Stigmasterol exerts antiglioma effects by regulating lipid metabolism.

Stigmasterol is a sterol compound found in various traditional Chinese medicines; however, its effects on glioma remain unclear. The present study aimed to investigate the effects of stigmasterol on the biological behaviors of glioblastoma (GBM) cells and to explore the underlying mechanisms. In vitro experiments assessed its effects on GBM cell proliferation, apoptosis, cell cycle progression, invasion, migration and vasculogenic mimicry (VM). The potential targets for stigmasterol in treating GBM were identified using databases and Venn diagram analysis, followed by enrichment analysis using R language. A prognostic model related to the target genes of stigmasterol was developed through univariate Cox regression and least absolute shrinkage and selection operator analyses. Stigmasterol was found to suppress the proliferation of GBM cells in a dose­ and time­dependent manner, to induce apoptosis, and to inhibit invasion, migration and VM formation. Additionally, 31 potential targets of stigmasterol were identified, linked to lipid metabolism and the G protein­coupled receptor signaling pathway. Lipid metabolism assays revealed that stigmasterol significantly reduced free fatty acids and total cholesterol levels. Furthermore, two prognosis­related target genes, fatty acid binding protein 5 and α­1B adrenergic receptor, were selected, and the prognostic model effectively predicted GBM outcomes. Moreover, molecular docking revealed strong binding affinities between stigmasterol and the target proteins. Overall, these findings suggested that stigmasterol may exert anti­glioma effects, which could be potentially mediated through the regulation of lipid metabolism.

Application of a single-cell-RNA-based biological-inspired graph neural network in diagnosis of primary liver tumors.

Single-cell technology depicts integrated tumor profiles including both tumor cells and tumor microenvironments, which theoretically enables more robust diagnosis than traditional diagnostic standards based on only pathology. However, the inherent challenges of single-cell RNA sequencing (scRNA-seq) data, such as high dimensionality, low signal-to-noise ratio (SNR), sparse and non-Euclidean nature, pose significant obstacles for traditional diagnostic approaches. The diagnostic value of single-cell technology has been largely unexplored despite the potential advantages. Here, we present a graph neural network-based framework tailored for molecular diagnosis of primary liver tumors using scRNA-seq data. Our approach capitalizes on the biological plausibility inherent in the intercellular communication networks within tumor samples. By integrating pathway activation features within cell clusters and modeling unidirectional inter-cellular communication, we achieve robust discrimination between malignant tumors (including hepatocellular carcinoma, HCC, and intrahepatic cholangiocarcinoma, iCCA) and benign tumors (focal nodular hyperplasia, FNH) by scRNA data of all tissue cells and immunocytes only. The efficacy to distinguish iCCA from HCC was further validated on public datasets. Through extending the application of high-throughput scRNA-seq data into diagnosis approaches focusing on integrated tumor microenvironment profiles rather than a few tumor markers, this framework also sheds light on minimal-invasive diagnostic methods based on migrating/circulating immunocytes.

Comparison of visual acuity outcome and choroidal thickness variation of intravitreal ranibizumab injection for myopic choroidal neovascularization with or without dome-shaped macula.

BACKGROUND: To investigate the visual acuity outcome and choroid thickness (CT) change after intravitreal ranibizumab in highly myopic eyes with or without dome-shaped macula (DSM) in Chinese patients. METHODS: This retrospective, observative study included 80 treatment-naive eyes (80 patients), which received ranibizumab according to the 1+PRN protocol. The best corrective visual acuity (BCVA) and CT change were compared between eyes with or without DSM. RESULTS: There was no significant difference between eyes with or without DSM in BCVA and central macular thickness (CMT). The recurrent rate was not different between the two groups during the first year of treatment. The CT was significantly thinner in eyes with DSM than in eyes without DSM before treatment (median 40.00um versus 71.00um), at 1 month after treatment (median 31.00um versus 65.50um), and in the last follow up (median, 32.00um versus 65.00um) (p=0.0101). Axial length (AL) was longer in eyes with DSM than those without DSM (median, 29.17mm versus 28.10mm) before treatment, and in the last follow up (median, 29.44mm versus 28.20mm) (p=0.0055). The CT was significantly correlated with AL (p<0.0001). CONCLUSIONS: No difference was found in visual outcome between eyes with or without DSM. The visual acuity significantly improved at 1 month after ranibizumab injection and it was recovery sooner in extrafoveal choroidal neovascularization (CNV) group than in subfoveal CNV group. The CT was thinner in eyes with DSM, which was significantly correlated with AL.

