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Concentrations of the secondary bile acid, deoxycholic acid (DCA), are aberrantly elevated in colorectal cancer (CRC) patients, but the consequences remain poorly understood. Here, we screened a library of gut microbiota-derived metabolites and identified DCA as a negative regulator for CD8+ T cell effector function. Mechanistically, DCA suppressed CD8+ T cell responses by targeting plasma membrane Ca2+ ATPase (PMCA) to inhibit Ca2+-nuclear factor of activated T cells (NFAT)2 signaling. In CRC patients, CD8+ T cell effector function negatively correlated with both DCA concentration and expression of a bacterial DCA biosynthetic gene. Bacteria harboring DCA biosynthetic genes suppressed CD8+ T cells effector function and promoted tumor growth in mice. This effect was abolished by disrupting bile acid metabolism via bile acid chelation, genetic ablation of bacterial DCA biosynthetic pathway, or specific bacteriophage. Our study demonstrated causation between microbial DCA metabolism and anti-tumor CD8+ T cell response in CRC, suggesting potential directions for anti-tumor therapy.
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Neoplasias Colorretais , Microbioma Gastrointestinal , Humanos , Camundongos , Animais , Ácidos e Sais Biliares , Ácido Desoxicólico/farmacologia , Linfócitos T CD8-PositivosRESUMO
MiRNAs are regulatory molecules that can be packaged into exosomes and secreted from cells. Here, we show that adipose tissue macrophages (ATMs) in obese mice secrete miRNA-containing exosomes (Exos), which cause glucose intolerance and insulin resistance when administered to lean mice. Conversely, ATM Exos obtained from lean mice improve glucose tolerance and insulin sensitivity when administered to obese recipients. miR-155 is one of the miRNAs overexpressed in obese ATM Exos, and earlier studies have shown that PPARγ is a miR-155 target. Our results show that miR-155KO animals are insulin sensitive and glucose tolerant compared to controls. Furthermore, transplantation of WT bone marrow into miR-155KO mice mitigated this phenotype. Taken together, these studies show that ATMs secrete exosomes containing miRNA cargo. These miRNAs can be transferred to insulin target cell types through mechanisms of paracrine or endocrine regulation with robust effects on cellular insulin action, in vivo insulin sensitivity, and overall glucose homeostasis.
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Tecido Adiposo/citologia , Resistência à Insulina , Macrófagos/metabolismo , MicroRNAs/metabolismo , Adipócitos/metabolismo , Animais , Células Cultivadas , Glucose/metabolismo , Hepatócitos/metabolismo , Fígado/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Células Musculares/metabolismo , Músculo Esquelético/metabolismo , Transdução de SinaisRESUMO
Mitochondrial DNA (mtDNA) escaping stressed mitochondria provokes inflammation via cGAS-STING pathway activation and, when oxidized (Ox-mtDNA), it binds cytosolic NLRP3, thereby triggering inflammasome activation. However, it is unknown how and in which form Ox-mtDNA exits stressed mitochondria in non-apoptotic macrophages. We found that diverse NLRP3 inflammasome activators rapidly stimulated uniporter-mediated calcium uptake to open mitochondrial permeability transition pores (mPTP) and trigger VDAC oligomerization. This occurred independently of mtDNA or reactive oxygen species, which induce Ox-mtDNA generation. Within mitochondria, Ox-mtDNA was either repaired by DNA glycosylase OGG1 or cleaved by the endonuclease FEN1 to 500-650 bp fragments that exited mitochondria via mPTP- and VDAC-dependent channels to initiate cytosolic NLRP3 inflammasome activation. Ox-mtDNA fragments also activated cGAS-STING signaling and gave rise to pro-inflammatory extracellular DNA. Understanding this process will advance the development of potential treatments for chronic inflammatory diseases, exemplified by FEN1 inhibitors that suppressed interleukin-1ß (IL-1ß) production and mtDNA release in mice.
