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Abstract Background Drug resistance remains a great challenge in the treatment of pancreatic cancer. The goal of this study was to determine whether TGF-β1 is associated with drug resistance in pancreatic cancer. Methods Pancreatic cancer BxPC3 cells were stably transfected with TGF-β1 cDNA. Cellular morphology and cell cycle were determined and the suppressive subtracted hybridization (SSH) assay was performed to identify differentially expressed genes induced by TGF-β1. Western blotting and immunohistochemistry were used to detect expression of TGF-β1-related genes in the cells and tissue samples. After that, the cells were further treated with an anti-cancer drug (e.g., cisplatin) after pre-incubated with the recombinant TGF-β1 plus PKCα inhibitor Gö6976. TGF-β1 type II receptor, TβRII was also knocked down using TβRII siRNA to assess the effects of these drugs in the cells. Cell viability was assessed by MTT assay. Results Overexpression of TGF-β1 leads to a markedly increased invasion potential but a reduced growth rate in BxPC3 cells. Recombinant TGF-β1 protein increases expression of PKCα in BxPC3 cells, a result that we confirmed by SSH. Moreover, TGF-β1 reduced the sensitivity of BxPC3 cells to cisplatin treatment, and this was mediated by upregulation of PKCα. However, blockage of PKCα with Gö6976 and TβRII with siRNA reversed the resistance of BxPC3 cells to gemcitabine, even in the presence of TGF-β1. Immunohistochemical data show that pancreatic cancers overexpress TGF-β1 and P-gp relative to normal tissues. In addition, TGF-β1 expression is associated with P-gp and membranous PKCα expression in pancreatic cancer. Conclusions TGF-β1-induced drug resistance in pancreatic cancer cells was associated with PKCα expression. The PKCα inhibitor Gö6976 could be a promising agent to sensitize pancreatic cancer cells to chemotherapy.

CD4+ T cells differentiate into T helper cell subsets in feedforward manners with synergistic signals from the T cell receptor (TCR), cytokines, and lineage-specific transcription factors. Naive CD4+ T cells avoid spontaneous engagement of feedforward mechanisms but retain a prepared state. T cells lacking the adaptor molecule LAT demonstrate impaired TCR-induced signals yet cause a spontaneous lymphoproliferative T helper 2 (TH2) cell syndrome in mice. Thus, LAT constitutes an unexplained maintenance cue. Here, we demonstrate that tonic signals through LAT constitutively export the repressor HDAC7 from the nucleus of CD4+ T cells. Without such tonic signals, HDAC7 target genes Nur77 and Irf4 are repressed. We reveal that Nur77 suppresses CD4+ T cell proliferation and uncover a suppressive role for Irf4 in TH2 polarization; halving Irf4 gene-dosage leads to increases in GATA3+ and IL-4+ cells. Our studies reveal that naive CD4+ T cells are dynamically tuned by tonic LAT-HDAC7 signals.

Objective To investigate the efficacy of transcranial direct current stimulation (tDCS) on sleep disorder in patients with Parkinson's disease (PD). Methods From July 2021 to July 2023, patients with PD and sleep disorders in the Department of Neurosurgery of the Second People's Hospital of Guangdong Province were selected. The enrolled patients were divided into sham stimulation group (n = 28 ) and true stimulation group (tDCS) (n = 29) according to the inclusion and exclusion criteria. MDS-UPDRS, PDSS and other rating scales were used to evaluate the patients. Before and after tDCS treatment, MS-11 was used for intelligent sleep monitoring. The baseline and improvement of sleep disorders in the two groups before and after treatment were analyzed. Results Before tDCS treatment, there was no significant difference in general conditions and scale scores between the two groups (P > 0.05). There was no significant difference in polysomnographic monitoring results between the two groups before treatment (P > 0.05). Compared with pre-treatment, there was no significant difference in sleep monitoring results in the sham stimulation group (P > 0.05), while the sleep duration and sleep efficiency significantly increased, the nighttime awakening duration, nighttime awakening frequency, MDS-UPDRS-III score, and LEDD dose significantly decreased in the true stimulation group, with statistical significance (P < 0.05). Conclusion Pharmacological treatment combined with tDCS treatment is effective for sleep disorders and motor function in patients with PD, which could increase the sleep duration and sleep efficiency of PD patients with sleep disorders to a certain extent, reduce the nighttime awakening duration and frequency, thereby improving the fatigue symptoms during the daytime, and improving the efficacy of conventional pharmacological treatment for PD. [ABSTRACT FROM AUTHOR]

