Precise Synthesis of Diastereomers of Spiro-oxindole Derivatives through Dynamic Covalent Transformation.

In this study, [1+2+2] cyclization of tryptamine-derived isocyanides with 3-ylideneoxindoles was systematically investigated. A series of structurally complex spiro-oxindole derivatives were obtained. Characteristic dynamic covalent chemistry was observed and confirmed by experiments and density functional theory calculation. Through the regulation of the solvent, temperature, and time, the precise and stereodivergent synthesis of spiro-oxindoles was achieved.

Governing cross-border healthcare in mainland China: a scoping review of national policies from 2002 to 2022.

This study reviews national-level policies regulating cross-border healthcare in mainland China after it acceded to the World Trade Organization (WTO). Policy documents from official websites of the State Council and 19 ministries were screened, from which 487 policy documents were analyzed. WTO's five modes of trade and WHO's six building blocks of healthcare system were used to guide the analysis of policymaking patterns, charting of policy evolution process, identification of key policy areas, differentiation of 29 detailed policy themes, and identification of major countries/regions involved in cross-border healthcare. The findings lead to four policy recommendations: (1) to establish a national-level committee to govern cross-border healthcare, (2) to build an information system to comprehensively integrate various information on cross-border healthcare consumption and provision, (3) to take more proactive policy actions in healthcare internationalization, and (4) to carry out reform experiments in key sub-national regions to fully explore various possibilities in developing and regulating cross-border healthcare.

A rare malignant mesothelioma of the tunica vaginalis testis: A case report.

Malignant mesothelioma of the tunica vaginalis testis is a rare, highly invasive urogenital malignant tumor with no specific clinical manifestations. Reported cases of this disease are limited. Therefore, an early preoperative diagnosis is difficult. The current study presents a case of malignant mesothelioma of the tunica vaginalis testis and a literature review. A 52-year-old man was admitted to Xiaoshan Affiliated Hospital of Wenzhou Medical University (Hangzhou, China) in December 2022 and underwent radical resection of the right testicle and epididymis but did not undergo radiotherapy or chemotherapy. The patient was followed up for 5 months, and no recurrence or metastasis was found. The rarity of testicular mesothelioma poses a challenge to its etiology and diagnosis, which is rarely achieved preoperatively. Malignant mesothelioma of the testicular tunica vaginalis has a poor prognosis and is not sensitive to radiotherapy or chemotherapy, requiring close postoperative follow-up. This condition is rare in clinical practice; therefore, it needs to be reported to aid clinicians' decision-making regarding diagnosis and treatment.

Insights into Molecular Diversity within the FUS/EWS/TAF15 Protein Family: Unraveling Phase Separation of the N-Terminal Low-Complexity Domain from RNA-Binding Protein EWS.

The FET protein family, comprising FUS, EWS, and TAF15, plays crucial roles in mRNA maturation, transcriptional regulation, and DNA damage response. Clinically, they are linked to Ewing family tumors and neurodegenerative diseases such as amyotrophic lateral sclerosis. The fusion protein EWS::FLI1, the causative mutation of Ewing sarcoma, arises from a genomic translocation that fuses a portion of the low-complexity domain (LCD) of EWS (EWSLCD) with the DNA binding domain of the ETS transcription factor FLI1. This fusion protein modifies transcriptional programs and disrupts native EWS functions, such as splicing. The exact role of the intrinsically disordered EWSLCD remains a topic of active investigation, but its ability to phase separate and form biomolecular condensates is believed to be central to EWS::FLI1's oncogenic properties. Here, we used paramagnetic relaxation enhancement NMR, microscopy, and all-atom molecular dynamics (MD) simulations to better understand the self-association and phase separation tendencies of the EWSLCD. Our NMR data and mutational analysis suggest that a higher density and proximity of tyrosine residues amplify the likelihood of condensate formation. MD simulations revealed that the tyrosine-rich termini exhibit compact conformations with unique contact networks and provided critical input on the relationship between contacts formed within a single molecule (intramolecular) and inside the condensed phase (intermolecular). These findings enhance our understanding of FET proteins' condensate-forming capabilities and underline differences between EWS, FUS, and TAF15.

Can 18F-FES PET Improve the Evaluation of 18F-FDG PET in Patients With Metastatic Invasive Lobular Carcinoma?

