Job burnout and anxiety among medical staff: A latent profile and moderated mediation analysis.

BACKGROUND: Due to work pressure, work intensity, and the impact of emergencies such as the epidemic, job burnout and mental health problems among medical staff have become increasingly prominent. OBJECTIVES: Our study aims to characterize the patterns of burnout in Chinese medical staff, explore the profile differences on anxiety and self-esteem, examine whether the differences in these profiles on anxiety were mediated by self-esteem, and investigate whether this mediating process was moderated by positive coping styles among medical staff. METHODS: Data were collected from 602 medical staff in China by a convenient sampling method. A latent profile and moderated mediation analysis were performed. RESULTS: Latent profile analysis on three burnout dimensions [emotional exhaustion, cynicism, and professional efficacy] indicated two burnout profiles: low burnout (82.47% of the sample) and high burnout (17.53%). Medical staff with a low burnout profile had lower levels of emotional exhaustion and cynicism than those with a high burnout profile. It was also determined that self-esteem mediates burnout and anxiety in both high- and low-burnout medical staff. The moderating role of positive coping styles was also identified (ß = 0.30, 95%CI: 0.058-0.550). CONCLUSIONS: The identification of two distinct burnout patterns (low burnout and high burnout) provides clinical administrators with clear goals for individualizing support and interventions for medical staff with different levels of burnout. Furthermore, attention should be given to self-esteem and positive coping styles, as they act as potential mediators and moderators of medical staff's mental health problems.

Differential effects of domesticated and wild Capsicum frutescens L. on microbial community assembly and metabolic functions in rhizosphere soil.

Objective: Rhizosphere microorganisms play crucial roles in the growth and development of plants, disease resistance, and environmental adaptability. As the only wild pepper variety resource in China, domesticated Capsicum frutescens Linn. (Xiaomila) exhibits varying beneficial traits and affects rhizosphere microbial composition compared with its wild counterparts. In this study, we aimed to identify specific rhizosphere microbiome and metabolism patterns established during the domestication process. Methods: The rhizosphere microbial diversity and composition of domesticated and wild C. frutescens were detected and analyzed by metagenomics. Non-targeted metabolomics were used to explore the differences of metabolites in rhizosphere soil between wild and domesticated C. frutescens. Results: We found that the rhizosphere microbial diversity of domesticated variety was significantly different from that of the wild variety, with Massilia being its dominant bacteria. However, the abundance of certain beneficial microbes such as Gemmatimonas, Streptomyces, Rambibacter, and Lysobacter decreased significantly. The main metabolites identified in the wild variety included serylthreonine, deoxyloganic acid, vitamin C, among others. In contrast, those identified in the domesticated group were 4-hydroxy-l-glutamic acid and benzoic acid. Furthermore, the differentially enriched pathways were concentrated in tyrosine and tryptophan biosynthesis, histidine and purine-derived alkaloids biosynthesis, benzoic acid family, two-component system, etc. Conclusion: This study revealed that C. frutescens established specific rhizosphere microbiota and metabolites during domestication, which has important significance for the efficient utilization of beneficial microorganisms in breeding and cultivation practices.

Characterization of Degraded Konjac Glucomannan from an Isolated Bacillus licheniformis Strain with Multi-Enzyme Synergetic Action.

The large molecular weight and high viscosity of natural konjac glucomannan (KGM) limit its industrial application. Microbial degradation of low-molecular-weight KGM has health benefits and various biological functions; however, the available KGM strains used in the industry have microbial contamination and low degradation efficiencies. Therefore, exploring novelly adaptable strains is critical for industrial processes. Here, the Bacillus licheniformis Z7-1 strain isolated from decaying konjac showed high efficiency for KGM degradation. The monosaccharide composition of the degradation products had a reduced molar ratio of mannose to glucose, indicating that Z7-1 preferentially degraded glucose in KGM. The degraded component was further characterized by ESI-MS, Fourier-transform infrared spectroscopy (FT-IR), and scanning electron microscopy (SEM), and it also exhibited good antibacterial activity against various food-spoilage bacteria. Genome sequencing and zymolytic analysis revealed that abundant carbohydrate-active enzymes exist in the Z7-1 genome, with at least five types of extracellular enzymes responsible for KGM degradation, manifesting multi-enzyme synergetic action. The extracellular enzymes had significant thermal stability, indicating their potential application in industry. This study provides an alternative method for obtaining low-molecular-weight KGM with antibacterial functions and supports foundational knowledge for its development as a biocatalyst for the direct conversion of biomass polysaccharides into functional components.

