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In this paper, we propose a deformed Reuleaux-triangle resonator (RTR) to form exceptional point (EP) which results in the detection sensitivity enhancement of nanoparticle. After introducing single nanoparticle to the deformed RTR at EP, frequency splitting obtains an enhancement of more than 6 times compared with non-deformed RTR. In addition, EP induced a result that the far field pattern of chiral mode responses significantly to external perturbation, corresponding to the change in internal chirality. Therefore, single nanoparticle with far distance of more than 4000 nm can be detected by measuring the variation of far field directional emission. Compared to traditional frequency splitting, the far field pattern produced in deformed RTR provides a cost-effective and convenient path to detect single nanoparticle at a long distance, without using tunable laser and external coupler. Our structure indicates great potential in high sensitivity sensor and label-free detector.
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Sepsis is a intricate pathological process characterized by life-threatening organ dysfunction resulting from a dysregulated host response to infection. It stands as a prominent cause of mortality among critically ill patients globally. The pivotal focus in sepsis management lies in the early identification and prompt administration of antimicrobial agents. Owing to the constraints of current diagnostic methodologies, marked by insufficient sensitivity and delayed outcomes, extensive research has been undertaken to ascertain novel biomarkers for sepsis. In this review, we provide an overview discussing the latest advancements in the study of PTX-3 as a biomarker for sepsis. We acknowledge pivotal discoveries from preceding research and engage in discourse regarding the challenges and limitations confronted by PTX-3 as a sepsis biomarker.
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We demonstrate a milli-Newton mechanical force sensor based on a whispering gallery mode microbottle resonator (MBR). A lever model is established by coupling the MBR with a tapered fiber, whose ratio of load arm to effort arm (RLE) is flexibly adjusted to enlarge the detection range. The mechanical force is induced by attaching a capillary on the MBR stem and applying the downward displacement, which deforms the MBR's radius and thus shifts the resonance wavelength. The dependence of the capillary displacement on the mechanical force is theoretically deduced and verified. Experimentally, the sensors with different RLEs are built, and the maximum sensitivity of -10.48â pm/mN with a resolution of 40â µN is obtained. The achieved detection range is 0-4â mN, which depends on the capillary displacement and RLE of the lever. With the merits of easy fabrication and flexible structure, the proposed sensor shows great potential in biomedical and structural health monitoring.
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In this study, PbS/Er co-doped fibers (PEDFs) were fabricated by atomic layer deposition (ALD) combined with modified chemical vapor deposition (MCVD). A pumping scheme based on two-photon absorption at 1310â nm of PEDF is proposed for L + band amplification. Through the theoretical analysis, the local environment of Er3+ is changed due to the co-doping of PbS, which improves the two-photon absorption efficiency near 1300â nm. Compared with the 980â nm pump, the PEDFs excited by the 1310â nm pump show better amplification performance in the L + band. And in a bi-directional pumping system, PEDF achieves over 22â dB of gain in the whole L band. In particular, the bandwidth of over 20â dB gain was extended to 1627â nm with a noise figure as low as 4.9â dB. To the best of our knowledge, this is the first time that a high-gain bandwidth of L band amplification has been extended to 1627â nm. The results of unsaturated loss also show that PbS co-doping improves the two-photon absorption efficiency of PEDF to broaden the amplification bandwidth of L + band. These results demonstrate that an effective L + band amplification method is practically provided for future ultra-wideband optical communications.
