ABSTRACT
Adipose dysfunction in lipodystrophic SEIPIN deficiency is associated with multiple metabolic disorders and increased risks of developing cardiovascular diseases, such as atherosclerosis, cardiac hypertrophy, and heart failure. Recently, adipose transplantation has been found to correct adipose dysfunction and metabolic disorders in lipodystrophic Seipin knockout mice; however, whether adipose transplantation could improve lipodystrophy-associated cardiovascular consequences is still unclear. Here, we aimed to explore the effects of adipose transplantation on lipodystrophy-associated metabolic cardiovascular diseases in Seipin knockout mice crossed into atherosclerosis-prone apolipoprotein E (Apoe) knockout background. At 2 months of age, lipodystrophic Seipin/Apoe double knockout mice and nonlipodystrophic Apoe knockout controls were subjected to adipose transplantation or sham operation. Seven months later, mice were euthanized. Our data showed that although adipose transplantation had no significant impact on endogenous adipose atrophy or gene expression, it remarkably increased plasma leptin but not adiponectin concentration in Seipin/Apoe double knockout mice. This led to significantly reduced hyperlipidemia, hepatic steatosis, and insulin resistance in Seipin/Apoe double knockout mice. Consequently, atherosclerosis burden, intraplaque macrophage infiltration, and aortic inflammatory gene expression were all attenuated in Seipin/Apoe double knockout mice with adipose transplantation. However, adipocyte morphology, macrophage infiltration, or fibrosis of the perivascular adipose tissue was not altered in Seipin/Apoe double knockout mice with adipose transplantation, followed by no significant improvement of vasoconstriction or relaxation. In conclusion, we demonstrate that adipose transplantation could alleviate lipodystrophy-associated metabolic disorders and atherosclerosis but has an almost null impact on perivascular adipose abnormality or vascular dysfunction in lipodystrophic Seipin/Apoe double knockout mice.NEW & NOTEWORTHY Adipose transplantation (AT) reverses multiply metabolic derangements in lipodystrophy, but whether it could improve lipodystrophy-related cardiovascular consequences is unknown. Here, using Seipin/Apoe double knockout mice as a lipodystrophy disease model, we showed that AT partially restored adipose functionality, which translated into significantly reduced atherosclerosis. However, AT was incapable of reversing perivascular adipose abnormality or vascular dysfunction. The current study provides preliminary experimental evidence on the therapeutic potential of AT on lipodystrophy-related metabolic cardiovascular diseases.
Subject(s)
Adipose Tissue , Atherosclerosis , GTP-Binding Protein gamma Subunits , Lipodystrophy , Mice, Knockout , Animals , Mice , Adipose Tissue/metabolism , Adipose Tissue/transplantation , Apolipoproteins E/genetics , Apolipoproteins E/deficiency , Apolipoproteins E/metabolism , Atherosclerosis/genetics , Atherosclerosis/metabolism , Atherosclerosis/pathology , GTP-Binding Protein gamma Subunits/deficiency , GTP-Binding Protein gamma Subunits/genetics , GTP-Binding Protein gamma Subunits/metabolism , Heterotrimeric GTP-Binding Proteins/genetics , Heterotrimeric GTP-Binding Proteins/metabolism , Insulin Resistance , Leptin/blood , Leptin/metabolism , Lipodystrophy/metabolism , Lipodystrophy/genetics , Lipodystrophy/pathology , Mice, Inbred C57BLABSTRACT
