Nanoparticle drug delivery system for the treatment of brain tumors: Breaching the blood-brain barrier.

The current status of clinical trials utilizing nanoparticle drug delivery system (NDDS) for brain tumors was summarized.Image 1.

Exosome-based anticancer vaccines: From Bench to bedside.

Exosomes, a subset of extracellular vesicles, are released by all active cells and play a crucial role in intercellular communications. Exosomes could facilitate the transfer of various biologically active molecules, such as DNA, non-coding RNAs, and proteins, from donor to recipient cells, thereby participating in diverse biological and pathological processes. Besides, exosomes possess unique characteristics, including non-toxicity, low-immunogenicity, and stability within biological systems, rendering them highly advantageous for cancer drug development. Meanwhile, accumulating evidence suggests that exosomes originating from tumor cells and immune cells possess distinct composition profiles that play a direct role in anticancer immunotherapy. Of note, exosomes can transport their contents to specific cells, thereby exerting an impact on the phenotype and immune-regulatory functions of targeted cells. Therapeutic cancer vaccines, an emerging therapeutics of immunotherapy, could enhance antitumor immune responses by delivering a large number of tumor antigens, thereby augmenting the immune response against tumor cells. Therefore, the therapeutic rationale of cancer vaccines and exosome-based immunotherapy are almost similar to some extent, but some challenges have hindered their application in the clinical setting. Here, in this review, we first summarized the biogenesis, structure, compositions, and biological functions of exosomes. Then we described the roles of exosomes in cancer biology, particularly in tumor immunity. We also comprehensively reviewed current exosome-based anticancer vaccine development and we divided them into three types. Finally, we give some insights into clinical translation and clinical trial progress of exosome-based anticancer vaccines for future direction.

Desertivirga arenae gen. nov., sp. nov. and Desertivirga brevis sp. nov., isolated from desert soil, and reclassification of Pedobacter xinjiangensis as Desertivirga xinjiangensis comb. nov. and Pedobacter mongoliensis as Paradesertivirga mongoliensis gen.nov., comb. nov.

Two novel bacterial strains, designated as SYSU D00823T and SYSU D00873T, were isolated from sandy soil of the Gurbantunggut Desert in Xinjiang, north-west China. SYSU D00823T and SYSU D00873T shared 99.0 % 16S rRNA gene sequence identity, and were both most closely related to Pedobacter xinjiangensis 12157T with 96.1 % and 96.0 % similarities, respectively. Phylogenetic and phylogenomic analyses revealed that the two isolates and P. xinjiangensis 12157T formed a separate distinct cluster in a stable subclade with the nearby species Pedobacter mongoliensis 1-32T, as well as the genera Pararcticibacter and Arcticibacter. Furthermore, P. mongoliensis 1-32T formed a separate deep-branching lineage and did not form a cluster with members of the genus Pedobacter. The average nucleotide identity and digital DNA-DNA hybridization values between SYSU D00823T and SYSU D00873T and related species were well below the thresholds for species delineation (<81.0 % and <24.0 %, respectively). The genomes of SYSU D00823T and SYSU D00873T were 6.19 and 6.43 Mbp in size with 40.4 % and 40.5 % DNA G+C contents, respectively. The predominant fatty acids (>10 %) of SYSU D00823T and SYSU D00873T were iso-C15 : 0, iso-C17 : 0 3-OH and summed feature 3 (C16 : 1 ω7c and/or C16 : 1 ω6c). Menaquinone-7 was the only respiratory quinone. The major polar lipids were phosphatidylethanolamine, glycosphingolipid, aminoglycolipid/glycolipid, aminophospholipid and three or four unidentified polar lipids. These data indicated that strains SYSU D00823T and SYSU D00873T should be assigned to two novel species of a new genus within the family Sphingobacteriaceae, for which the names Desertivirga arenae gen. nov., sp. nov. and Desertivirga brevis sp. nov. are proposed. The type strains are SYSU D00823T (=CGMCC 1.18630T=MCCC 1K04973T=KCTC 82278T) and SYSU D00873T (=CGMCC 1.18629T=MCCC 1K04974T=KCTC 82281T), respectively. Accordingly, the reclassification of P. xinjiangensis as Desertivirga xinjiangensis comb. nov., and P. mongoliensis as Paradesertivirga mongoliensis gen. nov., comb. nov. are also proposed.

