Galectin-3-upregulated FAK promotes angiogenesis through oral lichen planus-activated fibroblasts.

BACKGROUND: The specific mechanism underlying the role of oral lichen planus-activated fibroblasts in angiogenesis remains undefined. Herein, the expression of Galectin-3 in oral lichen planus and verifying whether Galectin-3 can promote angiogenesis through oral lichen planus-activated fibroblasts has been investigated. METHODS: The expression of Galectin-3 and CD34 in the oral lichen planus tissues (n = 30) and normal oral mucosa tissues (n = 15) was detected by immunohistochemistry. The expression of Galectin-3 in the oral lichen planus-activated fibroblasts was determined by reverse transcription-polymerase chain reaction, Western blot, and enzyme-linked immunosorbent assay. Galectin-3 overexpression lentiviral vector was constructed and transfected with oral lichen planus-activated fibroblasts. In addition, oral lichen planus-activated fibroblasts were treated with GB1107 (5 and 10 µM) to inhibit Galectin-3 expression and co-cultured with human umbilical vein vascular endothelial cells, and analyzed by Transwell and tube formation assays. The expression of VEGF and FGF2 in oral lichen planus-activated fibroblasts was detected, and the expression and phosphorylation levels of VEGFR2 and FAP in human umbilical vein vascular endothelial cells were determined. RESULTS: Oral lichen planus subcutaneous tissues highly expressed Galectin-3, positively correlated with angiogenesis. Oral lichen planus-activated fibroblasts expressed significantly higher Galectin-3 than NFs. Oral lichen planus-activated fibroblasts overexpressing Galectin-3 enhanced the migration and tube-forming capacity of co-cultured human umbilical vein vascular endothelial cells. In oral lichen planus-activated fibroblasts, 10 µM GB1107 reduced the proliferation and migration capacity, decreased the expression of α-SMA, FAP, VEGF, and FGF2, and inhibited the tube-forming capacity and the expression of VEGFR2 phosphorylation and FAK in co-cultured human umbilical vein vascular endothelial cells. CONCLUSIONS: The upregulation of Galectin-3 expression in oral lichen planus is associated with angiogenesis, and the oral lichen planus-activated fibroblasts promote human umbilical vein vascular endothelial cells migration and tube-forming differentiation through VEGFR2/FAP activation by Galectin-3.

Mannose-conjugated platinum complexes reveals effective tumor targeting mediated by glucose transporter 1.

Despite numerous studies that report the glucose derived glycoconjugates as antitumor candidates, using mannose as sugar motif for specific tumor targeting remains less studied. In this research, two novel mannose-conjugated platinum complexes 4a and 4b that target the Warburg effect were designed, synthesized and evaluated for their antitumor activities in vitro and in vivo. Compared with oxaliplatin, both complexes exhibited substantial enhancement in water solubility as well as excellent or comparative cytotoxicity in six human cancer cell lines. Cytotoxicity assessments on Glucose transporter 1 (GLUT1) down-regulated or overexpressed cells and platinum accumulation study demonstrated that cellular uptake of compound 4a was regulated by GLUT1. In particular, 4a induced apoptosis in HT29 cells by suppressing expression of Bcl-2 and Bcl-XL, which preliminary explained the mechanism origin of antitumor effect. As indicated by its maximum tolerated dose-finding assay and in vivo anticancer activity, compound 4a exhibits better safety and efficacy profile than oxaliplatin. The findings of this study indicate the possibility of subjecting mannose-conjugated platinum complexes as lead compounds for further preclinical evaluation.

Effect of working hours on prognosis of acute ischemic stroke patients following alteplase intravenous thrombolysis.

