Photo-electrochemical activation of persulfate for the simultaneous degradation of microplastics and personal care products.

The recent widespread use of microplastics (MPs), especially in pharmaceuticals and personal care products (PPCPs), has caused significant water pollution. This study presents a UV/electrically co-facilitated activated persulfate (PS) system to co-degrade a typical microplastic polyvinyl chloride (PVC) and an organic sunscreen p-aminobenzoic acid (PABA). We investigated the effect of various reaction conditions on the degradation. PVC and PABA degradation was 37% and 99.22%, respectively. Furthermore, we observed alterations in the surface topography and chemical characteristics of PVC throughout degradation. The possible degradation pathways of PVC and PABA were proposed by analyzing the intermediate products and the free radicals generated. This study reveals the co-promoting effect of multiple mechanisms in the activation by ultraviolet light and electricity.

Photocatalytic degradation of p-aminobenzoic acid on N-biomass charcoal etched with Fe-Al-bilayer hydroxide: New insights through spectroscopic investigation.

We investigated the photocatalytic property of etched iron­aluminum layered double hydroxide (LDH) composites using urea-modified biochar (N-BC) carrier to degrade para-aminobenzoic acid (PABA), a refractory organic pollutant. The prepared FeAl-LDH@FeSx-N-BC composite exhibited excellent photocatalytic performance, attributed to the enhanced photogenerated charge-carrier separation by the etched LDH and the improved comparative surface areas by the doped N-BC. The composite photocatalytically degraded 96 % of PABA. The performance was affected by solute concentration, pH and photocatalyst dose. Adding p-benzoquinone and EDTA-2Na significantly decreased the degradation rate, suggesting that superoxide radicals and holes were co-involved in PABA degradation. The excellent PABA removal efficiency was consistent for three consecutive runs. The samples' reactive oxygen species was confirmed, as electron paramagnetic reverberation explained the photodegradation mechanism. Under xenon lamp irradiation, two PABA photocatalytic degradation pathways were proposed using Liquid Chromatograph Mass Spectrometer (LCMS) and density functional theory. As expected, FeAl-LDH@FeSx-N-BC showed excellent photocatalytic performance, expanding a new direction and possibility for future photocatalytic treatment of water pollutants.

Angelica sinensis polysaccharide combined with cisplatin reverses cisplatin resistance of ovarian cancer by inducing ferroptosis via regulating GPX4.

Cisplatin (DDP) resistance poses a significant challenge in the treatment of ovarian cancer. Studies have shown that the combination of certain polysaccharides derived from plants with DDP is an effective approach to overcoming drug resistance in some cancers. Angelica sinensis (Oliv.) Diels has been used for centuries in China to treat gynecological ailments. Numerous studies indicate that Angelica sinensis polysaccharide (ASP), an extract from Angelica sinensis, can inhibit various forms of cancer. However, the impact of ASP on ovarian cancer remains unexplored. Through both in vitro and in vivo experiments, our study revealed the capability of ASP to effectively reversing DDP resistance in cisplatin-resistant ovarian cancer cells, while exhibiting acceptable safety profiles in vivo. To elucidate the mechanism underlying drug resistance reversal, we employed RNA-seq analysis and identified GPX4 as a key gene. Considering the role of GPX4 in ferroptosis, we conducted additional research to explore the effects of combining ASP with DDP on SKOV3/DDP cells. In summary, our findings demonstrate that the combination of ASP and DDP effectively suppresses GPX4 expression in SKOV3/DDP cells, thereby reversing their resistance to DDP.

Gender-specific abdominal fat distribution and insulin resistance associated with organophosphate esters and phthalate metabolites exposure.

