Search

Crocetin is a bioactive ingredient in saffron, derived from the Crocus sativus stigmas of the Iridaceae family. As a chemically carotenoid derivative, crocetin exhibites effects like anti-inflammatory, antioxidant, neuroprotective, etc. However, the protective effect of crocetin on glaucoma and its mechanism remains unclear. The current study assesed the neuroprotective and anti-inflammatory effects of crocetin on retinal neurons in glaucoma rats which were induced by 0.3% carbomer injection into the anterior chamber.The pathological structures on the retina and optic nerve were observed and examined by HE staining and transmission electron microscopy. Immunohistochemical staining was used to detect the expression of TNF-α, IL-1β, and IL-6 of the retina and the expression of a brain-derived neurotrophic factor (BDNF) in the primary visual cortex (PVC). Western blot was carried out to detect the expression of PI3K, Akt, and NF-κB in the retina. It was found that crocetin ameliorated the pathological changes of the retina and ON and reduced the number of apoptotic retinal ganglion cells. Immunohistochemical staining showed that crocetin could decrease the contents of TNF-α, IL-1β, and IL-6 and increase the contents of BDNF. Western blot showed that crocetin was found to suppress the expression of PI3K, Akt, and NF-κB.The results obtained in this study have indicated that crocetin showes neuroprotective effects on retinal ganglion cells in glaucoma rats and inhibits retinal dysfunction. Meanwhile, crocetin exerted an anti-inflammatory effect to protect the retina by inhibiting the expression of the PI3K/Akt/NF-κB signaling pathway. This work provides substantial evidence that crocetin may be a potential drug for the treatment of glaucoma.

Background The objective of this study was to investigate the treatment efficacy of stereotactic body radiotherapy (SBRT) and evaluate the influence of radiation dose on local control and survival in patients with abdominal lymph node metastases (LNM) from hepatocellular carcinoma (HCC). Patients and methods Between 2010 and 2020, data of 148 patients with HCC with abdominal LNM, including 114 who underwent SBRT and 34 who received conventional fractionation radiation therapy (CFRT), were collected. A total radiation dose of 28-60 Gy was delivered in 3-30 fractions, with a median biologic effective dose (BED) of 60 Gy (range, 39-105 Gy). Freedom from local progression (FFLP) and overall survival (OS) rates were analyzed. Results With a median follow-up of 13.6 months (range, 0.4-96.0 months), the 2-year FFLP and OS rates of the entire cohort were 70.6% and 49.7%, respectively. Median OS of the SBRT group was longer than the CFRT group (29.7 vs. 9.9 months, P = .007). A dose-response relationship was observed between local control and BED in either the entire cohort or the SBRT subgroup. Patients who received SBRT with a BED ≥60 Gy had significantly higher 2-year FFLP and OS rates than those who received a BED Conclusions SBRT achieved satisfactory local control and survival with feasible toxicities in patients with HCC with abdominal LNM. Moreover, the findings of this large series suggest a dose-response relationship between local control and BED.

To determine risk factors, treatment outcomes, and prognostic factors for esophageal fistula (EF) in patients with esophageal squamous cell carcinoma (ESCC) during radiotherapy.Between 2010 and 2018, 109 patients with EF during radiotherapy were retrospectively collected. A controlled cohort including 416 patients who received definitive chemoradiotherapy without EF was used to compare risk factors and survival outcomes. Univariate and multivariate logistic regression analyses were performed to identify predictors of EF. Propensity score matching (PSM) was applied to adjust for potential confounding factors.Multivariate analysis demonstrated that sex, body mass index, alcohol history, esophageal ulceration, primary tumor length, T stage, and absolute lymphocyte count were independent risk factors for EF. After PSM, patients with EF showed remarkably worse prognosis than those without EF (median overall survival: 13.0 versus 20.5 months; P = 0.009). For patients with EF, serum albumin level (≥ 35 g/L), subsequent radiotherapy, and fistula closure were associated with significantly prolonged survival. In addition, esophageal-mediastinum fistula and subsequent radiotherapy were positive predictors for fistula closure.We identified risk factors for radiotherapy-related EF and its unfavorable prognosis in patients with ESCC. Of them, patients with serum albumin level of ≥ 35 g/L, subsequent radiotherapy after EF, and fistula closure had a more favorable survival.