Analysis of risk factors associated with pre-myopia among primary school students in the Mianyang Science City.

Objectives To find out the prevalence rate of pre-myopia among primary school students in the Mianyang Science City Area, analyze its related risk factors, and thus provide a reference for local authorities to formulate policies on the prevention and control of myopia for primary school students. Methods From September to October 2021, Cluster sampling was adopted by our research group to obtain the vision levels of primary school students employing a diopter test in the Science City Area. In addition, questionnaires were distributed to help us find the risk factors associated with pre-myopia. Through the statistical analysis, we identify the main risk factors for pre-myopia and propose appropriate interventions. Results The prevalence rate of pre-myopia among primary school students in the Science City Area was 45.27% (1020/2253), of which 43.82% were boys and 46.92% were girls, with no statistically significant difference in the prevalence rate of myopia between boys and girls (2 =2.171, P=0.141). The results of the linear trend test showed that the prevalence rate of pre-myopia tends to decrease with increasing age (Z=296.521, P=0.000). Logistic regression analysis demonstrated that the main risk factors for pre-myopia were having at least one parent with myopia, spending less than 2 hours a day outdoors, using the eyes continuously for more than 1 hour, looking at electronic screens for more than 2 hours, and having an improper reading and writing posture. Conclusion The Science City Area has a high prevalence rate of pre-myopia among primary school students. It is proposed that students, schools, families, and local authorities work together to increase the time spent outdoors, reduce digital screens and develop scientific use of eye habits.

Comprehensive multi-omics analysis provides biological insights and therapeutic strategies for small-cell lung cancer.

Integration of multi-omics analysis into small-cell lung cancer (SCLC) research. In the research of small-cell lung cancer, the integration of multi-omics analysis has become an important research direction. Multi-omics analysis includes the study of genomics, transcriptomics, proteomics, metabolomics, and other levels, which can help us to understand the pathogenesis and development process of diseases more comprehensively as well as develop novel therapeutics and biomarkers for further precision oncology.

Genetically predicted blood metabolites mediate the association between circulating immune cells and pancreatic cancer: A Mendelian randomization study.

BACKGROUND: Pancreatic cancer is characterized by metabolic dysregulation and unique immunological profiles. Nevertheless, the comprehensive understanding of immune and metabolic dysregulation of pancreatic cancer remains unclear. In the present study, we aimed to investigate the causal relationship of circulating immune cells and pancreatic cancer and identify the blood metabolites as potential mediators. METHODS: The exposure and outcome genome-wide association studies (GWAS) data used in the present study were obtained from the GWAS open-access database (https://gwas.mrcieu.ac.uk). The study used 731 circulating immune cell features, 1400 types of blood metabolites and pancreatic cancer from GWAS. We then performed bidirectional Mendelian randomization (MR) analyses to explore the causal relationships between the circulating immune cells and pancreatic cancer, and two-step MR to discover potential mediating blood metabolites in this process. All statistical analyses were performed in R software. The STROBE-MR (i.e. Strengthening the Reporting of Observational Studies in Epidemiology using Mendelian Randomization) checklist for the reporting of MR studies was also used. RESULTS: MR analysis identified seven types of circulating immune cells causally associated with pancreatic cancer. Furthermore, there was no strong evidence that genetically predicted pancreatic cancer had an effect on these seven types of circulating immune cells. Further two-step MR analysis found 10 types of blood metabolites were causally associated with pancreatic cancer and the associations between circulating CD39+CD8+ T cells and pancreatic cancer were mediated by blood orotates with proportions of 5.18% (p = 0.016). CONCLUSIONS: The present study provides evidence supporting the causal relationships between various circulating immune cells, especially CD39+CD8+ T cells, and pancreatic cancer, with a potential effect mediated by blood orotates. Further research is needed on additional risk factors as potential mediators and establish a comprehensive immunity-metabolism network in pancreatic cancer.

