ABSTRACT
Magnetron-sputtered thermoelectric thin films have the potential for reproducibility and scalability. However, lattice mismatch during sputtering can lead to increased defects in the epitaxial layer, which poses a significant challenge to improving their thermoelectric performance. In this work, nanocrystalline n-type Bi2Te3 thin films with an average grain size of ≈110 nm are prepared using high-temperature sputtering and post-annealing. Herein, it is demonstrated that high-temperature treatment exacerbates Te evaporation, creating Te vacancies and electron-like effects. Annealing improves crystallinity, increases grain size, and reduces defects, which significantly increases carrier mobility. Furthermore, the pre-deposited Ti additives are ionized at high temperatures and partially diffused into Bi2Te3, resulting in a Ti doping effect that increases the carrier concentration. Overall, the 1 µm thick n-type Bi2Te3 thin film exhibits a room temperature resistivity as low as 3.56 × 10-6 Ωâm. Notably, a 5 µm thick Bi2Te3 thin film achieves a record power factor of 6.66 mW mK-2 at room temperature, which is the highest value reported to date for n-type Bi2Te3 thin films using magnetron sputtering. This work demonstrates the potential for large-scale of high-quality Bi2Te3-based thin films and devices for room-temperature TE applications.
ABSTRACT
Osteoarthritis (OA) is a joint disease caused by inflammation of cartilage and synovial tissue. Suppressing the process of inflammatory reaction and the generation of oxidative stress is an effective strategy to alleviate the progression of OA. Liensinine is one of the main components of lotus seeds, which has anti-hypertensive and anti-arrhythmia activities. In this study, we aimed to determine the anti-inflammatory effect of liensinine in an OA. Here, we found that liensinine significantly inhibited the inflammatory response of SW1353 cells and primary chondrocytes by inhibiting the release of inflammatory cytokines and oxidative stress. Moreover, we showed that liensinine was able to inhibit the activation of the NF-κB signaling pathway in IL-1ß-induced SW1353 cells. Lastly, we found that liensinine significantly ameliorated cartilage damage and inflammatory response in papain-induced rats. Our study demonstrated a significant protective effect of liensinine against OA, which might be by inhibiting the activation of the NF-κB signaling pathway, and provide a new insight for the treatment of OA using liensinine.
Subject(s)
Anti-Inflammatory Agents , Chondrocytes , Interleukin-1beta , NF-kappa B , Osteoarthritis , Animals , Humans , Male , Rats , Anti-Inflammatory Agents/pharmacology , Anti-Inflammatory Agents/therapeutic use , Cells, Cultured , Chondrocytes/drug effects , Cytokines/metabolism , Interleukin-1beta/metabolism , Isoquinolines , NF-kappa B/metabolism , Osteoarthritis/drug therapy , Osteoarthritis/chemically induced , Oxidative Stress/drug effects , Papain , Phenols , Rats, Sprague-Dawley , Signal Transduction/drug effectsABSTRACT
The concept of bio-inspired gradient hierarchies, in which the well-defined MOF nanocrystals serve as active nanodielectrics to create electroactive shell at poly(lactic acid) (PLA) nanofibers, is introduced to promote the surface activity and electroactivity of PLA nanofibrous membranes (NFMs). The strategy enabled significant refinement of PLA nanofibers during coaxial electrospinning (â¼40 % decline of fiber diameter), accompanied by remarkable increase of specific surface area (nearly 1.5 m2/g), porosity (approximately 85 %) and dielectric constants for the bio-inspired gradient PLA (BG-PLA) NFMs. It largely boosted initial electret properties and electrostatic adsorption capability of BG-PLA NFMs, as well as charge regeneration by TENG mechanisms even under high-humidity environment. The BG-PLA NFMs thus featured exceptionally high PM0.3 filtration efficiencies with well-controlled air resistance (94.3 %, 163.4 Pa, 85 L/min), in contrast to the relatively low efficiency of only 80.0 % for normal PLA. During the application evaluation of outdoor air purification, excellent long-term filtering performance was demonstrated for the BG-PLA for up to 4 h (nearly 98.0 %, 53 Pa), whereas normal PLA exhibited a gradually declined filtration efficiency and an increased pressure drop. Moreover, the BG-PLA NFMs of increased electroactivity were ready to generate tribo-output currents as driven by respiratory vibrations, which enabled real-time monitoring of electrophysiological signals. This bio-inspired gradient strategy opens up promising pathways to engender biodegradable nanofibers of high surface activity and electroactivity, which has significant implications for intelligent protective membranes.
