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Objective: Mitochondrial fatty acid oxidation is a metabolic pathway whose dysregulation is recognized as a critical factor in various cancers, because it sustains cancer cell survival, proliferation, and metastasis. The acyl-CoA synthetase long-chain (ACSL) family is known to activate long-chain fatty acids, yet the specific role of ACSL3 in breast cancer has not been determined. Methods: We assessed the prognostic value of ACSL3 in breast cancer by using data from tumor samples. Gain-of-function and loss-of-function assays were also conducted to determine the roles and downstream regulatory mechanisms of ACSL3 in vitro and in vivo . Results: ACSL3 expression was notably downregulated in breast cancer tissues compared with normal tissues, and this phenotype correlated with improved survival outcomes. Functional experiments revealed that ACSL3 knockdown in breast cancer cells promoted cell proliferation, migration, and epithelial–mesenchymal transition. Mechanistically, ACSL3 was found to inhibit β-oxidation and the formation of associated byproducts, thereby suppressing malignant behavior in breast cancer. Importantly, ACSL3 was found to interact with YES proto-oncogene 1, a member of the Src family of tyrosine kinases, and to suppress its activation through phosphorylation at Tyr419. The decrease in activated YES1 consequently inhibited YAP1 nuclear colocalization and transcriptional complex formation, and the expression of its downstream genes in breast cancer cell nuclei. Conclusions: ACSL3 suppresses breast cancer progression by impeding lipid metabolism reprogramming, and inhibiting malignant behaviors through phospho-YES1 mediated inhibition of YAP1 and its downstream pathways. These findings suggest that ACSL3 may serve as a potential biomarker and target for comprehensive therapeutic strategies for breast cancer.

In industrial settings, analyzing vibration signals from rolling bearings is a key method for diagnosing faults in rotating machinery. However, these faults often appear as a series of transient events with quickly changing frequencies, which makes it difficult for traditional time-frequency analysis techniques to accurately capture these characteristics. Methods like synchrosqueezing transmute and multi-synchrosqueezing transmute struggle with this task. In this study, we introduce a new method called the Wavelet-Enhanced Transient-Extracting Transform (WTET). Unlike traditional approaches that rely on instantaneous frequency in a time-domain model, WTET uses a group delay (GD) estimator in a frequency-domain model. This allows for more accurate characterization of bearing and rub impact fault signals. Additionally, WTET is better at resisting noise compared to the traditional wavelet transform because it isolates only the central coefficients in the time-frequency domain. WTET also retains the ability to reconstruct the original signal, which makes it effective at extracting different signal modes. Our analysis shows that WTET offers improved diagnostic capability for detecting bearing faults.

ObjectiveThe escalating prevalence of chronic pain poses a substantial socio-economic burden. Chronic pain primarily stems from musculoskeletal and nervous system impairments. Given cadmium's known toxicity to these systems, our study sought to investigate the correlation between blood cadmium levels and chronic pain.MethodsThe cross-sectional study was conducted from the National Health and Nutrition Examination Survey (NHANES, 1999–2004), and comprised US adults who participated in a chronic pain interview. We employed logistic regression models and smooth curve fitting to elucidate the relationship between blood cadmium levels and chronic pain.ResultsOur findings revealed a linear association between blood cadmium levels and chronic pain. Compared to the lower blood cadmium tertile 1 (

ObjectiveHigh-density lipoprotein cholesterol (HDL-C) has been reported to be associated with pain symptoms of various diseases, and its anti-inflammatory and antioxidant mediation is related to the pathogenesis of chronic pain. This study aims to evaluate the relationship between HDL-C levels and chronic pain in American adults.MethodsThis cross-sectional study used data from American adults aged 20 and above during the 2003–2004 National Health and Nutrition Examination Survey (NHANES) cycle. Participants were divided into 4 groups based on HDL-C quartiles. We used chi-square tests and Student’s t-tests or Mann-Whitney U tests to analyze categorical variables and continuous variables to compare differences between groups. Multivariate logistic regression analysis was used to study the association between HDL-C levels and the risk of chronic pain. Likelihood ratio tests were used to assess interactions between subgroups, and sensitivity analyses were conducted.ResultsOur final analysis included 4,688 participants, of which 733 (16.4%) had chronic pain. In the multivariate logistic regression model adjusted for covariates, there was a negative correlation between HDL-C levels and chronic pain. Specifically, for every 20 unit increase in HDL-C, the risk of chronic pain decreased by 26%. Compared with the lowest HDL-C quartile (< 43 mg/dL), the highest HDL-C quartile (≥ 64 mg/dL) was associated with a 24% reduction in the risk of chronic pain. No interaction factors affecting the relationship between HDL-C and chronic pain were found in the subgroup analysis.ConclusionThis study demonstrates a negative association between HDL-C levels and chronic pain in US adults, providing insights into the pathogenesis of chronic pain and potential improvements in chronic pain management strategies.