PURPOSE: Invasive lobular carcinoma (ILC) exhibits a low affinity for 18F-FDG. The estrogen receptor (ER) is commonly expressed in ILCs, suggesting a potential benefit of targeting with the ER probe 18F-FES in this patient population. The objective of this study was to evaluate the diagnostic performance of 18F-FES imaging in patients with metastatic ILC and compare it with that of 18F-FDG. METHODS: We conducted a retrospective analysis of 20 ILC patients who underwent concurrent 18F-FES and 18F-FDG PET/CT examinations in our center. 18F-FES and 18F-FDG imaging were analyzed to determine the total count of tracer-avid lesions in nonbone sites and their corresponding organ systems, assess the extent of anatomical regions involved in bone metastases, and measure the SUVmax values for both tracers. RESULTS: Among 20 ILC patients, 65 nonbone lesions were found to be distributed in 13 patients, and 16 patients were diagnosed with bone metastasis, which was distributed in 54 skeletal anatomical regions. The detection rate of 18F-FDG in nonbone lesions was higher than that of 18F-FES (57 vs 37, P < 0.001). 18F-FES demonstrated a superior ability to detect nonbone lesions in 4 patients, whereas 18F-FDG was superior in 5 patients (P > 0.05). Among 9/16 patients with bone metastasis, 18F-FES demonstrated a significant advantage in the detection of bone lesions compared with 18F-FDG (P = 0.05). Furthermore, patients with only 18F-FES-positive lesions (12/12) were administered endocrine regimens, whereas patients lacking 18F-FES uptake (2/3) predominantly received chemotherapy. CONCLUSIONS: 18F-FES is more effective than 18F-FDG in detecting bone metastasis in ILC, but it does not demonstrate a significant advantage in nonbone lesions. Additionally, the results of examination with 18F-FES have the potential to guide patient treatment plans.

Heterogeneity of Multiple Pancreatic Neuroendocrine Tumors Identified by 68Ga-DOTANOC and 68Ga-exendin-4 PET/CT in a Patient with Endogenous Hyperinsulinemic Hypoglycemia and Multiple Endocrine Neoplasia 1.

Insulinomas are the most frequent functional neuroendocrine tumors of pancreas. In about 10% cases, insulinomas are associated with hereditary syndrome including multiple endocrine neoplasia 1 (MEN1). Herein, we presented a case of 44-year-old female with recurrent hypoglycemia. In December 1998, this patient has undergone resection of two pancreatic lesions due to hypoglycemia and diagnosed as insulinoma. After operation, the symptom of hypoglycemia disappeared. However, from 2021, hypoglycemic symptoms reappeared frequently and even coma. In June 2023, enhanced CT showed multiple pancreatic lesions abundant with blood supply. Fasting serum blood glucose and insulin were 1.73mmol/L and 15.2U/L (2.6-11.8U/L). Germline genes suggested MEN1 pathogenic mutations. 68Ga-DOTANOC PET/CT indicated there were multiple lesions located in the pancreas and duodenum with high expression of somatostatin receptor (SSTR). 68Ga-exendin-4 PET/CT were added to localize the insulinoma. Most lesions with high expression of SSTR in body and tail of pancreas manifested part of them with high uptake of 68Ga-exendin-4, and an additional lesion with high expression of glucagon-like peptide 1 receptor was only detected by 68Ga-exendin-4 PET/CT. It showed highly heterogeneity. From the distal pancreatectomy, a total 5 tumors were found in the body and tail of pancreas, which were diagnosed as neuroendocrine tumors (NETs). After the operation, all the symptoms related to hypoglycemia disappeared. Immunohistochemical results of SSTR2 and insulin were consistent with the imaging finding of dual tracer PET/CT. From this case, combination of 68Ga-DOTANOC and 68Ga-exendin-4 PET/CT was recommended in the patients of MEN1 and insulinoma to estimate the heterogeneity of multiple neuroendocrine tumors that contributing to detect all the NET lesions and locate the tumors with secretion of insulin.

The clinical implication and translational research of OSCC differentiation.

