Secondary metabolites in host pears defense against two fruit borers and cytochrome-P450-mediated counter-defense.

Herbivorous insects have evolved metabolic strategies to survive the challenges posed by plant secondary metabolites (SMs). This study reports an exploration of SMs present in pears, which serve as a defense against invasive Cydia pomonella and native Grapholita molesta and their counter-defense response. The feeding preferences of fruit borers are influenced by the softening of two pear varieties as they ripen. The content of SMs, such as quercetin and rutin, increases due to feeding by fruit borers. Notably, quercetin levels only increase after C. pomonella feeding. The consumption of SMs affects the growth of fruit borer population differently, potentially due to the activation of P450 genes by SMs. These two fruit borers are equipped with specific P450 enzymes that specialize in metabolizing quercetin and rutin, enabling them to adapt to these SMs in their host fruits. These findings provide valuable insights into the coevolution of plants and herbivorous insects.

Integration of electronic nose, electronic tongue, and colorimeter in combination with chemometrics for monitoring the fermentation process of Tremella fuciformis.

This study proposes an efficient method for monitoring the submerged fermentation process of Tremella fuciformis (T. fuciformis) by integrating electronic nose (e-nose), electronic tongue (e-tongue), and colorimeter sensors using a data fusion strategy. Chemometrics was employed to establish qualitative identification and quantitative prediction models. The Pearson correlation analysis was applied to extract features from the e-nose and tongue sensor arrays. The optimal sensor arrays for monitoring the submerged fermentation process of T. fuciformis were obtained, and four different data fusion methods were developed by incorporating the colorimeter data features. To achieve qualitative identification, the physicochemical data and principal component analysis (PCA) results were utilized to determine three stages of the fermentation process. The fusion signal based on full features proved to be the optimal data fusion method, exhibiting the highest accuracy across different models. Notably, random forest (RF) was shown to be the most accurate pattern recognition method in this paper. For quantitative prediction, partial least squares regression (PLSR) and support vector regression (SVR) were employed to predict the sugar content and dry cell weight during fermentation. The best respective predictive R2 values for reducing sugar, tremella polysaccharide and dry cell weight were found to be 0.965, 0.988, and 0.970. Furthermore, due to its ability to capture nonlinear data relationships, SVR had superior performance in prediction modeling than PLSR. The results demonstrated that the combination of electronic sensor fusion signals and chemometrics provided a promising method for effectively monitoring T. fuciformis fermentation.

Association between visceral adipose tissue and total testosterone among the United States male adults: a cross-sectional study.

Visceral adipose tissue (VAT) is regarded as an important risk factor for obesity-related diseases. The results of the association between VAT and total testosterone (TT) are controversial and whether this association is nonlinear is still unknown. 3971 male participants who were aged 20-59 years from the National Health and Nutrition Examination Surveys 2011-2016 were included. VAT area was measured by dual-energy x-ray absorptiometry. TT in serum was assessed utilizing the isotope dilution liquid chromatography-tandem mass spectrometry technique. Linear regression models assessed the associations between VAT area and TT. A restricted cubic spline model was employed to investigate nonlinear relationships. A two-piecewise linear regression model was applied to determine the threshold effect. Subgroup analyses were conducted. The weighted methods were utilized in all analyses. VAT area was inversely associated with TT in the crude and adjusted models. In the fully adjusted model, VAT area was associated with TT (ß = -0.59, 95% confidence interval [CI] = -0.74, -0.43) and compared to the first tertile of VAT area, the second and the third tertile had a lower TT level, the ß and 95% CI = -65.49 (-83.72, -47.25) and -97.57 (-121.86, -73.27) respectively. We found these inverse associations were nonlinear. The cutoff point of the VAT area was 126 cm2. When the VAT area was <126 cm2, VAT area was significantly associated with a lower TT level (ß = -1.55, 95% CI = -1.93 to -1.17, p < 0.0001). However, when the VAT area was ≥126 cm2, this association was less apparent (ß = -0.26, 95% CI = -0.52 to 0.01, p = 0.06). No significant interactions among different ages (<50 or ≥50 years), marital, and physical activity status were found. These findings underscore the potential for VAT area as a modifiable indicator for improving testosterone deficiency.

