ABSTRACT
The widespread use of microplastics and their harmful effects on the environment have emerged as serious concerns. However, the effect of microplastics on the immune system of mammals, particularly their offspring, has received little attention. In this study, polystyrene microplastics (PS-MPs) were orally administered to male mice during lactation. Flow cytometry was used to assess the immune cells in the spleens of both adult male mice and their offspring. The results showed that mice exposed to PS-MPs exhibited an increase in spleen weight and an elevated number of B and regulatory T cells (Tregs), irrespective of dosage. Furthermore, the F1 male offspring of the PS-MPs-exposed group had enlarged spleens; an increased number of B cells, T helper cells (Th cells), and Tregs; and an elevated ratio of T helper cells 17 (Th17 cells) to Tregs and T helper cells 1 (Th1 cells) to T helper cells 2 (Th2 cells). These results suggested a pro-inflammatory state in the spleen. In contrast, in the F1 female offspring exposed to PS-MPs, the changes in splenic immune cells were less pronounced. In the F2 generation of mice with exposed to PS-MPs, minimal alterations were observed in spleen immune cells and morphology. In conclusion, our study demonstrated that exposure to real human doses of PS-MPs during lactation in male mice altered the immune status, which can be passed on to F1 offspring but is not inherited across generations.
ABSTRACT
Treatments of inflammatory bowel disease (IBD) are diverse, but their efficacy is limited, and it is therefore urgent to find better therapies. Controlling mucosal inflammation is a must in IBD drug treatment. The occurrence of anti-tumor necrosis factor α (TNF-α) monoclonal antibodies has provided a safer and more efficacious therapy. However, this kind of treatment still faces failure in the form of loss of response. ß-Carboline alkaloids own an anti-inflammatory pharmacological activity. While Kumujan B contains ß-carboline, its biological activity remains unknown. In this study, we attempted to determine the anti-inflammatory effects of Kumujan B using both the TNF-α- induced in vitro inflammation and DSS-induced in vivo murine IBD models. Our data show that Kumujan B attenuated the expression of interleukin 1ß (IL-1ß) and interleukin 6 (IL-6) induced by TNF-α in mouse peritoneal macrophages. Kumujan B suppressed c-Jun N-terminal protein kinases (JNK) signaling, especially c-Jun, for anti-inflammatory response. Furthermore, Kumujan B promoted K11-linked ubiquitination and degradation of c-Jun through the proteasome pathway. In an in vivo study, Kumujan B inhibited the expression of IL-1ß, IL-6, and TNF-α and improved the colon barrier function in dextran sulfate sodium salt (DSS)-induced experimental mice colitis. Kumujan B exhibited in vivo and in vitro anti-inflammatory effects, making it a potential therapeutic candidate for treating IBD.
ABSTRACT
Transcatheter arterial embolization (TAE) in interventional therapy and tumor embolism therapy plays a significant role. The choice of embolic materials that have good biocompatibility is an essential component of TAE. For this study, we produced a multifunctional PVA embolization material that can simultaneously encapsulate Ag2S quantum dots (Ag2S QDs) and BaSO4 nanoparticles (BaSO4 NPs), exhibiting excellent second near-infrared window (NIR-II) fluorescence imaging and X-ray imaging, breaking through the limitations of traditional embolic microsphere X-ray imaging. To improve the therapeutic effectiveness against tumors, we doped the doxorubicin (DOX) antitumor drug into microspheres and combined it with a clotting peptide (RADA16-I) on the surface of microspheres. Thus, it not only embolizes rapidly during hemostasis but also continues to release and accelerate tumor necrosis. In addition, Ag2S/BaSO4/PVA microspheres (Ag2S/BaSO4/PVA Ms) exhibited good blood compatibility and biocompatibility, and the results of embolization experiments on renal arteries in rabbits revealed good embolic effects and bimodal imaging stability. Therefore, they could serve as a promising medication delivery embolic system and an efficient biomaterial for arterial embolization. Our research work achieves the applicability of NIR-II and X-ray dual-mode images for clinical embolization in biomedical imaging.