OBJECTIVE: To investigate the effect of hospital working hours on outcomes of patients with acute ischemic stroke 3 months after receiving alteplase intravenous thrombolysis. METHODS: A retrospective analysis was performed on 254 individuals with acute ischemic stroke who received alteplase intravenous thrombolysis between January 2018 and December 2020 either during peak hospital working hours (08:00-17:59; Group A) or off-peak hours (18:00-07:59 the following day; Group B). Patients were also categorized according to which of four peak/off-peak-hour periods they received treatment in: Group 1 (08:00-11:59), Group 2 (12:00-17:59), Group 3 (18:00-21:59), Group 4 (22:00-07:59 the following day). Baseline data and 3-month prognosis were compared across groups. Logistic regression analysis was used to investigate the correlation between hospital working hours and 3-month prognosis. RESULTS: There were no significant differences in door-to-needle time, onset-to-needle time, 24-hour National Institutes of Health Stroke Scale (NIHSS) score, 7-day NIHSS score or Modified Rankin Score between Groups 1 to 4 or between Groups A and B. Whether treatment was administered during peak or off-peak hours did not significantly affect 3-month prognosis. CONCLUSION: At this hospital, differences in the time at which stroke patients were treated were not associated with outcomes.

Disparities in hepatitis B virus healthcare service access among marginalised poor populations: a mixed-method systematic review.

BACKGROUND: Marginalised poor populations, characterised by poverty and social exclusion, suffer disproportionately from hepatitis B virus (HBV) infections and encounter substantial disparities in access to healthcare. This has further exacerbated the global HBV burden and precluded progress towards HBV elimination. This mixed-method systematic review aimed to synthesise their utilisation and influencing factors in HBV healthcare services, including screening, vaccination, treatment, and linkage-to-care. METHODS: Eleven databases were searched from their inception to May 4, 2023. Quantitative and qualitative studies examining the factors influencing HBV healthcare access among marginalised poor populations were included. A meta-analysis was conducted to synthesise the pooled rates of HBV healthcare utilisation. The factors influencing utilisation were integrated and visualised using a health disparity research framework. RESULTS: Twenty-one studies were included involving 13,171 marginalised poor individuals: sex workers, rural migrant workers, irregular immigrants, homeless adults, and underprivileged individuals. Their utilisation of HBV healthcare ranged from 1.5% to 27.5%. Meta-analysis showed that the pooled rate of at least one dose of the HBV vaccine barely reached 37% (95% confidence interval: 0.26‒0.49). Fifty-one influencing factors were identified, with sociocultural factors (n = 19) being the most frequently reported, followed by behavioural (n = 14) and healthcare system factors (n = 11). Socio-cultural barriers included immigration status, prison history, illegal work, and HBV discrimination. Behavioural domain factors, including previous testing for sexually transmitted diseases, residential drug treatment, and problem-solving coping, facilitated HBV healthcare access, whereas hostility coping exerted negative influences. Healthcare system facilitators comprised HBV health literacy, beliefs, and physician recommendations, whereas barriers included service inaccessibility and insurance inadequacies. The biological and physical/built environments were the least studied domains, highlighting that geographical mobility, shelter capacity, and access to humanitarian health centres affect HBV healthcare for marginalised poor populations. CONCLUSIONS: Marginalised poor populations encounter substantial disparities in accessing HBV healthcare, highlighting the need for a synergistic management approach, including deploying health education initiatives to debunk HBV misperceptions, developing integrated HBV management systems for continuous tracking, conducting tailored community outreach programmes, and establishing a human rights-based policy framework to guarantee the unfettered access of marginalised poor populations to essential HBV services.

Marginal zone lymphoma with severe rashes: A case report.

BACKGROUND: Marginal zone lymphoma (MZL) is an indolent subtype of non-Hodgkin lymphoma (NHL), which is rare clinically with severe rashes as the initial symptom. CASE SUMMARY: This study reports a case of MZL with generalized skin rashes accompanied by pruritus and purulent discharge. First-line treatment with rituximab combined with zanubrutinib had poor effects. However, after switching to obinutuzumab combined with zanubrutinib, the case was alleviated, and the rashes disappeared. CONCLUSION: For patients with advanced stage MZL not benefiting from type I anti-CD20 monoclonal antibody (mAb) combination therapy, switching to a type II anti-CD20 mAb combination regimen may be considered. This approach may provide a new perspective in the treatment of MZL.