Key residues involved in the interaction between chlorpyrifos and a chemosensory protein in Rhopalosiphum padi: Implication for tracking chemical residues via insect olfactory proteins.

The development of advanced biosensors for tracking chemical residues and detecting environmental pollution is of great significance. Insect chemical sensory proteins, including chemosensory proteins (CSPs), are easy to synthesize and purify and have been used to design proteins for specific biosensor applications. Chlorpyrifos is one of the most commonly used chemicals for controlling insect pests in agriculture. This organophosphate is harmful to aquatic species and has long-term negative consequences for the ecosystem. CSPs can bind and carry a variety of environmental chemicals, including insecticides. However, the mechanism by which CSPs bind to insecticides in aphids has not been clarified. In this study, we discovered that RpCSP1 from Rhopalosiphum padi has a higher affinity for chlorpyrifos, with a Ki value of 4.763 ± 0.491 µM. Multispectral analysis revealed the physicochemical binding mechanism between RpCSP1 and chlorpyrifos. Computational simulation analysis demonstrated that the main factor promoting the development of the RpCSP1-chlorpyrifos complex is polar solvation energy. Four residues (Arg33, Glu94, Gln145, Lys153) were essential in facilitating the interaction between RpCSP1 and chlorpyrifos. Our research has improved knowledge of the relationship between CSPs and organophosphorus pesticides. This knowledge contributes to the advancement of biosensor chips for tracking chemical residues and detecting environmental pollution through the use of CSPs.

Rapid isolation of extracellular vesicles using covalent organic frameworks combined with microfluidic technique.

Extracellular vesicles (EVs) are nano-sized lipid-membrane vesicles involved in intercellular communication and reflecting the physiological and pathological processes of their parental cells. Rapid isolation of EVs with low cost is an essential precondition for downstream function exploration and clinical applications. In this work, we designed a novel EVs isolation device based on the boronated organic framework (BOF) coated recyclable microfluidic chip (named EVs-BD) to separate EVs from cell culture media. Using a reactive oxygen species responsive phenylboronic ester compound, the highly porous BOF with a pore size in the range of 10-300 nm was prepared by crosslinking γ-cyclodextrin metal-organic frameworks. A mussel-inspired polydopamine (PDA)/polyethyleneimine (PEI) coating was employed to pattern BOF on the PDMS substrate of microfluidic channels. The EVs-BD was demonstrated to offer distinct advantages over the traditional ultracentrifugation method, such as operation simplicity and safety, reduced time and expense, and low expertize requirements. All things considered, a novel approach of EV acquisition has been successfully developed, which can be customized easily to meet the requirements of various EV-relevant research.

Conjugated linoleic acid (CLA) reduces intestinal fatty acid uptake and chylomicron formation in HFD-fed mice associated with the inhibition of DHHC7-mediated CD36 palmitoylation and the downstream ERK pathway.

The anti-obesity effect of conjugated linoleic acid (CLA) has been well elucidated, but whether CLA affects fat deposition by regulating intestinal dietary fat absorption remains largely unknown. Thus, this study aimed to investigate the effects of CLA on intestinal fatty acid uptake and chylomicron formation and explore the possible underlying mechanisms. We found that CLA supplementation reduced the intestinal fat absorption in HFD (high fat diet)-fed mice accompanied by the decreased serum TG level, increased fecal lipids and decreased intestinal expression of ApoB48 and MTTP. Correspondingly, c9, t11-CLA, but not t10, c12-CLA induced the reduction of fatty acid uptake and TG content in PA (palmitic acid)-treated MODE-K cells. In the mechanism of fatty acid uptake, c9, t11-CLA inhibited the binding of CD36 with palmitoyltransferase DHHC7, thus leading to the decreases of CD36 palmitoylation level and localization on the cell membrane of the PA-treated MODE-K cells. In the mechanism of chylomicron formation, c9, t11-CLA inhibited the formation of the CD36/FYN/LYN complex and the activation of the ERK pathway in the PA-treated MODE-K cells. In in vivo verification, CLA supplementation reduced the DHHC7-mediated total and cell membrane CD36 palmitoylation and suppressed the formation of the CD36/FYN/LYN complex and the activation of the ERK pathway in the jejunum of HFD-fed mice. Altogether, these data showed that CLA reduced intestinal fatty acid uptake and chylomicron formation in HFD-fed mice associated with the inhibition of DHHC7-mediated CD36 palmitoylation and the downstream ERK pathway.