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Immunosenescence, the aging of the immune system, leads to functional deficiencies, particularly in T cells, which undergo significant changes. While numerous studies have investigated age-related T-cell phenotypes in healthy aging, senescent T cells have also been observed in younger populations during pathological conditions like cancer. This review summarizes the recent advancements in age-associated alterations and markers of T cells, mechanisms, and the relationship between senescent T cells and the tumor microenvironment. We also discuss potential strategies for targeting senescent T cells to prevent age-related diseases and enhance tumor immunotherapy efficacy.
ABSTRACT
Acute pancreatitis (AP) is a common disease caused by a variety of causes. Is uric acid associated with the onset of AP? The objective of this study was to assess whether uric acid concentration in AP patients was higher than that in healthy population, and whether there were associations between uric acid concentration and serological indicators related to AP. A total of 205 AP patients were included in this study. Two hundred and five people who underwent physical examination in our hospital were randomly selected as controls. We analyzed whether there was difference in uric acid concentrations between the two groups. If the difference was statistically significant, the correlations between uric acid concentration and serological indicators in AP patients was further analyzed. There was significant difference in uric acid concentration (P < 0.001) between AP patients and healthy population. Serum uric acid concentration in AP group was significantly higher than that in control group. Two hundred and five AP patients were divided into mild AP group and non-mild AP group. There was no statistically significant difference in uric acid concentration between the two groups (P = 0.176). There was a low linear correlation between serum uric acid concentration and triglyceride level (r = 0.316, P < 0.001). But there was no linear correlation between serum uric acid concentration and hypersensitive C-reactive protein (r = 0.126, P = 0.072), white blood cell (r = 0.192, P = 0.006), albumin (r = 0.183, P = 0.009), total cholesterol concentration (r = 0.133, P = 0.058), fasting blood-glucose (r = 0.133, P = 0.058) and blood calcium (r = 0.155, P = 0.026). Uric acid concentration in patients with AP was significantly higher than healthy population. There was correlation between uric acid concentration and triglyceride in AP patients.
Subject(s)
Pancreatitis , Uric Acid , Humans , Uric Acid/blood , Male , Female , Middle Aged , Pancreatitis/blood , Pancreatitis/diagnosis , Adult , Case-Control Studies , C-Reactive Protein/metabolism , C-Reactive Protein/analysis , Aged , Triglycerides/blood , Acute Disease , Biomarkers/bloodABSTRACT
BACKGROUND AND PURPOSE: Previous studies have suggested that music listening has the potential to positively affect cognitive functions and mood in individuals with post-stroke cognitive impairment (PSCI), with a preference for self-selected music likely to yield better outcomes. However, there is insufficient clinical evidence to suggest the use of music listening in routine rehabilitation care to treat PSCI. This randomized control trial (RCT) aims to investigate the effects of personalized music listening on mood improvement, activities of daily living (ADLs), and cognitive functions in individuals with PSCI. MATERIALS AND METHODS: A total of 34 patients with PSCI were randomly assigned to either the music group or the control group. Patients in the music group underwent a three-month personalized music-listening intervention. The intervention involved listening to a personalized playlist tailored to each individual's cultural, ethnic, and social background, life experiences, and personal music preferences. In contrast, the control group patients listened to white noise as a placebo. Cognitive function, neurological function, mood, and ADLs were assessed. RESULTS: After three months of treatment, the music group showed significantly higher Montreal Cognitive Assessment (MoCA) scores compared to the control group (p=0.027), particularly in the domains of delayed recall (p=0.019) and orientation (p=0.023). Moreover, the music group demonstrated significantly better scores in National Institutes of Health Stroke Scale (NIHSS) (p=0.008), Barthel Index (BI) (p=0.019), and Zarit Caregiver Burden Interview (ZBI) (p=0.008) compared to the control group. No effects were found on mood as measured by the Hamilton Anxiety Rating Scale (HAMA) and the Hamilton Depression Rating Scale (HAMD). CONCLUSION: Personalized music listening promotes the recovery of cognitive and neurological functions, improves ADLs, and reduces caregiver burden in patients with PSCI.