BACKGROUND: Imatinib-associated skin rash in gastrointestinal stromal tumor (GIST) patients is one of the most troublesome adverse effects, and can reduce imatinib adherence and persistence. However, the relationship between skin rash and adherence is unknown, and there are few published studies on the clinical outcomes of patients with severe skin rash. METHODS: Adult patients (≥18 years) who were treated with 400 mg/day imatinib for unresectable or metastatic GIST were enrolled in this retrospective study. The skin rash was graded by physicians according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.03. Progression-free survival (PFS) was compared using the Kaplan-Meier method between groups with and without skin rash. The risk factors for GIST progression were investigated by Cox regression analysis. RESULTS: A total of 125 GIST patients were finally included. Among them, 43 (34.4%) patients developed skin rash during imatinib treatment. Serial blood eosinophil levels were associated with skin rash and severity (P

Although Ti3C2Tx MXene is a promising material for many applications such as catalysis, energy storage, electromagnetic interference shielding due to its metallic conductivity and high processability, it’s poor resistance to oxidation at high temperatures makes its application under harsh environments challenging. Here, we report an air-stable Ti3C2Tx based composite with extracted bentonite (EB) nanosheets. In this case, oxygen molecules are shown to be preferentially adsorbed on EB. The saturated adsorption of oxygen on EB further inhibits more oxygen molecules to be adsorbed on the surface of Ti3C2Tx due to the weakened p-d orbital hybridization between adsorbed O2 and Ti3C2Tx, which is induced by the Ti3C2Tx/EB interface coupling. As a result, the composite is capable of tolerating high annealing temperatures (above 400 °C for several hours) both in air or humid environment, indicating highly improved antioxidation properties in harsh condition. The above finding is shown to be independent on the termination ratio of Ti3C2Tx obtained through different synthesis routes. Utilized as terahertz shielding materials, the composite retains its shielding ability after high-temperature treatment even up to 600 °C, while pristine Ti3C2Tx is completely oxidized with no terahertz shielding ability. Joule heating and thermal cycling performance are also demonstrated.

OBJECTIVE The main aim of this study was to optimize the formula of saffron compound essence (SCE) and investigate the protective effects and mechanisms of SCE against skin photoaging. MATERIALS AND METHODS The formula of SCE was optimized using single factor and orthogonal experiments. The optimized SCE was then applied on the back skin of mice under ultraviolet irradiation. The protective effect and possible mechanism of SCE on skin photoaging were investigated using macroscopic and histological evaluation, skin thickness tests, determination of skin microcirculation, and the skin content determination of type I and III collagen, matrix metalloproteinase-2 (MMP-2), and extracellular regulatory protein kinase (ERK1/2) on the skin of each group of photoaging mice model. RESULTS The SCE prepared using the optimal formula was golden yellow, uniform, fine, and viscous. The obtained results in the SCE high dose group indicated that SCE can inhibit the generation of wrinkles, decrease the skin thickness, reduce the microcirculation blood flow of the back skin of mice, alleviate the proliferation and abnormal accumulation of collagen fibers and elastic fibers, increase the content of skin type I and III collagen, up-regulate the expression MMP-2 protein, and down-regulate the expression ERK1/2 protein, when compared with the shave control group. CONCLUSION The results obtained in this study have indicated that the optimized SCE has the effect of preventing skin photoaging, and its mechanism may be associated with the ERK1/2 pathway. Therefore, SCE should be regarded as a potential therapeutic agent for preventing photoaging.

The development and evaluation of the transport capacity of oil and gas determine the location of the associated fractures based on the analysis of its ability to transport oil and gas and finding favorable locations in different periods of the faults. This paper also explored the distribution of oil and gas in different positions near the lower generation and upper reservoir faults in the petroliferous basin, while locations of the faults’ convex ridges with stronger oil and gas transporting ability are also determined and evaluated. A set of prediction methods in determining favorable locations for oil and gas transport capacity configured in different periods of fault are established and applied in different periods of the F3 fault in the Daliuquan area, Langgu Sag, Jizhong Depression, Bohai Bay Basin. The results of these two evaluations indicate that the development position of associated fractures of the F3 fault with strong oil and gas transport capacity was distributed primarily in the eastern part of the area. Sections of the convex ridge with stronger oil and gas transport capacity, on the other hand, are mainly distributed in the western, middle, and eastern faults. The favorable location of transporting oil and gas ability configuration of the F3 fault in different periods is distributed mainly in the east of the F3 fault, where oil and gas generated by the source rock of the Sha 4 Member (Es4) migrate and accumulate to the middle and lower sections of the Sha 3 Member (Es31−2) through the developmental position of associated fractures and convex ridges.

