Assessing the structural stability and drug encapsulation efficiency of poly(ethylene glycol)-poly(L-lactic acid) nanoparticles loaded with atorvastatin calcium: Based on dissipative particle dynamics.

Block polymer micelles have been proven highly biocompatible and effective in improving drug utilization for delivering atorvastatin calcium. Therefore, it is of great significance to measure the stability of drug-loading nano micelles from the perspective of block polymer molecular sequence design, which would provide theoretical guidance for subsequent clinical applications. This study aims to investigate the structural stability of drug-loading micelles formed by two diblock/triblock polymers with various block sequences through coarse-grained dissipative particle dynamics (DPD) simulations. From the perspectives of the binding strength of poly(L-lactic acid) (PLLA) and polyethylene glycol (PEG) in nanoparticles, hydrophilic bead surface coverage, and the morphological alteration of nanoparticles induced by shear force, the ratio of hydrophilic/hydrophobic sequence length has been observed to affect the stability of nanoparticles. We have found that for diblock polymers, PEG3kda-PLLA2kda has the best stability (corresponding hydrophilic coverage ratio is 0.832), while PEG4kda-PLLA5kda has the worst (coverage ratio 0.578). For triblock polymers, PEG4kda-PLLA2kda-PEG4kda has the best stability (0.838), while PEG4kda-PLLA5kda-PEG4kda possesses the worst performance (0.731), and the average performance on stability is better than nanoparticles composed of diblock polymers.

Predicting prostate cancer recurrence: Introducing PCRPS, an advanced online web server.

Background: Prostate cancer (PCa) is one of the leading causes of cancer death in men. About 30% of PCa will develop a biochemical recurrence (BCR) following initial treatment, which significantly contributes to prostate cancer-related deaths. In clinical practice, accurate prediction of PCa recurrence is crucial for making informed treatment decisions. However, the development of reliable models and biomarkers for predicting PCa recurrence remains a challenge. In this study, the aim is to establish an effective and reliable tool for predicting the recurrence of PCa. Methods: We systematically screened and analyzed potential datasets to predict PCa recurrence. Through quality control analysis, low-quality datasets were removed. Using meta-analysis, differential expression analysis, and feature selection, we identified key genes associated with recurrence. We also evaluated 22 previously published signatures for PCa recurrence prediction. To assess prediction performance, we employed nine machine learning algorithms. We compared the predictive capabilities of models constructed using clinical variables, expression data, and their combinations. Subsequently, we implemented these machine learning models into a user-friendly web server freely accessible to all researchers. Results: Based on transcriptomic data derived from eight multicenter studies consisting of 733 PCa patients, we screened 23 highly influential genes for predicting prostate cancer recurrence. These genes were used to construct the Prostate Cancer Recurrence Prediction Signature (PCRPS). By comparing with 22 published signatures and four important clinicopathological features, the PCRPS exhibited a robust and significantly improved predictive capability. Among the tested algorithms, Random Forest demonstrated the highest AUC value of 0.72 in predicting PCa recurrence in the testing dataset. To facilitate access and usage of these machine learning models by all researchers and clinicians, we also developed an online web server (https://urology1926.shinyapps.io/PCRPS/) where the PCRPS model can be freely utilized. The tool can also be used to (1) predict the PCa recurrence by clinical information or expression data with high accuracy. (2) provide the possibility of PCa recurrence by nine machine learning algorithms. Furthermore, using the PCRPS scores, we predicted the sensitivity of 22 drugs from GDSC2 and 95 drugs from CTRP2 to the samples. These predictions provide valuable insights into potential drug sensitivities related to the PCRPS score groups. Conclusion: Overall, our study provides an attractive tool to further guide the clinical management and individualized treatment for PCa.

Psoralen and Isopsoralen, Two Estrogen-Like Natural Products from Psoraleae Fructus, Induced Cholestasis via Activation of ERK1/2.

