Effects of silencing hsa_circ_0015326 on proliferation, migration, invasion, and apoptosis of epithelial ovarian cancer cells.

Although the treatment of ovarian cancer has made great progress, there are still many patients who are not timely detected and given targeted therapy due to unknown pathogenesis. Recent studies have found that hsa_circ_0015326 is upregulated in ovarian cancer and is involved in the proliferation, invasion, and migration of ovarian cancer cells. However, whether hsa_circ_0015326 can be used as a new target of ovarian cancer needs further investigation. Therefore, the effect of hsa_circ_0015326 on epithelial ovarian cancer was investigated in this study. At first, si-hsa_circ_0015326 lentivirus was transfected into epithelial ovarian cancer cells. Then real-time fluorescence quantitative PCR (qRT-PCR) was used to detect hsa_circ_0015326 level. The proliferation of ovarian cancer cells was detected by CCK-8 assay. The horizontal and vertical migration abilities of the cells were detected by wound-healing assay and Transwell assay, respectively. Transwell assay was also used to determine the invasion rate. As for the apoptosis rate, it was assessed by flow cytometry. As a result, the expression level of hsa_circ_0015326 in A2780 and SKOV3 was found to be higher than that in IOSE-80. However, after transfecting si-hsa_circ_0015326 and si-NC into the cells, the proliferation, migration, and invasion abilities of A2780 and SKOV3 cells in the si-hsa_circ_0015326 group were significantly reduced in comparison to those in the si-NC and mock groups, while their apoptosis rates were elevated. Collectively, silencing hsa_circ_0015326 bears the capability of inhibiting the proliferation, migration, and invasion of ovarian cancer cells while increasing apoptosis rate. It can be concluded that hsa_circ_0015326 promotes the malignant biological activities of epithelial ovarian cancer cells.

Colonic crypt stem cell functions are controlled by tight junction protein claudin-7 through Notch/Hippo signaling.

The tight junction protein claudin-7 is essential for tight junction function and intestinal homeostasis. Cldn7 deletion in mice leads to an inflammatory bowel disease-like phenotype exhibiting severe intestinal epithelial damage, weight loss, inflammation, mucosal ulcerations, and epithelial hyperplasia. Claudin-7 has also been shown to be involved in cancer metastasis and invasion. Here, we test our hypothesis that claudin-7 plays an important role in regulating colonic intestinal stem cell function. Conditional knockout of Cldn7 in the colon led to impaired epithelial cell differentiation, hyperproliferative epithelium, a decrease in active stem cells, and dramatically altered gene expression profiles. In 3D colonoid culture, claudin-7-deficient crypts were unable to survive and form spheroids, emphasizing the importance of claudin-7 in stem cell survival. Inhibition of the Hippo pathway or activation of Notch signaling partially rescued the defective stem cell behavior. Concurrent Notch activation and Hippo inhibition resulted in restored colonoid survival, growth, and differentiation to the level comparable to those of wild-type derived crypts. In this study, we highlight the essential role of claudin-7 in regulating Notch and Hippo signaling-dependent colonic stem cell functions, including survival, self-renewal, and differentiation. These new findings may shed light on potential avenues to explore for drug development in colorectal cancer.

Tigroid Enhancement: A Characteristic Enhancement Pattern of the Cerebellar Hemisphere on MRI With Intracranial Dural Arteriovenous Fistulas.