Adaptive sequential design for phase II single-arm oncology trials: an expansion of Simon's design.

Single-arm phase II trials are very common in oncology. A fixed sample trial may lack sufficient power if the true efficacy is less than the assumed one. Adaptive designs have been proposed in the literature. We propose a Simon's design based, adaptive sequential design. Simon's design is the most used fixed sample design for single-arm phase II oncology trials. A prominent feature of Simon's design is that it minimizes the sample size when there is no clinically meaningful efficacy. We identify Simon's trial as a special group sequential design. Established methods for sample size re-estimation (SSR) can be readily applied to Simon's design. Simulations show that simply adding SSR to Simon's design may still not provide desirable power. We propose some expansions to Simon's design. The expanded design with SSR can provide even more power.

Knockdown of the VEGFB/VEGFR1 signaling suppresses pubertal mammary gland development of mice via the inhibition of PI3K/Akt pathway.

Vascular endothelial growth factor B (VEGFB) has been well demonstrated to play a crucial role in regulating vascular function by binding to the VEGF receptors (VEGFRs). However, the specific role of VEGFB and VEGFRs in pubertal mammary gland development remains unclear. In this study, we observed that blocking the VEGF receptors with Axitinib suppressed the pubertal mammary gland development. Meanwhile, the proliferation of mammary epithelial cells (HC11) was repressed by blocking the VEGF receptors with Axitinib. Additionally, knockdown of VEGFR1 rather than VEGFR2 and NRP1 elicited the inhibition of HC11 proliferation, suggesting the essential role of VEGFR1 during this process. Furthermore, Axitinib or VEGFR1 knockdown led to the inhibition of the PI3K/Akt pathway. However, the inhibition of HC11 proliferation induced by Axitinib and or VEGFR1 knockdown was eliminated by the Akt activator SC79, indicating the involvement of the PI3K/Akt pathway. Finally, the knockdown of VEGFB and VEGFR1 suppressed the pubertal development of mice mammary gland with the inhibition of the PI3K/Akt pathway. In summary, the results showed that knockdown of the VEGFB/VEGFR1 signaling suppresses pubertal mammary gland development of mice via the inhibition of the PI3K/Akt pathway, which provides a new target for the regulation of pubertal mammary gland development.

Mechanism of astragaloside IV regulating NLRP3 through LOC102555978 to attenuate cerebral ischemia reperfusion induced microglia pyroptosis.

Astragaloside IV(ASⅣ), the main component of Radix Astragali, has been used to treat cerebral ischemia reperfusion injury (CIRI). However, the molecular mechanism of ASIV in CIRI needs to be further elucidated. Long non-coding RNA (lncRNA) is considered to be an important kind of regulatory molecule in CIRI. In this work, the biological effect and molecular mechanism of ASIV in CIRI through lncRNA were analyzed by using rat middle cerebral artery occlusion and reperfusion (MCAO/R) model and primary rat microglia (RM) cells oxygen and glucose deprivation/reoxygenation (OGD/R) model. The neurological deficit score was evaluated, the volume of cerebral infarction was calculated, and pyroptosis related molecules were detected by qPCR and western blot. Then, high-throughput sequencing was performed in sham and MCAO/R groups. The competitive endogenous RNA (ceRNA) networks associated with pyroptosis were constructed by functional enrichment analysis. CCK-8 detection of cell survival rate, qPCR and western blot were used to determine the specific molecular mechanism of ASⅣ through ceRNA in vitro. Results showed thatASⅣ could decrease the neurological deficit score, reduce the volume of cerebral infarction, inhibit inflammatory reaction and pyroptosis in MCAO/R model rats. Next, the ceRNA network was established, including the LOC102555978/miR-3584-5p/NLRP3 regulatory network. In vitro experiments showed that LOC102555978 promotes NLRP3 mediated pyroptosis of RM cells through sponge adsorption of miR-3584-5p, which may provide a potential therapeutic target for post-CIRI inflammation regulation. ASⅣ could inhibit pyroptosis of RM cells by down-regulating LOC102555978. LOC102555978/miR-3584-5p/NLRP3 may be the molecular mechanism of ASⅣ's CIRI protective effect.