ZnO/g-C3N4 photocatalyst activated by low-pressure ultraviolet for restoring the SWASV signals: A fast pretreatment method for electrochemically detecting Cd2+ and Pb2+ in soil extracts.

Soil organic matter (SOM) significantly impacts the detection accuracy of Cd2+ and Pb2+ using square wave anodic stripping voltammetry (SWASV) due to the complexation of SOM to heavy metal ions (HMIs), thereby attenuating SWASV signals. This study explored an effective pretreatment method that combined low-pressure ultraviolet (LPUV) photolysis with the ZnO/g-C3N4 photocatalyst, activating the photocatalyst to generate highly oxidative •OH radicals and O2•- radicals, which effectively disrupted this complexation, consequently restoring the electroactivity of HMIs and achieving high-fidelity SWASV signals. The parameters of the LPUV-ZnO/g-C3N4 photocatalytic system were meticulously optimized, including the pH of photolysis, duration of photolysis, g-C3N4 mass fraction, and concentration of the photocatalyst. Furthermore, the ZnO/g-C3N4 photocatalyst was thoroughly characterized, with an in-depth investigation on the synergistic interaction between ZnO and g-C3N4 and the mechanisms contributing to the restoration of SWASV signals. This synergistic interaction effectively separated charge carriers and reduced charge transfer resistance, enabling photogenerated electrons (e-) from the conduction band of g-C3N4 to be quickly transferred to the conduction band of ZnO, preventing the recombination of e- and hole (h+) and generating more radicals to disrupt complexation and restore the SWASV signals. Finally, the analysis of HMIs in real soil extracts using the proposed pretreatment method demonstrated high detection accuracy of 94.9% for Cd2+ and 99.8% for Pb2+, which validated the feasibility and effectiveness of the proposed method in environmental applications.

Single-Cell Transcriptional Profile Construction of Rat Pituitary Glands before and after Sexual Maturation and Identification of Novel Marker Spp1 in Gonadotropes.

The mammalian pituitary gland drives highly conserved physiological processes such as somatic cell growth, pubertal transformation, fertility, and metabolism by secreting a variety of hormones. Recently, single-cell transcriptomics techniques have been used in pituitary gland research. However, more studies have focused on adult pituitary gland tissues from different species or different sexes, and no research has yet resolved cellular differences in pituitary gland tissue before and after sexual maturation. Here, we identified a total of 15 cell clusters and constructed single-cell transcriptional profiles of rats before and after sexual maturation. Furthermore, focusing on the gonadotrope cluster, 106 genes were found to be differentially expressed before and after sexual maturation. It was verified that Spp1, which is specifically expressed in gonadotrope cells, could serve as a novel marker for this cell cluster and has a promotional effect on the synthesis and secretion of follicle-stimulating hormone. The results provide a new resource for further resolving the regulatory mechanism of pituitary gland development and pituitary hormone synthesis and secretion.

Effect of Chinese Medicine in Patients with COVID-19: A Multi-center Retrospective Cohort Study.

