Unexpected diagnosis of rare mesenteric Castleman disease: A case report and literature review.

In this report, we present an Asian male patient who was 30 years old and admitted to the hospital due to pancreatitis. While undergoing a CT scan, an isolated mass was unexpectedly discovered in the patient's abdomen. The patient's abdominal pain, which was caused by pancreatitis, had resolved before he underwent surgical resection to remove the mass. Subsequently, the patient was diagnosed with Castleman disease based on pathology. Castleman disease occurring in the mesentery is exceptionally rare. Therefore, we have reviewed the essential information regarding Castleman disease and have found that the crucial part lies in the diagnosis and the consideration of distinct treatment strategies based on different types.

Modified montmorillonite armed probiotics with enhanced on-site mucus-depleted intestinal colonization and H2S scavenging for colitis treatment.

Inflammatory bowel diseases (IBD) are often associated with dysregulated gut microbiota and excessive inflammatory microenvironment. Probiotic therapy combined with inflammation management is a promising approach to alleviate IBD, but the efficacy is hindered by the inferior colonization of probiotics in mucus-depleted inflammatory bowel segments. Here, we present modified montmorillonite armed probiotic Escherichia coli Nissle 1917 (MMT-Fe@EcN) with enhanced intestinal colonization and hydrogen sulfide (H2S) scavenging for synergistic alleviation of IBD. The montmorillonite layer that can protect EcN against environmental assaults in oral delivery and improve on-site colonization of EcN in the mucus-depleted intestinal segment due to its strong adhesive capability and electronegativity, with a 22.6-fold increase in colonization efficiency compared to EcN. Meanwhile, MMT-Fe@EcN can manage inflammation by scavenging H2S, which allows for enhancing probiotic viability and colonization for restoring the gut microbiota. As a result, MMT-Fe@EcN exhibits extraordinary therapeutic effects in the dextran sulfate sodium-induced mouse colitis models, including alleviating intestinal inflammation and restoring disrupted intestinal barrier function, and gut microbiota. These findings provide a promising strategy for clinical IBD treatment and potentially other mucus-depletion-related diseases.

Chloroplast and whole-genome sequencing shed light on the evolutionary history and phenotypic diversification of peanuts.

Cultivated peanut (Arachis hypogaea L.) is a widely grown oilseed crop worldwide; however, the events leading to its origin and diversification are not fully understood. Here by combining chloroplast and whole-genome sequence data from a large germplasm collection, we show that the two subspecies of A. hypogaea (hypogaea and fastigiata) likely arose from distinct allopolyploidization and domestication events. Peanut genetic clusters were then differentiated in relation to dissemination routes and breeding efforts. A combination of linkage mapping and genome-wide association studies allowed us to characterize genes and genomic regions related to main peanut morpho-agronomic traits, namely flowering pattern, inner tegument color, growth habit, pod/seed weight and oil content. Together, our findings shed light on the evolutionary history and phenotypic diversification of peanuts and might be of broad interest to plant breeders.

Air-Stable High-Entropy Layered Oxide Cathode with Enhanced Cycling Stability for Sodium-Ion Batteries.

O3-type layered oxides have been extensively studied as cathode materials for sodium-ion batteries due to their high reversible capacity and high initial sodium content, but they suffer from complex phase transitions and an unstable structure during sodium intercalation/deintercalation. Herein, we synthesize a high-entropy O3-type layered transition metal oxide, NaNi0.3Cu0.05Fe0.1Mn0.3Mg0.05Ti0.2O2 (NCFMMT), by simultaneously doping Cu, Mg, and Ti into its transition metal layers, which greatly increase structural entropy, thereby reducing formation energy and enhancing structural stability. The high-entropy NCFMMT cathode exhibits significantly improved cycling stability (capacity retention of 81.4% at 1C after 250 cycles and 86.8% at 5C after 500 cycles) compared to pristine NaNi0.3Fe0.4Mn0.3O2 (71% after 100 cycles at 1C), as well as remarkable air stability. Finally, the NCFMMT//hard carbon full-cell batteries deliver a high initial capacity of 103 mAh g-1 at 1C, with 83.8 mAh g-1 maintained after 300 cycles (capacity retention of 81.4%).

Cyy-272, an indazole derivative, effectively mitigates obese cardiomyopathy as a JNK inhibitor.

