Anti-angiogenic therapy has been successfully applied to treat colorectal cancer (CRC). Ginsenoside Rg3, derived from the Chinese herb ginseng, has anti-vascularization effects and can inhibit tumor ...growth and metastasis, and can sensitize cancer cells to chemotherapy. Therefore, in the present study, we investigated whether Rg3 could be appropriate for CRC treatment. Growth of CRC cells was assessed by an MTT (methyl thiazolyl tetrazolium) assay in vitro and using orthotopic xenograft models in vivo. mRNA expression was evaluated using real-time PCR. Protein levels were tested by western blotting, flow cytometry and immunohistochemistry. Migration was determined using a wound-healing assay. Stemness was further confirmed using a plate clone formation assay. We found that Rg3 repressed the growth and stemness of CRC cells both in vitro and in vivo. Rg3 also impaired the migration of CRC cells in vitro. Rg3 downregulated the expressions of angiogenesis-related genes, and repressed the vascularization of CRC xenografts. In addition, Rg3 strengthened the cytotoxicity of 5-Fluorouracil and oxaliplatin against orthotopic xenografts in vivo. Moreover, Rg3 downregulated the expressions of B7-H1 and B7-H3, high expressions of which were associated with reduced overall survival (OS) of CRC patients. Hence, Rg3 not only repressed the growth and stemness of CRC cells, but could also remodel the tumor microenvironment through repressing angiogenesis and promoting antitumor immunity. Therefore, Rg3 could be a novel therapeutic for the CRC treatment.
Abstract
Objective
Currently, among wounds with large skin tissue defects caused by various reasons, the treatment of refractory wounds is still a major clinical problem. This study is aimed to ...preliminarily assess the therapeutic potentials of platelet-rich plasma (PRP) in refractory wounds with exposed tendons, as well as corresponding efficacy and safety.
Methods
A total of 12 patients (5 males and 7 females) with refractory wounds and exposed tendons who were admitted to our hospital from June 2018 to December 2020 were included in this study. After the preparation of PRP, the included patients underwent the PRP injection after the debridement of wounds, and the efficacy and prognosis were assessed by the same group of senior surgeons.
Results
The average age of included patients was 42.7 ± 12.9 years, and the causes of injury included traffic accidents (3 cases), contusion (2 cases), burns (2 cases), diabetes complications (4 cases), and melanoma complications (1 cases). The average healing time was 23.0 ± 5.0 days, and the mean size of the wound was 3.1 × 5.1 cm
2
. During the whole treatment process, Vancouver Scar Scale (VSS) decreased from 7.4 ± 1.6 before PRP treatment to 3.6 ± 0.9 after treatment (
P
< 0.001), Manchester Scar Scale (MSS) decreased from 12.3 ± 4.5 before PRP treatment to 5.4 ± 1.2 after treatment (
P
< 0.001), and no redness and swelling were observed around wounds, the size and degree of wounds gradually reduced, the coverage rate of granulation tissue was acceptable, overall quality of scar was relatively good, skin sensitivity around wounds was normal, there was no local wounds secretion, and postoperative patient's satisfaction was relatively good during follow-up.
Conclusions
Our study has preliminarily indicated that PRP can promote the wounds healing, reduce the inflammation around wounds, and improve the granulation tissue and angiogenesis, thereby effectively polishing up the safety and efficacy.
SUMMARY
As an important method of 3-D seismic exploration, intelligent structural interpretation has been improved in recent years. Traditional human–computer interaction explanations typically ...assess fault risk on a hierarchical basis. However, the majority of intelligent fault interpretations utilize binary classification methods, which limits the utility and development of this technology to a certain extent. In order to break this limitation, a fault risk assessment scheme based on particle swarm optimization (PSO) and support vector machine (SVM) posterior probability model has been proposed. In this study, the fault exposure situations for 11 wells and 4 roadways of a coal mine in Yunnan Province, China, were identified. A total of 15 559 data points with known fault and non-fault information were obtained in the target coal seam. Based on these data, SVM fault recognition models were constructed. The key parameters of the SVM models were optimized by PSO, and the test accuracy of each model was above 87 per cent. Meanwhile, the SVM posterior probability model was introduced to evaluate the fault identification results in the study area. The SVM posterior probability model was used to convert the decision value of a standard SVM into a posterior probability value. Probability values in the range of 0, 0.5) are evaluated as non-fault points, 0.5, 0.7) as ‘unreliable’ fault points, 0.7, 0.9) as ‘less reliable’ fault points, and 0.9, 1 as ‘reliable’ fault points. By constructing data sets with different sample numbers and fault types, the influence of each factor on the evaluation of the SVM posterior probability model was analysed. The results show that the SVM posterior probability model can be used to hierarchically evaluate fault risk in the study area and provide decision makers with more accurate information for decision making.
