NFKBIE is a predictive factor of survival and is correlated with immune infiltration and antigen processing and presentation in hepatocellular carcinoma.

The important role of the nuclear factor κB (NFκB) pathway in tumour development has long been recognized; however, the role of the NFκB inhibitor family in liver cancer has not been elucidated. Hepatocellular carcinoma (HCC) is a serious public health burden with a high incidence, poor prognosis, and early detection, especially in Asia, where hepatitis is prevalent. In the present study, the mRNA expression level of the NFκB inhibitor family was assessed in HCC and normal tissues using the Metabolic Gene Rapid Visualizer, University of Alabama at Birmingham Cancer Data Analysis Portal, and the Tumor Immune Estimation Resource database (TIMER). Survival curves of nuclear factor of κ light polypeptide gene enhancer in B-cells inhibitor (NFKBI)E were obtained using the Kaplan-Meier method. Genes co-expressed with NFKBIE in HCC samples were studied using data from the LinkedOmics and the Hepatocellular Carcinoma Databases. Protein-protein interaction networks, Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment pathway analyses were used to assess the NFKBIE mechanism in HCC. Using the TIMER database, the association between immune infiltration and NFKBIE was determined. RNA-sequencing (RNA-seq) was used to evaluate the function of NFKBIE in HCC and its impact on proliferation and migration. Western blotting was used to confirm the expression of NFKBIE in HCC cell lines. In addition, NFKBIE overexpression in HCC was demonstrated using tissue microarrays encompassing 80 pairs of HCC and normal liver tissues. NFKBIE was the only NFκB inhibitor with high expression and an improved prognosis in HCC compared with other NFκB inhibitors. NFKBIE was correlated with clinical characteristics, such as tumour grade, tumour protein P53 mutation status and tumour stage. Data obtained from Gene Set Cancer Analysis suggested that NFKBIE may inhibit the PI3K/AKT, RAS/MAPK, RTK and TSC/mTOR pathways. In addition, NFKBIE was significantly associated with B-cell immune infiltration and the RNA-seq data demonstrated that knockdown of NFKBIE significantly affected 'Antigen processing and presentation' and 'hepatocellular carcinoma' pathways. Immunohistochemistry of microarrays of tissue samples revealed that NFKBIE was overexpressed in several stages of HCC. Finally, inhibition of NFKBIE decreased the proliferation and migration of HCC cells. In conclusion, due to its prognostic value and overexpression in HCC, NFKBIE distinguished itself from other NFκB inhibitors. As such, it may provide a novel prognostic indicator and immunotherapeutic target for HCC.

Developing a modified textbook outcome for elderly patients with gastric cancer: a multi-center study.

OBJECTIVE: Textbook outcome (TO) is widely recognized as a comprehensive prognostic indication for patients with gastric cancer (GC). This study aims to develop a modified TO (mTO) for elderly patients with GC. METHODS: Data from the elderly patients (aged ≥ 65 years) in two Chinese tertiary referral hospitals were analyzed. 1389 patients from Fujian Medical University Union Hospital were assigned as the training cohort and 185 patients from Affiliated Hospital of Putian University as the validation cohort. Nomogram was developed by the independent prognostic factors of Overall Survival (OS) based on Cox regression. RESULTS: In the training cohort, laparoscopic surgery was significantly correlated with higher TO rate (P < 0.05). Cox regression analysis revealed that surgical approach was also an independent factor of OS (P < 0.001), distinct from the traditional TO. In light of these findings, TO parameters were enhanced by the inclusion of surgical approach, rendering a modified TO (mTO). Further analysis showed that mTO, tumor size, pTNM staging, and adjuvant chemotherapy were independent prognostic factors associated with OS (all P < 0.05). Additionally, the nomogram incorporating these four indicators accurately predicted 1-, 3-, and 5-year OS in the training cohort, with AUC values of 0.793, 0.814, and 0.807, respectively, and exhibited outstanding predictive performance within the validation cohort. CONCLUSION: mTO holds a robust association with the prognosis of elderly patients with GC, meriting intensified attention in efforts aimed at enhancing surgical quality. Furthermore, the predictive model incorporating mTO demonstrates excellent predictive performance for elderly patients with GC.