Uridine Diphosphate-Glycosyltransferase RpUGT344D38 Contributes to λ-Cyhalothrin Resistance in Rhopalosiphum padi.

Uridine diphosphate-glycosyltransferase (UGT) is a key phase II enzyme in the insect detoxification system. Pyrethroids are commonly used to control the destructive wheat aphid Rhopalosiphum padi. In this study, we found a highly expressed UGT gene, RpUGT344D38, in both λ-cyhalothrin (LCR)- and bifenthrin (BTR)-resistant strains of R. padi. After exposure to λ-cyhalothrin and bifenthrin, the expression levels of RpUGT344D38 were significantly increased in the resistant strains. Knockdown of RpUGT344D38 did not affect the resistance of BTR, but it did significantly increase the susceptibility of LCR aphids to λ-cyhalothrin. Molecular docking analysis demonstrated that RpUGT344D38 had a stable binding interaction with both bifenthrin and λ-cyhalothrin. The recombinant RpUGT344D38 was able to metabolize 50% of λ-cyhalothrin. This study provides a comprehensive analysis of the role of RpUGT344D38 in the resistance of R. padi to bifenthrin and λ-cyhalothrin, contributing to a better understanding of aphid resistance to pyrethroids.

Enabling Rapid and Stable Sodium Storage via a P2-Type Layered Cathode with High-Voltage Zero-Phase Transition Behavior.

Currently, a major target in the development of Na-ion batteries is the concurrent attainment of high-rate capacity and long cycling stability. Herein, an advanced Na-ion battery with high-rate capability and long cycle stability based on Li/Ti co-doped P2-type Na0.67 Mn0.67 Ni0.33 O2 , a host material with high-voltage zero-phase transition behavior and fast Na+ migration/conductivity during dynamic de-embedding process, is constructed. Experimental results and theoretical calculations reveal that the two-element doping strategy promotes a mutually reinforcing effect, which greatly facilitates the transfer capability of Na+ . The cation Ti4+ doping is a dominant high voltage, significantly elevating the operation voltage to 4.4 V. Meanwhile, doping Li+ shows the function in charge transfer, improving the rate performance and prolonging cycling lifespan. Consequently, the designed P2-Na0.75 Mn0.54 Ni0.27 Li0.14 Ti0.05 O2 cathode material exhibits discharge capacities of 129, 104, and 85 mAh g- 1 under high voltage of 4.4 V at 1, 10, and 20 C, respectively. More importantly, the full-cell delivers a high initial capacity of 198 mAh g-1 at 0.1 C (17.3 mA g-1 ) and a capacity retention of 73% at 5 C (865 mA g-1 ) after 1000 cycles, which is seldom witnessed in previous reports, emphasizing their potential applications in advanced energy storage.

Porphyrin-Thiophene Based Conjugated Polymer Cathode with High Capacity for Lithium-Organic Batteries.

Organic electrode materials are promising for next-generation energy storage materials due to their environmental friendliness and sustainable renewability. However, problems such as their high solubility in electrolytes and low intrinsic conductivity have always plagued their further application. Polymerization to form conjugated organic polymers can not only inhibit the dissolution of organic electrodes in the electrolyte, but also enhance the intrinsic conductivity of organic molecules. Herein, we synthesized a new conjugated organic polymer (COPs) COP500-CuT2TP (poly [5,10,15,20-tetra(2,2'-bithiophen-5-yl) porphyrinato] copper (II)) by electrochemical polymerization method. Due to the self-exfoliation behavior, the porphyrin cathode exhibited a reversible discharge capacity of 420 mAh g-1, and a high specific energy of 900 Wh Kg-1 with a first coulombic efficiency of 96 % at 100 mA g-1. Excellent cycling stability up to 8000 cycles without capacity loss was achieved even at a high current density of 5 A g-1. This highly conjugated structure promotes COP500-CuT2TP combined high energy density, high power density, and good cycling stability, which would open new opportunity for the designable and versatile organic electrodes for electrochemical energy storage.