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The soft-shell clam Mya japonica (Jay, 1857) is a commercially important fishery resource. In this study, we identified the complete mitochondrial genome of M. japonica and performed a phylogenetic analysis to explore its genetic relationship with Mya arenaria. The genome is 21,396 bp in length and contains 13 protein-coding genes (PCGs), 23 transfer RNA genes (tRNAs), 2 ribosomal RNA genes (rRNAs), and 5 D-Loop control regions. The atp8 gene was annotated in Myidae for the first time. Notably, the genome contains an additional trnM, consistent with M. arenaria. The length of the cox2 gene is 1,947 bp, which is 513 bp longer than that in M. arenaria. Its base composition is 29.14% A, 37.26% T, 10.89% C, and 22.71% G. Phylogenetic analysis based on 12 PCGs and 2 rRNAs indicates that M. japonica and M. arenaria form a sister group. In this study, the identification and phylogenetic analysis of the complete mitochondrial genome of M. japonica provide significant information for future taxonomic and evolutionary research of the genus Mya.
ABSTRACT
Chromatin structure plays a critical role in the regulation of dynamic gene expression in response to different developmental and environmental cues, but as yet their involvement in fruit ripening is not well understood. Here, we profile seven histone modifications in the woodland strawberry (Fragaria vesca) genome and analyze the histone modification signatures during ripening. Collectively, segments painted by the seven marks cover ~85% of the woodland strawberry genome. We report an eight-state chromatin structure model of the woodland strawberry based on the above histone marks, which reveals a diverse chromatin environment closely associated with transcriptional apparatus. Upon this model we build a chromatin-centric annotation to the strawberry genome. Expression of many genes essential for fruit ripening, such as abscisic acid catabolism, anthocyanin accumulation and fruit softening, are associated with shifts of active genic states and polycomb-associated chromatin states. Particularly, the expression levels of ripening-related genes are well correlated with histone acetylation, indicating a regulatory role of histone acetylation in strawberry ripening. Our identification of the chromatin states underpinning genome expression during fruit ripening not only elucidates the coordination of different pathways of morphological and metabolic development but also provides a framework to understand the signals that regulate fruit ripening.
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Adjacent vertebral fracture (AVF) is a serious complication of percutaneous vertebroplasty (PVP) or kyphoplasty (PKP) for osteoporotic vertebral compression fracture (OVCF). This study aimed to explore the incidence and risk factors of AVF following PVP or PKP in postmenopausal women. The incidence of AVF was determined by spinal radiographic examinations. The potential risk factors of AVF were identified by univariate analysis, followed by multivariate logistic regression analyses to determine the independent risk factors. In total, 674 postmenopausal women who were treated with PVP or PKP from December 2019 to February 2022 were enrolled in the study. Among them, 58 (8.61%) women experienced an AVF following PVP or PKP. After adjusting for confounding factors, BMI (OR [95% CI] 0.863 [0.781-0.952]; p = 0.003), previous history of OVCF (OR [95% CI] 1.931 [1.044-3.571]; p = 0.036), and Hounsfield unit (HU) value (OR [95% CI] 0.979 [0.967-0.990]; p < 0.001) were found to be independent risk factors of AVF following PVP or PKP in postmenopausal women. The ROC analysis revealed that the BMI and HU thresholds were 21.43 and 65.15, respectively. In conclusion, the incidence of AVF was 8.61%. BMI, previous history of OVCF and HU value were independent risk factors of AVF following PVP or PKP in postmenopausal women.
Subject(s)
Kyphoplasty , Osteoporotic Fractures , Postmenopause , Spinal Fractures , Vertebroplasty , Humans , Female , Spinal Fractures/surgery , Spinal Fractures/epidemiology , Spinal Fractures/etiology , Risk Factors , Aged , Kyphoplasty/adverse effects , Kyphoplasty/methods , Incidence , Retrospective Studies , Vertebroplasty/adverse effects , Middle Aged , Osteoporotic Fractures/surgery , Osteoporotic Fractures/epidemiology , Osteoporotic Fractures/etiology , Fractures, Compression/surgery , Fractures, Compression/epidemiology , Fractures, Compression/etiology , Aged, 80 and overABSTRACT
OBJECTIVE: Colorectal cancer (CRC) is a form of malignancy that exhibits a comparatively elevated occurrence and fatality rate. Given the relatively slower progress in diagnostic and therapeutic approaches for CRC, there is a need to investigate more accurate and efficient biomarkers. METHODS: Core regulatory genes were screened using the TCGA database, and the expression of neurexophilin 4 (NXPH4) and its prognostic implications were validated using tissue microarray staining. The assessment of NXPH4 functions involved a range of experiments, including cellular, organoid, and murine models. Furthermore, a regulatory network between m5C, NXPH4, and HIF1A was established through several in vitro experiments. RESULTS: The overexpression of NXPH4 is associated with unfavorable prognoses in patients with CRC and hepatocellular carcinoma. Additionally, it facilitates the progression of malignant tumors both in laboratory settings and in living organisms of colorectal carcinoma. Our research also reveals that NXPH4 mRNA can avoid degradation through RNautophagy, relying on an m5C-dependent mechanism. Moreover, NXPH4 amplifies the HIF signaling pathway and stabilizes HIF1A by competitively binding to PHD4. CONCLUSIONS: NXPH4, regulated by m5C, promotes malignant tumor progression and regulates the HIF pathway. Consequently, targeting NXPH4 through molecular therapies could potentially serve as an efficacious therapeutic strategy for the management of CRC exhibiting elevated NXPH4 expression.
