IbNF-YA1 is a key factor in the storage root development of sweet potato.

As a major worldwide root crop, the mechanism underlying storage root yield formation has always been a hot topic in sweet potato [Ipomoea batatas (L.) Lam.]. Previously, we conducted the transcriptome database of differentially expressed genes between the cultivated sweet potato cultivar "Xushu18," its diploid wild relative Ipomoea triloba without storage root, and their interspecific somatic hybrid XT1 with medium-sized storage root. We selected one of these candidate genes, IbNF-YA1, for subsequent analysis. IbNF-YA1 encodes a nuclear transcription factor Y subunit alpha (NF-YA) gene, which is significantly induced by the natural auxin indole-3-acetic acid (IAA). The storage root yield of the IbNF-YA1 overexpression (OE) plant decreased by 29.15-40.22% compared with the wild type, while that of the RNAi plant increased by 10.16-21.58%. Additionally, IAA content increased significantly in OE plants. Conversely, the content of IAA decreased significantly in RNAi plants. Furthermore, real-time quantitative reverse transcription-PCR (qRT-PCR) analysis demonstrated that the expressions of the key genes IbYUCCA2, IbYUCCA4, and IbYUCCA8 in the IAA biosynthetic pathway were significantly changed in transgenic plants. The results indicated that IbNF-YA1 could directly target IbYUCCA4 and activate IbYUCCA4 transcription. The IAA content of IbYUCCA4 OE plants increased by 71.77-98.31%. Correspondingly, the storage root yield of the IbYUCCA4 OE plant decreased by 77.91-80.52%. These findings indicate that downregulating the IbNF-YA1 gene could improve the storage root yield in sweet potato.

The landscape of programmed cell death-related lncRNAs in Alzheimer's disease and Parkinson's disease.

This study delivers a thorough analysis of long non-coding RNAs (lncRNAs) in regulating programmed cell death (PCD), vital for neurodegenerative diseases like Alzheimer's disease (AD) and Parkinson's disease (PD). We propose a new framework PCDLnc, and identified 20 significant lncRNAs, including HEIH, SNHG15, and SNHG5, associated with PCD gene sets, which were known for roles in proliferation and apoptosis in neurodegenerative diseases. By using GREAT software, we identified regulatory functions of top lncRNAs in different neurodegenerative diseases. Moreover, lncRNAs cis-regulated mRNAs linked to neurodegeneration, including JAK2, AKT1, EGFR, CDC42, SNCA, and ADIPOQ, highlighting their therapeutic potential in neurodegenerative diseases. A further exploration into the differential expression of mRNA identified by PCDLnc revealed a role in apoptosis, ferroptosis and autophagy. Additionally, protein-protein interaction (PPI) network analysis exposed abnormal interactions among key genes, despite their consistent expression levels between disease and normal samples. The randomforest model effectively distinguished between disease samples, indicating a high level of accuracy. Shared gene subsets in AD and PD might serve as potential biomarkers, along with disease-specific gene sets. Besides, we also found the strong relationship between AD and immune infiltration. This research highlights the role of lncRNAs and their associated genes in PCD in neurodegenerative diseases, offering potential therapeutic targets and diagnostic markers for future study and clinical application.

A novel safer CD19CAR with shRNA interference of IFN-γ can reduce multiple cytokine levels without significantly compromising its killing efficacy.

Cytokine release syndrome (CRS) is a great challenge for the application of anti-CD19 CAR-T cell therapy. The aim of this study was to investigate the effect of knocking down interferon gamma (IFN-γ) by shRNA as a potential strategy to reduce the cytokine storms. A newly designed short hairpin interference RNA of IFN-γ (shIFN-γ) in CD19CAR gene was constructed. Several cellular model systems of approach using Nalm-6 cell lines including Nalm-6CD19pos and Nalm-6CD19neg with or without monocytes and endothelial cells were used to analyze the different levels of cytokines after shIFN-γ-anti-CD19CAR-T cell targeted therapy. The activity of this novel CD19CAR-T was evaluated both in vitro and in NSG mouse model. The killing efficacy of shIFN-γ-anti-CD19CAR-T at the E:T ratio of 2:1 was similar to that of regular anti-CD19CAR-T at the E:T ratio of 1:1. The IFN-γ level in the shIFN-γ-anti-CD19CAR-T cell group was (2673.1 ± 307.4) pg/ml at the E:T ratio of 2:1 which was significantly lower than that ((8261.5 ± 345.5) pg/ml) in the regular anti-CD19CAR-T group at the E:T ratio of 1:1. Cytotoxicity experiments in vitro showed significantly reduced concentrations of IFN-γ, IL-6 and TNFα in the shIFN-γ-anti-CD19CAR-T cell group compared to regular anti-CD19CAR-T cell group. Both regular anti-CD19CAR and shIFN-γ-CD19CAR-T exerted bystander killing effect in vitro. We conclude that shIFN-γ-anti-CD19CAR-T cells can reduce the generation of cytokine storms without significantly compromising their therapeutic efficacy in the preclinical setting. In mouse model, 3 × 106 shIFN-γ-anti-CD19CAR-T cells/mouse generated the similar killing efficacy to that with 2 × 106 regular anti-CD19CAR-T cells/mouse.