The impact of the COVID-19 pandemic on mental health care utilization among people living with HIV: A real-world data study.

Objective: The COVID-19 pandemic has profoundly impacted mental health worldwide, particularly among vulnerable populations such as people living with HIV (PLWH). However, large-scale, real-world data on mental health care utilization and associated factors among PLWH remain limited. This study leveraged electronic health records (EHR) and Basics survey data from the All of Us program to explore mental health care utilization and associated factors among PLWH during the COVID-19 pandemic. Methods: Using a retrospective cohort design, we identified and included 4,575 PLWH through computational phenotyping based on relevant Observational Medical Outcomes Partnership (OMOP) Common Data Model (CDM) concept sets from the All of Us program between March 2018 and March 2022. Mental health care utilization was measured using the yearly count of mental health care visits over this period. The pattern of mental health care utilization was compared between pre-pandemic (2018-2020) and during the pandemic (2020-2022). Incidence rate ratios (IRR) from the Poisson generalized linear mixed models (GLMM) were used to examine associations between mental health care utilization, history of COVID-19 infection, demographic factors, pre-existing chronic conditions (e.g., hypertension, diabetes), and socioeconomic status. Results: Among 4,575 PLWH, the annual number of mental health care visits decreased significantly during the pandemic period (March 2020 - March 2022) compared to the pre-pandemic period (March 2018 - February 2020) (IRR = 0.89, p < 0.001). The Poisson regression analysis found that a history of COVID-19 infection was associated with a higher number of mental health care visits (IRR = 1.35, p < 0.001). Middle-aged groups with participants aged 30-39 (IRR= 2.35, p = 0.002), 40-49 (IRR= 3.49, p < 0.001), and 50-64 (IRR= 2.07, p = 0.004) had significantly higher visit numbers compared to the youngest group (18-29 years). Black or African American participants were less likely to have visits compared to White participants (IRR = 0.71, p = 0.002). Medicaid health insurance was associated with an increase (IRR = 1.29, p = 0.007), while employer- or union-sponsored insurance was associated with a decrease in mental health care utilization (IRR = 0.54, p < 0.001, p < 0.001). Pre-existing comorbidities greatly increased the number of mental health care visits (one comorbidity: IRR = 5.49, two or more: IRR = 10.4, p < 0.001). Conclusion: Our study reveals a significant decrease in mental health care utilization and the diverse experiences of mental healthcare among PLWH during the COVID-19 pandemic. These findings underscore the importance of addressing disparities in mental health care access, particularly during public health emergencies, and suggest the need for tailored interventions to meet the mental health care needs of PLWH. Key Points: Question: How did the COVID-19 pandemic affect mental health care utilization among people living with HIV (PLWH)? What are the factors associated with mental care health utilization among PLWH across both the pre-pandemic and pandemic periods?Findings: Real-world data from a nationwide cohort of 4,575 PLWH identified from the All of Us program in the United States between March 2018 and March 2022 were used to investigate the effect of COVID-19 pandemic on mental health care utilization (i.e., the yearly count of mental healthcare visits). There was a considerable decrease in mental health care utilization during the pandemic (2020-2022) compared to the pre-pandemic period (2018-2020). Factors associated with higher mental health care utilization during the pandemic were the experience of COVID-19 infection, being middle-aged, Medicaid health coverage, and having comorbidities. Black African American participants, those with employer- or union health insurance, and high annual income (>$35,000), had lower mental health care utilization.Meaning: Our study highlights the diverse and unequal experiences of PLWH during the pandemic, with variations in mental health care utilization over time and across different disadvantaged subgroups. These findings underscore the need for timely and targeted mental health care services and delivery in future public health crises.

Autophagy Blockage Enhancing Photothermal and Chemodynamic Synergistic Therapy Based on HCQ/CuS Nanoplatform.