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Importance: Perceived social isolation is associated with negative health outcomes, including increased risk for altered eating behaviors, obesity, and psychological symptoms. However, the underlying neural mechanisms of these pathways are unknown. Objective: To investigate the association of perceived social isolation with brain reactivity to food cues, altered eating behaviors, obesity, and mental health symptoms. Design, Setting, and Participants: This cross-sectional, single-center study recruited healthy, premenopausal female participants from the Los Angeles, California, community from September 7, 2021, through February 27, 2023. Exposure: Participants underwent functional magnetic resonance imaging while performing a food cue viewing task. Main Outcomes and Measures: The main outcomes included brain reactivity to food cues, body composition, self-reported eating behaviors (food cravings, reward-based eating, food addiction, and maladaptive eating behaviors), and mental health symptoms (anxiety, depression, positive and negative affect, and psychological resilience). Results: The study included 93 participants (mean [SD] age, 25.38 [7.07] years). Participants with higher perceived social isolation reported higher fat mass percentage, lower diet quality, increased maladaptive eating behaviors (cravings, reward-based eating, uncontrolled eating, and food addiction), and poor mental health (anxiety, depression, and psychological resilience). In whole-brain comparisons, the higher social isolation group showed altered brain reactivity to food cues in regions of the default mode, executive control, and visual attention networks. Isolation-related neural changes in response to sweet foods correlated with various altered eating behaviors and psychological symptoms. These altered brain responses mediated the connection between social isolation and maladaptive eating behaviors (ß for indirect effect, 0.111; 95% CI, 0.013-0.210; P = .03), increased body fat composition (ß, -0.141; 95% CI, -0.260 to -0.021; P = .02), and diminished positive affect (ß, -0.089; 95% CI, -0.188 to 0.011; P = .09). Conclusions and Relevance: These findings suggest that social isolation is associated with altered neural reactivity to food cues within specific brain regions responsible for processing internal appetite-related states and compromised executive control and attentional bias and motivation toward external food cues. These neural responses toward specific foods were associated with an increased risk for higher body fat composition, worsened maladaptive eating behaviors, and compromised mental health. These findings underscore the need for holistic mind-body-directed interventions that may mitigate the adverse health consequences of social isolation.
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Señales (Psicología) , Salud Mental , Femenino , Humanos , Adulto , Estudios Transversales , Encéfalo/diagnóstico por imagen , Aislamiento Social , Conducta Alimentaria , ObesidadRESUMEN
Histamine receptor antagonists, which can bind to specific histamine receptors on target cells, exhibit substantial therapeutic efficacy in managing a variety of histamine-mediated disorders. Notably, histamine H1 and H2 receptor antagonists have been extensively investigated and universally acknowledged as recommended treatment agents for numerous allergic diseases and acid-related disorders, respectively. Historically, the combination of H1 and H2 receptor antagonists has been considered a classic treatment strategy, demonstrating relatively superior efficacy compared with single-drug therapies in the treatment of diverse histamine-mediated diseases. The latest emerging studies have additionally suggested the underlying roles of histamine and H1R and H2R in the development of anxiety disorders, arthritic diseases, and postexercise hypotension. Nevertheless, there is still a lack of systematic reviews on the clinical efficacy of combination therapy, greatly limiting our understanding of its clinical application. Here, we present a comprehensive overview of the current knowledge and perspectives regarding the combination of H1 and H2 histamine receptor antagonists in various histamine-mediated disorders. Furthermore, we critically analyze the adverse effects and limitations associated with combination therapy while suggesting potential solutions. Our review can offer a systematic summary and promising insights into the in-depth and effective application of the combination of H1 and H2 receptor antagonists.
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Sepsis-associated acute kidney injury presents as a critical condition characterized by prolonged hospital stays, elevated mortality rates, and an increased likelihood of transition to chronic kidney disease. Sepsis-associated acute kidney injury suppresses fatty acid oxidation and oxidative phosphorylation in the mitochondria of renal tubular epithelial cells, thus favoring a metabolic shift towards glycolysis for energy production. This shift acts as a protective mechanism for the kidneys. However, an extended reliance on glycolysis may contribute to tubular atrophy, fibrosis, and subsequent chronic kidney disease progression. Metabolic reprogramming interventions have emerged as prospective strategies to counteract sepsis-associated acute kidney injury by restoring normal metabolic function, offering potential therapeutic and preventive modalities. This review delves into the metabolic alterations of tubular epithelial cells associated with sepsis-associated acute kidney injury, stressing the importance of metabolic reprogramming for the immune response and the urgency of metabolic normalization. We present various intervention targets that could facilitate the recovery of oxidative phosphorylation-centric metabolism. These novel insights and strategies aim to transform the clinical prevention and treatment landscape of sepsis-associated acute kidney injury, with a focus on metabolic mechanisms. This investigation could provide valuable insights for clinicians aiming to enhance patient outcomes in the context of sepsis-associated acute kidney injury.
