Hyaluronic acid-zein shell-core biopolymer nanoparticles enhance hepatocellular carcinoma therapy of celastrol via CD44-mediated cellular uptake.

Low concentrations or limited residence times in tumor tissues, making celastrol (Cel) difficult to exert significant therapeutic effects. Thus, we developed Zein/hyaluronic acid core-shell nanoparticles (Cel/Zein@HA NPs) for active targeted delivery of Cel via CD44 receptor over-expression on cancer cells, which may strengthen the therapeutic efficacy of Cel and improve delivery targeting. Cel-loaded Zein nanoparticles (core), are elegantly enveloped by a hydrophilic HA coating that forms the shell, resulting in significantly improved encapsulation efficiency and ensured good stability. The cellular uptake of Cel/Zein@HA NPs in HepG2 cells was 1.57-fold higher than nontargeting Cel/Zein NPs. Near-infrared fluorescence imaging confirmed the accumulation of Cel/Zein@HA NPs in H22 liver cancer tumors in mice, resulting in effective antitumor effects and good biosafety. Besides, in vitro and in vivo experiments showed that compared with Cel/Zein NPs, Cel/Zein@HA NPs had more efficient inhibitory effect on tumor proliferation and lower systemic toxicity. Further studies revealed that Cel/Zein@HA NPs induced apoptosis in hepatocellular carcinoma cells by modulating Bax and Bcl-2 expression, while also inhibiting tumor angiogenesis by decreasing CD31 and VEGF levels. Overall, this study presents a promising strategy for enhancing targeted liver cancer therapy through the utilization of biopolymer nanoparticle-based nano-pharmaceuticals that facilitate CD44-mediated cellular uptake.

Mechanisms of action and applications of Polygonatum sibiricum polysaccharide at the intestinal mucosa barrier: a review.

As a medicinal and edible homologous Chinese herb, Polygonatum sibiricum has been used as a primary ingredient in various functional and medicinal products. Damage to the intestinal mucosal barrier can lead to or worsen conditions such as type 2 diabetes and Alzheimer's disease. Traditional Chinese medicine and its bioactive components can help prevent and manage these conditions by restoring the integrity of the intestinal mucosal barrier. This review delves into the mode of action of P. sibiricum polysaccharide in disease prevention and management through the restoration of the intestinal barrier. Polysaccharide from P. sibiricum effectively treats conditions by repairing the intestinal mucosal barrier, offering insights for treating complex diseases and supporting the application of P. sibiricum in clinical settings.

A novel electrochemical membrane filtration system operated with periodical polarity reversal for efficient resource recovery from nickel nitrate laden industrial wastewater.

The economical and efficient removal of nickel nitrate from industrial wastewater remains a challenge. Herein, we developed an innovative electrochemical membrane filtration system that used a periodic polarity reversal process to adjust the acid-base environment near membrane interface for the recovery of nickel (II) and ammonia. The Ru based electrocatalytic layer could boost the selective reduction of nitrate to ammonia by generating atomic hydrogen, resulting in the precipitation of Ni2+ by the increasing pH at the membrane interface. Then, the precipitation of Ni(OH)2 could be effectively stripped and collected under the periodic polarity reversal process. In-situ interfacial measurements demonstrated that the polarity reversal process enabled a reversible transformation between strongly acidic (pH < 2) and alkaline (pH > 13) environments within a 200 µm range at the membrane interface. In continuous flow operation treating real industrial wastewater containing 96.7 mg-N L-1 nitrate and 135.0 mg L-1 Ni2+, the system demonstrated the capability to achieve 92.5 ± 2.6 % nitrate removal (with a recovery efficiency of 15.1 ± 1.9 g-NH3 kWh-1) and 99.7 ± 0.1 % Ni²âº removal (with a recovery efficiency of 24.9 ± 2.4 g-Ni kWh-1). Additionally, the specific treatment cost was approximately $0.17 m-3, attributed to the recovery of Ni(OH)2 and ammonia. Furthermore, this system could deliver a significant economic benefit ($1.64 per m3) for treating a high concentration real wastewater (331.5 mg-N L-1 nitrate and 1496.3 mg L-1 Ni2+), outperforming traditional alkali precipitation and biological nitrification/denitrification processes. Overall, our study presents an economical and sustainable method for recovering valuable chemicals from wastewater containing heavy metals and inorganic nitrogen, potentially advancing cost-effective water treatment technologies.