AIMS/HYPOTHESIS: As the prevalence of insulin resistance and glucose intolerance is increasing throughout the world, diabetes-induced eye diseases are a global health burden. We aim to identify distinct optical bands which are closely related to insulin and glucose metabolism, using non-invasive, high-resolution spectral domain optical coherence tomography (SD-OCT) in a large, population-based dataset. METHODS: The LIFE-Adult-Study randomly selected 10,000 participants from the population registry of Leipzig, Germany. Cross-sectional, standardised phenotyping included the assessment of various metabolic risk markers and ocular imaging, such as SD-OCT-derived thicknesses of ten optical bands of the retina. Global and Early Treatment Diabetic Retinopathy Study (ETDRS) subfield-specific optical retinal layer thicknesses were investigated in 7384 healthy eyes of 7384 participants from the LIFE-Adult-Study stratified by normal glucose tolerance, prediabetes (impaired fasting glucose and/or impaired glucose tolerance and/or HbA1c 5.7-6.4% [39-47 mmol/mol]) and diabetes. The association of optical retinal band characteristics with different indices of glucose tolerance (e.g. fasting glucose, area under the glucose curve), insulin resistance (e.g. HOMA2-IR, triglyceride glucose index), or insulin sensitivity (e.g. estimated glucose disposal rate [eGDR], Stumvoll metabolic clearance rate) was determined using multivariable linear regression analyses for the individual markers adjusted for age, sex and refraction. Various sensitivity analyses were performed to validate the observed findings. RESULTS: In the study cohort, nine out of ten optical bands of the retina showed significant sex- and glucose tolerance-dependent differences in band thicknesses. Multivariable linear regression analyses revealed a significant, independent, and inverse association between markers of glucose intolerance and insulin resistance (e.g. HOMA2-IR) with the thickness of the optical bands representing the anatomical retinal outer nuclear layer (ONL, standardised ß=-0.096; p<0.001 for HOMA2-IR) and myoid zone (MZ; ß=-0.096; p<0.001 for HOMA2-IR) of the photoreceptors. Conversely, markers of insulin sensitivity (e.g. eGDR) positively and independently associated with ONL (ß=0.090; p<0.001 for eGDR) and MZ (ß=0.133; p<0.001 for eGDR) band thicknesses. These global associations were confirmed in ETDRS subfield-specific analyses. Sensitivity analyses further validated our findings when physical activity, neuroanatomical cell/tissue types and ETDRS subfield categories were investigated after stratifying the cohort by glucose homeostasis. CONCLUSIONS/INTERPRETATION: An impaired glucose homeostasis associates with a thinning of the optical bands of retinal ONL and photoreceptor MZ. Changes in ONL and MZ thicknesses might predict early metabolic retinal alterations in diabetes.
Subject(s)
Diabetic Retinopathy , Glucose Intolerance , Insulin Resistance , Prediabetic State , Adult , Humans , Cross-Sectional Studies , Retina , GlucoseABSTRACT
Ginsenoside Rb1 (Rb1), an active component isolated from traditional Chinese medicine Ginseng, is beneficial to many cardiovascular diseases. However, whether it can protect against doxorubicin induced cardiotoxicity (DIC) is not clear yet. In this study, we aimed to investigate the role of Rb1 in DIC. Mice were injected with a single dose of doxorubicin (20 mg/kg) to induce acute cardiotoxicity. Rb1 was given daily gavage to mice for 7 days. Changes in cardiac function, myocardium histopathology, oxidative stress, cardiomyocyte mitochondrion morphology were studied to evaluate Rb1's function on DIC. Meanwhile, RNA-seq analysis was performed to explore the potential underline molecular mechanism involved in Rb1's function on DIC. We found that Rb1 treatment can improve survival rate and body weight in Dox treated mice group. Rb1 can attenuate Dox induced cardiac dysfunction and myocardium hypertrophy and interstitial fibrosis. The oxidative stress increase and cardiomyocyte mitochondrion injury were improved by Rb1 treatment. Mechanism study found that Rb1's beneficial role in DIC is through suppressing of autophagy and ferroptosis. This study shown that Ginsenoside Rb1 can protect against DIC by regulating autophagy and ferroptosis.