With the increasing use of oral contraceptives and estrogen replacement therapy, the incidence of estrogen-induced cholestasis (EC) has tended to rise. Psoralen (P) and isopsoralen (IP) are the major bioactive components in Psoraleae Fructus, and their estrogen-like activities have already been recognized. Recent studies have also reported that ERK1/2 plays a critical role in EC in mice. This study aimed to investigate whether P and IP induce EC and reveal specific mechanisms. It was found that P and IP increased the expression of esr1, cyp19a1b and the levels of E2 and VTG at 80 µM in zebrafish larvae. Exemestane (Exe), an aromatase antagonist, blocked estrogen-like activities of P and IP. At the same time, P and IP induced cholestatic hepatotoxicity in zebrafish larvae with increasing liver fluorescence areas and bile flow inhibition rates. Further mechanistic analysis revealed that P and IP significantly decreased the expression of bile acids (BAs) synthesis genes cyp7a1 and cyp8b1, BAs transport genes abcb11b and slc10a1, and BAs receptor genes nr1h4 and nr0b2a. In addition, P and IP caused EC by increasing the level of phosphorylation of ERK1/2. The ERK1/2 antagonists GDC0994 and Exe both showed significant rescue effects in terms of cholestatic liver injury. In conclusion, we comprehensively studied the specific mechanisms of P- and IP-induced EC and speculated that ERK1/2 may represent an important therapeutic target for EC induced by phytoestrogens.

Gender potentially affects early postoperative hyponatremia in pituitary adenoma: XGBoost-based predictive modeling.

Purpose: The occurrence of hyponatremia is a prevalent complication following transnasal transsphenoidal surgery for pituitary adenoma surgery, which adversely affects patient prognosis, hospitalization duration, and rehospitalization risk. The primary objective of this study is to strengthen the correlation between clinical factors associated with pituitary adenoma and postoperative hyponatremia. Additionally, the study aims to develop a predictive model for postoperative hyponatremia in patients with pituitary adenoma, with the ultimate goal of establishing a basis for reducing the occurrence of postoperative hyponatremia following surgical interventions. Methods: The chi-square test or Fisher test was employed for nominal data, while the t-test or Mann-Whitney test was utilized for continuous data analysis. In cases where the data exhibited statistical differences, binary logistic analysis was conducted to examine the risk and protective factors associated with postoperative hyponatremia. XGBoost was employed to construct predictive models for hyponatremia in this study. The patients were partitioned into training and test sets, and the most suitable parameters were determined through five-fold cross-validation and subsequently utilized for training on the training set. The discriminatory capability was assessed on the internal validation set. Results and conclusions: Out of the total 280 patients included in this investigation, 82 patients experienced early postoperative hyponatremia. Among these individuals, male gender (P = 0.02, odds ratio = 1.98) was identified as a risk factor for early postoperative hyponatremia, while preoperative chloride levels (P = 0.021, odds ratio = 0.866) and surgery time (P = 0.039, odds ratio = 0.990) were identified as protective factors against postoperative hyponatremia. The XGBoost model exhibited a sensitivity of 94.2%, a specificity of 61.5%, a positive predictive value of 51.6%, a negative predictive value of 96%, and identified male gender, preoperative sodium, and preoperative cortisol as the most significant predictors. Our findings indicate that gender may have influence in the development of early postoperative hyponatremia in patients with pituitary adenomas.

[Mechanism of bulleyaconitine A in inhibiting bone destruction of rheumatoid arthritis via Src/PI3K/Akt signaling pathway].

Based on the sarcoma receptor coactivator(Src)/phosphatidylinositol 3-kinase(PI3K)/protein kinase B(Akt) signaling pathway, the mechanism of action of bulleyaconitine A in the treatment of bone destruction of experimental rheumatoid arthritis(RA) was explored. Firstly, key targets of RA bone destruction were collected through GeneCards, PharmGKB, and OMIM databa-ses. Potential targets of bulleyaconitine A were collected using SwissTargetPrediction and PharmMapper databases. Next, intersection targets were obtained by the Venny 2.1.0 platform. Protein-protein interaction(PPI) network and topology analysis were managed by utilizing the STRING database and Cytoscape 3.8.0. Then, Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment analyses were conducted in the DAVID database. AutoDock Vina was applied to predict the molecular docking and binding ability of bulleyaconitine A with key targets. Finally, a receptor activator of nuclear factor-κB(RANKL)-induced osteoclast differentiation model was established in vitro. Quantitative real-time polymerase chain reaction(qRT-PCR) was used to detect the mRNA expression levels of related targets, and immunofluorescence and Western blot were adopted to detect the protein expression level of key targets. It displayed that there was a total of 29 drug-disease targets, and Src was the core target of bulleyaconitine A in anti-RA bone destruction. Furthermore, KEGG enrichment analysis revealed that bulleyaconitine A may exert an anti-RA bone destruction effect by regulating the Src/PI3K/Akt signaling pathway. The molecular docking results showed that bulleyaconitine A had better bin-ding ability with Src, phosphatidylinositol-4,5-diphosphate 3-kinase(PIK3CA), and Akt1. The result of the experiment indicated that bulleyaconitine A not only dose-dependently inhibited the mRNA expression levels of osteoclast differentiation-related genes cathepsin K(CTSK) and matrix metalloproteinase-9(MMP-9)(P<0.01), but also significantly reduced the expression of p-c-Src, PI3K, as well as p-Akt in vitro osteoclasts(P<0.01). In summary, bulleyaconitine A may inhibit RA bone destruction by regulating the Src/PI3K/Akt signaling pathway. This study provides experimental support for the treatment of RA bone destruction with bulleyaconitine A and lays a foundation for the clinical application of bulleyaconitine A.