Subject(s)
Nanofibers , Polyesters , Nanofibers/chemistry , Polyesters/chemistry , Particulate Matter/chemistry , Humans , Air Pollutants/chemistry , Filtration , Environmental Monitoring/methodsABSTRACT
Non-alcoholic fatty liver disease (NAFLD) is closely related to metabolic syndrome and remains a major global health burden. The increased prevalence of obesity and type 2 diabetes mellitus (T2DM) worldwide has contributed to the rising incidence of NAFLD. It is widely believed that atherosclerotic cardiovascular disease (ASCVD) is associated with NAFLD. In the past decade, the clinical implications of NAFLD have gone beyond liver-related morbidity and mortality, with a majority of patient deaths attributed to malignancy, coronary heart disease (CHD), and other cardiovascular (CVD) complications. To better define fatty liver disease associated with metabolic disorders, experts proposed a new term in 2020 - metabolic dysfunction associated with fatty liver disease (MAFLD). Along with this new designation, updated diagnostic criteria were introduced, resulting in some differentiation between NAFLD and MAFLD patient populations, although there is overlap. The aim of this review is to explore the relationship between MAFLD and ASCVD based on the new definitions and diagnostic criteria, while briefly discussing potential mechanisms underlying cardiovascular disease in patients with MAFLD.
Subject(s)
Immunotherapy , Leukemia , Tumor Escape , Humans , Leukemia/therapy , Leukemia/immunology , Immunotherapy/methods , Animals , Tumor Microenvironment/immunologyABSTRACT
CD44 is a ubiquitous leukocyte adhesion molecule involved in cell-cell interaction, cell adhesion, migration, homing and differentiation. CD44 can mediate the interaction between leukemic stem cells and the surrounding extracellular matrix, thereby inducing a cascade of signaling pathways to regulate their various behaviors. In this review, we focus on the impact of CD44s/CD44v as biomarkers in leukemia development and discuss the current research and prospects for CD44-related interventions in clinical application.
Subject(s)
Biomarkers, Tumor , Hyaluronan Receptors , Leukemia , Neoplastic Stem Cells , Humans , Neoplastic Stem Cells/metabolism , Neoplastic Stem Cells/immunology , Hyaluronan Receptors/metabolism , Leukemia/metabolism , Leukemia/therapy , Leukemia/immunology , Biomarkers, Tumor/metabolism , Animals , Signal Transduction , Molecular Targeted TherapyABSTRACT
Despite significant advancements in multiple myeloma (MM) treatment in recent years, most patients will eventually develop resistance or experience relapse. Matrine, a primary active compound of traditional Chinese medicinal herb Sophora flavescens Ait, has been found to have anti-tumor properties in various types of malignant tumors. Whether autophagy plays a crucial role in the anti-MM effect of matrine remain unknown. Herein, we found that matrine could trigger apoptosis and cell cycle arrest, and meanwhile induce autophagy in MM cells in vitro. We further ascertained the role of autophagy by using ATG5 siRNA or the autophagy inhibitor spautin-1, which partially reversed matrine's inhibitory effect on MM cells. Conversely, the combination of matrine with the autophagy inducer rapamycin enhanced their anti-tumor activity. These findings suggest that autophagy induced by matrine can lead to cell death in MM cells. Further mechanism investigation revealed that matrine treatment increased the levels of reactive oxygen species (ROS) and AMPKα1 phosphorylation and decreased the phosphorylation of mTOR in MM cells. Additionally, co-treatment with AMPKα1 siRNA or the ROS scavenger N-acetyl-1-cysteine weakened the increase in autophagy that was induced by matrine. Finally, we demonstrated a synergistic inhibitory effect of matrine and rapamycin against MM in a xenograft mouse model. Collectively, our findings provided novel insights into the anti-MM efficacy of matrine and suggest that matrine induces autophagy by triggering ROS/AMPK/mTOR axis in MM cells, and combinatorial treatment of matrine and rapamycin may be a promising therapeutic strategy against MM.