Subject(s)
Colorectal Neoplasms , Gene Expression Regulation, Neoplastic , Hypoxia-Inducible Factor 1, alpha Subunit , Colorectal Neoplasms/metabolism , Colorectal Neoplasms/genetics , Colorectal Neoplasms/pathology , Humans , Hypoxia-Inducible Factor 1, alpha Subunit/metabolism , Hypoxia-Inducible Factor 1, alpha Subunit/genetics , Animals , Mice , Cell Line, Tumor , Prognosis , Mice, Nude , Proteolysis , Signal Transduction , Cell Proliferation/genetics , Mice, Inbred BALB CABSTRACT
OBJECTIVES: The prothrombin (PT) G20210A mutation is one of the most prevalent genetic variations associated with an increased susceptibility to the first episode of venous thromboembolism (VTE). However, it remains uncertain whether this inherited thrombophilic abnormality also poses a risk for recurrent VTE. This meta-analysis aimed to assess the relation of PT G20210A mutation to the risk of recurrent VTE. METHODS: PubMed and Scopus were systematically searched for pertinent prospective studies. Relative risks (RR) and 95% confidence intervals (CI) were used to test the association. Sixteen studies, with 16,174 participants, were included. RESULTS: Carriers of the G20210A mutation were at increased risk of recurrent VTE (RR=1.60, 95%CI=1.20-2.14), compared to noncarriers; the increased risk was observed in heterozygotes (GA vs. GG) (RR=1.79, 95%CI=1.24-2.57), but not in GA/AA mutation. CONCLUSIONS: This association was found to be significant in the long term (≥5 years of follow-up), but not in the short-term (<5 years of follow-up).
ABSTRACT
Over the decades, the management of osteochondral lesions remains a significant yet unmet medical challenge without curative solutions to date. Owing to the complex nature of osteochondral units with multi-tissues and multicellularity, and inherently divergent cellular turnover capacities, current clinical practices often fall short of robust and satisfactory repair efficacy. Alternative strategies, particularly tissue engineering assisted with biomaterial scaffolds, achieve considerable advances, with the emerging pursuit of a more cost-effective approach of in situ osteochondral regeneration, as evolving toward cell-free modalities. By leveraging endogenous cell sources and innate regenerative potential facilitated with instructive scaffolds, promising results are anticipated and being evidenced. Accordingly, a paradigm shift is occurring in scaffold development, from biodegradable and biocompatible to bioadaptable in spatiotemporal control. Hence, this review summarizes the ongoing progress in deploying bioadaptable criteria for scaffold-based engineering in endogenous osteochondral repair, with emphases on precise control over the scaffolding material, degradation, structure and biomechanics, and surface and biointerfacial characteristics, alongside their distinguished impact on the outcomes. Future outlooks of a highlight on advanced, frontier materials, technologies, and tools tailoring precision medicine and smart healthcare are provided, which potentially paves the path toward the ultimate goal of complete osteochondral regeneration with function restoration.
