RESUMEN
It is well-known that the bacterial microenvironment imposes restrictions on the growth and behavior of bacteria. The localized monitoring of microenvironmental factors is appreciated when consulting bacterial adaptation and behavior in the presence of chemical or mechanical stimuli. Herein, we developed a novel liquid crystal (LC) biosensor in a microsphere configuration for real-time 3D monitoring of the bacteria microenvironment, which was implemented by a microfluidic chip. As a proof of concept, a LC gel (LC-Gel) microsphere biosensor was prepared and employed in the localized pH changes of bacteria by observing the configuration change of LC under polarized optical microscopy. Briefly, the microsphere biosensor was constructed in core-shell configuration, wherein the core contained LCE7 (a nematic LC) doped with 4-pentylbiphenyl-4'-carboxylic acid (PBA), and the shell encapsulated the bacteria. The protonation of carboxyl functional groups of the PBA induced a change in charge density on the surface of LCE7 and the orientation of E7 molecules, resulting in the transitions of the LC nucleus from axial to bipolar. The developed LC-Gel microspheres pH sensor exhibited its dominant performance on localized pH real-time sensing with a resolution of 0.1. An intriguing observation from the prepared pH biosensor was that the diverse bacteria impelled distinct acidifying or alkalizing effects. Overall, the facile LC-Gel microsphere biosensor not only provides a versatile tool for label-free, localized pH monitoring but also opens avenues for investigating the effects of chemical and mechanical stimuli on cellular metabolism within bacterial microenvironments.
Asunto(s)
Técnicas Biosensibles , Cristales Líquidos , Microesferas , Concentración de Iones de Hidrógeno , Cristales Líquidos/química , Escherichia coliRESUMEN
INTRODUCTION AND OBJECTIVES: Prostate apoptosis response protein-4(PAR-4) is considered a tumor suppressor. However, the role of PAR-4 in hepatocellular carcinoma(HCC) has rarely been reported. The study explores the role of PAR-4 in the malignant behaviors of HCC cells. MATERIALS AND METHODS: TCGA database was applied to analyze the expression of PAR-4 in HCC. Evaluated PAR-4 relationship with clinical parameters and prognosis by tissue microarray; Expression of STAT3, p-STAT3, Src and Ras was detected by Western blotting or laser confocal microscopy. Cell scratch and flow cytometry assays were used to observe IL-6 regulation of the malignant behaviors of HCC cells. The tumorigenic potential of HCC cells in vivo was evaluated in a nude mouse tumor model. RESULTS: Analysis indicated that the expression of PAR-4 in HCC tissues was significantly higher than that in normal liver tissues; and PAR-4 interacted with STAT3. KEGG analysis showed that PAR-4 plays a role in the Janus kinase(JAK)/STAT signaling pathway. The positive expression rate of PAR-4 in HCC tissues was significantly higher than that in adjacent tissues. Positive correlation between IL-6 and PAR-4 expression in the HCC tissues. Exogenous IL-6 significantly promoted the proliferation and migration of HCC cells and up-regulated the expression of PAR-4 and p-STAT3 in HCC cells. Interference of the expression of PAR-4 could reduce the malignant behaviors of HCC cells and inhibit tumorigenesis in a nude mouse tumor model. CONCLUSIONS: PAR-4 expression is positively correlated with HCC; PAR-4 promotes malignant behavior of HCC cells mediated by the IL-6/STAT3 signaling pathway.