Pleurotus citrinopileatus Singer (PCS) has attracted increasing attention as a raw material for medicine and food. Its quality is greatly affected by the accumulation of metabolites, which varies with the applied drying methods. In this study, we utilize an approach based on ultra-high-performance liquid chromatography/Q Exactive mass spectrometry (UHPLC-QE-MS) to reveal the metabolic profiles of PCS from three different drying methods (natural air-drying, NAD; hot-air-drying, HAD; vacuum freeze-drying, VFD). The results showed that lipids, amino acids and their derivatives were all important secondary metabolites produced during NAD, HAD and VFD treatments, with the key differential metabolites of PCS during drying including fifteen lipids and seven amino acids. Meanwhile, VFD was the best way for long-term preservation of dried PCS. Hot-drying methods, especially HAD, can improve the medicinal component of PCS. Furthermore, KEGG enrichment analysis highlighted 16 pathways and indicated that amino acid metabolism might be the key metabolite pathway for the PCS drying process. Our study elucidates the relationship between drying methods and metabolites or metabolic pathways of PCS to determine the mechanisms affecting the quality of PCS, and finally provides reference values for further development and application in functional food and medications.

ABSTRACTThe demand for Al2O3-SiC-C castables (ASCs) with excellent strength and thermal shock resistance has expanded considerably. Here, the effects of Fe-Si3N4 on the thermal shock resistance and physical properties of ASCs were studied. The addition of Fe-Si3N4 to ASCs lead to the formation of SiC whiskers, enhancing the cold modulus of rupture and the cold crushing strength of the castables. The formed SiC can fill the pores left by the oxidation of carbon after heating at 1450°C for 3 h, thereby improving the bulk density of the castables. Additionally, the residual strength ratio of the castables after three thermal shock cycles was improved and this was attributed to the generation of microcracks due to the release of N2 and the generation of the whiskers. The optimal Fe-Si3N4 content was 4 wt%. Therefore, the results of this study revealed that the thermal shock resistance and physical properties of ASCs were enhanced by the addition of Fe-Si3N4.

Objective: Neoadjuvant chemotherapy (NAC) is currently used in both early stage and locally advanced breast cancers. The survival benefits of standard vs. non-standard NAC cycles are still unclear. This study aimed to investigate the relationship between NAC cycles and survival based on real world data. Methods: We identified patients diagnosed with invasive primary breast cancers who underwent NAC followed by surgery. Patients who received at least 4 NAC cycles were defined as having received standard cycles, while patients who received less than 4 NAC cycles were defined as having received non-standard cycles. Kaplan-Meier curves and Cox proportional hazard models were used to estimate the disease-free survival (DFS) and overall survival (OS). Results: Of the 1,024 included patients, 700 patients received standard NAC cycles and 324 patients received non-standard NAC cycles. The DFS estimates were 87.1% and 81.0% (P = 0.007) and the OS estimates were 90.0% and 82.6% (P = 0.001) in the standard and non-standard groups, respectively. Using multivariate analyses, patients treated with standard NAC cycles showed significant survival benefits in both DFS [hazard ratio (HR): 0.62, 95% confidence interval (CI): 0.44–0.88] and OS (HR: 0.54, 95% CI: 0.37–0.79). Using stratified analyses, standard NAC cycles were associated with improved DFS (HR: 0.59, 95% CI: 0.36–0.96) and OS (HR: 0.49, 95% CI: 0.28–0.86) in the HER2 positive group. Similar DFS (HR: 0.50, 95% CI: 0.25–0.98) and OS (HR: 0.45, 95% CI: 0.22–0.91) benefits were shown for the triple negative group. Conclusions: Standard NAC cycles were associated with a significant survival benefit, especially in patients with HER2 positive or triple negative breast cancer.