The Role of Phase Mixing Degree in Promoting C-C Coupling in Electrochemical CO2 Reduction Reaction on Cu-based Catalysts.

Cu-based catalysts have been identified as the most promising candidates for generation of C2+ products in electrochemical CO2 reduction reaction. Defect engineering in catalysts is a widely employed strategy for promoting C-C coupling on Cu. However, comprehensive understanding of defect structure-to-activity relationship has not been obtained. In this study, controllable defects generation is achieved, which leads to a series of Cu-based catalysts with various phase mixing degrees. It is observed that the Faradaic efficiency toward C2+ products increases with the phase mixing degree, reaching 81 % at maximum. In situ infrared absorption spectroscopy reveals that the catalysts with higher phase mixing degree tend to form *CO more easily and possess higher retention of *CO under high overpotential window, thereby promoting C-C coupling. This work sheds new light on the relationship between defects and C-C coupling, and the rational developed of more advanced Cu-base catalysts.

Coarse-Grained Model-Assisted Design of Polymer Prodrug Nanoparticles with Enhanced Cytotoxicity: A Combined Theoretical and Experimental Study.

To achieve drug release from polymer prodrug nanoparticles, the drug-polymer linker must be accessible for cleavage to release the drug, which can occur under certain physiological conditions (e.g., presence of specific enzymes). Supramolecular organization of polymer prodrug nanoparticles is crucial as it greatly affects the location of the linker, its surface exposure/solvation and thus its cleavage to release the drug. Since experimental access to these data is not straightforward, new methodologies are critically needed to access this information and to accelerate the development of more effective polymer prodrug nanoparticles, and replace the time-consuming and resource-intensive traditional trial-and-error strategy. In this context, we reported here the use of a coarse-grained model to assist the design of polymer prodrug nanoparticles with enhanced cytotoxicity. By choosing the solvent accessible surface area as the critical parameter for predicting drug release and hence cytotoxicity of polymer prodrug nanoparticles, we developed an optimized polymer-drug linker with enhanced hydrophilicity and solvation. Our hypothesis was then experimentally validated by the synthesis of the corresponding polymer prodrugs based on two different drugs (gemcitabine and paclitaxel), which demonstrated greater performances in terms of drug release and cytotoxicity on two cancer cell lines. Interestingly, our methodology can be easily applied to other polymer prodrug structures, which would contribute to the development of more efficient drug delivery systems via in silico screening.

Physical Fitness Parameters of Elite Chinese Wheelchair Curlers / Parámetros de Aptitud Física de Curlers en Silla de Ruedas Chinos de Élite

SUMMARY: Few international studies have analyzed the characteristics of elite wheelchair curlers competing on the international stage. This study aims to investigate the physical fitness parameters of elite Chinese wheelchair curlers and explore the corresponding training enlightenment. Sixteen wheelchair curlers from the Chinese national team, including six male and two female Winter Paralympic gold medalists, were selected as research participants. The following parameters were measured: age, training age, height, weight, body fat percentage, grip strength, absolute bench press strength, and 5-km wheelchair push-timing test. Compared with ordinary curlers of the Chinese wheelchair curling team, elite curlers were older in age and training age; male curlers were shorter, whereas female curlers were taller. However, their weight and body fat percentage were lower, and their grip strength, absolute strength in the bench press, and 5-k wheelchair push-timing test were better. From an athlete development and physical training perspective, wheelchair curlers should increase training years in order to accumulate competition experience. Additionally, these athletes should manage their body weight and fat percentage, and improve their upper limb strength and aerobic capacity.