RESUMEN
BACKGROUND: For patients with unresectable hepatocellular carcinoma (HCC), the first-line therapeutic options are still relatively limited, and treatment outcomes remain poor. We aimed to assess the efficacy and safety of anlotinib combined with toripalimab as first-line therapy for unresectable HCC. METHODS: In this single-arm, multicenter, phase II study (ALTER-H-003), patients with advanced HCC without previous systemic anticancer therapy were recruited. Eligible patients were given anlotinib (12 mg on days 1-14) combined with toripalimab (240 mg on day 1) in a 3-week cycle. The primary endpoint was the objective response rate (ORR) by immune-related Response Evaluation Criteria in Solid Tumours (irRECIST)/RECIST v1.1 and modified RECIST (mRECIST). Secondary endpoints included disease control rate (DCR), duration of response (DoR), progression-free survival (PFS), overall survival (OS), and safety. RESULTS: Between January 2020 and Jul 2021, 31 eligible patients were treated and included in the full analysis set. At data cutoff (January 10, 2023), the ORR was 29.0% (95% CI: 12.1%-46.0%) by irRECIST/RECIST v1.1, and 32.3% (95% CI: 14.8%-49.7%) by mRECIST criteria, respectively. Confirmed DCR and median DoR by irRECIST/RECIST v1.1 and mRECIST criteria were 77.4 % (95% CI: 61.8%-93.0%) and not reached (range: 3.0-22.5+ months), respectively. Median PFS was 11.0 months (95% CI: 3.4-18.5 months) and median OS was 18.2 months (95% CI: 15.8-20.5 months). Of the 31 patients assessed for adverse events (AEs), the most common grade ≥ 3 treatment-related AEs were hand-foot syndrome (9.7%, 3/31), hypertension (9.7%, 3/31), arthralgia (9.7%, 3/31), abnormal liver function (6.5%, 2/31), and decreased neutrophil counts (6.5%, 2/31). CONCLUSIONS: Anlotinib combined with toripalimab showed promising efficacy and manageable safety in Chinese patients with unresectable HCC in the first-line setting. This combination therapy may offer a potential new therapeutic approach for patients with unresectable HCC.
Asunto(s)
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/tratamiento farmacológico , Estudios Prospectivos , Neoplasias Hepáticas/tratamiento farmacológicoRESUMEN
Plyfluoroalkyl substance (PFAS), featured with incredible persistence and chronic toxicity, poses an emerging ecological and environmental crisis. Although significant progress has been made in PFAS metabolism in vivo, the underlying mechanism of metabolically active organ interactions in PFAS bioaccumulation remains largely unknown. We developed a microfluidic-based assay to recreate the intestine-vessel-liver interface in three dimensions, allowing for high-resolution, real-time images and precise quantification of intestine-vessel-liver interactions in PFAS biotransformation. In contrast to the scattered arrangement of vascular endothelium on the traditional d-polylysine-modified two-dimensional (2D) plate, the microtubules in our three-dimensional (3D) platform formed a dense honeycomb network through the ECM, with longer tubular structures. Additionally, the slope culture of epithelial cells in our platform exhibited a closely arranged and thicker cell layer than the planar culture. To dynamically monitor the metabolic crosstalk in the intestinal-vascular endothelium-liver interaction under exposure to fluorotelomer alcohols (FTOHs), we combined the chip with a solid-phase extraction-mass spectrometry (SPE-MS) system. Our findings revealed that endothelial cells were involved in the metabolic process of FTOHs. The transformation of intestinal epithelial and hepatic epithelial cells produces toxic metabolite fluorotelomer carboxylic acids (FTCAs), which circulate to endothelial cells and affect angiogenesis. This system shows promise as an enhanced surrogate model and platform for studying pollutant exposure as well as for biomedical and pharmaceutical research.
Asunto(s)
Células Endoteliales , Fluorocarburos , Células Endoteliales/metabolismo , Microfluídica , Fluorocarburos/análisis , Biotransformación , Hígado/metabolismoRESUMEN
A multifunctional platform that meets the demands of both bacterial detection and elimination is urgently needed because of their harm to human health. Herein, a "sense-and-treat" biosensor was developed by using immunomagnetic beads (IMBs) and AgPt nanoparticle-decorated PCN-223-Fe (AgPt/PCN-223-Fe, PCN stands for porous coordination network) metal-organic frameworks (MOFs). The synthesized AgPt/PCN-223-Fe not only exhibited excellent peroxidase-like activity but also could efficiently kill bacteria under near infrared (NIR) irradiation. This biosensor enabled the colorimetric detection of E. coli O157:H7 in the range of 103-108 CFU/mL with a limit of detection of 276 CFU/mL, accompanied with high selectivity, good reproducibility, and wide applicability in diverse real samples. Furthermore, the biosensor possessed a highly effective antibacterial rate of 99.94% against E. coli O157:H7 under 808 nm light irradiation for 20 min. This strategy can provide a reference for the design of novel versatile biosensors for bacterial discrimination and antibacterial applications.