Abstract This article proposes a current step‐up converter for high‐gain applications by combining a buck‐boost converter and a Cuk converter to form a buck‐boost‐Cuk converter with a shared input terminal. In order to further improve the performance of the converter and reduce the number of components, the primary side and secondary side of the coupled inductor are respectively connected to different branches, so that the diode‐capacitor branch in this structure could be used as a voltage doubler branch, and performed as a passive clamp circuit to absorb leakage inductance energy, which suppressed the voltage spike generated by the parasitic capacitance and the leakage inductance of the resonance; to some extent, it reduced the voltage stress of the power switch. This paper analyzed the operating principle and performance of the converter, then made the parameter design for the proposed converter, and compared the performance of different converter systems. At last, this paper built a 150 W experimental prototype to verify the correctness of the theoretical analysis.

In order to solve the problem of poor thermal insulation in the current wood-plastic building, two kinds of structural wood wall integrated with wood plastic composite (WPC) are designed, and the thermal insulation performances of the walls are studied. The results show that the WPC integrated wall with frame-shear structure has a good stability, and the excellent performance of the WPC can be fully realized. Wall studs and wall panels are important factors affecting the thermal performance of the walls. Wood plastic materials can meet the thermal performance requirements of the walls. The single-layer frame walls and double-layer frame walls integrated with the WPC both have a good thermal performance. According to ‘Design Standard for Energy Efficiency of Public Buildings (GB 50189-2015)’, the heat transfer coefficient of the single-layer frame wall integrated with 20 mm thick WPC wall boards and WPC wall studs is 0.414 W/(m2•K), which can meet the standard of wall thermal level Ⅱt and is suitable for cold areas. The heat transfer coefficient of the double-layer frame wall integrated with 50 mm thick WPC wall panel and WPC wall studs is 0.207 W/(m2•K), which can meet the standard of wall thermal level Ⅰt and is suitable for severe cold areas.

Summary: Recent studies have shown that PM2.5 may activate the hypothalamus-pituitary-adrenal (HPA) axis by inducing hormonal changes, potentially explaining the increase in neurological and cardiovascular risks. In addition, an association between PM2.5 and gut microbiota and metabolites was established. The above evidence represents crucial parts of the gut-brain axis (GBA). In view of this evidence, we proposed a hypothesis that PM2.5 exposure may affect the HPA axis through the gastrointestinal tract microbiota pathway (GBA mechanism), leading to an increased risk of neurological and cardiovascular diseases. We conducted a real-world prospective repeated panel study in Jinan, China. At each visit, we measured real-time personal PM2.5 and collected fecal and blood samples. A linear mixed-effects model was used to analyze the association between PM2.5 and serum biomarkers, gut microbiota, and metabolites. We found that PM2.5 was associated with increased serum levels of hormones, especially the adrenocorticotropic hormone (ACTH) and cortisol, which are reliable hormones of the HPA axis. Gut microbiota and tryptophan metabolites and inflammation, which are important components of the GBA, were significantly associated with PM2.5. We also found links between PM2.5 and changes in the nervous and cardiovascular outcomes, e.g., increases of 19.77% (95% CI: −36.44, 125.69) in anxiety, 1.19% (95% CI: 0.65, 1.74) in fasting blood glucose (FBG), 2.09% (95% CI: 1.48, 2.70) in total cholesterol (TCHOL), and 0.93% (95% CI: 0.14, 1.72) in triglycerides (TG), were associated with 10 μg/m3 increase in PM2.5 at the lag 0–72 h, which represent the main effects of GBA. This study indicated the link between PM2.5 and the microbiota GBA for the first time, providing evidence of the potential mechanism for PM2.5 with neurological and cardiovascular system dysfunction.