BACKGROUND: The clinical value and molecular characteristics of tumor differentiation in oral squamous cell carcinoma (OSCC) remain unclear. There is a lack of a related molecular classification prediction system based on pathological images for precision medicine. METHODS: Integration of epidemiology, genomics, experiments, and deep learning to clarify the clinical value and molecular characteristics, and develop a novel OSCC molecular classification prediction system. RESULTS: Large-scale epidemiology data (n = 118,817) demonstrated OSCC differentiation was a significant prognosis indicator (p < 0.001), and well-differentiated OSCC was more chemo-resistant than poorly differentiated OSCC. These results were confirmed in the TCGA database and in vitro. Furthermore, we found chemo-resistant related pathways and cell cycle-related pathways were up-regulated in well- and poorly differentiated OSCC, respectively. Based on the characteristics of OSCC differentiation, a molecular grade of OSCC was obtained and combined with pathological images to establish a novel prediction system through deep learning, named ShuffleNetV2-based Molecular Grade of OSCC (SMGO). Importantly, our independent multi-center cohort of OSCC (n = 340) confirmed the high accuracy of SMGO. CONCLUSIONS: OSCC differentiation was a significant indicator of prognosis and chemotherapy selection. Importantly, SMGO could be an indispensable reference for OSCC differentiation and assist the decision-making of chemotherapy.

68Ga-FAPI PET imaging monitors response to combined TGF-ßR inhibition and immunotherapy in metastatic colorectal cancer.

BACKGROUNDImproving and predicting tumor response to immunotherapy remains challenging. Combination therapy with a transforming growth factor-ß receptor (TGF-ßR) inhibitor that targets cancer-associated fibroblasts (CAFs) is promising for the enhancement of efficacy of immunotherapies. However, the effect of this approach in clinical trials is limited, requiring in vivo methods to better assess tumor responses to combination therapy.METHODSWe measured CAFs in vivo using the 68Ga-labeled fibroblast activation protein inhibitor-04 (68Ga-FAPI-04) for PET/CT imaging to guide the combination of TGF-ß inhibition and immunotherapy. One hundred thirty-one patients with metastatic colorectal cancer (CRC) underwent 68Ga-FAPI and 18F-fluorodeoxyglucose (18F-FDG) PET/CT imaging. The relationship between uptake of 68Ga-FAPI and tumor immunity was analyzed in patients. Mouse cohorts of metastatic CRC were treated with the TGF-ßR inhibitor combined with KN046, which blocks programmed death ligand 1 (PD-L1) and CTLA-4, followed by 68Ga-FAPI and 18F-FDG micro-PET/CT imaging to assess tumor responses.RESULTSPatients with metastatic CRC demonstrated high uptake rates of 68Ga-FAPI, along with suppressive tumor immunity and poor prognosis. The TGF-ßR inhibitor enhanced tumor-infiltrating T cells and significantly sensitized metastatic CRC to KN046. 68Ga-FAPI PET/CT imaging accurately monitored the dynamic changes of CAFs and tumor response to combined the TGF-ßR inhibitor with immunotherapy.CONCLUSION68Ga-FAPI PET/CT imaging is powerful in assessing tumor immunity and the response to immunotherapy in metastatic CRC. This study supports future clinical application of 68Ga-FAPI PET/CT to guide precise TGF-ß inhibition plus immunotherapy in CRC patients, recommending 68Ga-FAPI and 18F-FDG dual PET/CT for CRC management.TRIAL REGISTRATIONCFFSTS Trial, ChiCTR2100053984, Chinese Clinical Trial Registry.FUNDINGNational Natural Science Foundation of China (82072695, 32270767, 82272035, 81972260).

Adequate nutrient intake mitigate the toxic effects of bromate on the rotifer Brachionus calyciflorus.

Bromate is receiving increased attention as a typical disinfection by-product in aquatic environments, but bromate toxicity tests on invertebrate such as Brachionus calyciflorus rotifer are inadequate. In the present study, the long-term toxicity tests on B. calyciflorus were performed during 21 days under the exposure of different bromate concentrations and two algal density conditions. Furthermore, we evaluated the feeding behaviors of the rotifers under the impact of bromate. The maximum population density of rotifers was significantly reduced at 100 and 200 mg/L bromate exposure at the two algal density conditions. However, we observed that the maximum population density and population growth rate of rotifers were higher at 3.0 × 106 cells/mL algal density than those at 1.0 × 106 cells/mL under the same conditions of bromate exposure. These results suggest that higher food density may have alleviated the negative effects of bromate on rotifers. Meanwhile, the ingestion rate at an algal density of 3.0 × 106 cells/mL was higher than that at 1.0 × 106 cells/mL. The present study provides a basic reference to comprehensively evaluate the toxic effects of bromate on aquatic organisms.