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Inflamassomos , Proteína 3 que Contém Domínio de Pirina da Família NLR , Animais , DNA Mitocondrial/metabolismo , Inflamassomos/metabolismo , Interferons/metabolismo , Camundongos , Mitocôndrias/metabolismo , Poro de Transição de Permeabilidade Mitocondrial , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Nucleotidiltransferases/metabolismoRESUMO
In obesity, macrophages and other immune cells accumulate in insulin target tissues, promoting a chronic inflammatory state and insulin resistance. Galectin-3 (Gal3), a lectin mainly secreted by macrophages, is elevated in both obese subjects and mice. Administration of Gal3 to mice causes insulin resistance and glucose intolerance, whereas inhibition of Gal3, through either genetic or pharmacologic loss of function, improved insulin sensitivity in obese mice. In vitro treatment with Gal3 directly enhanced macrophage chemotaxis, reduced insulin-stimulated glucose uptake in myocytes and 3T3-L1 adipocytes and impaired insulin-mediated suppression of glucose output in primary mouse hepatocytes. Importantly, we found that Gal3 can bind directly to the insulin receptor (IR) and inhibit downstream IR signaling. These observations elucidate a novel role for Gal3 in hepatocyte, adipocyte, and myocyte insulin resistance, suggesting that Gal3 can link inflammation to decreased insulin sensitivity. Inhibition of Gal3 could be a new approach to treat insulin resistance.
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Galectina 3/sangue , Galectina 3/metabolismo , Adipócitos/metabolismo , Adipócitos/patologia , Animais , Quimiotaxia , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/patologia , Galectina 3/antagonistas & inibidores , Galectina 3/genética , Hepatócitos/metabolismo , Hepatócitos/patologia , Humanos , Insulina/sangue , Resistência à Insulina , Macrófagos/imunologia , Macrófagos/patologia , Camundongos , Camundongos Knockout , Células Musculares/metabolismo , Células Musculares/patologia , Obesidade/imunologia , Obesidade/metabolismo , Obesidade/patologiaRESUMO
Polar auxin transport is unique to plants and coordinates their growth and development1,2. The PIN-FORMED (PIN) auxin transporters exhibit highly asymmetrical localizations at the plasma membrane and drive polar auxin transport3,4; however, their structures and transport mechanisms remain largely unknown. Here, we report three inward-facing conformation structures of Arabidopsis thaliana PIN1: the apo state, bound to the natural auxin indole-3-acetic acid (IAA), and in complex with the polar auxin transport inhibitor N-1-naphthylphthalamic acid (NPA). The transmembrane domain of PIN1 shares a conserved NhaA fold5. In the substrate-bound structure, IAA is coordinated by both hydrophobic stacking and hydrogen bonding. NPA competes with IAA for the same site at the intracellular pocket, but with a much higher affinity. These findings inform our understanding of the substrate recognition and transport mechanisms of PINs and set up a framework for future research on directional auxin transport, one of the most crucial processes underlying plant development.
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Proteínas de Arabidopsis , Arabidopsis , Ácidos Indolacéticos , Proteínas de Membrana Transportadoras , Apoproteínas/metabolismo , Arabidopsis/metabolismo , Proteínas de Arabidopsis/metabolismo , Transporte Biológico , Ligação de Hidrogênio , Interações Hidrofóbicas e Hidrofílicas , Ácidos Indolacéticos/metabolismo , Proteínas de Membrana Transportadoras/metabolismo , Ftalimidas/metabolismo , Conformação Proteica , Especificidade por SubstratoRESUMO
Exosomes are small extracellular vesicles that carry lipids, proteins, and microRNAs (miRNAs). They are released by all cell types and can be found not only in circulation but in many biological fluids. Exosomes are essential for interorgan communication because they can transfer their contents from donor to recipient cells, modulating cellular functions. The miRNA content of exosomes is responsible for most of their biological effects, and changes in exosomal miRNA levels can contribute to the progression or regression of metabolic diseases. As exosomal miRNAs are selectively sorted and packaged into exosomes, they can be useful as biomarkers for diagnosing diseases. The field of exosomes and metabolism is expanding rapidly, and researchers are consistently making new discoveries in this area. As a result, exosomes have great potential for a next-generation drug delivery platform for metabolic diseases.