The worldwide prevalence of obesity highlights the potential contribution of endocrine-disrupting chemicals (EDCs). However, common epidemiological measures such as body mass index and waist circumference may misrepresent the intricate obesity risks these chemicals pose across genders. This study delves deeper into abdominal fat by differentiating between subcutaneous and visceral regions by analyzing data from National Health and Nutrition Examination Surveys (NHANES). We particularly investigated the gender-specific associations between organophosphorus flame-retardant metabolites (mOPFRs), phthalates (mPAEs) and accumulated fat indexes from 2536 people. Aiding by Bayesian Kernel Machine Regression (BKMR), we found while co-exposure to mOPFRs and mPAEs was linked to general and abdominal obesity across the entire and gender-specific populations, a gender-specific fat distribution emerged. For women, urinary BDCPP and MBzP were linked to an increased subcutaneous fat index (SFI) [BDCPP OR: 1.12 (95% CI: 1.03-1.21), MBzP OR: 1.09 (95% CI: 1.01-1.18)], but not to visceral fat index (VFI). These metabolites had a combined linkage with SFI, with BDCPP (weighting 22.0%) and DPHP (weighting 31.0%) being the most influential in Quantile g-computation model (qgcomp) model. In men, BCEP exposure exclusively associated with the elevated VFI [OR: 1.14 (95% CI: 1.03-1.26)], a trend further highlighted in mixture models with BCEP as the predominant association. Intriguingly, only males displayed a marked correlation between these metabolites and insulin resistance in subpopulation. An attempted mediation analysis revealed that elevated C-reactive protein mediated 12.1% of the association between urinary BCEP and insulin resistance, suggesting a potential role of inflammation. In conclusion, the gender-specific fat distribution and insulin resistance that associated with mOPFRs represented the potential risk of these chemicals to man.

Identifying the Main Components and Mechanisms of Action of Artemisia annua L. in the Treatment of Endometrial Cancer Using Network Pharmacology.

Artemisia annua L. (A. annua), a Traditional Chinese Medicine (TCM) that has been utilized in China for centuries, is known for its potential anticancer properties. However, the main components and mechanism of action of A. annua on endometrial carcinoma have not been reported. We used the TCMSP database to identify the active components of A. annua and their corresponding gene targets. We then obtained the gene targets specific to endometrial cancer from The Cancer Genome Atlas (TCGA) and GeneCards databases. The gene targets common to three databases were selected, and a "component-target" network was constructed. Protein-protein interaction (PPI) network analysis and ranking of the target proteins identified the key protein PTGS2 network analysis, and ranking of the target proteins identified the key protein PTGS2. We also screened the active components of A. annua and found that quercetin, kaempferol, luteolin, isorhamnetin, artemisin, and stigmasterol had the most targets. Molecular docking models were established for these six components with PTGS2, revealing strong binding activity for all of them. Finally, we conducted validation experiments to assess the effects of quercetin, an active component of A. annua, on endometrial cancer cells (HEC-1-A and Ishikawa cells). Our findings demonstrate that quercetin has the potential to inhibit both cell growth and migration, while also suppressing the expression of PTGS2.

Green space modified the association between air pollutants and hypertension in China.

Evidence regarding the combined effects of green space and air pollutants on hypertension remains limited and complex. This study aims to investigate the varying effects of greenness under different air pollution levels in China, using data from the wave 2018 China Health and Retirement Longitudinal Study (CHARLS) involving 17 468 adults (aged ≥ 45 years). As a result, the prevalence rate of hypertension was 42.04%. Logistic regression analyses revealed the positive associations between air pollution concentrations at the city level and prevalent hypertension and the negative associations between NDVI and prevalent hypertension, all of which were more prominent in the populations of the eastern and rural regions. Notably, the negative effect of green space was greater at the lowest quartiles of each air pollutant (OR for PM2.5 quartiles = 0.724, 0.792, 0.740, and 0.931) . Improving air quality and greenness could potentially reduce hypertension risk, and minimizing air pollution might optimize the protective effects of greenness.

The mechanism underlying pentabromoethylbenzene-induced adipogenesis and the obesogenic outcome in both cell and mouse model.