Identification of molecular characteristics of hepatocellular carcinoma with microvascular invasion based on deep targeted sequencing.

BACKGROUND: As an indicator of tumor invasiveness, microvascular invasion (MVI) is a crucial risk factor for postoperative relapse, metastasis, and unfavorable prognosis in hepatocellular carcinoma (HCC). Nevertheless, the genetic mechanisms underlying MVI, particularly for Chinese patients, remain mostly uncharted. METHODS: We applied deep targeted sequencing on 66 Chinese HCC samples. Focusing on the telomerase reverse transcriptase (TERT) promoter (TERTp) and TP53 co-mutation (TERTp+/TP53+) group, gene set enrichment analysis (GSEA) was used to explore the potential molecular mechanisms of the TERTp+/TP53+ group on tumor progression and metastasis. Additionally, we evaluated the tumor immune microenvironment of the TERTp+/TP53+ group in HCC using multiplex immunofluorescence (mIF) staining. RESULTS: Among the 66 HCC samples, the mutated genes that mostly appeared were TERT, TP53, and CTNNB1. Of note, we found 10 cases with TERTp+/TP53+, of which nine were MVI-positive and one was MVI-negative, and there was a co-occurrence of TERTp and TP53 (p < 0.05). Survival analysis demonstrated that patients with the TERTp+/TP53+ group had lower the disease-free survival (DFS) (p = 0.028). GSEA results indicated that telomere organization, telomere maintenance, DNA replication, positive regulation of cell cycle, and negative regulation of immune response were significantly enriched in the TERTp+/TP53+ group (all adjusted p-values (p.adj) < 0.05). mIF revealed that the TERTp+/TP53+ group decreased CD8+ T cells infiltration (p = 0.25) and enhanced PDL1 expression (p = 0.55). CONCLUSIONS: TERTp+/TP53+ was significantly enriched in MVI-positive patients, leading to poor prognosis for HCC patients by promoting proliferation of HCC cell and inhibiting infiltration of immune cell surrounding HCC. TERTp+/TP53+ can be utilized as a potential indicator for predicting MVI-positive patients and poor prognosis, laying a preliminary foundation for further exploration of co-mutation in HCC with MVI and clinical treatment.

Integrating transcriptomics, glycomics and glycoproteomics to characterize hepatitis B virus-associated hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) ranks as the third most common cause of cancer related death globally, representing a substantial challenge to global healthcare systems. In China, the primary risk factor for HCC is the hepatitis B virus (HBV). Aberrant serum glycoconjugate levels have long been linked to the progression of HBV-associated HCC (HBV-HCC). Nevertheless, few study systematically explored the dysregulation of glycoconjugates in the progression of HBV-associated HCC and their potency as the diagnostic and prognostic biomarker. METHODS: An integrated strategy that combined transcriptomics, glycomics, and glycoproteomics was employed to comprehensively investigate the dynamic alterations in glyco-genes, N-glycans, and glycoproteins in the progression of HBV- HCC. RESULTS: Bioinformatic analysis of Gene Expression Omnibus (GEO) datasets uncovered dysregulation of fucosyltransferases (FUTs) in liver tissues from HCC patients compared to adjacent tissues. Glycomic analysis indicated an elevated level of fucosylated N-glycans, especially a progressive increase in fucosylation levels on IgA1 and IgG2 determined by glycoproteomic analysis. CONCLUSIONS: The findings indicate that the abnormal fucosylation plays a pivotal role in the progression of HBV-HCC. Systematic and integrative multi-omic analysis is anticipated to facilitate the discovery of aberrant glycoconjugates in tumor progression.