Targeting nucleotide metabolic pathways in colorectal cancer by integrating scRNA-seq, spatial transcriptome, and bulk RNA-seq data.

BACKGROUND: Colorectal cancer is a malignant tumor of the digestive system originating from abnormal cell proliferation in the colon or rectum, often leading to gastrointestinal symptoms and severe health issues. Nucleotide metabolism, which encompasses the synthesis of DNA and RNA, is a pivotal cellular biochemical process that significantly impacts both the progression and therapeutic strategies of colorectal cancer METHODS: For single-cell RNA sequencing (scRNA-seq), five functions were employed to calculate scores related to nucleotide metabolism. Cell developmental trajectory analysis and intercellular interaction analysis were utilized to explore the metabolic characteristics and communication patterns of different epithelial cells. These findings were further validated using spatial transcriptome RNA sequencing (stRNA-seq). A risk model was constructed using expression profile data from TCGA and GEO cohorts to optimize clinical decision-making. Key nucleotide metabolism-related genes (NMRGs) were functionally validated by further in vitro experiments. RESULTS: In both scRNA-seq and stRNA-seq, colorectal cancer (CRC) exhibited unique cellular heterogeneity, with myeloid cells and epithelial cells in tumor samples displaying higher nucleotide metabolism scores. Analysis of intercellular communication revealed enhanced signaling pathways and ligand-receptor interactions between epithelial cells with high nucleotide metabolism and fibroblasts. Spatial transcriptome sequencing confirmed elevated nucleotide metabolism states in the core region of tumor tissue. After identifying differentially expressed NMRGs in epithelial cells, a risk prognostic model based on four genes effectively predicted overall survival and immunotherapy outcomes in patients. High-risk group patients exhibited an immunosuppressive microenvironment and relatively poorer prognosis and responses to chemotherapy and immunotherapy. Finally, based on data analysis and a series of cellular functional experiments, ACOX1 and CPT2 were identified as novel therapeutic targets for CRC. CONCLUSION: In this study, a comprehensive analysis of NMRGs in CRC was conducted using a combination of single-cell sequencing, spatial transcriptome sequencing, and high-throughput data. The prognostic model constructed with NMRGs shows potential as a standalone prognostic marker for colorectal cancer patients and may significantly influence the development of personalized treatment approaches for CRC.

Elongation and Ligation-Mediated Differential Coding for Label-Free and Locus-Specific Analysis of 8-Oxo-7,8-dihydroguanine in DNA.

Oxidative DNA damage is closely associated with the occurrence of numerous human diseases and cancers. 8-Oxo-7,8-dihydroguanine (8-oxoG) is the most prevalent form of DNA damage, and it has become not only an oxidative stress biomarker but also a new epigenetic-like biomarker. However, few approaches are available for the locus-specific detection of 8-oxoG because of the low abundance of 8-oxoG damage in DNA and the limited sensitivity of existing assays. Herein, we demonstrate the elongation and ligation-mediated differential coding for label-free and locus-specific analysis of 8-oxoG in DNA. This assay is very simple without the involvement of any specific labeled probes, complicated steps, and large sample consumption. The utilization of Bsu DNA polymerase can specifically initiate a single-base extension reaction to incorporate dATP into the opposite position of 8-oxoG, endowing this assay with excellent selectivity. The introduction of cascade amplification reaction significantly enhances the sensitivity. The proposed method can monitor 8-oxoG with a limit of detection of 8.21 × 10-19 M (0.82 aM), and it can identify as low as 0.001% 8-oxoG damage from a complex mixture with excessive undamaged DNAs. This method can be further applied to measure 8-oxoG levels in the genomic DNA of human cells under diverse oxidative stress, holding prospect potential in the dynamic monitoring of critical 8-oxoG sites, early clinical diagnosis, and gene damage-related biomedical research.

