C8-ceramide modulates microglia BDNF expression to alleviate postoperative cognition dysfunction via PKCδ/NF-κB signaling pathway.

Postoperative cognitive dysfunction (POCD) is a kind of serious postoperative complication in surgery with general anesthesia and it may affect patients' normal lives. Activated microglia are thought to be one of the key factors in the regulation of POCD process. Once activated, resident microglia change their phenotype and secrete kinds of cytokines to regulate inflammatory response in tissues. Among these secretory factors, brain-derived neurotrophic factor (BDNF) is considered to be able to inhibit inflammation response and protect nervous system. Therefore, the enhancement of BDNF expression derived from resident microglia is suggested to be potential treatment for POCD. In our study, we focused on the role of C8-ceramide (a kind of interventional drug) and assessed its regulatory effect on improving the expression of BDNF secreted from microglia to treat POCD. According to the results of our study, we observed that C8-ceramide stimulated primary microglia to up-regulate the expression of BDNF mRNA after being treated with lipopolysaccharide (LPS) in vitro. We proved that C8-ceramide had ability to effectively improve POCD of mice after being accepted carotid artery exposure and their abnormal behavior recovered better than that of mice from the surgery group. Furthermore, we also demonstrated that C8-ceramide enhanced the cognitive function of mice via the PKCδ/NF-κB signaling pathway. In general, our study has confirmed a potential molecular mechanism that led to the occurrence of POCD caused by surgery and provided a new clinical strategy to treat POCD.

Enhanced Bioactivity of Enzyme/MOF Biocomposite via Host Framework Engineering.

This study reports the successful development of a sustainable synthesis protocol for a phase-pure metal azolate framework (MAF-6) and its application in enzyme immobilization. An esterase@MAF-6 biocomposite was synthesized, and its catalytic performance was compared with that of esterase@ZIF-8 and esterase@ZIF-90 in transesterification reactions. Esterase@MAF-6, with its large pore aperture, showed superior enzymatic performance compared to esterase@ZIF-8 and esterase@ZIF-90 in catalyzing transesterification reactions using both n-propanol and benzyl alcohol as reactants. The hydrophobic nature of the MAF-6 platform was shown to activate the immobilized esterase into its open-lid conformation, which exhibited a 1.5- and 4-times enzymatic activity as compared to free esterase in catalyzing transesterification reaction using n-propanol and benzyl alcohol, respectively. The present work offers insights into the potential of MAF-6 as a promising matrix for enzyme immobilization and highlights the need to explore MOF matrices with expanded pore apertures to broaden their practical applications in biocatalysis.

Spinning Liquid Metal Droplets on Ice.

The non-contact and non-wetting droplet motion isolated from the solid surface has a high degree of freedom and thus can exhibit many peculiar interfacial phenomena. Here, an experimental phenomenon of spinning liquid metal droplets on an ice block is discovered, which adopts the dual solid-liquid phase transition of the liquid metal and the ice. The whole system is somewhat a variant of the classic Leidenfrost effect, which directly uses the latent heat released by the spontaneous solidification of the liquid metal droplet as a heat source to melt the ice and create an intervening lubricant water film. Interestingly, it is found that the droplets on ice become very mobile and undergo rapid spin as the solidification process proceeds. A series of comparative experiments clarify that the circumferential driving force comes from the escaping bubbles as the ice melts. Furthermore, by comparing the motion characteristics of different kinds of liquid metal droplets and solid balls on ice and investigating their physical properties and heat transfer, it is disclosed that the spin effect can be universal for objects of different materials, as long as the two necessary elements of rapid liquid film establishment and gas bubble release can be satisfied simultaneously.

Deep causal feature extraction and inference with neuroimaging genetic data.

