Hydroxychloroquine ameliorates immune functionality and intestinal flora disorders of IgA nephropathy by inhibition of C1GALT1/Cosmc pathway.

BACKGROUND: Hydroxychloroquine (HCQ) has emerged as a potential and secure antiproteinuric agent in IgA nephropathy (IgAN). This study endeavored to explore the impact of HCQ on the immune functionality and intestinal flora disorders in IgAN rats, as well as to elucidate the underlying mechanisms through in vivo and in vitro experiments. METHODS: IgAN model was established in Sprague-Dawley rats through the administration of BSA, LPS, and CCl4, and the IgAN rats received a continuous 8-week treatment with HCQ. Moreover, the human glomerular mesangial cells (HMCs) were incubated with IgA1 to establish an in vitro cellular model of IgAN. At the end of experimental period, samples were collected for further analysis. RESULTS: HCQ ameliorated the elevated levels of 24hUTP, SCr, BUN, the number of urinary RBC, and the activation of inflammation-related proteins within the TLR4/NF-κB signaling pathway. In the IgAN rat group, there was a pronounced escalation in IgA deposition, mesangial matrix hyperplasia, and glomerular inflammatory cell infiltration, while the administration of HCQ effectively mitigated these pathological changes. In addition, the reduced production of CD4+CD25+Foxp3+ Treg in the IgAN group was effectively reversed by HCQ. Furthermore, HCQ has the capacity to restore the compromised state of the intestinal mucosal barrier induced by IgAN and mitigate the circumstances of intestinal permeability and disruption in the intestinal flora. CONCLUSION: HCQ diminishes IgA aberrant glycosylation levels, ameliorates renal and intestinal histopathological damage, and attenuates intestinal flora disorders and immune dysfunction in IgAN rats by means of activating the C1GALT1/Cosmc pathway.

Effects of Aerobic Exercise on Executive and Memory Functions in Patients With Alzheimer's Disease: A Systematic Review.

BACKGROUND: Alzheimer's disease threatens the health of older adults, particularly by disrupting executive and memory functions, and many studies have shown that aerobic exercise prevents and improves the symptoms associated with the disease. OBJECTIVE: The objective was to systematically review the effects of aerobic exercise on executive and memory functions in patients with Alzheimer's disease and to determine the effect factors and mechanisms of the design of aerobic exercise intervention programs. METHOD: Relevant literature was searched in three databases (PubMed, Web of Science, and EBSCO) from January 1, 2014 to March 1, 2023, using a subject-word search method. Data on 10 items, including author and country, were extracted from the literature after screening. The quality of the literature was evaluated using the Physiotherapy Evidence Database scale, and a systematic review was performed. RESULTS: Twelve papers from seven countries were ultimately included, embodying 11 randomized controlled trials and one study with a repeated-measures design. The overall quality of the studies was good as 657 study participants, aged 45 years and older who had varying degrees of Alzheimer's disease and significant symptoms, were included. Aerobic exercise was found to have a significant positive impact on executive and memory functions in people with Alzheimer's disease. CONCLUSION: The effects of aerobic exercise on aspects of executive function were mainly characterized by improvements in inhibitory control, working memory, and cognitive flexibility, whereas the effects on aspects of memory function were mainly characterized by improvements in logical memory, situational memory, and short-term memory.

Carbon Free Radical (R⋠) Inactivates NF-κB for Radical Capping Therapy.

Inactivating hyperactivated transcription factors can overcome tumor therapy resistance, but their undruggable features limit the development of conventional inhibitors. Here, we report that carbon-centered free radicals (R⋅) can inactivate NF-κB transcription by capping the active sites in both NF-κB and DNA. We construct a type of thermosensitive R⋅ initiator loaded amphiphilic nano-micelles to facilitate intracellular delivery of R⋅. At a temperature of 43 °C, the generated R⋅ engage in electrophilic radical addition towards double bonds in nucleotide bases, and simultaneously cap the sulfhydryl residues in NF-κB through radical chain reaction. As a result, both NF-κB nuclear translocation and NF-κB-DNA binding are suppressed, leading to a remarkable NF-κB inhibition of up to 94.1 %. We have further applied R⋅ micelles in a clinical radiofrequency ablation tumor therapy model, showing remarkable NF-κB inactivation and consequently tumor metastasis inhibition. Radical capping strategy not only provides a method to solve the heat-sink effect in clinic tumor hyperthermia, but also suggests a new perspective for controllable modification of biomacromolecules in cancer therapy.

