A capillary electrophoresis-based assay for carrier screening of the hotspot mutations in the CYP21A2 gene.

Molecular genetic analysis of the cytochrome P450 family 21 subfamily A member 2 (CYP21A2) gene is challenging owing to the highly homologous with its pseudogene. A reliable approach for the large-scale population screening of CYP21A2 is required. This study aimed to establish and evaluate a capillary electrophoresis-based assay for hotspot mutation carrier screening of the CYP21A2 gene. A total of 22 different variants in the CYP21A2 gene were detected by a capillary electrophoresis-based assay consisting of single nucleotide primer extension (SNaPshot) and high-throughput ligation-dependent probe amplification (HLPA) in the Chinese population, and the results were validated by alternative methods. Among the 5376 subjects, 1.51 % (81/5376) individuals were identified as CYP21A2 pathogenic variant carriers, with a carrier rate of 1/66. A total of 11 different variants were identified, of which c.293-13A/C > G (33.33 %) was the most common variant, followed by c.844C > T (19.75 %), c.518T > A (19.75 %), and Del/Con (16.05 %). There was a 100 % concordance between capillary electrophoresis and alternative method results. Furthermore, a total of 63 individuals (1.17 %, 63/5376) carried the c.955C > T (p. Q319∗) variant, among which 61 (61/63, 96.83 %) had a duplicated CYP21A2 gene and are therefore not carriers of a CYP21A2 allele. In conclusion, the capillary electrophoresis-based assay is an accurate and effective approach for genotyping the CYP21A2 gene and has the potential for the large-scale population screening of CYP21A2.

Partitioned granular sludge coupling with membrane-aerated biofilm reactor for efficient autotrophic nitrogen removal.

The partial nitritation-anammox process based on a membrane-aerated biofilm reactor (MABR) faces several challenges, such as difficulty in suppressing nitrite-oxidizing bacteria (NOB), excessive effluent nitrate, and ineffective synergy between denitrification and anammox bacteria. Therefore, a novel partitioned granular sludge coupling with MABR (G-MABR) was constructed. The chemical oxygen demand (COD) and nitrogen removal efficiency were 88.8 ±â€¯1.8 %-92.6 ±â€¯1.2 % and 88.8 ±â€¯1.5 %-93.6 ±â€¯0.7 %, respectively. The COD was mainly lowered in the lower granular sludge-zone, while nitrogen was removed in the upper MABR-zone. NOB was significantly suppressed in the MABR-zone due to competition for substrate with denitrifying bacteria and anammox bacteria. This partitioned configuration reduced the C/N ratio in the MABR-zone, thus facilitating autotrophic nitrogen removal. Both partial nitrification and denitrification provided nitrite for anammox bacteria in granular sludge, whereas partial nitrification mainly supplied nitrite to the anammox bacteria in membrane biofilms.

Unveiling the Network regulatory mechanism of ncRNAs on the Ferroptosis Pathway: Implications for Preeclampsia.

Non-coding RNAs (ncRNAs) are transcripts originating from the genome that do not serve as templates for protein synthesis. They function as epigenetic and translational regulators in various pathophysiological mechanisms, including cell proliferation and apoptosis. The ferroptosis signaling pathway, a novel mode of cell death, participates in numerous pathophysiological processes. Its signaling transmission is both complex and precise, featuring interconnected and interdependent pathways. Recent studies suggest that ncRNAs can finely regulate key genes in the ferroptosis pathway, thus modulating cellular functions, reducing oxidative stress, and maintaining maternal-fetal interface homeostasis. Future strategies targeting the ncRNA/ferroptosis axis may provide new perspectives and potential intervention points for treating preeclampsia. This article clarifies how the ncRNA/ferroptosis axis impacts preeclampsia, revealing how ncRNAs interact with ferroptosis, and pinpointing new molecular targets for the treatment of preeclampsia, thereby providing theoretical support for clinical strategies.

MicroRNA-Triggered Programmable DNA-Encoded Pre-PROTACs for Cell-Selective and Controlled Protein Degradation.

