•Lactobacillus paracasei PS23 reverses corticosterone-induced depressive behaviors.•PS23 improves corticosterone-reduced hippocampal protein levels of MR, GR and BDNF.•Live PS23 reverses ...corticosterone-reduced 5-HT levels.•Heat-killed PS23 reverses corticosterone-reduced dopamine levels.•PS23 improves fecal microflora in corticosterone-treated mice.
Emerging evidence indicates that ingestion of specific probiotics, known as “psychobiotics”, confer beneficial effects on mental health. This study investigated antidepressant-like effects and possible underlying mechanisms of Lactobacillus paracasei PS23 (PS23), live or heat-killed, in a mouse model of corticosterone-induced depression using fluoxetine as standard drug. PS23 were orally gavaged to mice from day 1 to 41 or fluoxetine from day 17 to 41 and injected with corticosterone from day 17 to 37. After the last corticosterone treatment, anxiety- and depression-like behaviors were tested within 4 days. On day 42, serum and brain tissue were collected 24 min after forced swim stress. Abnormal behavioral changes induced by corticosterone were ameliorated by treatment with live PS23 in open field and sucrose preference tests, with heat-killed PS23 in open field, forced swim and sucrose preference tests, and with fluoxetine in open field and forced swim tests. Furthermore, both live and heat-killed PS23 and fluoxetine reversed corticosterone-reduced protein levels of brain-derived neurotropic factor, mineralocorticoid, and glucocorticoid receptors in the hippocampus. In addition, live PS23 also reverses corticosterone-reduced serotonin levels in hippocampus, prefrontal cortex and striatum; whereas heat-killed PS23 reverses corticosterone-reduced dopamine levels in hippocampus and prefrontal cortex. And fluoxetine normalized reduced corticosterone level in serum. These studies showed that both live and heat-killed PS23 can reverse chronic corticosterone-induced anxiety- and depression-like behaviors and that may provide insights into the mechanism and a potential psychobiotic for depression management.
Surface‐enhanced Raman spectroscopy (SERS)‐based biosensors have attracted much attention for their label‐free detection, ultrahigh sensitivity, and unique molecular fingerprinting. In this study, a ...wafer‐scale, ultrasensitive, highly uniform, paper‐based, portable SERS detection platform featuring abundant and dense gold nanopearls with narrow gap distances, are prepared and deposited directly onto ultralow‐surface‐energy fluorosilane‐modified cellulose fibers through simple thermal evaporation by delicately manipulating the atom diffusion behavior. The as‐designed paper‐based SERS substrate exhibits an extremely high Raman enhancement factor (3.9 × 1011), detectability at sub‐femtomolar concentrations (single‐molecule level) and great signal reproductivity (relative standard deviation: 3.97%), even when operated with a portable 785‐nm Raman spectrometer. This system is used for fingerprinting identification of 12 diverse analytes, including clinical medicines (cefazolin, chloramphenicol, levetiracetam, nicotine), pesticides (thiram, paraquat, carbaryl, chlorpyrifos), environmental carcinogens (benzoapyrene, benzog,h,iperylene), and illegal drugs (methamphetamine, mephedrone). The lowest detection concentrations reach the sub‐ppb level, highlighted by a low of 16.2 ppq for nicotine. This system appears suitable for clinical applications in, for example, i) therapeutic drug monitoring for individualized medication adjustment and ii) ultra‐early diagnosis for pesticide intoxication. Accordingly, such scalable, portable and ultrasensitive fibrous SERS substrates open up new opportunities for practical on‐site detection in biofluid analysis, point‐of‐care diagnostics and precision medicine.
A facile, scalable fabrication strategy for developing an ultrasensitive surface‐enhanced Raman spectroscopy (SERS) detection platform that serves as a rapid, label‐free point of care diagnostics device. Highly dense Au nanopearl arrays with narrow gap distances are formed directly through thermal evaporation on hydrophobic cellulose fibers to achieve excellent portable SERS performance (enhancement factor: 3.9 x 1011; detection limit: sub‐femtomolar single molecule level; reproductivity relative standard deviation ≤ 4%).