Tight sandstone reservoirs have complex pore throat structures and poor and large differences in petrophysical properties. In this study, taking the Chang 3 Member of Weibei Oilfield, Ordos Basin, China as an example, the microscopic mechanism of the differences in petrophysical properties of tight sandstone reservoirs was systematically studied by thin section observation, scanning electron microscope, whole-rock X-ray diffraction, and high-pressure mercury intrusion experiments. The research results show that the reservoir types of the Chang 3 Member are mainly feldspar lithic sandstone and lithic feldspar sandstone; the pore types include intergranular, intragranular dissolution pores, and a small amount of residual intergranular pores. Taking the permeability of 0.3 × 10−3 and 0.5 × 10−3 μm2 as the boundary, we divided the samples involved in high-pressure mercury intrusion into three categories according to the permeability from high to low: Type I, Type II, and Type III. Their proportions were 31.4, 20.0, and 48.6%, respectively. The study found that the smaller the sorting coefficient, the poorer the petrophysical properties of the samples; the pore throat distribution of different samples gradually changed to a uniform double peak–dominated type. The permeability of tight sandstone reservoirs is contributed by a small part of pore throats with a large radius, while the reservoir space is mainly contributed by a large number of pores connected with small throats. The porosity is negatively and positively correlated with the median pressure and mercury injection tortuosity, respectively. In addition, the pore throat radius corresponding to the maximum permeability contribution rate, maximum pore throat radius, and sorting coefficient are all positively correlated with the permeability. In general, the areas with larger pore throat radius, lower pore throat tortuosity, and larger pore throat sorting coefficient can be regarded as favorable areas for Chang 3 tight sandstone reservoirs.

Fiber length of cotton (Gossypium hirsutum L.) decreases under drought stress, potassium (K) could diminish the decreased caused by drought, but the mechanism associated with this alleviation effect is not clear. We evaluated the effect of K on fiber elongation using two cotton cultivars, Simian 3 and Siza 3, grown in well-watered and drought-stressed conditions. Potassium fertilizer (K2O) was applied 0, 150, or 300 kg ha−1 in each growing condition. Drought stress reduced the final fiber length due to a decline in the maximum rate of rapid elongation (Vmax, mm day−1). The application of K alleviated the drought-induced fiber length reduction by increasing Vmax. At 10 and 15 days post-anthesis (DPA), drought significantly reduced osmotic potential (OP) and increased K+ and malate contents at all K rates, relative to well-watered conditions, which was associated with increased activities of phosphoenolpyruvate carboxylase (PEPC), V-ATPase, PPase, and PM H+-ATPase in cotton fiber. However, the relative contribution of K+ and malate to OP declined under drought in comparison with well-watered condition. Compared with control without K, K application decreased OP and increased the accumulation of osmolytes (K+, malate and soluble sugar) as well as the activities of related enzymes in fiber irrespective of water treatments. Moreover, K application increased osmotic adjustment during drought, and improved the contribution of K+ and malate to OP, especially under drought stress. This study showed that drought decreased fiber length by reducing Vmax, and K application ameliorates the decline in fiber elongation due to drought by enhancing osmolytes accumulation and their contribution to OP in fiber cells. Keywords: Cotton (Gossypium hirsutum), Fiber length, Drought stress, Potassium application, Osmolyte

Human exposure to OPEs is pervasive and should be of great concern due to associations with adverse health effects, especially in susceptible populations. In this study, body burdens and exposure pathways of OPEs were investigated for 76 healthy elderly people in Jinan, China based on the measured OPE and metabolite concentrations in human bio-samples (whole blood and urine) and paired environmental matrices (air and dust), as well as food frequency questionnaire. Eight of 16 OPEs and 5 of 11 metabolites were detected in > 50% of whole blood and urine samples, respectively. Tri(1-chloro-2-propyl) phosphate (TCIPP), tris(2-chloroethyl) phosphate (TCEP), tri-phenyl phosphate (TPHP), and 2-ethylhexyl di-phenyl phosphate (EHDPP) were frequently detected and abundant in whole blood, while their corresponding metabolites were detected at low frequencies or levels in urine. The reduced metabolic and/or excretory capacity of elderly people may be an important reason, implying a higher health risk to them. Fourteen OPEs had over 50% detection frequencies in indoor air and dust, while 6 di-esters in indoor dust. Tris(2-ethylhexyl) phosphate (TEHP) in indoor dust and tri-n-butyl phosphate (TnBP) in indoor air were positively correlated with paired levels in blood but not with their metabolites (BEHP and DnBP) in urine. Combined with the direct intakes of BEHP and DBP from dust, blood is indicated as more suitable biomarker for TEHP and TnBP exposure. High consumption frequencies of several foods were associated with higher blood concentrations of three OPEs and urinary levels of four di-OPEs, indicating the importance of dietary exposure pathway. Estimated daily total intakes of OPEs via inhalation, dust ingestion, and dermal absorption ranged from 2.78 to 42.0 ng/kg bw/day, which were far less than the reference dosage values. Further studies were warranted to explore the potential health effects of OPE exposure in the elderly populations.