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This paper explores the relationship between the standardization studies of acupuncture prescriptions and translational medicine, elucidating the translational medical concepts in the standardization of acupuncture prescriptions. It emphasizes that the standardization of acupuncture prescriptions is a pivotal link in the transformation of foundational acupuncture research. Considering the current clinical status of acupuncture prescriptions, the paper proposes the elements for standardizing prescriptions to promote the translation of foundational acupuncture research into clinical practice. These elements encompass prescription structure, precise acupoint number, orderly techniques of acupuncture, quantification of procedures, and clarity in efficacy. The goal is to provide a new perspective for the development of translational medicine in acupuncture.
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Terapia por Acupuntura , Ciencia Traslacional Biomédica , Investigación , Prescripciones , Estándares de ReferenciaRESUMEN
Experiences of discrimination are associated with adverse health outcomes, including obesity. However, the mechanisms by which discrimination leads to obesity remain unclear. Utilizing multi-omics analyses of neuroimaging and fecal metabolites, we investigated the impact of discrimination exposure on brain reactivity to food images and associated dysregulations in the brain-gut-microbiome system. We show that discrimination is associated with increased food-cue reactivity in frontal-striatal regions involved in reward, motivation and executive control; altered glutamate-pathway metabolites involved in oxidative stress and inflammation as well as preference for unhealthy foods. Associations between discrimination-related brain and gut signatures were skewed towards unhealthy sweet foods after adjusting for age, diet, body mass index, race and socioeconomic status. Discrimination, as a stressor, may contribute to enhanced food-cue reactivity and brain-gut-microbiome disruptions that can promote unhealthy eating behaviors, leading to increased risk for obesity. Treatments that normalize these alterations may benefit individuals who experience discrimination-related stress.
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To enhance the capability of phase-sensitive optical time domain reflectometers (Φ-OTDR) to recognize disturbance events, an improved adaptive feature extraction method based on NMF-MFCC is proposed, which replaces the fixed filter bank used in the traditional method to extract the mel-frequency cepstral coefficient (MFCC) features by a spectral structure obtained from the Φ-OTDR signal spectrum using nonnegative matrix factorization (NMF). Three typical events on fences are set as recognition targets in our experiments, and the results show that the NMF-MFCC features have higher distinguishability, with the corresponding recognition accuracy reaching 98.47%, which is 7% higher than that using the traditional MFCC features.
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BACKGROUND: Cells and tissues, such as macrophages, express inducible nitric oxide synthase (INOS) after stimulation by certain factors. INOS helps mediate the macrophage inflammatory reaction, but few studies have explored how INOS affects macrophage function in nonalcoholic fatty liver disease (NAFLD). OBJECTIVE: This study investigated the role of INOS-mediated macrophage activity in NAFLD. METHODS: A high-fat diet was used to establish an NAFLD mouse model. After 12 weeks, blood was collected for immune cell and lipid analyses, and liver tissues were collected for pathological analyses with hematoxylin and eosin and Oil Red O staining. Peritoneal macrophages were extracted in situ, cultured in Dulbecco's modified Eagle's medium, and stimulated with palmitic acid to mimic in vivo conditions for further assays. Real-time polymerase chain reaction, western blot analysis, and immunofluorescence were used to verify the expression of target genes or proteins. RESULTS: In the NAFLD model, INOS expression in macrophages increased, and INOS knockdown significantly decreased the number of macrophages. Pathological examinations confirmed that INOS knockdown slowed NAFLD progression and macrophage infiltration during inflammation. INOS knockdown also enhanced phagocytosis and lipid transport by macrophages, and increased the expression of autophagy-related molecules in macrophages, which improved the autophagy level, promoted apoptotic cell degradation, and maintained intracellular environment homeostasis. CONCLUSIONS: These results indicate a correlation between INOS expression and macrophage function in NAFLD.