CAFs-derived exosomes promote the development of cervical cancer by regulating miR-18a-5p-TMEM170B signaling axis.

Mounting studies have showed that tumor microenvironment (TME) is crucial for cervical cancer (CC), and cancer-related fibroblasts (CAFs) play a major role in it. Recently, exosomal miRNAs secreted by CAFs have been found to be potential targets for cancer diagnosis and therapy. In this paper, we aimed to investigate the function of CAFs-mediated exosome miR-18a-5p (CAFs-exo-miR-18a-5p) in CC. First, in combination with bioinformatic data analysis of the GEO database (GSE86100) and RT-qPCR of CC clinical tissue samples and cell lines, miR-18a-5p was discovered to be markedly up-regulated in CC. Next, CAFs-secreted exosomes were isolated and it was found that miR-18a-5p expression was dramatically promoted in CC cell lines when treated with CAFs-exos. The CAFs-exo-miR-18a-5p was then elucidated to stimulate the proliferation and migration and inhibit the apoptosis of CC cells. In order to clarify the underlying mechanism, we further screened the target genes of miR-18a-5p. TMEM170B was selected by bioinformatic data analysis of online databases combined with RT-qPCR of CC clinical tissues and cells. Luciferase reporter gene analysis combined with molecular biology experiments further elucidated that miR-18a-5p suppressed TMEM170B expression in CC. Finally, both cell and animal experiments demonstrated that TMEM170B over-expression attenuated the oncogenic effect of CAFs-exo-miR-18a-5p. In conclusion, our study indicates that CAFs-mediated exosome miR-18a-5p promotes the initiation and development of CC by suppressing TMEM170B signaling axis, which provides a possible direction for the diagnosis and therapy of CC.

Integrated analysis of the transcriptome and metabolome reveals the molecular mechanism regulating cotton boll abscission under low light intensity.

BACKGROUND: Cotton boll shedding is one of the main factors adversely affecting the cotton yield. During the cotton plant growth period, low light conditions can cause cotton bolls to fall off prematurely. In this study, we clarified the regulatory effects of low light intensity on cotton boll abscission by comprehensively analyzing the transcriptome and metabolome. RESULTS: When the fruiting branch leaves were shaded after pollination, all of the cotton bolls fell off within 5 days. Additionally, H2O2 accumulated during the formation of the abscission zone. Moreover, 10,172 differentially expressed genes (DEGs) and 81 differentially accumulated metabolites (DAMs) were identified. A KEGG pathway enrichment analysis revealed that the identified DEGs and DAMs were associated with plant hormone signal transduction and flavonoid biosynthesis pathways. The results of the transcriptome analysis suggested that the expression of ethylene (ETH) and abscisic acid (ABA) signaling-related genes was induced, which was in contrast to the decrease in the expression of most of the IAA signaling-related genes. A combined transcriptomics and metabolomics analysis revealed that flavonoids may help regulate plant organ abscission. A weighted gene co-expression network analysis detected two gene modules significantly related to abscission. The genes in these modules were mainly related to exosome, flavonoid biosynthesis, ubiquitin-mediated proteolysis, plant hormone signal transduction, photosynthesis, and cytoskeleton proteins. Furthermore, TIP1;1, UGT71C4, KMD3, TRFL6, REV, and FRA1 were identified as the hub genes in these two modules. CONCLUSIONS: In this study, we elucidated the mechanisms underlying cotton boll abscission induced by shading on the basis of comprehensive transcriptomics and metabolomics analyses of the boll abscission process. The study findings have clarified the molecular basis of cotton boll abscission under low light intensity, and suggested that H2O2, phytohormone, and flavonoid have the potential to affect the shedding process of cotton bolls under low light stress.

Unraveling resistance mechanisms in anti-CD19 chimeric antigen receptor-T therapy for B-ALL: a novel in vitro model and insights into target antigen dynamics.