Proteolysis-targeting chimeras (PROTACs) have accelerated drug development; however, some challenges still exist owing to their lack of tumor selectivity and on-demand protein degradation. Here, we developed a miRNA-initiated assembled pre-PROTAC (miRiaTAC) platform that enables the on-demand activation and termination of target degradation in a cell type-specific manner. Using miRNA-21 as a model, we engineered DNA hairpins labeled with JQ-1 and pomalidomide and facilitated the modular assembly of DNA-encoded pre-PROTACs through a hybridization chain reaction. This configuration promoted the selective polyubiquitination and degradation of BRD4 upon miR-21 initiation, highlighting significant tumor selectivity and minimal systemic toxicity. Furthermore, the platform incorporates photolabile groups, enabling the precise optical control of pre-PROTACs during DNA assembly/disassembly, mitigating the risk of excessive protein degradation. Additionally, by introducing a secondary ligand targeting CDK6, these pre-PROTACs were used as a modular scaffold for the programmable assembly of active miRiaTACs containing two different warheads in exact stoichiometry, enabling orthogonal multitarget degradation. The integration of near-infrared light-mediated photodynamic therapy through an upconversion nanosystem further enhanced the efficacy of the platform with potent in vivo anticancer activity. We anticipate that miRiaTAC represents a significant intersection between dynamic DNA nanotechnology and PROTAC, potentially expanding the versatility of PROTAC toolkit for cancer therapy.

Ethnic sensitivity analyses of pharmacokinetics, efficacy and safety in polycythemia vera treatment with ropeginterferon alfa-2b.

Ropeginterferon alfa-2b (Ropeg) is approved for the treatment of adults with polycythemia vera (PV). This report aims to analyze the ethnic sensitivity of Ropeg for the treatment of PV, comparing the pharmacokinetics (PK), efficacy, and safety profiles across diverse ethnic groups. We conducted a relevant review of PV and analysis of data obtained from clinical studies involving Ropeg. The PK behavior of ropeg showed no significant differences between Chinese and overseas populations. Their efficacy and safety profiles were similar across the ethnic groups. The analyses indicated that the dose-exposure-response profile of Ropeg was consistent irrespective of ethnic variations. The results suggest that Ropeg exhibits a consistent PK and pharmacodynamics profile and a similar therapeutic effect across different ethnic groups, confirming its efficacy and safety in the global treatment of PV. More generally, these findings support the broader application of Ropeg in diverse patient populations and emphasize the need for an inclusive clinical practice.

Silver-catalyzed cascade cyclization for the synthesis of 4-aminotetrahydrocarbazole.

A silver-catalyzed cascade cyclization strategy has been developed for the synthesis of 4-aminotetrahydrocarbazole, a common core structure found in various alkaloids. This target molecule can be synthesized through a one-step tandem cyclization reaction, thereby eliminating the need for a prior synthesis of tetrahydrocarbazole. Furthermore, the use of chiral tert-butylsulfinamide facilitates in situ chiral resolution of the resulting product.

Comprehensive evaluation on phenolic derivatives and antioxidant activities of diverse yellow maize varieties.

The main phenolic derivatives and antioxidant capacity of ninety-three yellow maize varieties were investigated, together with their color parameters. Sixteen phenolics were identified in the free extract by UPLC-ESI-MS/MS, N', N″-diferuloyl putrescine and N', N″-dicoumaryl spermidine were the major phenolic derivatives. Fourteen phenolic compounds were found in the bound extract, with trans-p-coumaric acid, trans- and cis-ferulic acid being the predominant phenolic acids. The orange-yellow maize varieties presented the highest total phenolic content (TPC) and total flavonoid content (TFC), along with significantly higher antioxidant potential. Correlation analysis showed that b* value (corresponding to yellow degree) was positively correlated with the total carotenoid content (TCC), phenolic content, and antioxidant capacity (p < 0.05). Through Hierarchical Clustering Analysis (HCA), the 93 maize varieties could be divided into three categories according to b* value and antioxidant activity. The heatmap visualization further underscored the component differences across various varieties, unveiling the intricate phytochemical profiles of these maize varieties.

Effective protective mechanisms of HO-1 in diabetic complications: a narrative review.

