All‐polymer solar cells (all‐PSCs) have received attention in recent years for their desirable properties in power conversion efficiency and long‐term operational stability. However, it is still a ...big challenge to acquire an “ideal” vertical‐phase distribution of polymer/polymer blends due to the non‐ideal molecular conformations and mixing behaviors. Herein, a ternary‐assisted sequential solution deposition (SSD) strategy is adopted to regulate the vertical compositional profile of all‐PSCs. A favorable acceptor(donor)‐enriched phase near the cathode(anode) can be obtained by a ternary‐assisted SSD strategy. With such a compositional profile, the exciton yield and carrier density can be enhanced by the vertical component gradient. Remarkably, the non‐geminate recombination is suppressed with an improved exciton diffusion length (15.36 nm) that delivers an outstanding power conversion efficiency over 16% of the ternary PM6/PY‐IT:PDI‐2T SSD devices. This work demonstrates the success of ternary‐assisted SSD strategy in reorganizing the vertical‐phase distribution, which provides a feasible route for a potential ternary device construction toward efficient all‐polymer photovoltaics.
A vertical compositional gradient within the active layer with a donor‐enriched active‐anode interface and an acceptor‐enriched active‐cathode interface can be achieved by sequential solution deposition treatment in PM6/PY‐IT:PDI‐2T device. As a result, charge transfer properties and exciton diffusion length are promoted with suppressed non‐geminate recombination to deliver an outstanding power conversion efficiency of 16% in the all‐polymer solar cells, which are verified with transient absorption, time‐resolved photoluminescence, and capacitance‐voltage measurements.
Microglial polarization is one of the most promising therapeutic strategies for multiple central nervous system (CNS) disorders. However, safe, effective, and controllable microglial regulation still ...faces formidable challenges. Although some anti‐inflammatory factors promote microglia polarization, their short half‐life, high cost, unpredictable in vivo behavior, and complex delivery operations, hamper their clinical application. Here, inspired by the natural microhemorrhage cleaning mechanism, an MG1 peptide and RVG29 peptide engineered nanoerythrocyte (NEMR) that can reprogram microglia are developed from classical M1 toward alternative M2 by inducing heme oxygenase‐1 (HO‐1), stimulating Notch1/Hes1/Stat3 signaling, and further inhibiting NF‐κB p65 translocation. Moreover, anti‐inflammatory carbon monoxide (CO) and bilirubin produced by endogenous metabolism of heme further reinforces the anti‐inflammatory effect. In middle cerebral artery occlusion and experimental autoimmune encephalomyelitis models, a satisfactory prognosis is achieved, with precise regulation of inflammatory microglia in lesion sites, increased expression of anti‐inflammatory factors, reduced blood–brain barrier permeability, as well as promotion of neurogenesis and functional recovery. Furthermore, NEMR can be integrated with clinical therapeutic agents, which facilitates precise drug delivery to enhance therapeutic effects. Hence, the natural nanoerythrocytes, as a feasible, efficient, safe, and practical tool, provides a new strategy for rebalancing of the immune environment in the CNS disorders.
Microglia are the main regulator of inflammatory response in ischemic stroke and multiple sclerosis. An engineered nanoerythrocyte immunosuppressive platform is developed for precise targeting and efficient reprogramming of M1 microglia. The regulation of microglia function, protection of the blood–brain barrier, and neurons are realized through upregulation of heme oxygenase‐1 and reinforcement by intrinsic metabolism to generate anti‐inflammatory substances CO and bilirubin.
Colorectal cancer (CRC) is the second most common cause of cancer incidence worldwide. Oral drug delivery systems (ODDS) have shown great promise for CRC therapy, but the delivery efficiency is still ...challenged by the dense intestinal mucus barrier and nonspecific interception of abnormally proliferated pathogenic bacteria. Herein, self‐thermophoretic nanoparticles (CTPB) is presented to enhance intestinal mucus penetration and reduce pathogenic bacteria interception in CRC for efficient drug delivery. The nanoplatform introduces hollow mesoporous copper sulfide and is asymmetrically sprayed with titanium dioxide as the self‐thermophoretic matrix. Based on the close relationship between pathogenic bacteria and CRC, the nanoplatform is camouflaged by the biomimetic membrane of Staphylococcus aureus to precisely anchor in the intestinal segment of CRC. After near‐infrared laser irradiation, CTPB can effectively increase the intestinal mucus penetration efficiency by 2.7 folds, and decrease the pathogenic bacterial interception by 3.5 folds via the self‐thermophoretic propulsion force. In orthotopic CRC‐bearing mice, CTPB vastly improved the drug delivery efficiency to CRC after oral administration, thus showing a 99.4% antitumor rate after three weeks of treatment, which provides new insight into oral drug delivery for CRC therapy.
The delivery efficiency of oral nanoparticles is always limited by intestinal mucus and pathogenic bacteria interception. A self‐thermophoretic nanoparticle is developed for colorectal cancer therapy through penetrating intestinal mucus and detaching from pathogenic bacteria. With improved delivery efficiency, the nanoparticles showed a 99.4% antitumor efficiency in vivo, and provides a new strategy for orally targeted therapy of colorectal cancer.
