Search

Aims: The dysregulation of TGF‐β signaling is a crucial pathophysiological process in tumorigenesis and progression. LncRNAs have diverse biological functions and are significant participants in the regulation of tumor signaling pathways. However, the clinical value of lncRNAs related to TGF‐β signaling in glioma is currently unclear. Methods: Data on glioma's RNA‐seq transcriptome, somatic mutation, DNA methylation data, and clinicopathological information were derived from the CGGA and TCGA databases. A prognostic lncRNA signature was constructed by Cox and LASSO regression analyses. TIMER2.0 database was utilized to deduce immune infiltration characteristics. "ELMER v.2" was used to reconstruct TF‐methylation‐gene regulatory network. Immunotherapy and chemotherapy response predictions were implemented by the TIDE algorithm and GDSC database, respectively. In vitro and in vivo experiments were conducted to verify the results and clarify the regulatory mechanism of lncRNA. Results: In glioma, a TGF‐β signaling‐related 15‐lncRNA signature was constructed, including AC010173.1, HOXA‐AS2, AC074286.1, AL592424.1, DRAIC, HOXC13‐AS, AC007938.1, AC010729.1, AC013472.3, AC093895.1, AC131097.4, AL606970.4, HOXC‐AS1, AGAP2‐AS1, and AC002456.1. This signature proved to be a reliable prognostic tool, with high risk indicating an unfavorable prognosis and being linked to malignant clinicopathological and genomic mutation traits. Risk levels were associated with different immune infiltration landscapes, where high risk was indicative of high levels of macrophage infiltration. In addition, high risk also suggested better immunotherapy and chemotherapy response. cg05987823 was an important methylation site in glioma progression, and AP‐1 transcription factor family participated in the regulation of signature lncRNA expression. AGAP2‐AS1 knockdown in in vitro and in vivo experiments inhibited the proliferation, migration, and invasion of glioma cells, as well as the growth of glioma, by downregulating the expression levels of NF‐κB and ERK 1/2 in the TGF‐β signaling pathway. Conclusions: A prognostic lncRNA signature of TGF‐β signaling was established in glioma, which can be used for prognostic judgment, immune infiltration status inference, and immunotherapy response prediction. AGAP2‐AS1 plays an important role in glioma progression. [ABSTRACT FROM AUTHOR]

Antibody (Ab)‐based drugs have been widely used in targeted therapies and immunotherapies, leading to significant improvements in tumor therapy. However, the failure of Ab therapy due to the loss of target antigens or Ab modifications that affect its function limits its application. In this study, we expanded the application of antibodies (Abs) by constructing a fusion protein as a versatile tool for Ab‐based target cell detection, delivery, and therapy. We first constructed a SpaC Catcher (SpaCC for short) fusion protein that included the C domains of Staphylococcal protein A (SpaC) and the SpyCatcher. SpaCC conjugated with SpyTag‐X (S‐X) to form the SpaCC‐S‐X complex, which binds non‐covalently to an Ab to form the Ab‐SpaCC‐S‐X protein complex. The "X" can be a variety of small molecules such as fluoresceins, cell‐penetrating peptide TAT, Monomethyl auristatin E (MMAE), and DNA. We found that Ab‐SpaCC‐S‐FITC(−TAT) could be used for target cell detection and delivery. Besides, we synthesized the Ab‐SpaCC‐SN3‐MMAE complex by linking Ab with MMAE by SpaCC, which improved the cytotoxicity of small molecule toxins. Moreover, we constructed an Ab‐DNA complex by conjugating SpaCC with the aptamer (Ap) and found that Ab‐SpaCC‐SN3‐Ap boosted the tumor‐killing function of T‐cells by retargeting tumor cells. Thus, we developed a multifunctional tool that could be used for targeted therapies and immunotherapies, providing a cheap and convenient novel drug development strategy. [ABSTRACT FROM AUTHOR]