The effect of different treatment strategies on glycolipid metabolism disorders and cardiovascular events in primary aldosteronism.

Recent studies have explored the association between primary aldosteronism and cardiovascular disease incidence. The association between specific primary aldosteronism treatments and differential improvement in cardiovascular event rates is yet to be established. This study was designed to compare the relative effects of spironolactone therapy and surgical intervention on cardiovascular outcomes among primary aldosteronism patients. This retrospective observational study included 853 primary aldosteronism patients from the First Affiliated Hospital of China Medical University between 2014 and 2022. Patients who had completed abdominal computed tomography (CT) examinations with similar metabolic characteristics and 6-month follow-up analyses were included in this study. These patients were separated into a surgical treatment group (n = 33) and a spironolactone treatment group (n = 51). Demographic data, biochemical analysis results, liver/spleen (L/S) X-ray attenuation ratio, hospitalization frequency, and cardiovascular events were compared between the two groups. The spironolactone group demonstrated significantly improved metabolic characteristics compared to the surgical group, shown by lower BMI, blood pressure, total cholesterol (TC), insulin resistance index (IRI), and reduced non-alcoholic fatty liver disease prevalence. Metabolic parameters did not differ significantly within the surgical treatment group when comparing pre- and postoperative values. The incidence of cardiovascular events was lower in the spironolactone group compared to the surgery group (23/33 vs. 20/51, P < 0.001) despite higher hospitalization rates(37/31 vs. 61/53, P < 0.001). In patients with primary aldosteronism, spironolactone treatment is more effective than surgical intervention in remediating abnormal lipid and glucose metabolism while improving cardiovascular outcomes. Chinese clinical trial registry registration number: ChiCTR2300074574.

Residential mobility and liver cancer risk: findings from a prospective cohort study in Chinese women.

BACKGROUND: Residential mobility is believed to influence the occurrence and development of cancer; however, the results are inconclusive. Furthermore, limited studies have been conducted on Asian populations. This study aimed to evaluate the relationship between residential mobility and liver cancer risk among Chinese women. METHODS: We enrolled 72,818 women from urban Shanghai between 1996 and 2000, and then followed them until the end of 2016. Cox regression models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) to assess the association between residential mobility and liver cancer risk. A linear trend test was conducted by ranking variables. A sensitivity analysis was also conducted, excluding participants with follow-up times of less than 2 years, to prevent potential bias. RESULTS: During the 1,269,765 person-years of follow-up, liver cancer was newly diagnosed in 259 patients. Domestic migration (HR = 1.47, 95% CI, 1.44-1.50), especially immigration to Shanghai (HR = 1.47, 95% CI, 1.44-1.50) was associated with an increased risk of liver cancer. In addition, migration frequency, age at initial migration and first immigration to Shanghai had linear trends with an increased liver cancer risk (Ptrend <0.001). The results were similar when excluding participants with less than two years of follow-up. CONCLUSIONS: The possible association between residential mobility and a higher risk of liver cancer in women could suggest the need for effective interventions to reduce adverse environmental exposures and enhance people's health.

LncRNA NEAT1 promotes MPP+ induced injury of PC12 cells and accelerates the progression of Parkinson's disease in mice through FUS mediated inhibition of PI3K/AKT/mTOR signalling pathway.

Long noncoding RNA nuclear-enriched abundant transcript 1 (NEAT1) is involved in the progression of Parkinson's disease (PD), but the specific regulatory role needs further exploration. This study showed that the expression of NEAT1 was upregulated in the cerebrospinal fluid (CSF) and peripheral blood of patients with different stages of PD. 1-Methyl-4-phenylpyridine (MPP)-treated PC 12 cells were transfected with si-NEAT1, and MPP treatment promoted cell apoptosis, oxidative stress and inflammatory factor secretion. Si-NEAT1 reversed the effects of MPP. NEAT1 silencing eliminated the effect of MPP on the protein expression levels of LC3-II and p62/SQSTM1. By using an online bioinformatics database, Fused in Sarcoma (FUS) was confirmed to be an RNA binding protein of NEAT1, and it was highly expressed in the CSF and peripheral blood of patients with PD. Si-FUS was transfected into MPP-treated PC 12 cells to detect cell apoptosis, oxidative stress, inflammatory factor secretion and autophagy, and the results were the same as those of transfection of si-NEAT1. Furthermore, MPP treatment reduced the phosphorylation levels of PI3K, Akt and mTOR, whereas si-FUS reversed the effects of MPP. In vivo, compared with the model group, the PD mice showed reduced NEAT1 and FUS expression levels and activated PI3K pathway after being injected with si-NEAT1. The brain tissue of NEAT1-silenced PD mice had decreased inflammatory infiltration and apoptosis and increased neurological scores. In conclusion, NEAT1 is involved in PD progression through FUS-mediated inhibition of the PI3K/AKT/mTOR signalling pathway.