OBJECTIVE: To evaluate the effectiveness and safety of Chinese medicine (CM) in the treatment of coronavirus disease 2019 (COVID-19) in China. METHODS: A multi-center retrospective cohort study was carried out, with cumulative CM treatment period of ⩾3 days during hospitalization as exposure. Data came from consecutive inpatients from December 19, 2019 to May 16, 2020 in 4 medical centers in Wuhan, China. After data extraction, verification and cleaning, confounding factors were adjusted by inverse probability of treatment weighting (IPTW), and the Cox proportional hazards regression model was used for statistical analysis. RESULTS: A total of 2,272 COVID-19 patients were included. There were 1,684 patients in the CM group and 588 patients in the control group. Compared with the control group, the hazard ratio (HR) for the deterioration rate in the CM group was 0.52 [95% confidence interval (CI): 0.41 to 0.64, P<0.001]. The results were consistent across patients of varying severity at admission, and the robustness of the results were confirmed by 3 sensitivity analyses. In addition, the HR for all-cause mortality in the CM group was 0.29 (95% CI: 0.19 to 0.44, P<0.001). Regarding of safety, the proportion of patients with abnormal liver function or renal function in the CM group was smaller. CONCLUSION: This real-world study indicates that the combination of a full-course CM therapy on the basic conventional treatment, may safely reduce the deterioration rate and all-cause mortality of COVID-19 patients. This result can provide the new evidence to support the current treatment of COVID-19. Additional prospective clinical trial is needed to evaluate the efficacy and safety of specific CM interventions. (Registration No. ChiCTR2200062917).

Quadrotors' double-loop controller design with tensor product model transformation and partial fully actuated method.

In the existing work of tensor product (TP) model transformation, the TP model transformation-based work on the quadrotor's control system design is scarce, the direct TP model transformation control strategy that applied to the quadrotor fails due to the calculation complexity, infeasibility of the huge amount of linear matrix inequalities, and the complexity of solving the linear matrix inequalities. To solve this problem, a partial TP model transformation-based double loop fuzzy controller has been studied in this work, the double-loop hybrid control scheme combines the fully actuated control method and the TP model transformation, while the fully actuated control method is used to the position subsystem control loop, and the TP model transformation based fuzzy controller is applied to the attitude control of the quadrotor. Moreover, for comparison purpose, a varying-input method based on TP model transformation is extended to the quadrotor's system control. The double-loop hybrid control scheme could also be extended with other TP model transformation based tensor sampling methods, such as, uniform sampling method and varying-input method. At last, the proposed algorithms are evaluated and compared on Parrot Mambo Minidrone, MFP450 and CUAV V5+ based hexarotor.

Deleting SUV39H1 in CAR-T cells epigenetically enhances the antitumor function.

SUV39H1 ablation in CAR-T cells epigenetically enhances the antitumor function (by Figdraw). (A) Schematic illustration of SUV39H1 ablation-mediated enhanced antitumor function of CAR-T cells. Functional CAR-T cells eventually transformed into dysfunctional exhausted CAR-T cells under the exposure of chronic tumor antigens, accompanied by reduced proliferation level, effector function, and stemness/memory characteristics, thereby limiting the antitumor activity so as to cause the recurrence of solid tumors. Upon genetic engineering of SUV39H1 ablation, SUV KO CAR-T cells are endowed with increased proliferation level and stemness/memory properties, accompanied by reduced effector/exhausted phenotype. Augmented SUV KO CAR-T cells after in vitro expansion intravenously infusion to mice achieved stronger and more persistent tumor rejection. (B) SUV39H1 ablation-mediated epigenetic reprogramming mechanism of CAR-T cells. Epigenetically, under the stimulation of chronic tumor antigens, exhausted CAR-T cells were characterized by downregulation of proliferation, effector and stemness/memory-associated genes and upregulation of exhaustion-associated genes. SUV39H1 genetic ablation increased chromatin accessibility of stemness/memory-associated genes and reduced chromatin accessibility of inhibitory receptors and effector-associated genes in SUV KO CAR-T cells, epigenetically reprogramming human T cells to express higher levels of stemness/memory genes such as KLF2, LEF1 and TCF7 and lower levels of effector/exhaustion genes.

[Hydrochemical Characteristics, Controlling Factors and Water Quality Evaluation of Shallow Groundwater in Tan-Lu Fault Zone （Anhui Section）].