Background A substantial number of patients with esophageal squamous cell carcinoma (ESCC) do not achieve complete remission after definitive concurrent chemoradiotherapy (dCRT). We performed this retrospective study to evaluate the efficacy and safety of apatinib combined with S-1/capecitabine as the oral maintenance therapy for these patients. Methods Thirty-nine ESCC patients with residual disease after dCRT were included. Patients were treated with apatinib combined with S-1 /capecitabine after dCRT. Efficacy, toxicity, and survival were analyzed. Results Of the 39 patients, 5 (12.8%) achieved a partial response and 29 (74.4%) achieved stable disease, yielding a disease control rate of 87.2%. The median progression-free survival (PFS) and overall survival (OS) were 27.5 (95%CI: 14.9 - 40.1) and 38.1 (95%CI: 31.3 - 44.8) months. Most frequent adverse events were of grade 1 to 2. Multivariate analysis revealed the occurrence of any adverse events (HR = 0.274, 95%[CI] = 0.119 - 0.630) correlated to better PFS and occurrence of proteinuria (HR = 0.108, 95%[CI] = 0.025 - 0.456) predicted better OS. Conclusion The oral combination therapy consisting of apatinib and S-1/capecitabine showed a tolerable toxicity profile and achieved satisfactory disease control in ESCC patients with residual disease after dCRT.

Purpose This study aimed to develop a nomogram for predicting pathologic complete response (pCR) after neoadjuvant chemoradiotherapy (CRT) in patients with esophageal squamous cell carcinoma (ESCC) by integrating hematological biomarkers and clinicopathological characteristics.Materials and Methods Between 2003 and 2017, 306 ESCC patients who underwent neoadjuvant CRT followed by esophagectomy were analyzed. Besides clinicopathological factors, hematological parameters before, during, and after CRT were collected. Univariate and multivariate logistic regression analyses were performed to identify predictive factors for pCR. A nomogram model was built and internally validated.ResultsAbsolute lymphocyte count (ALC), lymphocyte to monocyte ratio, albumin, hemoglobin, white blood cell, neutrophil, and platelet count generally declined, whereas neutrophil to lymphocyte ratio (NLR) and platelet to lymphocyte ratio (PLR) increased significantly following neoadjuvant CRT. After surgery, 124 patients (40.5%) achieved a pCR. The pCR group demonstrated significantly more favorable survival than the non-pCR group. On multivariate analysis, significant factors associated with pCR included sex, chemotherapy regimen, post-CRT endoscopic finding, pre-CRT NLR, ALC nadir during CRT, and post-CRT PLR, which were incorporated into the prediction model. The nomogram indicated good accuracy in predicting pCR, with a C-index of 0.75 (95% confidence interval, 0.71 to 0.78).Conclusion Female, chemotherapy regimen of cisplatin/vinorelbine, negative post-CRT endoscopic finding, pre-CRT NLR (≤ 2.1), ALC nadir during CRT (> 0.35 ×109/L), and post-CRT PLR (≤ 83.0) were significantly associated with pCR in ESCC patients treated with neoadjuvant CRT. A nomogram incorporating hematological biomarkers to predict pCR was developed and internally validated, showing good predictive performance.

This article describes a novel strategy for assembling gold nanoparticles (AuNPs) into chainlike structures and modulating their assembly by surface engineering. The chainlike assemblies are induced to form by adding ethylamine (EA) into a suspension of AuNPs, and the volume ratio of ethanol/water greatly affects the assembly speed and length of the chainlike assemblies. By comparing various structural analogs of EA, it is demonstrated that the primary amine of EA is critically important for AuNP assembly. This study also reveals that besides dielectric surrounding and destabilizing agents, surface engineering also significantly influences the optical properties of plasmonic nanostructures. During this assembly, we have found that two kinds of additives could inhibit or mitigate the AuNP assembly, which were barely reported. The effects of AgNO3 and halogen compounds, especially KI, on the assembly of AuNPs were studied in detail. Possible mechanisms for controlling AuNP assembly through surface engineering are proposed. Taken together, this study provides a new strategy to regulate the assembly of plasmonic nanoparticles and points out the importance of surface engineering in assembly.

Two-dimensional (2D) transition metal di-nitrides (TMN2) have been arousing great interest for their unique mechanic, electronic, optoelectronic, and magnetic properties. The recent successful growth of monolayer MSi2N4 (M = Mo and W) further motivates us to explore new physics and unusual properties behind this family. By using first-principles calculations and Bardeen–Cooper–Schrieffer theory, we predicted the existence of the superconductivity in single-layer (SL) 1T- and 1H-TaN2 with superconducting transition temperatures (Tc) of ∼0.86 and 1.3 K. Specifically, the Tc could be greatly enhanced to ∼24.6 K by passivating the TaN2 monolayer with Si–N bilayers. Furthermore, the superconductivity could be increased to ∼30.4 K via substituting lighter Nb for Ta. This enhancement of superconductivity mainly stems from the softer vibration modes consisting of in-plane Ta/Nb vibrations mixed with Si-xy vibrations. The superconductivity can be further tuned by applying external strains and carrier doping. This enhancement strategy of surface passivation and light atom substitution would suggest a new platform for 2D superconductors and provide an instructive pathway for next-generation nanoelectronics.