PURPOSE: This study aims to investigate a characteristic cerebellar hemisphere enhancement pattern on magnetic resonance imaging (MRI) that could aid in early and specific diagnosis of intracranial dural arteriovenous fistulas (DAVFs). MATERIALS AND METHODS: Pretreatment MR images of 57 patients with intracranial DAVFs between January 1, 2017, and February 28, 2023, were retrospectively analyzed. A total of 128 patients with confirmed alternative cerebellar lesions during the same period were included as a control group. All patients underwent enhanced MRI with a 3.0T scanner. The presence or absence of parallel enhanced linear striations on the surface of the cerebellar lesions was documented. Statistically significant differences were determined by the Fisher exact test. RESULTS: Cerebellar lesions were identified in 4 intracranial DAVF patients (7.0%). All 4 patients were male, with an average age of 64 years (range: 58-76 years). The pretreatment MR images of all 4 DAVF patients with cerebellar lesions demonstrated the characteristic tigroid enhancement pattern. Tortuous flow voids were present in the MR images of 3 of the 4 patients. Tigroid enhancement pattern was not observed in the remaining 53 intracranial DAVF patients and all control patients. The differences in the incidence of the pattern were significant (p=0.01). CONCLUSION: A characteristic tigroid enhancement pattern of the cerebellar hemisphere on MRI may aid in the early and specific diagnosis of intracranial DAVFs, allowing timely treatment and improving outcomes. CLINICAL IMPACT: The identification of a characteristic tigroid enhancement pattern on MRI for cerebellar hemisphere lesions holds significant promise for clinical practice. This pattern serves as a distinctive marker aiding in the early and specific diagnosis of intracranial dural arteriovenous fistulas (DAVFs). Clinicians can now utilize this innovative finding to expedite diagnostic workflows, enabling timely intervention and management strategies. The incorporation of this novel imaging feature enhances diagnostic accuracy, potentially reducing misdiagnosis rates and preventing delays in treatment initiation. Ultimately, this advancement may lead to improved patient outcomes and quality of care in neurosurgical and neuroradiological practice.

The Bach1/HO-1 pathway regulates oxidative stress and contributes to ferroptosis in doxorubicin-induced cardiomyopathy in H9c2 cells and mice.

Doxorubicin (DOX) is one of the most frequently used chemotherapeutic drugs belonging to the class of anthracyclines. However, the cardiotoxic effects of anthracyclines limit their clinical use. Recent studies have suggested that ferroptosis is the main underlying pathogenetic mechanism of DOX-induced cardiomyopathy (DIC). BTB-and-CNC homology 1 (Bach1) acts as a key role in the regulation of ferroptosis. However, the mechanistic role of Bach1 in DIC remains unclear. Therefore, this study aimed to investigate the underlying mechanistic role of Bach1 in DOX-induced cardiotoxicity using the DIC mice in vivo (DOX at cumulative dose of 20 mg/kg) and the DOX-treated H9c2 cardiomyocytes in vitro (1 µM). Our results show a marked upregulation in the expression of Bach1 in the cardiac tissues of the DOX-treated mice and the DOX-treated cardiomyocytes. However, Bach1-/- mice exhibited reduced lipid peroxidation and less severe cardiomyopathy after DOX treatment. Bach1 knockdown protected against DOX-induced ferroptosis in both in vivo and in vitro models. Ferrostatin-1 (Fer-1), a potent inhibitor of ferroptosis, significantly alleviated DOX-induced cardiac damage. However, the cardioprotective effects of Bach1 knockdown were reversed by pre-treatment with Zinc Protoporphyrin (ZnPP), a selective inhibitor of heme oxygenase-1(HO-1). Taken together, these findings demonstrated that Bach1 promoted oxidative stress and ferroptosis through suppressing the expression of HO-1. Therefore, Bach1 may present as a promising new therapeutic target for the prevention and early intervention of DOX-induced cardiotoxicity.