The lipid-metabolism enzyme ECI2 reduces neutrophil extracellular traps formation for colorectal cancer suppression.

Abnormalities in ether lipid metabolism as well as the formation of neutrophil extracellular traps have recently been recognized as detrimental factors affecting tumorigenesis and progression. However, the role of abnormal ether lipid metabolism in colorectal cancer (CRC) evolution has not been reported. Here we show that the lipid metabolism-related gene enoyl-CoA δ-isomerase 2 (ECI2) plays a tumor-suppressor role in CRC and is negatively associated with poor prognosis in CRC patients. We mechanistically demonstrate that ECI2 reduces ether lipid-mediated Interleukin 8 (IL-8) expression leading to decreased neutrophil recruitment and neutrophil extracellular traps formation for colorectal cancer suppression. In particular, ECI2 inhibits ether lipid production in CRC cells by inhibiting the peroxisomal localization of alkylglycerone phosphate synthase (AGPS), the rate-limiting enzyme for ether lipid synthesis. These findings not only deepen our understanding of the role of metabolic reprogramming and neutrophil interactions in the progression of CRC, but also provide ideas for identifying potential diagnostic markers and therapeutic targets for CRC.

Construction and anti-pancreatic cancer activity of selenium nanoparticles stabilized by Prunella vulgaris polysaccharide.

Selenium nanoparticles (SeNPs), as a potential cancer therapeutic agent, have attracted extensive attention due to their high anticancer activity and low toxicity. Polysaccharides could be the modifiers and stabilizers to improve the stability and dispersibility of SeNPs in aqueous solution. This study aimed to investigate the physicochemical characterization, stability, and anti-pancreatic cancer cell activities of SeNPs stabilized by a heteroxylan PVP3-1 extracted from the clusters of Prunella vulgaris Linn. Our results showed that PVP3-1 with Mw of 154 kDa was composed of →4)-ß-D-Xylp(1→, →2, 4)-ß-D-Xylp(1→, t-α-L-Araf(1→ and 4-MeO-α-D-GlcpA(1→. Red, zero-valent, and uniform spherical SeNPs with an average diameter of about 60 nm and high stability in aqueous solution were constructed successfully by polysaccharide PVP3-1. Anti-pancreatic cancer cell activity assays showed that PVP3-1-SeNPs could inhibit the proliferation and migration of pancreatic cancer cells in vitro. Furthermore, PVP3-1-SeNPs induced apoptosis and autophagy of pancreatic cancer cells through inhibiting mTOR signaling pathway. In conclusion, these results indicated that PVP3-1-SeNPs could be potential anti-tumor nanoparticles for treating pancreatic cancer.

Exploring structural features of sleep-enhancing peptides derived from casein hydrolysates by chemometrics and random forest methodology.

Milk casein is regarded as source to release potential sleep-enhancing peptides. Although various casein hydrolysates exhibited sleep-enhancing activity, the underlying reason remains unclear. This study firstly revealed the structural features of potential sleep-enhancing peptides from casein hydrolysates analyzed through peptidomics and multivariate analysis. Additionally, a random forest model and a potential Tyr-based peptide library were established, and then those peptides were quantified to facilitate rapidly-screening. Our findings indicated that YP-, YI/L, and YQ-type peptides with 4-10 amino acids contributed more to higher sleep-enhancing activity of casein hydrolysates, due to their crucial structural features and abundant numbers. Furthermore, three novel strong sleep-enhancing peptides, YQKFPQY, YPFPGPIPN, and YIPIQY were screened, and their activities were validated in vivo. Molecular docking results elucidated the importance of the YP/I/L/Q- structure at the N-terminus of casein peptides in forming crucial hydrogen bond and π-alkyl interactions with His-102 and Asn-60, respectively in the GABAA receptor for activation.