Chimeric antigen receptor (CAR)‐positive cell therapy, specifically with anti‐CD19 CAR‐T (CAR19‐T) cells, achieves a high complete response during tumor treatment for hematological malignancies. Large‐scale production and application of CAR‐T therapy can be achieved by developing efficient and low‐cost enrichment methods for CAR‐T cells, expansion monitoring in vivo, and overcoming tumor escape. Here, novel CAR‐specific binding aptamers (CAR‐ap) to traceless sort CAR‐positive cells and obtain a high positive rate of CAR19‐T cells is identified. Additionally, CAR‐ap‐enriched CAR19‐T cells exhibit similar antitumor capacity as CAR‐ab (anti‐CAR antibody)‐enriched CAR‐T cells. Moreover, CAR‐ap accurately monitors the expansion of CAR19‐T cells in vivo and predicts the prognosis of CAR‐T treatment. Essentially, a novel class of stable CAR‐ap‐based bispecific circular aptamers (CAR‐bc‐ap) is constructed by linking CAR‐ap with a tumor surface antigen (TSA): protein tyrosine kinase 7 (PTK7) binding aptamer Sgc8. These CAR‐bc‐aps significantly enhance antitumor cytotoxicity with a loss of target antigens by retargeting CAR‐T cells to the tumor in vitro and in vivo. Overall, novel CAR‐aptamers are screened for traceless enrichment, monitoring of CAR‐positive cells, and overcoming tumor cell immune escape. This provides a low‐cost and high‐throughput approach for CAR‐positive cell‐based immunotherapy. [ABSTRACT FROM AUTHOR]

This study systematically reviewed the relevant studies and summarized the associations of objective measures of residential neighborhood built-environment attributes with sedentary time among adults. Published studies were obtained from PubMed and Scopus, restricting to those published in English language peer-reviewed journals to Oct. 2021. There were nine studies and 48 instances of estimated associations. Most instances showed no statistical-significant associations; by contrast, few instances showed that adults living in a neighborhood characterized by a high density of local destinations and connected intersections were associated with less sedentary time. The findings suggest that a high density of destinations and street intersections around residence may provide opportunities to transfer and access to services, thus reducing the sedentary time. Future research strengthening the research design and measurements are needed to investigate the potential explanations of the associations between residential neighborhood built environments and sedentary time in adults. [ABSTRACT FROM AUTHOR]

Analyzing the interspecific association of major tree populations of Cyclobalanopsis glauca community and revealing the coexistence among the populations would provide theoretical basis for the restoration and reconstruction, management and biodiversity conservation of Karst hills in Guilin. Based on field survey, the X1 test, association coefficient ( AC ), co-occurrence percentage ( PC), Ochiai index ( OI), Dice index ( DI), and principal component analysis ( PCA) were used to investigate the interspecific association and eco-taxonomic classification of the top 11 tree species in Cyclobalanopsis glauca community in Guilin Karst Rocky Mountains. The results showed that there was a significant positive correlation between the interspecific associations of the 11 main tree populations, indicating that this community was in a stable climax stage. The results of X1 test showed that 108 pairs of 131 species pairs had positive associations, 115 species pairs had negative associations, 8 species pairs were unrelated, with the positive and negative linkage ratio being 93.9%. The vast majority of species pairs showed no significant association. The strong independence between species might be mainly caused by the higher habitat heterogeneity of the Karst hills in Guilin which led to the differentiation of niches between species. The results of AC, PC, OI and DI were basically consistent with that ofX1 test, indicating that the analysis of interspecific association should be based on theX1 test and supplemented by AC, PC, OI and DI indices. According to the PCA and evaluation of interspecific relationships, the 11 main tree species were divided into three ecological groups. The species within each group had the same adaptability to habitat but different ecological requirements. [ABSTRACT FROM AUTHOR]

Antibody (Ab)-based drugs have been widely used in targeted therapies and immunotherapies, leading to significant improvements in tumor therapy. However, the failure of Ab therapy due to the loss of target antigens or Ab modifications that affect its function limits its application. In this study, we expanded the application of antibodies (Abs) by constructing a fusion protein as a versatile tool for Ab-based target cell detection, delivery, and therapy. We first constructed a SpaC Catcher (SpaCC for short) fusion protein that included the C domains of Staphylococcal protein A (SpaC) and the SpyCatcher. SpaCC conjugated with SpyTag-X (S-X) to form the SpaCC-S-X complex, which binds non-covalently to an Ab to form the Ab-SpaCC-S-X protein complex. The "X" can be a variety of small molecules such as fluoresceins, cell-penetrating peptide TAT, Monomethyl auristatin E (MMAE), and DNA. We found that Ab-SpaCC-S-FITC(-TAT) could be used for target cell detection and delivery. Besides, we synthesized the Ab-SpaCC-SN3-MMAE complex by linking Ab with MMAE by SpaCC, which improved the cytotoxicity of small molecule toxins. Moreover, we constructed an Ab-DNA complex by conjugating SpaCC with the aptamer (Ap) and found that Ab-SpaCC-SN3-Ap boosted the tumor-killing function of T-cells by retargeting tumor cells. Thus, we developed a multifunctional tool that could be used for targeted therapies and immunotherapies, providing a cheap and convenient novel drug development strategy., (© 2024 The Protein Society.)