Combining prognostic value of serum carbohydrate antigen 19-9 and tumor size reduction ratio in pancreatic ductal adenocarcinoma.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is a common cancer with increasing morbidity and mortality due to changes of social environment. AIM: To evaluate the significance of serum carbohydrate antigen 19-9 (CA19-9) and tumor size changes pre- and post-neoadjuvant therapy (NAT). METHODS: This retrospective study was conducted at the Chongqing Key Laboratory of Translational Research for Cancer Metastasis and Individualized Treatment, Chongqing University Cancer Hospital. This study specifically assessed CA19-9 levels and tumor size before and after NAT. RESULTS: A total of 156 patients who completed NAT and subsequently underwent tumor resection were included in this study. The average age was 65.4 ± 10.6 years and 72 (46.2%) patients were female. Before survival analysis, we defined the post-NAT serum CA19-9 level/pre-NAT serum CA19-9 level as the CA19-9 ratio (CR). The patients were divided into three groups: CR < 0.5, CR > 0.5 and < 1 and CR > 1. With regard to tumor size measured by both computed tomography and magnetic resonance imaging, we defined the post-NAT tumor size/pre-NAT tumor size as the tumor size ratio (TR). The patients were then divided into three groups: TR < 0.5, TR > 0.5 and < 1 and TR > 1. Based on these groups divided according to CR and TR, we performed both overall survival (OS) and disease-free survival (DFS) analyses. Log-rank tests showed that both OS and DFS were significantly different among the groups according to CR and TR (P < 0.05). CR and TR after NAT were associated with increased odds of achieving a complete or near-complete pathologic response. Moreover, CR (hazard ratio: 1.721, 95%CI: 1.373-3.762; P = 0.006), and TR (hazard ratio: 1.435, 95%CI: 1.275-4.363; P = 0.014) were identified as independent factors associated with OS. CONCLUSION: This study demonstrated that post-NAT serum CA19-9 level/pre-NAT serum CA19-9 level and post-NAT tumor size/pre-NAT tumor size were independent factors associated with OS in patients with PDAC who received NAT and subsequent surgical resection.

Biomimetic MDSCs membrane coated black phosphorus nanosheets system for photothermal therapy/photodynamic therapy synergized chemotherapy of cancer.

Photothermal therapy is favored by cancer researchers due to its advantages such as controllable initiation, direct killing and immune promotion. However, the low enrichment efficiency of photosensitizer in tumor site and the limited effect of single use limits the further development of photothermal therapy. Herein, a photo-responsive multifunctional nanosystem was designed for cancer therapy, in which myeloid-derived suppressor cell (MDSC) membrane vesicle encapsulated decitabine-loaded black phosphorous (BP) nanosheets (BP@ Decitabine @MDSCs, named BDM). The BDM demonstrated excellent biosafety and biochemical characteristics, providing a suitable microenvironment for cancer cell killing. First, the BDM achieves the ability to be highly enriched at tumor sites by inheriting the ability of MDSCs to actively target tumor microenvironment. And then, BP nanosheets achieves hyperthermia and induces mitochondrial damage by its photothermal and photodynamic properties, which enhancing anti-tumor immunity mediated by immunogenic cell death (ICD). Meanwhile, intra-tumoral release of decitabine induced G2/M cell cycle arrest, further promoting tumor cell apoptosis. In vivo, the BMD showed significant inhibition of tumor growth with down-regulation of PCNA expression and increased expression of high mobility group B1 (HMGB1), calreticulin (CRT) and caspase 3. Flow cytometry revealed significantly decreased infiltration of MDSCs and M2-macrophages along with an increased proportion of CD4+, CD8+ T cells as well as CD103+ DCs, suggesting a potentiated anti-tumor immune response. In summary, BDM realizes photothermal therapy/photodynamic therapy synergized chemotherapy for cancer.

Potential health risks of microplastic fibres release from disposable surgical masks: Impact of repeated wearing and handling.

Disposable surgical masks undeniably provide important personal protection in daily life, but the potential health risks by the release of microplastic fibres from masks should command greater attention. In this study, we conducted a microplastic fibre release simulation experiment by carrying masks in a pocket and reusing them, to reveal the number and morphological changes of microfibres released. Fourier transform infrared spectrometry, scanning electron microscopy, and optical microscopy were employed to analyse the physical and chemical characteristics of the mask fibres. The results indicated that the reuse of disposable masks led to a significant release of microplastic fibres, potentially leading to their migration into the respiratory system. Furthermore, the release of microplastic fibres increased with prolonged external friction, particularly when masks were stored in pockets. The large-scale release of microplastic fibres due to mask reuse raises concerns about potential health risks to the human respiratory system. The reuse of disposable masks should be also strictly avoided in daily life in the future. Furthermore, the current study also established a robust foundation for future research endeavours on health risks associated with microplastic fibres entering the respiratory system through improper mask usage.

Lymph node targeting strategy using a hydrogel sustained-release system to load effector memory T cells improves the anti-tumor efficacy of anti-PD-1.