P-doped RuSe2 on Porous N-doped Carbon Matrix as Catalysts for Accelerated Sulfur Redox Reactions.

Monocomponent catalysts exhibit the limited catalytic conversion of polysulfides due to their intrinsic electronic structure, but their catalytic activity can be improved by introducing heteroatoms to regulate its electronic structure. However, the rational selection principles of doping elements remain unclear. Here, we are guided by theoretical calculations to select the suitable doping elements based on the balanced relationship between the adsorption strength of lithium polysulfides (LiPSs) and catalytic activity of lithium sulfide. We apply the screening method to develop a new catalyst of phosphorus doped RuSe2, manifesting the further enhanced conductivity compared with original RuSe2, facilitating charge transfer and further modulating the d-band center of RuSe2, thereby augmenting its effectiveness in interacting with LiPSs. Consequently, the assembled cell exhibits an areal capacity of 7.7 mAh cm-2, even under high sulfur loading of 8.0 mg cm-2 and a lean electrolyte condition (5.0 µL mg-1). This rational screening strategy offers a robust solution for the design of advanced catalysts in the field of lithium-sulfur batteries and potentially other domains as well.

Nab-paclitaxel plus capecitabine as first-line treatment for advanced biliary tract cancers: An open-label, non-randomized, phase II clinical trial.

BACKGROUND: Biliary tract cancers (BTCs) are a heterogeneous group of tumors with high malignancy, poor prognosis, and limited treatment options. AIM: To explore the efficacy and safety of nab-paclitaxel plus capecitabine as first-line treatment for advanced and metastatic BTCs. METHODS: This open-label, non-randomized, double-center, phase II clinical trial recruited systemic therapy-naive patients with unresectable or metastatic BTCs between April 2019 and June 2022 at Beijing Cancer Hospital and the First Hospital of China Medical University. Eligible patients were administered nab-paclitaxel (150 mg/m2, day 1) and capecitabine (2000 mg/m2, twice daily, days 1-7) in 14-day cycles until experiencing intolerable toxicity or disease progression. The primary outcome was the objective response rate (ORR). The secondary outcomes included the disease control rate (DCR), overall survival (OS), progression-free survival (PFS), and safety. RESULTS: A total of 44 patients successfully completed the trial, with a median age of 64.00 years (interquartile range, 35.00-76.00), and 26 (59.09%) were females. Tumor response assessment was impeded for one patient due to premature demise from tumor hemorrhage. Among the remaining 43 patients undergoing at least one imaging assessment, the ORR was 23.26% [95% confidence interval (CI): 11.80%-38.60%], and the DCR was 69.77% (95%CI: 53.90%-82.80%). The median OS was 14.1 months (95%CI: 8.3-19.9), and the median PFS was 4.4 months (95%CI: 2.5-6.3). A total of 41 patients (93.18%) experienced at least one adverse event (AE), with 10 patients (22.73%) encountering grade ≥ 3 AEs, and the most frequent AEs of any grade were alopecia (79.50%), leukopenia (54.55%), neutropenia (52.27%), and liver dysfunction (40.91%), and no treatment-related deaths were documented. CONCLUSION: Nab-paclitaxel plus capecitabine may be an effective and safe first-line treatment strategy for patients with advanced or metastatic BTCs.

COL5A1 overexpression correlates with poor prognosis in human cervical cancer.

BACKGROUND: Cervical cancer is the most prevalent malignant tumor in women. This study aims to detect collagen type V α1 chain (COL5A1) expression and its clinical relevance in the prognosis of patients with cervical cancer. METHODS: Cervical cancer tissues and their paired adjacent normal tissues were prepared for tissue microarray. The expression of COL5A1 protein and the scores of the expression were evaluated by immunohistochemistry (IHC) staining. The prognostic value of COL5A1 was analyzed by R software version 4.2.1 with "survival, survminer, ggplot2" packages and Gene Expression Profiling Interactive Analysis (GEPIA). The cBioPortal database was utilized for the analysis of COL5A1 gene mutations. RESULTS: COL5A1 protein was overexpressed in human cervical cancer tissues compared to their paired adjacent normal tissues detected by IHC (P < 0.001). High expression of COL5A1 tends to be in elderly patients with cervical cancer. Survival analyses of clinical data of patients with cervical cancer showed that a high level of COL5A1 expression was significantly correlated with shorter overall survival (P = 0.031) and disease-free survival (P = 0.042) of patients. Further analyses of The Cancer Genome Atlas-Cervical Squamous Cell Carcinoma and the GEPIA survival datasets confirmed the association of high COL5A1 expression with poor overall survival of patients (P = 0.040 and P = 0.018, respectively). The analysis of genomic alterations of COL5A1 using the cBioPortal tool revealed that the COL5A1 gene was altered in 4% of cervical cancer patients and COL5A1 corresponding protein alterations with post-translational modifications were hydroxylation. CONCLUSION: COL5A1 is a tissue biomarker correlated with the poor prognosis of patients with cervical cancer, which may lead to a new clinical application.