Hyperhomocysteine promotes cataract development through mTOR-mediated inhibition of autophagy and connexins expression.

AIM: Hyperhomocysteine has been recognized as an independent risk factor of multiple diseases, including several eye diseases. In this study, we aim to investigate whether increased homocysteine (Hcy) is related to cataracts, and to explore whether dysregulation of mTOR-mediated autophagy and connexin expression are underlying mechanisms. METHOD: We first developed a method of liquid chromatography tandem mass spectrometry to accurately measure serum concentrations of Hcy in 287 cataract patients and 334 healthy controls. Next, we treated human lens epithelial (HLC-B3) cells with Hcy at different concentrations and durations, and then analyzed expression of autophagy-related markers and connexins, as well as phosphorylated mTOR (p-mTOR) in these cells by Western blotting. Formation of autophagic vacuoles and intracellular Ca2+ in the Hcy-treated cells were observed by fluorescence microscopy. Further, we performed a rescue experiment in the Hcy-treated HLC-B3 cells by pre-incubation with rapamycin, an mTOR inhibitor. RESULTS: The serum levels of Hcy in patients with cataracts were significantly increased compared to those in healthy controls. In cultured HLC-B3 cells, expression of autophagy related markers (LC3B and Beclin1) and connexins (Cx43 and Cx50) was inhibited by Hcy treatment in a dose- and duration-dependent manner. Accumulation of Ca2+ in the Hcy-treated lens epithelial cells was observed as a consequence of reduced connexin expression. Meanwhile, expression of p-mTOR increased, representing up-regulation of the mTOR pathway. Importantly, inhibition of autophagy and connexin expression due to hyperhomocysteine was rescued via mTOR suppression by pretreatment with rapamycin in HLC-B3 cells. CONCLUSION: Our results demonstrate that hyperhomocysteine might promote cataract development through two mTOR-mediated pathways in the lens epithelial cells: 1) dysregulation of autophagy and 2) accumulation of intracellular calcium via decreased connexin expression.

The influence of peritumoral parenchyma on local tumor progression of hepatocellular carcinoma after thermal ablation: a retrospective multicenter study.

BACKGROUND: With the increasing importance of thermal ablation (TA) in hepatocellular carcinoma (HCC) treatment, local tumor progression (LTP) has become a nonignorable recurrence type after ablation. PURPOSES: To analyze the influence of peritumoral liver parenchyma on LTP and to explore the possible reasons for this influence. METHODS: Ablated HCCs with peritumoral parenchymal biopsy and ablation margins greater than 5 mm were included from two hospitals. The grade of necroinflammatory activity (G) and stage of fibrosis (S) of the parenchyma were evaluated by Scheuer staging system. Univariate/multivariate Cox model was used to analyze the possible factors influencing LTP. Peritumoral satellite focus rate, ablation energy, ablation volume after treatment, ablation volume after one-month, and volume reduction rate were collected and analyzed to explore the possible reasons for influence. Propensity score matching (PSM) was used to balance baselines across different groups. RESULTS: 346 HCCs (64 with LTP, 282 without LTP) were enrolled from January 2013 to June 2022, with a median follow-up of 27 months. Univariate/multivariate analysis showed fibrosis was a protective factor in LTP (OR = 0.70, 95%CI: 0.55-0.89). The low-fibrosis group exhibited higher satellite focus rate (15.6% vs. 8.4%, p = 0.048), lower ablation energy (22637 ± 9424 J vs. 33352 ± 13779 J, p < 0.001) and higher volume reduction rate (0.33 ± 0.06 vs. 0.25 ± 0.06, p < 0.001) than the high-fibrosis group. Therefore, we speculated that the protective effect of fibrosis was due to its blocking of tumor invasion and reduction of sublethal zones. CONCLUSION: Fibrosis of the peritumoral liver parenchyma is a stable protective factor in LTP occurrence.

The B-box transcription factor BnBBX22.A07 enhances salt stress tolerance by indirectly activating BnWRKY33.C03.