Communication between tumors and lymph nodes carries substantial significance for antitumor immunotherapy. Remodeling the immune microenvironment of tumor-draining lymph nodes (TdLN) plays a key role in enhancing the anti-tumor ability of immunotherapy. In this study, we constructed a biomimetic artificial lymph node structure composed of F127 hydrogel loading effector memory T (TEM) cells and PD-1 inhibitors (aPD-1). The biomimetic lymph nodes facilitate the delivery of TEM cells and aPD-1 to the TdLN and the tumor immune microenvironment, thus realizing effective and sustained anti-tumor immunotherapy. Exploiting their unique gel-forming and degradation properties, the cold tumors were speedily transformed into hot tumors via TEM cell supplementation. Meanwhile, the efficacy of aPD-1 was markedly elevated compared with conventional drug delivery methods. Our finding suggested that the development of F127@TEM@aPD-1 holds promising potential as a future novel clinical drug delivery technique. STATEMENT OF SIGNIFICANCE: Bionic artificial lymph nodes(F127@TEM@aPD-1) show unique advantages in cancer treatment. When injected subcutaneously, the artificial lymph node can continuously supplement TEM cells and aPD-1 to tumor draining lymph nodes (TdLN) and the tumor microenvironment, not only improving the efficacy of ICB therapy through slow release, but also exhibiting dual regulatory effects on the tumor and TdLN.

Exosomes derived from vMIP-II-Lamp2b gene-modified M2 cells provide neuroprotection by targeting the injured spinal cord, inhibiting chemokine signals and modulating microglia/macrophage polarization in mice.

Inflammation is one of the key injury factors for spinal cord injury (SCI). Exosomes (Exos) derived from M2 macrophages have been shown to inhibit inflammation and be beneficial in SCI animal models. However, lacking targetability restricts their application prospects. Considering that chemokine receptors increase dramatically after SCI, viral macrophage inflammatory protein II (vMIP-II) is a broad-spectrum chemokine receptor binding peptide, and lysosomal associated membrane protein 2b (Lamp2b) is the key membrane component of Exos, we speculated that vMIP-II-Lamp2b gene-modified M2 macrophage-derived Exos (vMIP-II-Lamp2b-M2-Exo) not only have anti-inflammatory properties, but also can target the injured area by vMIP-II. In this study, using a murine contusive SCI model, we revealed that vMIP-II-Lamp2b-M2-Exo could target the chemokine receptors which highly expressed in the injured spinal cords, inhibit some key chemokine receptor signaling pathways (such as MAPK and Akt), further inhibit proinflammatory factors (such as IL-1ß, IL-6, IL-17, IL-18, TNF-α, and iNOS), and promote anti-inflammatory factors (such as IL-4 and Arg1) productions, and the transformation of microglia/macrophages from M1 into M2. Moreover, the improved histological and functional recoveries were also found. Collectively, our results suggest that vMIP-II-Lamp2b-M2-Exo may provide neuroprotection by targeting the injured spinal cord, inhibiting some chemokine signals, reducing proinflammatory factor production and modulating microglia/macrophage polarization.

Indisulam synergizes with melphalan to inhibit Multiple Myeloma malignancy via targeting TOP2A.

Multiple myeloma (MM) is the second most prevalent hematologic malignancy which remains uncurable. Numerous drugs have been discovered to inhibit MM cells. Indisulam, an aryl sulfonamide, has a potent anti-myeloma activity in vitro and in vivo. This study aims to explore the new mechanism of indisulam and investigate its potential use in combination with melphalan. We examined DNA damage in MM cells through various methods such as western blotting (WB), immunofluorescence, and comet assay. We also identified the role of topoisomerase IIα (TOP2A) using bioinformatic analyses. The impact of indisulam on the RNA and protein levels of TOP2A was investigated through qPCR and WB. Cell proliferation and apoptosis were assessed using CCK-8 assays, Annexin V/PI assays and WB. We predicted the synergistic effect of the combination treatment based on calculations performed on a website, and further explored the effect of indisulam in combination with melphalan on MM cell lines and xenografts. RNA sequencing data and basic experiments indicated that indisulam caused DNA damage and inhibited TOP2A expression by decreasing transcription and promoting degradation via the proteasome pathway. Functional experiments revealed that silencing TOP2A inhibited cell proliferation and induced apoptosis and DNA damage. Finally, Indisulam/melphalan combination treatment demonstrated a strong synergistic anti-tumor effect compared to single-agent treatments in vitro and in vivo. These findings suggest that combination therapies incorporating indisulam and melphalan have the potential to enhance treatment outcomes for MM.