Load shedding (LS) is an effective control strategy against voltage instability in power systems. With increasing uncertainties and complexity in modern power grids, there is a pressing need for faster and more accurate control decisions. In this article, a hierarchical data-driven method is proposed for the online prediction of event-based load shedding (ELS) against fault-induced delayed voltage recovery. The ELS problem is hierarchically modeled as a multi-output classification subproblem for identifying the best shedding location and a regression subproblem to predict the minimum shedding amount. To solve the two subproblems, the weighted kernel extreme learning machine is adopted to construct a direct mapping between the system pre-fault operating conditions and the corresponding control variables. The method is tested on the ELS database, which is analytically generated via a novel adaptive sensitivity-based process on the New England 39-bus system. Compared with other methods, the proposed method is very accurate in prediction with excellent control performance, which maintains superior prediction ability under an imbalanced data distribution.

As one of the largest pharmaceutical combinations used in therapeutic medicine and feed supplements, the problem of water pollution caused by antibiotics has been put in the spotlight. In this work, tetracycline hydrochloride (TC) was efficiently photocatalytically degraded over 2D/2D S-scheme Agx–g-C3N4–Bi2WO6 (AxC/B) photocatalysts, which were prepared using a simple hydrothermal method. Under visible-light irradiation, the TC degradation efficiency of A3C/B reached 81.4% in 60 min, which was 2.85 times and 1.52 times those of pure CN and pure BWO, respectively. The enhanced TC degradation performance of A3C/B was mainly due to the synergistic effect of the abundant active sites and efficient photo-generated carrier separation rate in the 2D/2D S-scheme system. In addition, Ag nanoparticles acted as cocatalysts, which would promote electron migration from the conduction band of CN by forming a Schottky barrier between CN and Ag. The main reactive species, superoxide radicals (˙O2−), hydroxyl radicals (˙OH) and holes (h+), were all involved in the reaction, which was proved by a trapping experiment. In summary, this research showed that A3C/B was significant for TC degradation under visible-light illumination and provided a novel strategy for TC degradation of various S-scheme 2D/2D-like photocatalysts.

Monthly runoff data of six hydrological control stations in Shiyang River Basin from 1961 to 2016

Depression is a serious mood disorder, and crocetin has a variety of pharmacological activities, including antidepressant effect. The alterations of intestinal flora have a significant correlation with depression, and crocetin can alter the composition of intestinal flora in mice with depression-like behaviors.This study investigated the underlying antidepressant mechanisms of crocetin through multi-omics coupled with biochemical technique validation.Chronic unpredictable stress (CUMS) was used to induce mice model of depression to evaluate the antidepressant effect of crocetin through behavioral tests, and the metagenomic and metabolomic were used to explore the potential mechanisms involved. In order to verify its underlying mechanism, western blot (WB), Elisa, immune histological and HPLC techniques were used to detect the level of inflammatory cytokines and the level of metabolites/proteins related to tryptophan metabolism in crocetin-treated mice.Crocetin ameliorated depression-like behaviors and increased mobility in depressive mice induced by CUMS. Metagenomic results showed that crocetin regulated the structure of intestinal flora, as well as significantly regulated the function gene related to derangements in energy metabolism and amino acid metabolism in mice with depression-like behaviors. Metabolomic results showed that the tryptophan metabolism, arginine metabolism and arachidonic acid metabolism played an essential role in exerting antidepressant-like effect of crocetin. According to multi-omics approaches and validation results, tryptophan metabolism and inflammation were identified and validated as valuable biological processes involved in the antidepressant effects of crocetin. Crocetin regulated the tryptophan metabolism in mice with depression-like behaviors, including increased aryl hydrocarbon receptor (AhR) expression, reduced indoleamine 2,3-dioxygenase 1 (IDO1) and serotonin transporter (SERT) expression in the hippocampus, elevated the content of 5-HT, kynurenic acid in serum and 5-HT, tryptophan in hippocampus. In addition, crocetin also attenuated inflammation in mice with depression-like behaviors, which presented with reducing the production of inflammatory cytokines in serum and colon. Meanwhile, crocetin up-regulated the expression of zonula occludens 1 (ZO-1) and occludin in ileum and colon to repair the intestinal barrier for preventing inflammation transfer.Our findings clarify that crocetin exerted antidepressant effects through its anti-inflammation, repairment of intestinal barrier, modulatory on the intestinal flora and metabolic disorders, which further regulated tryptophan metabolism and impacted mitogen-activated protein kinase (MAPK) signaling pathway to enhance neural plasticity, thereby protect neural.