Flexible pressure sensors have many potential applications in wearable electronics, robotics, health monitoring, and more. In particular, liquid‐metal‐based sensors are especially promising as they ...can undergo strains of over 200% without failure. However, current liquid‐metal‐based strain sensors are incapable of resolving small pressure changes in the few kPa range, making them unsuitable for applications such as heart‐rate monitoring, which require a much lower pressure detection resolution. In this paper, a microfluidic tactile diaphragm pressure sensor based on embedded Galinstan microchannels (70 µm width × 70 µm height) capable of resolving sub‐50 Pa changes in pressure with sub‐100 Pa detection limits and a response time of 90 ms is demonstrated. An embedded equivalent Wheatstone bridge circuit makes the most of tangential and radial strain fields, leading to high sensitivities of a 0.0835 kPa−1 change in output voltage. The Wheatstone bridge also provides temperature self‐compensation, allowing for operation in the range of 20–50 °C. As examples of potential applications, a polydimethylsiloxane (PDMS) wristband with an embedded microfluidic diaphragm pressure sensor capable of real‐time pulse monitoring and a PDMS glove with multiple embedded sensors to provide comprehensive tactile feedback of a human hand when touching or holding objects are demonstrated.
A flexible microfluidic diaphragm pressure sensor using liquid‐metal microchannels is presented. The sensor is capable of detecting sub‐100 Pa pressures with sub‐50 Pa resolution. As a proof of concept, both heart‐rate monitoring and tactile pressure mapping of a glove with multiple embedded sensors are demonstrated.
Enriched PD-L1 expression in cancer stem-like cells (CSCs) contributes to CSC immune evasion. However, the mechanisms underlying PD-L1 enrichment in CSCs remain unclear. Here, we demonstrate that ...epithelial-mesenchymal transition (EMT) enriches PD-L1 in CSCs by the EMT/β-catenin/STT3/PD-L1 signaling axis, in which EMT transcriptionally induces N-glycosyltransferase STT3 through β-catenin, and subsequent STT3-dependent PD-L1 N-glycosylation stabilizes and upregulates PD-L1. The axis is also utilized by the general cancer cell population, but it has much more profound effect on CSCs as EMT induces more STT3 in CSCs than in non-CSCs. We further identify a non-canonical mesenchymal-epithelial transition (MET) activity of etoposide, which suppresses the EMT/β-catenin/STT3/PD-L1 axis through TOP2B degradation-dependent nuclear β-catenin reduction, leading to PD-L1 downregulation of CSCs and non-CSCs and sensitization of cancer cells to anti-Tim-3 therapy. Together, our results link MET to PD-L1 stabilization through glycosylation regulation and reveal it as a potential strategy to enhance cancer immunotherapy efficacy.
To explore whether a cross-talk exists between PARP inhibition and PD-L1/PD-1 immune checkpoint axis, and determine whether blockade of PD-L1/PD-1 potentiates PARP inhibitor (PARPi) in tumor ...suppression.
Breast cancer cell lines, xenograft tumors, and syngeneic tumors treated with PARPi were assessed for PD-L1 expression by immunoblotting, IHC, and FACS analyses. The phospho-kinase antibody array screen was used to explore the underlying mechanism of PARPi-induced PD-L1 upregulation. The therapeutic efficacy of PARPi alone, PD-L1 blockade alone, or their combination was tested in a syngeneic tumor model. The tumor-infiltrating lymphocytes and tumor cells isolated from syngeneic tumors were analyzed by CyTOF and FACS to evaluate the activity of antitumor immunity in the tumor microenvironment.
PARPi upregulated PD-L1 expression in breast cancer cell lines and animal models. Mechanistically, PARPi inactivated GSK3β, which in turn enhanced PARPi-mediated PD-L1 upregulation. PARPi attenuated anticancer immunity via upregulation of PD-L1, and blockade of PD-L1 resensitized PARPi-treated cancer cells to T-cell killing. The combination of PARPi and anti-PD-L1 therapy compared with each agent alone significantly increased the therapeutic efficacy
Our study demonstrates a cross-talk between PARPi and tumor-associated immunosuppression and provides evidence to support the combination of PARPi and PD-L1 or PD-1 immune checkpoint blockade as a potential therapeutic approach to treat breast cancer.