A novel polyp retrieval bag reduces the polyp fragmentation rate in colon polypectomy: a single-blind randomized controlled study.

PURPOSE: The fragmentation of polyps affects complete resection confirmation. The primary aim of this study was to assess the feasibility of a novel polyp retrieval bag for reducing the fragmentation rate of colon polyps. METHODS: Patients with a 5-15 mm colon polyp were recruited and randomized into two groups at a 1:1 ratio. After polyp resection, polyps obtained from patients in the treatment group were extracted via a novel polyp retrieval bag without traversing the instrument channel, whereas polyps obtained from patients in the control group were collected through the instrument channel, attaching the polyp trap to the instrument channel port, and applying suction. RESULTS: From January to July 2022, 225 patients were assessed for eligibility. The study participants included 204 patients, and seven patients whose samples were not retrieved were excluded. Polyp fragmentation was significantly lower in the treatment group than in the control group (3.0% [3/100] vs. 17.5% [17/97], P = 0.001). The retrieval failure rates in the treatment group and control group were not significantly different (2.0% [2/102] vs. 4.9% [5/102], P = 0.442). There were fewer colonoscope insertions in the treatment group than in the control group (102 vs. 110), but a significant difference was not present (P = 0.065). No significant adverse events were observed during the follow-up. CONCLUSIONS: This study demonstrated that the polyp retrieval bag was safe and feasible for reducing the fragmentation rate of retrieved polyps. TRIAL REGISTRATION: The study was registered at ClinicalTrials.gov (NCT05189912, 1/12/2021).

Integrated meta-QTL and in silico transcriptome assessment pinpoint major genomic regions responsible for spike length in wheat (Triticum aestivum L.).

Spike length (SL) is one of the major contributors to wheat yield. Uncovering major genetic regions affecting SL is an integral part of elucidating the genetic basis of wheat yield traits and goes further pivotal for marker-assisted selection breeding. A genome-wide meta-quantitative trait locus (MQTL) analysis of wheat SL resulted in the refinement of 48 MQTLs using 227 initial QTLs retrieved from previous studies published over the past decades. The average confidence interval (CI) of these MQTLs amounted to a 5.16-fold reduction compared to the mean CI of the initial QTLs. As many as 2240 putative candidate genes (CGs) were identified from the MQTL intervals using transcriptomics data in silico of wheat, of which 58 CGs were identified based on wheat-rice homology analysis. For the key CG affecting SL, a functional kompetitive allele-specific PCR (KASP) marker, TaPP2C-3B-KASP, was developed to distinguish TaPP2C-3B-Hap I and TaPP2C-3B-Hap II based on the single nucleotide polymorphism at the 272 bp (A/G). The frequency of the elite allelic variation TaPP2C-3B-Hap II with high SL remained relatively stable at about 49.62% from the 1960s to 1990s. Integration of MQTL analysis and in silico transcriptome data led to a significant increase in the reliability of CGs for the genetic regulation of wheat SL, and the haplotype analysis for key CGs TaPP2C-3B of SL provided insights into the biological function of the TaPP2C-3B gene.

RACK1 enhances STAT3 stability and promotes T follicular helper cell development and function during blood-stage Plasmodium infection in mice.

