Tumor-to-stroma cd8+ t cells ratio combined with cancer-associated fibroblasts: an innovative approach to predicting lymph node metastases of cervical cancer.

PURPOSE: Precise identification of lymph node metastases is vital for the management of cervical cancer. However, the existing diagnostic methods for lymph node metastases have certain drawbacks. In this study, we aim to explore the expression of cancer-associated fibroblasts (CAFs) and tumor-to-stroma CD8+ T cells ratio (CD8+ T cells T:S ratio) and its association with lymph node metastases of cervical cancer. METHODS: Hundred and ten cervical cancer tissues and 39 biopsy tissues from patients were investigated immunocytochemically for the expression of CAFs and CD8+ T cells. The statistical correlation analysis was carried out using the SPSS system. RESULTS: A strong and statistically significant negative correlation (r= - 0.690; P < 0.001) was observed between CAF density and CD8+ T cells T:S ratio. Not only were CAFs density and CD8+ T cells T:S ratio correlated with lymph node metastases respectively (P < 0.001), but the combination of them also significantly correlated with lymph node metastases (P < 0.001). Then, we constructed the combined diagnosis model (Logit (P) = - 4.446 + 0.300 × CAFs + 0.752 × CD8+ T cells T:S Ratio) of cervical cancer lymph node metastases. ROC curves analysis showed that the ROC curves areas for CAFs, CD8+ T cells T:S ratio, and a combination of both are 0.879, 0.747, and 0.951. Then, the prediction model was verified by biopsy specimens and consistent results were obtained. CONCLUSIONS: The combination of CAF density and CD8+ T cells T:S ratio has a significant predictive value for lymph node metastases in patients with cervical cancer.

Implementation and evaluation of an EHR-integrated perpetual inventory system in a large tertiary hospital oncology pharmacy.

PURPOSE: This study aimed to compare the impact of an electronic health record (EHR)-integrated perpetual inventory management system (EIMS) versus a traditional inventory management system (TIMS) on inventory accuracy, visibility, and turnover in a large academic tertiary hospital. METHODS: The quasi-experimental study was conducted over 12 months (a 6-month preimplementation period and a 6-month postimplementation period, with an 11-month washout period) at Houston Methodist Hospital. The EIMS was implemented following the use of a TIMS. A total of 114 matched inventory items from both systems were identified and compared. The primary outcome was inventory accuracy, calculated as cycle count accuracy. The secondary outcomes were inventory visibility and monthly inventory turnover rate. RESULTS: Analysis demonstrated a 6.02% absolute increase in inventory accuracy (P < 0.001) with use of the EIMS versus the TIMS. After adjusting for inflation, there was an increase in the captured cost of goods sold from $4.16 million to $5.16 million. The monthly inventory value, adjusted for inflation in the prices of studied inventory items, increased from $2.05 million to $2.33 million. The monthly inventory turnover rate increased from 2.03 to 2.23 turns per month (P = 0.305) when comparing data for the pre- and postimplementation periods. Inventory visibility increased from 133 inventory items to 264 inventory items after EIMS implementation, indicating a 98% visibility increase compared to preimplementation levels. CONCLUSION: This study found that implementing an EIMS significantly increased pharmacy inventory accuracy and inventory visibility, which are essential for optimizing patient care and pharmacy financial management.

The role of cancer-associated fibroblasts in bladder cancer progression.

Cancer-associated fibroblasts (CAFs) are key stromal cells in the tumor microenvironment (TME) that critically contribute to cancer initiation and progression. In bladder cancer (BCa), there is emerging evidence that BCa CAFs are actively involved in cancer cell proliferation, invasion, metastasis, and chemotherapy resistance. This review outlines the present knowledge of BCa CAFs, with a particular emphasis on their origin and function in BCa progression, and provides further insights into their clinical application.

Cancer-associated fibroblast-derived PAI-1 promotes lymphatic metastasis via the induction of EndoMT in lymphatic endothelial cells.