Convergent evidence links traditional brominated flame retardants (BFRs) exposure to weight gain, while the obesogenic potency of new BFRs (NBFRs) remain largely unknown. Aiding by luciferase-reporter gene assay, the present study revealed only pentabromoethylbenzene (PBEB), an alternative for penta-BDEs, binds with retinoid X receptor α (RXRα) but not peroxisomeproliferator receptor γ (PPARγ) among the seven testing NBFRs. An apparent induction of adipogenesis in 3T3-L1 cells was observed at nanomolar of PBEB, much lower than penta-BFRs. Mechanistic research uncovered PBEB initiated the adipogenesis by demethylated CpG sites in the PPARγ promoter region. Specifically, activation RXRα by PBEB strengthened the activity of RXRα/PPARγ heterodimer, tightened the interaction between the heterodimer and PPAR response elements, and further enhanced adipogenesis. RNA sequencing combined with k-means clustering analysis exposed adenosine 5'-monophosphate (AMP)-activated protein kinase and phosphoinositide-3-kinase (PI3K)/protein kinase B (AKT) signaling as two predominant pathways that enriched in PBEB-induced lipogenesis. The obesogenic outcome was further corroborated in offspring mice when the maternal mice exposed to environmental relevant doses of PBEB. We found the male offspring exhibited adipocyte hypertrophy and increased weight gain in the epididymal white adipose tissue (eWAT). Consistent with in vitro findings, the reduction in protein phosphorylation of both AMPK and PI3K/AKT were observed within eWAT. Thus, we posited PBEB disrupts the pathways controlling adipogenesis and adipose tissue maintenance, supporting its potential as an environmental obesogen.

Effects of green spaces on alleviating mortality attributable to PM2.5 in China.

Increasing research suggested that green spaces are associated with many health benefits, but evidence for the quantitative relationship between green spaces and mortality attributable to particulate matter with an aerodynamic diameter of 2.5 µm or less (PM2.5) is limited. We collected disease-specific mortality and PM2.5 data for a period of 4 years (2015-2018) along with green space data for an 8-year duration (2010-2017) in 31 provincial-level administrative regions of China. First, this study used the Integrated Exposure-Response model to estimate the mortality of four diseases attributable to PM2.5, including chronic obstructive pulmonary diseases (COPD), lung cancer (LC), ischemic heart disease (IHD), and cerebrovascular disease (CBVD). Then we performed linear regression and mixed-effects model to investigate the counteracting effect of green spaces on death caused by PM2.5 exposure. The differences in impacts among the Eastern, Central, and Western regions were explored using stratified analysis. The most significant results from linear regression analysis indicated that per 100 km2 of green spaces increase, there was a decreased total mortality (10-5) (COPD, LC, IHD, and CBVD) attributable to PM2.5 by - 4.012 [95% confidence interval (CI): - 5.535, - 2.488], while the reduction by mixed-linear regression analysis was - 2.702/105 (95% CI = - 3.645, - 1.759). Of all hysteresis analyses, the effect estimates (ß) at lag3 and lag4 were the largest. The effect of green spaces was more advantageous when targeting CBVD and the Eastern region. We found a negative correlation between green space exposure and mortality attributable to PM2.5, which can provide further support for city planners, government personnel, and others to build a healthier city and achieve national health goals.

Sugar sensation and mechanosensation in the egg-laying preference shift of Drosophila suzukii.

The agricultural pest Drosophila suzukii differs from most other Drosophila species in that it lays eggs in ripe, rather than overripe, fruit. Previously, we showed that changes in bitter taste sensation accompanied this adaptation (Dweck et al., 2021). Here, we show that D. suzukii has also undergone a variety of changes in sweet taste sensation. D. suzukii has a weaker preference than Drosophila melanogaster for laying eggs on substrates containing all three primary fruit sugars: sucrose, fructose, and glucose. Major subsets of D. suzukii taste sensilla have lost electrophysiological responses to sugars. Expression of several key sugar receptor genes is reduced in the taste organs of D. suzukii. By contrast, certain mechanosensory channel genes, including no mechanoreceptor potential C, are expressed at higher levels in the taste organs of D. suzukii, which has a higher preference for stiff substrates. Finally, we find that D. suzukii responds differently from D. melanogaster to combinations of sweet and mechanosensory cues. Thus, the two species differ in sweet sensation, mechanosensation, and their integration, which are all likely to contribute to the differences in their egg-laying preferences in nature.