Alzheimer's disease (AD) is a severe public health issue in the world. Magnetic Resonance Imaging (MRI) offers a way to study brain differences between AD patients and healthy individuals through feature extraction and comparison. However, in most previous works, the extracted features were not aimed to be causal, hindering biological understanding and interpretation. In order to extract causal features, we propose using instrumental variable (IV) regression with genetic variants as IVs. Specifically, we propose Deep Feature Extraction via Instrumental Variable Regression (DeepFEIVR), which uses a nonlinear neural network to extract causal features from three-dimensional neuroimages to predict an outcome (eg, AD status in our application) while maintaining a linear relationship between the extracted features and IVs. DeepFEIVR not only can handle high dimensional individual-level data for model building, but also is applicable to GWAS summary data to test associations of the extracted features with the outcome in subsequent analysis. In addition, we propose an extension of DeepFEIVR, called DeepFEIVR-CA, for covariate adjustment (CA). We apply DeepFEIVR and DeepFEIVR-CA to the Alzheimer's Disease Neuroimaging Initiative (ADNI) individual-level data as training data for model building, then apply to the UK Biobank neuroimaging and the International Genomics of Alzheimer's Project (IGAP) AD GWAS summary data, showcasing how the extracted causal features are related to AD and various brain endophenotypes.

Silencing the triacylglycerol lipase (TGL) gene decreases the number of apyrene sperm and inhibits oviposition in Sitotroga cerealella.

Triacylglycerol lipase (TGL) is an essential lipid metabolism enzyme that also plays a critical role in energy metabolism; however, how it regulates other life processes is unknown. To investigate the functional role of TGL in moth reproduction, males Sitotroga cerealella were used as a model. The TGL gene was cloned and analysed. The results showed that the open reading frame of TGL was 1968 bp long and contained three conserved regions. TGL gene expression was higher in the larval and early adult stages than in the pupal stage, with the highest levels observed in the fat body, testis and accessory glands during the early adult stage. Moreover, after TGL in male adults was silenced through RNAi, the protein content in male accessory glands remained unchanged, and the spermatophore transferred into females mated with TGL-silenced males became small and empty; meanwhile, the number of apyrene sperm in the spermatophore was significantly reduced due to the reduction of apyrene sperm in males, which eventually led to the significant reduction of egg-laying amount. All of the findings suggest that TGL regulates the amount of sperm in male moths as well as the morphology and quality of spermatophores transferred to females after mating with treated males, implying that TGL is critical for Sitotroga cerealella's reproductive process.

Generation of rotational orbital angular momentum beams in the radio frequency based on an optical-controlled circular antenna array.

The orbital angular momentum (OAM) has been widely used in the wireless short-range communication system, but for long-distance communication, the huge difficulty of beam receiving is a great challenge. In this paper, to overcome this challenge, a generation system of radio-frequency rotational orbital angular momentum (RF-ROAM) beams based on an optical-controlled circular antenna array (CAA) is proposed. The ROAM beam is an OAM beam rotating at a certain speed around the beam axis. According to the rotational Doppler effect, the rotation of the OAM beam will induce a frequency shift proportional to the OAM mode and the rotation speed. Thereby, by rotating an OAM beam at a fixed speed scheduled in advance in the transmitting end, the beam can be mode-distinguished by just detecting the frequency shift without receiving the whole wavefront vertical to the beam axis in the receiving end. This provides a partial reception scheme for the OAM-based wireless communication system. The generation system of RF-ROAM beams is proposed and constructed, and the proof-of-concept experiment is performed. In the system, the optical-controlled CAA is constructed to generate the general RF-OAM beam, the optical signal processor (OSP) is employed to control the phase shifts to further control the OAM mode, and the signal with time-varying phase is generated as the rotation factor to control the rotation speed. In the experiment, the RF-ROAM beams with different mode and mode combination are generated and successfully measured by detecting the frequency shift of the signal received in a fixed point.

2-Methoxyestradiol synergizes with Erlotinib to suppress hepatocellular carcinoma by disrupting the PLAGL2-EGFR-HIF-1/2α signaling loop.