Assessment of chimerism by next generation sequencing: A comparison to STR/qPCR methods.

Chimerism analysis is used to evaluate patients after allogeneic hematopoietic stem cell transplant (allo-HSCT) for engraftment and minimal measurable residual disease (MRD) monitoring. A combination of short-tandem repeat (STR) and quantitative polymerase chain reaction (qPCR) was required to achieve both sensitivity and accuracy in the patients with various chimerism statuses. In this study, an insertion/deletion-based multiplex chimerism assay by next generation sequencing (NGS) was evaluated using 5 simulated unrelated donor-recipient combinations from 10 volunteers. Median number of informative markers detected was 8 (range = 5 - 11). The limit of quantitation (LoQ) was determined to be 0.1 % recipient. Assay sample number/batch was 10-20 and total assay time was 19-31 h (manual labor = 2.1 h). Additionally, 50 peripheral blood samples from 5 allo-HSCT recipients (related: N = 4; unrelated: N = 1) were tested by NGS and STR/qPCR. Median number of informative markers detected was 7 (range = 4 - 12). Results from both assays demonstrated a strong correlation (Y = 0.9875X + 0.333; R2 = 0.9852), no significant assay bias (difference mean - 0.08), and 100 % concordant detection of percent recipient increase ≥ 0.1 % (indicator of increased relapse risk). NGS-based chimerism assay can support all allo-HSCT for engraftment and MRD monitoring and simplify clinical laboratory workflow compared to STR/qPCR.

Research progress on the roles of dopamine and dopamine receptors in digestive system diseases.

Dopamine (DA) is a neurotransmitter synthesized in the human body that acts on multiple organs throughout the body, reaching them through the blood circulation. Neurotransmitters are special molecules that act as messengers by binding to receptors at chemical synapses between neurons. As ligands, they mainly bind to corresponding receptors on central or peripheral tissue cells. Signalling through chemical synapses is involved in regulating the activities of various body systems. Lack of DA or a decrease in DA levels in the brain can lead to serious diseases such as Parkinson's disease, schizophrenia, addiction and attention deficit disorder. It is widely recognized that DA is closely related to neurological diseases. As research on the roles of brain-gut peptides in human physiology and pathology has deepened in recent years, the regulatory role of neurotransmitters in digestive system diseases has gradually attracted researchers' attention, and research on DA has expanded to the field of digestive system diseases. This review mainly elaborates on the research progress on the roles of DA and DRs related to digestive system diseases. Starting from the biochemical and pharmacological properties of DA and DRs, it discusses the therapeutic value of DA- and DR-related drugs for digestive system diseases.

Use of hydroxocobalamin to treat intraoperative vasoplegic syndrome refractory to vasopressors and methylene blue during liver transplantation.

INTRODUCTION: For patients with catecholamine-resistant vasoplegic syndrome (VS) during liver transplantation (LT), treatment with methylene blue (MB) and/or hydroxocobalamin (B12) has been an acceptable therapy. However, data on the effectiveness of B12 is limited to case reports and case series. METHODS: We retrospectively reviewed records of patients undergoing LT from January 2016 through March 2022. We identified patients with VS treated with vasopressors and MB, and abstracted hemodynamic parameters, vasopressor requirements, and B12 administration from the records. The primary aim was to describe the treatment efficacy of B12 for VS refractory to vasopressors and MB, measured as no vasopressor requirement at the conclusion of the surgery. RESULTS: One hundred one patients received intraoperative VS treatment. For the 35 (34.7%) patients with successful VS treatment, 14 received MB only and 21 received both MB and B12. Of the 21 patients with VS resolution after receiving both MB and B12, 17 (89.5%) showed immediate, but transient, hemodynamic improvements at the time of MB administration and later showed sustained response to B12. CONCLUSION: Immediate but transient hemodynamic response to MB in VS patients during LT supports the diagnosis of VS and should prompt B12 administration for sustained treatment response.