Subject(s)
Cardiotoxicity , Ferroptosis , Ginsenosides , Animals , Mice , Apoptosis/drug effects , Autophagy/drug effects , Cardiotoxicity/drug therapy , Cardiotoxicity/metabolism , Cardiotoxicity/prevention & control , Doxorubicin/adverse effects , Doxorubicin/toxicity , Ginsenosides/pharmacology , Myocytes, Cardiac/metabolism , Oxidative StressABSTRACT
BACKGROUND: Oligoribonuclease (orn) of P. aeruginosa is a highly conserved exonuclease, which can regulate the global gene expression levels of bacteria through regulation of both the nanoRNA and c-di-GMP. NanoRNA can regulate the expression of the bacterial global genome as a transcription initiator, and c-di-GMP is the most widely second messenger in bacterial cells. OBJECTIVE: This study seeks to elucidate on the regulation by orn on pathogenicity of P. aeruginosa. METHODS: P. aeruginosa with orn deletion was constructed by suicide plasmid homologous recombination method. The possible regulatory process of orn was analyzed by TMT quantitative labeling proteomics. Then experiments were conducted to verify the changes of Δorn on bacterial motility, virulence and biofilm formation. Bacterial pathogenicity was further detected in cell and animal skin trauma models. ELISA detection c-di-GMP concentration and colony aggregation and biofilm formation were observed by scanning electron microscope. RESULTS: orn deletion changed the global metabolism of P. aeruginosa and reduced intracellular energy metabolism. It leads to the disorder of the quorum sensing system, the reduction of bacterial motility and virulence factors pyocyanin and rhamnolipids. But, orn deletion enhanced pathogenicity in vitro and in vivo, a high level of c-di-GMP and biofilm development of P. aeruginosa. CONCLUSION: orn regulates the ability of P. aeruginosa to adapt to the external environment.
Subject(s)
Bacterial Proteins , Exoribonucleases , Pseudomonas aeruginosa , Humans , Animals , Pseudomonas aeruginosa/metabolism , Bacterial Proteins/genetics , Bacterial Proteins/metabolism , Cyclic GMP/metabolism , Second Messenger Systems , Biofilms , Gene Expression Regulation, BacterialABSTRACT
Severe pneumonia caused by respiratory viruses has become a major threat to humans, especially with the SARS-CoV-2 outbreak and epidemic. The aim of this study was to investigate the universal molecular mechanism of severe pneumonia induced by multiple respiratory viruses and to search for therapeutic strategies targeting this universal molecular mechanism. The common differential genes of four respiratory viruses, including respiratory syncytial virus (RSV), rhinovirus, influenza, and SARS-CoV-2, were screened by GEO database, and the hub gene was obtained by Sytohubba in Cytoscape. Then, the effect of hub genes on inflammasome and pyrodeath was investigated in the model of RSV infection in vitro and in vivo. Finally, through virtual screening, drugs targeting the hub gene were obtained, which could alleviate severe viral pneumonia in vitro and in vivo. The results showed that CMPK2 is one of the hub genes after infection by four respiratory viruses. CMPK2 activates the inflammasome by activating NLRP3, and promotes the releases of inflammatory factors interleukin (IL)-1ß and IL-18 to induce severe viral pneumonia. Z25 and Z08 can reduce the expression level of CMPK2 mRNA and protein, thereby inhibiting NLRP3 and alleviating the development of severe viral pneumonia. In conclusion, the inflammatory response mediated by CMPK2 is the common molecular mechanism of severe pneumonia induced by viral infection, and Z25 and Z08 can effectively alleviate viral infection and severe pneumonia through this mechanism.
Subject(s)
Inflammasomes , Pyroptosis , Pyroptosis/drug effects , Humans , Animals , Inflammasomes/metabolism , Mice , NLR Family, Pyrin Domain-Containing 3 Protein/metabolism , NLR Family, Pyrin Domain-Containing 3 Protein/genetics , Interleukin-1beta/genetics , Interleukin-1beta/metabolism , Pneumonia, Viral/drug therapy , Pneumonia, Viral/virology , Interleukin-18/metabolism , Interleukin-18/genetics , SARS-CoV-2 , Respiratory Syncytial Virus Infections/drug therapy , Respiratory Syncytial Virus Infections/virologyABSTRACT
In this paper, we proposed an axially slow-variation microbubble resonator fabricated by an improved arc discharge method and applied to axial strain sensing. The prepared resonators are characterized by ultra-thin wall thickness and axial slow-variation. The wall thickness was experimentally measured to reach 938â nm and maintain a quality factor of an optical mode as large as 7.36 ×107. The main factors affecting the strain sensitivity of the microbubble resonators are investigated theoretically and experimentally. Experimentally, the maximum sensitivity measured was 13.08pm/µÎµ, which is three times higher than the microbubble resonators without this method. The device is simple to prepare and possesses ultra-thin wall thickness. It is promising for applications in high-precision sensing, such as single molecule and biological sensing.