The health impact of airborne contaminants has been challenging to assess due to current limitations in measurement technologies. The emergence of wearable passive samplers coupled with high resolution mass spectrometry (HR-MS) chemical analysis has enabled comprehensive characterization of personal exposures. We conducted a repeated-measure study among 84 older adults in Jinan, China, as part of the Biomarkers for Air Pollutants Exposure (China BAPE) study. Study objectives were: 1) to characterize the occurrence, magnitude, and distribution of personal exposure to airborne contaminants; 2) to evaluate the temporal variation of chemical exposures across the study population; and 3) to identify behavioral and environmental factors that influence the observed variance in chemical exposures. The FreshAir wristband was worn by participants for three consecutive days each month from September 2018 to January 2019 and collected with paired time-activity logs. Passive air samplers were also deployed in parallel at a local outdoor air monitoring station. Spearman’s Rho trend test and trajectory cluster analysis were used to identify exposure trends and variation patterns, respectively. Out of the 70 airborne compounds of potential concern screened, 26 compounds from 10 chemical classes were found to be above detection thresholds across >70% of the study population. Personal exposures were predominantly characterized by nine polycyclic aromatic hydrocarbons (PAHs), four phthalates, three nitroaromatics, and two volatile organic compounds (VOCs). Phthalate personal exposures were positively correlated with outdoor temperatures while the inverse relationship was observed for certain PAHs (p

Phellinus igniarius is a valuable medicinal fungus. P. igniarius is rich in a variety of chemical compounds with medicinal value, among which are flavonoids. Therefore, increasing the content of flavonoids in P. igniarius is beneficial for its potential use in medicinal applications. This study demonstrated that exogenous treatment with citric acid (CA) could significantly increase flavonoid accumulation in P. igniarius. Additionally, we found that CA induced the biosynthesis of flavonoids in a concentration- and time-dependent manner. The flavonoid content could be increased up to 60.96 mg/g when using the treatment with 2.77 mM citric acid for 69.74 h, which was determined by using the response surface method. The changes in the fingerprint profiles of P. igniarius flavonoids with the treatment of CA as an exogenous inducer were also analyzed. In this study, the effect of citric acid as the exogenous inducer on the flavonoid content of P. igniarius was studied, and the processing conditions were optimized through the surface response curve. This approach provides novel insights and a theoretical basis for the production of high-quality P. igniarius.

Mining of closely spaced multilayer orebodies brings the problems of significant disturbance between adjacent mining layers and drastic structural changes in surrounding rock, which brings the need for a more effective stope support method. Previous research has made sound analysis on filling or bolt support, but neither of them can solely provide ideal support effects. Thus, a novel bolt-filling support method is proposed by utilizing the synergistic effect of rock bolts (cable bolts) and filling. Numerical simulation and similarity experiments were conducted in this research to analyze the support effect of this method for multilayer ore mining. For numerical simulation, the distinct-element modelling framework PFC2D (Particle Flow Code in 2 Dimensions) was applied for four support scenarios based on the calibration of the microscopic parameters of particles in vanadium shale ores. The numerical simulation results show that the number of fractures decreases from 1311 without support through 652 with 95% filling support to 410 with bolt-filling support, which is resulted from the redistribution of the force chains due to support change. On the other hand, a 300 cm ×180 cm × 40 cm similarity model with a geometry similarity constant of 100 was established based on the 4# rock layer profile of Mount Shangheng. Two parts of similarity experiments were conducted to investigate the strains around the stopes in multi-layer ore mining for three support scenarios. The experiment results prove that the highest strain is in the center of the roof on the upper goaf, and the roof-bolt filling support induces smaller strains than zero support and conventional filling support. Finally, an effective bolt-filling support system has been developed and validated, which can improve the safety and the stability of the roofs and interlayers during the mining process of closely spaced multilayer orebody by reducing the overall load and fractures in surrounding rock.

Flexible DC distribution networks have a strong capacity for new energy consumption and have received extensive attention from scholars in recent years, but fault location for DC distribution lines is a difficult task. To solve this problem, we propose using a comprehensive grey correlation degree analysis to analyze the similarity of aerial mode traveling differential current waveforms at the first and last ends of a DC line, thus achieving fault location by obtaining the optimal time shift. Additionally, we built a six-terminal flexible DC distribution network model in Matlab/Simulink for simulation and validation, showing that the method can complete the rapid and accurate location of all types of faults on a DC line, and that it possesses an anti-transition resistance capability, making it suitable and highly reliable for cases of low sampling frequency.