Diabetes mellitus is a metabolic disorder with persistent hyperglycemia caused by a variety of underlying factors. Chronic hyperglycemia can lead to diverse serious consequences and diversified complications, which pose a serious threat to patients. Among the major complications are cardiovascular disease, kidney disease, diabetic foot ulcers, diabetic retinopathy, and neurological disorders. Heme oxygenase 1 (HO-1) is a protective enzyme with antioxidant, anti-inflammatory and anti-apoptotic effects, which has been intensively studied and plays an important role in diabetic complications. By inducing the expression and activity of HO-1, it can enhance the antioxidant, anti-inflammatory, and anti-apoptotic capacity of tissues, and thus reduce the degree of damage in diabetic complications. The present study aims to review the relationship between HO-1 and the pathogenesis of diabetes and its complications. HO-1 is involved in the regulation of macrophage polarization and promotes the M1 state (pro-inflammatory) towards to the M2 state (anti-inflammatory). Induction of HO-1 expression in dendritic cells inhibits them maturation and secretion of pro-inflammatory cytokines and promotes regulatory T cell (Treg cell) responses. The induction of HO-1 can reduce the production of reactive oxygen species, thereby reducing oxidative stress and inflammation. Besides, HO-1 also has an important effect in novel programmed cell death such as pyroptosis and ferroptosis, thereby playing a protective role against diabetes. In conclusion, HO-1 plays a significant role in the occurrence and development of diabetic complications and is closely associated with a variety of complications. HO-1 is anticipated to serve as a novel target for addressing diabetic complications, and it holds promise as a potential therapeutic agent for diabetes and its associated complications. We hope to provide inspiration and ideas for future studies in the mechanism and targets of HO-1 through this review.

Analyzing Risk Factors for Delayed Extubation Following Posterior Approach Surgery for Congenital Scoliosis: A Retrospective Cohort Study.

STUDY DESIGN: Retrospective cohort study. OBJECTIVES: Investigate the risk factors for delayed extubation after posterior approach orthopedic surgery in patients with congenital scoliosis. METHODS: The clinical data of patients who received surgery for congenital scoliosis at the First Affiliated Hospital of Xinjiang Medical University between January 2021 and July 2023 have been gathered. Patients are categorized into the usual and the delayed extubation groups, depending on the duration of tracheal intubation after surgery. The study employs univariate and multivariate logistic regression models to examine the clinical characteristics of the two cohorts and discover potential risk factors linked to delayed extubation. In addition, a prediction model is created to visually depict the significance of each risk factor in terms of weight according to the nomogram. RESULTS: A total of 119 patients (74.8% females), with a median age of 15 years, are included. A total of 32 patients, accounting for 26.9% of the sample, encountered delayed extubation. Additionally, 13 patients (10.9%) suffered perioperative complications, with pneumonia being the most prevalent. The multivariate regression analysis revealed that the number of osteotomy segments, postoperative hematocrit, postoperative Interleukin-6 levels, and weight are predictive risk factors for delayed extubation. CONCLUSIONS: Postoperative hematocrit and Interleukin-6 level, weight, and number of osteotomy segments can serve as independent risk factors for predicting delayed extubation, with combined value to assist clinicians in evaluating the risk of delayed extubation of postoperative congenital scoliosis patients, improving the success rate of extubation, and reducing postoperative treatment time in the intensive care unit.

Penicipyrrolizidinones A-C, three pyrrolizidinone alkaloids with unprecedented skeletons from the mangrove-derived fungus Penicillium sp. DM27.

Three previously undescribed pyrrolizidinone alkaloids, penicipyrrolizidinones A and B (1 and 2), possessing an unprecedented 2-methyl-2-(oct-6-enoyl)pyrrolizidin-3-one skeleton, and penicipyrrolizidinone C (3), featuring a rare 1-alkenyl-2-methyl-pyrrolizidin-3,7-dione skeleton, together with four known pyrrolidine derivatives (4-7) were isolated from the mangrove-derived fungus Penicillium sp. DM27. Their structures were elucidated through comprehensive spectroscopic analysis, theoretical calculations of ECD spectra, and the modified Mosher's method. A plausible biosynthetic pathway for penicipyrrolizidinones A-C (1-3) was proposed. Compounds 4 and 5 exhibited moderate cytotoxicity against B16-F10 melanoma cells with IC50 values of 10.5 µM and 15.5 µM, respectively.