BACKGROUND: Endothelial-mesenchymal transition (EndoMT) is an emerging adaptive process that modulates lymphatic endothelial function to drive aberrant lymphatic vascularization in the tumour microenvironment (TME); however, the molecular determinants that govern the functional role of EndoMT remain unclear. Here, we show that cancer-associated fibroblast (CAF)-derived PAI-1 promoted the EndoMT of lymphatic endothelial cells (LECs) in cervical squamous cell carcinoma (CSCC). METHODS: Immunofluorescent staining of α-SMA, LYVE-1 and DAPI were examined in primary tumour samples obtained from 57 CSCC patients. Assessment of cytokines secreted by CAFs and normal fibroblasts (NFs) was performed using human cytokine antibody arrays. The phenotype of EndoMT in lymphatic endothelial cells (LECs), gene expression levels, protein secretion and activity of signaling pathways were measured by real-time RT-PCR, ELISA or western blotting. The function of lymphatic endothelial monolayers was examined by transwell, tube formation assay, transendothelial migration assay in vitro. Lymphatic metastasis was measured using popliteal lymph node metastasis model. Furthermore, association between PAI-1 expression and EndoMT in CSCC was analyzed by immunohistochemistry. The Cancer Genome Atlas (TCGA) databases was used to assess the association of PAI-1 with survival rate in CSCC. RESULTS: CAF-derived PAI-1 promoted the EndoMT of LECs in CSCC. LECs undergoing EndoMT could initiate tumour neolymphangiogenesis that facilitated cancer cell intravasation/extravasation, which in turn promoted lymphatic metastasis in CSCC. Mechanistically, PAI-1 activated the AKT/ERK1/2 pathways by directly interacting with low-density lipoprotein receptor-related protein (LRP1), thereby leading to elevated EndoMT activity in LECs. Blockade of PAI-1 or inhibition of LRP1/AKT/ERK1/2 abrogated EndoMT and consequently attenuated CAF-induced tumour neolymphangiogenesis. Furthermore, clinical data revealed that increased PAI-1 levels positively correlated with EndoMT activity and poor prognosis in CSCC patients. CONCLUSION: Our data indicate that CAF-derived PAI-1 acts as an important neolymphangiogenesis-initiating molecular during CSCC progression through modulating the EndoMT of LECs, resulting in promotion of metastasis ability in primary site. PAI-1 could serve as an effective prognostic biomarker and therapeutic target for CSCC metastasis.

The Impact of Electronic Health Record Interventions on Patient Access to Post-Hospital Discharge Prescriptions.

Purpose: Assess the impact of electronic health record interventions on patient access to post-hospital discharge prescriptions. Methods: Five interventions were implemented in the electronic health record to improve patient access to prescriptions after discharge from hospital: electronic prior authorization, alternative medication suggestions, order sets, mail order pharmacy alerts, and medication interchange instructions. This was a retrospective cohort study of patient responses from discharges during 6 months before the first intervention implementation and 6 months after the last intervention implementation documented in the electronic health record and a transition-in-care platform. Primary endpoint was the proportion of discharges with patient-reported issues that would have been prevented by the studied interventions out of number of discharges with at least one prescription, analyzed using Chi-squared test (level of significance .05). Results: Discharges with patient-reported issues that would have been prevented by the studied interventions decreased from 1.68 to 1.07 out of 1000 discharges with prescriptions (P < .001). Conclusion: Interventions in the electronic health record reduced barriers faced by patients to picking up prescriptions post-discharge from hospital, potentially leading to improved patient satisfaction and improved health outcomes. Important factors to consider for electronic health record intervention implementation are workflow development and intrusiveness of clinical decision support. Multiple targeted electronic health record interventions can improve patients' access to prescriptions after discharge from hospital.

Wood-Based Self-Supporting Nanoporous Three-Dimensional Electrode for High-Efficiency Battery Deionization.

Developing highly efficient advanced battery deionization (BDI) electrode materials at a low cost is vital for seawater desalination. Herein, a high-efficiency wood-based BDI electrode has been fabricated for seawater desalination, benefiting from the self-supporting three-dimensional (3D) nanoporous structure and rich redox-active sites. The finely tuned rich electrochemical redox active C═O groups on the surface of the wood electrode derived from the facile thermochemical conversion of lignin play a crucial role in the Faradaic cation removal dynamics of BDI. Coupling the 3D wood electrode and a polyaniline-modified wood electrode as the cathode and anode, an all-wood-electrode-based deionization battery has been successfully assembled with a state-of-the-art ion removal capacity of up to 164 mg g-1 in seawater. Our work reported an example of utilizing wood as the BDI electrode via fine-tuning the redox-active sites, demonstrating a novel resource utilization pathway of converting cheap biomass into BDI electrodes for highly efficient seawater desalination.

Potential-Mediated Recycling of Copper From Brackish Water by an Electrochemical Copper Pump.