As an intracellular protective mechanism, autophagy has the potential to significantly impair the therapeutic effects of photothermal therapy (PTT) and chemodynamic therapy (CDT), which helps cancer cells survive under harsh conditions, such as high temperature and reactive oxygen species (ROS). In this study, an autophagy blockage enhanced PTT and CDT synergistic therapy nanoplatform is constructed by loading hydroxychloroquine (HCQ) with autophagy inhibitory effect into hollow copper sulfide (HCuS). Specifically, HCuS produces toxic ROS through Fenton-like reaction in the tumor microenvironment (TME). At the same time, PTT-mediated temperature elevation of the tumor region accelerates the Fenton-like reaction and ROS production, enhancing the therapeutic effect of CDT. Furthermore, the internal autophagy inhibitor HCQ significantly blocks the fusion of autophagosomes and lysosomes by deacidifying lysosomes, cutting off the self-protection mechanism of cancer cells, and amplifying the combined treatment of PTT and CDT. Both in vitro and in vivo results demonstrate that the combination of photothermal-enhanced chemodynamic therapy with inhibition of autophagy provides new insights into designing multifunctional therapeutic nanoagents.

Analysis of postoperative complications and long term survival following radical gastrectomy for patients with gastric cancer.

This study aimed to analyze the complications and long-term survival outcomes in patients who underwent radical gastrectomy for gastric cancer, as well as to identify the risk factors associated with postoperative complications. After conducting a comprehensive search within the medical records system, a total of 2508 patients who underwent radical gastrectomy and met the inclusion criteria were enrolled. Of the 2508 patients, 301 were diagnosed with postoperative complications. The pathological data, postoperative recovery, and survival outcome were compared between complication and control group. Subsequently, univariate and multivariate logistic regression analyses were conducted to identified the risk factors. According to the Clavien-Dindo grading criteria for postoperative complications, the proportions of grade I, II, III, IV, and V complications following radical gastrectomy were observed to be 28.2%, 42.9%, 19.6%, 8.0%, and 1.3%, respectively. The presence of postoperative complications significantly prolonged the duration of gastrointestinal decompression (P < 0.001), catheter retention (P < 0.001), fasting (P < 0.001), and hospitalization (P < 0.001). Additionally, it had a detrimental impact on survival outcomes. Age > 65years [odds ratio (OR) = 1.378, P = 0.020], presence of diabetes (OR = 2.042, P < 0.001), operative duration > 215 min (OR = 1.450, P = 0.006), intraoperative blood loss > 275 ml (OR = 1.474, P = 0.004), and Roux-en-Y anastomosis for both whole stomach (OR = 1.567, P = 0.021) and distal gastric cancer (OR = 2.083, P = 0.003) were identified as independent risk factors for postoperative complications. This study analyzed the complications and survival outcomes following radical gastrectomy, and investigated the predictors for postoperative complications, thereby providing valuable guidance on the prevention and management of surgical complications in gastric cancer.

Bone assessment of the sacroiliac joint in ankylosing spondylitis: Comparison between computed tomography and zero echo time MRI.

PURPOSE: To demonstrate the clinical applicability of zero echo time magnetic resonance imaging (ZTE MRI) in bone assessment of the sacroiliac joint in ankylosing spondylitis. METHOD: Between January 2021 and November 2021, twenty-one ankylosing spondylitis patients underwent clinically indicated MRI including ZTE sequence, in addition, all patients underwent a CT scan covering the sacroiliac joints within 6 months of the MRI examination. The sensitivity, specificity, and accuracy of ZTE MRI were calculated using CT as the reference standard. Cohen's κappa tests were applied to assess the agreement of positive imaging findings (including erosions, osteosclerosis, bony cystic changes, and joint space changes) between MRI and CT as well as the inter-reader agreement for the grading of sacroiliitis in AS patients. RESULTS: There was no statistical significance between ZTE MRI and CT in detecting of ankylosing spondylitis(p＞0.05). The consistency of the diagnosis of positive imaging findings between ZTE MRI and CT was moderate to excellent (ranging from 0.611 to 0.889), and the consistency of the scores of positive imaging was good to excellent (ranging from 0.857 to 0.979). CONCLUSIONS: ZTE MRI provides "CT-like" contrast for bony changes of the sacroiliac joint in ankylosing spondylitis and could simplify and reduce costs for some AS patients when both MRI and CT are typically required.

Standardized treatment of infection after anterior cruciate ligament reconstruction.