[Effects of Controlled-release Blended Fertilizer on Crop Yield and Greenhouse Gas Emissions in Wheat-maize Rotation System].

The increasing use of nitrogen fertilizers exerts extreme pressure on the environment (e.g., greenhouse gas emissions, GHGs) for winter wheat-summer maize rotation systems in the North China Plain. The application of controlled-release fertilizers is considered as an effective measure to improve crop yield and nitrogen fertilizer utilization efficiency. To explore the impact of one-time fertilization of controlled-release blended fertilizer on crop yield and GHGs of a wheat-maize rotation system, field experiments were carried out in Dezhou Modern Agricultural Science and Technology Park from 2020 to 2022. Five treatments were established for both winter wheat and summer maize, including no nitrogen control (CK), farmers' conventional nitrogen application (FFP), optimized nitrogen application (OPT), CRU1 (the blending ratio of coated urea and traditional urea on winter wheat and summer maize was 5:5 and 3:7, respectively), and CRU2 (the blending ratio of coated urea and traditional urea on winter wheat and summer maize was 7:3 and 5:5, respectively). The differences in yield, nitrogen fertilizer utilization efficiency, fertilization economic benefits, and GHGs among different treatments were compared and analyzed. The results showed that nitrogen application significantly increased the single season and annual crop yields of the wheat-maize rotation system (P < 0.05). Compared with those of FFP, the CRU1 and CRU2 treatments increased the yields of summer maize by 0.4% to 5.6%, winter wheat by -5.4% to 4.1%, and annual yields by -1.1% to 3.9% (P > 0.05). N recovery efficiency (NRE), N agronomic efficiency (NAE), and N partial factor productivity (NPFP) were increased by -8.6%-43.4%, 2.05-6.24 kg·kg-1, and 4.24-10.13 kg·kg-1, respectively. Annual net income increased by 0.2% to 6.3%. Nitrogen application significantly increased the annual emissions of soil N2O and CO2 in the rotation system (P < 0.05) but had no effect on the annual emissions of CH4 (except for in the FFP treatment in the first year). The annual total N2O emissions under the CRU1 and CRU2 treatments were significantly reduced by 23.4% to 30.2% compared to those under the FFP treatment (P < 0.05). Additionally, nitrogen application significantly increased the annual global warming potential (GWP) of the rotation system (P < 0.05), but the intensity of greenhouse gas emissions was reduced due to the increase in crop yields. Compared with that under FFP, the annual GWP under the CRU1 and CRU2 treatments decreased by 9.6% to 11.5% (P < 0.05), and the annual GHGs decreased by 11.2% to 13.8% (P > 0.05). In summary, the one-time application of controlled-release blended fertilizer had a positive role in improving crop yield and economic benefits, reducing nitrogen fertilizer input and labor costs, and GHGs, which is an effective nitrogen fertilizer management measure to promote cleaner production of food crops in the North China Plain.

Effect of Histamine H2 Receptor Antagonists on All-Cause Mortality in Critically Ill Patients With Essential Hypertension: A Retrospective Cohort Study.

Previous studies found that histamine H2 receptor antagonists (H2RAs) had blood pressure lowering and cardioprotective effects, but the impact of H2RAs on the survival outcomes of critically ill patients with essential hypertension is still unclear. The aim of this study was to investigate the association of H2RAs exposure with all-cause mortality in patients with essential hypertension based on Medical Information Mart for Intensive Care III database. A total of 17,739 patients were included, involving 8482 H2RAs users and 9257 non-H2RAs users. Propensity score matching (PSM) was performed to improve balance between 2 groups that were exposed to H2RAs or not. Kaplan-Meier survival curves were used to compare the cumulative survival rates and multivariable Cox regression models were performed to evaluate the association between H2RAs exposure and all-cause mortality. After 1:1 PSM, 4416 pairs of patients were enrolled. The results revealed potentially significant association between H2RAs exposure and decreased 30-day, 90-day, and 1-year mortalities in multivariate analyses (HR = 0.783, 95% CI: 0.696-0.882 for 30-day; HR = 0.860, 95% CI: 0.778-0.950 for 90-day; and HR = 0.883, 95% CI: 0.811-0.961 for 1-year mortality, respectively). Covariate effect analyses showed that the use of H2RAs was more beneficial in essential hypertension patients with age ≥ 60, BMI ≥ 25 kg/m2, coronary arteriosclerosis, stroke, and acute kidney failure, respectively. In conclusion, H2RAs exposure was related to lower mortalities in critically ill patients with essential hypertension, which provided novel potential strategy for the use of H2RAs in essential hypertension patients.