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Óxido Nítrico Sintasa de Tipo II , Enfermedad del Hígado Graso no Alcohólico , Animales , Ratones , Autofagia , Inflamación/metabolismo , Lípidos , Macrófagos/metabolismo , Óxido Nítrico Sintasa de Tipo II/genética , Óxido Nítrico Sintasa de Tipo II/metabolismoRESUMEN
Previously, we identified a highly conserved, γ-shaped RNA element (γRE) from satellite RNAs of cucumber mosaic virus (CMV), and we determined γRE to be structurally required for satRNA survival and the inhibition of CMV replication. It remains unknown how γRE biologically functions. In this work, pull-down assays were used to screen candidates of host factors from Nicotiana benthamiana plants using biotin-labeled γRE as bait. Nine host factors were found to interact specifically with γRE. Then, all of these host factors were down-regulated individually in N. benthamiana plants via tobacco rattle virus-induced gene silencing and tested with infection by GFP-expressing CMV (CMV-gfp) and the isolate T1 of satRNA (sat-T1). Out of nine candidates, three host factors, namely histone H3, GTPase Ran3, and eukaryotic translation initiation factor 4A, were extremely important for infection by CMV-gfp and sat-T1. Moreover, we found that cytosolic glyceraldehyde-3-phosphate dehydrogenase 2 contributed to the replication of CMV and sat-T1, but also negatively regulated CMV 2b activity. Collectively, our work provides essential clues for uncovering the mechanism by which satRNAs inhibit CMV replication.
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Cucumovirus , Infecciones por Citomegalovirus , Virus de Plantas , Satélite de ARN/genética , ARN , ARN de Planta , Plantas , Cucumovirus/genética , Nicotiana , Virus de Plantas/genética , Enfermedades de las Plantas , ARN Viral/genéticaRESUMEN
An extrinsic fiber optic Fabry-Perot interferometric (EFPI) ultrasonic sensor based on a grooved silicon diaphragm for partial discharge (PD) detection has been proposed. The size of the groove is determined by finite element simulation, which allows the resonant frequency of the sensor to meet the requirements of PD ultrasonic detection and improves the sensitivity of the sensor by 5.07 times compared with that based on a traditional circular diaphragm. The microelectro-mechanical system process is used to fabricate the diaphragm on a silicon-on-insulator wafer, and the prepared diaphragm has a grooved section with a diameter of 829.34 µm and a thickness of only 2.09 µm. At its resonant frequency of 61.5 kHz, the acoustic pressure sensitivity of the sensor is 172.42 mV/Pa. The ultrasonic signal detection capability of the sensor is verified in the PD experiment. Furthermore, the characteristics of the corona discharge are successfully manifested based on the ultrasonic waves detected by the EFPI sensor. It is demonstrated that the proposed sensor is suitable for PD detection due to its high sensitivity, simple production process, and good resistance to environmental interference.