Sex-dependent effect of triphenyl phosphate on hepatic energy metabolism at the intersection of diet pattern in pubertal mice.

Triphenyl phosphate (TPhP) is mostly residual in fat-rich foodstuff and ingestion is the main route for adolescents' exposure. As a typical metabolic disruptor, however, sex-specific effect of TPhP-high fat diet (HFD) co-exposure in adolescent remains unknown. This study revealed that HFD exacerbated systematic inflammation and insulin insensitivity in female mice at pubertal stage after exposure to 25 mg/kg TPhP or above. Notably, the pattern of sexual selective metabolic disruption caused by TPhP was irrespective of diet after examined mice both in HFD and normal diet feeding. Female mice favored the energy storage in forms of D-glucose 6-phosphate, D-fructose 6-phosphate and triglyceride. That was further supported by mRNA levels of key enzymes in glycolysis, gluconeogenesis, and lipid metabolism. Contrastingly, the elevation of the corresponding genes ensuing by the depleted metabolites were observed in males. In mechanistic investigation, we observed a declination of serum estrogen, a master of energy homeostasis, in both sexes, irrespective of diet. However, only male mice displayed estrogen-hypothalamus negative feedback, supporting by the upregulation of gonadotropin-releasing hormone. Rather than the well-recognized estrogen receptor α, hepatic G protein-coupled estrogen receptor manifested sexual dichotomy, which desensitized to estrogenic response only in females. Collectively, this study posited that females were more susceptible to store energy under TPhP-HFD than males during pubertal partially through estrogenic pathway.

Antibody-conjugated silica-coated gold nanoparticles in targeted therapy of cervical cancer.

This study aimed to synthesize silica-coated gold (Au@SiO2) nanoparticles coupled to antibodies against the scavenger receptor class B type I (SR-BI) and investigate their potential ability of visual tracking and treatment of cervical cancer. The fluorescein isothiocyanate (FITC)-labeled Au@SiO2-SR-BI antibody was synthesized, followed by characterization determination. The expression and location of SR-BI protein in cervical cancer cells were respectively detected by western blot and immunofluorescence assays. The effects of nanoparticles on cancer cells were determined by adsorption assay and apoptosis detection, respectively. The effects of nanoparticles on tumor formation in nude mice were determined. The particle sizes of Au@SiO2 ranged from 2-2.5 µm, and the particle size distribution was relatively uniform. MS751 showed the highest expression of SR-BI. SR-BI was located in the cytomembrane. There were more FITC-Au@SiO2-SR-BI nanoparticles on the surface of the cells compared to FITC-Au@SiO2. Significant apoptosis was observed in the FITC-Au@SiO2-SR-BI-treated group in both MS751 and H8 cells. Photothermal ablation of solid tumors was observed when FITC-Au@SiO2-SR-BI was activated using 808 nm wave. Expressions of the apoptosis-related markers including BCL2, BCLX, and p-AKT were significantly decreased, while those of caspase 3 and caspase 8 were significantly increased. The study presented a novel antibody-conjugated Au@SiO2 nanoparticle specifically targeting molecular receptors on cancer cell membranes. Antibody-conjugated Au@SiO2 nanoparticles may have therapeutic potential for the treatment of cervical cancer.

Remodeling on adipocytic physiology of organophosphorus esters in mature adipocytes.