CD4+ T cells are central mediators of protective immunity to blood-stage malaria, particularly for their capacity in orchestrating germinal center reaction and generating parasite-specific high-affinity antibodies. T follicular helper (Tfh) cells are predominant CD4+ effector T cell subset implicated in these processes, yet the factors and detailed mechanisms that assist Tfh cell development and function during Plasmodium infection are largely undefined. Here we provide evidence that receptor for activated C kinase 1 (RACK1), an adaptor protein of various intracellular signals, is not only important for CD4+ T cell expansion as previously implied but also plays a prominent role in Tfh cell differentiation and function during blood-stage Plasmodium yoelii 17XNL infection. Consequently, RACK1 in CD4+ T cells contributes significantly to germinal center formation, parasite-specific IgG production, and host resistance to the infection. Mechanistic exploration detects specific interaction of RACK1 with STAT3 in P. yoelii 17XNL-responsive CD4+ T cells, ablation of RACK1 leads to defective STAT3 phosphorylation, accompanied by substantially lower amount of STAT3 protein in CD4+ T cells, whereas retroviral overexpression of RACK1 or STAT3 in RACK1-deficient CD4+ T cells greatly restores STAT3 activity and Bcl-6 expression under the Tfh polarization condition. Further analyses suggest RACK1 positively regulates STAT3 stability by inhibiting the ubiquitin-proteasomal degradation process, thus promoting optimal STAT3 activity and Bcl-6 induction during Tfh cell differentiation. These findings uncover a novel mechanism by which RACK1 participates in posttranslational regulation of STAT3, Tfh cell differentiation, and subsequent development of anti-Plasmodium humoral immunity.

Promotion of mature angiogenesis in ischemic stroke by Taohong Siwu decoction through glycolysis activation.

Backgrounds: Mature angiogenesis plays a critical role in improving cerebral ischemia-reperfusion injury (CIRI). Glycolysis serves as the primary energy source for brain microvascular endothelial cells (BMECs), whereas other vascular cells rely on aerobic respiration. Therefore, intercellular variations in energy metabolism could influence mature angiogenesis. Taohong Siwu Decoction (THSWD) has demonstrated efficacy in treating ischemic stroke (IS), yet its potential to promote mature angiogenesis through glycolysis activation remains unclear. Methods: In this study, we established a middle cerebral artery occlusion/reperfusion (MCAO/R) model in vivo and an oxygen-glucose deprivation/reoxygenation (OGD/R) model in vitro. We assessed neuroprotective effects using neurobehavioral scoring, 2,3,5-triphenyltetrazolium chloride (TTC) staining, Hematoxylin-eosin (HE) staining, and Nissl staining in MCAO/R rats. Additionally, we evaluated mature angiogenesis and glycolysis levels through immunofluorescence, immunohistochemistry, and glycolysis assays. Finally, we investigated THSWD's mechanism in linking glycolysis to mature angiogenesis in OGD/R-induced BMECs. Results: In vivo experiments demonstrated that THSWD effectively mitigated cerebral damage and restored neurological function in MCAO/R rats. THSWD significantly enhanced CD31, Ang1, PDGFB, and PDGFR-ß expression levels, likely associated with improved glucose, pyruvate, and ATP levels, along with reduced lactate and lactate/pyruvate ratios. In vitro findings suggested that THSWD may boost the expression of mature angiogenesis factors (VEGFA, Ang1, and PDGFB) by activating glycolysis, increasing glucose uptake and augmenting lactate, pyruvate, and ATP content, thus accelerating mature angiogenesis. Conclusion: THSWD could alleviate CIRI by activating the glycolysis pathway to promote mature angiogenesis. Targeting the glycolysis-mediated mature angiogenesis alongside THSWD therapy holds promise for IS treatment.

Halogen Tailoring of Platinum Electrocatalyst with High CO Tolerance for Methanol Oxidation Reaction.

The catalytic activity of platinum for the CO oxidation depends on the interaction of electron donation and back-donation at the platinum center. Here we demonstrate that the platinum bromine nanoparticles with electron-rich properties on bromine bonded with sp-C in graphdiyne (PtBr NPs/Br-GDY), which is formed by bromine ligand and constitutes an electrocatalyst with a high CO-resistant for methanol oxidation reaction (MOR). The catalyst showed peak mass activity for MOR as high as 10.4 A mgPt-1, which is 20.8 times higher than the 20% Pt/C. The catalyst also showed robust long-term stability with slight current density decay after 100 hours at 35 mA cm-2. Structural characterization, experimental, and theoretical studies show that the electron donation from bromine makes the surface of platinum catalysts highly electron-rich, and can strengthen the adsorption of CO as well as enhance π back-donation of Pt to weaken the C-O bond to facilitate CO electrooxidation and enhance catalytic performance during MOR. The results highlight the importance of electron-rich structure among active sites in Pt-halogen catalysts and provide detailed insights into the new mechanism of CO electrooxidation to overcome CO poisoning at the Pt center on an orbital level.