The physiological function and prognostic significance of C-type lectin domain family 12 member A (CLEC12A) in acute myeloid leukemia (AML) patients are unclear. CLEC12A transcriptional expression in a variety of tumors from several public databases was collected and compared. We found that CLEC12A was highly expressed in AML cell lines and in tissues from AML patients and a higher CLEC12A expression in leukemia stem cells. CLEC12A low expression was associated with poor prognosis in the chemotherapy-only group and high CLEC12A expression may benefit from autologous or allogeneic hematopoietic stem cell transplantation (HSCT). CLEC12A expression was positively correlated with infiltrating levels of type 2 macrophages and monocytes and negatively associated with NK cells and regulatory T cells in AML. CLEC12A high was positively associated with immune checkpoint genes as well as macrophage associated genes. CLEC12A is an ideal chimeric antigen receptor T-cell (CAR-T) therapy target for AML and its expression level was closely linked to treatment response and patients' survival outcome. CLEC12A plays an important immunomodulatory role in AML.

Purpose: To investigate the comparative anti-thrombotic effects of saffron and Honghua, and also to explore possible mechanisms in thrombosis based on network pharmacology. Methods: A network pharmacology model was used for bioactive components, targets and pathways for saffron and HongHua via Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP), PharmMapper, Genecard, Uniprot and KEGG databases. In animal experiments, 72 rats were randomly divided into 9 groups: normal control group (NC), model control group (MC), crocetin groups (80, 40, 20 mg/kg), hydroxysafflor yellow A(HSYA) groups (80, 40, 20 mg/kg), and aspirin group (40 mg/kg). Using in vitro thrombosis models and an acute blood stasis model in vivo, the anti-thrombotic effects of these treatments on clotting time, hemorheology parameters, Thromboxane B2 (TXB2), plasmin activator inhibitor (PAI), protein C (PC), protein S (PS), and thrombinantithrombin complex (TAT) were determined and comparisons made for saffron and HongHua. Results: Five potential compounds, 16 anti-thrombotic targets and 27 pathways were predicted for saffron, while 22 compounds, 37 disease targets and 35 pathways were found for HongHua (p < 0.05). Pharmacological experiments revealed that crocetin and HSYA had significant effects on thrombus length, thrombus wet/dry mass, whole blood viscosity (WBV), erythrocyte aggregation index (EAI), clotting time and D-dimer for the high and middle groups. Unlike HSYA, crocetin also had significant and dose-dependent effects on PAI, prothrombin fragment 1+2 (F1+2) and PS and had highly significant effects on TXB2 and TAT. Conclusion: This research provides a systematic, comprehensive and comparative analysis of component, target and anti-thrombotic pathways of saffron and HongHua based on network pharmacology, and also shows that saffron has more significant anti-thrombotic effect than HongHua. Keywords: Saffron; HongHua; Network pharmacology; Anti-thrombosis; Network model

A novel 2D/2D Bi2MoO6/g-C3N4 step-scheme (S-scheme) composite by loading Au as cocatalyst was successfully fabricated using a photoreduction and hydrothermal route. The obtained Bi2MoO6/g-C3N4/Au photocatalysts were characterized by X-ray diffraction (XRD), transmission electron microscope (TEM), X-ray photo-electron spectroscopy (XPS), UV-vis diffuse reflectance spectra (UV-vis), Fourier transform infrared spectroscopy (FTIR), photoluminescence (PL), photocurrent response(I-t), and electrochemical impedance spectroscopy (EIS). The HRTEM images revealed that an intimate interface in composites were formed. The optimum photocatalytic activity of Rhodamine B degradation over Bi2MoO6/g-C3N4/Au was about 9.7 times and 13.1 times as high as those of Bi2MoO6 and g-C3N4, respectively. The notably improved photocatalytic activity of Bi2MoO6/g-C3N4/Au could be mainly ascribed to the abundant active sites and the enhanced separation efficiency of photogenerated carriers in Bi2MoO6/g-C3N4 S-scheme system. Notably, Au nanoparticles could act as a co-catalyst to further promote electron transfer and separation from the conduction band of g-C3N4. Additionally, a possible step-scheme photocatalytic reaction mechanism of RhB degradation over Bi2MoO6/g-C3N4/Au was tentatively proposed. PL and transient photocurrent analysis implied that Bi2MoO6/g-C3N4/Au photocatalysts possessed the lower recombination rate of photogenerated carriers compared with pure Bi2MoO6 and g-C3N4, respectively. The present work is expected to provide useful information in designing 2D/2D S-scheme heterojunction photocatalysts.