Branched hybridization chain reaction and tetrahedral DNA-based trivalent aptamer powered SERS sensor for ultra-highly sensitive detection of cancer-derived exosomes.

Exosomes have emerged as a promising noninvasive biomarker for early cancer diagnosis due to their ability to carry specific bioinformation related to cancer cells. However, accurate detection of trace amount of cancer-derived exosomes in complex blood remains a significant challenge. Herein, an ultra-highly sensitive SERS sensor, powered by the branched hybridization chain reaction (bHCR) and tetrahedral DNA-based trivalent aptamer (triApt-TDN), has been proposed for precise detection of cancer-derived exosomes. Taking gastric cancer SGC-7901 cells-derived exosomes as a test model, the triApt-TDNs were constructed by conjugating aptamers specific to mucin 1 (MUC1) protein with tetrahedral DNAs and subsequently immobilized on the surface of silver nanorods (AgNRs) arrays to create SERS-active sensing chips capable of specifically capturing exosomes overexpressing MUC1 proteins. The bHCR was further initiated by the trigger aptamers (tgApts) bound to exosomes, and as a result the SERS tags were assembled into AuNP network structures with abundant SERS hotspots. By optimizing the sensing conditions, the SERS sensor showed good performance in ultra-highly sensitive detection of target exosomes within 60 min detection time, with a broad response ranging of 1.44 to 1.44 × 104 particles·µL-1 and an ultralow limit of detection capable of detecting a single exosome in 2 µL sample. Furthermore, the SERS sensor exhibited good uniformity, repeatability and specificity, and capability to distinguish between gastric cancer (GC) patients and healthy controls (HC) through the detection of exosomes in clinical human serums, indicating its promising clinical potential for early diagnosis of gastric cancer.

High-risk screening for late-onset Pompe disease in China: An expanded multicenter study.

Late-onset Pompe disease (LOPD) is caused by a genetic deficiency of the lysosomal enzyme acid alpha-glucosidase (GAA), leading to progressive limb-girdle weakness and respiratory impairment. The insidious onset of non-specific early symptoms often prohibits timely diagnosis. This study aimed to validate the high-risk screening criteria for LOPD in the Chinese population. A total of 726 patients were included, including 96 patients under 14 years of age. Dried blood spots (DBS) and tandem mass spectrometry (MS/MS) were employed to evaluate serum GAA activity. Forty-four patients exhibited a decreased GAA activity, 16 (2.2%) of which were confirmed as LOPD by genetic testing. Three previously unreported GAA mutations were also identified. The median diagnostic delay was shortened to 3 years, which excelled the previous retrospective studies. At diagnosis, most patients exhibited impaired respiratory function and/or limb-girdle weakness. Elevated serum creatine kinase (CK) levels were more frequently observed in patients who manifested before age 16. Overall, high-risk screening is a feasible and efficient method to identify LOPD patients at an early stage. Patients over 1 year of age with either weakness in axial and/or proximal limb muscles, or unexplained respiratory distress shall be subject to GAA enzymatic test, while CK levels above 2 times the upper normal limit shall be an additional criterion for patients under 16. This modified high-risk screening criteria for LOPD requires further validation in larger Chinese cohorts.

Trifarotene alleviates skin photoaging injury by inhibition of JNK/c-Jun/MMPs.