Infection after anterior cruciate ligament reconstruction (ACLR) is a rare and catastrophic postoperative complication. The aims of this study were to investigate the diagnostic, treatment and rehabilitation measures for postoperative infection following after ACLR. A retrospective study was conducted on 1500 patients who underwent ACLR between January 2011 and January 2022. Twenty patients who met the criteria for summarizing the incidence patterns and treatment experiences were selected for a complete investigation of their diagnostic, therapeutic, and rehabilitation processes, as well as outpatient follow-up results. Among the 20 patients who developed postoperative infections, Staphylococcus aureus was the main pathogen (80%). The clinical manifestations mainly included fever (80%) and knee joint pain (100%). Laboratory tests demonstrated that C-reactive protein (CRP) levels were greater than 50 mmol/L in fifteen patients (75%). All of the patients received intravenous antibiotic therapy. Five patients (25%) of tendon socket infection were treated with continuous negative pressure suction irrigation, whereas the other fifteen patients with intra-articular infection were treated with arthroscopic debridement and continuous flushing. The Lysholm score of the affected knee was compared before treatment and 6 months after treatment, and the difference was statistically significant (t = 20.78, P < 0.001). The success rate of treatment was 100%, and there were no significant differences between patients who received secondary treatment and functional exercise and those who underwent ACLR in terms of knee joint function or range of motion during the same time period. Infection was rare after ACLR, however it was fatal, and the main pathogen was Staphylococcus aureus. Early diagnosis and a comprehensive treatment approach are pivotal for the successful management of postoperative infections following ACLR. The results of this study contribute valuable clinical insights for further refining surgical procedures, enhancing infection prevention measures, and optimizing rehabilitation protocols.

Artificial Intelligence-Augmented Clinical Decision Support Systems for Pregnancy Care: Systematic Review.

BACKGROUND: Despite the emerging application of clinical decision support systems (CDSS) in pregnancy care and the proliferation of artificial intelligence (AI) over the last decade, it remains understudied regarding the role of AI in CDSS specialized for pregnancy care. OBJECTIVE: To identify and synthesize AI-augmented CDSS in pregnancy care, CDSS functionality, AI methodologies, and clinical implementation, we reported a systematic review based on empirical studies that examined AI-augmented CDSS in pregnancy care. METHODS: We retrieved studies that examined AI-augmented CDSS in pregnancy care using database queries involved with titles, abstracts, keywords, and MeSH (Medical Subject Headings) terms. Bibliographic records from their inception to 2022 were retrieved from PubMed/MEDLINE (n=206), Embase (n=101), and ACM Digital Library (n=377), followed by eligibility screening and literature review. The eligibility criteria include empirical studies that (1) developed or tested AI methods, (2) developed or tested CDSS or CDSS components, and (3) focused on pregnancy care. Data of studies used for review and appraisal include title, abstract, keywords, MeSH terms, full text, and supplements. Publications with ancillary information or overlapping outcomes were synthesized as one single study. Reviewers independently reviewed and assessed the quality of selected studies. RESULTS: We identified 30 distinct studies of 684 studies from their inception to 2022. Topics of clinical applications covered AI-augmented CDSS from prenatal, early pregnancy, obstetric care, and postpartum care. Topics of CDSS functions include diagnostic support, clinical prediction, therapeutics recommendation, and knowledge base. CONCLUSIONS: Our review acknowledged recent advances in CDSS studies including early diagnosis of prenatal abnormalities, cost-effective surveillance, prenatal ultrasound support, and ontology development. To recommend future directions, we also noted key gaps from existing studies, including (1) decision support in current childbirth deliveries without using observational data from consequential fetal or maternal outcomes in future pregnancies; (2) scarcity of studies in identifying several high-profile biases from CDSS, including social determinants of health highlighted by the American College of Obstetricians and Gynecologists; and (3) chasm between internally validated CDSS models, external validity, and clinical implementation.

Microtubular and high porosity design of electrospun PEGylated poly (lactic-co-glycolic acid) fibrous implant for ocular multi-route administration and medication.

Electrospun fibers have been gaining popularity in ocular drug delivery and cellular therapies. However, most of electrospun fibers are planar-shape membrane with large dimension relative to intraocular space, making difficult to use as therapeutic implants. Herein, fibrous microtubes with a hollow center were fabricated by electrospinning using linear diblock mPEG2000-PLGA. Uniform microfibers with 0.809 µm diameter was tailored using Box-Behnken Design model for electrospinning process optimization. The microtubes were 1 mm long with a 0.386 mm diameter. Their suitability for intraocular administration was demonstrated by both injection via a 22-gauge needle and implant via integration of intraocular lens into the vitreous or anterior chamber of eyes, respectively. Electrospun mPEG2000-PLGA had higher porosity, smaller specific surface area, and smaller water contact angle, than that of PLGA. Macroscopically, mPEG2000-PLGA microfibers can maintain overall geometry upon exposure to aqueous buffer for 12 h while having high water uptake and exhibited good elasticity. Hydrolysis with 90 % polymeric degradation in 10.5 weeks underlied sustained slow release of anti-inflammatory drug dexamethasone. PEGylation of PLGA imparted preferential cell adhesion with markedly higher growth of human retinal epithelial cells than lens epithelial ones. This study highlights the potential utility of implantable electrospun PLGA-based microtubes for multiple intraocular delivery routes.