The emerging endocrine disruption chemicals organophosphate esters (OPEs) pose high risk of metabolic disruption. However, limited information is available on physiological disturbance of OPEs on adipose, a major endocrine and metabolic organ. In this study, physiological change was investigated after exposing 3T3-L1fully differentiated adipocytes to six OPEs at non-cytotoxic concentrations. We found two chlorinated-OPEs (tris-(2-chloro-1-(chloromethyl) ethyl) phosphate (TDCPP) and tris(2-chloroisopropyl) phosphate (TCPP)) and two alkyl-OPEs (tributyl phosphate (TBP) and tris (2-butoxyethyl) phosphate (TBEP)) induced inflammation-like adipokines (chemoattractant protein 1 and interleukin-6), respectively. Increment of insulin-resistance-related hormones (resistin and leptin) were observed under TDCPP, TCPP, and TBP exposure. Functional and mechanistic investigation revealed that all of the compounds inhibited lipolysis at basal level through dephosphorylated HSLser563, the rate limiting enzyme of lipolysis. Triphenyl phosphate (TPhP), tricresyl phosphate (TCP), TDCPP, TBP and TBEP enhanced glucose uptake at both basal and insulin-stimulated status. We evidenced that impact was independent of the classical pIRSser639/pAKTser473 nor the insulin-independent AMPK pathway. The elevated mRNA of slc2a4 and its transcriptional factor LXRα may, at least partially, explain for the increase of glucose uptake. Given the focus within the endocrine disruption on glands, it would be prudent not to ignore endocrinal impact on adipocytes.

Evaluation of a 3.8-µm laser-induced skin injury and their repair with in vivo OCT imaging and noninvasive monitoring.

To explore a 3.8-µm laser-induced damage and wound healing effect, we propose using optical coherence tomography (OCT) and a noninvasive monitoring-based in vivo evaluation method to quantitatively and qualitatively analyze the time-dependent biological effect of a 3.8-µm laser. The optical attenuation coefficient (OAC) is computed using a Fourier-domain algorithm. Three-dimensional (3-D) visualization of OCT images has been implemented to visualize the burnt spots. Furthermore, the burnt spots from the 3-D volumetric data was segmented and visualized, and the quantitative parameters of the burnt spots, such as the mean OACs, areas, and volumes, were computed. Then, OCT images and histological sections were analyzed to compare the structural changes. Within a certain radiation range, there is a linear relationship between radiation dose and temperature. Dermoscopic images, OCT images, and histological sections showed that, within a certain dose range, as the radiation doses increased, the cutaneous damage became more serious. One hour after laser radiation, the mean OACs increased and then decreased; the areas of burnt spots always increased and were 0.95 ± 0.07, 1.01 ± 0.06, 1.025 ± 0.07, 0.99 ± 0.07, 0.98 ± 0.07, 1.00 ± 0.07, 0.96 ± 0.05, and 0.98 ± 0.06 mm-1, respectively; the areas were 2.10 ± 0.63, 3.75 ± 1.85, 5.95 ± 1.62, 8.35 ± 0.88, 9.44 ± 1.28, 10.29 ± 0.49, 12.27 ± 0.96, and 13.127 ± 1.90 mm2; and the volumes were 1.54 ± 0.41, 2.86 ± 0.09, 3.73 ± 0.49, 4.14 ± 0.80, 7.21 ± 0.52, 6.77 ± 0.45, 8.36 ± 0.25, and 10.65 ± 0.51 mm3; and 21 days after laser radiation, the volumes were 0.67 ± 0.18, 1.64 ± 0.08, 1.87 ± 0.12, 2.57 ± 0.34, 3.43 ± 0.26, 3.64 ± 0.04, 3.84 ± 0.15, and 4.16 ± 0.53 mm3, respectively. We investigated the time-dependent biological effect of 3.8-µm laser-induced cutaneous damage and wound healing using the quantitative parameters of OCT imaging and noninvasive monitoring. The real-time temperature reflects the photothermal effect during laser radiation of mouse skin. OCT images of burnt spots were segmented to compute the mean OACs, burnt area, and quantitative volumes. This study has the potential for in vivo noninvasive and quantitative clinical evaluation in the future.