Salt stress has a detrimental impact on both plant growth and global crop yields. B-box proteins have emerged as pivotal players in plant growth and development regulation. Although the precise role of B-box proteins orchestrating salt stress responses in B. napus (Brassica napus) is not well understood in the current literature, further research and molecular explorations are required. Here, we isolated the B-box protein BnBBX22.A07 from B. napus. The overexpression of BnBBX22.A07 significantly improved the salt tolerance of Arabidopsis (Arabidopsis thaliana) and B. napus. Transcriptomic and histological analysis showed that BnBBX22.A07 enhanced the salt tolerance of B. napus by activating the expression of reactive oxygen species (ROS) scavenging-related genes and decreasing salt-induced superoxide anions and hydrogen peroxide. Moreover, BnBBX22.A07 interacted with BnHY5.C09, which specifically bound to and activated the promoter of BnWRKY33.C03. The presence of BnBBX22.A07 enhanced the activation of BnHY5.C09 on BnWRKY33.C03. Overexpression of BnHY5.C09 and BnWRKY33.C03 improved the salt tolerance of Arabidopsis. Functional analyses revealed that BnBBX22.A07-mediated salt tolerance was partly dependent on WRKY33. Taken together, we demonstrate that BnBBX22.A07 functions positively in salt responses not only by activating ROS scavenging-related genes but also by indirectly activating BnWRKY33.C03. Notably, our study offers a promising avenue for the identification of candidate genes that could be harnessed in breeding endeavours to develop salt-resistant transgenic crops.

A Prognostic Model Based on Nutritional Indexes for Patients With Pan-Cancer: A Real-World Cohort Study.

BACKGROUND: The aim was to identify the nutritional indexes, construct a prognostic model, and develop a nomogram for predicting individual survival probability in pan-cancers. METHODS: Nutritional indicators, clinicopathological characteristics, and previous major treatment details of the patients were collected. The enrolled patients were randomly divided into training and validation cohorts. Least absolute shrinkage and selection operator (Lasso) regression cross-validation was used to determine the variables to include in the cox regression model. The training cohort was used to build the prediction model, and the validation cohort was used to further verify the discrimination, calibration, and clinical effectiveness of the model. RESULTS: A total of 2020 patients were included. The median OS was 56.50 months (95% CI, 50.36-62.65 months). In the training cohort of 1425 patients, through Lasso regression cross-validation, 13 characteristics were included in the model. Cox proportional hazards model was developed and visualized as a nomogram. The C-indexes of the model for predicting 1-, 3-, 5-, and 10-year OS were 0.848, 0.826, 0.814, and 0.799 in the training cohort and 0.851, 0.819, 0.814, and 0.801 in the validation cohort. The model showed great calibration in the two cohorts. Patients with a score of less than 274.29 had a better prognosis (training cohort: HR, 6.932; 95% CI, 5.723-8.397; log-rank p < 0.001; validation cohort: HR, 8.429; 95% CI, 6.180-11.497; log-rank p < 0.001). CONCLUSION: The prognostic model based on the nutritional indexes of pan-cancer can divide patients into different survival risk groups and performed well in the validation cohort.

Metabolomics and network pharmacology exploration of the effects of bile acids on carotid atherosclerosis and potential underlying mechanisms.

Background: Bile acids (BAs), products of gut microbiota metabolism, have long been implicated in atherosclerotic disease pathogenesis. Characterizing the serum bile acid profile and exploring its potential role in carotid atherosclerosis (CAS) development are crucial tasks. Methods: In this study, we recruited 73 patients with CAS as the disease group and 77 healthy individuals as the control group. We systematically measured the serum concentrations of 15 bile acids using ultrahigh-performance liquid chromatography-mass spectrometry (UPLC-MS/MS). Multivariate logistic regression and least absolute shrinkage and selection operator (LASSO) regression were applied to analyze the impact of bile acids on the disease and select the key BAs. The possible molecular mechanism was elucidated by network pharmacology. Results: (1) The BA profile of patients with CAS significantly differed. (2) Multifactorial logistic regression analysis identified elevated levels of GCDCA (OR: 1.01, P < 0.001), DCA (OR: 1.01, P = 0.005), and TDCA (OR: 1.05, P = 0.002) as independent risk factors for CAS development. Conversely, GCA (OR: 0.99, P = 0.020), LCA (OR: 0.83, P = 0.002), and GUDCA (OR: 0.99, P = 0.003) were associated with protective effects against the disease. GCA, DCA, LCA, and TDCA were identified as the four key BAs. (3) TNF, FXR, GPBAR1, ESR1 and ACE were predicted to be targets of BAs against AS. These four BAs potentially impact AS progression by triggering signaling pathways, including cAMP, PPAR, and PI3K-AKT pathways, via their targets. Conclusion: This study offers valuable insights into potential therapeutic strategies for atherosclerosis that target bile acids.