Superficial vessel density and determinants of macular microvasculature in healthy Chinese subjects.

BACKGROUND: The purpose of this study was to investigate the vessel density (VD) of the macular superficial capillary plexus (SCP) and its associated factors in healthy subjects. METHODS: This prospective, cross-sectional study enrolled healthy Chinese volunteers. The optical coherence tomography angiography (OCTA) was used to measure the superficial VD in macula. A generalized estimation equation (GEE) model was used to analyze the ocular and systemic associated factors. RESULTS: A total of 516 eyes of 262 healthy subjects were included (mean age 38.59 ± 21.03 years). The total VD of macular SCP was 16.85 ± 2.28 mm-1. The VD in the inner ring and outer ring were significantly higher than that in the central ring, with the density being highest in nasal quadrant and lowest in the superior quadrant. After adjusting the ocular and systemic factors, age (ß=-0.0085, P = 0.0122) and SSI (ß=1.3261, P < 0.001) were significantly associated with total VD of the macular SCP. CONCLUSIONS: Among the healthy Chinese subjects included in the study, the mean total VD of macular SCP was 16.85 ± 2.28mm-1. The macular superficial capillary density was positively associated with age and SSI. Further studies are still required to better understand the change of macular VD in aging and other pathological conditions.

Deep learning-based image analysis predicts PD-L1 status from 18F-FDG PET/CT images in non-small-cell lung cancer.

Background: There is still a lack of clinically validated biomarkers to screen lung cancer patients suitable for programmed dead cell-1 (PD-1)/programmed dead cell receptor-1 (PD-L1) immunotherapy. Detection of PD-L1 expression is invasively operated, and some PD-L1-negative patients can also benefit from immunotherapy; thus, the joint modeling of both deep learning images and clinical features was used to improve the prediction performance of PD-L1 expression in non-small cell lung cancer (NSCLC). Methods: Retrospective collection of 101 patients diagnosed with pathology in our hospital who underwent 18F FDG PET/CT scans, with lung cancer tissue Tumor Propulsion Score (TPS) ≥1% as a positive expression. Lesions were extracted after preprocessing PET/CT images, and using deep learning 3D DenseNet121 to learn lesions in PET, CT, and PET/CT images, 1,024 fully connected features were extracted; clinical features (age, gender, smoking/no smoking history, lesion diameter, lesion volume, maximum standard uptake value of lesions [SUVmax], mean standard uptake value of lesions [SUVmean], total lesion glycolysis [TLG]) were combined for joint modeling based on the structured data Category Embedding Model. Results: Area under a receiver operating characteristic (ROC) curve (AUC) and accuracy of predicting PD-L1 positive for PET, CT, and PET/CT test groups were 0.814 ± 0.0152, 0.7212 ± 0.0861, and 0.90 ± 0.0605, 0.806 ± 0.023, 0.70 ± 0.074, and 0.950 ± 0.0250, respectively. After joint clinical feature modeling, the AUC and accuracy of predicting PD-L1 positive for PET/CT were 0.96 ± 0.00905 and 0.950 ± 0.0250, respectively. Conclusion: This study combines the features of 18F-FDG PET/CT images with clinical features using deep learning to predict the expression of PD-L1 in NSCLC, suggesting that 18F-FDG PET/CT images can be conducted as biomarkers for PD-L1 expression.

The Ciliate Euplotes balteatus Exhibits Removal Capacity upon the Dinoflagellates Karenia mikimotoi and Prorocentrum shikokuense.