Mesenchymal stem cells, as glioma exosomal immunosuppressive signal multipliers, enhance MDSCs immunosuppressive activity through the miR-21/SP1/DNMT1 positive feedback loop.

BACKGROUND: The immunosuppressive microenvironment in glioma induces immunotherapy resistance and is associated with poor prognosis. Glioma-associated mesenchymal stem cells (GA-MSCs) play an important role in the formation of the immunosuppressive microenvironment, but the mechanism is still not clear. RESULTS: We found that GA-MSCs promoted the expression of CD73, an ectonucleotidase that drives immunosuppressive microenvironment maintenance by generating adenosine, on myeloid-derived suppressor cells (MDSCs) through immunosuppressive exosomal miR-21 signaling. This process was similar to the immunosuppressive signaling mediated by glioma exosomal miR-21 but more intense. Further study showed that the miR-21/SP1/DNMT1 positive feedback loop in MSCs triggered by glioma exosomal CD44 upregulated MSC exosomal miR-21 expression, amplifying the glioma exosomal immunosuppressive signal. Modified dendritic cell-derived exosomes (Dex) carrying miR-21 inhibitors could target GA-MSCs and reduce CD73 expression on MDSCs, synergizing with anti-PD-1 monoclonal antibody (mAb). CONCLUSIONS: Overall, this work reveals the critical role of MSCs in the glioma microenvironment as signal multipliers to enhance immunosuppressive signaling of glioma exosomes, and disrupting the positive feedback loop in MSCs with modified Dex could improve PD-1 blockade therapy.

Physical activity interventions for cardiopulmonary fitness in obese children and adolescents: a systematic review and meta-analysis.

PURPOSE: This study [PROSPERO CRD42023416272] systematically analysed the effects of a physical activity intervention on cardiorespiratory fitness in obese children and adolescents and elucidated the factors that influenced those effects. METHODS: A systematic review of the literature on physical activity interventions for improving cardiopulmonary fitness in obese children and adolescents from January 1, 2011, to March 1, 2023, was conducted. The search was performed on the Web of Science and PubMed databases, and the selected literature was first screened and then assessed for quality. Finally, a systematic review was conducted. RESULTS: Out of the initially identified 1424 search records, 28 studies were eventually included in the systematic review. These studies encompassed a total of 2724 participants aged 5 to 18 years, with the publication dates of the literature primarily ranging from 2011 to 2023. Physical activity was found to effectively improve the following parameters in obese children and adolescents: weight [mean difference (MD), -2.03 (95% confidence interval, -2.59 to -1.47), p < 0.00001], maximal oxygen consumption [MD, -1.95 (95% CI, -1.06 to -2.84), p < 0.0001], heart rate [MD, -2.77 (95% CI, -4.88 to -0.67), p = 0.010], systolic blood pressure [MD, -8.11 (95% CI, -11.41 to -4.81), p < 0.00001], and diastolic blood pressure [MD, -4.18 (95% CI, -5.32 to -3.03), p < 0.00001]. High-intensity exercise was found to yield greater improvements than low- to moderate-intensity exercise in maximal oxygen consumption [MD, 1.43 (95% CI, 0.04 to 2.82), p = 0.04] and diastolic blood pressure [MD, -6.94 (95% CI, -10.61 to -3.26), p = 0.0002] in obese children and adolescents. CONCLUSION: Physical activity can effectively improve the body weight, maximal oxygen consumption, heart rate, systolic blood pressure, and diastolic blood pressure of obese children and adolescents. The type of physical activity directly influences the participation interest of obese children and adolescents, with moderate- to high-intensity physical activity showing the most significant impact on intervention outcomes. High-frequency, long-term interventions yield better results than short-term interventions.