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There is currently a pursuit of synthetic approaches for designing porous carbon materials with selective CO2 capture and/or excellent energy storage performance that significantly impacts the ...environment and the sustainable development of circular economy. In this study we prepared a new bio-based benzoxazine (AP-BZ) in high yield through Mannich condensation of apigenin, a naturally occurring phenol, with 4-bromoaniline and paraformaldehyde. We then prepared a PA-BZ porous organic polymer (POP) through Sonogashira coupling of AP-BZ with 1,3,6,8-tetraethynylpyrene (P-T) in the presence of Pd(PPh3)4. In situ Fourier transform infrared spectroscopy and differential scanning calorimetry revealed details of the thermal polymerization of the oxazine rings in the AP-BZ monomer and in the PA-BZ POP. Next, we prepared a microporous carbon/metal composite (PCMC) in three steps: Sonogashira coupling of AP-BZ with P-T in the presence of a zeolitic imidazolate framework (ZIF-67) as a directing hard template, affording a PA-BZ POP/ZIF-67 composite; etching in acetic acid; and pyrolysis of the resulting PA-BZ POP/metal composite at 500 °C. Powder X-ray diffraction, thermogravimetric analysis, scanning electron microscopy, transmission electron microscopy, and Brunauer–Emmett–Teller (BET) measurements revealed the properties of the as-prepared PCMC. The PCMC material exhibited outstanding thermal stability (Td10 = 660 °C and char yield = 75 wt%), a high BET surface area (1110 m2 g–1), high CO2 adsorption (5.40 mmol g–1 at 273 K), excellent capacitance (735 F g–1), and a capacitance retention of up to 95% after 2000 galvanostatic charge–discharge (GCD) cycles; these characteristics were excellent when compared with those of the corresponding microporous carbon (MPC) prepared through pyrolysis of the PA-BZ POP precursors with a ZIF-67 template at 500 °C.
Although pyroptosis is critical for macrophages against pathogen infection, its role and mechanism in cancer cells remains unclear. PD-L1 has been detected in the nucleus, with unknown function. Here ...we show that PD-L1 switches TNFα-induced apoptosis to pyroptosis in cancer cells, resulting in tumour necrosis. Under hypoxia, p-Stat3 physically interacts with PD-L1 and facilitates its nuclear translocation, enhancing the transcription of the gasdermin C (GSDMC) gene. GSDMC is specifically cleaved by caspase-8 with TNFα treatment, generating a GSDMC N-terminal domain that forms pores on the cell membrane and induces pyroptosis. Nuclear PD-L1, caspase-8 and GSDMC are required for macrophage-derived TNFα-induced tumour necrosis in vivo. Moreover, high expression of GSDMC correlates with poor survival. Antibiotic chemotherapy drugs induce pyroptosis in breast cancer. These findings identify a non-immune checkpoint function of PD-L1 and provide an unexpected concept that GSDMC/caspase-8 mediates a non-canonical pyroptosis pathway in cancer cells, causing tumour necrosis.
The increasing utilization of the internet has provided a better opportunity for people to search online for health information, which was not easily available to them in the past. Studies reported ...that searching on the internet for health information may potentially influence an individual's decision making to change her health-seeking behaviors.
The objectives of this study were to (1) develop and validate 2 questionnaires to estimate the strategies of problem-solving in medicine and utilization of online health information, (2) determine the association between searching online for health information and utilization of online health information, and (3) determine the association between online medical help-seeking and utilization of online health information.
The Problem Solving in Medicine and Online Health Information Utilization questionnaires were developed and implemented in this study. We conducted confirmatory factor analysis to examine the structure of the factor loadings and intercorrelations for all the items and dimensions. We employed Pearson correlation coefficients for examining the correlations between each dimension of the Problem Solving in Medicine questionnaire and each dimension of the Online Health Information Utilization questionnaire. Furthermore, we conducted structure equation modeling for examining the possible linkage between each of the 6 dimensions of the Problem Solving in Medicine questionnaire and each of the 3 dimensions of the Online Health Information Utilization questionnaire.