ABSTRACT
The multi-channel perfect vortex (PV) array based on metasurface has important applications in optical communication, particle manipulation, quantum optics, and other fields due to its ultra-thin structure and excellent wavefront control ability. However, it is very challenging to utilize a single metasurface to simultaneously achieve independent channel PV arrays at different wavelengths with low crosstalk and low structural complexity. Here, we propose and design a single rectangular structured metasurface based on TiO2, achieving a multi-channel PV beam array with dual-wavelength and dual-polarization multiplexing. Simulation and experimental results show that when two orthogonal linearly polarized beams with wavelengths of 532 nm and 633 nm are incident on the metasurface, clear PV arrays with corresponding topological charge arrangements can be obtained in different diffraction regions of the same observation plane. The metasurface proposed in this article can enhance the channel capacity of a PV beam array through wavelength-polarization-multiplexing, thus having important application potential in spatial information transmission, high-dimensional information storage, and secure information encryption.
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BACKGROUND: Sarcopenia, a hallmark of age-related muscle function decline, significantly impacts elderly physical health. This systematic review aimed to investigate the impact of gut microbiota on sarcopenia. METHODS: Publications up to September 24, 2023 were scrutinized on four databases - PubMed, Web of Science, Cochrane Library, and Embase - using relevant keywords. Non-English papers were disregarded. Data regarding gut microbiota alterations in sarcopenic patients/animal models were collected and examined. RESULTS: Thirteen human and eight animal studies were included. The human studies involved 732 sarcopenic or potentially sarcopenic participants (aged 57-98) and 2559 healthy subjects (aged 54-84). Animal studies encompassed five mouse and three rat experiments. Results indicated an increase in opportunistic pathogens like Enterobacteriaceae, accompanied by changes in several metabolite-related organisms. For example, Bacteroides fluxus related to horse uric acid metabolism exhibited increased abundance. However, Roseburia, Faecalibacterium, Faecalibacterium prausnitzii, Eubacterium retale, Akkermansiaa, Coprococcus, Clostridium_XIVa, Ruminococcaceae, Bacteroides, Clostridium, Eubacterium involved in urolithin A production, and Lactobacillus, Bacteroides, and Clostridium associated with bile acid metabolism displayed decreased abundance. CONCLUSIONS: Age-related sarcopenia and gut microbiota alterations are intricately linked. Short-chain fatty acid metabolism, urolithin A, and bile acid production may be pivotal factors in the gut-muscle axis pathway. Supplementation with beneficial metabolite-associated microorganisms could enhance muscle function, mitigate muscle atrophy, and decelerate sarcopenia progression.
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Al/Ni energetic structural material with both high strength structural properties and high energy release functional properties can undergo a strong exothermic reaction under heating or impact loading conditions. In order to investigate the influence of microstructure on the mechanical properties and energy release characteristics of the Al/Ni energetic structural material, the materials with different Ni contents were prepared by cold spraying. With the increase of Ni particles, the microstructure inside the energetic structural material gradually changes from a continuous network structure of Al to a continuous network structure of Ni. The contact between Ni particles will make the stress transfer more uniform during the compression process of the energetic structural material, which enhances their strength. The results of heat-induced exothermic and shock-induced energy release show that the Al/Ni energetic structural material exhibits the best exothermic performance when Ni particles are uniformly dispersed and there are enough Al and Ni to make the material completely transform into the AlNi phase. The increase in the contact interface between Al and Ni particles facilitates the occurrence of a solid/solid reaction exothermic reaction between Al and Ni as well as the diffusion of Ni into the Al melt to generate the AlNi phase. The formation of the Ni continuous phase will lead to a reduction in the contact interface between Al and Ni, as well as an increase in porosity, which will result in a decrease in the amount of heat released during the diffusion reaction. This study will provide insights into the preparation of an Al/Ni energetic structural material with excellent properties.