Asunto(s)
Escherichia coli O157 , Estructuras Metalorgánicas , Humanos , Reproducibilidad de los Resultados , Bacterias , AntibacterianosRESUMEN
Developing advanced tools for multicomponent analysis is an open challenge in engineering and life science. Herein, multicompartmental hydrogel microspheres with multi-material compatibility and structural scalability are developed as a tool for multicomponent analysis at a single-particle level. Microfluidic technology endows particles with adjustable sizes and super-segmented layouts that can be used to load various analyte probes. In order to perform multicomponent analysis, these microspheres are structurally divided into identifier regions for indicating reading direction and analyte regions for detecting target molecules. The multiplex detection ability of these particles is demonstrated in microRNA bioassays with high specificity and sensitivity. The multi-target analysis is performed on a single-particle level, and the bioassay is free of conventional labeling interference. We expect these particles to reach their potential in clinical diagnostics.
Asunto(s)
Hidrogeles , MicroARNs , Microesferas , Microfluídica , MicroARNs/análisis , BioensayoRESUMEN
Early detection of foodborne bacteria is urgently needed to ensure food quality and to avoid the outbreak of foodborne bacterial diseases. Here, a kind of metal-organic framework (Zr-MOF) modified with Pt nanoparticles (Pt-PCN-224) was designed as a peroxidase-like signal amplifier for microfluidic biosensing of foodborne bacteria. Taking Escherichia coli (E. coli) O157:H7 as a model, a linear range from 2.93 × 102 to 2.93 × 108 CFU/mL and a limit of detection of 2 CFU/mL were obtained. The whole detection procedure was integrated into a single microfluidic chip. Water, milk, and cabbage samples were successfully detected, showing consistency with the results of the standard culture method. Recoveries were in the range from 90 to 110% in spiked testing. The proposed microfluidic biosensor realized the specific and sensitive detection of E. coli O157:H7 within 1 h, implying broad prospects of MOF with biomimetic enzyme activities for biosensing.
Asunto(s)
Escherichia coli O157 , Enfermedades Transmitidas por los Alimentos , Humanos , Microfluídica , Bacterias , Amplificadores Electrónicos , BiomiméticaRESUMEN
Due to the shortage of pure water resources, seawater electrolysis is a promising strategy to produce green hydrogen energy. To avoid chlorine oxidation reactions (ClOR) and the production of more corrosive hypochlorite, enhancing OER electrocatalyst activity is the key to solving the above problem. Considering that transition metal phosphides (TMPs) are promising OER eletrocatalysts for seawater splitting, a method to regulate the electronic structure of FeP by introducing Mn heteroatoms and phosphorus vacancy on it (Mn-FePV ) is developed. As an OER electrocatalyst in seawater solution, the synthesized Mn-FePV achieves extremely low overpotentials (η500 = 376, η1000 = 395 mV). In addition, the Pt/C||Mn-FePV couple only requires the voltage of 1.81 V to drive the current density of 1000 mA cm-2 for overall seawater splitting. The density functional theory (DFT) calculation shows that Mn-FePV (0.21 e- ) has more charge transfer number compared with FeP (0.17 e- ). In-situ Raman analysis shows that phosphorus vacancy and Mn doping can synergistically regulate the electronic structure of FeP to induce rapid phase reconstruction, further improving the OER performance of Mn-FePV . The new phase species of FeOOH is confirmed to can enhance the adsorption kinetics of OER intermediates.