Effects of nanoplastic exposure routes on leaf decomposition in streams.

Polystyrene nanoparticles (PS NPs) released from plastic products have been demonstrated to pose a threat to leaf litter decomposition in streams. Given the multitrophic systems of species interactions, the effects of PS NPs through different exposure routes on ecosystem functioning remain unclear. Especially dietary exposure, a frequently overlooked pathway leading to toxicity, deserves more attention. A microcosm experiment was conducted in this study to assess the effects of waterborne and dietary exposure to PS NPs on the litter-based food chain involving leaves, microbial decomposers, and detritivores (river snails). Compared to waterborne contamination, dietary contamination resulted in lower microbial enzyme activities and a significantly higher decrease in the lipid content of leaves. For river snails, their antioxidant activity was significantly increased by 20.21%-69.93%, and their leaf consumption rate was significantly reduced by 16.60% through the dietary route due to the lower lipid content of leaves. Besides, the significantly decreased nutritional quality of river snails would negatively influence their palatability to predators. The findings of this study indicate that dietary exposure to PS NPs significantly impacts microbial and detritivore activities, thus affecting their functions in the detritus food chain as well as nutrient cycling.

Response of a simulated aquatic fungal community to nanoplastics exposure and functional consequence on leaf decomposition.

Nanoplastics pose a potential threat to a wide variety of aquatic organisms. Despite the awareness of this existing hazard, the impact of nanoplastics on natural fungal communities remains a research gap. In this study, five dominant fungi species, isolated from a stream ecosystem, were used to explore the effects of different nano-polystyrene (nano-PS) particles concentrations on a simulated fungal community. Specifically, the evaluation was conducted regarding the fungal growth, reproductivity, structural composition, and ecological function in leaf litter decomposition. A 15-day exposure experiment showed that 100 µg/L nano-PS significantly reduced the microcosm pH. The extracellular enzyme activities of ß-glucosidase, leucine-aminopeptidase, and peroxidase were significantly promoted by nano-PS exposure for 5 days or 15 days. Total sporulation rate significantly decreased after the 15-day exposure to 1 and 100 µg/L nano-PS and significantly increased under 10 µg/L nano-PS. In contrast, nano-PS concentrations had no effects on fungal biomass. In addition, the reduced relative abundance of Geotrichum candidum lowered its contribution to leaf decomposition, resulting in a decreased litter decomposition rate of a 24.5-27.9 % after exposure. This suggests that 1-100 µg/L nano-PS inhibited leaf decomposition by inhibiting fungal reproduction and reducing the contribution of specific fungal species. In addition, the findings highlight the importance of exploring the potential mechanisms of the interaction between nanoplastics and fungal species.

BPOZ-2-deficient mice exhibit aggravated inflammation-associated tissue damage after acute dextran sodium sulfate or diethylnitrosamine exposure.

An excessive inflammatory response plays an important role in pathological tissue damage associated with pathogen infection and tumorigenesis. Blood POZ-containing gene type 2 (BPOZ-2), an adaptor protein for the E3 ubiquitin ligase scaffold protein CUL3, is a negative regulator of the inflammatory response. In this study, we investigated the pathophysiological functions of BPOZ-2 in dextran sodium sulfate (DSS)-induced colon injury and diethylnitrosamine (DEN)-induced liver damage. Our results indicated that BPOZ-2 deficiency increased IL-1ß induction after DSS and DEN treatment. In addition, BPOZ-2-deficient mice were more susceptible to DSS-induced colitis. Notably, BPOZ-2 deficiency aggravated DEN-induced acute liver injury. These results revealed that BPOZ-2 protected against pathological tissue damage with a dysregulated inflammatory response.

A Blade-Type Triboelectric-Electromagnetic Hybrid Generator with Double Frequency Up-Conversion Mechanism for Harvesting Breeze Wind Energy.