Almost all of the previous studies related with co-administration of letrozole in IVF cycles were performed in poor responders and letrozole may reduce the total gonadotropin dose required for ...ovarian stimulation, and the pregnancy rate did not decrease in poor responders. This study aimed to assess whether high responders co-treatment with letrozole reduced supraphysiological late follicular phase estradiol levels and the incidence of premature progesterone elevated at the end of the follicular phase, thereby impacting positively on endometrial receptivity.
A randomized parallel controlled study in a university-affiliated center include 130 high responders between October 2015 and August 2016. The patients were randomized on the first stimulation day of the IVF cycle and from stimulation day 5 receive letrozole (group A) or without letrozole treatment (group B).
Although estradiol levels were significantly lower in the letrozole group (group A) (P < 0.001), progesterone elevation (> 1.5 ng/mL was considered as a rise) on the day of hCG triggering (15.4, 7.7%) was not statistically significant (P = 0.170). RecFSH, the recovery rate of eggs, the high-quality embryo rate, and the thickness of endometrium (P = 0.776) were similar between the letrozole group(group A) and control groups (group B). Clinical pregnancy rates were 53.1% (26/49) and 72.9% (35/48) in the letrozole and control groups, respectively, with a statistical significance (P = 0.043).Live birth rates were 42.9% (21/49) and 62.5% (30/48),showed a marginally significant difference (P = 0.053). The miscarriage rate did not significantly differ between the two groups.
In this pilot study, letrozole supplementation could not reduce the incidence of premature progesterone rise during the late follicular phase in stimulated in vitro fertilization cycles in expected high responders, producing a harmful effect on the pregnancy outcome.
China Clinical Trial Registration Center: ChiCTR-IPR-15006211 URL of the trial registry record: http://www.chictr.org.cn/showproj.aspx?proj=10731 . Trial registration date: 8 April, 2015. Date of first patient's enrolment: 5 October, 2015.
B cells contribute to the pathogenesis of polycystic ovary syndrome (PCOS). Clinically, metformin is used to treat PCOS, but it is unclear whether metformin exerts its therapeutic effect by ...regulating B cells. Here, we showed that the expression level of tumor necrosis factor-alpha (TNF-α) in peripheral blood B cells from PCOS patients was increased. Metformin used in vitro and in vivo was able to reduce the production of TNF-α in B cells from PCOS patients. Administration of metformin improved mouse PCOS phenotypes induced by dehydroepiandrosterone (DHEA) and also inhibited TNF-α expression in splenic B cells. Furthermore, metformin induced metabolic reprogramming of B cells in PCOS patients, including the alteration in mitochondrial morphology, the decrease in mitochondrial membrane potential, Reactive Oxygen Species (ROS) production and glucose uptake. In DHEA-induced mouse PCOS model, metformin altered metabolic intermediates in splenic B cells. Moreover, the inhibition of TNF-α expression and metabolic reprogramming in B cells of PCOS patients and mouse model by metformin were associated with decreased mTOR phosphorylation. Together, TNF-α-producing B cells are involved in the pathogenesis of PCOS, and metformin inhibits mTOR phosphorylation and affects metabolic reprogramming, thereby inhibiting TNF-α expression in B cells, which may be a new mechanism of metformin in the treatment of PCOS.