Erlotinib, an EGFR tyrosine kinase inhibitor has been introduced into cancer chemotherapy. However, the therapeutic effects of erlotinib in hepatocellular carcinoma (HCC) remain vaguely understood. Our previous study found that a hypoxia-mediated PLAGL2-EGFR-HIF-1/2α signaling loop in HCC decreased response to erlotinib. The current study has demonstrated that the combination of erlotinib and 2ME2 exerted synergistic antitumor effects against HCC. Further investigation showed that erlotinib increased the expression level of EGFR, HIF-2α, and PLAGL2, which contributes to the insensitivity of hypoxic HCC cells to erlotinib. The simultaneous exposure to 2ME2 effectively inhibited the expression level of EGFR, HIF-2α, and PLAGL2 that was induced by erlotinib. This contributes to the synergistic effect of the two therapeutic agents. Furthermore, the combination of erlotinib and 2ME2 induced apoptosis and inhibited the stemness of hypoxic HCC cells. Our findings potentially explain the mechanism of HCC insensitivity to erlotinib and provide a new strategy of combining EGFR and HIF1/2α inhibitors for HCC treatment.

The seasonal profile of proliferation and apoptosis in the prostate gland of the wild ground squirrel (Spermophilus dauricus).

The seasonal cycle of growth and regression in the prostate gland of wild ground squirrel provide a unique research model to understand the morphological changes of prostate glands. Our previous studies showed that the local production of dihydrotestosterone could affect the morphology and function of the prostate gland in either an autocrine or paracrine manner. In the present study, we attempted to gain more insight into this process by investigating the expression of key factors implicated in cell proliferation, apoptosis, and the cell cycle, including mechanistic target of rapamycin (mTOR), cyclin-D2, p21, p27 and retinoblastoma 1 (pRB). Morphological and histological observations confirmed that the prostate increased significantly in both size and weight during the breeding season. Positive immunostaining for proliferating cell nuclear antigen (PCNA) was mainly localized to the prostate epithelial cells during the breeding season, which is significantly higher in the prostate gland during the breeding season (2470 ± 81/mm2) than that in the nonbreeding season (324 ± 54/mm2). However, there was no significant difference in the prostate gland when compared between the breeding and nonbreeding seasons, with regards to TUNEL staining. Moreover, cell cycle regulators were mainly localized to the epithelial cells, including mTOR, cyclin-D2, p21, p27 and pRB. the immunostaining of mTOR and cyclin D2 were stronger during the breeding season, whereas the immunostaining of p27 and pRB were stronger during the nonbreeding season. The mRNA expression levels of mTOR, cyclin D2, and PCNA, were higher during the breeding season while those of p27 and p21 were higher during the nonbreeding season. Collectively, this study profiled the distinct expression pattern of key cell cycle regulators throughout the breeding and nonbreeding seasons. Collectively, these factors may play important roles in regulating the seasonal growth and regression of the prostatic epithelium in the wild ground squirrel.

Seasonal expressions of prostaglandin E synthases and receptors in the prostate of the wild ground squirrel (Spermophilus dauricus).

The prostate gland is a male accessory reproductive gland, whose vitality and function are under tight regulation of different hormones. Prostaglandins E2 (PGE2) is one of the major products generated by the actions of cyclooxygenases (COX) and prostaglandin E synthase (PTGES) on arachidonic acid, and is involved in a number of physiological and pathological processes. In this study, we investigated the seasonal immunolocalizations and expressions of COX-1, COX-2 and PTGES, as well as PGE2 receptors (PTGERs) subtypes 1-4 (EP1, EP2, EP3, EP4) in the prostate of the wild ground squirrel. Histological examination observed enlarged prostatic lumens in the breeding season and significantly shrunken lumens in the nonbreeding season. COX-1, COX-2, PTGES and PTGERs were mainly localized in epithelial and stromal cells in the breeding and nonbreeding seasons. The mRNA expression levels of Cox-1, Cox-2, Ptges, Ptger2 (encoding EP2) and Ptger4 (encoding EP4) were higher in the prostate of the breeding season than in the nonbreeding season. The relative mRNA levels of Cox-1, Cox-2, Ptges, Ptger2 and Ptger4 were positively correlated with prostatic weights. In addition, both the prostatic and plasma concentrations of PGE2 were significantly higher in the breeding season compared to the nonbreeding season. These results suggested that PGE2 synthesis and signaling might play an important autocrine or paracrine role in the regulation of seasonal changes in the prostatic function of the wild ground squirrel.

Integrin and transcriptomic profiles identify a distinctive synovial CD8+ T cell subpopulation in spondyloarthritis.