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Exossomos , Doenças Metabólicas , MicroRNAs , Humanos , MicroRNAs/genética , MicroRNAs/metabolismo , Biomarcadores/metabolismo , Doenças Metabólicas/metabolismoRESUMO
BACKGROUND AND AIMS: In obesity, depletion of KCs expressing CRIg (complement receptor of the Ig superfamily) leads to microbial DNA accumulation, which subsequently triggers tissue inflammation and insulin resistance. However, the mechanism underlying obesity-mediated changes in KC complement immune functions is largely unknown. APPROACH AND RESULTS: Using KC-specific deactivated Cas9 transgenic mice treated with guide RNA, we assessed the effects of restoring CRIg or the serine/arginine-rich splicing factor 3 (SRSF3) abundance on KC functions and metabolic phenotypes in obese mice. The impacts of weight loss on KC responses were evaluated in a diet switch mouse model. The role of SRSF3 in regulating KC functions was also evaluated using KC-specific SRSF3 knockout mice. Here, we report that overexpression of CRIg in KCs of obese mice protects against bacterial DNA accumulation in metabolic tissues. Mechanistically, SRSF3 regulates CRIg expression, which is essential for maintaining the CRIg+ KC population. During obesity, SRSF3 expression decreases, but it is restored with weight loss through a diet switch, normalizing CRIg+ KCs. KC SRSF3 is also repressed in obese human livers. Lack of SRSF3 in KCs in lean and obese mice decreases their CRIg+ population, impairing metabolic parameters. During the diet switch, the benefits of weight loss are compromised due to SRSF3 deficiency. Conversely, SRSF3 overexpression in obese mice preserves CRIg+ KCs and improves metabolic responses. CONCLUSIONS: Restoring SRSF3 abundance in KCs offers a strategy against obesity-associated tissue inflammation and insulin resistance by preventing bacterial DNA accumulation.
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Resistência à Insulina , Células de Kupffer , Obesidade , Fatores de Processamento de Serina-Arginina , Animais , Fatores de Processamento de Serina-Arginina/metabolismo , Fatores de Processamento de Serina-Arginina/genética , Obesidade/metabolismo , Camundongos , Células de Kupffer/metabolismo , Humanos , Masculino , Camundongos Transgênicos , Camundongos Knockout , Modelos Animais de Doenças , Camundongos Endogâmicos C57BLRESUMO
Bronchopulmonary dysplasia (BPD) is a severe complication of preterm births, which develops due to exposure to supplemental oxygen and mechanical ventilation. Published studies demonstrated that the number of endothelial progenitor cells (EPC) is decreased in mouse and human BPD lungs and that adoptive transfer of EPC is an effective approach in reversing the hyperoxia-induced lung damage in mouse model of BPD. Recent advancements in macrophage biology identified the specific subtypes of circulating and resident macrophages mediating the developmental and regenerative functions in the lungs. Several studies reported the successful application of macrophage therapy in accelerating the regenerative capacity of damaged tissues and enhancing the therapeutic efficacy of other transplantable progenitor cells. In the present study, we explored the efficacy of combined cell therapy with EPC and resident alveolar macrophages (rAM) in hyperoxia-induced BPD mouse model. rAM and EPC were purified from neonatal mouse lungs and were used for adoptive transfer to the recipient neonatal mice exposed to hyperoxia. Adoptive transfer of rAM alone did not result in engraftment of donor rAM into the lung tissue but increased the mRNA level and protein concentration of proangiogenic CXCL12 chemokine in recipient mouse lungs. Depletion of rAM by chlodronate-liposomes decreased the retention of donor EPC after their transplantation into hyperoxia-injured lungs. Adoptive transfer of rAM in combination with EPC enhanced the therapeutic efficacy of EPC as evidenced by increased retention of EPC, increased capillary density, improved arterial oxygenation, and alveolarization in hyperoxia-injured lungs. Dual therapy with EPC and rAM has promise in human BPD.NEW & NOTEWORTHY Recent studies demonstrated that transplantation of lung-resident endothelial progenitor cells (EPC) is an effective therapy in mouse model of bronchopulmonary dysplasia (BPD). However, key factors regulating the efficacy of EPC are unknown. Herein, we demonstrate that transplantation of tissue-resident alveolar macrophages (rAM) increases CXCL12 expression in neonatal mouse lungs. rAM are required for retention of donor EPC in hyperoxia-injured lungs. Co-transplantation of rAM and EPC improves the efficacy of EPC therapy in mouse BPD model.