Hepatocellular Carcinoma Patients with Hepatitis B Virus Infection Exhibited Favorable Survival from Immune Checkpoint Inhibitors: A Systematic Review and Meta-Analysis.

Background: Immune checkpoint inhibitors (ICIs) have demonstrated effectiveness for advanced hepatocellular carcinoma (HCC). However, the discrepancy in the efficacy of ICIs in HCC patients with distinct etiologies has not been systematically validated. Methods: PubMed, MEDLINE, Embase, clinicaltrials.gov, and abstracts from ASCO and ESMO conferences were searched for eligible trials that explored the impact of etiology factor on the ICI treatment in HCC patients. The pooled hazard ratio (HR) of overall survival (OS) and progression-free survival (PFS), as well as the pooled odds ratio (OR) of objective response rate (ORR), were calculated with stratification of hepatitis B virus (HBV), hepatitis C virus (HCV) and nonviral subgroup, and the heterogeneity between different etiological subgroups was assessed by using an interaction test. Results: Eight eligible studies with a total of 5,646 patients were identified from searching published articles and conference abstracts. ICI therapies were associated with significantly prolonged OS with the pooled HRs of 0.78 (95% CI 0.73-0.84, p < 0.001), 0.71 (95% CI 0.65-0.79, p < 0.001), 0.80 (95% CI 0.69-0.93, p = 0.003), and 0.87 (95% CI 0.77-0.97, p = 0.011) for the whole population, HBV subgroup, HCV subgroup, and non-viral subgroup, respectively. In addition, this analysis reported a significant PFS improvement with ICI therapies with HRs of 0.78 (p = 0.004), 0.53 (p < 0.001), 0.65 (p = 0.011), and 0.81 (p = 0.107) for whole population, HBV, HCV, and nonviral subgroup, respectively. The HBV-related HCC patients showed the more distinctive HRs for OS and PFS than other etiology subgroups, and this difference was significant in PFS (p for heterogeneity = 0.001), and there was a tendency of significance in OS (p for heterogeneity = 0.079). Furthermore, the ORR advantages of ICI therapies over control were also confirmed with the pooled ORs of 3.62 (p < 0.001), 3.84 (p < 0.001), 3.05 (p < 0.001), and 2.99 (p < 0.001) for whole population, HBV, HCV, and nonviral population, respectively (p for heterogeneity = 0.743). Conclusions: ICI therapies significantly improve OS, PFS, and ORR for HCC patients with different etiologies. HBV-related HCC patients could be the highlighted population to benefit from ICI treatment.

Metabolic reprogramming and heterogeneity during the decidualization process of endometrial stromal cells.

The human endometrial decidualization is a transformative event in the pregnant uterus that involves the differentiation of stromal cells into decidual cells. While crucial to the establishment of a successful pregnancy, the metabolic characteristics of decidual cells in vivo remain largely unexplored. Here, we integrated the single-cell RNA sequencing (scRNA-seq) datasets on the endometrium of the menstrual cycle and the maternal-fetal interface in the first trimester to comprehensively decrypt the metabolic characteristics of stromal fibroblast cells. Our results revealed that the differentiation of stromal cells into decidual cells is accompanied by increased amino acid and sphingolipid metabolism. Furthermore, metabolic heterogeneity exists in decidual cells with differentiation maturity disparities. Decidual cells with high metabolism exhibit higher cellular activity and show a strong propensity for signaling. In addition, significant metabolic reprogramming in amino acids and lipids also occurs during the transition from non-pregnancy to pregnancy in the uteri of pigs, cattle, and mice. Our analysis provides comprehensive insights into the dynamic landscape of stromal fibroblast cell metabolism, contributing to our understanding of the metabolism at the molecular dynamics underlying the decidualization process in the human endometrium.