OBJECTIVES: Current evidence suggests that immune events in the gut may impact joint inflammation in ankylosing spondylitis (AS) but the expression of gut-related trafficking molecules in the inflammed joint is poorly characterised. We aimed to (1) assess differential expression patterns of trafficking molecules between patients and controls, (2) generate joint-specific cellular signatures and (3) obtain transcriptomic profiles of noteworthy cell subpopulations. METHODS: Male subjects under 40 years of age fulfilling the mNY criteria were recruited. The following cells were surface stained using a 36-marker mass cytometry antibody panel: (1) peripheral blood mononuclear cells from AS patients, and healthy controls; (2) synovial fluid mononuclear cells from AS and rheumatoid arthritis (RA) patients. Additionally, RNA-seq was performed on CD8+ T cell subpopulations from the synovial fluid (SF). RESULTS: Mature CD8+ T cells were enriched in AS SF, with a distinct pattern of integrin expression (ß7, CD103, CD29 and CD49a). RNA-seq analysis of SF-derived CD103+CD49a+CD8+ T cells revealed elevated TNFAIP3, GZMB, PRF1 and IL-10. CONCLUSIONS: We have identified a novel integrin-expressing mature CD8+ T cell population (CD49a+CD103+ß7+CD29+) that appears to be more prevalent in AS SF than RA SF. These cells seem to possess dual cytotoxic and regulatory profiles which may play a role in AS pathogenesis.

Seasonal expressions of COX-1, COX-2 and EP4 in the uteri of the wild Daurian ground squirrels (Spermophilus dauricus).

Prostaglandins (PGs) play a pivotal role in uterine reproductive process including maternal recognition of pregnancy, cell proliferation, and myometrium contractions in mammals. In this study, we investigated the immunolocalizations and expression levels of Prostaglandin E2 synthases cyclo-oxygenase (COX)-1 and COX-2, as well as one of PGE2 receptor subtypes 4 (EP4) in the uteri of the wild Daurian ground squirrels (Spermophilus dauricus) during the breeding and non-breeding seasons. Histologically, the thickness of endometrium: myometrium ratio in the uteri of the breeding season was higher than that of the non-breeding season. The immunostainings of COX-1, COX-2 and EP4 were observed in stromal cells, glandular cells and myometrium cells in the breeding and non-breeding seasons. The protein and mRNA expression levels of COX-1, COX-2 and EP4 were higher in the uteri of the breeding season than those of in the non-breeding season. The mean mRNA levels of COX-1, COX-2 and EP4 were positively correlated with uterine weights. In addition, the PGE2 concentration of uterine tissues as well as plasma PGE2, 17ß-estradiol, progesterone, LH and FSH levels were also significantly higher in the breeding season compared to those of the non-breeding season. These results suggested that PGE2 might play an important autocrine or paracrine role in the regulation of seasonal changes in the uterine functions of the wild Daurian ground squirrels during the breeding and non-breeding seasons.

IL-7 primes IL-17 in mucosal-associated invariant T (MAIT) cells, which contribute to the Th17-axis in ankylosing spondylitis.

OBJECTIVE: Ankylosing spondylitis (AS) is a chronic inflammatory disease of unknown origin in which interleukin (IL) 17 has been genetically and therapeutically recognised as a key player. Identification of the cellular sources and inducers of IL-17 is crucial in our understanding of the drivers of inflammation in AS. Recently, mucosal-associated invariant T (MAIT) cells have been implicated in autoimmune diseases. Their gut origin, effector phenotype and expression of multiple AS-associated genes, such as IL7R and IL23R, makes them potential contributors to the pathogenesis of AS. METHODS: Mononuclear cells from patients with AS, healthy controls (HCs) and patients with rheumatoid arthritis were isolated from blood and synovial fluid (SF). Flow cytometry was used to identify MAIT cells. Phenotype was assessed by intracellular staining for cytokines and granzyme. Function was assessed by antigen-specific stimulation using Salmonella, or antigen non-specific activation via priming with IL-7 or IL-23. RESULTS: MAIT cells were reduced in frequency in the blood of patients with AS compared with HCs, yet patients with AS had an elevated frequency IL-17A+ MAIT cells. There was an enrichment of MAIT cells in SF, which had an exaggerated IL-17 phenotype. IL-17 elevation in AS MAIT cells was dependent on priming with IL-7 but not IL-23 or antigen stimulation. The AS-associated IL7R single nucleotide polymorphism (SNP), rs11742270, had no effect on IL-7R expression or function in the experiments performed. CONCLUSIONS: This study reveals a potential role for MAIT cells in patients with AS and is the first linking IL-7 to the elevated IL-17 profile in patients through the AS-associated risk gene IL7R.