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The CRISPR/Cas9 system has shown great potential for treating human genetic diseases through gene therapy. However, there are concerns about the safety of this system, specifically related to the use of guide-free Cas9. Previous studies have shown that guide-free Cas9 can induce genomic instability in vitro. However, the in vivo safety risks associated with guide-free Cas9 have not been evaluated, which is necessary for the development of gene therapy in clinical settings. In this study, we used doxycycline-inducible Cas9-expressing pigs to evaluate the safety risks of guide-free Cas9 in vivo. Our findings demonstrated that expression of guide-free Cas9 could induce genomic damages and transcriptome changes in vivo. The severity of the genomic damages and transcriptome changes were correlate with the expression levels of Cas9 protein. Moreover, prolonged expression of Cas9 in pigs led to abnormal phenotypes, including a significant decrease in body weight, which may be attributable to genomic damage-induced nutritional absorption and metabolic dysfunction. Furthermore, we observed an increase in whole-genome and tumor driver gene mutations in pigs with long-term Cas9 expression, raising the risk of tumor occurrence. Our in vivo evaluation of guide-free Cas9 in pigs highlights the necessity of considering and monitoring the detrimental effects of Cas9 alone as genome editing via the CRISPR/Cas9 system is implemented in clinical gene therapy. This research emphasizes the importance of further study and implementation of safety measures to ensure the successful and safe application of the CRISPR/Cas9 system in clinical practice.
Subject(s)
CRISPR-Associated Protein 9 , CRISPR-Cas Systems , Gene Editing , Animals , Swine , CRISPR-Cas Systems/genetics , CRISPR-Associated Protein 9/genetics , CRISPR-Associated Protein 9/metabolism , RNA, Guide, CRISPR-Cas Systems/genetics , Humans , Genetic TherapyABSTRACT
The lack of diagnostic markers limits the window of effectiveness for rheumatoid arthritis (RA) therapies. Here, we isolated exosomes of serum samples from four distinct groups RA patients, according to disease activity and with/without medication. Then, total RNA of exosomes was extracted for whole-transcriptome sequencing. Focusing on lncRNA sequencing, gene ontology (GO) and kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analyses were performed. We found that the number of upregulated lncRNAs were significantly higher than that of downregulated lncRNAs in each four RA groups. And most importantly, we identified two specific lncRNAs from differentially expressed lncRNAs, TCONS_I2_00013502 (up-regulated) and ENST00000363624 (down-regulated) in RA. Receiver Operating Characteristic (ROC) curve analysis showed that the two lncRNAs were promising biomarkers for RA diagnosis. These findings highlight lncRNAs of the serum exosome are important biomarkers and provide application potential for diagnosis of RA.
Subject(s)
Arthritis, Rheumatoid , Biomarkers , Exosomes , RNA, Long Noncoding , Arthritis, Rheumatoid/diagnosis , Arthritis, Rheumatoid/genetics , Arthritis, Rheumatoid/blood , Humans , RNA, Long Noncoding/blood , RNA, Long Noncoding/genetics , Exosomes/genetics , Exosomes/metabolism , Biomarkers/blood , Female , Male , Middle Aged , Gene Expression Profiling , Adult , ROC Curve , AgedABSTRACT
Minimally invasive percutaneous nephrolithotomy (mini-PCNL) maintains a stone clearance rate similar to standard PCNL while reducing blood loss. Bleeding is a complex and serious complication that can arise after PCNL surgery. Pseudoaneurysm (PA) is an uncommon type of delayed bleeding problem, which affects less than 1% of patients after PCNL. The most effective treatment for severe post-PCNL hemorrhage is super-selective renal angiographic embolization (SRAE), but it can fail in some patients and require additional surgical intervention. This report details the case of a male patient, 55 years old, who experienced severe bleeding four times and had three SRAE procedures and one laparoscopic procedure after PCNL. The presence of a renal artery pseudoaneurysm was not initially identified during the first two attempts of angiography due to arterial spasm and a small, undeveloped lesion. This case report is intended to enhance awareness of tiny pseudoaneurysms, emphasizing the importance of avoiding oversight to improve the success rate of embolization.