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Calcium is a highly demanded metal, and its transport across the intestine of Daphnia magna remains a significant unresolved question. Due to technical constraints, the visualization of the kinetic process of Ca passage through D. magna has been challenging. Here, we developed the second near-infrared Ca sensor (NIR-II Ca) and conducted real-time in vivo imaging of Ca in daphnids with a high signal-to-noise ratio, deep tissue penetration, and minimal damage. Through the utilization of the NIR-II Ca sensor, we for the first time visualized and quantified the kinetic process of Ca passage in the intestine in real time. The results revealed that trophically available Ca passed through the intestines in 24 h, whereas waterborne Ca required only 35 min. This rapid "flushing through" mechanism established waterborne Ca as the primary source of Ca absorption. However, environmental stressors such as water acidification and cadmium significantly delayed the Ca passage and absorption. The development of NIR imaging and sensors allows for real-time dynamic visualization of contaminants/nutrients in organisms and holds great potential as a powerful tool for future studies into material kinetic processes in living animals.
Subject(s)
Cadmium , Water Pollutants, Chemical , Animals , Calcium , Daphnia magna , Daphnia , Water Pollutants, Chemical/analysis , Hydrogen-Ion ConcentrationABSTRACT
On the basis of good phosphate solubilization ability of a lactic acid bacteria (LAB) strain Limosilactobacillus sp. LF-17, bacterial agent was prepared and applied to calcareous soil to solubilize phosphate and promote the growth of maize seedlings in this study. A pot experiment showed that the plant growth indicators, phosphorus content, and related enzyme activity of the maize rhizospheric soils in the LF treatment (treated with LAB) were the highest compared with those of the JP treatment (treated with phosphate solubilizing bacteria, PSB) and the blank control (CK). The types of organic acids in maize rhizospheric soil were determined through LC-MS, and 12 acids were detected in all the treatments. The abundant microbes belonged to the genera of Lysobacter, Massilia, Methylbacillus, Brevundimonas, and Limosilactobacillus, and they were beneficial to dissolving phosphate or secreting growth-promoting phytohormones, which were obviously higher in the LF and JP treatments than in CK as analyzed by high-throughput metagenomic sequencing methods. In addition, the abundance values of several enzymes, Kyoto Encyclopedia of Genes and Genomes (KEGG) orthology, and Carbohydrate-Active Enzymes (CAZys), which were related to substrate assimilation and metabolism, were the highest in the LF treatment. Therefore, aside from phosphate-solubilizing microorganisms, LAB can be used as environmentally friendly crop growth promoters in agriculture and provide another viable option for microbial fertilizers. KEY POINTS: ⢠The inoculation of LAB strain effectively promoted the growth and chlorophyll synthesis of maize seedlings. ⢠The inoculation of LAB strain significantly increased the TP content of maize seedlings and the AP concentration of the rhizosphere soil. ⢠The inoculation of LAB strain increased the abundances of the dominant beneficial functional microbes in the rhizosphere soil.