Obesity has shown a global epidemic trend. The high-lipid state caused by obesity can maintain the heart in a prolonged low-grade inflammatory state and cause ventricular remodeling, leading to a series of pathologies, such as hypertrophy, fibrosis, and apoptosis, which eventually develop into obese cardiomyopathy. Therefore, prolonged low-grade inflammation plays a crucial role in the progression of obese cardiomyopathy, making inflammation regulation an essential strategy for treating this disease. Cyy-272, an indazole derivative, is an anti-inflammatory compound independently synthesized by our laboratory. Our previous studies revealed that Cyy-272 can exert anti-inflammatory effects by inhibiting the phosphorylation and activation of C-Jun N-terminal kinase (JNK), thereby alleviating lipopolysaccharide (LPS)-induced acute lung injury (ALI). The current study aimed to evaluate the potential of Cyy-272 to mitigate the occurrence and progression of obese cardiomyopathy through the inhibition of the JNK signaling pathway. Our results indicate that the compound Cyy-272 has encouraging therapeutic effects on obesity-induced cardiac injury. It significantly inhibits inflammation in cardiomyocytes and heart tissues induced by high lipid concentrations, further alleviating the resulting hypertrophy, fibrosis, and apoptosis. Mechanistically, the protective effect of Cyy-272 on obese cardiomyopathy can be attributed to its direct inhibition of JNK protein phosphorylation. In conclusion, we identified a novel compound, Cyy-272, capable of alleviating obese cardiomyopathy and confirmed that its effect is achieved through direct inhibition of JNK.

Reversible Local Protonation-Deprotonation: Tuning Stimuli-Responsive Circularly Polarized Luminescence in Chiral Hybrid Zinc Halides for Anti-Counterfeiting and Encryption.

Precise control over the organic composition is crucial for tailoring the distinctive structures and properties of hybrid metal halides. However, this approach is seldom utilized to develop materials that exhibit stimuli-responsive circularly polarized luminescence (CPL). Herein, we present the synthesis and characterization of enantiomeric hybrid zinc bromides: biprotonated ((R/S)-C12H16N2)ZnBr4 ((R/S-LH2)ZnBr4) and monoprotonated ((R/S)-C12H15N2)2ZnBr4 ((R/S-LH1)2ZnBr4), derived from the chiral organic amine (R/S)-2,3,4,9-Tetrahydro-1H-carbazol-3-amine ((R/S)-C12H14N2). These compounds showcase luminescent properties; the zero-dimensional biprotonated form emits green light at 505 nm, while the monoprotonated form, with a pseudo-layered structure, displays red luminescence at 599 and 649 nm. Remarkably, the reversible local protonation-deprotonation behavior of the organic cations allows for exposure to polar solvents and heating to induce reversible structural and luminescent transformations between the two forms. Theoretical calculations reveal that the lower energy barrier associated with the deprotonation process within the pyrrole ring is responsible for the local protonation-deprotonation behavior observed. These enantiomorphic hybrid zinc bromides also exhibit switchable circular dichroism (CD) and CPL properties. Furthermore, their chloride counterparts were successfully obtained by adjusting the halogen ions. Importantly, the unique stimuli-responsive CPL characteristics position these hybrid zinc halides as promising candidates for applications information storage, anti-counterfeiting, and information encryption.

Breaking Boundaries in Spinal Surgery: GPT-4's Quest to Revolutionize Surgical site Infection Management.

BACKGROUND: Surgical site infection (SSI) is a common and costly complication in spinal surgery. Identifying risk factors and preventive strategies is crucial for reducing SSIs. GPT-4 has evolved from a simple text-based tool to a sophisticated multimodal data expert, invaluable for clinicians. This study explored GPT-4's applications in SSI management across various clinical scenarios. METHODS: GPT-4 was employed in various clinical scenarios related to SSIs in spinal surgery. Researchers designed specific questions for GPT-4 to generate tailored responses. Six evaluators assessed these responses for logic and accuracy using a 5-point Likert scale. Inter-rater consistency was measured with Fleiss' kappa, and radar charts visualized GPT-4's performance. RESULTS: The inter-rater consistency, measured by Fleiss' kappa, ranged from 0.62 to 0.83. The overall average scores for logic and accuracy were 24.27±0.4 and 24.46±0.25 on 5-point Likert scale. Radar charts showed GPT-4's consistently high performance across various criteria. GPT-4 demonstrated high proficiency in creating personalized treatment plans tailored to diverse clinical patient records and offered interactive patient education. It significantly improved SSI management strategies, infection prediction models, and identified emerging research trends. However, it had limitations in fine-tuning antibiotic treatments and customizing patient education materials. CONCLUSIONS: GPT-4 represents a significant advancement in managing SSIs in spinal surgery, promoting patient-centered care and precision medicine. Despite some limitations in antibiotic customization and patient education, GPT-4's continuous learning, attention to data privacy and security, collaboration with healthcare professionals, and patient acceptance of AI recommendations suggest its potential to revolutionize SSI management, requiring further development and clinical integration.