Effectiveness of different antithrombotic agents in combination with tranexamic acid for venous thromboembolism prophylaxis and blood management after total knee replacement: a prospective randomized study.

BACKGROUND: Tranexamic acid (TXA) has been widely applied in total knee arthroplasty (TKA) to significantly reduce perioperative blood loss and improve knee function recovery in patients after surgery. The choice of antithrombotic agents for venous thromboembolism (VTE) prevention after TKA is controversial. Therefore, this study aimed to compare the effects of different antithrombotic agents on patients after primary unilateral TKA in the context of applied TXA. METHODS: A total of 180 patients undergoing primary unilateral TKA from October 2020 to December 2021 were included in this study. All patients were given an intraoperative drip of 60 mg/kg TXA. Thereafter, patients were divided into three groups (n = 60 each). Baseline data were comparable among the three groups. The average follow-up time was 3.02 ± 0.09 months. Group 1 enrolled patients receiving oral rivaroxaban (RA) at 10 mg, Group 2 included patients who received subcutaneous Dalteparin sodium at 2500 IU, while Group 3 included patients taking oral aspirin (ASA) at 100 mg. Patients in all the three groups received treatment once a day for 30 days at 12 h postoperatively. The primary outcomes in this study were post-treatment drainage volume and thrombotic complication rate. The secondary outcomes included hematologic parameters, transfusion rate, intraoperative blood loss, total blood loss (TBL), and bleeding complication rate. RESULTS: The average drainage volume after treatment was significantly lower in Group 3 than in Group 1 and Group 2 (205.2 ± 69.0 vs 243.4 ± 72.5 vs 295.4 ± 72.5 ml, P < 0.001), and there was a significant difference between Group 1 and Group 2 (243.4 ± 72.5 mL vs 295.4 ± 72.5 mL, P < 0.001). The blood transfusion rate of Group 2 dramatically increased compared with Group 1 and Group 3 (20.0% vs 6.7% vs 5.0%, P = 0.01). The bleeding complication rate in Group 1 apparently increased relative to Group 2 and Group 3 (26.7% vs 10.0% vs 8.3%, P = 0.008). Besides, there was no significant difference in the thrombotic complication rate among the three groups. CONCLUSION: Under the background of TXA application, ASA, RA, and Dalteparin sodium were all effective on preventing VTE after TKA. In addition, ASA effectively reduced post-treatment Hemoglobin (Hb) loss, drainage volume, TBL, transfusion rate, and bleeding complications compared with RA and Dalteparin sodium. TRIAL REGISTRATION: The trial was registered at the Chinese Clinical Trial Registry (ChiCTR2200060169). Date of Registration: 21/05/2022.

A Temporal and Space Anti-counterfeiting Based on the Four-Modal Luminescent Ba2Zr2Si3O12 Phosphors.

Fluorescent anti-counterfeiting materials have been widely studied due to their high resolution and convenient identification by direct visualization of the color output. To date, the anti-counterfeiting technology of single ultraviolet excitation mode still has security problems because the single mode could be imitated easily. Here, we have successfully developed four modes of anti-counterfeiting from Eu2+ and Er3+ co-doped Ba2Zr2Si3O12 phosphors with photo, long persistent, photo-stimulated, and up-conversion luminescence behavior. The as-fabricated phosphors can emit an intense blue-green luminescence originating from the characteristic transition of Eu2+ ions and exhibit a blue-green long persistent luminescence phenomenon. Moreover, the enhancement of photo-stimulated luminescence that contributed to the effectively increased trap concentration is observed, along with the produced up-conversion phenomenon thanks to the introduction of Er3+ ions. Notably, the fluorescence rapidly changes from blue-green to stable green luminescence with the delay of excitation time under the excitation of a 980 nm laser diode. Herein, this work realizes the fast down- to up-conversion luminescence output over time, which provides the basis for its possible application in advanced multi-mode anti-counterfeiting.

Interference of Interleukin-1ß Mediated by Lentivirus Promotes Functional Recovery of Spinal Cord Contusion Injury in Rats via the PI3K/AKT1 Signaling Pathway.