Reproductive attributes and functional response of Anastatus japonicus on eggs of Antheraea pernyi, a factitious host.

BACKGROUND: Anastatus japonicus Ashmead (Hymenoptera: Eupelmidae) is a solitary egg endoparasitoid that has been studied for inundative biological control of Halyomorpha halys Stål (Hemiptera: Pentatomidae) in China. In this study, we assessed the reproductive attributes and functional response of Anastatus japonicus on a factitious host, Antheraea pernyi (Guérin-Méneville) (Lepidoptera: Anthelidae) at 25 ± 1 °C, 70 ± 5% relative humidity and 16 h:8 h light/dark photoperiod. RESULTS: The mean lifetime fecundity of Anastatus japonicus females was 404.3 progeny produced over an average oviposition period of 42.3 days. The sex ratio of adult progeny was slightly male biased (51.2%), whereas more female progeny were produced before day 20 of a female's life. Single 1-day-old mated Anastatus japonicus females exhibited a type II functional response to increasing host densities (1-50 eggs), with an inverse host density-dependent pattern of percent parasitism. The upper limit to the daily attack rate was estimated as 7.6 Antheraea pernyi eggs. Furthermore, mutual interference among Anastatus japonicus females occurred when increasing densities of parasitoids (1, 2, 4, 8, 16) were exposed to 30 host eggs. CONCLUSION: Laboratory functional response result revealed that individual Anastatus japonicus might be unable to respond effectively to increasing host density in the field, which could be compensated by releasing larger numbers of wasps. Strong mutual interference among foraging Anastatus japonicus females should be considered in any future inundative biological control programs for the sustainable management of Halyomorpha halys or other host insect pests. © 2022 The Authors. Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

Electrospinning of Flexible Poly(vinyl alcohol)/MXene Nanofiber-Based Humidity Sensor Self-Powered by Monolayer Molybdenum Diselenide Piezoelectric Nanogenerator.

Two-dimensional material has been widely investigated for potential applications in sensor and flexible electronics. In this work, a self-powered flexible humidity sensing device based on poly(vinyl alcohol)/Ti3C2Tx (PVA/MXene) nanofibers film and monolayer molybdenum diselenide (MoSe2) piezoelectric nanogenerator (PENG) was reported for the first time. The monolayer MoSe2-based PENG was fabricated by atmospheric pressure chemical vapor deposition techniques, which can generate a peak output of 35 mV and a power density of 42 mW m-2. The flexible PENG integrated on polyethylene terephthalate (PET) substrate can harvest energy generated by different parts of human body and exhibit great application prospects in wearable devices. The electrospinned PVA/MXene nanofiber-based humidity sensor with flexible PET substrate under the driven of monolayer MoSe2 PENG, shows high response of ∼40, fast response/recovery time of 0.9/6.3 s, low hysteresis of 1.8% and excellent repeatability. The self-powered flexible humidity sensor yields the capability of detecting human skin moisture and ambient humidity. This work provides a pathway to explore the high-performance humidity sensor integrated with PENG for the self-powered flexible electronic devices.

Multifunctional Latex/Polytetrafluoroethylene-Based Triboelectric Nanogenerator for Self-Powered Organ-like MXene/Metal-Organic Framework-Derived CuO Nanohybrid Ammonia Sensor.