Effect of bile duct resection on the prognosis of patients with hepatocellular carcinoma combined with extrahepatic bile duct tumor thrombus.

BACKGROUND: Surgical therapy is the most optimal treatment for hepatocellular carcinoma (HCC) combined with bile duct tumor thrombus (BDTT) patients. However, whether to perform bile duct resection (BDR) is still controversial. The purpose of this multicenter research is to compare the effect of BDR on the prognosis of extrahepatic BDTT patients. METHODS: We collected the data of 111 HCC patients combined with extrahepatic BDTT who underwent radical hepatectomy from June 1, 2004 to December 31, 2021. Those patients had either received hepatectomy with extrahepatic bile duct resection (BDR group) or hepatectomy without bile duct resection (NBDR group). Inverse probability of treatment weighting (IPTW) was used to reduce the potential bias between two groups and balance the influence of confounding factors in baseline data. Then compare the prognosis between the two groups of patients. Cox regression model was used for univariate and multivariate analysis to further determine the independent risk factors that influence the prognosis of HCC-BDTT patients. RESULTS: There were 38 patients in the BDR group and 73 patients in the NBDR group. Before and after IPTW, there were no statistical significance in OS, RFS and intraoperative median blood loss between the two groups (all P > 0.05). Before IPTW, the median postoperative hospital stay in the NBDR group was shorter (P = 0.046) and the grade of postoperative complications was lower than BDR group (P = 0.014). After IPTW, there was no difference in postoperative hospital stay between the two groups (P > 0.05). The complication grade in the NBDR group was still lower than that in the BDR group (P = 0.046). The univariate analysis showed that TNM stage and portal vein tumor thrombus (PVTT) were significantly correlated with OS (both P < 0.05). Preoperative AFP level, TNM stage and prognostic nutritional index (PNI) were significantly correlated with postoperative RFS (all P < 0.05). Multivariate analysis showed that tumor TNM stage was an independent risk factor for the OS rate (P = 0.014). TNM stage, PNI and AFP were independent predictors of RFS after radical hepatectomy (all P < 0.05). CONCLUSIONS: For HCC-BDTT patients, hepatocellular carcinoma resection combined with choledochotomy to remove the tumor thrombus may benefit more.

A case report of interstitial pneumonia induced by vedolizumab in a patient with ulcerative colitis.

RATIONALE: The interstitial pneumonia (IP) linked to vedolizumab (VDZ) in patients with ulcerative colitis (UC) is rare. Prompt diagnosis and treatment can improve patient outcomes. PATIENT CONCERNS: A 39-year-old man with UC who received VDZ as sole therapy developed symptoms such as chest tightness, cough, and suffocation. DIAGNOSES: IP was confirmed through pulmonary function tests, chest computed tomography, and bronchoscopic biopsy. INTERVENTIONS: The patient was given methylprednisolone and VDZ cessation. OUTCOMES: The patient's symptoms improved and remained symptom-free after nearly 2 years. LESSONS: VDZ-induced IP should be considered when evaluating pulmonary infections in UC patients treated with VDZ.

Association between rheumatoid arthritis and serum vitamin C levels in Adults: Based on the National health and Nutrition Examination survey database.