Delta-secretase cleaves both APP and Tau to mediate the formation of amyloid plaques and neurofibrillary tangle in Alzheimer's disease (AD). However, how aging contributes to an increase in ...delta-secretase expression and AD pathologies remains unclear. Here we show that a CCAAT-enhancer-binding protein (C/EBPβ), an inflammation-regulated transcription factor, acts as a key age-dependent effector elevating both delta-secretase (AEP) and inflammatory cytokines expression in mediating pathogenesis in AD mouse models. We find that C/EBPβ regulates delta-secretase transcription and protein levels in an age-dependent manner. Overexpression of C/EBPβ in young 3xTg mice increases delta-secretase and accelerates the pathological features including cognitive dysfunctions, which is abolished by inactive AEP C189S. Conversely, depletion of C/EBPβ from old 3xTg or 5XFAD mice diminishes delta-secretase and reduces AD pathologies, leading to amelioration of cognitive impairment in these AD mouse models. Thus, our findings support that C/EBPβ plays a pivotal role in AD pathogenesis via increasing delta-secretase expression.
In the plastic extrusion process, most of the equipment is not production record and manufacturing information integrated, some production lines are not even installed sensors to monitor basic ...signals. This will cause the production line not being able to manufacture in optimal mode and cannot troubleshoot when exceptions occur. This research is mainly verified by the pressure instability of the extrusion system, unmelted resin will lead to the extrusion instability. The single-screw extruder is used as the experimental process machine (screw diameter is 25mm, screw diameter ratio is 26D, four temperature zones). Since there are many melt properties that cannot be measured by physical sensors, the melt pressure spectrum as input features, and used a regression model to design a soft sensor. To develop a monitoring system to monitor the melt state of the extrusion process. Thus, the pressure signal is captured on the adapter flow channel. The spectrum of the pressure signal is obtained using FFT after analog signal processing. To apply the spectrum to the analysis extrusion instability, this research extracted the Top-10 frequency components in the spectrum. The machine learning model of soft sensor predicts the perturbation frequency of the pressure and other related numerical results. The model dataset contains process parameters, variables and spectral feature. The models used are random forest classification and regression. According to the model results, the classification prediction accuracy is at least 0.91, the R 2 score based on the proposed dataset can reach 0.97. The classification and regression results of the proposed model are satisfactory.
• Basic helix–loop–helix (bHLH) proteins are involved in transcriptional networks controlling a number of biological processes in plants. However, little information is known on the roles of bHLH ...proteins in cotton fibre development so far.
• Here, we show that a cotton bHLH protein (GhFP1) positively regulates fibre elongation. GhFP1 transgenic cotton and Arabidopsis plants were generated to study how GhFP1 regulates fibre cell elongation.
• Fibre length of the transgenic cotton overexpressing GhFP1 was significantly longer than that of wild-type, whereas suppression of GhFP1 expression hindered fibre elongation. Furthermore, overexpression of GhFP1 in Arabidopsis promoted trichome development. Expression of the brassinosteroid (BR)-related genes was markedly upregulated in fibres of GhFP1 overexpression cotton, but downregulated in GhFP1-silenced fibres. BR content in the transgenic fibres was significantly altered, relative to that in wild-type. Moreover, GhFP1 protein could directly bind to the promoters of GhDWF4 and GhCPD to activate expression of these BR-related genes.
• Therefore, our data suggest that GhFP1 as a positive regulator participates in controlling fibre elongation by activating BR biosynthesis and signalling. Additionally, homodimerisation of GhFP1 may be essential for its function, and interaction between GhFP1 and other cotton bHLH proteins may interfere with its DNA-binding activity.
BDNF/TrkB neurotrophic signaling regulates neuronal development, differentiation, and survival, and deficient BDNF/TrkB activity underlies neurodegeneration in Alzheimer’s disease (AD). However, ...exactly how BDNF/TrkB participates in AD pathology remains unclear. Here, we show that deprivation of BDNF/TrkB increases inflammatory cytokines and activates the JAK2/STAT3 pathway, resulting in the upregulation of transcription factor C/EBPβ. This, in turn, results in increased expression of δ-secretase, leading to both APP and Tau fragmentation by δ-secretase and neuronal loss, which can be blocked by expression of STAT3 Y705F, knockdown of C/EBPβ, or the δ-secretase enzymatic-dead C189S mutant. Inhibition of this pathological cascade can also rescue impaired synaptic plasticity and cognitive dysfunctions. Importantly, reduction in BDNF/TrkB neurotrophic signaling is inversely coupled with an increase in JAK2/STAT3, C/EBPβ, and δ-secretase escalation in human AD brains. Therefore, our findings provide a mechanistic link between BDNF/TrkB reduction, C/EBPβ upregulation, δ-secretase activity, and Aβ and Tau alterations in murine brains.