Long-term exposure to ultraviolet (UV) radiation induces skin photoaging, which manifests as oxidative stress, inflammation, and collagen degradation. Multiple approaches (topical or systemic retinoids, antioxidants, alpha-hydroxy acids, laser, surgery) are used in the treatment of photoaged skin, and the use of topical retinoids is currently a primary clinical treatment. Previous studies revealed that retinoic acid promotes keratinocyte proliferation and reduces melanin deposition and matrix metalloproteinase (MMP) secretion; it also causes potential allergic and inflammatory damage to the skin. This study aimed to investigate the therapeutic effects and mechanisms of trifarotene, a functional retinoic acid analog, on UV-irradiated photoaging ICR and BALB/c nude mice and UVB photodamaged human epidermal keratinocyte (HaCaT) cells by examining indicators such as collagen, oxidoreductase, and inflammatory factor presence through histochemical staining, Western blot, and ELISA. Results suggested that trifarotene significantly reduced UV-induced photoaging in mouse skin tissue, potentially by reducing oxidative stress damage and inflammatory factor release, and inhibiting melanin deposition and collagen degradation by downregulating MMP expression. Concentrations of malondialdehyde, tyrosinase, interleukin-6, interleukin- 12, and tumor necrosis factor-alpha in photoaged skin decreased, while SOD content in photodamaged HaCaT cells significantly increased. Trifarotene (3.3 µmol L-1) inhibited phosphorylated JNK and c-Jun expression both independently and collaboratively with the JNK activator anisomycin, demonstrating that trifarotene mitigates UV-induced collagen degradation and apoptosis through inhibition of the JNK/c-Jun/MMPs signaling pathway.

Association between long-term exposure to PM2.5 chemical components and metabolic syndrome in middle-aged and older adults.

Background: Previous studies indicated that exposure to ambient fine particulate matter (PM2.5) could increase the risk of metabolic syndrome (MetS). However, the specific impact of PM2.5 chemical components remains uncertain. Methods: A national cross-sectional study of 12,846 Chinese middle-aged and older adults was conducted. Satellite-based spatiotemporal models were employed to determine the 3-year average PM2.5 components exposure, including sulfates (SO4 2-), nitrates (NO3 -), ammonia (NH4 +), black carbon (BC), and organic matter (OM). Generalized linear models were used to investigate the associations of PM2.5 components with MetS and the components of MetS, and restricted cubic splines curves were used to establish the exposure-response relationships between PM2.5 components with MetS, as well as the components of MetS. Results: MetS risk increased by 35.1, 33.5, 33.6, 31.2, 32.4, and 31.4% for every inter-quartile range rise in PM2.5, SO4 2-, NO3 -, NH4 +, OM and BC, respectively. For MetS components, PM2.5 chemical components were associated with evaluated risks of central obesity, high blood pressure (high-BP), high fasting glucose (high-FBG), and low high-density lipoprotein cholesterol (low-HDL). Conclusion: This study indicated that exposure to PM2.5 components is related to increased risk of MetS and its components, including central obesity, high-BP, high-FBG, and low-HDL. Moreover, we found that the adverse effect of PM2.5 chemical components on MetS was more sensitive to people who were single, divorced, or widowed than married people.

Role of FGF21 in mediating the effect of phosphatidylcholine on GBM.

Objective: The causal relationship and mechanisms between lipids and glioblastoma (GBM) remain unclear. This study aims to investigate the independent causal relationship between liposomal phosphatidylcholine 16:0_22:6 (PC16) and GBM, and to identify the potential mediating role of the inflammatory factor-fibroblast growth factor 21(FGF21). Methods: Utilizing summary statistics from genome-wide association studies (GWAS) of lipids (179 types in 7174 Finnish individuals), GBM (243 cases and 287137 controls), and inflammatory factors (91 types in 14824 European individuals), a two-sample Mendelian Randomization (MR) approach was employed to establish the causal link between liposomal PC16 and GBM. Additionally, a two-step MR method was used to quantify the proportion of the causal effect of PC16 on GBM that is mediated by the inflammatory factor FGF21. Results: MR analyses revealed a strong causal relationship between PC16 and GBM (OR=1.72, 95% CI: 1.11-2.68, P=0.016), but no reverse causality was observed from GBM to PC16 (OR=1.01, 95% CI: 0.99-1.02, P=0.38). Mediation analysis showed a strong causal relationship between PC16 and the FGF21 (OR = 0.94, 95% CI: 0.89-0.99, P=0.018) as well as between FGF21 and GBM (OR = 0.42, 95% CI: 0.25-0.71, P=0.001), with the mediation effect accounting for 9.78% of the total effect. This suggests that the causal relationship between PC16 and GBM is likely mediated by the intermediary factor FGF21. No evidence of pleiotropy was found in the sensitivity analysis of these positive results. Conclusion: In summary, the findings of this study suggest that liposomal PC16 may increase the risk of GBM occurrence, and FGF21 may play a significant mediating role in this causal relationship.