Copper ions (Cu2+ ) disposed to the environment at massive scale pose severe threat to human health and waste of resource. Electrochemical deionization (EDI) which captures ions by electrical field is a promising technique for water purification. However, the removal capacity and selectivity toward Cu2+ are unsatisfying, yet the recycling of the captured copper in EDI systems is yet to be explored. Herein, an efficient electrochemical copper pump (ECP) that can deliver Cu2+ from dilute brackish water into much more concentrated solutions is constructed using carbon nanosheets for the first time, which works based on reversible electrosorption and electrodeposition. The trade-off between the removal capacity and reversibility is mediated by the operation voltage. The ECP exhibits a removal capacity of 702.5 mg g-1 toward Cu2+ and a high selectivity coefficient of 64 for Cu2+ /Na+ in the presence of multiple cations; both are the highest reported to date. The energy consumption of 1.79 Wh g-1 is among the lowest for EDI of copper. More importantly, the Cu species captured can be released into a 20-fold higher concentrated solution. Such a high performance is attributed to the optimal potential distribution between the two electrodes that allows reversible electrodeposition and efficient electrosorption.

Molecular Dynamics Beyond the Monolayer Adsorption as Derived from Langmuir Curve Fitting.

Langmuir adsorption model is a classic physical-chemical adsorption model and is widely used to describe the monolayer adsorption behavior at the material interface in environmental chemistry. Traditional adsorption dynamic modeling solely considered the surface physiochemical interaction between the adsorbent and adsorbate. The surface reaction dynamics resulting from the heterogeneous surface and intrinsic electronic structure of absorbents were rarely considered within the reported adsorption experiments. Herein, by employing the chlorine hybrid graphene oxide (GO-Cl) to adsorb Ag+ in an aqueous solution, complicated molecular dynamics significantly deviated from the monolayer adsorption mechanism, as suggested by Langmuir adsorption curve fitting, has been elucidated down to atomic scale. In the time-dependent Ag adsorption experiments, both Ag single atoms and Ag/AgCl nanoparticle heterostructures are observed to be formed sequentially on GO-Cl. These observations indicate that for the surface adsorption dynamics, not only the surface chemical adsorption process involved but also photoreduction and the C-Cl bond cleavage reaction has been heavily engaged within the GO-Cl interface, suggesting a much more complicated vision rather than the monolayered adsorption algorithm as derived from curve fitting. This study uses GO-Cl as a simple example to disclose the complicated adsorption dynamic process underneath Langmuir adsorption curve fitting. It advocates the necessity of imaging the interfacial atomic-scale dynamic structure with high-resolution microscopy techniques in modern adsorption studies, rather than simply explaining the adsorption dynamics relying on the curve fitting results due to the complicated physiochemical reactivity of the adsorbents.

Unlocking bimetallic active sites via a desalination strategy for photocatalytic reduction of atmospheric carbon dioxide.

Ultrathin two-dimensional (2D) metal oxyhalides exhibit outstanding photocatalytic properties with unique electronic and interfacial structures. Compared with monometallic oxyhalides, bimetallic oxyhalides are less explored. In this work, we have developed a novel top-down wet-chemistry desalination approach to remove the alkali-halide salt layer within the complicated precursor bulk structural matrix Pb0.6Bi1.4Cs0.6O2Cl2, and successfully fabricate a new 2D ultrathin bimetallic oxyhalide Pb0.6Bi1.4O2Cl1.4. The unlocked larger surface area, rich bimetallic active sites, and faster carrier dynamics within Pb0.6Bi1.4O2Cl1.4 layers significantly enhance the photocatalytic efficiency for atmospheric CO2 reduction. It outperforms the corresponding parental matrix phase and other state-of-the-art bismuth-based monometallic oxyhalides photocatalysts. This work reports a top-down desalination strategy to engineering ultrathin bimetallic 2D material for photocatalytic atmospheric CO2 reduction, which sheds light on further constructing other ultrathin 2D catalysts for environmental and energy applications from similar complicate structure matrixes.

Direct, four-step synthetic pathway to iheyamine A and several analogues.

A novel synthetic route toward the pentacyclic azepinobisindole alkaloid iheyamine A and its several analogues has been developed in four steps from commercially available isatins and tryptamines. This crucial transformation involves the Bischler-Napieralski cyclization to deliver the characteristic seven-membered framework. Then the ester intermediate undergoes a hydrolyzation-decarboxylation-dehydrogenation cascade to yield the final product.

Bi2O3/BiO2 Nanoheterojunction for Highly Efficient Electrocatalytic CO2 Reduction to Formate.