Takotsubo Syndrome in Patients With COVID-19: A Systematic Review.

Background: Respiratory conditions are major physical triggers of takotsubo syndrome (TTS) and portend worse outcomes. However, data on TTS in patients with coronavirus disease-2019 infection (COVID-19) are limited. Methods: We searched PubMed, Embase, and Cochrane Library databases for case reports for the period 2019-2022 describing TTS in patients with COVID-19 pneumonia (TTS-COVID). We summarized the clinical data and outcomes and compared them to those in patients with TTS with an acute respiratory disease other than COVID-19 as a trigger (TTS-acute respiratory disease) and those with TTS with no respiratory disease (TTS-no respiratory disease). Results: The mortality rate was higher in those with TTS-COVID (26.0%) than those with TTS-acute respiratory disease (5.7%) or TTS-no respiratory disease (4.2%; P < 0.001 for both). The proportion of men was higher in TTS-COVID (33.3%) than it was in TTS-no respiratory disease (9.1%; P < 0.001). The manifestations of TTS in COVID patients were atypical (dyspnea [70.3%] and cough [40.6%]); few had chest pain (23.4%). Cardiovascular risk factors were common in the TTS-COVID cohort, but fewer patients were on cardioprotective medications in this group than in the other 2 groups. Level of catecholamine use was higher in the TTS-COVID group (37.7%) than it was in the TTS-no respiratory disease (10.9%; P < 0.001) group. Apical ballooning (72.6%) was the most common TTS subtype, and basal segment type was seen in 11.0% of TTS-COVID patients. Conclusions: COVID-19 patients who developed TTS had high mortality rates and unique features, compared with those in the TTS-acute respiratory disease group or the TTS-no respiratory disease group. Understanding the pathophysiology of TTS in COVID-19 may help prevent TTS and direct therapy in this setting.

Contexte: Les troubles respiratoires sont des déclencheurs physiques importants du syndrome de Takotsubo (STT) et présagent une issue funeste. Les données sur le STT chez les personnes ayant contracté la maladie à coronavirus de 2019 (COVID-19) sont néanmoins limitées. Méthodologie: Nous avons fait une recherche dans les bases de données PubMed, Embase et Cochrane Library pour trouver des rapports de cas signalés entre 2019 et 2022 faisant état du STT chez des patients ayant contracté une pneumonie associée à la COVID-19 (STT-COVID). Nous avons synthétisé les données cliniques et les résultats pour les comparer à ceux de patients atteints du STT déclenché par une autre maladie respiratoire aiguë que la COVID-19 (STT-maladie respiratoire aiguë) et de patients atteints du STT sans maladie respiratoire (STT-sans maladie respiratoire). Résultats: Le taux de mortalité a été plus élevé chez les patients atteints du STT-COVID (26,0 %) que chez ceux atteints du STT-maladie respiratoire aiguë (5,7 %) ou du STT-sans maladie respiratoire (4,2 %; p < 0,001 dans les deux cas). La proportion d'hommes était plus élevée dans le groupe STT-COVID (33,3 %) que dans le groupe STT-sans maladie respiratoire (9,1 %; p < 0,001). Les manifestations du STT chez les patients atteints de la COVID étaient atypiques (dyspnée [70,3 %] et toux [40,6 %]); quelques patients présentaient une douleur thoracique (23,4 %). Les facteurs de risque cardiovasculaires étaient courants dans la cohorte STT-COVID, mais les patients qui prenaient des médicaments cardioprotecteurs étaient moins nombreux dans ce groupe que dans les deux autres groupes. Le taux d'utilisation de la catécholamine était plus élevé dans le groupe STT-COVID (37,7 %) que dans le groupe STT-sans maladie respiratoire (10,9 %; p < 0,001). La ballonisation de l'apex (72,6 %) était le sous-type de STT le plus courant, et le type caractérisé par un trouble du segment basal a été observé chez 11,0 % des patients atteints du STT-COVID. Conclusions: Les patients atteints de la COVID-19 ayant développé un STT présentaient des taux de mortalité élevés et des manifestations singulières, comparativement à ceux du groupe STT-maladie respiratoire aiguë ou du groupe STT-sans maladie respiratoire. Comprendre la physiopathologie du STT chez les patients atteints de la COVID-19 pourrait contribuer à prévenir le STT et à orienter le traitement dans ce contexte.