Association between base excess and mortality in critically ill patients with ischemic stroke: a retrospective cohort study.

BACKGROUND: Base excess (BE) is associated with mortality from many diseases. However, the relationship between BE and mortality in patients with ischemic stroke remains uncertain. Our aim is to investigate the relationship between BE values upon admission to the ICU and mortality rates in critically ill stroke patients. METHODS: The current study enrolled 1,572 patients with ischemic stroke (863 males and 709 females). The associations of BE with intensive care unit (ICU), hospital, 28-day, and 1-year mortalities were assessed using multivariable logistic regression or Cox proportional hazards model. The potential impact of the Sequential Organ Failure Assessment (SOFA) score (< 5 or ≥ 5) on the prognostic value of BE was further evaluated with interaction and subgroup analyses. RESULTS: BE values less than - 3 mmol/L, greater than 3 mmol/L, and within - 3 to 3 mmol/L (normal BE) were observed in 316 (20.1%), 175 (11.1%), and 1,081 (68.8%) patients, respectively. The restricted cubic splines analyses revealed that a U-shaped curve between BE and the mortality risk. Multivariable analysis indicated that patients with low BE (<-3 mmol/L) had higher rates of ICU mortality (odds ratio [OR], 1.829; 95% confidence interval [CI], 1.281-2.612; P = 0.001), hospital mortality (OR, 1.484; 95% CI, 1.077-2.045; P = 0.016), 28-day mortality (hazard ratio [HR], 1.522; 95% CI, 1.200-1.929; P = 0.001), and 1-year mortality (HR, 1.399; 95% CI, 1.148-1.705; P = 0.001) than patients with normal BE. Subgroup analyses showed consistent results pertaining to SOFA scores ≥ 5. CONCLUSIONS: In critically ill patients with ischemic stroke, an initial BE of <-3 mmol/L at ICU admission may indicate an increased risk of ICU, hospital, 28-day, and 1-year mortalities.

Electroacupuncture Promotes the Generation of Intestinal Treg Cells After Ischemic Stroke by Foxp3 Acetylation Regulation.

Electroacupuncture (EA) has been shown to ameliorate brain injury and protect against intestinal injury after ischemic stroke. These protective effects are closely associated with the enhancement of regulatory T (Treg) cell numbers and function in the intestine, as well as the inhibition of intestinal γδ T cell production and their migration to the brain. This study aimed to elucidate the potential mechanism by which EA regulates intestinal Treg cell differentiation after stroke. Sprague-Dawley rats were divided into three groups: the sham group, the middle cerebral artery occlusion (MCAO) group, and the MCAO plus EA (MEA) group. The MCAO model was generated by occluding the middle cerebral artery. EA was applied to Baihui (GV20) acupoint once daily. Samples were collected 3 days after reperfusion. Our results showed that EA reduced the inflammatory response in the brain and intestine after ischemic stroke. EA treatment increased the percentage of Treg cells in the small intestine of rats. EA increased the levels of SCFAs, while also inhibiting histone deacetylase activity (HDAC). Additionally, acetylated Foxp3 protein in the small intestine was increased after EA treatment. These results suggest that EA at GV20 alleviates brain and intestinal inflammatory injury in stroke rats, potentially through the enhancement of SCFA-mediated Foxp3 acetylation in Treg cells.

Vertical variation of antibiotic resistance genes and their interaction with environmental nutrients in sediments of Taihu lake.