Tumor microenvironment has been increasingly proved to be crucial during the development of breast cancer. The theory about the conversion of cold and hot tumor attracted the attention to the influences of traditional therapeutic strategies on immune system. Various genetic models have been constructed, although the relation between immune system and local microenvironment still remains unclear. In this study, we tested and collected the immune index of 262 breast cancer patients before and after neoadjuvant chemotherapy. Five indexes were selected and analyzed to form the prediction model, including the ratio values between after and before neoadjuvant chemotherapy of CD4+/CD8+ T cell ratio; lymphosum of T, B, and natural killer (NK) cells; CD3+CD8+ cytotoxic T cell percent; CD16+CD56+ NK cell absolute value; and CD3+CD4+ helper T cell percent. Interestingly, these characters are both the ratio value of immune status after neoadjuvant chemotherapy to the baseline. Then the prediction model was constructed by support vector machine (accuracy rate = 75.71%, area under curve = 0.793). Beyond the prognostic effect and prediction significance, the study instead emphasized the importance of immune status in traditional systemic therapies. The result provided new evidence that the dynamic change of immune status during neoadjuvant chemotherapy should be paid more attention.

The technology of integrating nanoscale zero-valent iron (nZVI) and functional anaerobic bacteria has broad prospects for groundwater remediation. This review focuses on the interactions between nZVI and three kinds of functional anaerobic bacteria: organohalide-respiring bacteria (OHRB), sulfate reducing bacteria (SRB) and iron reducing bacteria (IRB), which are commonly used in the anaerobic bioremediation. The coupling effects of nZVI and the functional bacteria on the contaminant removal in the integrated system are summarized. Generally, nZVI could create a suitable living condition for the growth and activity of anaerobic bacteria. OHRB and SRB could synergistically degrade organic halides and remove heavy metals with nZVI, and IRB could reactive the passivated nZVI by reducing the iron (hydr)oxides on the surface of nZVI. Moreover, the roles of these anaerobic bacteria in contaminant removal coupling with nZVI and the degradation mechanisms are illustrated. In addition, this review also discusses the main factors influencing the removal efficiency of contaminants in the integrated treatment system, including nZVI species and dosage, inorganic ions, organic matters, pH, type of pollutants, temperature, and carbon/energy sources, etc. Among these factors, the nZVI species and dosage play a fundamental role due to the potential cytotoxicity of nZVI, which might exert a negative impact on the performance of this integrated system. Lastly, the future research needs are proposed to better understand this integrated technology and effectively apply it in groundwater remediation. Keywords: Nanoscale zero-valent iron, Organohalide-respiring bacteria, Sulfate reducing bacteria, Iron reducing bacteria, Groundwater remediation

Bufei Yishen formula (BYF) is a Traditional Chinese Medicine (TCM) reported to ameliorate chronic obstructive pulmonary disease (COPD) by regulating the balance between T helper (Th) 17 and regulatory T (Treg) cells. However, its mechanism remains unknown. Therefore, this study aimed to explore the underlying mechanisms of BYF. Naïve CD4+ T cells were exposed to anti-CD3, anti-CD28, transforming growth factor (TGF)-β, and/or interleukin (IL)-6 to promote their differentiation into Th17 or Treg cells. A rat model of cigarette smoke- and bacterial infection-induced COPD was established and orally treated with BYF and/or an adenosine 2a receptor (A2aR) antagonist. Then, the rats were sacrificed, their lung tissues were removed for histological analysis, and their spleens were collected to evaluate Th17 and Treg cells. The results showed that BYF significantly suppressed Th17 cell differentiation and its related cytokines and enhanced Treg cell differentiation and its related cytokines. In addition, BYF activated the A2aR, increased the levels of p-signal transducer and activator of transcription (STAT)5, and decreased the level of p-STAT3 in Treg and Th17 cells. The A2aR antagonist suppressed the changes induced by BYF treatment in Th17 and Treg cells. Furthermore, the A2aR antagonist diminished the therapeutic effect of BYF on COPD, as indicated by the lung injury scores, bronchiole wall thickness, small pulmonary vessels wall thickness, bronchiole stenosis, alveolar diameters, decrease in inflammatory cytokines, increase in alveolar number, and lung functions. Similarly, the A2aR antagonist reversed the effects of BYF on the proportion of Th17 and Treg cells in the spleen. Additionally, BYF increased the protein and mRNA levels of A2aR and regulated the phosphorylation of STAT3 and STAT5 in spleen and lung tissues, which were inhibited by cotreatment with the A2aR antagonist. In conclusion, this study suggested that BYF exhibited its anti-COPD efficacy by restoring the Th17/Treg balance via activating A2aR, which may provide evidence for the clinical application of BYF in the treatment of COPD.