Joint artifact correction and super-resolution of image slicing and mapping system via a convolutional neural network.

As the key component of the image mapping spectrometer, the image mapper introduces complex image degradation in the reconstructed images, including low spatial resolution and intensity artifacts. In this paper, we propose a novel image processing method based on the convolutional neural network to perform artifact correction and super-resolution (SR) simultaneously. The proposed joint network contains two branches to handle the artifact correction task and SR task in parallel. The artifact correction module is designed to remove the artifacts in the image and the SR module is used to improve the spatial resolution. An attention fusion module is constructed to combine the features extracted by the artifact correction and SR modules. The fused features are used to reconstruct an artifact-free high-resolution image. We present extensive simulation results to demonstrate that the proposed joint method outperforms state-of-the-art methods and can be generalized to other image mapper designs. We also provide experimental results to prove the efficiency of the joint network.

Evolutionary shifts in taste coding in the fruit pest Drosophila suzukii.

Although most Drosophila species lay eggs in overripe fruit, the agricultural pest Drosophila suzukii lays eggs in ripe fruit. We found that changes in bitter taste perception have accompanied this adaptation. We show that bitter-sensing mutants of Drosophila melanogaster undergo a shift in egg laying preference toward ripe fruit. D. suzukii has lost 20% of the bitter-sensing sensilla from the labellum, the major taste organ of the head. Physiological responses to various bitter compounds are lost. Responses to strawberry purées are lost from two classes of taste sensilla. Egg laying is not deterred by bitter compounds that deter other species. Profiling of labellar transcriptomes reveals reduced expression of several bitter Gr genes (gustatory receptors). These findings support a model in which bitter compounds in early ripening stages deter egg laying in most Drosophila species, but a loss of bitter response contributes to the adaptation of D. suzukii to ripe fruit.

A new agricultural pest has recently emerged in the United States and Northern Europe. The invasive species is a type of fruit fly that normally lives in Southeast Asia called Drosophila suzukii (also known as the spotted wing Drosophila). This fly poses a threat to fruit crops ­ including strawberries, blueberries, cherries, peaches and grapes ­ because, while other fruit flies lay eggs in overripe fruit, D. suzukii lays eggs in ripe fruit, leading to agricultural losses. This shift in where fruit flies prefer to lay their eggs is related to changes in the senses of smell and touch, and taste could also play a role. Insects have evolved mechanisms that dissuade them from eating or laying eggs in plants with high levels of toxins, which taste bitter. If D. suzukii is less sensitive to bitter tastes than other flies, this could help explain why it lays eggs in just-ripe fruit, since the levels of certain bitter compounds are higher in the early stages of ripening than later on. To figure out if this is the case, Dweck et al. studied different species of fruit fly. Compared to Drosophila melanogaster (a fruit fly common in America and Europe that is regularly used in scientific studies), D. suzukii had fewer bitter taste receptor neurons on the major taste organ of the fly head. These receptor neurons were also less responsive to a variety of bitter compounds. Next, Dweck et al. tested whether D. melanogaster and D. suzukii showed different preferences for where to lay their eggs by offering them strawberry purées made from fruit at different ripening stages. In this experiment, D. suzukii preferred to lay its eggs on purées made from unripe or just-ripe strawberries, while D. melanogaster showed a preference for fermented (overripe) purée. Furthermore, when D. melanogaster flies were genetically modified so that they became less sensitive to bitter taste, they preferred to lay their eggs in ripe (rather than overripe) fruit, similar to D. suzukii. These results suggest that taste has a major role in the egg laying preferences of D. suzukii. Further research is needed to determine which bitter compounds influence egg-laying decisions in each species of fruit fly, and what receptors respond to these compounds. However, Dweck et al.'s results lay the groundwork for new approaches to reducing D. suzukii's impact on agriculture.