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Displasia Broncopulmonar , Quimiocina CXCL12 , Modelos Animais de Doenças , Células Progenitoras Endoteliais , Hiperóxia , Macrófagos Alveolares , Animais , Displasia Broncopulmonar/terapia , Displasia Broncopulmonar/patologia , Células Progenitoras Endoteliais/transplante , Células Progenitoras Endoteliais/metabolismo , Macrófagos Alveolares/metabolismo , Camundongos , Quimiocina CXCL12/metabolismo , Hiperóxia/terapia , Camundongos Endogâmicos C57BL , Animais Recém-Nascidos , Pulmão/patologia , Pulmão/metabolismo , Humanos , Transferência Adotiva/métodos , Transplante de Células-Tronco/métodosRESUMO
With the increasing demand for trace sample analysis, injecting trace samples into liquid chromatography-mass spectrometry (LC-MS) systems with minimal loss has become a major challenge. Herein, we describe an in situ LC-MS analytical probe, the Falcon probe, which integrates multiple functions of high-pressure sample injection without sample loss, high-efficiency LC separation, and electrospray. The main body of the Falcon probe is made of stainless steel and fabricated by the computer numerical control (CNC) technique, which has ultrahigh mechanical strength. By coupling a nanoliter-scale droplet reactor made of polyether ether ketone (PEEK) material, the Falcon probe-based LC-MS system was capable of operating at mobile-phase pressures up to 800 bar, which is comparable to those of conventional ultraperformance liquid chromatography (UPLC) systems. Using the probe pressing microamount in situ (PPMI) injection approach, the Falcon probe-based LC-MS system showed high separation efficiency and good repeatability with relative standard deviations (RSDs) of retention time and peak area of 1.8% and 9.9%, respectively, in peptide mixture analysis (n = 6). We applied this system to the analysis of a trace amount of 200 pg of HeLa protein digest and successfully identified an average of 766 protein groups (n = 5). By combining in situ sample pretreatment at the nanoliter range, we further applied the present system in single-cell proteomic analysis, and 241 protein groups were identified in single 293 cells, which preliminarily demonstrated its potential in the analysis of trace amounts of samples with complex compositions.
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Pressão , Humanos , Cromatografia Líquida/métodos , Espectrometria de Massas/métodos , Nanotecnologia , Polietilenoglicóis/química , Peptídeos/análise , Cromatografia Líquida de Alta Pressão , Células HeLa , Benzofenonas/análise , Benzofenonas/química , Polímeros/química , Cetonas/química , Cetonas/análise , Proteômica/métodosRESUMO
Characterizing the profiles of proteome and metabolome at the single-cell level is of great significance in single-cell multiomic studies. Herein, we proposed a novel strategy called one-shot single-cell proteome and metabolome analysis (scPMA) to acquire the proteome and metabolome information in a single-cell individual in one injection of LC-MS/MS analysis. Based on the scPMA strategy, a total workflow was developed to achieve the single-cell capture, nanoliter-scale sample pretreatment, one-shot LC injection and separation of the enzyme-digested peptides and metabolites, and dual-zone MS/MS detection for proteome and metabolome profiling. Benefiting from the scPMA strategy, we realized dual-omic analysis of single tumor cells, including A549, HeLa, and HepG2 cells with 816, 578, and 293 protein groups and 72, 91, and 148 metabolites quantified on average. A single-cell perspective experiment for investigating the doxorubicin-induced antitumor effects in both the proteome and metabolome aspects was also performed.
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Proteoma , Espectrometria de Massas em Tandem , Humanos , Proteoma/metabolismo , Cromatografia Líquida , Metaboloma , Células HeLaRESUMO
Discrete organometallic complexes with defined structures are proceeding rapidly in combating malignant tumors due to their multipronged treatment modalities. Many innovative superiorities, such as high antitumor activity, extremely low systemic toxicity, active targeting ability, and enhanced cellular uptake, make them more competent for clinical applications than individual precursors. In particular, coordination-induced regulation of luminescence and photophysical properties of organic light-emitting ligands has demonstrated significant potential in the timely evaluation of therapeutic efficacy by bioimaging and enabled synergistic photodynamic therapy (PDT) or photothermal therapy (PTT). This review highlights instructive examples of multimodal radiochemotherapy platforms for cancer ablation based on self-assembled metallacycles/metallacages, which would be classified by functions in a progressive manner. Finally, the essential demands and some plausible prospects in this field for cancer therapy are also presented.
