Efficacy of epigallocatechin gallate (EGCG) and its underlying mechanism in preventing bisphenol-A-induced metabolic disorders in mice.

To investigate the efficacy of epigallocatechin gallate (EGCG) and its underlying mechanism in preventing bisphenol-A-induced metabolic disorders, in this study, a mice model of metabolic disorders induced by BPA was developed to investigate the efficacy and mechanism of EGCG using microbiomes and metabolomics. The results showed that EGCG reduced body weight, liver weight ratio, and triglyceride and total cholesterol levels in mice by decreasing the mRNA expression of genes related to fatty acid synthesis (Elov16) and cholesterol synthesis (CYP4A14) and increasing the mRNA expression of genes related to fatty acid oxidation (Lss) and cholesterol metabolism (Cyp7a1). In addition, EGCG normalized BPA-induced intestinal microbial dysbiosis. Metabolic pathway analysis showed that low-dose EGCG was more effective than high-dose EGCG at affecting the biosynthesis of L-cysteine, glycerophosphorylcholine, and palmitoleic acid. These results provide specific data and a theoretical basis for the risk assessment of BPA and the utilization of EGCG.

Association of educational environment with the prevalence of myopia: a cross-sectional study in central China.

Purposes: This study was to estimate the prevalence of myopia among primary school students in Hefei, China, and evaluate the association of educational environment with myopia. Methods: This study was a cross-sectional study, and recruited primary school students in grades 1-6. Children underwent a stepwise ophthalmic examination, which included visual acuity and objective cycloplegic refraction to identify children with myopia. Under the guidance of parents, children completed a questionnaire, including gender, region, grade and several indicators related to education. The study analyzed the risk factors by using a logistic regression and assessed feature importance by using a random forest algorithm. Results: A total of 3,596 primary school students were involved in this analysis, and the overall prevalence of myopia was 27.1%. Gender, grade, education level of the father, education level of the mother, academic level of children, hours of homework per day on weekends, number of after-school tutoring per week and frequency of extracurricular reading were significantly associated with myopia. There was no significant association between the amount of homework per day on school days and myopia after adjusting for covariates. In terms of educational environment, the top 3 factors were academic level of children, homework on weekends and after-school tutoring. Conclusions: Educational environment with high educational loads was associated with the high prevalence of myopia. Reducing the burden of studying, especially that after class, was an effective way to prevent myopia.

Lactobacillus gasseri LGV03 isolated from the cervico-vagina of HPV-cleared women modulates epithelial innate immune responses and suppresses the growth of HPV-positive human cervical cancer cells.

Persistent human papillomavirus (HPV) infections is necessary for the development of cervical cancers. An increasing number of retrospective studies have found the depletion of Lactobacillus microbiota in the cervico-vagina facilitate HPV infection and might be involved in viral persistence and cancer development. However, there have been no reports confirming the immunomodulatory effects of Lactobacillus microbiota isolated from cervico-vaginal samples of HPV clearance in women. Using cervico-vaginal samples from HPV persistent infection and clearance in women, this study investigated the local immune properties in cervical mucosa. As expected, type I interferons, such as IFN-α and IFN-ß, and TLR3 globally downregulated in HPV+ persistence group. Luminex cytokine/chemokine panel analysis revealed that L. jannaschii LJV03, L. vaginalis LVV03, L. reuteri LRV03, and L. gasseri LGV03 isolated from cervicovaginal samples of HPV clearance in women altered the host's epithelial immune response, particularly L. gasseri LGV03. Furthermore, L. gasseri LGV03 enhanced the poly (I:C)-induced production of IFN by modulating the IRF3 pathway and attenuating poly (I:C)-induced production of proinflammatory mediators by regulating the NF-κB pathway in Ect1/E6E7 cells, indicating that L. gasseri LGV03 keeps the innate system alert to potential pathogens and reduces the inflammatory effects during persistent pathogen infection. L. gasseri LGV03 also markedly inhibited the proliferation of Ect1/E6E7 cells in a zebrafish xenograft model, which may be attributed to an increased immune response mediated by L. gasseri LGV03.

Enhancing Thermo-Osmotic Low-Grade Heat Recovery by Applying a Negative Pressure to the Feed.