Antibiotic resistance is a growing environmental issue. As a sink for antibiotic resistance genes (ARGs), lake surface sediments are well known for the spread of ARGs. However, the distribution pattern of ARGs and their relationship with environmental factors in vertical sediment layers are unclear. In this study, we investigated the resistome distribution in sediment cores from Taihu Lake using metagenomic analysis. The results showed that the abundance of total ARGs increased by 153% as the sediment depth rose from 0 to 50 cm, and the ARG Shannon index significantly increased. Among all the ARG types, efflux pump genes (e.g., mexT and mexW) were dominant, especially in 40-50 cm sediment. The variation in ARG with depth described above was related to the changes in bacterial adaptation to environmental gradients. Specifically, sulfate and nitrate concentrations decreased with depth, and random forest analysis showed that they were the main factors affecting the changes in ARG abundance. Environmental factors were also found to indirectly impact the distribution of ARGs by affecting the bacterial community. Potential sulfate-reducing gene/nitrate-reducing gene-ARG co-hosts were annotated through metagenomic assembly. The dominant co-hosts, Curvibacter, and Comamonas, which were enriched in deeper sediments, may have contributed to the enrichment of ARGs in deep sediments. Overall, our findings demonstrated that bacterial-mediated sulfate and nitrate reduction was closely related to sediment resistance, which provided new insights into the control of antibiotic resistance.

Non-discriminating engineered masking of immuno-evasive ligands on tumour-derived extracellular vesicles enhances tumour vaccination outcomes.

The success of personalized cancer immunotherapy depends on the initial tumour antigenic presentation to dendritic cells and macrophages. Tumour-derived extracellular vesicles (TEVs) contain abundant tumour antigenic molecules. The presence of anti-phagocytotic signals such as cluster of differentiation 47 (CD47) on the surface of the TEVs, however, leads to evasion of the same dendritic cells and macrophages. Here we show that iron oxide hydroxide nanocomposites can successfully mask TEV surfaces and unblock phagocytosis without affecting extracellular vesicles' elicited immune goals. After internalization, the mask disintegrates in the lysosome, releasing the tumour antigenic cargo. This triggers antigen presentation and promotes dendritic cell activation and maturation and macrophage reprogramming in animal models, leading to a drastic reduction of tumour volume and metastasis, and in human malignant pleural effusion clinical samples. This straightforward masking strategy eliminates the ubiquitous anti-phagocytosis block found in clinical samples and can be applied universally across all patient-specific TEVs as tumour antigenic agents for enhanced immunotherapy.

Enhancing work safety behavior through supply chain safety management in small and medium sized manufacturing suppliers.

Enhancing work safety behaviors among Small and Medium-Sized Manufacturing Suppliers (SMMs) is crucial for establishing a more secure and efficient supply chain. Since the foundation of safety lies in positive prevention, it is crucial that SMMs adopt proactive and pro-social work safety behaviors that transcend mere compliance with standard regulations. Present-day diversified supply chain safety management apply varying degrees of pressures on SMMs. The effectiveness of such pressures, as well as their potential to spawn advanced safety behaviors in SMMs, is a matter of investigation. This research investigates the impact of Supply Chain Safety Management Pressure(SCSMP) on the SMMs' Work Safety Behaviors(WSB). A theoretical framework is constructed, grounded in institutional theory and theory of planned behavior, which earmarks three distinct dimensions of SCSMP: Coercive Pressure(CP), Mimetic Pressure(MP), and Normative Pressure(NP). The survey of 265 SMMs facilitated an assessment of the SMMs' Willingness for Responses(WR), which includes their Willingness for Adaptive Responses(WAR) and Willingness for Co-creative Responses(WCR). Subsequently, the resulting WSB entail Safety Compliance Behavior(SCB), Proactive Safety Behavior(PSB), and Pro-social Safety Behavior(PsSB). Among these, SCB is categorized as a basic safety behavior, while PSB and PsSB which emphasize voluntary, active, and cooperative actions, are classified as advanced safety behaviors. Our research findings underscore the substantial influence of the SCSMP in shaping WSB. WR serves as a critical intermediary, connecting external pressures with internal organizational practices. In particular, WCR is instrumental in the formation of advanced safety behavior. The theoretical contribution of this research is manifested in its enhancement of our comprehension regarding the determinants of WSB among SMMs. Furthermore, it addresses the literature gap in elucidating the effectiveness of supply chain safety management and the mechanisms behind the formation of WSB. The practical significance lies in elevating the overall safety standards throughout the supply chain and minimizing safety-related hazards among SMMs.