This study attempted to investigate relationship between rheumatoid arthritis and serum vitamin C levels using data from National Health and Nutrition Examination Survey (NHANES). The NHANES database aims to collect health, nutrition, biological, and behavioral data from a nationally representative sample of the population. This study utilizes NHANES data from three cycles: 2003-2004, 2005-2006, and 2017-2018, extracting data on the prevalence of rheumatoid arthritis and serum vitamin C levels. A generalized linear model is used to evaluate the association between the two. A total of 12,665 participants were included in the final analysis. Serum vitamin C levels were significantly higher in the non-rheumatoid arthritis group compared to the rheumatoid arthritis group (0.63 vs. 0.59, P = 0.042). Generalized linear model analysis showed that higher serum vitamin C levels were associated with a decreased risk of rheumatoid arthritis (OR = 0.62, 95 %CI: 0.40-0.98, P = 0.034). Stratified analysis revealed a significant interaction between non-hypertensive individuals and rheumatoid arthritis with serum vitamin C levels (P < 0.05). After adjusting for confounding factors, serum vitamin C levels remained significantly associated with rheumatoid arthritis in all models (P < 0.05). Restricted cubic spline results indicated that serum vitamin C levels above 0.95 mg/dL could help prevent rheumatoid arthritis. Increasing dietary vitamin C intake through supplementation was found to raise serum vitamin C levels. There was a significant association between rheumatoid arthritis and serum vitamin C levels, indicating that high levels of serum vitamin C may be a protective factor against rheumatoid arthritis.

Forensic significance of VOCs profiling in decayed ante- and post-mortem injuries by GC×GC-TOF/MS.

Accurately identifying and differentiating the types of injuries in decomposed corpses is a major challenge in forensic identification. Forensic investigations involving decomposed cadavers pose challenges in determining the cause of death. Traditional methods often lack conclusive evidence. However, the implementation of advanced analytical techniques, such as comprehensive two-dimensional gas chromatography coupled with time-of-flight mass spectrometry (GC × GC-TOF/MS), shows promise in overcoming these limitations, but the potential in this area remains limited. Therefore, this study aims to bridge this gap by exploring the potential of GC × GC-TOF/MS in the analysis of volatile organic compounds (VOCs) changes within decaying ante- and post-mortem injuries.The research emphasizes the forensic significance of VOCs changes in decomposed cadavers. We used GC × GC-TOF/MS analysis to identify the specific volatile compounds in putrefied corpse tissue samples from mice. The GC × GC-TOF/MS analysis results showed that under winter conditions, PC1 explained 57.16% of the variance, and PC2 explained 25.23% of the variance; while under summer conditions, PC1 explained 71.89% of the variance, and PC2 explained 24.49% of the variance. This demonstrates the potential of GC × GC-TOF/MS in identifying specific VOCs present in tissue samples that can serve as potential biomarkers for distinguishing between antemortem and postmortem injury. GC × GC-TOF/MS analysis revealed distinct VOC patterns in both conditions. Comprehensive use of GC × GC-TOF/MS analysis enhances accuracy in identifying and characterizing ante- and post-mortem injuries in decomposed cadavers. This study can significantly contribute to the field of forensic medicine and improve the accuracy of forensic investigations.

Association of Geriatric Nutritional Risk Index with short-term mortality in patients with severe acute kidney injury: a retrospective cohort study.

OBJECTIVES: Geriatric Nutritional Risk Index (GNRI) is a new and simple index recently introduced to assess nutritional status, and its predictive value for clinical outcomes has been demonstrated in patients with chronic kidney disease. However, the association between the GNRI and prognosis has not been evaluated so far in patients with acute kidney injury (AKI), especially in those receiving continuous renal replacement therapy (CRRT). METHODS: A total of 1096 patients with severe AKI initiating CRRT were identified for inclusion in this retrospective observational study. Patients were divided into three groups according to GNRI tertiles, with tertile 1 as the reference. The outcomes of interest were the 28- and 90-days of all-cause mortality. The associations between GNRI and clinical outcomes were estimated using multivariate Cox proportional hazards model analysis. RESULTS: The overall mortality rates at 28- and 90-days were 61.6% (675/1096) and 71.5% (784/1096), respectively. After adjusting for multiple confounding factors, GNRI was identified as an independent prognostic factor for 28-days all-cause mortality (HR, 0.582; 95% CI, 0.467-0.727; p < .001 for tertile 3 vs. tertile 1) as well as 90-days all-cause mortality (HR, 0.540; 95% CI, 0.440-0.661; p < .001 for tertile 3 vs. tertile 1). The observed inverse associations were robust across subgroup analysis, and were more pronounced in elderly patients over 65 years of age. Finally, incorporating GNRI in a model with established risk factors might significantly improve its predictive power for the short-term death. CONCLUSIONS: GNRI is considered to be a useful prognostic factor in patients with severe AKI initiating CRRT, especially in elderly patients.

Structural Engineering of Prussian Blue Analogues Enabling All-Climate and Ultralong Cycling Sodium-Ion Batteries.