The influence of marital status at diagnosis on survival of adult patients with mantle cell lymphoma.

PURPOSE: Marital status has been reported to influence the survival outcomes of various cancers, but its impact on patients with mantle cell lymphoma (MCL) remains unclear. This study aimed to assess the influence of marital status at diagnosis on overall survival (OS) and cancer-specific survival (CSS) in patients with MCL. METHODS: The study utilized data from the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER)-18 databases, including 6437 eligible individuals diagnosed with MCL from 2000 to 2018. A 1:1 propensity matching method (PSM) minimized confounding factor. Univariate and multivariate analyses determined hazard ratios (HR). Stratified hazard models were developed for married and unmarried statuses across time intervals. RESULTS: Married patients exhibited better 5-year OS and CSS rates compared to unmarried patients (54.2% vs. 39.7%, log-rank p < 0.001; 62.6% vs. 49.3%, log-rank p < 0.001). Multivariate analysis indicated that being unmarried was an independent risk factor for OS (adjusted HR 1.420, 95% CI 1.329-1.517) and CSS (adjusted HR 1.388, 95% CI 1.286-1.498). After PSM, being unmarried remained an independent risk factor for both OS and CSS. Among unmarried patients, widowed individuals exhibited the poorest survival outcomes compared to patients with other marital statuses, with 5-year OS and CSS rates of 28.5% and 41.0%, respectively. Furthermore, in the 10-year OS and CSS hazard model for widowed individuals had a significantly higher risk of mortality, with the probability of overall and cancer-specific mortality increased by 1.7-fold and 1.6-fold, respectively. CONCLUSION: Marital status at diagnosis is an independent prognostic factor for MCL patients, with widowed individuals showing worse OS and CSS than those who are married, single, or divorced/separated. Adequate psychological and social support for widowed patients is crucial for improving outcomes in this patient population.

Breaking Physical Barrier of Fibrotic Breast Cancer for Photodynamic Immunotherapy by Remodeling Tumor Extracellular Matrix and Reprogramming Cancer-Associated Fibroblasts.

Cancer-associated fibroblasts (CAFs) assist in breast cancer (BRCA) invasion and immune resistance by overproduction of extracellular matrix (ECM). Herein, we develop FPC@S, a photodynamic immunomodulator that targets the ECM, to improve the photodynamic immunotherapy for fibrotic BRCA. FPC@S combines a tumor ECM-targeting peptide, a photosensitizer (protoporphyrin IX) and an antifibrotic drug (SIS3). After anchoring to the ECM, FPC@S causes ECM remodeling and BRCA cell death by generating reactive oxygen species (ROS) in situ. Interestingly, the ROS-mediated ECM remodeling can normalize the tumor blood vessel to improve hypoxia and in turn facilitate more ROS production. Besides, upon the acidic tumor microenvironment, FPC@S will release SIS3 for reprograming CAFs to reduce their activity but not kill them, thus inhibiting fibrosis while preventing BRCA metastasis. The natural physical barrier formed by the dense ECM is consequently eliminated in fibrotic BRCA, allowing the drugs and immune cells to penetrate deep into tumors and have better efficacy. Furthermore, FPC@S can stimulate the immune system and effectively suppress primary, distant and metastatic tumors by combining with immune checkpoint blockade therapy. This study provides different insights for the development of fibrotic tumor targeted delivery systems and exploration of synergistic immunotherapeutic mechanisms against aggressive BRCA.

Superhydrophobic Co-MOF-based sponge for efficient oil-water separation utilizing photothermal effect.

Effectively addressing crude oil spills remains a global challenge due to its high viscosity and limited flow characteristics. In this study, we successfully prepared a modified sponge (PCP@MS) by embedding the photothermal material of Co-HHTP and coating the melamine sponge (MS) with low-surface-energy polydimethylsiloxane (PDMS). The PCP@MS exhibited outstanding hydrophobicity with WCA of 160.2° and high oil absorption capacity of 59-107 g/g. The PCP@MS showed high separation efficiency of 99.2% for various oil-water mixtures, along with notable self-cleaning properties and mechanical stability. The internal micro-nano hierarchical structure on the sponge surface significantly enhanced light absorption, synergizing with the photo-thermal conversion properties of Co-HHTP, enabled PCP@MS to achieve a surface temperature of 109.2 °C under 1.0 solar light within 300 s. With the aid of solar radiation, PCP@MS is able to heat up quickly and successfully lowering the viscosity of the surrounding crude oil, resulting in an oil recovery rate of 8.76 g/min. Density functional theory (DFT) calculation results revealed that Co-HHTP featured a zero-gap band structure, rendering advantageous electronic properties for full-wavelength light absorption. This in situ solar-heated absorbent design is poised to advance the practical application of viscous oil spill cleanup and recovery.