RESUMEN
We report on a Kerr-lens mode-locked laser based on an Yb3+-doped disordered calcium lithium niobium gallium garnet (Yb:CLNGG) crystal. Pumping by a spatially single-mode Yb fiber laser at 976â nm, the Yb:CLNGG laser delivers soliton pulses as short as 31 fs at 1056.8â nm with an average output power of 66â mW and a pulse repetition rate of â¼77.6â MHz via soft-aperture Kerr-lens mode-locking. The maximum output power of the Kerr-lens mode-locked laser amounted to 203â mW for slightly longer pulses of 37 fs at an absorbed pump power of 0.74 W, which corresponds to a peak power of 62.2â kW and an optical efficiency of 20.3%.
RESUMEN
We report on sub-40 fs pulse generation from a Yb:Sc2SiO5 laser pumped by a spatially single-mode fiber-coupled laser diode at 976â nm. A maximum output power of 545â mW was obtained at 1062.6â nm in the continuous-wave regime, corresponding to a slope efficiency of 64% and a laser threshold of 143â mW. A continuous wavelength tuning across 80â nm (1030 -1110â nm) was also achieved. Implementing a SESAM for starting and stabilizing the mode-locked operation, the Yb:Sc2SiO5 laser delivered soliton pulses as short as 38 fs at 1069.5â nm with an average output power of 76â mW at a pulse repetition rate of â¼79.8â MHz. The maximum output power was scaled to 216â mW for slightly longer pulses of 42 fs, which corresponded to a peak power of 56.6â kW and an optical efficiency of 22.7%. To the best of our knowledge, these results represent the shortest pulses ever achieved with any Yb3+-doped rare-earth oxyorthosilicate crystal.
RESUMEN
We report on the first sub-60 fs pulse generated from a diode-pumped SESAM mode-locked Yb-laser based on a non-centrosymmetric Yb:YAl3(BO3)4 crystal as a gain medium. In the continuous-wave regime, pumping with a spatially single-mode, fiber-coupled 976â nm InGaAs laser diode, the Yb:YAl3(BO3)4 laser generated 391â mW at 1041.7â nm with a slope efficiency as high as 65.1%, and a wavelength tuning across 59â nm (1019 to 1078â nm) was achieved. By implementing a commercial SESAM to initiate and sustain the soliton type mode-locking, and using only a 1â mm-thick laser crystal, the Yb:YAl3(BO3)4 laser delivered pulses as short as 56 fs at a central wavelength of 1044.6â nm with an average output power of 76â mW at a pulse repetition rate of â¼67.55â MHz. To the best of our knowledge, this result represents the shortest pulses ever achieved from Yb:YAB crystal.
RESUMEN
Straight-tusked elephants (genus: Palaeoloxodon) including their island dwarf forms are extinct enigmatic members of the Pleistocene megafauna and the most common Pleistocene elephants after the mammoths. Their taxonomic placement has been revised several times. Using palaeogenomic evidence, previous studies suggested that the European P. antiquus has a hybrid origin, but no molecular data have been retrieved from their Asian counterparts, leaving a gap in our knowledge of the global phylogeography and population dynamics of Palaeoloxodon. Here, we captured a high-quality complete mitogenome from a Pleistocene Elephantidae molar (CADG841) from Northern China, which was previously morphologically assigned to the genus Elephas (Asian elephant), and partial mitochondrial sequences (838 bp) of another Palaeoloxodon sp. specimen (CADG1074) from Northeastern China. We found that both Chinese specimens cluster with a 244 000-year-old P. antiquus (specimen name: WE) from Western Europe, suggesting that this clade may represent a population with a large spatial span across Eurasia. Based on the fossil record and the molecular dating of both the divergences of different Palaeoloxodon mitochondrial clades and previously determined hybridization events, we propose that this Eurasian-wide WE clade provides evidence for an earlier migration and/or another hybridization event that happened in the evolutionary history of straight-tusked elephants.