A Comparative Study of the Stability, Transport, and Structure-Activity Relationship of Round Scad Derived Peptides with Antineuroinflammatory Ability.

Our previous study identified round scad neuroprotective peptides with different characteristics. However, the intrinsic relationship between their structure and bioactivity, as well as their bioavailability, remains unclear. The aim of this study is to elucidate the bioavailability of these peptides and their structure-activity relationship against neuroinflammation. Results showed that the SR and WCP peptides were resistant to gastrointestinal digestion. Additionally, peptides SR, WCP, and WCPF could transport Caco-2 monolayers as intact peptides. The permeability coefficients (Papp) of SR, WCP, and WCPF in Caco-2 monolayer were (1.53 ± 0.01) × 10-5, (2.12 ± 0.01) × 10-5, and (8.86 ± 0.03) × 10-7 cm/s, respectively. Peptides SR, WCP, and WCPF, as promising inhibitors of JAK2 and STAT3, could attenuate the levels of pro-inflammatory cytokines and regulate the NFκB and JAK2/STAT3 signaling pathway in LPS-treated BV-2 cells. WCPF exerted the highest anti-inflammatory activity. Moreover, bioinformatics, molecular docking, and quantum chemistry studies indicated that the bioactivity of SR was attributed to Arg, whereas those of WCP and WCPF were attributed to Trp. This study supports the application of round-scad peptides and deepens the understanding of the structure-activity relationship of neuroprotective peptides.

Regioselective Condensation Polymerization of Propargylic Electrophiles Enabled by Catalytic Element-Cupration.

Here, we report a set of new polymerization reactions enabled by the 1,2-regioselective hydro- and silylcupration of enyne-type propargylic electrophiles. Highly regioregular head-to-tail poly(2-butyne-1,4-diyl)s (HT-PBD), bearing either methyl or silylmethyl side chains, are synthesized for the first time. A rapid entry into carbon-rich copolymers with adjustable silicon content is developed via in situ monomer bifurcation. Furthermore, a one-pot polymerization/semireduction sequence is developed to access a cis-poly(butadiene)-derived backbone by a ligand swap on copper hydride species. Interestingly, borocupration, typically exhibiting identical regioselectivity with its hydro- and silyl analogues, seems to proceed in a 3,4-selective manner. Computational studies suggest the possible role of the propargylic leaving group in this selectivity switch. This work presents a new class of regioregular sp-carbon-rich polymers and meanwhile a novel approach to organosilicon materials.

Evaluation of the extended Japan NBI expert team classification of subtype 2B in laterally spreading colorectal tumors based on blue laser imaging.

