization experiment demonstrated that hsa_circ_0008234 is primarily found in the cytoplasm, implying that it potentially functions via a competitive endogenous RNA pathway. These findings indicated that hsa_circ_0008234 may act as a "molecular sponge" for miR-338-3p, increasing the expression of miR-338-target 3p's ETS1. In addition, the traditional oncogenic pathway PI3K/AKT/mTOR signaling was found to be the potential downstream pathway of the hsa_circ_0008234/miR-338-3p/ETS1 axis. In conclusion, hsa_circ_0008234 increases colon cancer proliferation, infiltration, and migration via the miR-338-3p/ETS1/PI3K/AKT axis; therefore, it could serve as a target and a focus for colon cancer therapy.

CASPR2 antibody associated neurological syndromes in children.

To strengthen the understanding of the clinical features for CASPR2 neurological autoimmunity in children. A multicenter retrospective and prospective analysis of CASPR2 autoimmunity was conducted. Twenty-six patients were enrolled, including 25 with serum positivity and 3 with cerebrospinal fluid (CSF) positivity; 5 patients were co-positive with anti-NMDAR or anti-GABABR antibodies. Eleven patients (who manifested with refractory epilepsy, psychobehavioral abnormalities or germinoma) presented with low antibody titers, relatively normal MRI/EEG/CSF examinations, and poor response to immunotherapy and were thus considered false positive (42.3%). Fifteen patients were diagnosed with autoimmune encephalitis/ encephalopathy/ cerebellitis (including 1 whose condition was secondary to Japanese encephalitis). The most common symptoms included disorders of consciousness (10/15), fever (8/15), psychological symptoms/abnormal behaviors (8/15), sleep disorders (8/15), seizures (7/15), movement disorders (5/15), autonomic symptoms (5/15). Brain MRI revealed abnormalities in 10 patients (66.7%). Electroencephalography (EEG) recordings revealed a slow wave background in 13 patients (86.7%). Five patients showed elevated WBCs in CSF, and 4 patients showed elevated protein levels in the CSF. Thirteen patients received immunotherapy (rituximab was adopted in 2 cases) and recovered well. Two patients received symptomatic treatment, and the recovery was slow and accompanied by emotional abnormalities and developmental delay. Autoimmune encephalitis is the most common clinical phenotype; it can be secondary to Japanese encephalitis. Rituximab can be used in patients who respond poorly to conventional immunotherapy. The high false-positive rate of anti-CASPR2 in refractory epilepsy and the psychobehavioral abnormalities needs to be explored further.

Online dynamic nomogram for predicting pain recurrence after microvascular decompression in trigeminal neuralgia.

Trigeminal neuralgia (TN) is one of the most common causes of facial pain. Microvascular decompression (MVD) is the first-choice surgical treatment. The present study aimed to develop a novel practical assessment system based on preoperative clinical and imaging factors for clinicians to predict the likelihood of pain recurrence following MVD in TN. A total of 56 patients with primary unilateral TN who underwent MVD were retrospectively analyzed. Patients were followed up to observe pain recurrence 1 year after MVD. An online dynamic nomogram was constructed for predicting the probability of pain recurrence after MVD in patients with TN based on multivariate logistic model. The concordance index (C-index) and receiver operating characteristic (ROC) were used to measure model discrimination. Bootstrap resampling was used for internal validation of the model and calibration curve was constructed. Decision curve analysis (DCA) was used to assess clinical applicability. Factors such as numeric rating scale (to score pain degree of patients with TN), response to neuroanalgesic drugs and neurovascular contact on magnetic resonance imaging were independent risk factors affecting the pain recurrence rate (all P<0.05). C-index was 0.973 (95%CI, 0.938-1.000) and the area under the ROC was 0.973 (95%CI, 0.938-1.000). Calibration curve with a 1,000 bootstrap resampling showed a good fit between dynamic nomogram prediction and actual observations. The DCA showed that at a threshold probability between 0 and 100%, this model can achieve a greater net benefit than if all patients had surgery or none had surgery. In conclusion, this online dynamic nomogram reliably predicted risk of pain recurrence in patients with TN following MVD.

Ellagic acid induces apoptosis and autophagy in colon cancer through the AMPK/mTOR pathway.

Ellagic acid (EA), found in fruits and foods, has been shown to be effective in the treatment of breast, colon and bladder cancer. However, due to the complexity of colon cancer, the therapeutic mechanism of EA for colon cancer is still unclear. Cell Counting Kit-8 (CCK-8) assay were employed to investigate the cell proliferation. Western blotting and flow cytometry assays were utilized to investigate apoptosis and autophagy in CRC cells (HCT116), respectively. Moreover, western blotting and luciferase reporter assays were evaluated the effect of EA on AMPK/mTOR pathway. Through flow cytometry analysis, EA could promote the apoptosis of HCT116 cells. In addition, EA can reduce the phosphorylation of mTOR, promoted phosphorylation of AMPK, and induced autophagy in HCT116 cells. Also, Dorsomorphin pretreatment can reduce the expression of autophagy protein, which indicates that EA induces autophagy through AMPK/mTOR pathway. These results suggest that EA inhibits the growth of colon cancer through AMPK/mTOR pathway and induces apoptosis and protective autophagy.