Perioperative nutrition management in patients with spinal tuberculosis taking ERAS measures.

BACKGROUND AND OBJECTIVES: To explore the effect of nutrition management under ERAS concept in patients with spinal tuberculosis. METHODS AND STUDY DESIGN: The study was conducted in an orthopedic ward of a tertiary grade A special hospital in Beijing. The patients admitted from January 1, 2021 to June 27, 2023 were screened for inclusion. The qualified patients were randomized into experimental group or control group. The experimental group received perioperative nutrition management under the concept of ERAS while the control group received routine perioperative management in hospital. The data was collected on the next day of admission, the next day and the sixth day after operation, including laboratory indicators (lymphocyte count, hemoglobin level, etc), intraoperative bleeding volume, postoperative exhaust, defecation time, drainage volume, albumin infusion amount, nutritional risk score, length of stay, hospitalization costs, etc. Univariate analysis and multivariate analysis correcting for gender, age, and baseline values were performed using SPSS24.0. RESULTS: A total of 127 patients with spinal tuberculosis completed the study. Compared with the control group, the intraoperative blood loss (p=0.028) in the experimental group was significantly reduced, the postoperative exhaust time (p=0.012) and defecation time (p=0.012) were significantly shortened, and the nutritional status (p<0.001) was significantly improved. Besides, the results of multivariate analysis are robust after correcting potential confounding factors. CONCLUSIONS: Nutrition management under the concept of ERAS is helpful to reduce intraoperative bleeding, promote postoperative flatus and defecation, and improve nutritional status in patients with spinal tuberculosis, which may further improve their clinical outcome and prognosis.

Neobractatin induces pyroptosis of esophageal cancer cells by TOM20/BAX signaling pathway.

BACKGROUND: Emerging evidence suggests that pyroptosis, a form of programmed cell death, has been implicated in cancer progression. The involvement of specific proteins in pyroptosis is an area of growing interest. TOM20, an outer mitochondrial membrane protein, has recently garnered attention for its potential role in pyroptosis. Our previous study found that NBT could induce pyroptosis by ROS/JNK pathway in esophageal cancer cells. PURPOSE: This study aims to investigate whether NBT induces pyroptosis and verify whether such effects are involved in up-regulation of TOM20 in esophageal cancer cells. METHODS: The University of ALabama at Birmingham CANcer data analysis Portal (UALCAN) was used to analyze the clinical significance of GSDME in esophageal cancer. MTT assay, morphological observation and Western blot were performed to verify the roles of TOM20 and BAX in NBT-induced pyroptosis after CRISPR-Cas9-mediated knockout. Immunofluorescence was used to determine the subcellular locations of BAX and cytochrome c. MitoSOX Red was employed to assess the mitochondrial reactive oxygen species (ROS) level. KYSE450 and TOM20 knockout KYSE450-/- xenograft models were established to elucidate the mechanisms involved in NBT-induced cell death. RESULTS: In this study, NBT effectively upregulated the expression of TOM20 and facilitated the translocation of BAX to mitochondria, which promoted the release of cytochrome c from mitochondria to the cytoplasm, leading to the activation of caspase-9 and caspase-3, and finally induced pyroptosis. Knocking out TOM20 by CRISPR-Cas9 significantly inhibited the expression of BAX and the downstream BAX/caspase-3/GSDME pathway, which attenuated NBT-induced pyroptosis. The elevated mitochondrial ROS level was observed after NBT treatment. Remarkably, the inhibition of ROS by N-acetylcysteine (NAC) effectively suppressed the activation of TOM20/BAX pathway. Moreover, in vivo experiments demonstrated that NBT exhibited potent antitumor effects in both KYSE450 and TOM20 knockout KYSE450-/- xenograft models. Notably, the attenuated antitumor effects and reduced cleavage of GSDME were observed in the TOM20 knockout model. CONCLUSION: These findings reveal that NBT induces pyroptosis through ROS/TOM20/BAX/GSDME pathway, which highlight the therapeutic potential of targeting TOM20 and GSDME, providing promising prospects for the development of innovative and effective treatment approaches for esophageal cancer.