Subject(s)
Lactobacillales , Phosphates , Phosphates/metabolism , Soil/chemistry , Lactobacillales/metabolism , Phosphorus/metabolism , Seedlings , Lactic Acid , Soil MicrobiologyABSTRACT
BACKGROUND: In this research, the effects caused by ultrafine grinding (U), high-temperature cooking (HTC), microwave (M) and combined treatment (U-HTC, U-M) were evaluated on the functional properties and structural characteristics of soluble dietary fiber (SDF) obtained from soybean dregs. RESULTS: Physical treatments could increase the extraction yield of SDF and improve the functional properties of SDF. The highest extraction yield (277.15 ± 5.87 g kg-1 based on the weight of soybean dregs) and purity (863.37 ± 5.15 g kg-1 based on the extract weight) of SDF was found in the sample by U-M treatment. U-HTC and U-M combined treatments significantly improved the water solubility and oil holding capacity of SDF. U-M treatment significantly increased the ability of SDF to adsorb cholesterol and perform cationic exchange; compared to the control, these abilities were increased by 138.46% and 10.38%, respectively. At pH 2.0, the nitrite ion adsorption capacity (NIAC) of SDF obtained by U-M combined treatment was 184.55 µg g-1 , which was significantly higher by 32.10% compared with that of the control. The results obtained by X-ray diffraction and scanning electron microscopy showed that the structure of SDF generated from soybean dregs became coarser and more porous, and the crystallinity decreased after physical treatments. CONCLUSION: Combined physical treatment is an effective way to improve the extracted yield and functional properties of SDF from soybean dregs. © 2023 Society of Chemical Industry.
Subject(s)
Dietary Fiber , Glycine max , Dietary Fiber/analysis , Solubility , Adsorption , CookingABSTRACT
China's local chicken breeds are rich in resources, and have formed different germplasm characteristics in the process of long-term selection and evolution. Scientific assessment of population genetic diversity and identification of inter-breed genetic structure are of great value to the protection and innovative utilization of local chicken breed resource. In order to evaluate the application effectiveness of 23K SNP chip "Youxin-1" in the analysis of genetic diversity and genetic structure of local chickens, we used RADseq to identify genomic genetic variation of 21 local chicken breeds and developed 23K chip "Youxin-1". The genetic statistics of each variety were calculated based on two sets of SNP data, and correlation, fitting and phylogenetic analysis were carried out to evaluate the application effectiveness of the chip. The results showed that the observed heterozygosity (Ho), polymorphism information content (PIC), inbred coefficient (FROH) and genetic differentiation coefficient (Fst) calculated based on the two SNP data sets were basically consistent in the 21 local chicken breeds. The genetic diversity of Langya chicken (LA), Piao chicken (PJ) and Wenchang chicken (WC) was relatively rich. The genetic diversity of Bian chickens (BJ), Langshan chickens (LS), Gushi chickens (GS), Dongxiang blue-eggshell chickens (DX) and Beijing fatty chickens (BY) was relatively poor, and the correlation coefficients of Ho, PIC, FROH and average Fst in the two groups were 0.794, 0.901, 0.926 and 0.984, respectively, all reaching extremely significant levels (P<0.01) with a high degree of fit (P<0.001) and R2 were 0.644, 0.827, 0.916 and 0.927. For the two sets of SNP data, the evolutionary tree constructed by neighbor-joining (NJ) method and maximum likelihood (ML) method was reasonable, and the 21 local chicken breeds were generally divided into six categories, which was consistent with the formation history and geographical distribution of the varieties. The 23K chip also realized reasonable clustering of the five new varieties without individual deviation. There are some differences in the estimation of genetic statistics using SNP with different densities, and data standardization is needed. 23K chip has good efficacy in the analysis of genetic diversity and structure of local chickens.