BACKGROUND: Cellular immunotherapy, represented by the chimeric antigen receptor T cell (CAR-T), has exhibited high response rates, durable remission, and safety in vitro and in clinical trials. Unfortunately, anti-CD19 CAR-T (CART-19) treatment alone is prone to relapse and has a particularly poor prognosis in relapsed/refractory (r/r) B-ALL patients. To date, addressing or reducing relapse remains one of the research priorities to achieve broad clinical application. METHODS: We manufactured second generation CART-19 cells and validated their efficacy and safety in vitro and in vivo. Through co-culture of Nalm-6 cells with short-term cultured CART-19 cells, CD19-negative Nalm-6 cells were detected by flow cytometry, and further investigation of the relapsed cells and their resistance mechanisms was evaluated in vitro. RESULTS: In this study, we demonstrated that CART-19 cells had enhanced and specific antileukemic activities, and the survival of B-ALL mouse models after CART-19 treatment was significantly prolonged. We then shortened the culture time and applied the serum-free culture to expand CAR-T cells, followed by co-culturing CART-19 cells with Nalm-6 cells. Surprisingly, we observed the proliferation of CD19-negative Nalm-6 cells around 28 days. Identification of potential resistance mechanisms showed that the relapsed cells express truncated CD19 proteins with decreased levels and, more importantly, CAR expression was detected on the relapsed cell surface, which may ultimately keep them antigen-negative. Furthermore, it was validated that CART-22 and tandem CART-22/19 cells could effectively kill the relapsed cells, but neither could completely eradicate them. CONCLUSIONS: We successfully generated CART-19 cells and obtained a CD19-negative refractory relapsed B-ALL cell line, providing new insights into the underlying mechanisms of resistance and a new in vitro model for the treatment of r/r B-ALL patients with low antigen density.

Fecal microbiota transplantation alleviates mild-moderate COVID-19 associated diarrhoea and depression symptoms: A prospective study of a randomized, double-blind clinical trial.

Currently, the emergence of the endemic Coronavirus disease (COVID-19) situation still poses a serious threat to public health. However, it remains elusive about the role of fecal microbiota transplantation in treating COVID-19. We performed a randomized, double-blind, placebo-controlled clinical trial enrolling a cohort of 40 COVID-19 patients with mild-moderate symptoms. Our results showed that fecal microbiota transplantation provided an amelioration in diarrhoea (p = 0.026) of digestive system and depression (p = 0.006) of neuropsychiatric-related symptom in COVID-19 patients, respectively. Meanwhile, we found that the number of patients with diarrhoea decreased from 19 to 0 on day 7 after fecal microbiota transplantation treatment, and it was statistically changed compared to the placebo group (p = 0.047). Of note, the serum concentration of aspartate aminotransferase-to-alanine aminotransferase ratio (AST/ALT, fecal microbiota transplantation, pre vs. post: 0.966 vs. 0.817), a biomarker for predicting long COVID-19, was significantly reduced by fecal microbiota transplantation. In all, our study supports that fecal microbiota transplantation could be a novel therapeutic strategy for COVID-19 patients with diarrhoea and depressive symptoms, which is potentially valuable in ameliorating long COVID-19 symptoms.

Novel Systemic Inflammatory Markers Predict All-Cause Mortality in Patients Undergoing Endovascular Abdominal Aortic Aneurysm Repair.

Background: Clinically useful predictors for risk stratification of long-term survival may assist in selecting patients for endovascular abdominal aortic aneurysm (EVAR) procedures. This study aimed to analyze the prognostic significance of peroperative novel systemic inflammatory markers (SIMs), including the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), hemoglobin-to-red cell distribution width ratio (HRR), systemic immune-inflammatory index (SIII), and systemic inflammatory response index (SIRI), for long-term mortality in EVAR. Methods: A retrospective analysis was performed on 147 consecutive patients who underwent their first EVAR procedure at the Department of Vascular Surgery, Beijing Hospital. The patients were divided into the mortality group (n = 37) and the survival group (n = 110). The receiver operating characteristic curves were used to ascertain the threshold value demonstrating the most robust connection with mortality. The Kaplan-Meier survival analysis was performed between each SIM and mortality. The relationship between SIMs and survival was investigated using restricted cubic splines and multivariate Cox regression analysis. Results: The study included 147 patients, with an average follow-up duration of 34.28 ± 22.95 months. Deceased patients showed significantly higher NLR (p < 0.001) and reduced HRR (p < 0.001). The Kaplan-Meier estimates of mortality were considerably greater in the higher-NLR group (NLR > 2.77) and lower-HRR group (HRR < 10.64). The hazard ratio (HR) of 0.833 (95% confidence interval (95% CI): 0.71-0.97, p < 0.021) was determined to be statistically significant in predicting death in the multivariable analysis. Conclusions: Preoperative higher-NLR and lower-HRR have been associated with a lower long-term survival rate in abdominal aortic aneurysm (AAA) patients undergoing elective EVAR. Multivariate Cox regression showed that decreased preoperative HRR is an independent risk factor that increases mortality risk following EVAR. SIMs, such as the NLR and HRR, could be used in future clinical risk prediction methodologies for AAA patients undergoing EVAR. However, additional prospective cohort studies are needed to identify these findings.