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Neoplasias , Fotoquimioterapia , Humanos , Neoplasias/tratamento farmacológico , LuminescênciaRESUMO
Inspired by the superglue fuming method for fingerprint collection, this study developed a novel interfacial-fuming-induced surface instability process to generate wrinkled patterns on polymeric substrates. High-electronegativity groups are introduced on the substrate surface to initiate the polymerization of monomer vapors, such as ethyl cyanoacrylate, which results in the formation of a stiff poly(ethyl cyanoacrylate) capping layer. Moreover, interfacial polymerization resulted in the covalent bonding of the substrate, which led to the volumetric shrinkage of the composite and the accumulation of compressive strain. This process ultimately resulted in the development and stabilization of wrinkled surface morphologies. The authors systematically examined parameters such as the modulus of the epoxy substrate, prestrain, the flow rate of fuming, and operating temperature. The aforementioned technique can be easily applied to architectures with complex outer morphologies and inner surfaces, thereby enabling the construction of surface patterns under ambient conditions without vacuum limitations or precise process control. This study is the first to combine fuming-induced interfacial polymerization with surface instability to create robust wrinkles. The proposed method enables the fabrication of intricate microwrinkled patterns and has considerable potential for use in various practical applications, including microfluidics, optical components, bioinspired adhesive devices, and interfacial engineering.
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Gastroesophageal reflux disease (GERD) is a prevalent chronic ailment, and present therapeutic approaches are not always effective. This study aimed to find new drug targets for GERD and Barrett's esophagus (BE). We obtained genetic instruments for GERD, BE, and 2004 plasma proteins from recently published genome-wide association studies (GWAS), and Mendelian randomization (MR) was employed to explore potential drug targets. We further winnowed down MR-prioritized proteins through replication, reverse causality testing, colocalization analysis, phenotype scanning, and Phenome-wide MR. Furthermore, we constructed a protein-protein interaction network, unveiling potential associations among candidate proteins. Simultaneously, we acquired mRNA expression quantitative trait loci (eQTL) data from another GWAS encompassing four different tissues to identify additional drug targets. Meanwhile, we searched drug databases to evaluate these targets. Under Bonferroni correction (P < 4.8 × 10-5), we identified 11 plasma proteins significantly associated with GERD. Among these, 7 are protective proteins (MSP, GPX1, ERBB3, BT3A3, ANTR2, CCM2, and DECR2), while 4 are detrimental proteins (TMEM106B, DUSP13, C1-INH, and LINGO1). Ultimately, C1-INH and DECR2 successfully passed the screening process and exhibited similar directional causal effects on BE. Further analysis of eQTLs highlighted 4 potential drug targets, including EDEM3, PBX3, MEIS1-AS3, and NME7. The search of drug databases further supported our conclusions. Our study indicated that the plasma proteins C1-INH and DECR2, along with 4 genes (EDEM3, PBX3, MEIS1-AS3, and NME7), may represent potential drug targets for GERD and BE, warranting further investigation.
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Esôfago de Barrett , Refluxo Gastroesofágico , Estudo de Associação Genômica Ampla , Análise da Randomização Mendeliana , Locos de Características Quantitativas , Humanos , Esôfago de Barrett/genética , Esôfago de Barrett/tratamento farmacológico , Esôfago de Barrett/patologia , Refluxo Gastroesofágico/genética , Refluxo Gastroesofágico/tratamento farmacológico , Predisposição Genética para Doença , Mapas de Interação de Proteínas/genética , Polimorfismo de Nucleotídeo ÚnicoRESUMO
Three novel phragmalin-type limonoids, swieteliacates S-U (1-3), were isolated from Swietenia macrophylla leaves, alongside four previously identified limonoids (4-7). The structures, encompassing absolute configurations, were delineated through 1D and 2D NMR analyses, high-resolution mass spectrometry (HR-MS), and NMR and ECD calculations. Swieteliacate S (1) is a distinctive cryptate comprising a tricyclo[4.2.110,30.11,4]decane fragment and an additional five-membered oxygen ring. Compounds 3 and 5 exhibited inhibition rates of 26.08 ± 2.26% and 15.42 ± 3.66%, respectively, on triglyceride (TG) production in Hep G2 cells at 40 µM.