SUMMARY
The key issue in the 3-D seismic exploration of geothermal reservoirs is to determine how the petrophysical properties of geothermal reservoirs change with temperature. In this paper, ...physical experiments on six rock samples from the Yunnan Lufeng geothermal field were used to analyse the effect of temperature on the elastic moduli of dry rock. The laboratory measurements show that under formation pressure conditions, the bulk modulus and shear modulus of the studied rock decrease linearly with increasing temperature, and the rock moduli exhibit approximately linear relationships with temperature. Gassmann's equation can be used to predict the influence of pore fluid on the P- and S-wave velocities of the rocks. To include the temperature effect in Gassmann's equation, we separately considered the rock matrix and pore fluid; we combined thermoelastic theory to introduce the influence of temperature on the rock into Gassmann's equation and directly considered the influence of temperature on the pore fluid. The effects of fluid on the physical properties of rocks were evaluated based on Gassmann's equation while considering the effect of temperature. The results show that the rock shear modulus is affected by temperature more than the bulk modulus is, which implies that the S-wave information is more sensitive to temperature. When the uniform water saturation is less than 95 per cent, temperature is the main factor influencing the rock bulk modulus. When the uniform water saturation is greater than 95 per cent, the fluid is the main factor influencing the rock bulk modulus, and the rock shear modulus is affected by only temperature. Fluid replacement with Gassmann's equation achieves results that are more consistent with laboratory measurements when the influence of temperature is considered. Gassmann's equation considering the effect of temperature reveals crucial dependences of the seismic wave velocities and elastic moduli on temperature and fluid content.
Sonodynamic therapy (SDT) has attracted widespread interest in biomedicine, owing to its novel and noninvasive therapeutic method triggered by ultrasound (US). Herein, the Ti3C2 MXene nanosheets ...(Ti3C2 NSs) are developed as good sonosensitizers via a two-step method of chemical exfoliation and high-temperature treatment. With the high-temperature treatment, the oxygen defect of Ti3C2 MXene nanosheets (H–Ti3C2 NSs) is greatly increased. Therefore, the electron (e−) and hole (h+) generated by US can be separated faster due to the improved degree of oxidation, and then the recombination of e−-h+ can be prevented with the abundant oxygen defect under US irradiation, which induced the sonodynamic efficiency greatly to improve around 3.7-fold compared with Ti3C2 NSs without high-temperature treatment. After PEGylation, the H–Ti3C2-PEG NSs show good stability and biocompatibility. In vitro studies exhibit that the inherent property of mild photothermal effect can promote the endocytosis of H–Ti3C2-PEG NSs, which can improve the SDT efficacy. In vivo studies further display that the increased blood supply by the mild photothermal effect can significantly relieve hypoxia in the tumor microenvironment, showing photothermal therapy (PTT) enhanced SDT. Most importantly, the H–Ti3C2-PEG NSs can be biodegraded and excreted out of the body, showing no significant long-term toxicity. Our work develops the defective H–Ti3C2 NSs as high-efficiency and safe sonosensitizers for photothermal-enhanced SDT of cancer, extending the biomedical application of MXene-based nanoplatforms.
Display omitted
•Two-step high-temperature methods were used to construct oxygen-defective Ti3C2 nanosheets.•The oxygen-defective H–Ti3C2 NSs displayed an excellent sonodynamic efficacy.•The good photothermal efficacy of H–Ti3C2-PEG NSs enhanced SDT efficacy.•The biodegradable H–Ti3C2-PEG NSs showed no significant long-term toxicity.
To explore whether SARS-CoV-2 infection affects the pregnancy outcomes of assisted reproductive techniques (ART).
A prospective cohort study recruited patients for embryo transfer from December 01, ...2022, to December 31, 2022. All patients were closely followed up for SARS-CoV-2 infection after embryo transfer. The SARS-CoV-2 "diagnosed group" was defined as RNA or antigen-positive. The SARS-CoV-2 "suspected infection group" was defined as having apparent SARS-CoV-2 symptoms without an RNA or antigen test, while the "uninfected group" was defined as having a negative SARS-CoV-2 RNA or antigen test and no SARS-CoV-2 symptoms.
A total of 1330 patients participated in the study, 687 of whom were in the SARS-CoV-2 diagnosed group, 219 in the suspected infection group, and 424 in the uninfected group. There was no significant difference in basic characteristics among the three groups. The clinical pregnancy rate was 68% in the SARS-CoV-2 diagnosed group, 63% in the uninfected group, and 51% in the suspected infection group (P < 0.001). The ongoing pregnancy rate was 58% in the SARS-CoV-2 diagnosed group, 53% in the uninfected group, and 45% in the suspected infection group (P < 0.001). Upon analyzing the factors influencing clinical pregnancy, it was found that suspected infection (odds ratio OR 0.618, 95% CI 0.444-0.862, P = 0.005) and the short time (≤ 22 days) between embryo transfer and SARS-CoV-2 infection (OR 3.76, 95% CI 1.92-8.24, P < 0.001) were not conducive to clinical pregnancy. In addition, the concurrent presence of fever and dizziness/headache SARS-CoV-2 symptoms (OR 0.715, 95% CI 0.526-0.972, P = 0.032) decreased the clinical pregnancy rate. However, vaccination administered 2-3 times (OR 1.804, 95% CI 1.332-2.444, P < 0.001) was associated with an improvement in clinical pregnancy rate.