Subject(s)
AMP-Activated Protein Kinases , Alkaloids , Apoptosis , Autophagic Cell Death , Matrines , Multiple Myeloma , Quinolizines , Reactive Oxygen Species , Signal Transduction , TOR Serine-Threonine Kinases , Quinolizines/pharmacology , Multiple Myeloma/drug therapy , Multiple Myeloma/pathology , Multiple Myeloma/metabolism , Alkaloids/pharmacology , Reactive Oxygen Species/metabolism , Humans , Apoptosis/drug effects , Animals , TOR Serine-Threonine Kinases/metabolism , Cell Line, Tumor , AMP-Activated Protein Kinases/metabolism , Autophagic Cell Death/drug effects , Signal Transduction/drug effects , Xenograft Model Antitumor Assays , Mice , Autophagy/drug effectsABSTRACT
Primates rely on two eyes to perceive depth, while maintaining stable vision when either one eye or both eyes are open. Although psychophysical and modeling studies have investigated how monocular signals are combined to form binocular vision, the underlying neuronal mechanisms, particularly in V1 where most neurons exhibit binocularity with varying eye preferences, remain poorly understood. Here, we used two-photon calcium imaging to compare the monocular and binocular responses of thousands of simultaneously recorded V1 superficial-layer neurons in three awake macaques. During monocular stimulation, neurons preferring the stimulated eye exhibited significantly stronger responses compared to those preferring both eyes. However, during binocular stimulation, the responses of neurons preferring either eye were suppressed on the average, while those preferring both eyes were enhanced, resulting in similar neuronal responses irrespective of their eye preferences, and an overall response level similar to that with monocular viewing. A neuronally realistic model of binocular combination, which incorporates ocular dominance-dependent divisive interocular inhibition and binocular summation, is proposed to account for these findings.
Subject(s)
Dominance, Ocular , Eye , Animals , Vision, Binocular , Macaca , NeuronsABSTRACT
BACKGROUND: Diabetic retinopathy (DR) frequently results in compromised visual function, with hyperglycemia-induced disruption of the blood-retinal barrier (BRB) through various pathways as a critical mechanism. Existing DR treatments fail to address early and potentially reversible microvascular alterations. This study examined the effects of empagliflozin (EMPA), a selective Sodium-glucose transporter 2 (SGLT2) inhibitor, on the retina of db/db mice. The objective of this study is to investigate the potential role of EMPA in the prevention and delay of DR. METHODS: db/db mice were randomly assigned to either the EMPA treatment group (db/db + Emp) or the model group (db/db), while C57 mice served as the normal control group (C57). Mice in the db/db + Emp group received EMPA for eight weeks. Body weight, fasting blood glucose (FBG), and blood VEGF were subsequently measured in all mice, along with the detection of specific inflammatory factors and BRB proteins in the retina. Retinal SGLT2 protein expression was compared using immunohistochemical analysis, and BRB structural changes were observed via electron microscopy. RESULTS: EMPA reduced FBG, blood VEGF, and retinal inflammatory factors TNF-α, IL-6, and VEGF levels in the eye tissues of db/db mice. EMPA also increased Claudin-1, Occludin-1, and ZO-1 levels while decreasing ICAM-1 and Fibronectin, thereby preserving BRB function in db/db mice. Immunohistochemistry revealed that EMPA reduced SGLT2 expression in the retina of diabetic mice, and electron microscopy demonstrated that EMPA diminished tight junction damage between retinal vascular endothelial cells and prevented retinal vascular basement membrane thickening in diabetic mice. CONCLUSION: EMPA mitigates inflammation and preserves BRB structure and function, suggesting that it may prevent DR or serve as an effective early treatment for DR.
