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Red ginseng polysaccharide (RGP) is an active component of the widely used medicinal plant Panax ginseng C. A. Meyer (Araliaceae), which has displayed promising activities against cancer cells. However, the detailed molecular mechanism of RGP in ferroptosis is still unknown. This study evaluates the effects of RGP in cancer cells. A549 and MDA-MB-231 cells were used. Cell proliferation was measured by CCK-8 assay after being treated with RGP at concentrations of 0, 50, 100, 200, 400, 800 and 1600 μg/mL at 0, 12, 24 and 48 h. Lipid reactive oxygen species (ROS) levels were assessed by C11-BODIPY assay. The control group was treated with PBS. RGP inhibited human A549 (IC 50 : 376.2 μg/mL) or MDA-MB-231(IC 50 : 311.3 μg/mL) proliferation and induced lactate dehydrogenase (LDH) release, promoted ferroptosis and suppressed the expression of GPX4. Moreover, the effects of RGP were enhanced by the ferroptosis inducer erastin, while abolished by ferroptosis inhibitor ferrostatin-1. Our study is the first to demonstrate (1) the anticancer activity of RGP in human lung cancer and breast cancer. (2) RGP presented the anti-ferroptosis effects in lung and breast cancer cells via targeting GPX4.

Breast cancer rises as the most commonly diagnosed cancer in 2020. Among women, breast cancer ranks first in both cancer incidence rate and mortality. Treatment resistance developed from the current clinical therapies limits the efficacy of therapeutic outcomes, thus new treatment approaches are urgently needed. Chimeric antigen receptor (CAR) T cell therapy is a type of immunotherapy developed from adoptive T cell transfer, which typically uses patients' own immune cells to combat cancer. CAR-T cells are armed with specific antibodies to recognize antigens in self-tumor cells thus eliciting cytotoxic effects. In recent years, CAR-T cell therapy has achieved remarkable successes in treating hematologic malignancies; however, the therapeutic effects in solid tumors are not up to expectations including breast cancer. This review aims to discuss the development of CAR-T cell therapy in breast cancer from preclinical studies to ongoing clinical trials. Specifically, we summarize tumor-associated antigens in breast cancer, ongoing clinical trials, obstacles interfering with the therapeutic effects of CAR-T cell therapy, and discuss potential strategies to improve treatment efficacy. Overall, we hope our review provides a landscape view of recent progress for CAR-T cell therapy in breast cancer and ignites interest for further research directions.

Recent evidence suggests that musicians may have an advantage over non-musicians in perceiving speech against noisy backgrounds. Previously, musicians have been compared as a homogenous group, despite demonstrated heterogeneity, which may contribute to discrepancies between studies. Here, we investigated whether “quasi”-absolute pitch (AP) proficiency, viewed as a general trait that varies across a spectrum, accounts for the musician advantage in hearing-in-noise (HIN) performance, irrespective of whether the streams are speech or musical sounds. A cohort of 12 non-musicians and 42 trained musicians stratified into high, medium, or low AP proficiency identified speech or melody targets masked in noise (speech-shaped, multi-talker, and multi-music) under four signal-to-noise ratios (0, − 3, − 6, and − 9 dB). Cognitive abilities associated with HIN benefits, including auditory working memory and use of visuo-spatial cues, were assessed. AP proficiency was verified against pitch adjustment and relative pitch tasks. We found a domain-specific effect on HIN perception: quasi-AP abilities were related to improved perception of melody but not speech targets in noise. The quasi-AP advantage extended to tonal working memory and the use of spatial cues, but only during melodic stream segregation. Overall, the results do not support the putative musician advantage in speech-in-noise perception, but suggest a quasi-AP advantage in perceiving music under noisy environments.

A systematic evaluation of eight different coatings made of solid phase extraction (SPE) and carbon-based sorbents immobilized with polyacrylonitrile in the thin-film microextraction (TFME) format using LC-MS/MS was described. The investigated coatings included graphene, graphene oxide, multi-walled carbon nanotubes (MWCNTs), carboxylated MWCNTs, as carbon-based coatings, and polystyrene-divinylbenzene (PS-DVB), octadecyl-silica particles (C18), hydrophilic–hydrophobic balance particles (HLB) and phenyl-boronic acid modified particles (PBA), as SPE-based coatings. A total of 24 compounds of diverse moieties and of a wide range of polarities (log P from −2.99 to 6.98) were selected as probes. The investigated coatings were characterized based on their extraction performance toward the selected probes at different pH values and at optimized desorption conditions. In the case of SPE-based coatings, PS-DVB and HLB exhibited a balanced extraction for compounds within a wide range of polarities, and C18 showed superior extraction recoveries for non-polar analytes. Carbon-based coatings showed high affinity for non-polar compounds given that their main driving force for extraction is hydrophobic interactions. Interestingly, among the studied carbon-based coatings, graphene oxide showed the best extraction capabilities toward polar compounds owing to its oxygen-containing groups. Overall, this work provided important insights about the extraction mechanisms and properties of the investigated coatings, facilitating the coating selection when developing new TFME applications.