Triboelectric nanogenerators (TENGs) have garnered substantial attention in breeze wind energy harvesting. However, how to improve the output performance and reduce friction and wear remain challenging. To this end, a blade-type triboelectric-electromagnetic hybrid generator (BT-TEHG) with a double frequency up-conversion (DFUC) mechanism is proposed. The DFUC mechanism enables the TENG to output a high-frequency response that is 15.9 to 300 times higher than the excitation frequency of 10 to 200 rpm. Coupled with the collisions between tribomaterials, a higher surface charge density and better generating performance are achieved. The magnetization direction and dimensional parameters of the BT-TEHG were optimized, and its generating characteristics under varying rotational speeds and electrical boundary conditions were studied. At wind speeds of 2.2 and 10 m/s, the BT-TEHG can generate, respectively, power of 1.30 and 19.01 mW. Further experimentation demonstrates its capacity to charge capacitors, light up light emitting diodes (LEDs), and power wireless temperature and humidity sensors. The demonstrations show that the BT-TEHG has great potential applications in self-powered wireless sensor networks (WSNs) for environmental monitoring of intelligent agriculture.

Treating ischemic stroke by improving vascular structure and promoting angiogenesis using Taohong Siwu Decoction: An integrative pharmacology strategy.

ETHNOPHARMACOLOGICAL RELEVANCE: Neovessels represent a crucial therapeutic target and strategy for repairing ischemic tissue. Taohong Siwu Decoction (THSWD) exhibits potential in promoting angiogenesis to address ischemic stroke (IS). However, its impact on neovessel structure and function, alongside the underlying molecular mechanisms, remains elusive. AIM OF THE STUDY: Our aim is to investigate the protective effects of THSWD on neovessel structure and function, as well as the associated molecular mechanisms, utilizing an integrative pharmacological approach. MATERIALS AND METHODS: We initially employed behavioral tests, 2,3,5-triphenyltetrazolium chloride (TTC) staining, Haematoxylin-eosin (HE) staining, enzyme-linked immunosorbent assay (ELISA), Laser Doppler flowmetry (LDF), Evans blue staining, and immunofluorescence to evaluate the protective effects of THSWD on neovascular structure and function in middle cerebral artery occlusion/reperfusion (MCAO/R) rats. Subsequently, we utilized network pharmacology, metabolomics, and experimental validation to elucidate the underlying molecular mechanisms of THSWD in enhancing neovascular structure and function. RESULT: In addition to significantly reducing neurological deficits and cerebral infarct volume, THSWD mitigated pathological damage, blood-brain barrier (BBB) leakage, and cerebral blood flow disruption. Moreover, it preserved neovascular structure and stimulated angiogenesis. THSWD demonstrated potential in ameliorating cerebral microvascular metabolic disturbances including lipoic acid metabolism, fructose and mannose metabolism, purine metabolism, and ether lipid metabolism. Consequently, it exhibited multifaceted therapeutic effects, encompassing anti-inflammatory, antioxidant, energy metabolism modulation, and antiplatelet aggregation properties. CONCLUSION: THSWD exhibited protective effects on cerebral vascular structure and function and facilitated angiogenesis by rectifying cerebral microvascular metabolic disturbances in MCAO/R rats. Furthermore, integrated pharmacology offers a promising approach for studying the intricate traditional Chinese medicine (TCM) system in IS treatment.

Biological fermentation pilot-scale systems and evaluation for commercial viability towards sustainable biohydrogen production.

Featuring high caloric value, clean-burning, and renewability, hydrogen is a fuel believed to be able to change energy structure worldwide. Biohydrogen production technologies effectively utilize waste biomass resources and produce high-purity hydrogen. Improvements have been made in the biohydrogen production process in recent years. However, there is a lack of operational data and sustainability analysis from pilot plants to provide a reference for commercial operations. In this report, based on spectrum coupling, thermal effect, and multiphase flow properties of hydrogen production, continuous pilot-scale biohydrogen production systems (dark and photo-fermentation) are established as a research subject. Then, pilot-scale hydrogen production systems are assessed in terms of sustainability. The system being evaluated, consumes 171,530 MJ of energy and emits 9.37 t of CO2 eq when producing 1 t H2, and has a payback period of 6.86 years. Our analysis also suggests future pathways towards effective biohydrogen production technology development and real-world implementation.

Leaf nutrient traits of planted forests demonstrate a heightened sensitivity to environmental changes compared to natural forests.