A propensity score-matched analysis of laparoscopic versus open pancreaticoduodenectomy: Is there value to a laparoscopic approach?

BACKGROUND: Laparoscopic pancreaticoduodenectomy has been found safe and associated with advantages over open pancreaticoduodenectomy in prior studies. We compared outcomes of laparoscopic pancreaticoduodenectomy versus open pancreaticoduodenectomy at a single institution after applying technical aspects and perioperative care learned from laparoscopic pancreaticoduodenectomy to the open pancreaticoduodenectomy practice. METHODS: From January 2010 to December 2020, all patients undergoing pancreaticoduodenectomy were identified, and information was collected in a prospective fashion. Open pancreaticoduodenectomy (n = 347) and laparoscopic pancreaticoduodenectomy (n = 242) were performed using the same selection criteria, operative technique, and recovery protocols at a single institution. Propensity score matching was performed, and then perioperative data and 90-day outcomes were compared, and statistical analysis was performed. RESULTS: A total of 589 patients underwent pancreaticoduodenectomy, including open pancreaticoduodenectomy (n = 347) and laparoscopic pancreaticoduodenectomy (n = 242). After excluding those undergoing total pancreatectomy or major vascular or concomitant organ resection, there were 497 patients (open pancreaticoduodenectomy = 301 and laparoscopic pancreaticoduodenectomy = 196). Propensity score matching was performed, and 187 open pancreaticoduodenectomy patients were matched to 187 laparoscopic pancreaticoduodenectomy patients. Operative time (475 vs 280 minutes) was longer, and estimated blood loss (150 vs 212 mL) was less for laparoscopic pancreaticoduodenectomy than open pancreaticoduodenectomy, respectively. Pancreatic fistula (18.8% vs 5.4%) and delayed gastric emptying (18.8% vs 9.7%) were higher for laparoscopic pancreaticoduodenectomy than open pancreaticoduodenectomy, respectively. Postpancreatectomy hemorrhage, major morbidity, mortality, hospital stay, and readmissions were nonsignificantly higher for laparoscopic pancreaticoduodenectomy than open pancreaticoduodenectomy. Intensive care use and overall costs were significantly higher for laparoscopic pancreaticoduodenectomy than open pancreaticoduodenectomy. CONCLUSION: In our experience, open pancreaticoduodenectomy offers similar to improved outcomes over laparoscopic pancreaticoduodenectomy, with less use of perioperative resources, thereby offering better value to patients requiring pancreaticoduodenectomy.

Association between brominated flame retardants and risk of endocrine-related cancer: A systematic review and meta-analysis.

BACKGROUND: The incidence of endocrine-related cancer, which includes tumors in major endocrine glands such as the breast, thyroid, pituitary, and prostate, has been increasing year by year. Various studies have indicated that brominated flame retardants (BFRs) are neurotoxic, endocrine-toxic, reproductive-toxic, and even carcinogenic. However, the epidemiological relationship between BFR exposure and endocrine-related cancer risk remains unclear. METHODS: We searched the PubMed, Google Scholar, and Web of Science databases for articles evaluating the association between BFR exposure and endocrine-related cancer risk. The odds ratio (OR) and its corresponding 95% confidence interval (95% CI) were used to assess the association. Statistical heterogeneity among studies was assessed with the Q-test and I2 statistics. Begg's test was performed to evaluate the publication bias. RESULTS: We collected 15 studies, including 6 nested case-control and 9 case-control studies, with 3468 cases and 4187 controls. These studies assessed the risk of breast cancer, thyroid cancer, and endocrine-related cancers in relation to BFR levels. Our findings indicate a significant association between BFR exposure in adipose tissue and an increased risk of breast cancer. However, this association was not observed for thyroid cancer. Generally, BFR exposure appears to elevate the risk of endocrine-related cancers, with a notable increase in risk linked to higher levels of BDE-28, a specific polybrominated diphenyl ether congener. CONCLUSIONS: In conclusion, although this meta-analysis has several limitations, our results suggest that BFR exposure is a significant risk factor for breast cancer, and low-brominated BDE-28 exposure could significantly increase the risk of endocrine-related cancers. Further research is essential to clarify the potential causal relationships between BFRs and endocrine-related cancers, and their carcinogenic mechanisms.