A newly developed technology, thermo-osmotic energy conversion (TOEC), is supposed to convert low-grade heat into power. However, the performance of existing TOEC experiments is deficient. This paper discusses the feasibility of strengthening TOEC by applying negative pressure to the feed liquid, which can reduce air pressure in the membrane pores and molecular diffusion resistance. Theoretical calculation shows that when the cooling and heating temperatures are 40 and 80 °C, respectively, and the transmembrane pressure difference is 5.0 MPa, the TOEC system with a negative pressure of 0.5 bar at the feed side can approach an efficiency of 3.01% and a power density of 16.85 W m-2, which increases by 20% and 27% compared with no negative pressure, respectively. Given the nonuniformity in the real system, computational fluid dynamics simulation is used to obtain the correction factor, which is then used to revise the theory prediction results for the first time. Moreover, a lab-scale experiment also proves that a negative pressure at the feed benefits the performance of the TOEC device. Overall, this research presents a feasible method to enhance a TOEC system, which may promote the development of a more-efficiently TOEC system for low-grade heat utilization.

Mesoscopic Simulations of Diselenide-Containing Crosslinked Doxorubicin-Loaded Micelles and Their Tumor Microenvironment Responsive Release Behaviors.

There is currently limited research on the structure-property relationship of reduction stimuli-responsive polymeric crosslinked micelles using mesoscopic simulations. Herein, dissipative particle dynamics (DPD) simulations were used to simulate the self-assembly process of the blank non-crosslinked micelle, the structure and doxorubicin (DOX) distribution of diselenide crosslinked micelle with different crosslinker contents (CCs) based on the nearest-neighbor bonding principle. The results revealed that the formation of a three-layer spherical micelle and the loaded DOX mainly distributed in the polycaprolactone (PCL) core and hydroxyethyl methacrylate (HEMA) mesosphere. The larger the dosage of DOX, the more DOX encapsulated, but the encapsulation of DOX in the hydrophobic domain would reach saturation when the dosage increased to 6.0 %. In micelles with lower CCs or crosslinking levels (CLs), DOX entered the middle layer and the inner core faster. Then, based on the nearest media-bead bond breaking principle and subsequently DPD simulation, the effects of different CCs on the micelle structure and DOX release properties were investigated. Low CC could cause fast drug release. With the increase of CCs, the micelle showed a slower DOX release trend. The multilayer crosslinked network system also affected the DOX release rate. Hence, this work can provide some mesoscale guidance for the structural design and structure-property relationship of stimuli-responsive reversible crosslinked micelles for drug delivery.

Boosting algorithm improves the accuracy of juvenile forensic dental age estimation in southern China population.

Age estimation based on the mineralized morphology of teeth is one of the important elements of forensic anthropology. To explore the most suitable age estimation protocol for adolescents in the South China population, 1477 panoramic radiograph images of people aged 2-18 years in the South were collected and staged by the Demirjian mineralization staging method. The dental ages were estimated using the parameters of the Demirjian and Willems. Mathematical optimization and machine learning optimization were also performed in the data processing process in an attempt to obtain a more accurate model. The results show that the Willems method was more accurate in the dental age estimation of the southern China population and the model can be further optimized by reassigning the model through a nonintercept regression method. The machine learning model presented excellent results in terms of the efficacy comparison results with the traditional mathematical model, and the machine learning model under the boosting framework, such as gradient boosting decision tree (GBDT), significantly reduced the error in dental age estimation compared to the traditional mathematical method. This machine learning processing method based on traditional estimation data can effectively reduce the error of dental age estimation while saving arithmetic power. This study demonstrates the effectiveness of the GBDT algorithm in optimizing forensic age estimation models and provides a reference for other regions to use this parameter for age estimation model establishment, and the lightweight nature of machine learning offers the possibility of widespread forensic anthropological age estimation.

A chimeric switch-receptor PD1-DAP10-41BB augments NK92-cell activation and killing for human lung Cancer H1299 Cell.

Engineered natural killer (NK) cell-based therapies have been potentially broadly applicable and exhibited promising results in clinical trials, particularly in the fight against cancers. NK cell immunotherapy however always remains variable. One major obstacle is the inhibitory pathway including PD1/PDL1, providing tumor cells an escape mechanism from immunosurveillance. In this regard, we rationally designed a chimeric switch-receptor (CSR) PD1-DAP10-41BB, which comprising the ectodomain of PD1 fused to the co-stimulatory receptor DAP10 and 41BB. Therefore, by exchanging the transmembrane and cytoplasmic tail of PD1 with positive costimulatory molecules DAP10 and 41BB signaling domains, the negative PD1/PDL1 signal pathway was thus converted into a positive one. This CSR-expressing NK92 cells showed a typical parental NK92 phenotype and improved cytotoxicity against human lung cancer H1299 cells. Besides, the expression of CSR elicited a significant increase of effector molecules such as perforin and granzymes, which can induce apoptosis of H1299 cells. More importantly, in the solid tumor cell H1299-bearing mice model, the CSR-modified NK92 cells significantly inhibited tumor growth. Collectively, we demonstrated that expression of PD1-DAP10-41BB augmented NK92-cell activation and killing in vitro and in vivo, which provides a considerable avenue of using NK-tailored chimeric receptor engineered NK92 cells to treat a wide range of solid tumors.