To study the hydrochemical characteristics, controlling factors, and groundwater quality of the Tan-Lu fault zone (Anhui section), 86 groundwater samples were taken from the areas surrounding the Tan-Lu fault zone (Anhui section), which included the Jianghuai Wavy Plain, the Yanjiang Hill Plain, and the Dabie Mountains in western Anhui. Descriptive statistics, Piper diagram, Gibbs diagram, ion ratio analysis, saturation index, chloride-alkalinity index, and entropy weight water quality index (EWQI) were used to comprehensively study the hydrochemical characteristics and controlling factors of groundwater and to evaluate its quality. The results showed that the shallow groundwater in the Tan-Lu fault zone (Anhui section) was weakly alkaline, with dominant anions and cations of HCO3-, Ca2+ and Na+, respectively, and the hydrochemical types were mainly HCO3-Ca·Mg and HCO3-Na·Ca. The solute source of groundwater was mainly controlled by water-rock interactions, and the weathering of silicate and carbonate rocks jointly contributed to the formation of the chemical components of groundwater. Strong cation exchange adsorption was an important factor causing Na+ enrichment. The overall quality of groundwater in the study area was good but was polluted to a certain extent by human activities. Most of the groundwater in the Jianghuai Wavy Plain and Yanjiang Hill Plain was not suitable for direct drinking. The results of this research have important implications for the sustainable development and utilization of shallow groundwater resources and environmental protection in the Tan-Lu fault zone (Anhui section).

Unlocking the power of nanomedicine: Cell membrane-derived biomimetic cancer nanovaccines for cancer treatment.

Over the past decades, nanomedicine researchers have dedicated their efforts to developing nanoscale platforms capable of more precisely delivering drug payloads to attack tumors. Cancer nanovaccines are exhibiting a distinctive capability in inducing tumor-specific antitumor responses. Nevertheless, there remain numerous challenges that must be addressed for cancer nanovaccines to evoke sufficient therapeutic effects. Cell membrane-derived nanovaccines are an emerging class of cancer vaccines that comprise a synthetic nanoscale core camouflaged by naturally derived cell membranes. The specific cell membrane has a biomimetic nanoformulation with several distinctive abilities, such as immune evasion, enhanced biocompatibility, and tumor targeting, typically associated with a source cell. Here, we discuss the advancements of cell membrane-derived nanovaccines and how these vaccines are used for cancer therapeutics. Translational endeavors are currently in progress, and additional research is also necessary to effectively address crucial areas of demand, thereby facilitating the future successful translation of these emerging vaccine platforms.

Determining the effects of genetic linkage when using a combination of STR and SNP loci for kinship testing.

The pedigree likelihood ratio (LR) can be used for determining kinship in the forensic kinship testing. LR can be obtained by analyzing the DNA data of Short tandem repeat (STR) and single nucleotide polymorphism (SNP) loci. With the advancement of biotechnology, increasing number of genetic markers have been identified, thereby expanding the pedigree range of kinship testing. Moreover, some of the loci are physically closer to each other and genetic linkage between loci is inevitable. LRs can be calculated by accounting for linkage or ignoring linkage (LRlinkage and LRignore, respectively). GeneVisa is a software for kinship testing (www.genevisa.net) and adopts the Lander-Green algorithm to deal with genetic linkage. Herein, we used the simulation program of the software GeneVisa to investigate the effects of genetic linkage on 1st-degree, 2nd-degree, and 3rd-degree kinship testing. We used this software to simulate LRlinkage and LRignore values based on 43 STRs and 134 SNPs in commercial kits by using the allele frequency rate and genetic distance data of the European population. The effects of linkage on LR distribution and LRs of routine cases were investigated by comparing the LRlinkage values with the LRignore values. Our results revealed that the linkage effect on LR distributions is small, but the effect on LRs of routine cases may be large. Moreover, the results indicated that the discriminatory power of genetic markers for kinship testing can be improved by accounting for linkage.