The development of cost-efficient, long-lifespan, and all-climate sodium-ion batteries is of great importance for advancing large-scale energy storage but is plagued by the lack of suitable cathode materials. Here, we report low-cost Na-rich Mn-based Prussian blue analogues with superior rate capability and ultralong cycling stability over 10,000 cycles via structural optimization with electrochemically inert Ni atoms. Their thermal stability, all-climate properties, and potential in full cells are investigated in detail. Multiple in situ characterizations reveal that the outstanding performances benefit from their highly reversible three-phase transformations and trimetal (Mn-Ni-Fe) synergistic effects. In addition, a high sodium diffusion coefficient and a low volume distortion of 2.3% are observed through in situ transmission electron microscopy and first-principles calculations. Our results provide insights into the structural engineering of Prussian blue analogues for advanced sodium-ion batteries in large-scale energy storage applications.

Deep learning methods for diagnosis of graves' ophthalmopathy using magnetic resonance imaging.

Background: The effect of diagnosing Graves' ophthalmopathy (GO) through traditional measurement and observation in medical imaging is not ideal. This study aimed to develop and validate deep learning (DL) models that could be applied to the diagnosis of GO based on magnetic resonance imaging (MRI) and compare them to traditional measurement and judgment of radiologists. Methods: A total of 199 clinically verified consecutive GO patients and 145 normal controls undergoing MRI were retrospectively recruited, of whom 240 were randomly assigned to the training group and 104 to the validation group. Areas of superior, inferior, medial, and lateral rectus muscles and all rectus muscles on coronal planes were calculated respectively. Logistic regression models based on areas of extraocular muscles were built to diagnose GO. The DL models named ResNet101 and Swin Transformer with T1-weighted MRI without contrast as input were used to diagnose GO and the results were compared to the radiologist's diagnosis only relying on MRI T1-weighted scans. Results: Areas on the coronal plane of each muscle in the GO group were significantly greater than those in the normal group. In the validation group, the areas under the curve (AUCs) of logistic regression models by superior, inferior, medial, and lateral rectus muscles and all muscles were 0.897 [95% confidence interval (CI): 0.833-0.949], 0.705 (95% CI: 0.598-0.804), 0.799 (95% CI: 0.712-0.876), 0.681 (95% CI: 0.567-0.776), and 0.905 (95% CI: 0.843-0.955). ResNet101 and Swin Transformer achieved AUCs of 0.986 (95% CI: 0.977-0.994) and 0.936 (95% CI: 0.912-0.957), respectively. The accuracy, sensitivity, and specificity of ResNet101 were 0.933, 0.979, and 0.869, respectively. The accuracy, sensitivity, and specificity of Swin Transformer were 0.851, 0.817, and 0.898, respectively. The ResNet101 model yielded higher AUC than models of all muscles and radiologists (0.986 vs. 0.905, 0.818; P<0.001). Conclusions: The DL models based on MRI T1-weighted scans could accurately diagnose GO, and the application of DL systems in MRI may improve radiologists' performance in diagnosing GO and early detection.

The impact of Paclitaxel-based hyperthermic intraperitoneal chemotherapy in advanced high-grade serous ovarian cancer patients - interim analysis of safety and immediate efficacy of a randomized control trial (C-HOC trial).

OBJECTIVE: This study evaluates the potential superiority of combining paclitaxel-based hyperthermic intraperitoneal chemotherapy (HIPEC) with sequential intravenous neoadjuvant chemotherapy over intravenous neoadjuvant chemotherapy alone in Chinese patients with Federation of Gynecology and Obstetrics (FIGO) stage IIIC, IVA and IVB high-grade serous ovarian/fallopian tube carcinoma (HGSOC). This interim analysis focuses on the safety and immediate efficacy of both regimens to determine the feasibility of the planned trial (C-HOC Trial). METHODS: In a single-center, open-label, randomized control trial, FIGO stage IIIC, IVA, and IVB HGSOC patients (FAGOTTI score ≥ 8 during laparoscopic exploration) unsuitable for optimal cytoreduction in primary debulking surgery (PDS) were randomized 2:1 during laparoscopic exploration. The Experiment Group (HIPEC Group) received one cycle of intraperitoneal neoadjuvant laparoscopic hyperthermic intraperitoneal chemotherapy (paclitaxel) followed by three cycles of intravenous chemotherapy (paclitaxel plus carboplatin), while the Control Group received only three cycles of intravenous chemotherapy. Both groups subsequently underwent interval debulking surgery (IDS). The adverse effects of chemotherapy, postoperative complications, and pathological chemotherapy response scores (CRS) after IDS were compared. RESULTS: Among 65 enrolled patients, 39 HIPEC Group and 21 Control Group patients underwent IDS. Grade 3-4 chemotherapy-related adverse effects were primarily hematological with no significant differences between the two groups. The HIPEC Group exhibited a higher proportion of CRS 3 (20.5% vs. 4.8%; P = 0.000). R0 resection rates in IDS were 69.2% (HIPEC Group) and 66.7% (Control Group). R2 resection occurred in 2.6% (HIPEC Group) and 14.3% (Control Group) cases. No reoperations or postoperative deaths were reported, and complications were managed conservatively. CONCLUSIONS: Combining HIPEC with IV NACT in treating ovarian cancer demonstrated safety and feasibility, with no increased chemotherapy-related adverse effects or postoperative complications. HIPEC improved tumor response to neoadjuvant chemotherapy, potentially enhancing progression-free survival (PFS). However, the final overall survival results are pending, determining if HIPEC combined with IV NACT is superior to IV NACT alone.