Purpose: Inflammation and apoptosis after spinal cord contusion (SCC) are important causes of irreversible spinal cord injury. Interleukin-1ß (IL-1ß) is a key inflammatory factor that promotes the aggravation of spinal cord contusion. However, the specific role and regulatory mechanism of IL-1ß in spinal cord contusion is still unclear. Therefore, this study applied bioinformatics to analyze and mine potential gene targets interlinked with IL-1ß, animal experiments and lentiviral interference technology were used to explore whether IL-1ß affected the recovery of motor function in spinal cord contusion by interfering with PI3K/AKT1 signaling pathway. Method: This study used bioinformatics to screen and analyze gene targets related to IL-1ß. The rat SCC animal model was established by the Allen method, and the Basso Beattie Bresnahan (BBB) score was used to evaluate the motor function of the spinal cord-injured rats. Immunohistochemistry and immunofluorescence were used to localize the expression of IL-1ß and AKT1 proteins in spinal cord tissue. Quantitative polymerase chain reaction and Western blot were used to detect the gene and protein expressions of IL-1ß, PI3K, and AKT1. RNAi technology was used to construct lentivirus to inhibit the expression of IL-1ß, lentiviral interference with IL-1ß was used to investigate the effect of IL-1ß and AKT1 on the function of spinal cord contusion and the relationship among IL-1ß, AKT1, and downstream signaling pathways. Results: Bioinformatics analysis suggested a close relationship between IL-1ß and AKT1. Animal experiments have confirmed that IL-1ß is closely related to the functional recovery of spinal cord contusion. Firstly, from the phenomenological level, the BBB score decreased after SCC, IL-1ß and AKT1 were located in the cytoplasm of neurons in the anterior horn of the spinal cord, and the expression levels of IL-1ß gene and protein in the experimental group were higher than those in the sham operation group. At the same time, the expression of AKT1 gene decreased, the results suggested that the increase of IL-1ß affected the functional recovery of spinal cord contusion. Secondly, from the functional level, after inhibiting the expression of IL-1ß with a lentivirus-mediated method, the BBB score was significantly increased, and the motor function of the spinal cord was improved. Thirdly, from the mechanistic level, bioinformatics analysis revealed the relationship between IL-1ß and AKT1. In addition, the experiment further verified that in the PI3K/AKT1 signaling pathway, inhibition of IL-1ß expression upregulated AKT1 gene expression, but PI3K expression was unchanged. Conclusion: Inhibition of IL-1ß promotes recovery of motor function after spinal cord injury in rats through upregulation of AKT1 expression in the PI3K/AKT1 signaling pathway. Bioinformatics analysis suggested that IL-1ß may affect apoptosis and regeneration by inhibiting the expression of AKT1 in the PI3K/AKT1 signaling pathway to regulate the downstream FOXO, mTOR, and GSK3 signaling pathways; thereby hindering the recovery of motor function in rats after spinal cord contusion. It provided a new perspective for clinical treatment of spinal cord contusion in the future.

miR-221-5p and miR-186-5p Are the Critical Bladder Cancer Derived Exosomal miRNAs in Natural Killer Cell Dysfunction.

Bladder cancer (BC) is the tenth most commonly diagnosed cancer worldwide, and its carcinogenesis mechanism has not been fully elucidated. BC is able to induce natural killer (NK) cell dysfunction and escape immune surveillance. The present study found that exosomes derived from the urinary bladder cancer cell line (T24 cell) contribute in generating NK cell dysfunction by impairing viability, and inhibiting the cytotoxicity of the NK cell on target cells. Meanwhile, T24 cell-derived exosomes inhibited the expression of the important functional receptors NKG2D, NKp30, and CD226 on NK cells as well as the secretion of perforin and granzyme-B. The critical miRNAs with high expression in T24 cell-derived exosomes were identified using high-throughput sequencing. Furthermore, following dual-luciferase reporter assay and transfection experiments, miR-221-5p and miR-186-5p were confirmed as interfering with the stability of the mRNAs of DAP10, CD96, and the perforin gene in NK cells and may be potential targets used in the therapy for BC.