This prospective cohort study shows that SARS-CoV-2 infection in a short period of time after embryo transfer is not conducive to clinical pregnancy. Reproductive physicians should advise patients to avoid SARS-CoV-2 infection shortly after embryo transfer. Meanwhile, women should be encouraged to vaccinate at least 2-3 times before embryo transfer or pregnancy.
To investigate the contribution of parental genomes to early embryogenesis, we profiled the single-cell transcriptomes of human biparental and uniparental embryos systematically from the 1-cell to ...the morula stage. We observed that uniparental embryos exhibited variable and decreased embryonic genome activation (EGA). Comparative transcriptome analysis identified 807 maternally biased expressed genes (MBGs) and 581 paternally biased expressed genes (PBGs) in the preimplantation stages. MBGs became apparent at the 4-cell stage and contributed to the initiation of EGA, whereas PBGs preferentially appeared at the 8-cell stage and might affect embryo compaction and trophectoderm specification. Regulatory network analysis revealed that DUX4, EGR2, and DUXA are key transcription factors in MBGs’ expression; ZNF263 and KLF3 are important for PBGs’ expression. We demonstrated that parent-specific DNA methylation might account for the expression of most PBGs. Our results provide a valuable resource to understand parental genome activation and might help to elucidate parent-of-origin effects in early human development.
Display omitted
•scRNA-seq of human biparental and uniparental embryos revealed parent-of-origin effects•1,388 MBGs and PBGs are involved in initiation of EGA and early differentiation•Transcriptional regulatory networks uncovered key transcription factors for MBGs and PBGs•WGBS demonstrated parent-specific DNA methylation pattern in early embryos
Leng et al. performed a comprehensive survey of transcriptional activities between biparental and uniparental embryos by single-cell RNA sequencing. They provide insights into the critical features of parental genome activation before implantation and help elucidate parent-of-origin effects in early human development.
Rigid aryl ring-based triphosphine can be used to construct highly emissive Cu(I) halide complexes applied in OLEDs, but rigid heteroaryl ring-based triphosphine Cu(I) halide complexes are rarely ...reported. Here, six mononuclear copper(I) halide complexes with two thiophenyl rings triphosphine CuX (L1) and CuX (L2) L1 = (2,5-Me-3-PPh2-C4S)2PPh, X = I (1), Br (2) Cl (3); L2 = (3-PPh2-C4H2S)2PPh, X = I (4), Br (5) Cl (6), were successfully synthesized and characterized on their structures and photophysical properties. The introduction of four methyl groups into two thiophenyl rings, improves the solubility and quantum yield, and fine-tunes the light-emitting color of complexes. At room temperature, complexes 1–6 in powder state exhibit intense green to yellow green delayed fluorescence (λem = 502–528 nm, τ = 16.1–63.0 μs, Φ = 0.21–0.35 for 1–3; λem = 507–559 nm, τ = 3.9–13.3 μs; Φ = 0.04–0.27 for 4–6). The emissions of the complexes 1–6 are originated from (metal + halide) to ligand and intra-ligand charge transitions. Solution-processed, complex 3-based nondoped and doped devices emit yellow and yellow green light with CIE of (0.48, 0.48) and (0.41, 0.51), respectively. The doped device achieves a maximum external quantum efficiency (EQE) of 3.12%, and a maximum luminance of 2280 cd/m2. The EQE value is the highest among reported mononuclear Cu(I) halide complexes with triphosphine based devices by solution-processed method.
The introduction of two thiophenyl rings and four methyl groups can increase the solubility and quantum yields, fine-tune the emission color of Cu(I) halide complexes. Display omitted
•Mononuclear Cu(I) complexes based on electron-rich heteroaryl rings triphosphine ligands are firstly reported.•The introduction of two thiophenyl rings and four methyl groups can increase the solubility and PLQY of complexes.•Doped device shows the maximum EQE of 3.12%, which is the highest among reported Cu(I) complexes with triphosphine.
PDF