Rates and Impact of Serious Adverse Events after Endovascular Thrombectomy among Large Vessel Occlusion Stroke Patients.

Objective Complications or serious adverse events (SAEs) are common in the treatment of patients with large vessel occlusion stroke. There has been limited study of the impact of SAEs for patients after endovascular thrombectomy (EVT). The goal of this study was to characterize the rates and clinical impact of SAEs following EVT. Methods A post-hoc analysis was performed using pooled databases of the 'DEVT' and 'RESCUE BT' trials. SAEs were designated as symptomatic intracranial hemorrhage, brain herniation or craniectomy, respiratory failure, circulatory failure, pneumonia, deep venous thrombosis, and systemic bleeding. The primary endpoint was functional independence (modified Rankin Scale score 0-2 within 90 days). Logistic regression analysis was used to determine the predictors and associations between SAEs and outcomes. Results Of 1182 enrolled patients, 402 (34%) had a procedural complication, 745 (63%) had 1404 SAEs occurrences with 4.65% in-hospital mortality. The three most frequent SAEs were pneumonia (620, 52.5%), systemic bleeding (174, 14.7%) and respiratory failure (173, 14.6%). Pneumonia, systemic bleeding or deep venous thrombosis were less life-threatening. Patients with advanced age (adjusted odds ratio, 1.28 [95% confidence interval, 1.14-1.43]), higher NIHSS (1.09 [1.06-1.11]), occlusion site (middle cerebral artery-M1 vs. intracranial cerebral artery [ICA]: 0.75 [0.53-1.04]; M2 vs. ICA: 1.30 [0.80-2.12]), longer procedure time (1.01 [1.00-1.01]) and unsuccessful vessel recanalization (1.79 [1.06-2.94]) were more likely to experience SAEs. Compared with no SAE, patients with SAEs had lower odds of functional independence (0.46 [0.40-0.54]). Conclusions Overall, SAEs diagnosed following thrombectomy in patients with stroke were common (more than 60%) and associated with functional dependence. Patients with advanced age, higher NIHSS, longer procedure time and failed recanalization were more likely to experience SAEs. There was no statistical difference in the risk of SAEs among patient with M1 and M2 occluded compared with those ICA occluded. An understanding of the prevalence and predictors of SAEs could alert clinicians to the estimated risk of an SAE for a patient after EVT.

Exploring the prognostic value of BRMS1 + microglia based on single-cell anoikis regulator patterns in the immunologic microenvironment of GBM.

BACKGROUND: Anoikis is a specialized form of programmed cell death induced by the loss of cell adhesion to the extracellular matrix (ECM). Acquisition of anoikis resistance is a significant marker for cancer cell invasion, metastasis, therapy resistance, and recurrence. Although current research has identified multiple factors that regulate anoikis resistance, the pathological mechanisms of anoikis-mediated tumor microenvironment (TME) in glioblastoma (GBM) remain largely unexplored. METHODS: Utilizing single-cell RNA sequencing (scRNA-seq) data and employing non-negative matrix factorization (NMF), we identified and characterized TME cell clusters with distinct anoikis-associated gene signatures. Prognostic and therapeutic response analyses were conducted using TCGA and CGGA datasets to assess the clinical significance of different TME cell clusters. The spatial relationship between BRMS1 + microglia and tumor cells was inferred from spatial transcriptome RNA sequencing (stRNA-seq) data. To simulate the tumor immune microenvironment, co-culture experiments were performed with microglia (HMC3) and GBM cells (U118/U251), and microglia were transfected with a BRMS1 overexpression lentivirus. Western blot or ELISA were used to detect BRMS1, M2 macrophage-specific markers, PI3K/AKT signaling proteins, and apoptosis-related proteins. The proliferation and apoptosis capabilities of tumor cells were evaluated using CCK-8, colony formation, and apoptosis assays, while the invasive and migratory abilities of tumor cells were assessed using Transwell assays. RESULTS: NMF-based analysis successfully identified CD8 + T cell and microglia cell clusters with distinct gene signature characteristics. Trajectory analysis, cell communication, and gene regulatory network analyses collectively indicated that anoikis-mediated TME cell clusters can influence tumor cell development through various mechanisms. Notably, BRMS1 + AP-Mic exhibited an M2 macrophage phenotype and had significant cell communication with malignant cells. Moreover, high expression of BRMS1 + AP-Mic in TCGA and CGGA datasets was associated with poorer survival outcomes, indicating its detrimental impact on immunotherapy. Upregulation of BRMS1 in microglia may lead to M2 macrophage polarization, activate the PI3K/AKT signaling pathway through SPP1/CD44-mediated cell interactions, inhibit tumor cell apoptosis, and promote tumor proliferation and invasion. CONCLUSION: This pioneering study used NMF-based analysis to reveal the important predictive value of anoikis-regulated TME in GBM for prognosis and immunotherapeutic response. BRMS1 + microglial cells provide a new perspective for a deeper understanding of the immunosuppressive microenvironment of GBM and could serve as a potential therapeutic target in the future.