Variation from Zero to Negative Thermal Quenching of Phosphor with Assistance of Defect States.

Proper defect states are demonstrated to be beneficial to overcome thermal quenching of the corresponding phosphors. In this work, a cyan-emitting KGaGeO4/Bi3+ phosphor with abundant defect states is reported, the emission intensity of which exhibits an abnormal thermal quenching performance under excitation with different photon energies. A 100% emission intensity is achieved at 393 K under 325 nm excitation compared with that at room temperature, while significantly enhanced intensities of 207% at 393 K and even 351% at 513 K under 365 nm excitation are recorded. The excellent thermal stability performance is confirmed to be not only related to the direct energy transfer from the defect states but also depended on the efficiency of capturing carriers for the trap centers, which is clarified in this work. In addition, the mechanism of the double tunneling process of carriers from trap centers to luminescence centers and luminescence centers to trap centers is studied. These results are believed to provide new insights into the thermal stability of the corresponding fluorescent materials and could inspire studies to further explore novel fluorescent materials with high thermal stability based on defect state engineering.

Intravoxel incoherent motion magnetic resonance imaging in predicting IDH1 gene mutations in high-grade gliomas.

BACKGROUND: Intravoxel incoherent motion (IVIM) magnetic resonance imaging (MRI) has been applied to gliomas; however, the relationships between its parameters and isocitrate dehydrogenase 1 (IDH1) mutations in gliomas remain to be investigated. PURPOSE: To investigate the value of IVIM in predicting IDH1 mutations in high-grade gliomas before surgery. MATERIAL AND METHODS: A total of 72 patients with pathologically confirmed high-grade gliomas underwent conventional brain MRI and IVIM from September 2016 to May 2020. Among them, 22 cases were IDH1 mutant and 50 cases were IDH1 wild type. The independent samples t test (normal distribution and homogeneity of variance) or Mann-Whitney rank-sum test (non-normal distribution or heterogeneity of variance) was conducted, and receiver operating characteristic curves were generated to determine parameters for distinguishing IDH1-mutated from IDH1 wild-type high-grade gliomas. These parameters included apparent diffusion coefficient (ADC), true diffusivity (D), pseudo-diffusivity (D*), and perfusion fraction (f). RESULTS: ADC, D, and f were significantly higher in IDH1-mutated gliomas than in IDH1 wild-type gliomas (P < 0.05 for all). There was no significant difference in the D* value between the two groups (P = 0.053). The areas under the curve of ADC, D, and f in predicting IDH1 mutations in gliomas were 0.798, 0.810, and 0.823, respectively. The specificity of ADC was highest (80.0%), and the sensitivity of the f value was the highest (100.0%). CONCLUSION: IVIM can be used for the quantitative prediction of IDH1 mutations in high-grade gliomas before surgery, and the f value is the most effective.

Application of Medical Adhesive in Emergency Treatment of Head and Face Injury.

PURPOSE: The aim of this study was to analyze the application effect of medical adhesive in emergency surgical scalp and facial skin treatment. To explore the better application of medical adhesive in emergency work. METHODS: A total of 180 patients with scalp and facial skin laceration admitted to the emergency department of the Affiliated Hospital of Southwest Medical University from August 2018 to August 2019 were selected. The patients were divided into the control group (n = 70) and the treatment group (n = 110) using the random number table method. The control group was treated with debridement, local anesthesia, and suture technique without medical adhesive, whereas the treatment group was treated with medical adhesive after debridement without local anesthesia. The operation time, pain degree, total cost, and satisfaction of the 2 groups were compared. RESULTS: The operation time in treatment group was shorter than that in control group (12.0 ±â€Š2.6 minutes versus 17.7 ±â€Š2.5 minutes, P < 0. 05), and the visual simulation score (VAS) of treatment group were lower than that in control group (2.45 ±â€Š1.63 versus 5.66 ±â€Š1.65, P < 0. 05), and the total cost in treatment group was higher than that in control group (¥906.6 ±â€Š69.0 versus ¥329.8 ±â€Š76.4, P < 0. 05). In control group 17 not satisfiedpatients, satisfied 37 patients, and 16 patients felt excellent; in treatment group, there are 7 not satisfiedpatients, 21 satisfied patients, and 82 felt excellent. Patients' satisfaction was compared between the 2 groups, the difference was statistically significant (P < 0.05). CONCLUSIONS: The results suggest that Medical adhesive used in scalp skin trauma and facial wounds had the advantages of shorter operation time, less pain, and higher postoperative satisfaction of patients, but higher cost than conventional suture. Medical adhesive has obvious advantages and high feasibility in the treatment of scalp and facial skin wounds.