Nonantibiotic approaches must be developed to kill pathogenic bacteria and ensure that clinicians have a means to treat wounds that are infected by multidrug-resistant bacteria. This study prepared matchstick-like Ag 2 S-ZnS heteronanostructures (HNSs). Their hydrophobic surfactants were then replaced with hydrophilic poly(ethylene glycol) (PEG) and thioglycolic acid (TGA) through the ligand exchange method, and this was followed by ascorbic acid (AA) conjugation with TGA through esterification, yielding well-dispersed PEGylated Ag 2 S-ZnS@TGA-AA HNSs. The ZnS component of the HNSs has innate semiconductivity, enabling the generation of electron-hole pairs upon irradiation with a light of wavelength 320 nm. These separate charges can react with oxygen and water around the HNSs to produce reactive oxygen species. Moreover, some holes can oxidize the surface-grafted AA to produce protons, decreasing the local pH and resulting in the corrosion of Ag 2 S, which releases silver ions. In evaluation tests, the PEGylated Ag 2 S-ZnS@TGA-AA had synergistic antibacterial ability and inhibited Gram-negative Escherichia coli and Gram-positive methicillin-resistant Staphylococcus aureus (MRSA). Additionally, MRSA-infected wounds treated with a single dose of PEGylated Ag 2 S-ZnS@TGA-AA HNSs under light exposure healed significantly more quickly than those not treated, a result attributable to the HNSs' excellent antibacterial and Bohr effects.

Quantifying the contribution of transport processes to air pollution events has been a prominent challenge and an important need in regional air pollution prevention and control. The WRF-Chem model was used to simulate a typical regional ozone (O 3 ) pollution event in Foshan, and the four-dimensional flux method was applied to quantify the transport fluxes of ozone and its precursors from the surrounding areas to Foshan and to clarify the contributions of the direct transport of ozone and transport of precursors. The average ozone flux from the surrounding areas to Foshan was 120.3 t·h -1 , the volatile organic compound (VOCs) flux was 30.2 t·h -1 , and the corresponding ozone formation potential (OFP) was 114.8 t·h -1 . By counting the transport fluxes of each ozone pollution event, it was found that the city with the largest ozone flux into Foshan during the pollution period was Guangzhou (contributed 44%); the city with the largest input VOCs flux was Zhaoqing (contributed 48%). The analysis of ozone generation potential due to transported VOCs emissions found that oxygenated volatile organic compounds (OVOCs) contributed the most to OFP, accounting for 47% of the "maximum input events." OVOCs and aromatic hydrocarbons such as formaldehyde, xylenes, aldehydes, acetone, and phenols were the top five species contributing to the OFP, contributing more than 50% of the total OFP, mainly from industrial solvent sources.

Objective: To study the medication rules of traditional Chinese medicine (TCM) in the treatment of premature ejaculation., Methods: We searched the databases of CNKI, Wan Fang, VIP, SinoMed (CBM) and PubMed for studies on the treatment of PE with TCM prescriptions and performed statistical analyses on the data obtained using the TCM inheritance auxiliary platform software., Results: Totally 180 prescriptions were identified, involving 209 TCM drugs. The results of statistical analysis showed that the TCM drugs for the treatment of premature ejaculation were mostly warm, flat or cold in nature, sweet or spicy in taste, and with the kidney, liver and spleen meridian tropisms. The single TCM drugs most commonly used included Lycium barbarum L (Gouqizi), followed by Epimedium brevicornum Maxim (Yinyanghuo), Os draconis (Longgu), Fructus rosae laevigatae (Jinyingzi), and the drugs most frequently used in combination with others in a prescription were Os draconis (Longgu) and Concha ostreae (Muli). Seven newly derived prescriptions were identified in addition., Conclusions: The compatibility of TCM in the treatment of premature ejaculation is characterized by the combination of the drugs for tonifying the kidney and arresting seminal emission as the main medication strategy, with those for soothing the liver and invigorating the spleen as the adjuvant agents, which has a certain clinical application value.