OBJECTIVES: The Japan NBI Expert Team (JNET) classification has good diagnostic potential for colorectal diseases. We aimed to explore the diagnostic value of the JNET classification type 2B (JNET2B) criteria for colorectal laterally spreading tumors (LSTs) based on magnifying endoscopy with blue laser imaging (ME-BLI) examination. METHODS: Between January 2017 and June 2023, 218 patients who were diagnosed as having JNET2B-type LSTs using ME-BLI were included retrospectively. Endoscopic images were reinterpreted to categorize the LSTs as JNET2B-low (n = 178) and JNET2B-high (n = 53) LSTs. The JNET2B-low and JNET2B-high LSTs were compared based on their histopathological and morphological classifications. RESULTS: Among the 178 JNET2B-low LSTs, 86 (48.3%) were histopathologically classified as low-grade intraepithelial neoplasia, 54 (30.3%) as high-grade intraepithelial neoplasia (HGIN), 37 (20.8%) as intramucosal carcinoma (IMC), and one (0.6%) as superficial invasive submucosal carcinoma (SMC1). Among the 53 JNET2B-high LSTs, five (9.4%) were classified as HGIN, 28 (52.9%) as IMC, 15 (28.3%) as SMC1, and 5 (9.4%) as deep invasive submucosal carcinoma. There were significant differences in this histopathological classification between the two groups (P < 0.001). However, there was no significant difference between JNET2B-low and JNET2B-high LSTs based on their morphological classification (granular vs nongranular) or size (<20 mm vs ≥20 mm). Besides, the κ value for JNET2B subtyping was 0.698 (95% confidence interval 0.592-0.804) between the two endoscopists who reassessed the endoscopic images. CONCLUSION: The JNET2B subtyping of LSTs has a diagnostic potential in the preoperative setting, and may be valuable for treatment decision-making.

Comparative genomics of Tn6411 transposons carrying the blaIMP-1 gene in Pseudomonas aeruginosa.

We aimed to determine the molecular characteristics of carbapenem-resistant Pseudomonas aeruginosa strains 18081308 and 18083286, which were isolated from the urine and the sputum of two Chinese patients, respectively. Additionally, we conducted a comparative analysis between Tn6411 carrying blaIMP-1 in strain 18083286 and transposons from the same family available in GenBank. Bacterial genome sequencing was carried out on strains 18081308 and 18083286 to obtain their whole genome sequence. Average nucleotide identity (ANI) was used for their precise species identification. Serotyping and multilocus sequence typing were performed. Furthermore, the acquired drug resistance genes of these strains were identified. The carbapenem-resistant P. aeruginosa strains isolated in the present study were of sequence type ST865 and serotype O6. They all carried the same resistance genes (aacC2, tmrB, and blaIMP-1). Tn6411, a Tn7-like transposon carrying blaIMP-1, was found in strain 18083286 by single molecule real time (SMRT) sequencing. We also identified the presence of this transposon sequence in other chromosomes of P. aeruginosa and plasmids carried by Acinetobacter spp. in GenBank, indicating the necessity for heightening attention to the potential transferability of this transposon.

Nuclear factors NF-YC3 and NF-YBs positively regulate arbuscular mycorrhizal symbiosis in tomato.

The involvement of nuclear factor Y (NF-Y) in transcriptional reprogramming during arbuscular mycorrhizal symbiosis has been demonstrated in several plant species. However, a comprehensive picture is lacking. We showed that the spatial expression of NF-YC3 was observed in cortical cells containing arbuscules via the cis-regulatory element GCC boxes. Moreover, the NF-YC3 promoter was transactivated by the combination of CYCLOPS and autoactive calcium and calmodulin-dependent kinase (CCaMK) via GCC boxes. Knockdown of NF-YC3 significantly reduced the abundance of all intraradical fungal structures and affected arbuscule size. BCP1, SbtM1, and WRI5a, whose expression associated with NF-YC3 levels, might be downstream of NF-YC3. NF-YC3 interacted with NF-YB3a, NF-YB5c, or NF-YB3b, in yeast (Saccharomyces cerevisiae) and in planta, and interacted with NF-YA3a in yeast. Spatial expression of three NF-YBs was observed in all cell layers of roots under both mock and mycorrhizal conditions. Simultaneous knockdown of three NF-YBs, but not individually, reduced the fungal colonization level, suggesting that there might be functional redundancy of NF-YBs to regulate AM symbiosis. Collectively, our data suggest that NF-YC3 and NF-YBs positively regulate AM symbiosis in tomato, and arbuscule-related NF-YC3 may be an important downstream gene of the common symbiosis signaling pathway.