Coaxial nanofibrous aerogel featuring porous network-structured channels for ovarian cancer treatment by sustained release of chitosan oligosaccharide.

Ovarian cancer, the deadliest gynecological malignancy, primarily treated with chemotherapy. However, systemic chemotherapy often leads to severe toxic side effects and chemoresistance. Drug-loaded aerogels have emerged as a promising method for drug delivery, as they can improve drug solubility and bioavailability, control drug release, and reduce drug distribution in non-targeted tissues, thereby minimizing side effects. In this research, chitosan oligosaccharide (COS)-loaded nanofibers composite chitosan (CS) aerogels (COS-NFs/CS) with a porous network structure were created using nanofiber recombination and freeze-drying techniques. The core layer of the aerogel has a COS loading rate of 60 %, enabling the COS-NFs/CS aerogel to significantly inhibit the migration and proliferation of ovarian cancer cells (resulting in a decrease in the survival rate of ovarian cancer cells to 33.70 % after 48 h). The coaxial fiber's unique shell-core structure and the aerogel's porous network structure enable the COS-NFs/CS aerogels to release COS steadily and slowly over 30 days, effectively reducing the initial burst release of COS. Additionally, the COS-NFs/CS aerogels exhibit good biocompatibility, degradability (only retaining 18.52 % of their weight after 6 weeks of implantation), and promote angiogenesis, thus promoting wound healing post-oophorectomy. In conclusion, COS-NFs/CS aerogels show great potential for application in the treatment of ovarian cancer.

IGF2BP3 participates in the pathogenesis of recurrent spontaneous abortion by regulating ferroptosis.

The aberrant invasive capability of trophoblast cells is widely acknowledged as a primary mechanism underlying RSA. Recently, IGF2BP3 has been implicated in various cancers due to its influence on cellular invasion and migration. However, whether IGF2BP3 involve in the occurrence of RSA and the specific functions it assumes in the development of RSA remain elusive. In our study, we firstly collected villous tissues from RSA and those with normal pregnancies individuals to performed Protein sequencing and then detected the expression of IGF2BP3 through Western blot, qRT-PCR and immunohistochemistry. Secondly, we analyzed the single-cell data (GSE214607) to assess the expression of IGF2BP3 in invasive EVT trophoblasts. Thirdly, we utilized lentivirus technology to establish HTR-8/SVneo cell lines with stable IGF2BP3 knockdown and RNA-seq analysis was employed to investigate the GO functional pathway enrichment of IGF2BP3. Meanwhile, the effect of IGF2BP3 knockdown on trophoblast cells apoptosis, migration, and ferroptosis was evaluated through functional experiments. Additionally, LPS-induced abortion animal model was constructed to evaluate IGF2BP3 expression in placental tissues. A significant downregulation of IGF2BP3 was observed in the villous tissues of RSA patient, a finding corroborated by subsequent single cell sequencing results. Furthermore, it suggested that IGF2BP3 may be involved in the migration and apoptotic processes of trophoblast cells. Mechanistic research indicated that IGF2BP3 knockdown could compromise GPX4 mRNA stability, leading to the promotion of ferroptosis. Finally, our investigation observed the down-regulation of IGF2BP3 expression in placental villous tissues of an LPS-induced abortion animal model. Our findings revealed that IGF2BP3 was downregulated in the villous tissues of RSA patients. Mechanically, down-regulation of IGF2BP3 may induce RSA by promoting GPX4-mediated ferroptosis and inhibiting trophoblast invasion and migration. Our study may provide new targets and research directions for the pathogenesis of RSA.