A total of 457 patients participated in this study. Pearson correlation coefficients ranged from .12 to .41, all with statistical significance, implying that each dimension of the Problem Solving in Medicine questionnaire was significantly associated with each dimension of the Online Health Information Utilization questionnaire. Patients with the strategy of online health information search for solving medical problems positively predicted changes in medical decision making (P=.01), consulting with others (P<.001), and promoting self-efficacy on deliberating the online health information (P<.001) based on the online health information they obtained.
Present health care professionals have a responsibility to acknowledge that patients' medical decision making may be changed based on additional online health information. Health care professionals should assist patients' medical decision making by initiating as much dialogue with patients as possible, providing credible and convincing health information to patients, and guiding patients where to look for accurate, comprehensive, and understandable online health information. By doing so, patients will avoid becoming overwhelmed with extraneous and often conflicting health information. Educational interventions to promote health information seekers' ability to identify, locate, obtain, read, understand, evaluate, and effectively use online health information are highly encouraged.
Micro- and mesoporous carbons are known to be effective anode materials for sodium-ion (Na+) batteries (SIBs). In contrast, macroporous and gigaporous carbons have rarely been studied for this ...purpose, even though their porous structure may facilitate electrolyte infiltration to enhance cell performance. Here, a series of gigaporous carbon microspheres (GCS) was synthesized by carbonizing gigaporous polymeric microspheres at different temperatures (700–2500 °C) and adopted as anode-active material of SIBs. All GCS samples exhibited a particle size of 10–15 μm and an average pore size of 0.3–0.5 μm. Nevertheless, their specific surface areas decreased over a large range with increasing carbonization temperature from >400 m2 g−1 to <30 m2 g−1. The GCS samples fabricated at higher temperatures demonstrated better electronic conductivity and a larger contribution from Na + insertion/extraction instead of adsorption/desorption to the capacity of constructed cells during charge/discharge. GCS carbonized at 850–1000 °C resulted in cells with the best capacity performance (>300 mAh g−1). The reason is that GCS produced at lower temperatures had insufficient conductivity and underwent limited electrochemical reactions with Na+, leading to a low capacity. On the other hand, an excessively high carbonization temperature produced carbons having a small d-spacing and lacking the beneficial carbonyl groups, which hindered both Na+ insertion/extraction and adsorption/desorption and therefore also reduced the cell capacity.
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•A series of carbon microspheres with gigapores were synthesized and proposed.•As-synthesized gigaporous carbon microspheres have a pore size of 0.3–0.5 μm.•As-synthesized gigaporous carbon microspheres have a surface area >400 m2 g−1.•Carbon microspheres with gigapores are potential anode-active materials of SIBs.
The Ni-rich Li(Ni0.8Co0.1Mn0.1)O2 (NCM811) is surface-modified using phosphoric acid (HPO) and silane reagents, and water-based cathode slurries of unmodified and modified NCM811 are prepared with ...poly(acrylonitrile) (PAN) or poly(acrylic acid) (PAA) added as the binder to compare the electrochemical performances of the constructed cells. Surface modification using HPO or the addition of PAA as the binder can substantially reduce the alkalinity of the prepared aqueous slurry of NCM811, thereby preventing the slurry from corroding the aluminum current collector, as well as retaining the good structural integrity of the dried electrode. The aforementioned advantage about the reduction in the alkalinity is not achieved when the hydrophobic silane-modified NCM811 or the neutral binder PAN is used. The best cell performance in terms of electrochemical reversibility, ionic and electronic impedance, and cycle stability is obtained when the water-based cathode slurry is prepared using HPO-modified NCM811 as the cathode active and PAA as the binder simultaneously. Moreover, the addition of PAA rather than the adoption of HPO-modified NCM811 contributes more to the improvement of cell performance.
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•Poly(acrylic acid) is an ideal binder for water-processed Li(Ni0.8Co0.1Mn0.1)O2 cathode.•Phosphoric acid modification improves the electrochemistry of Li(Ni0.8Co0.1Mn0.1)O2.•Good cell performance of water-processed Li(Ni0.8Co0.1Mn0.1)O2 cathode is obtained.
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