Asunto(s)
Elefantes , Animales , Evolución Biológica , ADN Mitocondrial/genética , Elefantes/genética , Fósiles , Filogenia , FilogeografíaRESUMEN
Photocatalytic water splitting over semiconductors is believed as a promising avenue to obtain H2 fuel from renewable solar energy. However, developing highly active and non-noble-metal photocatalysts for H2 evolution is still quite challenging to date. In this work, by constructing nanosheet-based nanotubes with Cd-doping and S vacancies, a highly improved visible-light-driven H2 production for ZnIn2S4 is achieved. Unlike nanoflowers aggregated with nanosheets, the nanosheet-assembled hierarchical nanotubes allow multiple scattering and reflection of incident light within the interior space, leading to an enhanced light-harvesting efficiency. Together with the benefits from Cd doping and S-vacancy engineering, including narrowed band gaps, efficient transmission and separation of charge carriers, abundant catalytically active sites, heightened photo-stability and photo-electron reduction capacity, as well as a strong electrostatic attraction to protons, the synthesized S-deficient CdxZn1-xIn2S4 hierarchical nanotubes exhibit an extraordinary photocatalytic H2 evolution capability under visible-light irradiation, delivering an outstanding H2-generation activity of 28.99 mmol·g-1·h-1 (corresponding to an apparent quantum yield of 37.1% at 400 nm), which is much superior to that of CdxZn1-xIn2S4 nanoflowers, Pt-loaded ZnIn2S4 nanotubes, and most ever reported ZnIn2S4-based photocatalysts. Our study could inspire the development of low-cost and high-performance photocatalysts via rational structural design and optimization.
RESUMEN
Water molecules were easy to combine with organic molecules and embed into the lattice of solid molecules to form a hydrate. Compared with anhydrous compounds, a hydrate has completely different physical and chemical properties. In this paper, terahertz (THz) spectra of five nucleosides in the solid and liquid phases were studied experimentally by Fourier-transform infrared spectroscopy (FTIR) in the frequency of 0.5-9 THz. In addition, the lattice energy, geometric structure, and vibration spectrum of the molecular crystal of the nucleosides were analyzed theoretically by the generalized energy-based fragmentation approach under periodic boundary conditions (denoted as PBC-GEBF). Furthermore, different nucleoside molecular morphology (monomer, polymer, and crystal), solvent (implicit and explicit water), and temperature/theoretical model effect on the THz spectra were mainly investigated. It was found that in the low-frequency band, the vibrational modes were generally originated from the collective vibration of all molecules involved (more than 99% of them were vibration; only less than 1% of them were rotation and translation), which can reflect the molecular structure and spatial distribution of different substances. The Gibbs free energy of thymidine monomer, dimer, tetramer, and crystal was studied. It was found that the cell-stacking energy had the greatest influence on the spectrum, indicating that only the crystal structure constrained by the periodic boundary conditions could well describe the experimental results. In addition, hydrophobic forces dominated the formation of new chemical bonds and strong inter-molecular interactions; the free water had little contribution to the THz spectrum of nucleosides, while crystalline water had a great influence on the spectrum.
Asunto(s)
Nucleósidos , Agua , Solventes , Temperatura , Espectroscopía Infrarroja por Transformada de Fourier , VibraciónRESUMEN
A portable microfluidic biosensor was developed for the detection of E. coli O157:H7 using finger actuation. The chip was assembled with three functional zones, immunomagnetic separation, nucleic acid extraction and purification, and signal detection. First, antibody-modified magnetic nanoparticles (MNPs) were used to separate the target bacteria from the sample. The captured bacteria were then lysed and silica-coated MNPs were used to absorb DNA, followed by washing and eluting to obtain purified DNA. The obtained DNA was subjected to amplification and fluorescence detection based on the recombinase polymerase amplification-clustered regularly interspaced short palindromic repeat-associated protein/Cas12a reaction. The fluorescence images were collected and analyzed using a smartphone app under a 3D-printed detection device. It could quantitatively detect E. coli O157:H7 from 102 to 108 CFU/mL in 2.5 h with a limit of detection (LOD) of 10 CFU/mL. The recovery rate ranged from 104 to 120%. Overall, the biosensor realizes "sample-in and answer-out" assay for E. coli O157:H7 and eliminates the need for external pumps and skilled personnel.