Influence of Cation-Size Effects of Alkaline Earth (Ae) Metals on Dimensionality and Optical Anisotropy Regulation in K4AeP2S8 Thiophosphates.

Cationic substitution demonstrates significant potential for regulating structural dimensionality and physicochemical performance owing to the cation-size effect. Leveraging this characteristic, this study synthesized a new family of K4AeP2S8 (Ae = alkaline earth elements: Mg, Ca, Sr, and Ba) thiophosphates, involving the substitution of Ae2+ cations. The synthesized compounds crystallized in distinct space groups, monoclinic P2/c (Ae = Mg) versus orthorhombic Ibam (Ae = Ca, Sr, and Ba), exhibiting intriguing dimensionality transformations from zero-dimensional (0D) [Mg2P4S16]8- clusters in K4MgP2S8 to 1D ∞[AeP2S8]4- chains in other K4AeP2S8 thiophosphates owing to the varying ionic radii of Ae2+ cations, Ae-S bond lengths, and coordination numbers of AeSn (Mg: n = 6 versus other: n = 8). Experimental investigations revealed that K4AeP2S8 thiophosphates featured wide optical bandgaps (3.37-3.64 eV), and their optical absorptions were predominantly influenced by the S 3p and P 3s orbitals, with negligible contributions from the K and Ae cations. Notably, within the K4AeP2S8 series, birefringence (Δn) increased from K4MgP2S8 (Δn = 0.034) to other K4AeP2S8 (Δn = 0.050-0.079) compounds, suggesting that infinite 1D chains more significantly influence Δn origins than 0D clusters, thus offering a feasible approach for enhancing optical anisotropy and exploring potential new birefringent materials.

Ocean carbon emission prediction and management measures based on artificial intelligence remote sensing estimation in the context of carbon neutrality.

With rapid economic development, the gradual deterioration of the natural environment has posed unprecedented challenges to human social civilization. The marine economy, as an important part of economic development, is the breakthrough of economic transformation for many coastal countries. Additionally, green development and environmental impact assessment have become the focus of research in these countries. This study employs remote sensing technology, an efficient observational method, to significantly enhance the efficiency of ocean information observation. It investigates ocean carbon emissions within the framework of carbon neutrality. First, we identified the ships along the coastline based on marine remote sensing information through the YOLO (you only look once) framework. Second, we applied the LSTM (long short-term memory) method to combine the target identification results and the historical data of carbon emissions to complete the corresponding carbon emission data fitting. Finally, carbon emission data from the past three years in the offshore area of Dalian were used to make accurate predictions. The results suggested that the recognition rate of the proposed target detection method could reach 88%, and the LSTM method has shown the best performance in terms of absolute error for the subsequent short-term carbon emission prediction. This framework not only provides essential technical support for analyzing remote sensing information within the context of carbon neutrality but also introduces innovative insights for carbon emission prediction.

How public environmental appeals affect the collaborative governance in pollution and carbon reduction: Evidence from spatial effects across Chinese cities.