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Angiogenesis is essential for the growth and metastasis of several malignant tumors including colorectal cancer (CRC). The molecular mechanism underlying CRC angiogenesis has not been fully elucidated. Emerging evidence indicates that secreted microRNAs (miRNAs) may mediate the intercellular communication between tumor cells and neighboring endothelial cells to regulate tumor angiogenesis. In addition, exosomes have been shown to carry and deliver miRNAs to regulate angiogenesis. miRNA N-72 is a novel miRNA that plays a regulatory role in the EGF-induced migration of human amnion mesenchymal stem cells. However, the relation between miRNA N-72 and cancer remains unclear. We here found that CRC cells could secrete miRNA N-72. A high miRNA N-72 level was detected in the serum of CRC patients and the cultured CRC cells. Moreover, the CRC cell-secreted miRNA N-72 could promote the migration, tubulogenesis, and permeability of endothelial cells. In addition, the mouse xenograft model was used to verify the facilitating effects of miRNA N-72 on CRC growth, angiogenesis, and metastasis in vivo. Further mechanism analysis revealed that CRC cell-secreted miRNA N-72 could be delivered into endothelial cells via exosomes, which then inhibited cell junctions of endothelial cells by targeting CLDN18 and consequently promoted angiogenesis. Our findings reveal a novel mechanism of CRC angiogenesis and highlight the potential of secreted miRNA N-72 as a therapeutic target and a biomarker for CRC.
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Regulatory T cells (Tregs) are an important component of the tumor microenvironment; however, the interaction between Tregs and gastric cancer cells is not completely understood. Recent studies have shown that Tregs participate in cancer cell stemness maintenance. In this study, we performed single-cell RNA sequencing of gastric cancer and adjacent tissues and found that Tregs with high TNF expression were recruited to gastric cancer tissues and were significantly correlated with patient survival. TNF+ Tregs significantly contribute to tumor growth and progression. Our studies have further demonstrated that TNF+ Tregs promote the stemness of gastric cancer cells through the IL13/STAT3 pathway. Therefore, blocking the interaction between TNF+ Tregs and gastric cancer cells may be a new approach in the treatment of gastric cancer.
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The interlayer distance optimized for low-loss and low-crosstalk double-layer polymer optical waveguides was investigated to enhance their transmission performance. Simulations were conducted to determine the minimal interlayer distances for double-layer optical waveguides with different core sizes. An optimal interlayer distance of 24â µm was identified for a 20â µm × 20â µm double-layer waveguide, which ensured interlayer crosstalk below -30â dB when roughness remained under 80â nm. The double-layer waveguides were fabricated employing ultraviolet lithography combined with the overlay alignment method. Based on experimental optimization, the important fabrication parameters were optimized, such as a plasma treatment time of 10 s, a core exposure dose of 500 mJ/cm2, and a cladding exposure dose of 240 mJ/cm2. Additionally, the fabricated double-layer waveguides, with an interlayer distance of 24.5â µm, exhibited low transmission losses of less than 0.25â dB/cm at 850â nm and 0.40â dB/cm at 1310â nm, respectively. The low interlayer crosstalk values were less than -52â dB at 850â nm and -60â dB at 1310â nm, respectively. The agreement between the experimental results and the simulation findings indicates that this method offers a promising approach for fabricating double-layer waveguides with good performances.
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In order to efficiently select the optimal cutting position of x-ray mono-capillary lenses, an improved sine cosine algorithm-crow search algorithm (SCA-CSA) algorithm is proposed, which combines the sine cosine algorithm with the crow search algorithm, with further enhancements. The fabricated capillary profile is measured using an optical profiler; then the surface figure error for interest regions of the mono-capillary can be evaluated using the improved SCA-CSA algorithm. The experimental results indicate that the surface figure error in the final capillary cut region is about 0.138 µm, and the runtime is 2.284 s. When compared with the traditional metaheuristic algorithm, the particle swarm optimization algorithm, the improved SCA-CSA algorithm, enhances the surface figure error metric by two orders of magnitude. Furthermore, the standard deviation index of the surface figure error metric for 30 runs also improves by more than 10 orders of magnitude, demonstrating the superior performance and robustness of the algorithm. The proposed method provides significant support for the development of precise cuttings of mono-capillaries.