Pocos estudios internacionales han analizado las características de los curlers en silla de ruedas de élite que compiten en el escenario internacional. Este estudio tiene como objetivo investigar los parámetros de aptitud física de los bigudíes chinos en silla de ruedas de élite y explorar la iluminación del entrenamiento correspondiente. Se seleccionaron como participantes de la investigación dieciséis curlers en silla de ruedas del equipo nacional chino, incluidos seis medallistas de oro masculinos y dos femeninos de los Juegos Paralímpicos de Invierno. Se midieron los siguientes parámetros: edad, edad de entrenamiento, altura, peso, porcentaje de grasa corporal, fuerza de agarre, fuerza absoluta en press de banca y prueba de sincronización de empuje en silla de ruedas de 5 km. En comparación con los curlers ordinarios del equipo chino de curling en silla de ruedas, los curlers de élite eran mayores en edad y tiempo de entrenamiento; Los curlers masculinos eran más bajos, mientras que las mujeres eran más altas. Sin embargo, su peso y porcentaje de grasa corporal fueron menores, y su fuerza de agarre, fuerza absoluta en press de banca y prueba de sincronización de empuje en silla de ruedas de 5-k fueron mejores. Desde la perspectiva del desarrollo del atleta y del entrenamiento físico, los curlers en silla de ruedas deberían aumentar los años de entrenamiento para acumular experiencia en competencia. Además, estos deportistas deben controlar su peso corporal y porcentaje de grasa, y mejorar la fuerza de sus miembros superiores y su capacidad aeróbica.

Novel order-level lineage of ammonia-oxidizing archaea widespread in marine and terrestrial environments.

Ammonia-oxidizing archaea (AOA) are among the most ubiquitous and abundant archaea on Earth, widely distributed in marine, terrestrial, and geothermal ecosystems. However, the genomic diversity, biogeography, and evolutionary process of AOA populations in subsurface environments are vastly understudied compared to those in marine and soil systems. Here, we report a novel AOA order Candidatus (Ca.) Nitrosomirales which forms a sister lineage to the thermophilic Ca. Nitrosocaldales. Metagenomic and 16S rRNA gene-read mapping demonstrates the abundant presence of Nitrosomirales AOA in various groundwater environments and their widespread distribution across a range of geothermal, terrestrial, and marine habitats. Terrestrial Nitrosomirales AOA show the genetic capacity of using formate as a source of reductant and using nitrate as an alternative electron acceptor. Nitrosomirales AOA appear to have acquired key metabolic genes and operons from other mesophilic populations via horizontal gene transfer, including genes encoding urease, nitrite reductase, and V-type ATPase. The additional metabolic versatility conferred by acquired functions may have facilitated their radiation into a variety of subsurface, marine, and soil environments. We also provide evidence that each of the four AOA orders spans both marine and terrestrial habitats, which suggests a more complex evolutionary history for major AOA lineages than previously proposed. Together, these findings establish a robust phylogenomic framework of AOA and provide new insights into the ecology and adaptation of this globally abundant functional guild.

GPR97 deficiency suppresses Wnt/ß-catenin signaling in hypertensive nephropathy.

Accumulating evidence shows that renal fibrosis plays a key role in the development of hypertensive nephropathy (HTN). Therefore, a better understanding of the underlying mechanism of renal fibrosis regulation in HTN would be critical for designing rational strategies for therapeutic interventions. In this study, we revealed that GPR97, a novel identified adhesion G coupled receptor, plays an important role in the regulation of Wnt/ß-catenin signaling, which is the crucial driver of renal fibrosis in HTN. First, we identified that the expression of GPR97 correlated with the ß-catenin expression in renal biopsy from patients with HTN. Moreover, we found that GPR97 deficiency inhibited Wnt/ß-catenin signaling in mice with HTN, as evidenced by the reduction of ß-catenin expression and downstream target proteins, including MMP7 and Fibronectin. Mechanistically, we found that GPR97 could directly bind with Wnt1 in cultured tubular cells and TGF-ß1 treatment enhanced the binding ability of GPR97 and Wnt1. In addition, the gene silencing of GPR97 could decrease the Wnt1-induced fibrotic phenotype of tubular cells and inflammatory responses, suggesting that the binding of GPR97 and Wnt1 promoted Wnt/ß-catenin signaling. Collectively, our studies reveal that GPR97 is a regulator of Wnt/ß-catenin signaling in HTN, and targeting GPR97 may be a novel therapeutic strategy for HTN treatment.

Contextual modulation of the red-attractiveness effect: Differences in affiliation and competitive settings.

