Curcuma Longa Induces the Transcription Factor FOXP3 to Downregulate Human Chemokine CCR5 Expression and Inhibit HIV-1 Infection.

HIV mutations occur frequently despite the substantial success of combination antiretroviral therapy, which significantly impairs HIV progression. Failure to develop specific vaccines, the occurrence of drug-resistant strains, and the high incidence of adverse effects due to combination antiviral therapy regimens call for novel and safer antivirals. Natural products are an important source of new anti-infective agents. For instance, curcumin inhibits HIV and inflammation in cell culture assays. Curcumin, the principal constituent of the dried rhizomes of Curcuma longa L. (turmeric), is known as a strong anti-oxidant and anti-inflammatory agent with different pharmacological effects. This work aims to assess curcumin's inhibitory effects on HIV in vitro and to explore the underpinning mechanism, focusing on CCR5 and the transcription factor forkhead box protein P3 (FOXP3). First, curcumin and the RT inhibitor zidovudine (AZT) were evaluated for their inhibitory properties. HIV-1 pseudovirus infectivity was determined by green fluorescence and luciferase activity measurements in HEK293T cells. AZT was used as a positive control that inhibited HIV-1 pseudoviruses dose-dependently, with IC50 values in the nanomolar range. Then, a molecular docking analysis was carried out to assess the binding affinities of curcumin for CCR5 and HIV-1 RNase H/RT. The anti-HIV activity assay showed that curcumin inhibited HIV-1 infection, and the molecular docking analysis revealed equilibrium dissociation constants of [Formula: see text]9.8[Formula: see text]kcal/mol and [Formula: see text]9.3[Formula: see text]kcal/mol between curcumin and CCR5 and HIV-1 RNase H/RT, respectively. To examine curcumin's anti-HIV effect and its mechanism in vitro, cell cytotoxicity, transcriptome sequencing, and CCR5 and FOXP3 amounts were assessed at different concentrations of curcumin. In addition, human CCR5 promoter deletion constructs and the FOXP3 expression plasmid pRP-FOXP3 (with an EGFP tag) were generated. Whether FOXP3 DNA binding to the CCR5 promoter was blunted by curcumin was examined using transfection assays employing truncated CCR5 gene promoter constructs, a luciferase reporter assay, and a chromatin immunoprecipitation (ChIP) assay. Furthermore, micromolar concentrations of curcumin inactivated the nuclear transcription factor FOXP3, which resulted in decreased expression of CCR5 in Jurkat cells. Moreover, curcumin inhibited PI3K-AKT activation and its downstream target FOXP3. These findings provide mechanistic evidence encouraging further assessment of curcumin as a dietary agent used to reduce the virulence of CCR5-tropic HIV-1. Curcumin-mediated FOXP3 degradation was also reflected in its functions, namely, CCR5 promoter transactivation and HIV-1 virion production. Furthermore, curcumin inhibition of CCR5 and HIV-1 might constitute a potential therapeutic strategy for reducing HIV progression.

Skin-Inspired Highly Sensitive Tactile Sensors with Ultrahigh Resolution over a Broad Sensing Range.

Flexible tactile sensors with high sensitivity, a broad pressure detection range, and high resolution are highly desired for the applications of health monitoring, robots, and the human-machine interface. However, it is still challenging to realize a tactile sensor with high sensitivity and resolution over a wide detection range. Herein, to solve the abovementioned problem, we demonstrate a universal route to develop a highly sensitive tactile sensor with high resolution and a wide pressure range. The tactile sensor is composed of two layers of microstructured flexible electrodes with high modulus and conductive cotton fabric with low modulus. By optimizing the sensing films, the fabricated tactile sensor shows a high sensitivity of 8.9 × 104 kPa-1 from 2 Pa to 250 kPa because of the high structural compressibility and stress adaptation of the multilayered composite films. Meanwhile, a fast response speed of 18 ms, an ultrahigh resolution of 100 Pa over 100 kPa, and excellent durability over 20 000 loading/unloading cycles are demonstrated. Moreover, a 6 × 6 tactile sensor array is fabricated and shows promising potential application in electronic skin (e-skin). Therefore, employing multilayered composite films for tactile sensors is a novel strategy to achieve high-performance tactile perception in real-time health monitoring and artificial intelligence.