Digital financial inclusion and upgrading of consumption structure: Evidence from rural China.

Based on the perspective of spatial economy, this paper focuses on the primary effects and spatial characteristics of Digital Financial Inclusion (DFI) on the upgrading of rural consumption structure (URCS) in China, conducting a literature review and theoretical analysis. It then uses statistical data collected over the years and the Digital Financial Inclusion Index (DFII) of Peking University to prepare panel data for 31 provinces in China (aside from Hong Kong, Macao, and Taiwan) from 2011 to 2020 for empirical testing. The results are as follows: DFI can considerably boost URCS, and there is a strong spatial neighbor impact, that is, it is affected by random shocks in surrounding provinces via its spatial effect; DFI has nonlinear characteristics in the process of fostering URCS, with the threshold variables of income level and family sizes; the impact of DFI on URCS is spatially heterogeneous, and the promotion of the eastern region is better than other zones. These results can inform policymakers about rural development and provide valuable references to push forward rural vitalization.

Biochemical characterization of a novel ß-galactosidase from Pedobacter sp. with strong transglycosylation activity at low lactose concentration.

A novel ß-galactosidase gene (PbBgal35A) from Pedobacter sp. CAUYN2 was cloned and expressed in Escherichia coli. The gene had an open reading frame of 1917 bp, encoding 638 amino acids with a predicted molecular mass of 62.3 kDa. The deduced amino acid sequence of the gene shared the highest identity of 41% with a glycoside hydrolase family 35 ß-galactosidase from Xanthomonas campestris pv. campestris (AAP86763.1). The recombinant ß-galactosidase (PbBgal35A) was purified to homogeneity with a specific activity of 65.9 U/mg. PbBgal35A was optimally active at pH 5.0 and 50 °C, respectively, and it was stable within pH 4.5‒7.0 and up to 45 °C. PbBgal35A efficiently synthesized galacto-oligosaccharides from lactose with a conversion ratio of 32% (w/w) and fructosyl-galacto-oligosaccharides from lactulose with a conversion ratio of 21.9% (w/w). Moreover, the enzyme catalyzed the synthesis of galacto-oligosaccharides from low-content lactose in fresh milk, and the GOS conversion ratios of 17.1% (w/w) and 7.8% (w/w) were obtained when the reactions were performed at 45 and 4 °C, respectively. These properties make PbBgal35A an ideal candidate for commercial use in the manufacturing of GOS-enriched dairy products.

Near-infrared AIEgens for sulfatase imaging in breast cancer in vivo.

Aggregation-induced emission luminogens (AIEgens) enable highly sensitive and in situ visualization of sulfatase to benefit the early diagnosis of breast cancer (BC), but current sulfatase AIEgens always emit visible light (<650 nm). Herein, a near-infrared (NIR) AIEgen QMT-SFA is developed for sulfatase imaging in vivo. Hydrophilic QMT-SFA is cleaved by sulfatase to yield hydrophobic QMT-OH, which subsequently aggregates into nanoparticles to turn the AIE fluorescence "on", enabling sensitive sulfatase imaging in 4T1 cells and mouse models.

Multi-stimulus perception and visualization by an intelligent liquid metal-elastomer architecture.

Multi-stimulus responsive soft materials with integrated functionalities are elementary blocks for building soft intelligent systems, but their rational design remains challenging. Here, we demonstrate an intelligent soft architecture sensitized by magnetized liquid metal droplets that are dispersed in a highly stretchable elastomer network. The supercooled liquid metal droplets serve as microscopic latent heat reservoirs, and their controllable solidification releases localized thermal energy/information flows for enabling programmable visualization and display. This allows the perception of a variety of information-encoded contact (mechanical pressing, stretching, and torsion) and noncontact (magnetic field) stimuli as well as the visualization of dynamic phase transition and stress evolution processes, via thermal and/or thermochromic imaging. The liquid metal-elastomer architecture offers a generic platform for designing soft intelligent sensing, display, and information encryption systems.