Heterostructure engineering plays a vital role in regulating the material interface, thus boosting the electron transportation pathway in advanced catalysis. Herein, a novel Bi2O3/BiO2 heterojunction catalyst was synthesized via a molten alkali-assisted dealumination strategy and exhibited rich structural dynamics for an electrocatalytic CO2 reduction reaction (ECO2RR). By coupling in situ X-ray diffraction and Raman spectroscopy measurements, we found that the as-synthesized Bi2O3/BiO2 heterostructure can be transformed into a novel Bi/BiO2 Mott-Schottky heterostructure, leading to enhanced adsorption performance for CO2 and *OCHO intermediates. Consequently, high selectivity toward formate larger than 95% was rendered in a wide potential window along with an optimum partial current density of -111.42 mA cm-2 that benchmarked with the state-of-the-art Bi-based ECO2RR catalysts. This work reports the construction and fruitful structural dynamic insights of a novel heterojunction electrocatalyst for ECO2RR, which paves the way for the rational design of efficient heterojunction electrocatalysts for ECO2RR and beyond.

Enhanced Cr(VI) reduction on natural chalcopyrite mineral modulated by degradation intermediates of RhB.

Wastewater with complex compositions of both heavy metals and organic pollutants is of critical environmental and socioeconomic threat worldwide, which urgently requires feasible remediation technologies to target this challenge. In this study, natural chalcopyrite (CuFeS2, NCP), the most abundant copper-based mineral in the Earth's crust, has been discovered to be a heterogeneous catalyst that can activate peroxydisulfate (PDS) for the simultaneous degradation of organic pollutant Rhodamine B (RhB) and reduction of hexavalent chromium (Cr(VI)). Batch experimental results indicate that both RhB and Cr(VI) could be simultaneously removed under a near-neutral condition in NCP/PDS combined system. The radicals SO4•- and •OH generated from PDS activation are the main oxidative species detected by electron paramagnetic resonance (EPR) spectroscopy. SO4•- acted as a predominant role in RhB degradation, while Cr(VI) reduction is mainly attributed to the oxidization of S2- and S22- species on NCP surface, as well as the photoreduction performance of NCP, which could be enhanced by the intermediates generated from RhB degradation. Density functional theory (DFT) calculation results disclose that Fe is the critical catalytic site for PDS activation. This work demonstrates a user-friendly strategy for remediation of complex wastewater containing both heavy metal and organic pollutants by combining photoreduction and advanced oxidation processes (AOPs) with natural minerals. It paves a way for wastewater treatment by utilizing low-cost natural abundant minerals as catalysts.

Transferring waste red mud into ferric oxide decorated ANA-type zeolite for multiple heavy metals polluted soil remediation.

Herein, a novel "waste reclamation for soil remediation" strategy has been developed for both alkaline waste red mud (RM) recycling and heavy metal (HM) polluted soil remediation. Through a direct one-pot hydrothermal reaction process, the Al, Si, alkali, and Fe2O3 components in waste RM have been transferred into ferric oxide decorated ANA-type zeolite (Fe2O3-ANA). As tested by the HMs polluted soil remediation and oilseed rape planting experiment, when 25 g/kg Fe2O3-ANA is added into the Pb2+, Cu2+, Cr3+ and anionic AsO2- polluted soil (HM concentration: 100-200 mg/kg), it can effectively suppress the HMs mobility in soil and reduce the bio-accumulation concentrations of HMs in the harvested oilseed rape (reduce ratio: 37.9-69.5%). The detailed mechanism study using energy dispersive X-ray energy spectroscopy, in-depth X-ray photoelectron spectroscopy and density function theory calculation concludes that the Cu2+, Pb2+ and Cr3+ in soil have been adsorbed and trapped in the framework structure of ANA in Fe2O3-ANA mainly via the cation exchange process. While the anionic AsO2- species are mainly caught by the Fe2O3 component in Fe2O3-ANA via surface adsorption. Overall, this work firstly transforms waste RM into Fe2O3-ANA for soil remediation, which is valuable to waste resource recycling and environmental conservation.

Cancer-Associated Fibroblast Heterogeneity: A Factor That Cannot Be Ignored in Immune Microenvironment Remodeling.

Cancer-associated fibroblasts (CAFs) are important, highly heterogeneous components of the tumor extracellular matrix that have different origins and express a diverse set of biomarkers. Different subtypes of CAFs participate in the immune regulation of the tumor microenvironment (TME). In addition to their role in supporting stromal cells, CAFs have multiple immunosuppressive functions, via membrane and secretory patterns, against anti-tumor immunity. The inhibition of CAFs function and anti-TME therapy targeting CAFs provides new adjuvant means for immunotherapy. In this review, we outline the emerging understanding of CAFs with a particular emphasis on their origin and heterogeneity, different mechanisms of their regulation, as well as their direct or indirect effect on immune cells that leads to immunosuppression.