Emerging Functional Polymer Composites for Tactile Sensing.

In recent years, extensive research has been conducted on the development of high-performance flexible tactile sensors, pursuing the next generation of highly intelligent electronics with diverse potential applications in self-powered wearable sensors, human-machine interactions, electronic skin, and soft robotics. Among the most promising materials that have emerged in this context are functional polymer composites (FPCs), which exhibit exceptional mechanical and electrical properties, enabling them to be excellent candidates for tactile sensors. Herein, this review provides a comprehensive overview of recent advances in FPCs-based tactile sensors, including the fundamental principle, the necessary property parameter, the unique device structure, and the fabrication process of different types of tactile sensors. Examples of FPCs are elaborated with a focus on miniaturization, self-healing, self-cleaning, integration, biodegradation, and neural control. Furthermore, the applications of FPC-based tactile sensors in tactile perception, human-machine interaction, and healthcare are further described. Finally, the existing limitations and technical challenges for FPCs-based tactile sensors are briefly discussed, offering potential avenues for the development of electronic products.

Recent Advances in Polymer Composites for Flexible Pressure Sensors.

Pressure sensors show significant potential applications in health monitoring, bio-sensing, electronic skin, and tactile perception. Consequently, tremendous research interest has been devoted to the development of high-performance pressure sensors. In this paper, recent progress on the polymer composite-based flexible pressure sensor is reviewed. The parameters of pressure sensors, including sensitivity, linear response range, detection limit, response speed, and reliability, are first introduced. Secondly, representative types of pressure sensors and relevant working principles are introduced and discussed. After that, the applications in human physiology monitoring, health monitoring, artificial skin, and self-powered smart system are listed and discussed in detail. Finally, the remaining challenges and outlook of polymer composite-based flexible sensors are summarized at the end of this review paper. This work should have some impact on the development of high-performance flexible pressure sensors.

Distinct Roles of Adenosine Deaminase Isoenzymes ADA1 and ADA2: A Pan-Cancer Analysis.

Objective: Adenosine deaminase (ADA) plays an important role in immune response, which includes two isoenzymes: ADA1 and ADA2. This study aims to explore the roles of ADA1 and ADA2 in cancers. Methods: Human Protein Atlas (HPA) and Gene Expression Profiling Interactive Analysis (GEPIA2) databases were used to analyze the mRNA expression of ADA1 and ADA2 in human normal cells and tumor tissues. The enzyme assay was used to detect the ADA1 and ADA2 activities in serum from cancer patients. The Kaplan-Meier (KM) plotter was used to analyze the prognostic value of ADA1 and ADA2. TIMER2.0 was used to explore how ADA1 and ADA2 correlate with immune infiltration and immune checkpoints. cBioPortal database was used to investigate the mutations of ADA1 and ADA2. LinkedOmics was used to screen the ADA1 and ADA2 expression-related genes. Results: ADA1 was significantly increased in several tumor tissues, including cholangiocarcinoma (CHOL), lymphoid neoplasm diffuse large B-cell lymphoma (DLBC), head and neck squamous cell carcinoma (HNSC), kidney renal clear cell carcinoma (KIRC), ovarian serous cystadenocarcinoma (OV), pancreatic adenocarcinoma (PAAD), thymoma (THYM), and uterine carcinosarcoma (UCS). ADA2 expression was significantly increased in esophageal carcinoma (ESCA), glioblastoma multiforme (GBM), acute myeloid leukemia (LAML), OV, PAAD, skin cutaneous melanoma (SKCM), and stomach adenocarcinoma (STAD). There were no significant changes in serum ADA1 activities in most cancers, while serum ADA2 activities were increased in most cancers. For prognosis, high ADA1 expression was associated with the poor survival in several cancers, including esophageal squamous cell carcinoma (ESCC), HNSC, KIRC, kidney renal papillary cell carcinoma (KIRP), liver hepatocellular carcinoma (LIHC), lung adenocarcinoma (LUAD), and uterine corpus endometrial carcinoma (UCEC). However, high ADA2 expression showed a favorable prognosis in breast invasive carcinoma (BRCA), cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC), HNSC, KIRC, KIRP, LUAD, OV, PAAD, sarcoma, and THYM. ADA1 showed a moderate positive correlation with multiple infiltrating immune cells in most cancers. ADA2 was positively correlated with B cells, CD8 T cells, monocytes/macrophages, and dendritic cells (DCs) and was strongly negatively correlated with myeloid-derived suppressor cells. Function analysis showed that ADA1 expression-related genes were mainly enriched in cell division biological progression. However, ADA2-related genes were mainly associated with immune response. Conclusion: As isoenzymes, ADA1 and ADA2 showed opposite prognostic values and different correlative patterns with immune infiltrating. These data demonstrated the distinct roles of ADA1 and ADA2 in cancer. ADA2 might act as a protective factor in cancer.