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Limoninas , Meliaceae , Limoninas/química , Limoninas/farmacologia , Estrutura Molecular , Espectroscopia de Ressonância Magnética , Meliaceae/químicaRESUMO
INTRODUCTION: Comprehensive geriatric assessment (CGA) is used to thoroughly assess and identify complex healthcare problems among older adults. However, administration of CGA is time-consuming and labor intensive. A simple screening tool with the mnemonic "FIND-NEEDS" was developed to quickly identify common geriatric conditions. The present study was to evaluate the clinimetric properties of the FIND-NEEDS. METHODS: The participants comprised first-visiting older adults aged 65 years and above (and who were able to communicate by themselves or with the help of a caregiver) who were assessed (October to December, 2021) using the FIND-NEEDS and CGA at geriatric outpatient clinics of a tertiary, referred medical center. The FIND-NEEDS was examined for its criterion-related validity and compared with the CGA results. Two types of scoring (summed score and binary score) of FIND-NEEDS and CGA were analyzed using Spearman correlation, sensitivity and specificity, and area under receiver operating characteristic curve (AUC). RESULTS: The mean age of the 114 outpatients was 78.3 ± 7.6 years, and 79 (69.3%) were female. The internal consistency was excellent when using all FIND-NEEDS items, and was acceptable when using domain scores. Exploratory factor analysis showed that most of the FIND-NEEDS domain scores had factor loadings higher than 0.3. Intercorrelations of binary scores between domains of FIND-NEEDS and CGA showed most domains were moderately correlated. The overall correlation of summed scores between FIND-NEEDS and CGA was high. The FIND-NEEDS summed score was moderately correlated with CGA score (r = 0.494; p < 0.001), and the binary score showed excellent correlation (r = 0.944; p < 0.001). When using the CGA score as the gold standard, the FIND-NEEDS showed excellent AUC (0.950), sensitivity (1.00), and specificity (0.90). DISCUSSION/CONCLUSION: The present study demonstrated that the FIND-NEEDS had acceptable clinimetric properties to screen for geriatric problems among older adults. Further in-depth assessment and care plan can then be conducted afterwards.
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Innovative design of smart organic materials is of great importance for the advancement of modern technology. Macrocycle hosts, possessing cyclic skeletons, intrinsic cavities, and specific guest binding properties, have demonstrated pronounced potential for the elaborate fabrication of a variety of functional organic materials with smart stimuli-responsive characteristics. In this tutorial review, we outline the current development of smart organic materials based on macrocycle hosts as key building blocks, focusing on the design principles and functional mechanisms of the tailored systems. Three main types of macrocycle-based smart organic materials are exemplified as follows according to the distinct forms of construction patterns: (1) supramolecular polymeric materials and nanoassemblies; (2) adaptive molecular crystals; (3) smart porous organic materials. The responsive performances of macrocycle-containing smart materials in versatile aspects, including mechanically adaptive polymers, soft optoelectronic devices, data encryption, drug delivery systems, artificial transmembrane channels, crystalline-state gas adsorption/separation, and fluorescence sensing, are illustrated by discussing the representative studies as paradigms, where the roles of macrocycles in these systems are highlighted. We also provide in the conclusion part the perspectives and remaining challenges in this burgeoning field.
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Environmental mapping and robot navigation are the basis for realizing robot automation in modern agricultural production. This study proposes a new autonomous mapping and navigation method for gardening scene robots. First, a new LiDAR slam-based semantic mapping algorithm is proposed to enable the robots to analyze structural information from point cloud images and generate roadmaps from them. Secondly, a general robot navigation framework is proposed to enable the robot to generate the shortest global path according to the road map, and consider the local terrain information to find the optimal local path to achieve safe and efficient trajectory tracking; this method is equipped in apple orchards. The LiDAR was evaluated on a differential drive robotic platform. Experimental results show that this method can effectively process orchard environmental information. Compared with vnf and pointnet++, the semantic information extraction efficiency and time are greatly improved. The map feature extraction time can be reduced to 0.1681 s, and its MIoU is 0.812. The resulting global path planning achieved a 100% success rate, with an average run time of 4ms. At the same time, the local path planning algorithm can effectively generate safe and smooth trajectories to execute the global path, with an average running time of 36 ms.