Genetical engineering for NK and T cell immunotherapy with CRISPR/Cas9 technology: Implications and challenges.

Immunotherapy has become one of the most promising strategies in cancer therapies. Among the therapeutic alternatives, genetically engineered NK/T cell therapies have emerged as powerful and innovative therapeutic modalities for cancer patients with precise targeting and impressive efficacy. Nonetheless, this approach still faces multiple challenges, such as immunosuppressive tumor microenvironment, exhaustion of immune effector cells in tumors, off-target effects manufacturing complexity, and poor infiltration of effector cells, all of which need to be overcome for further utilization to cancers. Recently, CRISPR/Cas9 genome editing technology, with the goal of enhancing the efficacy and increasing the availability of engineered effector cell therapies, has shown considerable potential in the novel strategies and options to overcome these limitations. Here we review the current progress of the applications of CRISPR in cancer immunotherapy. Furthermore, we discuss issues related to the NK/T cell applications, gene delivery methods, efficiency, challenges, and implications of CRISPR/Cas9.

Stack Thermo-Osmotic System for Low-Grade Thermal Energy Conversion.

Thermo-osmotic energy conversion (TOEC) technology, developed from membrane distillation, is an emerging method that has the potential of obtaining electricity efficiently from a low-grade heat source but faces the difficult problem of pump power loss. In this study, we build a novel TOEC system with a multistage architecture that can work without pump assistance. The experiment system, made of cheap commercial materials, can obtain a power density of 1.39 ± 0.25 W/m2, with a heating temperature of 80 °C, and its efficiency increased linearly with the total stage number. A theory calculation shows that a 30-stage system with a specific membrane and a working pressure of 5.0 MPa can obtain an efficiency of 2.72% with a power density of 14.0 W/m2. By a molecular dynamics simulation, it is shown that a high-performance membrane has the potential to work at 40 MPa. This study proves that TOEC technology is a practical and competitive approach to covert low-grade thermal energy into power efficiently.

[Laboratory testing techniques for SARS-CoV-2].

The ongoing epidemic of caused by the coronavirus SARS-CoV-2 starting in December 2019 poses a serious public health threat globally. The virus is highly infectious and transmitted mainly through droplets and contacts, and is associated with a high risk of pneumonia. A small number of patients may present with acute respiratory distress syndrome with severe respiratory complications, which can lead even to death. The selection of appropriate detection techniques and methods for accurate and rapid identification of pathogens therefore plays a key role in improving the diagnosis and treatment of the patients and containing the outbreak. In this review, the authors gives an overview of the virus laboratory detection technology, including virus isolation and culture, real-time fluorescent PCR, gene sequencing, serological antibody detection, and the gene editing technology based on CRISPR/Cas13 system. These techniques are expected to provide valuable assistance in controlling the epidemic and new ideas for future researches.

Ilamycin C induces apoptosis and inhibits migration and invasion in triple-negative breast cancer by suppressing IL-6/STAT3 pathway.

BACKGROUND: Triple-negative breast cancer (TNBC) is the most aggressive subtype of breast cancer with poor prognosis, and its treatment remains a challenge due to few targeted medicines and high risk of relapse, metastasis, and drug resistance. Thus, more effective drugs and new regimens for the therapy of TNBC are urgently needed. Ilamycins are a kind of cyclic peptides and produced by Streptomyces atratus and Streptomyces islandicus with effective anti-tuberculosis activity. Ilamycin C is a novel compound isolated from the deep South China Sea-derived Streptomyces atratus SCSIO ZH16 and exhibited a strong cytotoxic activity against several cancers including breast cancer cell line MCF7. However, the cytotoxic activity of Ilamycin C to TNBC cells and a detailed antitumor mechanism have not been reported. METHODS: CCK-8 assays were used to examine cell viability and cytotoxic activity of Ilamycin C to TNBC, non-TNBC MCF7, and nonmalignant MCF10A cells. EdU assays and flow cytometry were performed to assess cell proliferation and cell apoptosis. Transwell migration and Matrigel invasion assays were utilized to assess the migratory and invading capacity of TNBC cells following the treatment of Ilamycin C. The expressions of proteins were detected by western blot. RESULTS: In this study, we found that Ilamycin C has more preferential cytotoxicity in TNBC cells than non-TNBC MCF7 and nonmalignant MCF10A cells. Notably, our studies revealed the mechanism that Ilamycin C can induce Bax/Bcl-2-related caspase-dependent apoptosis and inhibit migration and invasion through MMP2/MMP9/vimentin/fascin in TNBC by suppressing IL-6-induced STAT3 phosphorylation. CONCLUSIONS: This study provides the first evidence that Ilamycin C has significant implications for the potential as a novel IL-6/STAT3 inhibitor for TNBC treatment in the future.