Identification of a novel allele, MICA*088N, in a Chinese Kazakh individual.

The novel MICA*088N allele has a single nucleotide mismatch in exon 4 compared to MICA*027.

Effects of temperature and fatigue on the metabolism and swimming capacity of juvenile Chinese sturgeon (Acipenser sinensis).

Chinese sturgeon (Acipenser sinensis) is a critically endangered species. A flume-type respirometer, with video, was used to conduct two consecutive stepped velocity tests at 10, 15, 20, and 25 °C. Extent of recovery was measured after the 60-min recovery period between trials, and the recovery ratio for critical swimming speed (U crit) averaged 91.88% across temperatures. Temperature (T) effects were determined by comparing U crit, oxygen consumption rate (MO 2), and tail beat frequency (TBF) for each temperature. Results from the two trials were compared to determine the effect of exercise. The U crit occurring at 15 °C in both trials was significantly higher than that at 10 and 25 °C (p < 0.05). The U crit was plotted as a function of T and curve-fitting allowed calculation of the optimal swimming temperature 3.28 BL/s at 15.96 °C (trial 1) and 2.98 BL/s at 15.85 °C (trial 2). In trial 1, MO 2 increased rapidly with U, but then declined sharply as swimming speed approached U crit. In trial 2, MO 2 increased more slowly, but continuously, to U crit. TBF was directly proportional to U and the slope (dTBF/dU) for trial 2 was significantly lower than that for trial 1. The inverse slope (tail beats per body length, TB/BL) is a measure of swimming efficiency and the significant difference in slopes implies that the exercise training provided by trial 1 led to a significant increase in swimming efficiency in trial 2.

Association between Caspase-9 promoter region polymorphisms and discogenic low back pain.

Caspase-9 (CASP-9) is an initiator caspase protease for apoptosis, and plays an important role in the development and progression of lumbar disc disease (LDD). The expression and/or activity of CASP-9 are significantly enhanced in the degenerated disc. The polymorphism in the promoter region of CASP-9 enhances the transcriptional activity of this gene, thereby modulating the susceptibility to LDD. The current study investigated the relationship between the CASP-9 -1263A/G (rs4645978) and -712C/T (rs4645981) polymorphisms and discogenic low back pain (LBP). The CASP-9 -1263A/G and -712C/T genotypes in this study were defined by polymerase chain reaction in 154 patients with discogenic LBP and 216 controls that were frequency-matched by age, gender, and occupation. The results showed that the CASP-9 -1263 GG genotype, compared with the AA and AG genotypes [odds ratio (OR) = 1.997, 95% confidence interval (95% CI) = 1.216-3.279, p = 0.006] or the AA genotype (OR = 2.760, 95% CI = 1.464-5.203, p = 0.002), is associated with a significant increased risk of discogenic LBP, but the -712 TT or TT and CT genotypes do not contribute to discogenic LBP compared with the CC genotype (OR = 0.547, 95% CI = 0.200-1.494, p = 0.234 and OR = 0.669, 95% CI = 0.439-1.021, p = 0.062, respectively). These results indicated that the CASP-9 -1263A/G polymorphism is associated with a high risk of discogenic LBP.