[Elesclomol-Cu Induces Cuproptosis in Human Acute Myeloid Leukemia Cells].

OBJECTIVE: To investigate the effects of elesclomol-Cu (ES-Cu) on the proliferation and cuproptosis of human acute myeloid leukemia (AML) cells. METHODS: The effects of ES-Cu on the proliferation of AML cells and the AML cells pre-treated with ammonium tetrathiomolybdate (TTM) were examined by CCK-8 assay. The Calcein/PI kit was used to detected the changes in activity and cytotoxicity of AML cells induced by ES-Cu. Flow cytometry and Cytation3 fully automated cell imaging multifunctional detection system were used to analyze DCFH-DA fluorescence intensity, so as to determine the level of reactive oxygen species (ROS). The GSH and GSSG detection kits were used to measure the intracellular GSH content. Western blot was used to detected the expression of cuproptosis-related proteins ATP7B, FDX1, DLAT and DPYD. RESULTS: ES-Cu inhibited the proliferation of Kasumi-1 and HL-60 cells in a concentration-dependent manner (r Kasumi-1=-0.99， r HL-60=-0.98). As the concentration of ES-Cu increased, the level of intracellular ROS also increased (P <0.01-0.001). TTM could significantly reverse the inhibitory effect of ES-Cu on cell proliferation and its promoting effect on ROS. With the increase of ES-Cu concentration, the content of GSH was decreased (r =-0.98), and Western blot showed that the protein expressions of ATP7B, FDX1, DLAT and DPYD were significantly reduced (P <0.05). CONCLUSION: ES-Cu can induce cuproptosis in AML cells, which provides a new idea for the treatment of AML.

The beneficial effect of α-lipoic acid on spinal cord injury repair in rats is mediated through inhibition of oxidative stress: A transcriptomic analysis.

BACKGROUND: Oxidative stress is a crucial factor contributing to the occurrence and development of secondary damage in spinal cord injuries (SCI), ultimately impacting the recovery process. α-lipoic acid (ALA) exhibits potent antioxidant properties, effectively reducing secondary damage and providing neuroprotective benefits. However, the precise mechanism by which ALA plays its antioxidant role remains unknown. METHODS: We established a model of moderate spinal cord contusion in rats. Experimental rats were randomly divided into 3 distinct groups: the sham group, the model control group (SCI_Veh), and the ALA treatment group (SCI_ALA). The sham group rats were exposed only to the SC without contusion injury. Rats belonging to SCI_Veh group were not administered any treatment after SCI. Rats of SCI_ALA group were intraperitoneally injected with the corresponding volume of ALA according to body weight for three consecutive days after the surgery. Subsequently, three days after SCI, spinal cord samples were obtained from three groups of rats: the sham group, model control group, and administration group. Thereafter, total RNA was extracted from the samples and the expression of three sets of differential genes was analyzed by transcriptome sequencing technology. Real-time PCR was used to verify the sequencing results. The impact of ALA on oxidative stress in rats following SCI was assessed by measuring their total antioxidant capacity and hydrogen peroxide (H2O2) content. The effects of ALA on rat recovery following SCI was investigated through Beattie and Bresnahan (BBB) score and footprint analysis. RESULTS: The findings from the transcriptome sequencing analysis revealed that the model control group had 2975 genes with altered expression levels when compared to the ALA treatment group. Among these genes, 1583 were found to be upregulated while 1392 were down-regulated. Gene ontology (GO) displayed significant enrichment in terms of functionality, specifically in oxidative phosphorylation, oxidoreductase activity, and signaling receptor activity. The Kyoto encyclopedia of genes and genomes (KEGG) pathway was enriched in oxidative phosphorylation, glutathione metabolism and cell cycle. ALA was found to have multiple benefits for rats after SCI, including increasing their antioxidant capacity and reducing H2O2 levels. Additionally, it was effective in improving motor function (such as 7 days after SCI, the BBB score for SCI_ALA was 8.400 ± 0.937 compared to 7.050 ± 1.141 for SCI_Veh) and promoting histological recovery after SCI (The results of HE demonstrated that the percentage of damage area in was 44.002 ± 6.680 in the SCI_ALA and 57.215 ± 3.964 in the SCI_Veh at the center of injury.). The sequence data from this study has been deposited into Sequence Read Archive (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE242507). CONCLUSION: Overall, the findings of this study confirmed the beneficial effects of ALA on recovery in SCI rats through transcriptome sequencing, behavioral, as well histology analyses.