Overexpression of Nrf2 in bone marrow mesenchymal stem cells promotes B-cell acute lymphoblastic leukemia cells invasion and extramedullary organ infiltration through stimulation of the SDF-1/CXCR4 axis.

Background: Tumor microenvironment (TME) represents the key factor inducing leukemia development. As stromal cells within the leukemia microenvironment, Bone Marrow Mesenchymal Stem Cells (BM-MSCs) can trigger leukemia progression under certain conditions. As a critical transcription factor, nuclear factor erythroid related factor 2 (Nrf2) can modulate antioxidant response and antioxidant enzyme gene expression, and prevent various oxidative changes. We previously identified a novel mechanism by which Nrf2 promotes leukemia resistance, providing a potential therapeutic target for the treatment of drug-resistant/refractory leukemias. However, the role of Nrf2 in BM-MSCs from B-cell acute lymphoblastic leukemia (B-ALL) patients has not been clearly reported. The present work focused on investigating the effect of Nrf2 overexpression within MSCs on leukemia cell invasion, extramedullary infiltration and proliferation as well as its downstream pathway. Methods: Through clinical sample detection, in vitro cell experiments and in vivo animal experiments, the role of Nrf2 within MSCs within adult B-ALL cell migration and invasion and its potential molecular mechanism was explored through transcriptome sequencing analysis, RT-PCR, Western blot, cell migration, cell invasion, lentivirus transfection and other experiments. Results: Nrf2 was highly expressed in BM-MSCs from patients with B-ALL as well as in BM-MSCs co-cultured with leukemia cells. Overexpression of Nrf2 within MSCs significantly promoted leukemia cell migration, invasion and proliferation. The extramedullary organ infiltration rate in B-ALL model mice receiving the combined infusion of both cell types dramatically increased relative to that of leukemia cells alone, accompanied by the significantly shortened survival time. Mechanism study found that Nrf2 overexpression within MSCs promoted PI3K-AKT/ERK1/2 phosphorylation in the downstream pathway by activating SDF-1/CXCR4 axis, ultimately leading to extramedullary infiltration of leukemia cells. Conclusion: High Nrf2 expression with in MSCs enhances leukemia cell invasion and migration, which then accelerates infiltration in leukemic extramedullary organs. Targeting Nrf2 or inhibiting its downstream signal molecules may be the effective interventions for B-ALL patients treatment.

A Case of Gastric Thickening and a Large Ovarian Mass.

A 35-year-old female patient with hypothyroidism and Ehler-Danlos syndrome presents with fatigue, abdominal distension, and dyspnea. What is your diagnosis?

A gelatin methacryloyl (GelMA) treated with gallic acid and coated with specially designed nanoparticles derived from ginseng enhances the healing of wounds in diabetic rats.

Due to persistent inflammation and oxidative stress reactions, achieving drug absorption in diabetic wounds is challenging. To overcome this problem, our article presents a composite hydrogel, GelMA-GA/DMOG@GDNP, which consists of gelatin methacryloyl (GelMA) treated with gallic acid (GA) and encapsulating ginseng-derived nanoparticles (GDNPs) loaded with dimethyloxallyl glycine (DMOG). The composite hydrogel demonstrates excellent biocompatibility. In laboratory settings, the hydrogel inhibits the production of nitric oxide synthase 2 (iNOS) in mouse immune cells (RAW264.7 cells), enhances the growth and migration of mouse connective tissue cells (L929 cells) and human endothelial cells (HUVECs), and promotes tube formation in HUVECs. In a rat model of type 1 diabetes-induced wounds, the composite hydrogel attenuates inflammatory reactions, facilitates the formation of fibres and blood vessels, accelerates wound healing, and elucidates specific pathway mechanisms through transcriptome sequencing. Therefore, the GelMA-GA/DMOG@GDNP hydrogel can serve as a safe and efficient wound dressing to regulate the inflammatory response, promote collagen fiber and blood vessel formation, and accelerate wound healing. These findings suggest that utilizing this multifunctional engineered nanoparticle-loaded hydrogel in a clinical setting may be a promising strategy for diabetic wound healing.