Orchestrating NK and T cells via tri-specific nano-antibodies for synergistic antitumor immunity.

The functions of natural killer (NK) and T cells in innate and adaptive immunity, as well as their functions in tumor eradication, are complementary and intertwined. Here we show that utilization of multi-specific antibodies or nano-antibodies capable of simultaneously targeting both NK and T cells could be a valuable approach in cancer immunotherapy. Here, we introduce a tri-specific Nano-Antibody (Tri-NAb), generated by immobilizing three types of monoclonal antibodies (mAbs), using an optimized albumin/polyester composite nanoparticle conjugated with anti-Fc antibody. This Tri-NAb, targeting PDL1, 4-1BB, and NKG2A (or TIGIT) simultaneously, effectively binds to NK and CD8+ T cells, triggering their activation and proliferation, while facilitating their interaction with tumor cells, thereby inducing efficient tumor killing. Importantly, the antitumor efficacy of Tri-NAb is validated in multiple models, including patient-derived tumor organoids and humanized mice, highlighting the translational potential of NK and T cell co-targeting.

A study of prehospital EMS response time and influencing factors in the main urban area of Chongqing, China.

Shortening the prehospital emergency medical service (EMS) response time is crucial for saving lives and lowering mortality and disability rates in patients with sudden illnesses. Descriptive analyses of prehospital EMS response time and each component were conducted separately using ambulance trip data from the 120 Dispatch Command Centre in the main urban area of Chongqing in 2021, and then, logistic regression analyses were used to explore the influencing factors. The median prehospital EMS response time in the main urban area of Chongqing was 14.52 min and the mean was 16.14 min. A 44.89% of prehospital EMS response time exceeded 15 min. Response time was more likely to surpass this threshold during peak hours and in high population density areas. Conversely, lower probabilities exceeding 15 min were observed during the night shift, summer, and autumn seasons, and areas with a high density of emergency station. 33.28% of preparation time was >3 min, with the night shift and high population density areas more likely to be >3 min, while for the summer and autumn seasons, high Gross National Product (GDP) per capita areas had a lower likelihood of having preparation time >3 min. 45.52% of travel time was >11 min, with peak hours, summer and autumn, and high GDP per capita areas more likely to have had a travel time >11 min, while night shift and high emergency station density areas had a lower likelihood of travel time >11 min. The primary factors influencing prehospital EMS response time were shifts, traffic scenarios, seasons, GDP per capita, emergency station density, and population density. Relevant departments can devise effective interventions to reduce response time through resource allocation and department coordination, staff training and work arrangement optimisation, as well as public participation and education, thereby enhancing the efficiency of prehospital emergency medical services.

Global analysis of DNA methylation changes during experimented lingual carcinogenesis.

OBJECTIVES: This study aims to assess the role of DNA methylation changes in tongue cancer through a comprehensive analysis of global DNA methylation alterations during experimental lingual carcinogenesis. METHODS: C57BL/6J mice were subjected to 16-week oral administration of 4-nitroquinoline-1-oxide (4NQO, 50 mg/L). Lingual mucosa samples, being representative of normal tissue (week 0) and early (week 12) and advanced (week 28) tumorigenesis, were harvested for microarray and methylated DNA immunoprecipitation sequencing (MeDIP-Seq). The mRNA and promoter methylation of transforming growth factor-beta-signaling protein 1 (SMAD1) were evaluated with real-time quantitative reverse transcription polymerase chain reaction and Massarray in human lingual mucosa and tongue cancer cell lines. RESULTS: The cytosine guanine island (CGI) methylation level observed at 28 weeks surpassed that of both 12 weeks and 0 weeks. The promoter methylation level at 12 weeks exceeded that at 0 weeks. Notably, 208 differentially expressed genes were negatively correlated to differential methylation in promoters among 0, 12, and 28 weeks. The mRNA of SMAD1 was upregulated, concurrent with a decrease in promoter methylation levels in cell lines compared to normal mucosa. CONCLUSIONS: DNA methylation changed during lingual carcinogenesis. Overexpression of SMAD1 was correlated to promoter hypomethylation in tongue cancer cell lines.