ABSTRACT
Asian soybean rust (ASR) is one of the major diseases that causes serious yield loss worldwide, even up to 80%. Early and accurate detection of ASR is critical to reduce economic losses. Hyperspectral imaging, combined with deep learning, has already been proved as a powerful tool to detect crop diseases. However, current deep learning models are limited to extract both spatial and spectral features in hyperspectral images due to the use of fixed geometric structure of the convolutional kernels, leading to the fact that the detection accuracy of current models remains further improvement. In this study, we proposed a deformable convolution and dilated convolution neural network (DC2Net) for the ASR detection. The deformable convolution module was used to extract the spatial features, while the dilated convolution module was applied to extract features from the spectral dimension. We also adopted the Shapley value and the channel attention methods to evaluate the importance of each wavelength during decision-making, thereby identifying the most contributing ones. The proposed DC2Net can realize early asymptomatic detection of ASR even when visual symptoms have not appeared. The results of the experiment showed that the detection performance of DC2Net dominated state-of-the-art methods, reaching an overall accuracy at 96.73%. Meanwhile, the experimental result suggested that the Shapley Additive exPlanations method was able to extract feature wavelengths correctly, thereby helping DC2Net achieve reasonable performance with less input data. The research result of this study could provide early warning of ASR outbreak in advance, even at the asymptomatic period.
ABSTRACT
BACKGROUND: Coronary heart disease (CHD) is a common heart disease and a leading cause of death in developed countries and some developing countries such as China. It is recognized as a multifactorial disease, with dyslipidemia being closely associated with the progression of coronary atherosclerosis. Numerous studies have confirmed the relationship between a single indicator of low-density lipoprotein cholesterol (LDL-C) or high-density lipoprotein cholesterol (HDL-C) and CHD. However, the association between LDL-C to HDL-C ratio (LHR) and CHD remains unclear. This study aimed to comprehensively explore the association between LHR and CHD. METHODS: This meta-analysis was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses. PubMed, Embase, Web of Science, and China National Knowledge Infrastructure databases were comprehensively searched up to June 15, 2023, to find the studies that indicated the connection between LHR and CHD. A total of 12 published studies were selected. The random-effects model was used to pool the data and mean difference (MD), and the 95% confidence intervals (CI) were taken as the overall outcome. No language restrictions existed in the study selection. The Review Manager 5.4 and Stata 12 were used to analyze the data. RESULTS: Twelve high-quality clinical studies involving 5544 participants, including 3009 patients with CHD, were enrolled in the meta-analysis. The findings revealed that the LHR was higher by 0.65 in patients with CHD than in those without CHD (MD, 0.65; 95% CI, 0.50-0.80). CONCLUSION: The LHR was found to be positively correlated with CHD, suggesting that it may serve as a potential indicator of CHD.
Subject(s)
Biomarkers , Cholesterol, HDL , Cholesterol, LDL , Coronary Disease , Humans , Coronary Disease/blood , Coronary Disease/epidemiology , Cholesterol, HDL/blood , Cholesterol, LDL/blood , Biomarkers/blood , Global Health , Risk FactorsABSTRACT
Diabetes is known to negatively affect male reproduction. Recent clinical results have confirmed that mesenchymal stem cell (MSC)-based therapies are safe and effective for the treatment of diabetes. However, the effect and potential mechanism through which MSC transplantation improves diabetes-derived male reproductive dysfunction are still unknown. In the present study, we first established a male T1D mouse model through intraperitoneal injection of streptozotocin for five consecutive days. Subsequently, we evaluated the blood glucose levels, fertility, and histology and immunology of the pancreas, testes, and penis of T1D mice with or without transplantation of menstrual blood-derived endometrial stem cells (MenSCs) or umbilical cord mesenchymal stem cells (UCMSCs). Glucose was added to the medium in which the Leydig cells were cultured to imitate high glucose-injured cell viability. Subsequently, we evaluated the cellular viability, ROS levels, and mitochondrial membrane potential of Leydig cells treated with or without MenSC-conditioned medium (MenSC-CM) using a CCK8 assay, immunofluorescence, and flow cytometry. The targeted proteins are involved in the potential mechanism underlying MenSC-derived improvements, which was further validated via Western blotting. Collectively, our results indicated that MenSC transplantation significantly ameliorated reproductive dysfunction in male T1D mice by enhancing cellular antioxidative capacity and promoting angiogenesis. This study provides solid evidence and support for the application of MSCs to improve diabetes-induced male reproductive dysfunction.