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The prosperous advancement of supramolecular chemistry has motivated us to construct supramolecular hybrid materials with integrated functionalities. Herein, we report an innovative type of macrocycle-strutted coordination microparticle (MSCM) using pillararenes as the struts and "pockets", which performs unique activities of fluorescence-monitored photosensitization and substrate-selective photocatalytic degradation. Prepared via a convenient one-step solvothermal method, MSCM showcases the incorporation of supramolecular hybridization and macrocycles, endowed with well-ordered spherical architectures, superior photophysical properties, and photosensitizing capacity, where a self-reporting fluorescence response is exhibited upon photoinduced generation of multiple reactive oxygen species. Importantly, photocatalytic behaviors of MSCM show marked divergence toward three different substrates and reveal pronounced substrate-selective catalytic mechanisms, attributing to the variety in the affinity of substrates toward MSCM surfaces and pillararene cavities. This study brings new insight into the design of supramolecular hybrid systems with integrated properties and further exploration of functional macrocycle-based materials.
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OBJECTIVES: This study aimed to investigate the integrative effects and mechanisms of transcutaneous electrical acustimulation (TEA) on postprocedural recovery from endoscopic retrograde cholangio-pancreatography (ERCP). MATERIALS AND METHODS: A total of 86 patients for elective ERCP were randomly ordered to receive TEA (n = 43) at acupoints PC6 and ST36 or Sham-TEA (n = 43) at sham points from 24 hours before ERCP (pre-ERCP) to 24 hours after ERCP (PE24). Scores of gastrointestinal (GI) motility-related symptoms and abdominal pain, gastric slow waves, and autonomic functions were recorded through the spectral analysis of heart rate variability; meanwhile, circulatory levels of inflammation cytokines of tumor necrosis factor-α (TNF-α) and interleukin (IL)-10 and GI hormones of motilin, ghrelin, cholecystokinin (CCK), and vasoactive intestinal peptide (VIP) were assessed by enzyme-linked immunosorbent assay. RESULTS: 1) TEA, but not Sham-TEA, decreased the post-ERCP GI motility-related symptom score (2.4 ± 2.6 vs 7.9 ± 4.6, p < 0.001) and abdominal pain score (0.5 ± 0.7 vs 4.1 ± 2.7, p < 0.001) at PE24, and decreased the post-ERCP hospital day by 20.0% (p ï¼0.05 vs Sham-TEA); 2) TEA improved the average gastric percentage of normal slow waves and dominant frequency by 34.6% and 33.3% at PE24, respectively (both p < 0.001 vs Sham-TEA); 3) TEA, but not Sham-TEA, reversed the ERCP-induced increase of TNF-α but not IL-10 at PE24, reflected as a significantly lower level of TNF-α in the TEA group than in the Sham-TEA group (1.6 ± 0.5 pg/mL vs 2.1 ± 0.9 pg/mL, p ï¼ 0.01); 4) compared with Sham-TEA, TEA increased vagal activity by 37.5% (p ï¼ 0.001); and 5) TEA caused a significantly higher plasma level of ghrelin (1.5 ± 0.8 ng/ml vs 1.1 ± 0.7 ng/ml, p ï¼ 0.05) but not motilin, VIP, or CCK than did Sham-TEA at PE24. CONCLUSION: TEA at PC6 and ST36 accelerates the post-ERCP recovery, reflected as the improvement in GI motility and amelioration of abdominal pain, and suppression of the inflammatory cytokine TNF-α may mediate through both autonomic and ghrelin-related mechanisms.
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OBJECTIVES: To investigate community health centers' (CHCs) health literacy. DESIGN: A cross-sectional study. SAMPLE: A total of 374 CHCs were surveyed and 258 CHCs responded, with an effective questionnaire response rate of 69.0%. MEASUREMENTS: Data were collected by using a self-developed health literacy assessment tool to survey CHCs' health literacy throughout Taiwan from January to December 2019. RESULTS: The item of organizational health literacy (OHL) with the highest proportion of CHCs not implementing them was "Design of easy-to-use computer applications and new media" (47.3% not yet achieved), followed by "Involving target audiences in document and service development" (34.9% not yet achieved). CHCs located in northern Taiwan had higher health literacy achievement scores than those in other regions, and those in urban areas had higher health literacy achievement scores than those in general and remote areas. CONCLUSIONS: This study identified items with poor implementation of OHL and found regional differences in health literacy among CHCs. The findings can inform the development of targeted interventions to improve health literacy in underperforming CHCs and guide policymakers in allocating resources to regions and areas in need of.