Natural products for treating colorectal cancer: A mechanistic review.

Colorectal cancer (CRC) is one of the most common types of cancers in humans and is closely linked to the global cancer-related mortalities worldwide. Molecular pathological epidemiology studies can reveal the risk factors of CRC and contribute to biomarker research and precision medicine. The current clinical treatment for CRC mainly involves surgery and chemotherapy. However, because of the occurrence of side effects and the emergence of drug resistance, there is an urgent need to find new and more effective drugs for CRC treatment. An increasing number of studies have demonstrated that many natural products possess effective anti-CRC effects and may serve as alternative chemotherapy agents for CRC treatment. In this review, we summarize the natural products with anti-CRC effects from different sources based on the chemical structures such as alkaloids, polysaccharides, polyphenols, terpenoid, unsaturated fatty acids, and discuss the natural product-derived drugs used clinically for colorectal cancer treatment. Furthermore, natural products of marine origin are also discussed for their enormous potential to serve as the candidate drugs. Notably, we generalize the experiment-based molecular mechanisms and the regulatory networks whereby natural products exert anticancer effects on cell proliferation, metastasis, apoptosis, autophagy, and angiogenesis.

Circular RNA: new star, new hope in cancer.

BACKGROUND: Circular RNAs are a new class of endogenous non-coding RNA that can function as crucial regulators of diverse cellular processes. The diverse types of circular RNAs with varying cytogenetics in cancer have also been reported. Circular RNAs can act as a microRNA sponge or through other mechanisms to regulate gene expression as either tumor inhibitors or accelerators, suggesting that circular RNAs can serve as newly developed biomarkers with clinic implications. Here, we summerized recent advances on circular RNAs in cancer and described a circular RNA network associated with tumorigenesis. The clinical implications of circular RNAs in cancer were also discussed in this paper. SHORT CONCLUSION: Growing evidence has revealed the crucial regulatory roles of circular RNAs in cancer and the elucidation of functional mechanisms involving circular RNAs would be helpful to construct a circRNA-miRNA-mRNA regulatory network. Moreover, circular RNAs can be easily detected due to their relative stability, widespread expression, and abundance in exosomes, blood and saliva; thus, circular RNAs have potential as new and ideal clinical biomarkers in cancer.

Protein kinase inhibitors for acute leukemia.

Conventional treatments for acute leukemia include chemotherapy, radiation therapy, and intensive combined treatments (including bone marrow transplant or stem cell transplants). Novel treatment approaches are in active development. Recently, protein kinase inhibitors are on clinical trials and offer hope as new drugs for acute leukemia treatment. This review will provide a brief summary of the protein kinase inhibitors in clinical applications for acute leukemia treatment.

Protein Kinase Inhibitors as Therapeutic Drugs in AML: Advances and Challenges.

Acute myeloid leukemia (AML) is a malignant blood disorder and the cure rate has been remarkably improved over the past decade. However, recurrent or refractory leukemia remains the major problem of the AML and no clearly effective therapy has been established so far. Traditional treatments such as chemotherapy and hematopoietic stem cell transplantation are both far dissatisfying the patients partly for their individual variety. Besides, conventional treatments usually have many side effects to result in poor prognosis. Therefore, an urgent need is necessary to update therapies of AML. To date, protein kinase inhibitors as new drugs offer hope for AML treatment and many of them are on clinical trials. Here, this review will provide a brief summary of protein kinase inhibitors investigated in AML thus far, mainly including tyrosine protein kinase inhibitors and serine/threonine kinase inhibitors. We also presented the sketch of signal pathways involving protein kinase inhibitors, as well as discussed the clinical applications and the challenges of inhibitors in AML treatment.