Therapeutic effects of ginsenosides on osteoporosis for novel drug applications.

Osteoporosis (OP) is a metabolic bone disease with a high incidence rate worldwide. Its main features are decreased bone mass, increased bone fragility and deterioration of bone microstructure. It is caused by an imbalance between bone formation and bone resorption. Ginsenoside is a safe and effective traditional Chinese medicine (TCM) usually extracted from ginseng plants, having various therapeutic effects, of which the effect against osteoporosis has been extensively studied. We searched a total of 44 relevant articles with using keywords including osteoporosis, ginsenosides, bone mesenchymal cells, osteoblasts, osteoclasts and bone remodeling, all of which investigated the cellular mechanisms of different types of ginsenosides affecting the activity of bone remodeling by mesenchymal stem cells, osteoblasts and osteoclasts to counteract osteoporosis. This review describes the different types of ginsenosides used to treat osteoporosis from different perspectives, providing a solid theoretical basis for future clinical applications.

Photo-induced tungsten-catalyzed cascade synthesis of pyrrolo[2,1-a]isoquinoline-1,3-dicarboxylate and its reaction mechanism.

A pyrrolo[2,1-a]isoquinoline core structure is prevalent in marine and other natural products. This article describes a tungsten-catalyzed [3+2] cycloaddition aromatization of dihydroisoquinoline ester and maleic anhydride or an acrylate. The photochemical reaction tolerates a range of functional groups such as ester, cyano, ketone, bromide, and alkene. It is shown that the cycloaddition-aromatization of 2-substitued acrylate catalyzed by a tungsten photocatalyst can be used to evaluate the leaving ability of the leaving group. Experiments done to determine the reaction mechanism revealed that the formation of an ion-pair intermediate generated in situ from dihydroisoquinoline ester and (Z)-4-methoxy-4-oxobut-2-enoic acid via the solvolysis of maleic anhydride with methanol is crucial for the cascade process to occur. The key cycloadduct acid intermediate derived from [3+2] cycloaddition was isolated and determined by X-ray crystallography.

IRF4-BLOC1S5: the first rearrangement gene identified in TEMPI syndrome.

Not available.

Short-term forecasting approach of single well production based on multi-intelligent agent hybrid model.

The short-term prediction of single well production can provide direct data support for timely guiding the optimization and adjustment of oil well production parameters and studying and judging oil well production conditions. In view of the coupling effect of complex factors on the daily output of a single well, a short-term prediction method based on a multi-agent hybrid model is proposed, and a short-term prediction process of single well output is constructed. First, CEEMDAN method is used to decompose and reconstruct the original data set, and the sliding window method is used to compose the data set with the obtained components. Features of components by decomposition are described as feature vectors based on values of fuzzy entropy and autocorrelation coefficient, through which those components are divided into two groups using cluster algorithm for prediction with two sub models. Optimized online sequential extreme learning machine and the deep learning model based on encoder-decoder structure using self-attention are developed as sub models to predict the grouped data, and the final predicted production comes from the sum of prediction values by sub models. The validity of this method for short-term production prediction of single well daily oil production is verified. The statistical value of data deviation and statistical test methods are introduced as the basis for comparative evaluation, and comparative models are used as the reference model to evaluate the prediction effect of the above multi-agent hybrid model. Results indicated that the proposed hybrid model has performed better with MAE value of 0.0935, 0.0694 and 0.0593 in three cases, respectively. By comparison, the short-term prediction method of single well production based on multi-agent hybrid model has considerably improved the statistical value of prediction deviation of selected oil well data in different periods. Through statistical test, the multi-agent hybrid model is superior to the comparative models. Therefore, the short-term prediction method of single well production based on a multi-agent hybrid model can effectively optimize oilfield production parameters and study and judge oil well production conditions.