Subject(s)
Diabetes Mellitus, Experimental , Endometrium , Animals , Male , Mice , Diabetes Mellitus, Experimental/therapy , Female , Endometrium/metabolism , Endometrium/pathology , Leydig Cells/metabolism , Antioxidants/pharmacology , Infertility, Male/therapy , Diabetes Mellitus, Type 1/metabolism , Diabetes Mellitus, Type 1/therapy , Mesenchymal Stem Cell Transplantation/methods , Reactive Oxygen Species/metabolism , Mice, Inbred C57BLABSTRACT
RESEARCH QUESTION: Does type 1 diabetes mellitus (T1DM) affect reproductive health of female patients? What is the potential mechanism of reproductive dysfunction in female patients caused by T1DM? DESIGN: Preliminary assessment of serum levels of female hormones in women with or without T1DM. Then histological and immunological examinations were carried out on the pancreas, ovaries and uteri at different stages in non-obese diabetic (NOD) and Institute of Cancer Research (ICR) mice, as well as assessment of their fertility. A protein array was carried out to detect the changes in serum inflammatory cytokines. Furthermore, RNA-sequencing was used to identify the key abnormal genes/pathways in ovarian and uterine tissues of female NOD mice, which were further verified at the protein level. RESULTS: Testosterone levels were significantly increased (Pâ¯=â¯0.0036) in female mice with T1DM. Increasing age in female NOD mice was accompanied by obvious lymphocyte infiltration in the pancreatic islets. Moreover, the levels of serum inflammatory factors in NOD mice were sharply increased with increasing age. The fertility of female NOD mice declined markedly, and most were capable of conceiving only once. Furthermore, ovarian and uterine morphology and function were severely impaired in NOD female mice. Additionally, ovarian and uterine tissues revealed that the differentially expressed genes were primarily enriched in metabolism, cytokine-receptor interactions and chemokine signalling pathways. CONCLUSION: T1DM exerts a substantial impairment on female reproductive health, leading to diminished fertility, potentially associated with immune disorders and alterations in energy metabolism.
Subject(s)
Diabetes Mellitus, Type 1 , Islets of Langerhans , Humans , Female , Animals , Mice , Diabetes Mellitus, Type 1/genetics , Diabetes Mellitus, Type 1/metabolism , Diabetes Mellitus, Type 1/pathology , Mice, Inbred NOD , Pancreas/metabolism , Pancreas/pathology , Islets of Langerhans/metabolism , Islets of Langerhans/pathology , Cytokines/metabolism , Inflammation/metabolismABSTRACT
Despite great potential in fabrication of biodegradable protective membranes by electrospinning of poly(lactic acid) (PLA) nanofibers, it is still thwarted by smooth surfaces and poor electroactivity that challenge the promotion of electret properties and long-term air filtration performance. Here, a microwave-assisted synthetic method was used to customize dielectric TiO2 nanocrystals of ultrasmall and uniform dimensions (â¼30 nm), which were homogeneously embedded at beaded PLA nanofibers (PLA@TiO2, diameter of around 280 nm) by the combined "electrospinning-electrospray" approach. With small amounts of TiO2 (2, 4 and 6 wt%), the nanopatterned PLA@TiO2 nanofibrous membranes (NFMs) were characterized by largely increased dielectric constants (nearly 1.9), surface potential (up to 1.63 kV) and triboelectric properties (output voltage of 12.2 V). Arising from the improved electroactivity and self-charging mechanisms, the nanopatterned PLA@TiO2 NFMs exhibited remarkable PM0.3 filtration properties (97.9 %, 254.6 Pa) even at the highest airflow rate of 85 L/min, surpassing those of pure PLA membranes (86.2 %, 483.7 Pa). This was moreover accompanied by inhibition rates of 100 % against both E. coli and S. aureus, as well as excellent UV-blocking properties (UPF as high as 3.8, TUVA of 50.9 % and TUVB of 20.1 %). The breathable and electroactive nanopatterned PLA NFMs permit promising applications in multifunctional protective membranes toward excellent UV shielding and high-efficiency removal of both PMs and pathogens.