Imaging of Tumor Stroma Using 68Ga-FAPI PET/CT to Improve Diagnostic Accuracy of Primary Tumors in Head and Neck Cancer of Unknown Primary: A Comparative Imaging Trial.

The low detection rate of primary tumors by current diagnostic techniques remains a major concern for patients with head and neck cancer of unknown primary (HNCUP). Therefore, in this study, we aimed to investigate the potential role of 68Ga-labeled fibroblast activation protein inhibitor (68Ga-FAPI) PET/CT compared with 18F-FDG PET/CT for the detection of primary tumors of HNCUP. Methods: In this prospective comparative imaging trial conducted at Fudan University Shanghai Cancer Center, 91 patients with negative or equivocal findings of a primary tumor by comprehensive clinical examination and conventional imaging were enrolled from June 2020 to September 2022. The presence of a primary tumor was recorded by 3 experienced nuclear medicine physicians. Primary lesions were validated by histopathologic analysis and a composite reference standard. Results: Of the 91 patients (18 women, 73 men; median age, 60 y; age range, 24-76 y), primary tumors were detected in 46 (51%) patients after a thorough diagnostic work-up. 68Ga-FAPI PET/CT detected more primary lesions than 18F-FDG PET/CT (46 vs. 17, P < 0.001) and showed better sensitivity, positive predictive value, and accuracy in locating primary tumors (51% vs. 25%, 98% vs. 43%, and 51% vs. 19%, respectively). Furthermore, 68Ga-FAPI PET/CT led to treatment changes in 22 of 91 (24%) patients compared with 18F-FDG PET/CT. The Kaplan-Meier curve illustrated that patients with unidentified primary tumors had a significantly worse prognosis than patients with identified primary tumors (hazard ratio, 5.77; 95% CI, 1.86-17.94; P = 0.0097). Conclusion: 68Ga-FAPI PET/CT outperforms 18F-FDG PET/CT in detecting primary lesions and could serve as a sensitive, reliable, and reproducible imaging modality for HNCUP patients.

Preclinical Evaluation and a Pilot Clinical Positron Emission Tomography Imaging Study of [68Ga]Ga-FAPI-FUSCC-II.

Fibroblast activation protein (FAP), a type II integral membrane serine protease, is a promising target for tumor diagnosis and therapy. OncoFAP has been recently discovered for PET imaging procedures for various solid malignancies. In this study, we presented the development of manual radiolabeling procedures for the preparation of OncoFAP-based radiopharmaceuticals for cancer imaging. A novel series of [68Ga/177Lu]Ga/Lu-FAPI-FUSCC-I/II were produced with high radiochemical yields. [68Ga]Ga-FAPI-FUSCC-I/II and [177Lu]Lu-FAPI-FUSCC-I/II were stable in phosphate-buffered saline, fetal bovine serum, and human serum for at least 3 h. In vitro cellular uptake and blocking experiments implied that they had specificity to FAP. Additionally, the low nanomolar IC50 values of FAPI-FUSCC-II indicated that it had a high target affinity to FAP. The in vivo biodistribution and blocking study in mice bearing HT-1080-FAP tumors showed that both exhibited specific tumor uptake. [68Ga]Ga-FAPI-FUSCC-II showed a higher tumor uptake and a higher tumor/nontarget ratio than [68Ga]Ga-FAPI-FUSCC-I and [68Ga]Ga-FAPI-04. The results of ex vivo biodistribution were in accordance with the biodistribution results. Clinical [68Ga]Ga-FAPI-FUSCC-II-PET/CT imaging further demonstrated its favorable biodistribution and kinetics with elevated and reliable uptake by primary tumors (maximum standardized uptake value (SUVmax), 12.17 ± 6.67) and distant metastases (SUVmax, 9.24 ± 4.28). In summary, [68Ga]Ga-FAPI-FUSCC-II displayed increased tumor uptake and retention compared to [68Ga]Ga-FAPI-04, giving it potential as a promising tracer for the diagnostic imaging of malignant tumors with positive FAP expression.