In this study, a series of dual two-dimensional (2D/2D) Z-scheme g-C3N4/BiVO4 ultrathin nanosheets were successfully fabricated by coupling 2D g-C3N4 and 2D BiVO4 ultrathin nanosheets via a thermal-polymerization and subsequent hydrothermal method. The mass ratio between g-C3N4 and BiVO4 was optimized to improve the visible-light photocatalytic performance of CO2 reduction. Significantly, g-C3N4/BiVO4 (5:5) composite exhibited the optimal CO2 conversion efficiency towards CH4 (4.57 μmol g−1 h−1) and CO (5.19 μmol g−1 h−1), which were 4.8 and 4.4 folds higher than that of g-C3N4. The suitable band structures of single components induced the formed direct Z-scheme heterojunction, which efficiently suppressed the photoinduced carrier recombination and remained the strong redox capability. Moreover, the tight face-to-face interfacial contact between 2D g-C3N4 and 2D BiVO4 increased the transmission channels and accessible area for charges, and thereby facilitated charge transfer and provided abundant active sites for the photocatalytic reaction. Based on the trapping experiments, the photocatalytic mechanisms of g-C3N4/BiVO4 were reasonably proposed and validated by the photoluminescence spectra associated with time-resolved fluorescence decay. Furthermore, the repetitive photocatalytic experiments demonstrated the advantage of recyclability, which endowed 2D/2D Z-scheme g-C3N4/BiVO4 heterojunctions a promising application prospect.

The Sugan Lake Basin is located in the inland arid region of northwestern China, in which groundwater is of great significance to human and ecology. Therefore, it is necessary to understand the chemical characteristics and quality of groundwater in the basin. Based on samples collected from 35 groundwater wells in Sugan Lake Basin, the spatial distribution characteristics of groundwater chemistry, main hydrogeochemical processes and groundwater quality have been discussed in this paper by using the multivariate statistics and hydrochemistry analysis methods. The results showed that the groundwater is weakly alkaline, and its total dissolved solid (TDS) and total hardness (TH) are high, with the average values of 1244.03 mg/L and 492.10 mg/L, respectively. The types of groundwater are mainly HCO3−-SO42−-Ca2+ type in the runoff area and Cl−-SO42−-Na+ type in the catchment area. Rock weathering and ion exchange are the main controlling factors of regional groundwater chemistry, followed by evaporative crystallization, and human activities have less impact on groundwater. The spatial difference of groundwater quality is obvious, the water quality of the catchment area is not suitable for drinking, and the suitability for plant growth is also poor. The groundwater in the runoff area can be used for drinking, but the hardness is slightly higher, which is more suitable for ecological purpose.

Numerous hydrophobic compounds are important ingredients for drug discovery and development. Hydrophobicity has been a major hurdle limiting the therapeutic efficacy of drugs. Drugs with low solubility are biopharmaceutically classified as class II and class IV drugs. Other challenges facing the pharmaceutical industry include low bioavailability, poor dissolution and erratic absorption of various compounds. In recent years, several technologies and methods have been developed to improve the solubility of drugs, meanwhile various mechanisms of improving solubility of compounds have been proposed. This review explores recent advances and techniques used to enhance solubility of lipophilic or low-solublility drugs. We summarize several strategies, such as rotor stator colloid mill, jet mill, ball mill, spray drying, hot melt extrusion, supercritical fluid and structural modification, including salt formation, and co-crystallization.

Background: Gut microbiota and their secreted metabolites influence the initiation, progression, and treatment responsiveness of colon cancer. Microbiota-based therapy regulated by probiotics has been considered as an effective strategy for prevention and therapeutic of colon cancer, whereas the antitumor mechanisms influenced by microbiota and their metabolites with intervention of probiotic remain further investigated.Results: Here, we investigated the preventive and therapeutic efficiency of commensal Lactobacillus in subcutaneous tumor models, and the underlying antitumor mechanism through the alteration of gut microbiota and their metabolites regulated by commensal Lactobacillus. Interestingly, we found that tumor formation rate in subcutaneous tumor models reduced 86.21% and 82.76%, in comparison to tumor controls when administrated with living or inactivated Lactobacillus (JY300-8 and JMR-01) for 20 days in advance. Subsequently, continuously oral administration for living or inactivated commensal Lactobacillus suppressed significantly the growth of tumor, and the tumor volumes declined 65.2% and 61.18%, respectively. Furthermore, microbiome and metabolome analyses revealed that commensal Lactobacillus suppressed colon tumorigenesis and progression through the modulation of gut microbiota and metabolites which included the down-regulation of secondary bile acids, sphingosine 1-phosphate (S1P) signaling in cancer and pyrimidine metabolism, as well as the production of anticarcinogenic compounds in tumor-bearing mice. Particularly, limitation the effects of S1P signaling via the modulation of sphingosine expression using probiotics, exerted antitumor efficiency.Conclusions: The work indicated the feasibility of using an effectively safe strategy to prevent the occurrence of colon cancer, and provided a potential therapeutic target for new therapeutics strategy via altering S1P signaling in cancer.