China has always adhered to the strategy of sustainable development. It is prevalent the public want a good living environment, which requires local governments and businesses to enhance their environmental governance capabilities. Using the panel data from Chinese cities from 2012 to 2019 and econometrics models, we examine the impact mechanisms of public environmental appeals (PEA) on efficiency of collaborative governance in pollution reduction and carbon mitigation (GPC). Results indicate that there is a positive spatial clustering of GPC across cities, with high-high clustering is notably concentrated in the southern regions of China and low-low clustering is prevalent in the northern regions. Spatial econometrics model results reveal that the stronger PEA, the higher GPC. The result of mechanism analysis shows the mediation of environmentally friendly technological innovation is crucial. Subsequent inquiry uncovers that the digital economy positively moderates the impact of PEA on GPC. The Belt and Road policy region exhibits heightened sensitivity to PEA, thereby enhancing the positive impact of PEA on GPC.

HPV18 E6/E7 activates Ca2+ influx to promote the malignant progression of cervical cancer by inhibiting Ca2+ binding protein 1 expression.

Mounting studies have shown that the oncoproteins E6 and E7 encoded by the human papillomavirus (HPV) genome are essential in HPV-induced cervical cancer (CC). Ca2+ binding protein 1 (CABP1), a downstream target of HPV18-positive HeLa cells that interferes with E6/E7 expression, was identified through screening the GEO Database (GSE6926). It was confirmed to be down-regulated in CC through TCGA prediction and in vitro detection. Subsequent in vitro experiments revealed that knocking down E6/E7 inhibited cell proliferation, migration, and invasion, whereas knocking down CABP1 promoted these processes. Simultaneously knocking down CABP1 reversed these effects. Additionally, the results were validated in vivo. Previous studies have indicated that CABP1 can regulate Ca2+ channels, influencing Ca2+ influx and tumor progression. In this study, it was observed that knocking down CABP1 enhanced Ca2+ inflow, as demonstrated by flow cytometry and confocal microscopy. Knocking down E6/E7 inhibited these processes, whereas simultaneously knocking down E6/E7 and CABP1 restored the inhibitory effect of knocking down E6/E7 on Ca2+ inflow. To further elucidate that E6/E7 promotes CC progression by inhibiting CABP1 expression and activating Ca2+ influx, BAPTA/AM treatment was administered during CABP1 knockdown. It was discovered that Ca2+ chelation could reverse the effect of CABP1 knockdown on CC cells. In conclusion, our results offer a novel target for the diagnosis and treatment of HPV-induced CC.

FNDC5/Irisin protects neurons through Caspase3 and Bax pathways.

Irisin is a glycosylated protein formed from the hydrolysis of fibronectin type III domain-containing protein 5 (FNDC5). Recent studies have demonstrated that FNDC5/Irisin is involved in the regulation of glucose and lipid metabolism, it can inhibit inflammation and have neuroprotective effects. However, the effect and mechanism of FNDC5/Irisin on motor neuron-like cell lines (NSC-34) have not been reported. In this study, we used lipopolysaccharide to construct cellular oxidative stress injury models and investigated the potential roles of FNDC5/Irisin on neurons by different cellular and molecular pathways. Taken together, our findings showed that FNDC5/Irisin can protect neurons, and this effect might be associated with Caspase3 and Bax pathways. These results laid the foundation for neuronal protection and clinical translation of FNDC5/Irisin therapy.

A "twelve-section ultrasonic screening and diagnosis method" and management system for screening and treating neonatal congenital heart disease at the grassroots level in Tang County, Hebei Province, China.

BACKGROUND: To explore a method for screening and diagnosing neonatal congenital heart disease (CHD) applicable to grassroots level, evaluate the prevalence of CHD, and establish a hierarchical management system for CHD screening and treatment at the grassroots level. METHODS: A total of 24,253 newborns born in Tang County between January 2016 and December 2020 were consecutively enrolled and screened by trained primary physicians via the "twelve-section ultrasonic screening and diagnosis method" (referred to as the "twelve-section method"). Specialized staff from the CHD Screening and Diagnosis Center of Hebei Children's Hospital regularly visited the local area for definite diagnosis of CHD in newborns who screened positive. Newborns with CHD were managed according to the hierarchical management system. RESULTS: The centre confirmed that, except for 2 newborns with patent ductus arteriosus missed in the diagnosis of ventricular septal defect combined with severe pulmonary hypertension, newborns with other isolated or concomitant simple CHDs were identified at the grassroots level. The sensitivity, specificity and diagnostic coincidence rate of the twelve-section method for screening complex CHD were 92%, 99.6% and 84%, respectively. A total of 301 children with CHD were identified. The overall CHD prevalence was 12.4‰. According to the hierarchical management system, 113 patients with simple CHD recovered spontaneously during local follow-up, 48 patients continued local follow-up, 106 patients were referred to the centre for surgery (including 17 patients with severe CHD and 89 patients with progressive CHD), 1 patient died without surgery, and 8 patients were lost to follow-up. Eighteen patients with complex CHD were directly referred to the centre for surgery, 3 patients died without surgery, and 4 patients were lost to follow-up. Most patients who received early intervention achieved satisfactory results. The mortality rate of CHD was approximately 28.86 per 100,000 children. CONCLUSIONS: The "twelve-section method" is suitable for screening neonatal CHD at the grassroots level. The establishment of a hierarchical management system for CHD screening and treatment is conducive to the scientific management of CHD, which has important clinical and social significance for early detection, early intervention, reduction in mortality and improvement of the prognosis of complex and severe CHDs.