Optimizing backwash control using data on seasonal changes in the invertebrate community of granular activated carbon filters.

Problems associated with the colonization and leakage of invertebrates in the granular activated carbon (GAC) filters of waterworks have received increased attention in recent years. To study the effect of environmental factors and water quality on invertebrate abundances, and the backwash control for minimizing invertebrate abundance. A survey of the invertebrate community of GAC filters was carried out monthly from March 2021 to May 2022. A pilot-scale GAC system established in the laboratory alongside a lake, with a volume of 35.3 L. 45 invertebrate species were detected, and 40 of these were rotifers. Significant variation in abundance was observed among seasons before and after GAC filtration, the average invertebrate abundance in the inlet water was 11.1 times that in the filtrate. The GAC filter contained invertebrates that might be responsible for the large number of organisms in the filtrate. Invertebrate abundance in the GAC filter decreased gradually with the carbon layer depth, which the mean invertebrate abundances were 6,926, 5,232, and 3818 ind./kg in the top layer (TL), middle layer (ML), and bottom layer (BL), respectively. Invertebrate abundance was correlated with water temperature and varied seasonally. Among eight water quality parameters, chlorophyll a (Chla) and the total plate count (TPC) were most significantly correlated with invertebrate abundance. According to the statistical modeling and the optimization process of response surface methodology (RSM). The predicted optimal values were a flow rate of 6.36 L/h, a backwash cycle of 3.26 d, and a backwash intensity of 14.97 L/(m2·s) for a minimum invertebrate abundance of 3013 ind./kg in the GAC filter. To maintain invertebrate abundance within an acceptable range, some of these measures might need to be modified depending on the actual conditions.

Differentiation of cancer of unknown primary and lymphoma in head and neck metastatic poorly differentiated cancer using 18 F-FDG PET/CT tumor metabolic heterogeneity index.

OBJECTIVE: To explore the value of 18 F-FDG PET/CT tumor metabolic heterogeneity index (HI) and establish and validate a nomogram model for distinguishing head and neck cancer of unknown primary (HNCUP) from lymphoma with head and neck metastatic poorly differentiated cancer. METHODS: This retrospective analysis was conducted on 1242 patients with cervical metastatic poorly differentiated cancer. 108 patients, who were clinically and pathologically confirmed as HNCUP or lymphoma, were finally enrolled. Two independent sample t-tests and χ 2 test were used to compare the clinical and imaging features. Binary logistic regression was used to screen for independent predictive factors. RESULTS: Among the 108 patients), 65 patients were diagnosed with HNCUP and 43 were lymphoma. Gender ( P  = 0.001), SUV max ( P  < 0.001), SUV mean ( P  < 0.001), TLG ( P  = 0.012), and HI ( P  < 0.001) had statistical significance in distinguishing HNCUP and lymphoma. Female ( OR  = 4.546, P  = 0.003) and patients with HI ≥ 2.37 ( OR  = 3.461, P  = 0.047) were more likely to be diagnosed as lymphoma. CONCLUSION: For patients with cervical metastatic poorly differentiated cancer, gender and HI were independent predictors of pathological type. For such patients, clinical attention should be paid to avoid misdiagnosing lymphoma as HNCUP, which may delay treatment.

Integrated Metabolomic and Transcriptomic Analyses Reveal the Potential Regulation of Flavonoids in the Production of Embryogenic Cultures during Early Somatic Embryogenesis of Longan (Dimocarpus longan Lour.).

Embryogenic cultures of longan (Dimocarpus longan Lour.) contain various metabolites with pharmacological properties that may function in the regulation of somatic embryogenesis (SE). In this study, based on widely targeted metabolomics, 501 metabolites were obtained from the embryogenic calli, incomplete compact proembryogenic cultures, and globular embryos during early SE of longan, among which 41 flavonoids were differentially accumulated during the SE. Using RNA sequencing, 36 flavonoid-biosynthesis-related genes and 43 MYB and 52 bHLH transcription factors were identified as differentially expressed genes. Furthermore, Kyoto Encyclopedia of Genes and Genomes enrichment analysis revealed that the flavonoid metabolism-related pathways were significantly enriched during the early SE. These results suggested that the changes in flavonoid levels in the embryogenic cultures of longan were mediated by MYBs and bHLHs via regulating flavonoid-biosynthesis-related genes, thus potentially regulating early SE. The identified metabolites in the embryogenic cultures of longan can be used to develop pharmaceutical ingredients.