Neoadjuvant chemoradiotherapy followed by esophagectomy is the standard treatment for patients with locally advanced esophageal squamous cell carcinoma (ESCC). This study explored correlations of clinical factors and dose-volume histogram (DVH) parameters with postoperative cardiopulmonary complications and predicted their risk by establishing a nomogram model.Clinical and DVH parameters of ESCC patients who underwent trimodality treatment from 2002 to 2020 were collected. Postoperative cardiopulmonary complications were recorded. Logistic regression analysis was applied, and a nomogram model was constructed. Area under the receiver operating characteristic (AUC) curve, calibration curve, and decision curve analyses were performed to evaluate the performance of the nomogram.Of the 307 ESCC patients enrolled in this study, 65 (21.2%) experienced pulmonary complications and 57 (18.6%) experienced cardiac complications. The following six risk factors were identified as independent risk factors for pulmonary complications by multivariate logistic regression analyses in the integrated model: male sex (odds ratio [OR], 3.26; 95% confidence interval [CI], 1.27-9.70; P = 0.021), post-radiation therapy (RT) forced expiratory volume in 1 s (FEV1) (OR, 0.51; 95% CI 0.28-0.90; P = 0.023), mean lung dose (MLD) (OR, 1.13; 95% CI 1.01-1.28; P = 0.041), and pre-RT monocyte (OR, 8.36; 95% CI 1.23-11.7; P = 0.03). The AUC of this integrated model was 0.705 (95% CI 0.64-0.77). The paclitaxel and cisplatin (TP) concurrent chemotherapy regimen was the independent predictor of cardiac complication (OR, 2.50; 95% CI 1.22-5.55; P = 0.016).For ESCC patients who underwent trimodality treatment, male sex, post-RT FEV1, MLD, and pre-RT monocyte were confirmed as significant predictors of postoperative pulmonary complications. A nomogram model including six risk factors was further established. The independent predictor of cardiac complication was TP concurrent chemotherapy.

Cardioembolic stroke (CS) is the most common type of ischemic stroke in the clinic, leading to high morbidity and mortality worldwide. Although many studies have been conducted, the molecular mechanism underlying CS has not been fully grasped. This study was aimed at exploring the molecular mechanism of CS using comprehensive bioinformatics analysis and providing new insights into the pathophysiology of CS. We downloaded the public datasets GSE58294 and GSE16561. Differentially expressed genes (DEGs) were screened via the limma package using R software. CIBERSORT was used to estimate the proportions of 22 immune cells based on the gene expression profiling of CS patients. Using weighted gene correlation network analysis (WGCNA) to cluster the genes into different modules and detect relationships between modules and immune cell types, hub genes were identified based on the intersection of the protein-protein interaction (PPI) network analysis and WGCNA, and their clinical significance was then verified using another independent dataset GSE16561. Totally, 319 genes were identified as DEGs and 5413 genes were clustered into nine modules using WGCNA. The blue module, with the highest correlation coefficient, was identified as the key module associated with stroke, neutrophils, and B cells naïve. Based on the PPI analysis and WGCNA, five genes (MCEMP1, CLEC4D, GPR97, TSPAN14, and FPR2) were identified as hub genes. Correlation analysis indicated that hub genes had general association with infiltration-related immune cells. ROC analysis also showed they had potential clinical significance. The results were verified using another dataset, which were consistent with our analysis. Five crucial genes determined using integrative bioinformatics analysis might play significant roles in the pathophysiological mechanism in CS and be potential targets for pharmaceutic therapies.

Recently, the MXene-like MOenes provide a novel combination of mechanical, electronic, and optical properties attractive for next-generation low-dimensional quantum and optoelectronic devices. The Janus structure induced by asymmetric surfaces could bring about unique features due to the existence of a built-in electric field. In this study, Janus 2H- and 1T-Ti2OFCl monolayers are systematically scrutinized via the first-principle calculations. 2H- and 1T-Ti2OFCl monolayers are direct semiconductors with a bandgap of 0.75 and 1.12 eV, respectively. Intriguingly, biaxial strains can lead to a three-component 2D pseudospin-1 fermion and a two-component 2D double Weyl fermion during the quantum phase transitions. The effective k· p models further help to characterize these emergent fermions. In addition, the light absorbance calculations including the excitonic effect show that Ti2OFCl monolayers can be potentially applied in infrared detectors and exciton solar cells. This work would further understand the inherently chemical and physical features of the MOene family.