Leaf nutrient content (nitrogen, phosphorus) and their stoichiometric ratio (N/P) as key functional traits can reflect plant survival strategies and predict ecosystem productivity responses to environmental changes. Previous research on leaf nutrient traits has primarily focused on the species level with limited spatial scale, making it challenging to quantify the variability and influencing factors of forest leaf nutrient traits on a macro scale. This study, based on field surveys and literature collected from 2005 to 2020 on 384 planted forests and 541 natural forests in China, investigates the differences in leaf nutrient traits between forest types (planted forests, natural forests) and their driving factors. Results show that leaf nutrient traits (leaf nitrogen content (LN), leaf phosphorus content (LP), and leaf N/P ratio) of planted forests are significantly higher than those of natural forests (P< 0.05). The impact of climatic and soil factors on the variability of leaf nutrient traits in planted forests is greater than that in natural forests. With increasing forest age, natural forests significantly increase in leaf nitrogen and phosphorus content, with a significant decrease in N/P ratio (P< 0.05). Climatic factors are key environmental factors dominating the spatial variability of leaf nutrient traits. They not only directly affect leaf nutrient traits of planted and natural forest communities but also indirectly through regulation of soil nutrients and stand factors, with their direct effects being more significant than their indirect effects.

Insecure Parental Attachment and Anxiety in Vocational College Students: The Mediating Role of Subjective Well-Being and the Moderating Role of Self-Esteem.

Purpose: Although insecure parental attachment (IPA) has been shown to play an important role in anxiety, little is known about the mediating and moderating mechanisms underlying this relationship. Patients and Methods: In the present study, we examined the mediating role of subjective well-being (SWB) in the association between IPA and anxiety and the moderating role of self-esteem. 947 Chinese vocational college students completed the measures of IPA, anxiety, SWB, and self-esteem. Results: The results indicated that IPA was significantly and positively associated with anxiety, and SWB partially mediated this relationship. Moreover, the results indicated that self-esteem moderated the relationship between IPA and anxiety. The higher the level of self-esteem, the weaker the effect of insecure attachment on the anxiety of vocational college students. Conclusion: This study highlights the significance of identifying the mechanisms of mediating and moderating paths between IPA and anxiety in vocational college students.

High-frequency neural activity dysregulation is associated with sleep and psychiatric disorders in BMAL1-deficient animal models.

Sleep disturbance led by BMAL1-deficiency has been recognized both in rodent and non-human primate models. Yet it remained unclear how their diurnal brain oscillations were affected upon BMAL1 ablation and what caused the discrepancy in the quantity of sleep between the two species. Here, we investigated diurnal electroencephalographs of BMAL1-deficient mice and cynomolgus monkeys at young adult age and uncovered a shared defect of dysregulated high-frequency oscillations by Kullback-Leibler divergence analysis. We found beta and gamma oscillations were significantly disturbed in a day versus night manner in BMAL1-deficient monkeys, while in mice the beta band difference was less evident. Notably, the dysregulation of beta oscillations was particularly associated with psychiatric behaviors in BMAL1-deficient monkeys, including the occurrence of self-injuring and delusion-like actions. As such psychiatric phenotypes were challenging to uncover in rodent models, our results offered a unique method to study the correlation between circadian clock dysregulation and psychiatric disorders.

A Polymer Nanocomposite with Strong Full-Spectrum Solar Absorption and Infrared Emission for All-Day Thermal Energy Management and Conversion.

Realizing efficient energy utilization from the heat source of the sun and the cold source of outer space is of great significance for addressing the global energy and environmental crisis. Materials with ideal full-spectrum solar absorption and infrared emission are highly desirable for adapting to the continuous weather dynamic throughout the day, nonetheless, their development remains challenging. Here, a polymer nanocomposite with full-spectrum strong solar (280-2500 nm) absorption ranging from 88.8% to 94.8% with an average value of 93.2% and full-spectrum high infrared (8-13 µm) emission ranging from 81.3% to 90.0% with an average value of 84.2%, is reported by melt-processing polypropylene and uniformly dispersed low-loading MXene nanosheets (1.9 vol%). The nanocomposite can achieve daytime photothermal enhancement of ≈50 °C and nighttime radiative cooling of 8 °C. The temperature difference throughout the day ensures all-day uninterrupted thermoelectric generation, yielding a power density output of 1.5 W m-2 (daytime) and 7.9 mW m-2 (nighttime) in real outdoor environment without any additional energy consumption. This work provides an impressive polymer nanocomposite with ideal full-spectrum solar absorption and infrared emission for all-day uninterrupted thermal energy management and conversion.