Insights into Molecular Diversity within the FET Family: Unraveling Phase Separation of the N-Terminal Low Complexity Domain from RNA-Binding Protein EWS.

The FET family proteins, which includes FUS, EWS, and TAF15, are RNA chaperones instrumental in processes such as mRNA maturation, transcriptional regulation, and the DNA damage response. These proteins have clinical significance: chromosomal rearrangements in FET proteins are implicated in Ewing family tumors and related sarcomas. Furthermore, point mutations in FUS and TAF15 are associated with neurodegenerative conditions like amyotrophic lateral sclerosis and frontotemporal lobar dementia. The fusion protein EWS::FLI1, the causative mutation of Ewing sarcoma, arises from a genomic translocation that fuses the low-complexity domain (LCD) of EWS (EWSLCD) with the DNA binding domain of the ETS transcription factor FLI1. This fusion not only alters transcriptional programs but also hinders native EWS functions like splicing. However, the precise function of the intrinsically disordered EWSLCD is still a topic of active investigation. Due to its flexible nature, EWSLCD can form transient interactions with itself and other biomolecules, leading to the formation of biomolecular condensates through phase separation - a mechanism thought to be central to the oncogenicity of EWS::FLI1. In our study, we used paramagnetic relaxation enhancement NMR, analytical ultracentrifugation, light microscopy, and all-atom molecular dynamics (MD) simulations to better understand the self-association and phase separation tendencies of EWSLCD. Our aim was to elucidate the molecular events that underpin EWSLCD-mediated biomolecular condensation. Our NMR data suggest tyrosine residues primarily drive the interactions vital for EWSLCD phase separation. Moreover, a higher density and proximity of tyrosine residues amplify the likelihood of condensate formation. Atomistic MD simulations and hydrodynamic experiments revealed that the tyrosine-rich N and C-termini tend to populate compact conformations, establishing unique contact networks, that are connected by a predominantly extended, tyrosine-depleted, linker region. MD simulations provide critical input on the relationship between contacts formed within a single molecule (intramolecular) and inside the condensed phase (intermolecular), and changes in protein conformations upon condensation. These results offer deeper insights into the condensate-forming abilities of the FET proteins and highlights unique structural and functional nuances between EWS and its counterparts, FUS and TAF15.

Risk factors for lower extremity deep vein thrombosis in acute stroke patients following endovascular thrombectomy: a retrospective cohort study.

Background: Deep vein thrombosis (DVT) in lower extremities as a common complication of acute ischemic stroke (AIS) has long been studied. However, as the therapeutic options for AIS continue to advance, the pathogenic mechanisms behind DVT may change. Endovascular thrombectomy (EVT) has replaced intravenous thrombolysis and become the preferred treatment for AIS patients with large vessel occlusions. Therefore, it is important to update our understanding of DVT and its management. This study aimed to determine the prevalence and risk factors of DVT in AIS patients following EVT. Methods: In this retrospective study, 245 AIS patients who had received EVT were recruited between January 2020 and December 2021. Within 10 days (median 4 days) of thrombectomy, DVT was diagnosed by ultrasonography. Demographic characteristics, clinical findings, and therapeutic procedures were compared between patients with and without DVT using univariate analysis. Cutoff points were defined for EVT time and plasma D-dimer concentration. Multivariable logistic regression was then used to determine the independent risk factors for DVT and evaluate their predictive power. Results: The prevalence of DVT in AIS patients after EVT was 27.3%. Multifactorial logistic regression analysis showed that age (OR 1.036, 95% CI 1.001-1.073; P = 0.045), female sex (OR 3.015, 95% CI 1.446-6.289; P = 0.003), lower limb muscle strength less than grade three (OR 7.015, 95% CI 1.887-26.080; P = 0.004), longer EVT time (OR 1.012, 95% CI 1.004-1.020; P = 0.003), and higher D-dimer levels (OR 1.350, 95% CI 1.150-1.585; P < 0.001) were independently associated with higher DVT risk in AIS patients following EVT. The cutoff points for operative time of EVT and plasma D-dimer were 65.5 min and 1.62 mg/L, respectively, above which the risk for DVT was dramatically increased with OR > 4 in AIS patients. Conclusion: AIS patients are at increased risk of developing DVT following EVT particularly if they have undergone prolonged thrombectomy procedures and exhibit high plasma levels of D-dimers. However, the results of our study need to be validated by a multicenter prospective study with a larger population of stroke patients.