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In-fiber whispering gallery mode (WGM) microsphere resonators have received remarkable attention due to the superiorities of compact structure, high stability and self-alignment. As an in-fiber structure, WGM microsphere resonators have been demonstrated in various applications, such as sensors, filters and lasers, which have significant impacts on modern optics. Herein, we review recent progress of in-fiber WGM microsphere resonators, which involve fibers of diverse structures and microspheres of different materials. First, a brief introduction is given to in-fiber WGM microsphere resonators, from structures to applications. Then, we focus on recent progresses in this field, including in-fiber couplers based on conventional fibers, capillaries and micro-structure hollow fibers, and passive/active microspheres. Finally, future developments of the in-fiber WGM microsphere resonators are envisioned.
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It has been proposed that cancer stem cells (CSCs) are responsible for almost all malignant phenotypes of tumors. Long non-coding RNA WT1 antisense RNA (WT1-AS) has been found to be implicated in lung cancer cell stemness. However, the roles and molecular mechanisms of WT1-AS in the development of gastric cancer stem cells (GCSCs) remain unknown. Our present study showed that WT1-AS negatively regulated WT1 expression in GCSCs. WT1-AS knockdown or Wilms' tumor 1 (WT1) overexpression improved GCSC proliferative and migratory capacities, inhibited GCSC apoptosis, potentiated the resistance of GCSCs to 5-FU, promoted GCSC EMT, induced HUVEC angiogenesis, enhanced GCSC stemness, and facilitated in-vitro 3D GCSC aggregate formation. WT1-AS overexpression exerted reverse effects. WT1-AS ameliorated the malignant phenotypes of GCSCs by down-regulating WT1 in vitro. WT1-AS inhibited tumor growth and metastasis, and reduced tumor stemness in GCSCs-derived (s.c., i.p., and i.v.) xenografts in vivo. Moreover, XBP1 was identified as an upstream regulator of WT1-AS in GCSCs. Also, 4 potential WT1-AS downstream targets (i.e. PSPH, GSTO2, FYN, and PHGDH) in GCSCs were identified. Additionally, CACNA2D1 was demonstrated to be a downstream target of the WT1-AS/WT axis. XBP1 or CACNA2D1 knockdown exerted an adverse effect on the maintenance of stem cell-like behaviors and characteristics of GCSCs. In conclusion, WT1-AS weakened the stem cell-like behaviors and characteristics of GCSCs in vitro and in vivo by down-regulating WT1. Investigations into the molecular mechanisms underlying the complex phenotypes of GCSCs might contribute to the better management of gastric cancer.
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Neuroticism is one of the most robust risk factors for addictive behaviors including food addiction (a key contributor to obesity), although the associated mechanisms are not well understood. A transdiagnostic approach was used to identify the neuroticism-related neuropsychological and gut metabolomic patterns associated with food addiction. Predictive modeling of neuroticism was implemented using multimodal features (23 clinical, 13,531 resting-state functional connectivity (rsFC), 336 gut metabolites) in 114 high body mass index (BMI ≥25 kg/m2) (cross-sectional) participants. Gradient boosting machine and logistic regression models were used to evaluate classification performance for food addiction. Neuroticism was significantly associated with food addiction (P < 0.001). Neuroticism-related features predicted food addiction with high performance (89% accuracy). Multimodal models performed better than single-modal models in predicting food addiction. Transdiagnostic alterations corresponded to rsFC involved in the emotion regulation, reward, and cognitive control and self-monitoring networks, and the metabolite 3-(4-hydroxyphenyl) propionate, as well as anxiety symptoms. Neuroticism moderated the relationship between BMI and food addiction. Neuroticism drives neuropsychological and gut microbial signatures implicated in dopamine synthesis and inflammation, anxiety, and food addiction. Such transdiagnostic models are essential in identifying mechanisms underlying food addiction in obesity, as it can help develop multiprong interventions to improve symptoms.