Analyzing the interspecific association of major tree populations of Cyclobalanopsis glauca community and revealing the coexistence among the populations would provide theoretical basis for the restoration and reconstruction, management and biodiversity conservation of Karst hills in Gui-lin. Based on field survey, the χ 2 test, association coefficient (AC), co-occurrence percentage (PC), Ochiai index (OI), Dice index (DI), and principal component analysis (PCA) were used to investigate the interspecific association and eco-taxonomic classification of the top 22 tree species in Cyclobalanopsis glauca community in Guilin Karst Rocky Mountains. The results showed that there was a significant positive correlation between the interspecific associations of the 22 main tree populations, indicating that this community was in a stable climax stage. The results of χ 2 test showed that 108 pairs of 231 species pairs had positive associations, 115 species pairs had negative associations, 8 species pairs were unrelated, with the positive and negative linkage ratio being 93.9%. The vast majority of species pairs showed no significant association. The strong indepen-dence between species might be mainly caused by the higher habitat heterogeneity of the Karst hills in Guilin which led to the differentiation of niches between species. The results of AC, PC, OI and DI were basically consistent with that of χ 2 test, indicating that the analysis of interspecific association should be based on the χ 2 test and supplemented by AC, PC, OI and DI indices. According to the PCA and evaluation of interspecific relationships, the 22 main tree species were divided into three ecological groups. The species within each group had the same adaptability to habitat but different ecological requirements.

Objective: To understand the prevalence of HIV-1 drug resistance and its main factors in AIDS patients receiving to HAART in Zhecheng county, Henan province., Methods: By cross-sectional survey, 378 AIDS patients who had received the national free antiretroviral therapy from July 2003 to March 2009 in Zhecheng county of Henan were selected. All recruits were interviewed and blood samples were collected. HIV-1 viral loads were measured by real-time polymerase chain reaction, HIV genotypic resistance was determined by an in-house polymerase chain reaction to amplify the HIV-1 pol gene region., Results: Among 378 subjects receiving antiretroviral therapy, the prevalence of successful viral suppression was 42.9% (162/378), and HIV-1 drug resistance was detected in 47.1% (178/378) patients. The rate of resistance-associated mutations to non-nucleotide reverse transcriptase inhibitors (NNRTIs), nucleotide reverse transcriptase inhibitors (NRTIs) and protease inhibitors (PIs) was 46.6% (176/378), 37.8% (143/378) and 1.9% (7/378), respectively. Multivariate logistic regression analysis showed that the main risk factors associated with the prevalence of drug resistance included drug non-adherence (ratio of on-time drug intake in the past month < 90%:≥ 90% = 64.5% (40/62):43.7% (138/316), OR = 2.3, 95%CI: 1.3 - 4.1), and initiation of anti-retroviral therapy (ART) with didanosine (DDI) (ART with DDI:ART with lamivudine (3TC) = 53.3% (137/257):33.9% (41/121), OR = 2.3, 95%CI = 1.1 - 4.5)., Conclusion: The prevalence of HIV-1 drug resistance among ART patients in Zhecheng county of Henan was high. Drug non-adherence and initiation of ART with DDI were the main factors of drug resistance.