Coupling-Spirocyclization Cascade of Tryptamine-Derived Isocyanides with Iodonium Ylides and Despirocyclization Reactions.

A cobalt(II)-catalyzed coupling-cyclization cascade reaction between tryptamine-derived isocyanides and iodonium ylides is investigated, which allowed for the synthesis of different types of spiroindoline compounds by variation of substituents at the N1- and C2-positions in the indole skeleton. More interesting is that the spiroindoline products could undergo despirocyclization in the presence of amines, enabling efficient construction of enamine compounds.

Knowledge and awareness of viral hepatitis and influencing factors among the general population aged 15-69 years in Zhejiang Province, China.

This study aimed to determine the level of viral hepatitis knowledge as well as the self-awareness of hepatitis B virus surface antigen (HBsAg) positive individuals, to provide data support for the next steps in viral hepatitis prevention and control. We conducted a cross-sectional survey to assess the knowledge of viral hepatitis among the general population aged 15-69 years in Zhejiang Province, China. A total of 3,626 individuals were surveyed with 10 questions. The knowledge level of the participants is reflected by the scores from the survey. Adequate knowledge was defined as a score of ≥ 6. The knowledge rate was defined as the ratio of the number of individuals with adequate knowledge to the total number of individuals. The knowledge rate of viral hepatitis among the general population aged 15-69 years in Zhejiang Province was 52.34% (mean score, 5.23). The majority of participants (52.51%) had adequate knowledge of viral hepatitis. Multiple logistic regression analysis showed that medical staff had the best knowledge of viral hepatitis, followed by individuals with university or higher education, those aged 40-49 years, and those with a history of hepatitis B vaccination. 34.16% of HBsAg positive participants were aware of their infection status before. The mean score of knowledge of viral hepatitis was significantly lower among HBsAg-positive than HBsAg-negative individuals. Knowledge of viral hepatitis in Zhejiang Province was still low, especially among HBsAg-positive individuals with no awareness of their infection status. More effort should be needed to improve public awareness of viral hepatitis.

A simple and efficient strategy for cell-based and cell-free-based therapies in acute liver failure: hUCMSCs bioartificial liver.

Acute liver failure (ALF) is a life-threatening condition. Cell-based and cell-free-based therapies have proven to be effective in treating ALF; however, their clinical application is limited by cell tumorigenicity and extracellular vesicle (EV) isolation in large doses. Here, we explored the effectiveness and mechanism of umbilical cord mesenchymal stem cells (hUCMSCs)-based bioartificial liver (hUCMSC-BAL), which is a simple and efficient strategy for ALF. D-galactosamine-based pig and mouse ALF models were used to explore the effectiveness of hUCMSC-BAL and hUCMSC-sEV therapies. Furthermore, high-throughput sequencing, miRNA transcriptome analysis, and western blot were performed to clarify whether the miR-139-5p/PDE4D axis plays a critical role in the ALF model in vivo and in vitro. hUCMSC-BAL significantly reduced inflammatory responses and cell apoptosis. hUCMSC-sEV significantly improved liver function in ALF mice and enhanced the regeneration of liver cells. Furthermore, hUCMSC-sEV miRNA transcriptome analysis showed that miR-139-5p had the highest expression and that PDE4D was one of its main target genes. The sEV miR-139-5p/PDE4D axis played a role in the treatment of ALF by inhibiting cell apoptosis. Our data indicate that hUCMSC-BAL can inhibit cytokine storms and cell apoptosis through the sEV miR-139-5p/PDE4D axis. Therefore, we propose hUCMSC-BAL as a therapeutic strategy for patients with early ALF.