The significant threat posed by the ichthyotoxic dinoflagellate Karenia mikimotoi to coastal aquaculture, resulting in substantial economic losses, underscores the need for control and mitigation strategies. Bio-mitigation of algal blooms through grazers presents advantages in sustainability compared to methods relying on chemical or physical procedures. This study explored the inhibitory effect of nine Euplotes spp. (Alveolata, Ciliophora) isolates on simulated blooms, with E. balteatus W413 displaying removal capacity for K. mikimotoi and robust growth in co-cultivation. The unique size plasticity in W413 revealed an efficient predation strategy, as an increase in cellular size enables it to shift prey from bacteria to algal cells. The enlarged cell volume facilitates W413 to accommodate more algal cells, bestowing it with a high ingestion rate and removal capacity upon K. mikimotoi. Furthermore, W413 exhibited considerable inhibition towards co-occurring bloom species, specifically Prorocentrum shikokuense and Karenia spp., implying its potential to mitigate mixed-species blooms. The study enhances our understanding of the prey selectivity of Euplotes species and proposes E. balteatus as a potential bio-mitigation candidate for K. mikimotoi blooms, emphasizing the significance of micro-grazers in marine ecosystems.

Colletotrichum species (Glomerellales, Glomerellaceae) causing walnut anthracnose in China.

Colletotrichum species can function as plant pathogens, saprobes or endophytes on a wide variety of plant hosts and are considered amongst the ten most significant genera of plant pathogens globally. China contributes almost half the walnut production in the world. However, Colletotrichum species occurring on walnut remain largely unresolved in China. To explore the Colletotrichum species found on walnut in China, 470 walnut fruit or leaf samples with anthracnose were collected from 14 main walnut-producing regions across seven provinces. A total of 165 Colletotrichum strains were isolated from these samples. The Colletotrichum isolates were identified, based on morphological characteristics and sequence analyses of ACT, CHS-1, GAPDH, ITS and TUB2. Twelve species, including 11 known Colletotrichum species (C.boninense, C.citrulli, C.fioriniae, C.fructicola, C.godetiae, C.juglandicola, C.karsti, C.mengyinense, C.pandanicola, C.peakense and C.siamense) and a novel species (C.chinensis sp. nov.) were identified. The species distribution revealed regional prevalence as follows: C.mengyinense was the most dominant species in Gansu, C.mengyinense and C.siamense in Shandong, C.chinensis in Beijing, C.pandanicola in Shaanxi and C.godetiae in Yunnan. Colletotrichumsiamense was the sole species isolated in Sichuan and Xinjiang Provinces. Koch's postulates were fulfilled, demonstrating that all 12 species cause anthracnose on walnut. This is the first report of C.boninense, C.citrulli and C.karsti as pathogens of walnut anthracnose worldwide.

Spatially explicit analysis of production and consumption responsibility for the PM2.5-related health burden towards beautiful China.

Promoting good health and ensuring responsible production and consumption are essential components of the Sustainable Development Goals (SDGs) established by of the United Nations, as well as the goals of beautiful China. While the health impacts of air pollution have garnered significant attention, there remains a paucity of studies comparing the disparities in responsibility arising from production versus consumption. This paper integrates the Weather Research and Forecasting - Comprehensive Air Quality Model with Extensions (WRF-CAMx) model, the multiregional input‒output (MRIO) model, and the global exposure mortality model (GEMM) to assess the extent of PM2.5-related premature deaths caused by production and consumption activities in 30 Chinese provinces. The findings reveal a spatial mismatch in health burdens between production and consumption. Considering pollutant emissions and their transfer only through the supply chain leads to the finding that the net outflow of emissions from producers is mainly located in most of the northern provinces of China. However, when atmospheric transport and health impacts are included, the producing provinces are mainly located in central China, while the consuming provinces are located in the southeastern coastal and remote western and northern regions. Additionally, the long-range impact of consumption provinces with respect to the health burden is more than twice as large as that of production provinces, and its potential impact on the health burden cannot be ignored. From a sectoral perspective, production emissions from the non-electricity industry and services sectors contribute to 60% of the health burden, while their consumption emissions contribute to over 80% of the health burden. Furthermore, consumption activities in the non-electricity industry and services sectors significantly influence production emissions in the transport, agriculture, and electricity sectors. The geographical separation of consumption and production regions facilitated by trade is a critical yet often overlooked aspect in current regional air quality planning in China. A more comprehensive analysis of life-cycle emissions driven by final consumption could yield greater reductions compared to direct production reductions.

VEGF165b mutant can be used as a protein carrier to form a chimeric tumor vaccine with Mucin1 peptide to elicit an anti-tumor response.