Acetylation-stabilized chloride intracellular channel 1 exerts a tumor-promoting effect on cervical cancer cells by activating NF-κB.

PURPOSE: Cervical cancer remains a major cause of cancer-related death in women, especially in developing countries. Previously, we found that the acetylation levels of chloride intracellular channel 1 (CLIC1) at lysine 131 were increased in cervical cancer tissues using a label-free proteomics approach. The aim of this study was to further determine the role of CLIC1 expression and its acetylation in cervical cancer. METHODS: CLIC1 expression and its implications for the prognosis of cervical cancer were analyzed using primary patient samples and cells, and the Gene Expression Profiling Interactive Analysis (GEPIA) database (gepia.cancer-pku.cn). The effect of CLIC1 on cervical cancer cells was evaluated using Cell Counting Kit (CCK)-8, flow cytometry, scratch wound healing, transwell, Western blotting and co-immunoprecipitation (Co-IP) assays. In vivo tumor growth was assessed using mouse xenograft models. RESULTS: We found that CLIC1 expression was increased in cervical cancer tissues and cells and that patients with a high CLIC1 expression tended to have a shorter overall survival time. Knockdown of CLIC1 significantly reduced in vitro cervical cancer cell proliferation, migration and invasion, and in vivo tumorigenesis. At the molecular level, we found that nuclear factor kappa B (NF-κB) activity was positively regulated by CLIC1. Pyrrolidine dithiocarbamate (PDTC), an inhibitor of NF-κB, attenuated the tumor-promoting effect of CLIC1. Moreover, we found that CLIC1 acetylation at K131 was upregulated in cervical cancer cells, which stabilized CLIC1 by inhibiting its ubiquitynation. Substitution of K131 inhibited CLIC1 ubiquitynation and promoted in vitro cervical cancer cell proliferation, migration and invasion, and in vivo tumor growth. In addition, we found that acetyltransferase HAT1 was responsible for CLIC1 acetylation at K131. CONCLUSION: Our data indicate that CLIC1 acts as a tumor promoter in cervical cancer, suggesting a potential treatment strategy for cervical cancer by regulating CLIC1 expression and/or acetylation.

Association of forkhead box P3 gene polymorphisms with premature ovarian insufficiency in Chinese women.

OBJECTIVE: Forkhead box P3 (FOXP3), a transcription factor, is regarding critical regulator of the function of regulatory T (Treg) cells and plays a crucial role in the development of autoimmune diseases. Premature ovarian insufficiency (POI) is an autoimmune disease; however, little is known about the association between FOXP3 variants and the susceptibility to POI. METHODS: Long-range polymerase chain reaction was used to analyze complete FOXP3 gene sequences from 153 patients with POI. The frequencies of genotypes and alleles of the FOXP3 gene were compared between patients with POI and 269 East Asian women from the Genome Aggregation (gnomAD) database. RESULTS: Forty-three single-nucleotide polymorphisms (SNPs) were detected, including 25 known SNPs and 18 novel SNPs. The genotype distributions and allele frequencies of two known SNPs (rs17847094 and rs76798919) and three novel SNPs (NC_000023.11:g.49112832G > A, NC_000023.11:g.49112833G > A, and NC_000023.11:g.49120479CT > C) were significantly different between the two groups. Linkage disequilibrium and haplotype analyses of the rs57734889, rs2232365, rs3761548, and rs34629506 SNPs in FOXP3 were performed and compared, and the high D' (standardized disequilibrium coefficients) value indicated that these polymorphisms may contribute to the risk of POI. CONCLUSIONS: This study is the first to show that genetic variants in the regulatory regions of FOXP3 play a vital role in idiopathic POI in the Chinese population.

Identification of lysine acetylome in cervical cancer by label-free quantitative proteomics.