Nanosonosensitizers-engineered injectable thermogel for augmented chemo-sonodynamic therapy of melanoma and infected wound healing.

Easy recurrence and bacteria infected-wound healing after surgery excision pose severe challenges to clinical melanoma therapy. Herein, an injectable CuO2 nanodots-engineered thermosensitive chitosan hydrogel (CuO2-BSO@Gel) for enhanced melanoma chemo-sonodynamic therapy and improved infected wound healing was rationally constructed by facilely integrating the CuO2 nanodots and L-Buthionine-(S, R)-sulfoximine (BSO) with thermoresponsive hydrogel. Favored by the Fenton catalytic activity of Cu2+, the CuO2 nanodots can achieve enhanced chemodynamic therapy (CDT) by self-supplying H2O2 under acidic tumor microenvironment. Simultaneously, the CuO2 nanodots with a narrow bandgap (2.29 â€‹eV) were proven to be the efficient sonosensitizers, and the corresponding quantum yield of singlet oxygen (1O2) could be boosted by the O2 generation during Fenton-like reactions. Additionally, combining with the glutathione (GSH) depletion of loaded BSO, intracellular oxidative stress induced by SDT and CDT was further amplified, leading to the specific ferroptosis. Importantly, this multifunctional hydrogel significantly promoted the proliferation of normal skin cells and accelerated the bacteria-infected wound healing by the effective chemo-sonodynamic antibacterial activity and the enhanced angiogenesis. Thus, the engineered thermogel features the distinct chemo-sonodynamic performance, desirable biocompatibility and bioactivity, providing a competitive strategy for eradicating melanoma and infected wound healing.

AL360181.1 promotes proliferation and invasion in colon cancer and is one of ten m6A-related lncRNAs that predict overall survival.

Background: N6-methyladenosine (m6A) exerted a pivotal role in colon cancer. Nevertheless, the long non-coding RNAs (lncRNAs) associated with this process have yet to be elucidated. Methods: The open-access data used for analysis was downloaded from The Cancer Genome Atlas (TCGA) database for analysis, employing the R software for computational evaluations. The RNA level of specific molecules was assessed using the quantitative real-time PCR. CCK8, colony formation and transwell assay were used to evaluate the proliferation, invasion and migration ability of colon cancer cells. Results: Here, we identified the m6A regulators from TCGA data and subsequently pinpointed lncRNAs with a -Cor- > 0.3 and P < 0.05, categorizing them as m6A-associated lncRNAs. Moreover, we formulated a prognosis signature rooted in ten m6A-related lncRNAs, consisting of AL360181.1, PCAT6, SNHG26, AC016876.1, AC104667.2, AL114730.3, LINC02257, AC147067.1, AP006621.3 and AC009237.14. This signature exhibited notable predictive accuracy in gauging patient survival. Immune-related evaluations revealed varied immune cell infiltration patterns across different risk groups, with our findings suggesting superior immunotherapy response in low-risk patients. Biological enrichment analysis indicated that the high-risk patients had a higher activity of multiple carcinogenic pathways, including glycolysis. The previously unreported lncRNA, AL360181.1, displayed a connection to glycolytic activity and diminished survival rates, warranting further investigation. The result indicated that AL360181.1 was correlated with more aggressive clinical characteristics. Immune infiltration assessments found AL360181.1 to have a positive correlation with Tcm infiltration, but an inverse relationship with entities like Th2 cells, T cells, neutrophils and macrophages. Biological enrichment analysis indicated that the pathways of WNT/ß-catenin, pancreas beta cells, hedgehog signaling and some metabolism pathways were upregulated in high AL360181.1 patients. In vitro experiments showed that AL360181.1 was upregulated in the colon cancer cells. Moreover, AL360181.1 significantly promotes the proliferation, invasion and migration of colon cancer cells. Conclusions: Our results can provide direction for future studies on m6A-related lncRNA in colon cancer.

Harnessing immunotherapy for brain metastases: insights into tumor-brain microenvironment interactions and emerging treatment modalities.

Brain metastases signify a deleterious milestone in the progression of several advanced cancers, predominantly originating from lung, breast and melanoma malignancies, with a median survival timeframe nearing six months. Existing therapeutic regimens yield suboptimal outcomes; however, burgeoning insights into the tumor microenvironment, particularly the immunosuppressive milieu engendered by tumor-brain interplay, posit immunotherapy as a promising avenue for ameliorating brain metastases. In this review, we meticulously delineate the research advancements concerning the microenvironment of brain metastases, striving to elucidate the panorama of their onset and evolution. We encapsulate three emergent immunotherapeutic strategies, namely immune checkpoint inhibition, chimeric antigen receptor (CAR) T cell transplantation and glial cell-targeted immunoenhancement. We underscore the imperative of aligning immunotherapy development with in-depth understanding of the tumor microenvironment and engendering innovative delivery platforms. Moreover, the integration with established or avant-garde physical methodologies and localized applications warrants consideration in the prevailing therapeutic schema.