Purpose The goal of this study was to create a cleaning procedure by comparing the performance of six different cleaning methods on the surfaces in pharmacy intravenous admixture service (PIVAS) work area. Method A stainless steel plate was simulating contaminated by gemcitabine, cyclophosphamide, epirubicin, etoposide, and paclitaxel, which was then dried and cleaned by per current cleaning protocols. The residues were collected and quantified by ultra-performance liquid chromatography–tandem mass spectrometry (UPLC–MS/MS). Based on the most appropriate cleaning protocol, three cleaning variables were optimized: (1) use of dry gauze after cleaning agent application; (2) cleaning paths (inside-out vs. outside-in); (3) cleaning times (once or twice). Best conditions were tested with real samples from a hospital PIVAS. Results This 10–2 M sodium dodecyl sulfate (SDS) and dry gauze cleaning protocol increases cleaning efficiency as well as saves time. Different from the traditional cleaning manner, we found that cleaning from outside to inside can not only improve the cleaning efficiency but also overcome the uneven distribution of drug residues caused by cleaning action. When simulating contamination at a high dose (4 mg/mL) level, it was found that the decontamination efficacy increased with repeating one more time. Conclusion The 10–2 M SDS and dry gauze cleaning protocol could obtain the best cleaning effect. The success of cytotoxic drug decontamination is determined not only by the cleaning solution, but also by the cleaning route and frequency. Compared with the traditional cleaning manner, there was a significant reduction in the contamination levels in the PIVAS work area after the cleaning protocol with 10–2 M SDS and dry gauze.

Two-dimensional (2D) transition metal di-nitrides (TMN

Tumor-associated macrophages (TAMs), which display a tumor-supportive M2 phenotype, are closely related to tumor growth and metastasis. The reprogramming of TAMs toward a tumoricidal M1 profile has emerged as an attractive strategy for cancer immunotherapy. In this study, we found that the intratumoral injection of PcrV protein, a component of the Pseudomonas aeruginosa type 3 secretion system, suppressed tumor growth and increased apoptosis, inducible nitric oxide synthase (iNOS) expression, and the percentage of M1-polarized TAMs in tumor tissues. Furthermore, the intratumoral injection of PcrV-primed macrophages exerted a similar tumoricidal effect. In vitro analyses revealed that PcrV reeducated TAMs toward an antitumoral M1 phenotype and augmented their nitric oxide (NO)-mediated cytotoxicity against cancer cells. Mechanistically, we found that these effects were dependent on the activation of Toll-like receptor 4 (TLR4)/myeloid differentiation factor 88 (MyD88)-mediated regulation of a PI3K/AKT/mTOR-glycolysis-NO feedback loop via direct interaction with TLR4. Collectively, these results revealed a potential role for PcrV in cancer immunotherapy through the targeting of TAM plasticity.

Scientific understanding of regional wind speed variation characteristics and driving mechanisms is of great practical significance to the management and rational utilization of wind energy resources, ecological protection and governance, and sustainable development of agriculture. Taking the Shiyang River Basin in inland river basin of monsoon marginal zone as the study area, this paper analyzed wind speed changes and influencing factors at different time and space scales. The results showed that, first of all, the annual average wind speed showed a downward trend as a whole in Shiyang River Basin, and the change of spring wind speed and the decreasing frequency of daily max-wind speed above Grade 5 were the main contributors. The turning point of annual average wind speed was consistent with that in spring and autumn (1981) and earlier than that in winter and summer (1982). Secondly, as far as the wind speed change tendency rate is concerned, before the turning point, Yongchang area had the largest decline rate with obvious “2000 m effect”, while after the turning point, Wuwei Basin had the largest rise rate with obvious “basin effect”. Focusing on the downstream desert oasis region, the sand-driving wind speed showed a decreasing trend as a whole, and showed a “cliff-like” decline after 1988. The rising trend of sand-driving wind speed after 2014 will pose greater challenges to ecological governance. Finally, under the background of unbalanced global warming, the wind speed changes in different periods were driven by the circulation system changes. In 1970–1981, the decline of the wind speed was the result of the combined action of Arctic Oscillation and Asia Polar Vortex. However, after 1981, it was affected by North Atlantic Oscillation, Asian Meridional Circulation, Tibet Plateau Circulation, India-Burma Trough, Western Pacific Subtropical High and Northern Hemisphere Subtropical High.