Subject(s)
Chickens , Genetic Variation , Polymorphism, Single Nucleotide , Animals , Chickens/genetics , Phylogeny , Breeding , China , Oligonucleotide Array Sequence AnalysisABSTRACT
We demonstrate for the first time the measurement of CO2 isotope ratios (13C/12C and 18O/16O) in a hollow waveguide (HWG) fiber using a mid-infrared heterodyne phase-sensitive dispersion spectrometer (HPSDS). A 4.329 µm interband cascade laser is used to target the absorption lines of three CO2 isotopes (13C16O2, 18O12C16O, and 12C16O2) in a 1 m long and 1 mm inner diameter HWG fiber. The detection limits are 0.29 ppm, 65.78 ppb, and 14.65 ppm with an integration time of 218 s for 13C16O2, 18O12C16O, and 12C16O2, respectively, at a modulation frequency of 160 MHz and a pressure of 230 mbar. The measurement precisions of δ13C and δ18O are 0.89 and 0.88 , respectively, corresponding to an integration time of 167 s. An experimental comparison between a HPSDS and a built wavelength modulation system with second-harmonic detection (WMS-2f) is conducted. The results show that compared to the WMS-2f, the developed HPSDS exhibits a greater linear dynamic range and excellent long-term stability. This work aims to demonstrate a detection technique of CO2 isotope dispersion spectroscopy with a large dynamic range for relevant applications focusing on samples with high concentrations of CO2 (% volume fraction), such as respiratory analysis in medical diagnostics.
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PURPOSE: Immune checkpoint inhibitors (ICIs) have shown durable responses in various malignancies. However, the response to ICI therapy is unpredictable, and investigation of predictive biomarkers needs to be improved. EXPERIMENTAL DESIGN: In total, 120 patients receiving ICI therapy and 40 patients receiving non-ICI therapy were enrolled. Peripheral blood immune cell markers (PBIMs), as liquid biopsy biomarkers, were analyzed by flow cytometry before ICI therapy, and before the first evaluation. In the ICI cohort, patients were randomly divided into training (n = 91) and validation (n = 29) cohorts. Machine learning algorithms were applied to construct the prognostic and predictive immune-related models. RESULTS: Using the training cohort, a peripheral blood immune cell-based signature (BICS) based on four hub PBIMs was developed. In both the training and the validation cohorts, and the whole cohort, the BICS achieved a high accuracy for predicting overall survival (OS) benefit. The high-BICS group had significantly shorter progression-free survival and OS than the low-BICS group. The BICS demonstrated the predictive ability of patients to achieve durable clinical outcomes. By integrating these PBIMs, we further constructed and validated the support vector machine-recursive and feature elimination classifier model, which robustly predicts patients who will achieve optimal clinical benefit. CONCLUSIONS: Dynamic PBIM-based monitoring as a noninvasive, cost-effective, highly specific and sensitive biomarker has broad potential for prognostic and predictive utility in patients receiving ICI therapy.
Subject(s)
Immune Checkpoint Inhibitors , Neoplasms , Humans , Immune Checkpoint Inhibitors/pharmacology , Immune Checkpoint Inhibitors/therapeutic use , Neoplasms/drug therapy , Algorithms , Flow Cytometry , Liquid BiopsyABSTRACT
Heterodyne phase-sensitive dispersion spectrometer (HPSDS) retrieves the concentration of gas samples by measuring the refractive index fluctuations near the molecular resonance. Compared to previous HPSDS studies focusing on pure intensity modulation, it is attractive to investigate the performance of HPSDS sensor based on a distributed feedback (DFB) laser under conditions where frequency modulation is much higher than intensity modulation. In this work, we report the implementation of a near-infrared HPSDS for methane detection based on the direct modulation of a DFB laser. The performance of our HPSDS is assessed using the characteristic absorption peak of methane near 1653.7â nm. Long-time measurements show that our HPSDS has a detection limit (MDL) of 1.22â ppm at standard atmospheric pressure and room temperature. In the same experimental conditions, we have experimentally compared HPSDS to wavelength modulation spectroscopy (WMS) to evaluate the dynamical range, long-term stability, and precision limits of the two methods.