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Background: Previous observational studies have shown a correlation between leisure sedentary behaviors (LSB) and physical activity (PA) with the incidence of obstructive sleep apnea (OSA). However, the causal associations remain unknown. Therefore, our study used bidirectional two-sample Mendelian randomization (MR) to identify potential causal relationships between LSB/PA and OSA. Methods: We sourced genetic variation data for LSB and PA from the UK Biobank, while data on OSA were collected from the FinnGen study. The primary analysis method employed was the inverse variance weighted (IVW) approach, complemented by the weighted median and MR-Egger methods. For sensitivity analyses, we conducted Cochran's Q test, the MR-Egger intercept test, the MR-PRESSO global test, and the leave-one-out analysis. Results: IVW analyses showed that genetically predicted leisure television watching (odds ratio [OR] = 1.38, 95% confidence interval [CI] = 1.09-1.75, p = 0.007) and computer use (OR = 1.48, 95% CI = 1.15-1.92, p = 0.002) significantly increased the risk of OSA. Conversely, self-reported vigorous physical activity (VPA) (OR = 0.33, 95% CI = 0.11-0.98, p = 0.046) may reduce the risk of OSA. No causal effects on OSA risk were observed for driving or self-reported moderate-to-vigorous physical activity. Furthermore, the reverse MR analysis indicated no significant causal relationship between OSA and any LSB/PA phenotype. Sensitivity tests showed no significant heterogeneity or horizontal pleiotropy. Conclusion: This study suggests that leisurely television watching and computer use are risk factors for OSA, while VPA may be a protective factor. Additionally, OSA does not affect PA or LSB levels. We recommend reducing sedentary activities, particularly television watching and computer use, and prioritizing VPA to reduce the risk of OSA. Further research in diverse populations and settings is needed to validate these findings.
Subject(s)
Exercise , Leisure Activities , Mendelian Randomization Analysis , Sedentary Behavior , Sleep Apnea, Obstructive , Humans , Sleep Apnea, Obstructive/genetics , Sleep Apnea, Obstructive/epidemiology , Male , Female , Middle Aged , Risk Factors , Causality , United Kingdom/epidemiology , Adult , AgedABSTRACT
BACKGROUND: Epithelial cell adhesion molecule (EpCAM) has been widely studied as a tumor antigen due to its expression in varieties of solid tumors. Moreover, the glycoprotein contributes to critical cancer-associated cellular functionalities via its extracellular (EpEX) and intracellular (EpICD) domains. In colorectal cancer (CRC), EpCAM has been implicated in the Wnt signaling pathway, as EpICD and ß-Catenin are coordinately translocated to the nucleus. Once in the nucleus, EpICD transcriptionally regulates EpCAM target genes that; however, remains unclear whether Wnt signaling is modulated by EpICD activity. METHODS: Patient-derived organoids (PDOs), patient-derived xenografts (PDXs), and various CRC cell lines were used to study the roles of EpCAM and EpICD in Wnt receptor expression. Fluorescence and confocal microscopy were used to analyze tumors isolated from PDX and other xenograft models as well as CRC cell lines. EpCAM signaling was intervened with our humanized form of EpCAM neutralizing antibody, hEpAb2-6. Wnt receptor promoters under luciferase reporters were constructed to examine the effects of EpICD. Luciferase reporter assays were performed to evaluate promoter, γ-secretase and Wnt activity. Functional assays including in vivo tumor formation, organoid formation, spheroid and colony formation experiments were performed to study Wnt related phenomena. The therapeutic potential of EpCAM suppression by hEpAb2-6 was evaluated in xenograft and orthotopic models of human CRC. RESULTS: EpICD interacted with the promoters of Wnt receptors (FZD6 and LRP5/6) thus upregulated their transcriptional activity inducing Wnt signaling. Furthermore, activation of Wnt-pathway-associated kinases in the ß-Catenin destruction complex (GSK3ß and CK1) induced γ-secretase activity to augment EpICD shedding, establishing a positive-feedback loop. Our hEpAb2-6 antibody blocked EpICD-mediated upregulation of Wnt receptor expressions and conferred therapeutic benefits in both PDX and orthotopic models of human CRC. CONCLUSIONS: This study uncovers relevant functions of EpCAM where Wnt receptors are upregulated via the transcriptional co-factor activity of EpICD. The resultant enhancement of Wnt signaling induces γ-secretase activity further stimulating EpICD cleavage and its nuclear translocation. Our humanized anti-EpCAM antibody hEpAb2-6 blocks these mechanisms and may thereby provide therapeutic benefit in CRC.