Self-powered sensors are crucial in the field of wearable devices and the Internet of Things (IoT). In this paper, an organ-like Ti3C2Tx MXene/metal-organic framework-derived copper oxide (CuO) gas sensor was powered by a triboelectric nanogenerator (TENG) based on latex and polytetrafluoroethylene for the detection of ammonia (NH3) at room temperature. The peak-to-peak value of open-circuit voltage and short-circuit current generated by the prepared TENG can reach up to 810 V and 34 µA, respectively. The TENG can support a maximum peak power density of 10.84 W·m-2 and light at least 480 LEDs. Moreover, a flexible TENG under a single-electrode working mode was demonstrated for human movement stimulation, which exhibits great potential in wearable devices. The self-powered NH3 sensor driven by TENG has an excellent response (Vg/Va = 24.8 @ 100 ppm) at room temperature and exhibits a great potential in monitoring pork quality. Ti3C2Tx MXene and CuO were characterized by SEM, TEM, EDS, XRD, and XPS to analyze the properties of the materials. The NH3 sensing performance of the self-powered sensor based on MXene/CuO was greatly improved, and the mechanism of the enhanced sensing properties was systematically discussed.

Mechanistic and biological characteristics of different sugar conjugated 2-methyl malonatoplatinum(II) complexes as new tumor targeting agents.

Novel cis-2-methylmalonato(trans-R,R-cyclohexane-1,2-diamine)platinum(II) glycoconjugates derived from different sugar motifs, namely, glucose (Glu-Me-Pt), mannose (Man-Me-Pt) and galactose (Gal-Me-Pt) were designed and synthesized based on the third generation clinical drug oxaliplatin for potential glucose transporters (GLUTs) mediated tumor targeting. All platinum(II) glycoconjugates were characterized by 1H NMR, 13C NMR, IR, HRMS as well as 195Pt-NMR analysis. Despite their substantial improvement in water solubility, the conjugates exhibited comparable or better in vitro cytotoxicities than oxaliplatin determined in six different human cancer cell lines. Glu-Me-Pt has been shown to be more effective than cisplatin and oxaliplatin with improved therapeutic index in leukemia-bearing DBA/2 mice model. The potential GLUT transportability of the complexes was investigated using cell-based fluorescent competition assay and GLUT inhibitor mediated cell viability analysis in GLUT over-expressing HT29 cell line. Each sugar motif was found to be useful to enable the platinum(II) complexes as substrate for GLUT mediated cell uptake. In vitro DNA adduct formation analysis has been investigated for the first time for this class of compounds to reveal the intrinsic differences in antitumor activity between the malonatoplatinum(II) glycoconjugates and oxaliplatin. The intrinsic DNA reactivity of the platinum(II)-sugar conjugates was found as Gal-Me-Pt > Glu-Me-Pt > Man-Me-Pt ≈ oxaliplatin by kinetic study on the formation of platinum(II) adducts with guanosine-5'-monophosphate (5'-GMP). The results from this study demonstrate the usefulness of glucose, mannose and galactose as alternative sugar motif on glycoconjugation for GLUT mediated drug design and pharmaceutical R&D, and the obtained fundamental results also support the potential of the GLUT targeted platinum(II)-sugar conjugates as lead compounds for further pre-clinical evaluation.

GLUT1-mediated selective tumor targeting with fluorine containing platinum(II) glycoconjugates.

Increased glycolysis and overexpression of glucose transporters (GLUTs) are physiological characteristics of human malignancies. Based on the so-called Warburg effect, 18flurodeoxyglucose-positron emission tomography (FDG-PET) has successfully developed as clinical modality for the diagnosis and staging of many cancers. To leverage this glucose transporter mediated metabolic disparity between normal and malignant cells, in the current report, we focus on the fluorine substituted series of glucose, mannose and galactose-conjugated (trans-R,R-cyclohexane-1,2-diamine)-2-flouromalonato-platinum(II) complexes for a comprehensive evaluation on their selective tumor targeting. Besides highly improved water solubility, these sugar-conjugates presented improved cytotoxicity than oxaliplatin in glucose tranporters (GLUTs) overexpressing cancer cell lines and exhibited no cross-resistance to cisplatin. For the highly water soluble glucose-conjugated complex (5a), two novel in vivo assessments were conducted and the results revealed that 5a was more efficacious at a lower equitoxic dose (70% MTD) than oxaliplatin (100% MTD) in HT29 xenograft model, and it was significantly more potent than oxaliplatin in leukemia-bearing DBA/2 mice as well even at equimolar dose levels (18% vs 90% MTD). GLUT inhibitor mediated cell viability analysis, GLUT1 knockdown cell line-based cytotoxicity evaluation, and platinum accumulation study demonstrated that the cellular uptake of the sugar-conjugates was regulated by GLUT1. The higher intrinsic DNA reactivity of the sugar-conjugates was confirmed by kinetic study of platinum(II)-guanosine adduct formation. The mechanistic origin of the antitumor effect of the fluorine complexes was found to be forming the bifunctional Pt-guanine-guanine (Pt-GG) intrastrand cross-links with DNA. The results provide a rationale for Warburg effect targeted anticancer drug design.