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Backward stimulated Brillouin scattering (SBS) in optical microcavities has been widely used in nonlinear optics and microwave photonics. Compared with glass material microcavity, magnesium fluoride crystal microcavity has the advantages of small absorption coefficient, fewer defects and larger nonlinear coefficient, moreover, it usually has a narrow gain bandwidth of tens of megahertz. Here, we design a high precision machining system to produce ultra-smooth surface magnesium fluoride crystal disk cavities with a diameter of about 5 mm, Q value exceeding 108, FSR matching material Brillouin gain. By simply modulating the pump wavelength and coupling power, we observe SBS phenomena with a 13.47â GHz Brillouin frequency shift near 1.55µm and cascaded stimulated Brillouin lasers (SBL) of up to 12 orders. In addition, the Brillouin-Kerr optical frequency comb in this device is demonstrated, observing nearly 300 comb lines spanning across a spectral window of 250â nm. Our research provides a way to fabricate high-Q crystal microcavities and demonstrates the potential of these devices in applications such as microwave sources and nonlinear optics.
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The metalens has vast applications in biomedicine and industrial manufacturing due to their ultrathin structure and vital ability to manipulate the properties of light waves for long-infrared systems. However, it is difficult for metalens to achieve the confocal function with high focusing efficiency, wide wavelength bandwidth, and low structural complexity. Here, we propose and experimentally demonstrate an all-silicon dielectric metalens composed of arrays of minimalist meta-atoms with a single rectangular nanopillar arranged on a periodic square lattice substrate, which realizes the confocal function of the orthogonal-linear-polarized light with wavelengths of 10.6â µm and 9.3â µm, with focusing efficiencies of 64.94% and 60.03%, respectively. Also, it reveals nearly the diffraction-limited focusing performance. In addition, the metalens can realize precise long-infrared thermal imaging. Moreover, the proposed metalens is compatible with the standard complementary metal oxide semiconductor processes, which can effectively reduce the manufacturing cost and provide a feasible solution for developing planar integrated multifunctional micro-nanophotonic devices in the long-infrared field.
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In this work, a simple dielectric metasurface hologram is proposed and designed by combining the electromagnetic vector analysis method and the immune algorithm, which can realize the holographic display of dual wavelength orthogonal-linear polarization light in visible light band, solve the problem of low efficiency of the traditional design method of metasurface hologram, and effectively improve the diffraction efficiency of metasurface hologram. The titanium dioxide metasurface nanorod based on rectangular structure is optimized and designed. When the x-linear polarized light with wavelength of 532â nm and y-linear polarized light with wavelength of 633â nm are incident on the metasurface respectively, different display output images with low cross-talk can be obtained on the same observation plane, and the transmission efficiencies of x-linear and y-linear polarized light are as high as 68.2% and 74.6% respectively in simulation. Then the metasurface is fabricated by Atomic Layer Deposition method. The experimental results are consistent with the design results, which proves that the metasurface hologram designed by this method can completely realize the feasibility of wavelength and polarization multiplexing holographic display, and has potential application value in holographic display, optical encryption, anti-counterfeiting, data storage and other fields.
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A novel microfluidic DNA extraction protocol based on integrated diaphragm microvalves/pumps and silica-deposited open-channel columns was developed specifically for automated and parallel DNA solid-phase extraction (SPE). The method uses microfluidic chips with a sandwiched structure containing three layers, which are the upper fluidic layer with surface-deposited silica on glass open channels as the extraction phase, the lower actuation layer with valve actuation channels on a glass wafer, and the middle poly(dimethylsiloxane) (PDMS) membrane for reversible bonding of the two glass substrates. These two glass substrates can be reused after thoroughly cleaning and the PDMS membrane can be replaced conveniently, which could effectively decrease the time and cost of chip manufacturing. The normally closed microvalves/pumps were used to automatically control all processes of the on-chip DNA SPE without cross-contamination and leakage, enabling the processing of multiple samples in parallel without changing the microvalve control module. Using the microchip device with integrated microvalves/pumps, automated, programmable, and simultaneous λ-DNA extractions from different samples could be attained, even from complex solutions such as human blood, and the silica-deposited open-channel columns could be reused stably and reliably. Results have demonstrated that most of the eluted λ-DNA was recovered in the second 2 µL of elution buffer with high-purity suitable for successful polymerase chain reaction amplification, making it possible for further integration into microfluidic devices for fully functional and high-throughput genetic analysis.