A study of patients' choice of medical treatment based on rational choice theory: a cross-sectional survey from China.

OBJECTIVE: To describe how patients choose between primary care institutions (PCIs) and non-PCIs using rational choice theory from the perspective of survival rationality, economic rationality, and social rationality. METHODS: Multi-stage stratified sampling and convenience sampling were applied to select 1723 patients to conduct the questionnaire survey. Chi-square test and binary logistic regression were performed to analyze the factors associated with patients' choice of PCIs. RESULTS: In total 55.83% of 1723 patients would attend a PCIs for healthcare. The results of the univariate analysis revealed that patients who are female (58.46%, P = .015), suffering from chronic diseases (56.26%, P = .047), inpatients (67.58%, P < .001), Beijing (59.62%, P = .002), partial understanding of the family doctor contracting system (62.30%, P < .001), and not understanding of the medical alliance policy (58.04%, P = .031) had significantly higher probability of choosing PCIs. Logistic regression analysis showed that females were more unwilling to attend PCIs (odds ratio (OR) = 0.822, 95%CI: 0.676-0.999). Following survival rationality, patients without chronic diseases were more likely to attend PCIs (OR = 1.834, 95%CI: 1.029-3.268), and inpatients were more unlikely to attend PCIs (OR = 0.581, 95%CI: 0.437-0.774). From an economic rationality perspective, patients from the Fujian province were more likely to attend PCIs (OR = 1.424, 95%CI: 1.081-1.876). From a social rationality perspective, patients who partial understanding of the family doctor contracting system were more unlikely to attend PCIs (OR = 0.701, 95%CI: 0.551-0.892), and patients who partial and complete understanding of the medical alliance policy were more likely to attend PCIs (OR = 1.340, 95%CI: 1.064-1.687; OR = 1.485, 95%CI: 1.086-2.030). CONCLUSIONS: Survival, economic, and social rationality are involved in patients' choice to attend PCIs. Compared to survival rationality and social rationality, economic rationality showed a lower association with patients' choice to attend PCIs. Medical institutions are recommended to adopt a "patient health-centered" approach when providing medical services and further optimize the family doctor contracting system and construction of medical alliances.

Factors influencing contracting of residents with family doctors in China: a national cross-sectional survey.

BACKGROUND: Family doctor contract services (FDCS) have been introduced in China in 2009 [1] and rapidly expanded recently. This study sought to investigate factors that influenced the willingness of Chinese residents to use FDCS. METHODS: We employed multistage stratified and convenience sampling to administer questionnaires to 1455 Beijing, Qinghai, and Fujian residents. The willingness of residents in each province to contract family doctors was analyzed using the chi-square test and binary logistic regression. RESULTS: The analysis in this study found that the signing rate of family doctors in China was about 27.77%, with differences in the signing up levels in Beijing (13.68%), Fujian (64.49%) and Qinghai (11.22%). In addition, the binary logistic regression results emphasized the relative importance of age, education, medical preference and policy knowledge on the willingness to sign up. Distrust of family doctors' medical skills (65.7%), not knowing how to contract (47.8%), and not knowing what medical problems can be solved (41.1%) were the top three reasons accounting for the reluctance of residents to contract with family doctors. CONCLUSION: Residents from different backgrounds have different willingness to sign up, so the specific circumstances and needs of different groups should be taken into account. In order to increase the signing-up rate, consideration can be given to promoting the family doctor model in Fujian throughout the country. Individual hesitation can be eliminated by increasing the reimbursement rate of health insurance, reducing the out-of-pocket expenses of contracted patients, and providing incentives of certain discounts for consecutive contracted patients.