Subject(s)
Colorectal Neoplasms , Epithelial Cell Adhesion Molecule , Wnt Signaling Pathway , Humans , Colorectal Neoplasms/metabolism , Colorectal Neoplasms/genetics , Epithelial Cell Adhesion Molecule/metabolism , Epithelial Cell Adhesion Molecule/genetics , Mice , Animals , Cell Line, Tumor , Disease ProgressionABSTRACT
BACKGROUND: The optimal extent of lymphadenectomy in esophageal squamous cell carcinoma (ESCC) patients remained debatable. AIM: To explore the ideal number of cleared lymph nodes in ESCC patients undergoing upfront surgery. METHODS: In this retrospective, propensity score-matched study, we included 1042 ESCC patients who underwent esophagectomy from November 2008 and October 2019. Patients who underwent neoadjuvant therapy were excluded. We collected patients' clinicopathological features and information regarding lymph nodes, including the total number of resected lymph nodes (NRLN), and pathologically diagnosed positive lymph nodes (RPLN). SPSS and R software were used for statistical analysis. RESULTS: Among the included 1042 patients, two cohorts: ≤ 21 (n = 664) and > 21 NRLN (n = 378) were identified. The final prognostic model included four variables: T stage, N, venous thrombus, and the number of removed lymph nodes. Among them, NRLN > 21 was determined as an independent prognosticator after surgery for esophageal cancer (hazards regression = 0.66, 95% confidence interval: 0.50-0.87, P = 0.004). A nomogram was created based on the regression coefficients of the variables in the final model. In the training cohort, the predictive model displayed an uncorrected five-year overall survival C-index of 0.659, with a bootstrap-corrected C-index of 0.654. In the subgroup analysis, adjuvant chemotherapy was beneficial in the subgroup with NRLN > 21 and RPLN ≤ 0.16 and NRLN ≤ 21 and RPLN > 0.16. CONCLUSION: NRLN > 21 was an independent prognostic factor after ESCC surgery. The combination of NRLN and RPLN may provide a reference for adjuvant chemotherapy use in potential beneficiaries.
ABSTRACT
Aqueous zinc-iodine (Zn-I2) batteries hold potential for large-scale energy storage but struggle with shuttle effects of I2 cathodes and poor reversibility of Zn anodes. Here, an interfacial gelation strategy is proposed to suppress the shuttle effects and improve the Zn reversibility simultaneously by introducing silk protein (SP) additive. The SP can migrate bidirectionally toward cathode and anode interfaces driven by the periodically switched electric field direction during charging/discharging. For I2 cathodes, the interaction between SP and polyiodides forms gelatinous precipitate to avoid the polyiodide dissolution, evidenced by excellent electrochemical performance, including high specific capacity and Coulombic efficiency (CE) (215 mAh g-1 and 99.5% at 1 C), excellent rate performance (≈170 mAh g-1 at 50 C), and extended durability (6000 cycles at 10 C). For Zn anodes, gelatinous SP serves as protective layer to boost the Zn reversibility (99.7% average CE at 2 mA cm-2) and suppress dendrites. Consequently, a 500 mAh Zn-I2 pouch cell with high-loading cathode (37.5 mgiodine cm-2) and high-utilization Zn anode (20%) achieves remarkable energy density (80 Wh kg-1) and long-term durability (>1000 cycles). These findings underscore the simultaneous modulation of both cathode and anode and demonstrate the potential for practical applications of Zn-I2 batteries.
ABSTRACT
The development of high-performance biodegradable polylactic acid (PLA) materials integrating high strength, malleability and toughness is desired but an ongoing challenge. In this work, a novel full-biobased block copolymer was designed and synthesized by grafting L (+)-lactide (L-LA) and ε-caprolactone (ε-CL) onto lignin via ring-opening polymerization. The obtained lignin-PLA-PCL block copolymer was composed of rigid lignin and poly (LA-CL) rubber segment, could self-assemble into uniform nano-micelles with average diameters of 80-100 nm regulated by simply altering copolymer content. The incorporation of lignin-PLA-PCL copolymers into PLA matrix induced the formation of many cavities, promoted free volume between PLA matrix and copolymer to accelerate chain mobility, achieving excellent ductility and stretchability with maximum stretching deformation of 64.8 %. The resultant PLA composites with the copolymer content as low as 5 wt% displayed simultaneously improved strength (41.84 MPa) and toughness (8.1 MJ/m3), 6.7 % and 1520 % increment than those of neat PLA, respectively. The reinforcing and toughening mechanisms were explored and verified that the combination of cavity growth and fibrillation, followed by extensive shear yielding of matrix, causing substantial plastic deformation. This study extended the design strategy and the foundation for simultaneous reinforcing and toughening PLA plastics using lignin-derived rubbery micelles.