Photothermal therapy is favored by cancer researchers due to its advantages such as controllable initiation, direct killing and immune promotion. However, the low enrichment efficiency of photosensitizer in tumor site and the limited effect of single use limits the further development of photothermal therapy. Herein, a photo-responsive multifunctional nanosystem was designed for cancer therapy, in which myeloid-derived suppressor cell (MDSC) membrane vesicle encapsulated decitabine-loaded black phosphorous (BP) nanosheets (BP@ Decitabine @MDSCs, named BDM). The BDM demonstrated excellent biosafety and biochemical characteristics, providing a suitable microenvironment for cancer cell killing. First, the BDM achieves the ability to be highly enriched at tumor sites by inheriting the ability of MDSCs to actively target tumor microenvironment. And then, BP nanosheets achieves hyperthermia and induces mitochondrial damage by its photothermal and photodynamic properties, which enhancing anti-tumor immunity mediated by immunogenic cell death (ICD). Meanwhile, intra-tumoral release of decitabine induced G2/M cell cycle arrest, further promoting tumor cell apoptosis. In vivo, the BMD showed significant inhibition of tumor growth with down-regulation of PCNA expression and increased expression of high mobility group B1 (HMGB1), calreticulin (CRT) and caspase 3. Flow cytometry revealed significantly decreased infiltration of MDSCs and M2-macrophages along with an increased proportion of CD4 + , CD8 + T cells as well as CD103 + DCs, suggesting a potentiated anti-tumor immune response. In summary, BDM realizes photothermal therapy/photodynamic therapy synergized chemotherapy for cancer.

Thermal properties significantly affect extrusion energy efficiency and polymer processing. Relevant parameters include melt temperature, viscosity, and specific heat impact energy consumption, while thermal degradation limits processing temperatures within the screw and barrel. Traditional empirical methods used in polymer extrusion are often hindered by the complex relationship between screw speed and energy efficiency. Numerical simulations, particularly those using ANSYS Polyflow, offer a more precise approach for visualizing temperature, pressure, and shear rate distributions in the molten polymer, enabling better control of extrusion conditions. The screw’s geometric configuration, which includes sections for conveying, compressing, kneading, and mixing, plays a key role in determining flow behavior and performance. Studies on polymers using various screw configurations have revealed that screw designs with lower compression ratios enhance throughput and reduce melt temperature. Additionally, barrier screw designs improve the polymer melting efficiency. In this study, ANSYS Polyflow simulations were applied to analyze the flow behavior of molten PVC in a counter-rotating twin-screw extruder, focusing on the effects of screw speed and inlet flow rate on pressure, temperature, and velocity distributions. The results indicated optimal extrusion conditions for preventing degradation, with an ideal outlet rate of 439 kg/h at a screw rotational speed of 43 rpm. The pumping pressure of molten PVC by a twin-screw approach would be enough for entering the extrusion die.

We fabricated tantalum pentoxide (Ta 2 O 5 ) channel waveguides and used them to experimentally demonstrate higher-order mode supercontinuum (SC) generation. The Ta 2 O 5 waveguide has a high nonlinear refractive index which was in an order magnitude of 10 –14 cm 2 /W and was designed to be anomalously dispersive at the pumping wavelength. To the best of our knowledge, this is the first time a higher-order mode femtosecond pump based broadband SC has been measured from a nonlinear waveguide using the phase-matching method. This enabled us to demonstrate a SC spectrum spanning from 842 to 1462 nm (at − 30 dB), which corresponds to 0.83 octaves, when using the TM 10 waveguide mode. When using the TE 10 mode, the SC bandwidth is slightly reduced for the same excitation peak power. In addition, we theoretically estimated and discussed the possibility of using the broadband higher-order modes emitted from the Ta 2 O 5 waveguide for trapping nanoparticles. Hence, we believe that demonstrated Ta 2 O 5 waveguide are a promising broadband light source for optical applications such as frequency metrology, Raman spectroscopy, molecular spectroscopy and optical coherence tomography.