Asunto(s)
Técnicas Biosensibles , Escherichia coli O157 , Escherichia coli O157/genética , Microfluídica , Técnicas Biosensibles/métodos , Separación Inmunomagnética/métodos , Límite de DetecciónRESUMEN
Tigers (Panthera tigris) are flagship big cats and attract extensive public attention due to their charismatic features and endangered status. Despite this, little is known about their prehistoric lineages and detailed evolutionary histories. Through palaeogenomic analyses, we identified a Pleistocene tiger from northeastern China, dated to beyond the limits of radiocarbon dating (greater than 43 500 years ago). We used a simulated dataset and different reads processing pipelines to test the validity of our results and confirmed that, in both mitochondrial and nuclear phylogenies, this ancient individual belongs to a previously unknown lineage that diverged prior to modern tiger diversification. Based on the mitochondrial genome, the divergence time of this ancient lineage was estimated to be approximately 268 ka (95% CI: 187-353 ka), doubling the known age of tigers' maternal ancestor to around 125 ka (95% CI: 88-168 ka). Furthermore, by combining our findings with putative mechanisms underlying the discordant mito-nuclear phylogenetic placement for the South China tigers, we proposed a more complex scenario of tiger evolution that would otherwise be missed using data from modern tigers only. Our study provides the first glimpses of the genetic antiquity of tigers and demonstrates the utility of aDNA-based investigation for further understanding tiger evolution.
Asunto(s)
Tigres , Animales , China , Filogenia , Tigres/genéticaRESUMEN
We report on sub-30 fs pulse generation from a semiconductor saturable absorber mirror mode-locked Yb:YAP laser. Pumping by a spatially single-mode Yb fiber laser at 979 nm, soliton pulses as short as 29 fs were generated at 1091 nm with an average output power of 156 mW and a pulse repetition rate of 85.1 MHz. The maximum output power of the mode-locked Yb:YAP laser amounted to 320 mW for slightly longer pulses (32 fs) at an incident pump power of 1.52 W, corresponding to a peak power of 103 kW and an optical efficiency of 20.5%. To the best of our knowledge, this result represents the shortest pulses ever achieved from any solid-state Yb laser mode-locked by a slow, i.e., physical saturable absorber.
RESUMEN
We report on the continuous-wave (CW) and mode-locked (ML) laser performance of an Yb3+-doped yttrium-gadolinium orthoaluminate crystal, Yb:(Y,Gd)AlO3. Pumping by a single-transverse-mode fiber-coupled 976 nm InGaAs laser diode, the maximum output power in the CW regime amounted to 429 mW at 1041.8 nm corresponding to a slope efficiency of 51.1% and a continuous wavelength tuning across 84 nm (1011-1095 nm) was achieved. The self-starting ML operation of the Yb:(Y,Gd)AlO3 laser was stabilized by a semiconductor saturable absorber mirror. Soliton pulses as short as 43 fs were generated at 1052.3 nm with an average output power of 103 mW and a pulse repetition rate of â¼70.8 MHz. To the best of our knowledge, our result represents the first report on the passively mode-locked operation of a Yb:(Y,Gd)AlO3 laser, and the shortest pulse duration ever achieved from any Yb3+-doped orthorhombic perovskite aluminate crystals.
RESUMEN
We report on a soliton mode-locked Yb:Ca3Gd2(BO3)4 laser at â¼1.06 µm stabilized by a semiconductor saturable absorber mirror. Pumping with a single-transverse mode, fiber-coupled laser diode at 976 nm, the Yb:Ca3Gd2(BO3)4 laser delivers soliton pulses as short as 39 fs at a central wavelength of 1059.2 nm with an average output power of 70 mW and a pulse repetition rate of â¼67.3 MHz.
RESUMEN
We demonstrate the first sub-40 fs soliton pulse generation from a diode-pumped Yb:Sr3Y2(BO3)4 laser passively mode-locked by a semiconductor saturable absorber mirror. Pulses as short as 38 fs at a central wavelength of 1051.7 nm were achieved with an average output power of 115 mW and a pulse repetition rate of 67.7 MHz. The maximum average output power reached 303 mW at 1057.8 nm with a slightly longer pulse duration of 52 fs, which corresponded to a peak power of 76.9 kW and an optical efficiency of 25.3%.