In-hospital outcomes in metabolically healthy and unhealthy individuals over 65 years of age with obesity undergoing percutaneous intervention for acute coronary syndrome: A nationwide propensity-matched analysis (2016-2020).

Background: The obesity paradox in patients with coronary artery disease is well established, but the role of the metabolic syndrome associated with obesity is not well studied. Our study aims to evaluate the in-hospital outcomes of percutaneous coronary intervention (PCI) in metabolically healthy individuals with obesity (MHO) and metabolically unhealthy (MUHO) individuals with obesity over 65 years of age with acute coronary syndrome (ACS) between 2016 and 2020. Methods: This was a retrospective and observational study. Patients were identified through utilizing the National Inpatient Sample (NIS) Database (2016-2020) and ICD-10 codes. By employing a t-test and Pearson's Chi-square test, we assessed and contrasted the initial attributes, concurrent conditions, and results pertaining to all-cause mortality (ACM), cardiogenic shock (CS), length of stay (LOS), and hospitalization expense. Moreover, propensity score matching was conducted in a 1:1 ratio with respect to age, gender, and race. We also utilized multivariable logistic regression to compare MHO and MUHO in terms of the impact on all-cause mortality. Results: Out of a total of 135,395 patients identified, 2995 patients with MUHO were matched with 2995 MHO patients. Patients in the MUHO group had a higher prevalence of chronic pulmonary disease (24.9 % vs. 19.5 %), peripheral vascular disease (9.3 % vs. 6.7 %), hypothyroidism (16 % vs. 11.5 %), prior myocardial infarction (15.9 % vs. 6.2 %), and prior stroke (7.5 % vs. 2.8 %). Patients in the MHO group had a higher ACM (12.4 % vs. 2.8 %, p < 0.001), CS (18.55 % vs. 7 %, p < 0.001), stroke (2.2 % vs. 1 %, p < 0.001), ventricular assist device insertions (5.2 % vs. 2.7 %, p < 0.001), and IABP insertions (8.8 % vs. 3.8 %) compared to the MUHO cohort. Conclusion: Our study revealed an obesity paradox in individuals over 65 years of age undergoing PCI demonstrating worse outcomes, including higher in-hospital mortality, CS, stroke, Ventricular assist device and IABP insertion in MHO patients compared to the MUHO cohort.

The effect of social activities on the alienation and family resilience of Chinese caregivers for children with autism: a latent class analysis.

Introduction: Caregivers of children with autism spectrum disorder (ASD) in China often experience alienation due to societal stigma. While this alienation detrimentally impacts their mental well-being, family resilience serves as a protective factor. Previous research has predominantly examined the social support derived from social activities but has neglected to delve into the specific patterns of these activities. The primary objective of this study was twofold: firstly, to gain insights into the various social activities engaged in by caregivers of children with autism in China, and secondly, to ascertain the influence of these social activities on alienation and family resilience. Methods: Between June and August 2023, a cross-sectional survey was carried out across multiple cities in Jilin Province, aiming to gather data from a total of 205 Chinese caregivers of children with autism. Data collection was conducted through the utilization of a structured questionnaire. The assessment of social activity involved the completion of 12 questionnaires, while alienation was evaluated using the Generalized Alienation Scale (GSAS), and family resilience was gauged through the Chinese version of the Family Resilience Scale (FaRE). The classification of social activities was conducted through latent class analysis (LCA), while the impact of these social activities on alienation and family resilience was examined using linear regression analysis. Results: The findings revealed that social activities can be categorized into five types (Low, Self-Recreation, Communication, Web Surfing, High). Communication social activities were found to reduce family resilience(ß=.332, p<0.01), while high social activities were associated with reduced alienation(ß=-.349, p<0.05) and increased family resilience(ß=.417, p<0.01). Conclusion: Supporting these particular types of social activities has the potential to reduce alienation and bolster family resilience among caregivers for children with autism in China.