Peptide-based anticancer vaccines have shown some efficacy in generating cancer-specific immune responses in various cancer studies, but clinical success is limited, one of the reasons is due to its prone degradation and weak immunogenicity. So some tumor epitope peptide vaccines often require coupling or forming fusion proteins with corresponding protein carriers to enhance their stability and immunogenicity. Given the scarcity of validated carriers for clinical trials, there is an urgent requirement for the development of novel protein carrier. Our previous work has demonstrated that VEGF165b mutant could be used as an effective immunization adjunct to enhance anti-tumor immune response. By analyzing and evaluating the gene structure of VEGF, we speculated that mVEGF165b has the potential to be utilized as a tumor peptide vaccine carrier. An mVEGF165b-MUC1 chimeric tumor vaccine was produced by fusing the MUC1 peptide （(MUC1, a T-cell epitope dominant peptide from Mucin1） to the C-terminus of mVEGF165b, expressing the fusing protein in pichia yeast, followed by purification with a HiTrap heparin affinity chromatography column. We found that immunizing mice with mVEGF165b-MUC1 fusion protein induced high-titer antibodies against VEGF in a preventive context, which in turn reduced the proportion of Tregs and further stimulated mice to produce T-cell responses specific to mucin1. The high-titer VEGF antibody stimulated by mVEGF165b also promoted tumor blood vessel maturation and facilitated T-cell infiltration. In conclusion，immunized with mVEGF165b-MUC1 protein are beneficial for eliciting immune responses targeting Mucin1, mVEGF165b have the potential to be utilized as a peptide tumor vaccine carrier.

G3BP2 promotes tumor progression and gemcitabine resistance in PDAC via regulating PDIA3-DKC1-hENT in a stress granules-dependent manner.

Pancreatic ductal adenocarcinoma (PDAC) is distinguished by its aggressive malignancy, limited treatment avenues and a tendency towards chemotherapy resistance, underscoring the critical need for advanced research to uncover new therapeutic approaches. Stress granules (SGs) that is implicated in cellular self-protection mechanism, along with its associated family molecules have shown pro-cancer effects and are closely related to tumor chemotherapy resistance. In this study we investigated the relationship between Ras GTPase-activating protein-binding proteins 2 (G3BP2), a core component of SGs, and the malignancy of PDAC as well as its resistance to the chemotherapy drug gemcitabine. Analyzing TCGA dataset revealed that the expression of G3BP1 and G3BP2 was significantly upregulated in PDAC compared with adjacent normal pancreatic tissues, and the high expression of G3BP2 rather than G3BP1 was significantly associated with poorer overall survival (OS) in PDAC patients. We demonstrated that knockdown of G3BP2 inhibited the proliferation and invasion of PANC-1 and CFPAC-1 cells in vitro and in vivo. By analyzing the differentially expressed genes in G3BP2 knockdown and overexpressed PANC-1 cells, we identified DKC1 that was associated with RNA stability and regulation as the target of G3BP2. We demonstrated that G3BP2 bound to PDIA3 mRNA and recruited them into SGs, increasing the stability of PDIA3 mRNA and attenuating its translation efficiency, thereby promoting DKC1 expression. Furthermore, DKC1 could bind to hENT mRNA and inhibited its expression, which enhanced gemcitabine resistance of PDAC. Therefore, we propose a novel mechanism wherein G3BP2 facilitates PDAC's resistance to chemotherapy by modulating PDIA3-DKC1-hENT in a SGs-dependent way, suggesting G3BP2 SGs a protentional therapeutic target for the treatment in PDAC.

Inhibition of CTLA-4 accelerates atherosclerosis in hyperlipidemic mice by modulating the Th1/Th2 balance via the NF-κB signaling pathway.