[One new cembranoid diterpene from gum resin of Boswellia carterii].

This study aims to study the chemical components from the gum resin of Boswellia carterii. Five cembranoid diterpenes were isolated from the gum resin of B. carterii by various of column chromatographies including silica gel, Sephadex LH-20, and semi-preparative HPLC. Their structures were identified on the basis of physicochemical properties, mass spectrometry(MS), nuclear magnetic resonance(NMR), Ultraviolet(UV) and infrared(IR) spectroscopic data. These compounds were identified as(1S,2E,4R,5S,7E,11E)-4-methoxy-5-hydroxycembrane(1),(1R~*,4R~*,5E,8E,12E,15E)-4-hydroxycembra-5,8,12,15-tetraene(2), cembrene A(3),(3S,4S,7R)-4-hydroxycembrane(4), and pavidolide D(5). Compound 1 was a new compound. Compounds 2, 4, and 5 were obtained from the gum resin of B. carterii for the first time. Compound 2 showed weak inhibition on the human liver cancer cell line HepG2.

NIR-Triggered Intracellular H+ Transients for Lamellipodia-Collapsed Antimetastasis and Enhanced Chemodynamic Therapy.

In solid tumors, tumor invasion and metastasis account for 90 % of cancer-related deaths. Cell migration is steered by the lamellipodia formed at the leading edge. These lamellipodia can drive the cell body forward by its mechanical deformation regulated by cofilin. Inhibiting cofilin activity can cause significant defects in directional lamellipodia formation and the locomotory capacity of cell invasion, thus contributing to antimetastatic treatment. Herein, a near infrared light (NIR)-controlled nanoscale proton supplier was designed with upconversion nanoparticles (UCNPs) as a core coated in MIL-88B for interior photoacids loading; this photoacids loading can boost H+ transients in cells, which converts the cofilin to an inactive form. Strikingly, inactive cofilin loses the ability to mediate lamellipodia deformation for cell migration. Additionally, the iron, which serves as a catalyticaly active center in MIL-88B, initiates an enhanced Fenton reaction due to the increased H+ in the tumor, ultimately achieving intensive chemodynamic therapy (CDT). This work provides new insight into H+ transients in cells, which not only regulates cofilin protonation for antimetastatic treatment but also improves chemodynamic therapy.

Ki-67 labeling index and the grading of cerebral gliomas by using intravoxel incoherent motion diffusion-weighted imaging and three-dimensional arterial spin labeling magnetic resonance imaging.

BACKGROUND: Intravoxel incoherent motion diffusion-weighted imaging (IVIM-DWI) and three-dimensional arterial spin labeling (3D-ASL) have been applied to brain tumors; however, the relationship between their parameters and the Ki-67 labeling index (Ki-67 LI) for the grading of gliomas have yet to be investigated. PURPOSE: The aim of this study is to compare multiple parameters obtained from IVIM-DWI and 3D-ASL with the Ki-67 LI when grading gliomas. MATERIAL AND METHODS: Fifty-two patients with pathologically confirmed gliomas had undergone magnetic resonance imaging (MRI), including IVIM-DWI and 3D-ASL imaging. Mann-Whitney U tests were conducted and receiver operating characteristic (ROC) curves were generated to determine parameters for distinguishing high-grade gliomas (HGGs) from low-grade gliomas (LGGs). These parameters included the apparent diffusion coefficient (ADC), true diffusivity (D), pseudo diffusivity (D*), perfusion fraction (f), cerebral blood flow (CBF), and their relative values (rADC, rD, rD*, rf, and rCBF). Spearman correlation analysis was used to assess the correlations of the parameters of MRI with the Ki-67 LI. RESULTS: The rADC, rD, and rf were significantly lower in HGGs than in LGGs (P < 0.005 for all). The rD had a significantly greater area under the ROC curve than that of the other parameters in the differentiation of HGGs from LGGs (P < 0.05). Both the rD and rf were moderately negatively correlated with the Ki-67 LI. CONCLUSION: Both the rD and rf can be used for the quantitative prediction of the Ki-67 LI. Among the extracted parameters, the rD had the significantly greatest diagnostic efficacy.