The broad applications of ultrawide-band signals and terahertz waves in quantum measurements.sup.1,2, imaging and sensing techniques.sup.3,4, advanced biological treatments.sup.5, and very-high-data-rate communications.sup.6 have drawn extensive attention to ultrafast electronics. In such applications, high-speed operation of electronic switches is challenging, especially when high-amplitude output signals are required.sup.7. For instance, although field-effect and bipolar junction devices have good controllability and robust performance, their relatively large output capacitance with respect to their ON-state current substantially limits their switching speed.sup.8. Here we demonstrate a novel on-chip, all-electronic device based on a nanoscale plasma (nanoplasma) that enables picosecond switching of electric signals with a wide range of power levels. The very high electric field in the small volume of the nanoplasma leads to ultrafast electron transfer, resulting in extremely short time responses. We achieved an ultrafast switching speed, higher than 10 volts per picosecond, which is about two orders of magnitude larger than that of field-effect transistors and more than ten times faster than that of conventional electronic switches. We measured extremely short rise times down to five picoseconds, which were limited by the employed measurement set-up. By integrating these devices with dipole antennas, high-power terahertz signals with a power-frequency trade-off of 600 milliwatts terahertz squared were emitted, much greater than that achieved by the state of the art in compact solid-state electronics. The ease of integration and the compactness of the nanoplasma switches could enable their implementation in several fields, such as imaging, sensing, communications and biomedical applications. An on-chip, all-electronic device based on the formation of a nanoplasma provides ultrafast electron transfer, enabling picosecond switching of electric signals and the generation of high-power terahertz pulses., Author(s): Mohammad Samizadeh Nikoo [sup.1] , Armin Jafari [sup.1] , Nirmana Perera [sup.1] , Minghua Zhu [sup.1] , Giovanni Santoruvo [sup.1] , Elison Matioli [sup.1] Author Affiliations: (1) Power and [...]

A novel high contrast emissive projection display (EPD) on black screen is developed, using a set of RGB emissive nanomaterials that can be selectively excited by digital projection of 3 violet‐blue wavebands. The new photoluminescent display enables a scalable and freeform emissive display onto any vehicle interior surface, without covering or hiding the original surface. For example, the set of RGB emissive materials can be applied as clear topcoat onto pitch‐black foil or substrate on vehicle dashboard or center console, showing superior image contrast in bright ambient light under lower power projection. Such high contrast free‐form emissive projection will be discussed with demos for many new vehicle interior display applications. [ABSTRACT FROM AUTHOR]

Antibiotics are emerging pollutants widely existing in the aquatic environment with adverse effects on both humans and organisms. Understanding bioaccumulation of antibiotics in aquatic organisms is important for their risk assessment. Observations on the bioaccumulation metrics (including bioconcentration factor, biomagnification factor, trophic magnification factor, bioaccumulation factor, and biota-sediment accumulation factor) of antibiotics in aquatic organisms are reviewed in this contribution. It is revealed that close attention should be paid to enrofloxacin, sulfamethiazole, doxycycline, sulfadimidine, clarithromycin, azithromycin, and chloramphenicol, because they have high bioaccumulation potential with the logarithm of bioaccumulation factor values beyond a threshold (3.3 L/kg) stipulated in the REACH regulation. Physicochemical properties of antibiotics (e.g., pH-dependent octanol-water partition coefficient and liposome-water distribution coefficient), biological characteristics of organisms (e.g., lipid content, biotransformation potential, growth stages, and feeding habits) as well as environmental factors (e.g., the presence of sediment, pH, salinity, exposure concentrations, as well as co-existence with dissolved organic matter, heavy metals, and microplastics) can control the bioaccumulation of antibiotics in aquatic organisms. One-compartment and multi-compartment toxicokinetic models on the bioaccumulation of antibiotics in aquatic organisms are summarized. The existing models of antibiotics mainly focused on fish, suggesting more efforts are needed to construct models on other aquatic species. Knowledge gaps and critical research directions on antibiotics bioaccumulation were highlighted. [ABSTRACT FROM AUTHOR]