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•Deprivation of BDNF increases inflammatory cytokines•Deprivation of BDNF upregulates C/EBPβ by JAK2/STAT3 pathway•BDNF knockout increases expression of AEP by C/EBPβ•Inhibition of JAK2/STAT3/C/EBPβ/AEP prevents BDNF-depletion-mediated pathology
Deficient BDNF/TrkB activity underlies AD pathogenesis. Wang et al. report that deprivation of BDNF/TrkB increases inflammatory cytokines and activates the JAK2/STAT3 pathway, resulting in the upregulation of C/EBPβ/AEP signaling. Reduction of BDNF is inversely coupled with the aforementioned pathway in AD brains. Inhibition of JAK2/STAT3/C/EBPβ/AEP prevents BDNF-depletion-mediated pathology.
•The prevalence of anxiety and depression symptom was 7.7% and 12.2%, respectively.•Having confirmed and suspected cases in family members or relatives was associated with the higher risk of ...depression symptom.•Self-reported health condition was strongly associated with risk of anxiety and depression symptom.
: Although studies have suggested experiencing the epidemic of severe infectious diseases increased the prevalence of mental health problems, the association between COVID-19 epidemic and risk of anxiety and depression symptom in college students in China was unclear.
: A large cross-sectional online survey with 44,447 college students was conducted in Guangzhou, China. The Zung's Self-rating Anxiety Scale (SAS) and the Center for Epidemiologic Studies Depression Scale (CES-D Scale) were used to define the anxiety and depression symptom, respectively. Multivariable logistic regression models were used to analyze the association between COVID-19 epidemic and risk of anxiety and depression symptom.
: The prevalence of anxiety and depression symptom was 7.7% (95% confidence interval CI: 7.5%, 8.0%) and 12.2% (95%CI: 11.9%, 12.5%), respectively. Compared with students who reported have not infected or suspected cases in family members and relatives, students who reported having confirmed (OR=4.06; 95%CI: 1.62, 10.19; P = 0.003), and suspected (OR=2.11; 95%CI: 1.11, 4.00; P = 0.023) cases in family members and relatives had higher risk of depression symptom. Additionally, the proportions of students with anxiety and depression symptom reported more demand of psychological knowledge and interventions than those without (P<0.001).
: All the data in this study was collected through online questionnaire, and we did not evaluate the reliability and validity.
: The prevalence of anxiety and depression symptom was relatively low in college students, but the COVID-19 epidemic-related factors might be associated with higher depression symptom risk.
Arbuscular mycorrhizal (AM) symbiosis is known to stimulate plant drought tolerance. However, the molecular basis for the direct involvement of AM fungi (AMF) in plant water relations has not been ...established.
Two full-length aquaporin genes, namely GintAQPF1 and GintAQPF2, were cloned by rapid amplification of cDNA 5'- and 3'-ends from an AMF, Glomus intraradices. Aquaporin localization, activities and water permeability were examined by heterologous expression in yeast. Gene expression during symbiosis was also analyzed by quantitative real-time polymer-ase chain reaction.
GintAQPF1 was localized to the plasma membrane of yeast, whereas GintAQPF2 was localized to both plasma and intracellular membranes. Transformed yeast cells exhibited a signifi-cant decrease in cell volume on hyperosmotic shock and faster protoplast bursting on hypo-osmotic shock. Polyethylene glycol (PEG) stimulated, but glycerol inhibited, the aquaporin activities. Furthermore, the expression of the two genes in arbuscule-enriched cortical cells and extraradical mycelia of maize roots was also enhanced significantly under drought stress.
GintAQPF1 and GintAQPF2 are the first two functional aquaporin genes from AMF reported to date. Our data strongly support potential water transport via AMF to host plants, which leads to a better understanding of the important role of AMF in plant drought tolerance.
Pyridine-based ring systems are one of the most extensively used heterocycles in the field of drug design, primarily due to their profound effect on pharmacological activity, which has led to the ...discovery of numerous broad-spectrum therapeutic agents. In the US FDA database, there are 95 approved pharmaceuticals that stem from pyridine or dihydropyridine, including isoniazid and ethionamide (tuberculosis), delavirdine (HIV/AIDS), abiraterone acetate (prostate cancer), tacrine (Alzheimer's), ciclopirox (ringworm and athlete's foot), crizotinib (cancer), nifedipine (Raynaud's syndrome and premature birth), piroxicam (NSAID for arthritis), nilvadipine (hypertension), roflumilast (COPD), pyridostigmine (myasthenia gravis), and many more. Their remarkable therapeutic applications have encouraged researchers to prepare a larger number of biologically active compounds decorated with pyridine or dihydropyridine, expandeing the scope of finding a cure for other ailments. It is thus anticipated that myriad new pharmaceuticals containing the two heterocycles will be available in the forthcoming decade. This review examines the prospects of highly potent bioactive molecules to emphasize the advantages of using pyridine and dihydropyridine in drug design. We cover the most recent developments from 2010 to date, highlighting the ever-expanding role of both scaffolds in the field of medicinal chemistry and drug development.
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