Proton-coupled monocarboxylate transporters (MCTs), representing the first four isoforms of the SLC16A gene family, mainly participate in the transport of lactate, pyruvate, and other monocarboxylates. Cancer cells exhibit a metabolic shift from oxidative metabolism to an enhanced glycolytic phenotype, leading to a higher production of lactate in the cytoplasm. Excessive accumulation of lactate threatens the survival of cancer cells, and the overexpression of proton-coupled MCTs observed in multiple types of cancer facilitates enhanced export of lactate from highly glycolytic cancer cells. Proton-coupled MCTs not only play critical roles in the metabolic symbiosis between hypoxic and normoxic cancer cells within tumors but also mediate metabolic interaction between cancer cells and cancer-associated stromal cells. Of the four proton-coupled MCTs, MCT1 and MCT4 are the predominantly expressed isoforms in cancer and have been identified as potential therapeutic targets in cancer. Therefore, in this review, we primarily focus on the roles of MCT1 and MCT4 in the metabolic reprogramming of cancer cells under hypoxic and nutrient-deprived conditions. Additionally, we discuss how MCT1 and MCT4 serve as metabolic links between cancer cells and cancer-associated stromal cells via transport of crucial monocarboxylates, as well as present emerging opportunities and challenges in targeting MCT1 and MCT4 for cancer treatment.

Metastasis and drug resistance are the leading causes of death for breast cancer patients. Epithelial–mesenchymal transition (EMT), a transition from polarized epithelial cells to motile mesenchymal cells mediated by a series of activation signals, confers breast tumor cells with enhanced stem cell, invasive, and metastatic properties. Metabolic reprogramming is an emerging hallmark of cancer cells, which have a complex mutual effect with EMT process. Under hypoxic and nutrient-deprived conditions, metabolic rewiring can rapidly provide ATP and sufficient metabolic intermediates for fueling breast cancer metastasis and progression. In this review, we primarily focus on how these altered metabolic phenotypes of breast tumor cells activate the EMT transcription factors and induce the EMT process to further promote metastasis and resistance to therapy. This review is divided to glucose, lipid, and amino acid metabolism to explore for potential metabolic vulnerabilities, which may provide new insights for blocking the EMT process in breast cancer.

Personal exposure to air pollution is affected by its concentration in the microenvironment and individual time-activity patterns. To investigate personal black carbon (BC) exposure levels and identify their potential determinants, we conducted a panel study among 67 elderly residents aged 60–69 years in Jinan, China. Personal BC exposure was measured using portable real-time monitors, while corresponding ambient BC concentrations and meteorological conditions were also collected from the local central site. Time-activity and household characteristics were recorded. A linear mixed-effects model was used to identify potential determinants of personal BC exposure. The daily average personal BC exposure concentration was 4.1 ± 2.0 μg/m3 (±standard deviation, SD), which was significantly lower than the ambient concentration (4.6 ± 2.5 μg/m3) (p

Metabolic reprogramming is an emerging hallmark of cancer cells, in which cancer cells exhibit distinct metabolic phenotypes to fuel their proliferation and progression. The significant advancements made in the area of metabolic reprogramming make possible new strategies for overcoming malignant cancer, including triple-negative breast cancer. Triple-negative breast cancer (TNBC) is associated with high histologic grade, aggressive phenotype, and poor prognosis. Even though triple-negative breast cancer patients benefit from standard chemotherapy, they still face high recurrence rates and are more likely to develop resistance to chemotherapeutic drugs. Therefore, there is an urgent need to explore vulnerabilities of triple-negative breast cancer and develop novel therapeutic drugs to improve clinical outcomes for triple-negative breast cancer patients. Metabolic reprogramming may provide promising therapeutic targets for the treatment of triple-negative breast cancer. In this paper, we primarily discuss how triple-negative breast cancer cells reprogram their metabolic phenotype and that of stromal cells in the microenvironment to survive under nutrient-poor conditions. Considering that metastasis and chemoresistance are the main contributors to mortality in triple-negative breast cancer patients, we also focus on the role of metabolic adaption in mediating metastasis and chemoresistance of triple-negative breast cancer tumors.