Phase change composites of octadecane and gallium with expanded graphite as a carrier.

Phase change materials (PCMs) have attracted more and more attention in the field of energy and thermal management due to the characteristic of exchanging heat with small temperature change. In order to obtain perfect PCMs, previous researchers usually prepared various phase change composites (PCCs), but there is still a gap toward the goal. Perhaps the development of PCMs with adjustable properties in a wide range to meet different needs is a feasible option. Given that the properties of organic PCMs and metal PCMs are highly complementary, using expanded graphite (EG) as a mediator, a stable PCC of octadecane and gallium that are difficult to directly mix, was successfully prepared. Octadecane and gallium are stored in the microstructures of EG, and the microstructures of EG play the role of storing nucleation embryos, and the suppression of supercooling can reach more than 86.82%. The test results showed that the properties of the PCC are indeed a balance between octadecane and gallium, and can be adjusted in a wide range. The PCC also has good structural and chemical stability, which can effectively avoid the corrosion risk caused by gallium leakage. The PCC samples containing equal amounts of gallium and paraffin were selected for thermal management performance tests. The results indicated that the PCC has application potential in related fields, and can provide a reference for the development of other PCCs.

LM-Jelly: Liquid Metal Enabled Biomimetic Robotic Jellyfish.

Jellyfish have attracted worldwide attention owing to their fantastic moving styles, which also inspired development in soft robotics to meet the demands of underwater surveillance. In this study, a soft robotic jellyfish integrated liquid metal coil, and magnetic field is proposed for the first time to mimic the soft rowing propulsion of oblate jellyfish. The soft robotic jellyfish is actuated by the entirely soft electromagnetic actuators that enabled the gentle motion. Through conceptual experiments and computational fluid dynamics simulations, we systematically interpreted the mechanism of this robotic jellyfish and various factors to dominate its movement behaviors, which involve vortex formation and ascending modalities. Besides, underwater monitoring and bio-friendliness of robotic jellyfish were also demonstrated to illustrate its potential application scenarios and gentle motion characteristics. This study will help to broaden the vistas for liquid metal enabled bionic robotics in a wide range of underwater applications.

Synergistic Effect of Two Plasticizers on Thermal Stability, Transparency, and Migration Resistance of Zinc Arginine Stabilized PVC.

The effect of different plasticizers on thermal stability, transparency, and migration resistance of the PVC stabilized with zinc arginine [Zn(Arg)2] was investigated. The thermal stability, migration resistance, and transparency of PVC with tributyl citrate (TBC) were better than PVC with dioctyl phthalate (DOP) characterized by oven aging method, migration test, and near infrared-visible-ultraviolet spectrophotometer. At the same time, the longer the carbon chain in citric acid esters, the better the thermal stability and transparency of PVC sample. The hydroxyl group in citric acid esters is helpful to improve the thermal stability of PVC samples. However, the elongation at break and Tg value of PVC containing DOP were very close to those of PVC containing TBC. The calculation results of Hansen solubility parameters also illustrated that DOP had better compatibility with PVC than TBC. Therefore, the excellent transparency and thermal stability of TBC plasticized PVC were attributed to the good compatibility between TBC and Zn(Arg)2, which was verified by the solubility test. Lastly, the mixture of dioctyl terephthalate (DOTP) and TBC was used as plasticizers for Zn(Arg)2 stabilized PVC. When the ratio of TBC and DOTP was 1:1, the transparency, thermal stability, and migration resistance of Zn(Arg)2 stabilized PVC samples were better than those of PVC plasticized by DOP or TBC alone. The mechanism was that the compatibility between Zn(Arg)2 and PVC was greatly improved by the synergetic effect of TBC and DOTP, resulting in the improvement of thermal stability, migration resistance, and transparency of PVC samples.