BACKGROUND: Lysine acetylation is a post-translational modification that regulates a diversity of biological processes, including cancer development. METHODS: Here, we performed the quantitative acetylproteomic analysis of three primary cervical cancer tissues and corresponding adjacent normal tissues by using the label-free proteomics approach. RESULTS: We identified a total of 928 lysine acetylation sites from 1547 proteins, in which 495 lysine acetylation sites corresponding to 296 proteins were quantified. Further, 41 differentially expressed lysine acetylation sites corresponding to 30 proteins were obtained in cervical cancer tissues compared with adjacent normal tissues (Fold change > 2 and P < 0.05), of which 1 was downregulated, 40 were upregulated. Moreover, 75 lysine acetylation sites corresponding to 58 proteins were specifically detected in cancer tissues or normal adjacent tissues. Motif-X analysis showed that kxxxkxxxk, GkL, AxxEk, kLxE, and kkxxxk are the most enriched motifs with over four-fold increases when compared with the background matches. KEGG analysis showed that proteins identified from differently and specifically expressed peptides may influence key pathways, such as Notch signaling pathway, viral carcinogenesis, RNA transport, and Jak-STAT, which play an important role in tumor progression. Furthermore, the acetylated levels of CREBBP and S100A9 in cervical cancer tissues were confirmed by immunoprecipitation (IP) and Western blot analysis. CONCLUSIONS: Taken together, our data provide novel insights into the role of protein lysine acetylation in cervical carcinogenesis.

Neural control of arm movements reveals a tendency to use gravity to simplify joint coordination rather than to decrease muscle effort.

How gravity influences neural control of arm movements remains under debate. We tested three alternative interpretations suggested by previous research: (1) that muscular control includes two components, tonic which compensates for gravity and phasic which produces the movement; (2) that there is a tendency to exploit gravity to reduce muscle effort; and (3) that there is a tendency to use a trailing pattern of joint control during which either the shoulder or elbow is rotated actively and the other joint rotates predominantly passively, and to exploit gravity for control of the passively rotated joint. A free-stroke drawing task was performed that required production of center-out strokes within a circle while selecting stroke directions randomly. The circle was positioned in the horizontal, sagittal, and frontal plane. The arm joints freely rotated in space. In each plane, the distribution of the strokes across directions was non-uniform. Directional histograms were built and their peaks were used to identify preferred movement directions. The directional preferences were especially pronounced in the two vertical planes. The upward directions were most preferred. To test the three interpretations, we used a kinetic analysis that determined the role of gravitational torque in the production of movement in the preferred directions. The results supported the third interpretation and provided evidence against the first and second interpretation. The trailing pattern has been associated with reduced neural effort for joint coordination, and therefore, we conclude that the major tendency with respect to gravity is to exploit it for simplification of joint coordination.

Influence of workspace constraints on directional preferences of 3D arm movements.

We previously demonstrated a tendency to perform arm movements by using a trailing joint control pattern during which either the shoulder or elbow is rotated actively and the other (trailing) joint is rotated predominantly passively, by interaction torque during horizontal movements and by interaction and gravitational torque during 3D arm movements. This tendency was established with a free-stroke drawing task that required production of series of strokes in randomly selected directions from the center to the perimeter of a horizontal circle. The studies demonstrated that within a planar workspace, the usage of the trailing pattern depends on movement direction and the most frequently selected directions are those providing the opportunity to use the trailing pattern. Here, we studied whether the opportunity to use the preferred trailing pattern also depends on the orientation of the planar workspace. The free-stroke drawing task was performed with unconstrained arm movements within circles of a left-diagonal (LD) and right-diagonal (RD) orientation. Two pronounced preferred directions were revealed in the LD condition, and they were the directions in which the trailing pattern was used. Directional preferences were less pronounced, and the trailing pattern was not observed in any directions in the RD condition. Also, subjects identified the RD condition as inconvenient. The results reinforce the previous finding of the propensity to use the trailing pattern during arm movements. They also suggest that orientations of the workspaces in manual activities should be designed to support the trailing pattern as a favored type of joint control.