Neuropeptides are ubiquitous intercellular signaling molecules in the CNS and play diverse roles in modulating physiological functions by acting on specific G-protein coupled receptors (GPCRs). Among them, the elevenin signaling system is now believed to be present primarily in protostomes. Although elevenin was first identified from the L11 neuron of the abdominal ganglion in mollusc Aplysia californica , no receptors have been described in Aplysia , nor in any other molluscs. Here, using two elevenin receptors in annelid Platynereis dumerilii , we found three putative elevenin GPCRs in Aplysia . We cloned the three receptors and tentatively named them apElevR1, apElevR2, and apElevR3. Using an inositol monophosphate (IP1) accumulation assay, we demonstrated that Aplysia elevenin with the disulfide bond activated the three putative receptors with low EC50 values (ranging from 1.2 to 25 nM), supporting that they are true receptors for elevenin. In contrast, elevenin without the disulfide bond could not activate the receptors, indicating that the disulfide bond is required for receptor activity. Using alanine substitution of individual conserved residues other than the two cysteines, we showed that these residues appear to be critical to receptor activity, and the three different receptors had different sensitivities to the single residue substitution. Finally, we examined the roles of those residues outside the disulfide bond ring by removing these residues and found that they also appeared to be important to receptor activity. Thus, our study provides an important basis for further study of the functions of elevenin and its receptors in Aplysia and other molluscs.

Purposes This article describes an interesting phenomenon in which optimized freeze-dried (FD) biopharmaceutical formulations are generally more prone to degradation than their liquid counterparts during dropping and proposes an underlying cause for this surprising phenomenon. Methods Two monoclonal antibodies (mAbs) and a fusion protein (FP) were used as model biopharmaceuticals. The stability after dropping stress was determined by ultraviolet–visible (UV–Vis), size exclusion high-performance liquid chromatography (SE–HPLC), micro-flow imaging (MFI), and dynamic light scattering (DLS). Results Contrary to what we would normally assume, the FD formulations of the three biopharmaceuticals studied here generally showed much higher amounts of protein sub-visible particles (SbVPs) than liquid formulations after applying the same dropping stress as determined by MFI and DLS. Traditional techniques, such as UV–Vis and SE–HPLC, could hardly detect such degradation. Conclusions We propose that the higher temperature caused by dropping for the FD powders than the liquid formulations was probably one of the root causes for the higher amount of particles formed for the FD powders. We also recommend that dropping stress should be included for early-stage screening and choosing liquid versus FD biopharmaceutical formulations.

Neuropeptides, as pervasive intercellular signaling molecules in the CNS, modulate a variety of behavioral systems in both protostomes and deuterostomes. Allatostatins are neuropeptides in arthropods that inhibit the biosynthesis of juvenile hormones. Based on amino acid sequences, they are divided into three different types in arthropods: allatostatin A, allatostatin B, allatostatin C. Allatostatin C (AstC) was first isolated from Manduca sexta , and it has an important conserved feature of a disulfide bridge formed by two cysteine residues. Moreover, AstC appears to be the ortholog of mammalian somatostatin, and it has functions in common with somatostatin, such as modulating feeding behaviors. The AstC signaling system has been widely studied in arthropods, but minimally studied in molluscs. In this study, we seek to identify the AstC signaling system in the marine mollusc Aplysia californica . We cloned the AstC precursor from the cDNA of Aplysia . We predicted a 15-amino acid peptide with a disulfide bridge, i.e., AstC, using NeuroPred. We then cloned two putative allatostatin C-like receptors and through NCBI Conserved Domain Search we found that they belonged to the G protein-coupled receptor (GPCR) family. In addition, using an inositol monophosphate 1 (IP1) accumulation assay, we showed that Aplysia AstC could activate one of the putative receptors, i.e., the AstC-R, at the lowest EC 50 , and AstC without the disulfide bridge (AstC') activated AstC-R with the highest EC 50 . Moreover, four molluscan AstCs with variations of sequences from Aplysia AstC but with the disulfide bridge activated AstC-R at intermediate EC 50 . In summary, our successful identification of the Aplysia AstC precursor and its receptor (AstC-R) represents the first example in molluscs, and provides an important basis for further studies of the AstC signaling system in Aplysia and other molluscs.