[A new nor-sesquiterpene glycoside from Corydalis edulis].

This study is to investigate the chemical constituents from the whole plant Corydalis edulis. The chemical constituents were separated and purified by macroporous resin D101, silica gel, Sephadex LH-20, ODS, and semi-preparative HPLC. Their structures were determined by physicochemical properties and spectroscopic data. Four compounds were isolated from the dichloromethane and water extracts of the whole plant C. edulis, and identified as 6'-ß-D-xylosylicariside B2(1),(3S,5R,6S,7E)-5,6-epoxy-3-hydroxy-7-megastigmen-9-one(2), loliolide(3), and 5,5'-dimethoxybiphenyl-2,2'-diol(4), respectively. Compound 1 is a new compound, of which the absolute configuration was established by electronic circular dichroism(ECD) calculations. Compound 4 is obtained from the plants of Papaveraceae family for the first time. Compounds 2 and 3 are firstly isolated from the Corydalis genus.

Near-Infrared Light-Triggered Chlorine Radical (. Cl) Stress for Cancer Therapy.

Free radicals with reactive chemical properties can fight tumors without causing drug resistance. Reactive oxygen species (ROS) has been widely used for cancer treatment, but regrettably, the common O2 and H2 O2 deficiency in tumors sets a severe barrier for sufficient ROS production, leading to unsatisfactory anticancer outcomes. Here, we construct a chlorine radical (. Cl) nano-generator with SiO2 -coated upconversion nanoparticles (UCNPs) on the inside and Ag0 /AgCl hetero-dots on the outside. Upon near-infrared (NIR) light irradiation, the short-wavelength emission UCNP catalyzes . Cl generation from Ag0 /AgCl with no dependence on O2 /H2 O2 . . Cl with strong oxidizing capacity and nucleophilicity can attack biomolecules in cancer cells more effectively than ROS. This . Cl stress treatment will no doubt broaden the family of oxidative stress-induced antitumor strategies by using non-oxygen free radicals, which is significant in the development of new anticancer agents.

Mucin O-glycosylating enzyme GALNT2 facilitates the malignant character of glioma by activating the EGFR/PI3K/Akt/mTOR axis.

N-Acetylgalactosaminyltransferase 2 (GALNT2), the enzyme that regulates the initial step of mucin O-glycosylation, has been reported to play a role in influencing the malignancy of various cancers. However, the mechanism through which it influences gliomas is still unknown. In the current study, the Cox proportional hazards model was used to select genes. Data obtained from The Cancer Genome Atlas (TCGA) database and immunohistochemistry (IHC) of clinical specimens showed that increased GALNT2 expression levels were associated with an unfavorable prognosis and a higher tumor grade in human gliomas. Then, GALNT2 knockdown and overexpression were performed in glioma cell lines and verified by quantitative real-time PCR (qRT-PCR) and Western blotting. Functional assays demonstrated that GALNT2 was closely related to glioma cell proliferation, cycle transition, migration and invasion. Western blot analysis and lectin pull-down assays indicated that GALNT2 knockdown decreased the level of phosphorylated epidermal growth factor receptor (EGFR) and the expression of the Tn antigen on EGFR and affected the expression levels of p21, cyclin-dependent kinase 4 (CDK4), cyclinD1, matrix metalloproteinase 2 (MMP2) and matrix metalloproteinase 9 (MMP9) through the EGFR/PI3K/Akt/mTOR pathway. GALNT2 overexpression had the opposite effects. In vivo, the growth of orthotopic glioma xenografts in nude mice was distinctly inhibited by the expression of GALNT2 shRNA, and the tumors with GALNT2 shRNA exhibited less aggressiveness and reduced expression of Ki67 and MMP2. Overall, GALNT2 facilitates the malignant characteristics of glioma by influencing the O-glycosylation and phosphorylation of EGFR and the subsequent downstream PI3K/Akt/mTOR axis. Therefore, GALNT2 may serve as a novel biomarker and a potential target for future therapy of glioma.