Neutrophil Extracellular Traps Regulate Surgical Brain Injury by Activating the cGAS-STING Pathway.

Surgical brain injury (SBI), induced by neurosurgical procedures or instruments, has not attracted adequate attention. The pathophysiological process of SBI remains sparse compared to that of other central nervous system diseases thus far. Therefore, novel and effective therapies for SBI are urgently needed. In this study, we found that neutrophil extracellular traps (NETs) were present in the circulation and brain tissues of rats after SBI, which promoted neuroinflammation, cerebral edema, neuronal cell death, and aggravated neurological dysfunction. Inhibition of NETs formation by peptidylarginine deiminase (PAD) inhibitor or disruption of NETs with deoxyribonuclease I (DNase I) attenuated SBI-induced damages and improved the recovery of neurological function. We show that SBI triggered the activation of cyclic guanosine monophosphate-adenosine monophosphate synthase stimulator of interferon genes (cGAS-STING), and that inhibition of the cGAS-STING pathway could be beneficial. It is worth noting that DNase I markedly suppressed the activation of cGAS-STING, which was reversed by the cGAS product cyclic guanosine monophosphate-adenosine monophosphate (cGMP-AMP, cGAMP). Furthermore, the neuroprotective effect of DNase I in SBI was also abolished by cGAMP. NETs may participate in the pathophysiological regulation of SBI by acting through the cGAS-STING pathway. We also found that high-dose vitamin C administration could effectively inhibit the formation of NETs post-SBI. Thus, targeting NETs may provide a novel therapeutic strategy for SBI treatment, and high-dose vitamin C intervention may be a promising translational therapy with an excellent safety profile and low cost.

Explainable machine learning in outcome prediction of high-grade aneurysmal subarachnoid hemorrhage.

OBJECTIVE: Accurate prognostic prediction in patients with high-grade aneruysmal subarachnoid hemorrhage (aSAH) is essential for personalized treatment. In this study, we developed an interpretable prognostic machine learning model for high-grade aSAH patients using SHapley Additive exPlanations (SHAP). METHODS: A prospective registry cohort of high-grade aSAH patients was collected in one single-center hospital. The endpoint in our study is a 12-month follow-up outcome. The dataset was divided into training and validation sets in a 7:3 ratio. Machine learning algorithms, including Logistic regression model (LR), support vector machine (SVM), random forest (RF), and extreme gradient boosting (XGBoost), were employed to develop a prognostic prediction model for high-grade aSAH. The optimal model was selected for SHAP analysis. RESULTS: Among the 421 patients, 204 (48.5%) exhibited poor prognosis. The RF model demonstrated superior performance compared to LR (AUC = 0.850, 95% CI: 0.783-0.918), SVM (AUC = 0.862, 95% CI: 0.799-0.926), and XGBoost (AUC = 0.850, 95% CI: 0.783-0.917) with an AUC of 0.867 (95% CI: 0.806-0 .929). Primary prognostic features identified through SHAP analysis included higher World Federation of Neurosurgical Societies (WFNS) grade, higher modified Fisher score (mFS) and advanced age, were found to be associated with 12-month unfavorable outcome, while the treatment of coiling embolization for aSAH drove the prediction towards favorable prognosis. Additionally, the SHAP force plot visualized individual prognosis predictions. CONCLUSIONS: This study demonstrated the potential of machine learning techniques in prognostic prediction for high-grade aSAH patients. The features identified through SHAP analysis enhance model interpretability and provide guidance for clinical decision-making.