Palmitic acid-activated GPRs/KLF7/CCL2 pathway is involved in the crosstalk between bone marrow adipocytes and prostate cancer.

BACKGROUND: Obesity-induced abnormal bone marrow microenvironment is one of the important risk element for bone metastasis in prostate cancer (PCa). The present study aimed to determine whether obesity-induced elevation in palmitic acid (PA), which is the most abundant of the free fatty acids (FFAs), increased CCL2 via the GPRs/KLF7 pathway in bone marrow adipocytes (BMA) to facilitate PCa growth and metastasis. METHODS: We constructed a bone-tumor bearing mouse model with obesity through high-fat diet, and observed the tumor formation ability of PCa cells. In vitro, observe the effect of PA on the expression level of CCL2 in BMA through GPRs/KLF7 signaling pathway. After co-culture of BMA and PCa cells, CCK8 assay and transwell experiment were used to detect the changes in biological behavior of PCa cells stimulated by BMA. RESULTS: The BMA distribution in the bone marrow cavity of BALB/c nude mice fed with the high-fat diet (HFD) was evidently higher than that in the mice fed with the normal diet (ND). Moreover, HFD-induced obesity promoted KLF7/CCL2 expression in BMA and PCa cell growth in the bone marrow cavity of the mice. In the vitro experiment, a conditioned medium with increased CCL2 obtained from the BMA cultured with PA (CM-BMA-PA) was used for culturing the PCa cell lines, which evidently enhanced the proliferation, invasion, and migration ability. KLF7 significantly increased the CCL2 expression and secretion levels in BMA by targeting the promoter region of the CCL2 gene. In addition, GPR40/120 engaged in the PA-induced high KLF7/CCL2 levels in BMA to facilitate the malignant progression of PC-3 cells. CONCLUSIONS: PA-activated GPRs/KLF7/CCL2 pathway in BMA facilitates prostate cancer growth and metastasis.

The role of estrogen receptors (ERs)-Notch pathway in thyroid toxicity induced by Di-2-ethylhexyl phthalate (DEHP) exposure: Population data and in vitro studies.

BACKGROUND: This study aimed to assess the exposure level and risk of Di-2-ethylhexyl Phthalate (DEHP) among adults in Jilin Province, China, clarify the impact of DEHP on human thyroid function, and to explore the role of estrogen receptors (ERs)-Notch signaling pathway in the effect of DEHP metabolites on thyroid hormones based on population data and in vitro experiments. METHODS: 312 adults participated in this study. Urinary DEHP metabolites were determined by high performance liquid chromatography coupled to a tandem mass spectrometer (HPLC-MS/MS). Two pharmacokinetic models were used to evaluate the estimated daily intake (EDI) and hazard quotient (HQ) of the adults. Multiple linear regression and mediating effect models were used to evaluate the target associations. In cell experiments, thyroid follicular epithelial (Nthy-ori3-1) cells were exposed to mono (2-ethylhexyl) phthalate (MEHP) for testing. The inhibitions of ERα and Notch pathway were conducted by siRNA and Notch pathway inhibitor DAPT. RESULTS: The detection rate of five DEHP metabolites was 97.1∼100.0%. The HQ value of 0.3% of adults was higher than 1. The levels of urinary DEHP metabolites were significantly correlated with thyrotropin (TSH), thyrotropin-releasing hormone (TRH), total triiodothyronine (TT3), total thyroxine (TT4), free triiodothyronine (FT3) and free thyroxine (FT4) and gene (estrogen receptor α (ERα), Notch1, Dll4) levels. The ERα-Notch pathway played a mediating role in the association between DEHP metabolite levels and FT4. The cell results showed, the levels of FT3 and FT4 in cell supernatant decreased after MEHP exposure, and the downward trend was reversed after ERα and notch pathways were inhibited, notch pathway genes also decreased after ERα inhibition. CONCLUSION: Adults in the Jilin Province of China were widely exposed to DEHP. ERs-Notch pathway played an important role in the effect of DEHP metabolites on thyroid hormones.