Objective: Though an increased risk of atherosclerosis is associated with anti-CTLA-4 antibody therapy, the underlying mechanisms remain unclear. Methods: C57BL/6 mice were treated with anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) antibody twice a week for 4 weeks, after being injected with AAV8-PCSK9 and fed a Paigen diet (PD). The proportion of aortic plaque and lipid accumulation were assessed using Oil Red O staining, while the morphology of atherosclerotic lesions was analyzed with hematoxylin and eosin staining. Collagen content was evaluated through Picrosirius Red (PSR) staining, while inflammatory cell infiltration was examined with immunofluorescence staining. CD4+ T cells secreting IFN-γ and IL-4, which represent Th1 and Th2 cells respectively, were detected by flow cytometry and real-time PCR. Protein levels of p-IκBα, IκBα, p-p65, and p65 were determined by Western blot. Results: Inhibiting CTLA-4 exacerbated PD-induced plaque progression and promoted CD4+ T cell infiltration in the aortic root. The anti-CTLA-4 antibody promoted CD4+ T cell differentiation toward the Th1 type, as indicated by an increase in the Th1/Th2 ratio. Compared to the anti-IgG group, treatment with anti-CTLA-4 antibody significantly elevated the protein levels of p-IκBα and p-p65, as well as the mRNA levels of TNF-α, IL-6, ICAM-1, and VCAM-1. Inhibiting the NF-κB signaling pathway attenuated the overall pathological phenotype induced by the anti-CTLA-4 antibody treatment. Conclusion: Anti-CTLA-4 treatment promotes the progression of atherosclerosis by activating NF-κB signaling and modulating the Th1/Th2 balance. Our results provide a rationale for preventing and/or treating atherosclerosis accelerated by anti-CTLA-4 antibody therapy in cancer patients.

Paenibacillus polymyxa J2-4 induces cucumber to enrich rhizospheric Pseudomonas and contributes to Meloidogyne incognita management under field conditions.

BACKGROUND: Root knot nematodes (RKNs) pose a great threat to agricultural production worldwide. The bacterial nematocides have received increasing attention due to their safe and efficient control against RKNs. Here, we investigated the biocontrol efficacy of Paenibacillus polymyxa J2-4 against Meloidogyne incognita in the field and analyzed the rhizosphere microbiome of cucumber under nematode infection after application of the J2-4 strain. Furthermore, a biomarker strain of Pseudomonas spp. was isolated from the J2-4-inoculated rhizosphere soil, and its nematocidal activity and growth-promoting effect on host plants were determined. In addition, chemotaxis assay of P. fluroescens ZJ5 toward root exudates was carried out. RESULTS: The field experiment demonstrated that P. polymyxa J2-4 could effectively suppressed gall formation in cucumber plants, with the galling index reduced by 67.63% in 2022 and 65.50% in 2023, respectively, compared with controls. Meanwhile, plant height and yield were significantly increased in J2-4 treated plants compared with controls. Metagenomic analysis indicated that J2-4 altered the rhizosphere microbial communities. The relative abundance of Pseudomonas spp. was notably enhanced in the J2-4 group, which was consistent with Linear discriminant analysis Effect Size results that Pseudomonas was determined as one of the biomarkers in the J2-4 group. Furthermore, the ZJ5 strain, one of the biomarker Pseudomonas strains, was isolated from the J2-4-inoculated rhizosphere soil and was identified as Pseudomonas fluorescens. In addition, P. fluorescens ZJ5 exhibited high nematicidal activity in vitro and in vivo, with 99.20% of the mortality rate of M. incognita at 24 h and 69.75% of gall index reduction. The biocontrol efficiency of the synthetic community of ZJ5 plus J2-4 was superior to that of any other single bacteria against M. incognita. Additionally, ZJ5 exhibited great chemotaxis ability toward root exudates inoculated with J2-4. CONCLUSION: Paenibacillus polymyxa J2-4 has good potential in the biological control against M. incognita under field conditions. Enrichment of the beneficial bacteria Pseudomonas fluorescens ZJ5 in the J2-4-inoculated rhizosphere soil contributes to M. incognita management. © 2024 Society of Chemical Industry.

Evaluation of passive samplers as a cost-effective method to predict the impact of wildfire smoke in grapes and wines.

Wildfire smoke exposure alters grape composition, potentially resulting in "smoke tainted" wines. This has been correlated with elevated levels of smoke-derived volatile phenols (VPs) in grapes and wines. This work sought to create a predictive tool that could correlate levels of VPs in smoke with concentrations in grapes and wines. Therefore, passive samplers and Cabernet Sauvignon grapes were intentionally exposed to various smoke intensities, and wines were made thereafter. As expected, concentrations of VPs in grapes and wines were positively associated with the intensity of smoke exposure. Interestingly, levels of guaiacol in the passive samplers had a strong positive correlation with concentrations in grapes (R2 = 0.9999) and wines (R2 = 0.9998). The passive samplers were able to accurately predict guaiacol levels in smoke exposed grapes and wines with percent errors ranging from 0.08 to 11.3 %. These results suggest the capability of passive samplers to act as a monitoring system in vineyards during smoke events.