Novel nanomedicine with a chemical-exchange saturation transfer effect for breast cancer treatment in vivo.

BACKGROUND: Nanomedicine is a promising new approach to cancer treatment that avoids the disadvantages of traditional chemotherapy and improves therapeutic indices. However, the lack of a real-time visualization imaging technology to monitor drug distribution greatly limits its clinical application. Image-tracked drug delivery is of great clinical interest; it is useful for identifying those patients for whom the therapy is more likely to be beneficial. This paper discusses a novel nanomedicine that displays features of nanoparticles and facilitates functional magnetic resonance imaging but is challenging to prepare. RESULTS: To achieve this goal, we synthesized an acylamino-containing amphiphilic block copolymer (polyethylene glycol-polyacrylamide-polyacetonitrile, PEG-b-P(AM-co-AN)) by reversible addition-fragmentation chain transfer (RAFT) polymerization. The PEG-b-P(AM-co-AN) has chemical exchange saturation transfer (CEST) effects, which enable the use of CEST imaging for monitoring nanocarrier accumulation and providing molecular information of pathological tissues. Based on PEG-b-P(AM-co-AN), a new nanomedicine PEG-PAM-PAN@DOX was constructed by nano-precipitation. The self-assembling nature of PEG-PAM-PAN@DOX made the synthesis effective, straightforward, and biocompatible. In vitro studies demonstrate decreased cytotoxicity of PEG-PAM-PAN@DOX compared to free doxorubicin (half-maximal inhibitory concentration (IC50), mean ~ 0.62 µg/mL vs. ~ 5 µg/mL), and the nanomedicine more efficiently entered the cytoplasm and nucleus of cancer cells to kill them. Further, in vivo animal experiments showed that the nanomedicine developed was not only effective against breast cancer, but also displayed an excellent sensitive CEST effect for monitoring drug accumulation (at about 0.5 ppm) in tumor areas. The CEST signal of post-injection 2 h was significantly higher than that of pre-injection (2.17 ± 0.88% vs. 0. 09 ± 0.75%, p < 0.01). CONCLUSIONS: The nanomedicine with CEST imaging reflects the characterization of tumors and therapeutic functions has great potential medical applications.

Slot Self-Allocation Based MAC Protocol for Energy Harvesting Nano-Networks.

Nano-networks are composed of interconnected nano-nodes and can enable unprecedented applications in various fields. Due to the peculiarities of nano-networks, such as high density, extremely limited energy and computational resources, traditional carrier-sensing based Media Access Control (MAC) protocols are not suitable for nano-networks. In this paper, a Slot Self-Allocation based MAC protocol (SSA-MAC) is proposed for energy harvesting nano-networks. Two transmission schemes for centralized and distributed nano-networks are designed, respectively. In centralized nano-networks, nano-nodes can only send packets to the nano-controller in their Self-Allocation Slots (SASs), while, in distributed nano-networks, nano-nodes can only receive packets from surrounding nano-nodes in their SASs. Extensive simulations were conducted to compare the proposed SSA-MAC with PHysical LAyer aware MAC (PHLAME), Receiver-Initiated Harvesting-aware MAC (RIH-MAC) and Energy Efficient Wireless NanoSensor Network MAC (EEWNSN). From the results, it can be concluded that the proposed SSA-MAC achieves better performance and can reduce the collision probability, while improving the energy efficiency of nano-networks.