Color is not just about aesthetics but also communicates specific information and has important implications for psychological functioning. It has been shown that the color red enhances perceived attractiveness when evaluating the opposite sex, which we call the red-attractiveness effect. However, few studies have attached importance to the social context in which attractiveness ratings are made, which means that the red-attractiveness effect is rarely explained by analyzing the role of social context. We conducted two experiments to test the red-attractiveness effect in Chinese culture and the influence of context (affiliation or competitive) on the red-attractiveness effect. Experiment 1 (160 Chinese college students, 80 males) showed that the opposite-sex target in red, compared to white, was rated more attractive, and the red-attractiveness effect was applicable to Chinese culture. Experiment 2 (480 Chinese college students, 240 males) found that perceived attractiveness was strengthened in the affiliation context and weakened in the competitive context, that is, the main effect of context was significant. We did not find any significant effect of the color red in either context, that is, the color main effect was not significant. However, the results indicate that red can enhance perceived attractiveness when evaluating the opposite sex. This study demonstrates that the red attractiveness effect may exist in different cultural backgrounds and contexts.

HKDC1 promotes tumor immune evasion in hepatocellular carcinoma by coupling cytoskeleton to STAT1 activation and PD-L1 expression.

Immune checkpoint blockade (ICB) has shown considerable promise for treating various malignancies, but only a subset of cancer patients benefit from immune checkpoint inhibitor therapy because of immune evasion and immune-related adverse events (irAEs). The mechanisms underlying how tumor cells regulate immune cell response remain largely unknown. Here we show that hexokinase domain component 1 (HKDC1) promotes tumor immune evasion in a CD8+ T cell-dependent manner by activating STAT1/PD-L1 in tumor cells. Mechanistically, HKDC1 binds to and presents cytosolic STAT1 to IFNGR1 on the plasma membrane following IFNγ-stimulation by associating with cytoskeleton protein ACTA2, resulting in STAT1 phosphorylation and nuclear translocation. HKDC1 inhibition in combination with anti-PD-1/PD-L1 enhances in vivo T cell antitumor response in liver cancer models in male mice. Clinical sample analysis indicates a correlation among HKDC1 expression, STAT1 phosphorylation, and survival in patients with hepatocellular carcinoma treated with atezolizumab (anti-PD-L1). These findings reveal a role for HKDC1 in regulating immune evasion by coupling cytoskeleton with STAT1 activation, providing a potential combination strategy to enhance antitumor immune responses.

Conjugated linoleic acid (CLA) reduces HFD-induced obesity by enhancing BAT thermogenesis and iWAT browning via the CD36-AMPK pathway.

The antiobesity effect of conjugated linoleic acid (CLA) has been reported. However, the underlying mechanisms have not been fully clarified. Thus, this study aimed to investigate the effects of CLA on thermogenesis of interscapular brown adipose tissue (iBAT) and browning of inguinal subcutaneous white adipose tissue (iWAT) and explore the possible signaling pathway. The in vivo results showed that CLA enhanced the O2 consumption and heat production in HFD (high-fat diet)-fed female mice by roughly 38%. Meanwhile, CLA increased the average iBAT temperature by 2°C at the room temperature and cold exposure, respectively. Correspondingly, CLA caused 1.6- and 2.4-fold increases in the expression of UCP1 (uncoupling protein 1) of BAT and iWAT, respectively, suggesting the activated iBAT thermogenesis and iWAT browning in HFD-fed female mice. Meanwhile, CLA could promote the formation of brown and beige adipocytes in differentiated stromal vascular cells (SVCs) isolated from iBAT and iWAT (the expressions of UCP1 were promoted by about twofold changes). In possible mechanisms, CLA stimulated the expression of CD36 and the activation of the AMPK pathway in mice iBAT and iWAT as well as the differentiated SVCs. However, inhibition of CD36 and AMPK (adenosine 5'-monophosphate-activated protein kinase) abolished the promotive effects of CLA on brown and beige adipocytes formation. Hence, we showed that CLA reduced HFD-induced obesity through enhancing iBAT thermogenesis and iWAT browning via the  CD36-AMPK pathway.