Objective: To investigate the detection rate of impaired fasting glycaemia (IFG), the prevalence of diabetes mellitus (DM) and related risk factors, the current situation on awareness, treatment and the rate of control on diabetes mellitus in residents living in Nangang district of Harbin city, Heilongjiang province., Methods: A cross-sectional cluster sampling was carried out in residents aged over 35 years, living in Fendou community of Harbin city., Results: Data from 3017 out of 3183 residents were analyzed. In men, women and overall residents, the detection rates of IFG were 5.38%, 2.44% and 3.75%, respectively. After standardization, the detection rates became 5.41%, 2.18% and 3.59%, respectively. The prevalence rates of DM were 12.40%, 8.46%, 10.21% and 11.80%, 8.20% and 9.77%, before and after standardization. Results showed statistical difference between age, sex and levels of fasting glycaemia. Data from single factor analysis revealed that smoking, BMI, hypertension and high triglyceride were risk factors on the levels of high fasting glycaemia. Results from multivariable stepwise analysis showed that sex, age, BMI, hypertension and high triglyceride were significant factors influencing the levels of high fasting glycaemia with the OR (95% CI) is 1.546 (1.250-1.912), 1.308 (1.171-1.461), 1.038 (1.010-1.066), 1.388 (1.106-1.741) and 1.700 (1.370-2.110), respectively. The rates on awareness, treatment and control in DM were 73.38%, 59.42% and 36.36% respectively. Among those who had knowledge on DM, the rates on treatment and on control were 80.97% and 61.20%., Conclusion: Our results showed that the prevalence of DM was high in the communities and it is essential to further increase the awareness, treatment and control rates on DM.

Objective: To access the prevalence of prehypertensive stage and its associated risk factors in rural inhabitants from Lanxi county in Heilongjiang province., Methods: Through cluster multistage and random sampling methods, local people aged > or = 15 years old in Lanxi county were selected. A survey on blood pressure and associated risk factors was carried out. Overnight fasting blood specimen of people aged > or = 35 years old was collected. Chi-square test, t-test and logistic regression analyses were then performed., Results: 5272 residents were surveyed including 2539 male and 2733 female subjects. The overall prevalence of prehypertension was 36.34%. The prevalence of prehypertension appeared to be higher in males (39.50%) than in females (33.41%) (chi2 = 58.9887, P < 0.0001). The prevalence of prehypertension decreased with increasing age in men > or = 25 years old (chi2 = 96.0698, P < 0.0001), and in women > or = 35 years old (chi2 = 11.5784, P = 0.0208). Data from multivariable logistic regression showed that being male, aged (> or = 55 years old), with waist circumference as > or = 85 cm for men and > or = 80 cm for women, BMI > or = 25.0 kg/m2 and fasting plasma glucose > or = 7.0 mmol/L were risk factors of prehypertension while high-density lipoprotein cholesterol < 0.9 mmol/L was shown as a protective factor (OR = 0.740, P = 0.0036). Dose-response relationships were seen between prehypertension and age, BMI and FPG., Conclusion: Prehypertension was popular in the rural area, with high prevalence seen in teenagers. Programs on prehypertension prevention should start from teenagers. Risk factors of prehypertension increased when people became age 55 or older. There was a need to monitor BP more often and to control BP through non-drug methods.

Objective: To investigate the current status of impaired fasting glycaemia (IFG), diabetes mellitus (DM) and correlated factors, as well as on the awareness, treatment and control rate of diabetes mellitus in rural residents of Lanxi, Heilongjiang., Methods: Cross-sectional and cluster sampling method was carried out on 3480 residents over 35 years of age, in rural residents of Lanxi Pingshan, Heilongjiang province., Results: To male, female and all, the detecting rate of IFG were 5.06%, 4.38% and 4.68% respectively, and the standardization rate of IFG became 4.71%, 4.24% and 4.47% respectively. The prevalence rates of DM were 7.85%, 6.57% and 7.15% but after standardization, they became 7.22%, 6.62% and 6.80% respectively. Results did not show statistical difference between sex and the level of fasting glycaemia (chi2 = 2.725, P = 0.256). The prevalence rates of IFG and DM increased with age and difference was seen between age and fasting glycaemia level (chi2 = 58.115, P= 0.000). Data from multivariable stepwise analysis showed that age, smoking, BMI and high triglyceride were the significant factors in fasting glycaemia level, and the ORs (95% CI) were 1.518 (1.360-1.694), 1.277 (1.134-1.439), 1.187 (1.014-1.391) and 1.754 (1.385-2.220) respectively. The rates of awareness, treatment and control rate in DM were 12.74%, 9.43% and 4.72% respectively while the treatment rate among those who knew the disease was 74.07%., Conclusion: Our result showed that the isolating rate of IFG and the prevalence rate DM were high in this region, but the awareness, treatment and control rate in DM were low. It is essential to strengthen health promotion program on diabetic knowledge and to elevate the primary and secondary prevention in the rural of Heilongjiang, so as to raise the rate of control.