Subject(s)
Nanofibers , Nanofibers/chemistry , Staphylococcus aureus , Escherichia coli , Polyesters/chemistry , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistryABSTRACT
Despite the great promise in the development of biodegradable and ecofriendly air filters by electrospinning of poly(lactic acid) (PLA) nanofibrous membranes (NFMs), the as-electrospun PLA nanofibers are generally characterized by poor electroactivity and smooth surface, challenging the exploitation of electrostatic adsorption and physical interception that are in need for efficient removal of pathogens and particulate matters (PMs). Herein, a combined "electrospinning-electrospray" strategy was disclosed to functionalize the PLA nanofibers by direct anchoring of highly dielectric BaTiO3@ZIF-8 nanohybrids (BTO@ZIF-8), conferring simultaneous promotion of surface roughness, electret properties (surface potential as high as 7.5 kV), and self-charging capability (â¼190% increase in tribo-output voltage compared to that of pure PLA). Benefiting from the well-tailored morphology and increased electroactivity, the electrospun-electrosprayed PLA/BTO@ZIF-8 exhibited excellent PM-capturing performance (up to 96.54% for PM0.3 and 99.49% for PM2.5) while providing desirable air resistance (only 87 Pa at 32 L/min) due primarily to the slip flow of air molecules over the nanohybrid protrusions. This was accompanied by excellent antibacterial properties (99.9% inhibition against both Staphylococcus aureus and Escherichia coli), arising presumably from the synergistic effects of enhanced reactive oxygen species (ROS) generation, plentiful ion release, and surface charges. Our proposed strategy opens up pathways to afford exceptional combination of high-efficiency and low-resistance filtration, excellent antibacterial performance, and mechanical robustness without sacrificing the biodegradation profiles of PLA NFMs, holding potential implications for efficient and long-term healthcare.
ABSTRACT
Chemotherapy can cause ovarian dysfunction and infertility since the ovary is extremely sensitive to chemotherapeutic drugs. Apart from the indispensable role of the ovary in the overall hormonal milieu, ovarian dysfunction also affects many other organ systems and functions including sexuality, bones, the cardiovascular system, and neurocognitive function. Although conventional hormone replacement therapy can partly relieve the adverse symptoms of premature ovarian insufficiency (POI), the treatment cannot fundamentally prevent deterioration of POI. Therefore, effective treatments to improve chemotherapy-induced POI are urgently needed, especially for patients desiring fertility preservation. Recently, mesenchymal stem cell (MSC)-based therapies have resulted in promising improvements in chemotherapy-induced ovary dysfunction by enhancing the anti-apoptotic capacity of ovarian cells, preventing ovarian follicular atresia, promoting angiogenesis and improving injured ovarian structure and the pregnancy rate. These improvements are mainly attributed to MSC-derived biological factors, functional RNAs, and even mitochondria, which are directly secreted or indirectly translocated with extracellular vesicles (microvesicles and exosomes) to repair ovarian dysfunction. Additionally, as a novel source of MSCs, menstrual blood-derived endometrial stem cells (MenSCs) have exhibited promising therapeutic effects in various diseases due to their comprehensive advantages, such as periodic and non-invasive sample collection, abundant sources, regular donation and autologous transplantation. Therefore, this review summarizes the efficacy of MSCs transplantation in improving chemotherapy-induced POI and analyzes the underlying mechanism, and further discusses the benefit and existing challenges in promoting the clinical application of MenSCs in chemotherapy-induced POI.