Coronary Artery Tree Description and Lesion Evaluation (CatLet) score for functional evaluation of coronary stenosis: a comparison study with pressure wire fractional flow reserve.

Background: Pressure wire fractional flow reserve (FFR) and its derivatives, such as quantitative flow ratio (QFR), computational pressure flow-derived FFR (caFFR), coronary angiography-derived FFR (FFRangio), and computed tomography-derived FFR (FFRCT), have been validated for identifying functionally significant stenosis and guiding revascularization strategy. The limitations of using these methods include the side effects of hyperemia-induced agents, additional costs, and vulnerability to microvascular resistance. FFR is related both to the degree of a stenotic coronary artery and to its subtended myocardial territory. Coronary Artery Tree Description and Lesion Evaluation (CatLet) score (also known as Hexu) is a product of the degree of a stenosis and the weighting of the affected coronary artery (myocardial territory). Hence, we hypothesized that the CatLet score could predict hemodynamically significant coronary stenosis. Methods: We retrospectively enrolled consecutive patients with stable coronary artery disease. They attended Sichuan Science City Hospital with at least one lesion of 50-90% diameter stenosis in a coronary artery of 2 mm or larger. FFR measurement was obtained during invasive coronary angiography. The CatLet score was obtained by multiplying a fixed value of 2.0 (for non-occlusive lesions) and the weight of the affected coronary artery. The primary endpoint was the CatLet score's diagnostic accuracy in identifying hemodynamically significant coronary stenosis, with a pressure wire FFR of ≤0.80 being used as reference. Results: We analyzed the FFR and CatLet scores from 206 vessels in 175 patients with stable coronary disease and intermediate coronary lesions. The per-vessel analysis revealed an overall good correlation between the CatLet score and the FFR [r=-0.61; 95% confidence interval (95% CI): -0.69 to -0.52; P<0.01]. We also noted a significant CatLet score-FFR correlation for each of the left anterior descending artery (LAD), left circumflex (LCX), and right coronary artery (RCA). With a CatLet score ≥10 as a predictor of FFR ≤0.80, the overall diagnostic accuracy included a sensitivity of 78.80% (95% CI: 67.00-87.90%), a specificity of 85.00% (95% CI: 78.00-90.50%), a positive likelihood ratio of 5.25, a negative likelihood ratio of 0.25, and an area under the curve of 0.90 (95% CI: 0.85-0.94). Equivalent vessel-specific results were also achieved for each of the LAD, LCX, and RCA. Conclusions: The CatLet score, solely based on visual estimation of the results of coronary angiography, demonstrated good diagnostic performance with respect to myocardial ischemia. Its clinical values in guiding revascularization warrant further investigation.

The use of amino acids and their derivates to mitigate against pesticide-induced toxicity.

Exposure to pesticides induces oxidative stress and deleterious effects on various tissues in non-target organisms. Numerous models investigating pesticide exposure have demonstrated metabolic disturbances such as imbalances in amino acid levels within the organism. One potentially effective strategy to mitigate pesticide toxicity involves dietary intervention by supplementing exogenous amino acids and their derivates to augment the body's antioxidant capacity and mitigate pesticide-induced oxidative harm, whose mechanism including bolstering glutathione synthesis, regulating arginine-NO metabolism, mitochondria-related oxidative stress, and the open of ion channels, as well as enhancing intestinal microecology. Enhancing glutathione synthesis through supplementation of substrates N-acetylcysteine and glycine is regarded as a potent mechanism to achieve this. Selection of appropriate amino acids or their derivates for supplementation, and determining an appropriate dosage, are of the utmost importance for effective mitigation of pesticide-induced oxidative harm. More experimentation is required that involves large population samples to validate the efficacy of dietary intervention strategies, as well as to determine the effects of amino acids and their derivates on long-term and low-dose pesticide exposure. This review provides insights to guide future research aimed at preventing and alleviating pesticide toxicity through dietary intervention of amino acids and their derivates.