Hesperidin, a natural compound, suppresses the epithelial-to-mesenchymal transition through the TGF-β1/Smad signaling pathway. However, studies on the detailed effects and mechanisms of hesperidin are rare. The present study showed that, for A549 alveolar epithelial cells, the anti-proliferative effects of hesperidin occurred in a dose-dependent manner, with an IC50= 216.8 µM at 48 h. TGF-β1 was used to activate the Smad signaling pathway and induce the epithelial to mesenchymal transition in cells. Treatment with hesperidin or SB431542 was used for antagonism of Smad pathway activation. Hesperidin inhibited the increase in ɑ-SMA and Col1ɑ-1 and the decrease in E-cadherin in a dose-dependent manner from concentration of 20 µM to 60 µM, as assessed by both ELISA and Western blotting assays; however, there was no significant effect on cellular morphological alterations. Moreover, the Western blotting assay showed that, in the cytoplasm, hesperidin and SB431542 had no significant effect on the protein expression of Smad 2, 3, 4, or 7 as well as 2/3. However, 60 µM hesperidin and SB431542 significantly decreased p-Smad2/3 protein expression. From the above results, it is concluded that hesperidin can partly inhibit the epithelial to mesenchymal transition in human alveolar epithelial cells; the effect accounts for the blockage of the phosphorylation of Smad2/3 in the cytoplasm rather than a change in Smad protein production in the cytoplasm.

BACKGROUND: Evidence suggested that abiotic airborne exposures may be associated with changes in body composition. However, more evidence is needed to identify key pollutants linked to adverse health effects and their underlying biomolecular mechanisms, particularly in sensitive older adults. OBJECTIVES: Our research aimed to systematically assess the relationship between abiotic airborne exposures and changes in body composition among healthy older adults, as well as the potential mediating mechanisms through the serum lipidome. METHODS: From September 2018 to January 2019, we conducted a monthly survey among 76 healthy adults (60–69 years old) in the China Biomarkers of Air Pollutant Exposure (BAPE) study, measuring their personal exposures to 632 abiotic airborne pollutions using MicroPEM and the Fresh Air wristband, 18 body composition indicators from the InBody 770 device, and lipidomics from venous blood samples. We used an exposome-wide association study (ExWAS) and deletion/substitution/addition (DSA) model to unravel complex associations between exposure to contaminant mixtures and body composition, a Bayesian kernel machine regression (BKMR) model to assess the overall effect of key exposures on body composition, and mediation analysis to identify lipid intermediators. RESULTS: The ExWAS and DSA model identified that 2,4,5-T methyl ester (2,4,5-TME), 9,10-Anthracenedione (ATQ), 4b,8-dimethyl-2-isopropylphenanthrene, and 4b,5,6,7,8,8a,9,10-octahydro-(DMIP) were associated with increased body fat mass (BFM), fat mass indicators (FMI), percent body fat (PBF), and visceral fat area (VFA) in healthy older adults [Bonferroni-Hochberg false discovery rate (FDRBH)<0.05]. The BKMR model demonstrated a positive correlation between contaminants (anthracene, ATQ, copaene, di-epi-a-cedrene, and DMIP) with VFA. Mediation analysis revealed that phosphatidylcholine [PC, PC(16:1e/18:1), PC(16:2e/18:0)] and sphingolipid [SM, SM(d18:2/24:1)] mediated a significant portion, ranging from 12.27% to 26.03% (푝-value <0.05), of the observed increase in VFA. DISCUSSION: Based on the evidence from multiple model results, ATQ and DMIP were statistically significantly associated with the increased VFA levels of healthy older adults, potentially regulated through lipid intermediators. These findings may have important implications for identifying potentially harmful environmental chemicals and developing targeted strategies for the control and prevention of chronic diseases in the future, particularly as the global population is rapidly aging. [ABSTRACT FROM AUTHOR]