Subject(s)
Antineoplastic Agents , Mesenchymal Stem Cell Transplantation , Mesenchymal Stem Cells , Primary Ovarian Insufficiency , Pregnancy , Humans , Female , Mesenchymal Stem Cell Transplantation/methods , Follicular Atresia , Primary Ovarian Insufficiency/chemically induced , Primary Ovarian Insufficiency/therapy , Antineoplastic Agents/adverse effectsABSTRACT
Biodegradable polylactic acid (PLA) nanofibrous membranes (NFMs) hold great potential to address the increasing airborne particulate matter (PM) and dramatic accumulation of plastic/microplastic pollution. However, the field of PLA NFM-based filters is still in its infancy, frequently dwarfed by the bottlenecks regarding relatively low surface activity, poor electroactivity, and insufficient PM capturing mechanisms. This effort discloses a microwave-assisted approach to minute-level synthesis of dielectric ZIF-8 nanocrystals with high specific surface area (over 1012 m2/g) and ultrasmall size (â¼240 nm), which were intimately anchored onto PLA nanofibers (PLA@ZIF-8) by a combined "electrospinning-electrospray" strategy. This endowed the PLA@ZIF-8 NFMs with largely increased electroactivity in terms of elevated dielectric coefficient (an increase of 202%), surface potential (up to 5.8 kV), and triboelectric properties (output voltage of 30.8 V at 10 N, 0.5 Hz). Given the profound control over morphology and electroactivity, the PLA@ZIF-8 NFMs exhibited efficient filtration of PM0.3 (97.1%, 85 L/min) with a decreased air resistance (592.5 Pa), surpassing that of the pure PLA counterpart (88.4%, 650.9 Pa). This was essentially ascribed to realization of multiple filtration mechanisms for PLA@ZIF-8 NFMs, including enhanced physical interception, polar interactions, and electrostatic adsorption, and the unique self-charging function triggered by airflow vibrations. Moreover, perfect antibacterial performance was achieved for PLA@ZIF-8, showing ultrahigh inhibition rates of 99.9 and 100% against E. coli and S. aureus, respectively. The proposed hierarchical structuring strategy, offering the multifunction integration unattainable with conventional methods, may facilitate the development of biodegradable long-term air filters.
Subject(s)
Nanofibers , Nanofibers/chemistry , Plastics , Escherichia coli , Staphylococcus aureus , Polyesters/chemistry , Filtration/methodsABSTRACT
Parkinson's disease (PD) is the second largest neurodegenerative disorder caused by the decreased number of dopaminergic (DAc) neurons in the substantia nigra pars compacta (SNpc). There is evidence that oxidative stress can contribute degeneration of DAc neurons in SNpc which is mainly caused by apoptotic cell death. Thus, suppressing oxidative stress and apoptosis of DAc neurons is an effective strategy to mitigate the progress of PD. Astaxanthin (AST) is a carotenoid, which mainly exists in marine organisms and is a powerful biological antioxidant. In this study, we aimed to determine the neuroprotective effect of AST on paraquat (PQ) -induced models of PD in vitro and in vivo. Here, we showed that AST significantly enhanced cell survival of SH-SY5Y cells against PQ toxicity by suppressing apoptotic cell death and oxidative stress. Moreover, we found that AST significantly ameliorated PQ-induced behavioral disorders associated with PD in C57BL/6 J mice and the damage to DAc neurons in the SNpc of mice. Lastly, we found that the neuroprotective effects of AST were conducted through inhibiting PQ-induced activation of MAPK signaling. In conclusion, our study indicates that AST had a strong protective effect on PQ-induced oxidative stress and antagonized apoptotic cell death in SH-SY5Y cells and PQ-induced mice PD model, which might provide new insights of AST for PD treatment.