2-Deoxyglucose conjugated platinum (II) complexes for targeted therapy: design, synthesis, and antitumor activity.

Malignant neoplasms exhibit an elevated rate of glycolysis over normal cells. To target the Warburg effect, we designed a new series of 2-deoxyglucose (2-DG) conjugated platinum (II) complexes for glucose transporter 1 (GLUT1)-mediated anticancer drug delivery. The potential GLUT1 transportability of the complexes was investigated through a comparative molecular docking analysis utilizing the latest GLUT1 protein crystal structure. The key binding site for 2-DG as GLUT1's substrate was identified with molecular dynamics simulation, and the docking study demonstrated that the 2-DG conjugated platinum (II) complexes can be recognized by the same binding site as potential GLUT1 substrate. The conjugates were synthesized and evaluated for in vitro cytotoxicity study with seven human cancer cell lines. The results of this study revealed that 2-DG conjugated platinum (II) complexes are GLUT1 transportable substrates and exhibit improved cytotoxicities in cancer cell lines that over express GLUT1 when compared to the clinical drug, Oxaliplatin. The correlation between GLUT1 expression and antitumor effects are also confirmed. The study provides fundamental information supporting the potential of the 2-DG conjugated platinum (II) complexes as lead compounds for further pharmaceutical R&D.

Overexpression of a GmCnx1 gene enhanced activity of nitrate reductase and aldehyde oxidase, and boosted mosaic virus resistance in soybean.

Molybdenum cofactor (Moco) is required for the activities of Moco-dependant enzymes. Cofactor for nitrate reductase and xanthine dehydrogenase (Cnx1) is known to be involved in the biosynthesis of Moco in plants. In this work, a soybean (Glycine max L.) Cnx1 gene (GmCnx1) was transferred into soybean using Agrobacterium tumefaciens-mediated transformation method. Twenty seven positive transgenic soybean plants were identified by coating leaves with phosphinothricin, bar protein quick dip stick and PCR analysis. Moreover, Southern blot analysis was carried out to confirm the insertion of GmCnx1 gene. Furthermore, expression of GmCnx1 gene in leaf and root of all transgenic lines increased 1.04-2.12 and 1.55-3.89 folds, respectively, as compared to wild type with GmCnx1 gene and in line 10 , 22 showing the highest expression. The activities of Moco-related enzymes viz nitrate reductase (NR) and aldehydeoxidase (AO) of T1 generation plants revealed that the best line among the GmCnx1 transgenic plants accumulated 4.25 µg g(-1) h(-1) and 30 pmol L(-1), respectively (approximately 2.6-fold and 3.9-fold higher than non-transgenic control plants).In addition, overexpression ofGmCnx1boosted the resistance to various strains of soybean mosaic virus (SMV). DAS-ELISA analysis further revealed that infection rate of GmCnx1 transgenic plants were generally lower than those of non-transgenic plants among two different virus strains tested. Taken together, this study showed that overexpression of a GmCnx1 gene enhanced NR and AO activities and SMV resistance, suggesting its important role in soybean genetic improvement.