Subject(s)
Neuroblastoma , Parkinson Disease , Humans , Animals , Mice , Mice, Inbred C57BL , Parkinson Disease/drug therapy , Paraquat/toxicity , Dopaminergic Neurons , Disease Models, AnimalABSTRACT
BACKGROUND: The inexpensive and readily available biomarkers for cytokine release syndrome (CRS) grading and prognosis assessment in chimeric antigen receptor (CAR)-T therapy are currently lacking. This study examined the significance of alkaline phosphatase (ALP) after CAR-T therapy in patients with relapsed/refractory multiple myeloma (MM). METHODS: This cohort study included 27 patients with relapsed/refractory MM who were treated with CAR-T cells between December 2017 and October 2021. Patients were classified into 2 groups: normal ALP group (peak ALP <125 U/L, n = 10) and high ALP group (peak ALP ≥125 U/L, n = 17). RESULTS: Within 1 month of CAR-T cell infusion, the incidence of ALP increases was 63%. We found that ALP levels began to rise in the second week, peaked in the third and fourth weeks, and began to decline in the second month. Moreover, the ALP levels in previous chemotherapy-responsive period were significantly lower than those after CAR-T therapy. Statistical analysis found that patients with increased ALP exhibited higher alanine aminotransferase and aspartate aminotransferase levels, higher and longer CAR-T cell proliferation, more serious CRS, higher cytokine and ferritin levels, and higher initial response rates. In addition, the duration of ALP increase was parallel to the duration of CAR-T expansion. Multivariable Cox-regression analysis showed that peak ALP was the independent predictor for progression-free survival (PFS) (HR = 0.029, 95% CI: 0.002-0.369). CONCLUSIONS: Our results suggest that the ALP levels after CAR-T therapy could serve as a suitable biomarker for monitoring CAR-T cell proliferation, CRS grading, and prognosis in patients with MM.
Subject(s)
Multiple Myeloma , Receptors, Chimeric Antigen , Humans , Multiple Myeloma/therapy , Alkaline Phosphatase , Cohort Studies , Immunotherapy, Adoptive/adverse effects , Immunotherapy, Adoptive/methods , Cytokine Release Syndrome , Cell- and Tissue-Based TherapyABSTRACT
Traditional polymeric fibrous membranes have been extensively used to reduce the health risks caused by airborne particulate matter (PM), leading to the dramatically increasing pollution of plastics and microplastics. Although great efforts have been made to develop poly(lactic acid) (PLA)-based membrane filters, they are frequently dwarfed by their relatively poor electret properties and electrostatic adsorptive mechanisms. To resolve this dilemma, a bioelectret approach was proposed in this work, strategically involving the bioinspired adhesion of dielectric hydroxyapatite nanowhiskers as a biodegradable electret to promote the polarization properties of PLA microfibrous membranes. In addition to significant improvements in tensile properties, the incorporation of hydroxyapatite bioelectret (HABE) enabled remarkable increase in the removal efficiencies of ultrafine PM0.3 in a high-voltage electrostatic field (10 and 25 kV). This was exemplified by the largely increased filtering performance (69.75%, 23.1 Pa) for PLA membranes loaded with 10 wt% HABE at the normal airflow rate (32 L/min) compared to the pristine PLA counterpart (32.89%, 7.2 Pa). Although the filtration efficiency of PM0.3 for the counterpart dramatically decreased to 21.6% at 85 L/min, the increment was maintained at nearly 196% for the bioelectret PLA, while an ultralow pressure drop (74.5 Pa) and high humidity resistance (RH 80%) were achieved. The unusual property combination were ascribed to the HABE-enabled realization of multiple filtration mechanisms, including the simultaneous enhancement of physical interception and electrostatic adsorption. The significant filtration applications, unattainable with conventional electret membranes, demonstrate the bioelectret PLA as a promising biodegradable platform that allows high filtration properties and humidity resistance.