ABSTRACT
Background: The novel coronavirus disease 2019 (COVID-19) pandemic spread worldwide and brought unprecedented challenges to healthcare systems. Healthcare workers experienced tremendous pressure and psychological issues. Methods: A cross-sectional online survey was conducted from January 2022 to April 2022 among healthcare workers in Anyang, Henan Province, China. Insomnia, anxiety, depression, post-traumatic stress disorder (PTSD), and problematic internet use (PIU) were evaluated. Logistic regression analyses were used to explore the factors that were associated with mental health problems. Results: A total of 242 participants (mean [SD] age, 34.7 [6.6] years, 187 female [77.3 %]) were included in the study. The prevalence of symptoms of insomnia, anxiety, depression, PTSD and PIU during the COVID-19 pandemic in China was 53.7 %, 100.0 %, 7.0 %, 20.3 %, and 19.4 %, respectively. Participants who smoked, used sedative-hypnotic drugs and may need psychological assistance were at a higher risk for mental health problems. Respondents who were older than 45 years and were married displayed a lower risk of insomnia and PTSD, respectively. Conclusions: Mental health symptoms are pervasive among healthcare workers in specialized COVID-19 hospitals during the outbreak. Risk factors include smoking, sedative-hypnotic drug use, and the need for psychological assistance, while protective factors include age and marital status. Developing social media platforms and providing psychological assistance may be effective interventions for healthcare workers.
ABSTRACT
The central histaminergic system has a pivotal role in emotional regulation and psychiatric disorders, including anxiety, depression and schizophrenia. However, the effect of histamine on neuronal activity of the centrolateral amygdala (CeL), an essential node for fear and anxiety processing, remains unknown. Here, using immunostaining and whole-cell patch clamp recording combined with optogenetic manipulation of histaminergic terminals in CeL slices prepared from histidine decarboxylase (HDC)-Cre rats, we show that histamine selectively suppresses excitatory synaptic transmissions, including glutamatergic transmission from the basolateral amygdala, on both PKC-δ- and SOM-positive CeL neurons. The histamine-induced effect is mediated by H3 receptors expressed on VGLUT1-/VGLUT2-positive presynaptic terminals in CeL. Furthermore, optoactivation of histaminergic afferent terminals from the hypothalamic tuberomammillary nucleus (TMN) also significantly suppresses glutamatergic transmissions in CeL via H3 receptors. Histamine neither modulates inhibitory synaptic transmission by presynaptic H3 receptors nor directly excites CeL neurons by postsynaptic H1, H2 or H4 receptors. These results suggest that histaminergic afferent inputs and presynaptic H3 heteroreceptors may hold a critical position in balancing excitatory and inhibitory synaptic transmissions in CeL by selective modulation of glutamatergic drive, which may not only account for the pathophysiology of psychiatric disorders but also provide potential psychotherapeutic targets. KEY POINTS: Histamine selectively suppresses the excitatory, rather than inhibitory, synaptic transmissions on both PKC-δ- and SOM-positive neurons in the centrolateral amygdala (CeL). H3 receptors expressed on VGLUT1- or VGLUT2-positive afferent terminals mediate the suppression of histamine on glutamatergic synaptic transmission in CeL. Optogenetic activation of hypothalamic tuberomammillary nucleus (TMN)-CeL histaminergic projections inhibits glutamatergic transmission in CeL via H3 receptors.
ABSTRACT
To address the global energy shortage and mitigate greenhouse gas emissions on a massive scale, it is critical to explore novel and efficient photocatalysts for the utilization of renewable resources. Bi-based metal oxide (BixMOy) semiconductors composed of bismuth, transition metal, and oxygen atoms have demonstrated improved photocatalytic activity and product selectivity. The vast number of element combinations available for BixMOymaterials provides a huge compositional space for the rational design and isolation of promising photocatalysts for specific applications. In this study, we have systematically investigated the electronic and optical properties over Bi2O3and a series of selected BixMOygroup materials (BiVO4, BiFeO3, BiCoO3, and BiCrO3) by calculating band structure, basic optical property features, mobility and separation of charge carriers. It is clearly noted that the band gap and band edge position of the BixMOygroup materials can be tuned in a wide range in comparison to Bi2O3. Similarly, the light response of BixMOyalso can be broadened from the ultraviolet to the visible light region by adjusting the selection of transition metals. Additionally, the analysis of the effective mass of charge carriers of these materials further confirms their possibility in photocatalytic reaction applications because of the appropriate separation efficiency and mobility of carriers. A selection of experimental investigations on the crystal structure, composition, and optical properties of Bi2O3, BiVO4, and BiFeO3as well as their catalytic performance in the degradation of methylene blue over was also conducted, which agree well with the theoretical predictions.
ABSTRACT
Tetrachloroethylene ï¼PCEï¼ and trichloroethylene ï¼TCEï¼ are typical volatile halogenated organic compounds in groundwater that pose serious threats to the ecological environment and human health. To obtain an anaerobic microbial consortium capable of efficiently dechlorinating PCE and TCE to a non-toxic end product and to explore its potential in treating contaminated groundwaterï¼ an anaerobic microbial consortium W-1 that completely dechlorinated PCE and TCE to ethylene was obtained by repeatedly feeding PCE or TCE into the contaminated groundwater collected from an industrial site. The dechlorination rates of PCE and TCE were ï¼120.1 ±4.9ï¼ µmol·ï¼L·dï¼-1 and ï¼172.4 ±21.8ï¼ µmol·ï¼L·dï¼-1 in W-1ï¼ respectively. 16S rRNA gene amplicon sequencing and quantitative PCR ï¼qPCRï¼ showed that the relative abundance of Dehalobacter increased from 1.9% to 57.1%ï¼ with the gene copy number increasing by 1.7×107 copies per 1 µmol Cl- released when 98.3 µmol of PCE was dechlorinated to cis-1ï¼2-dichloroethylene ï¼cis-1ï¼2-DCEï¼. The relative abundance of Dehalococcoides increased from 1.1% to 53.8% when cis-1ï¼2-DCE was reductively dechlorinated to ethylene. The growth yield of Dehalococcoides gene copy number increased by 1.7×108 copies per 1 µmol Cl- released for the complete reductive dechlorination of PCE to ethylene. The results indicated that Dehalobacter and Dehalococcoides cooperated to completely detoxify PCE. When TCE was used as the only electron acceptorï¼ the relative abundance of Dehalococcoides increased from ï¼29.1 ±2.4ï¼% to ï¼7.7 ±0.2ï¼%ï¼ and gene copy number increased by ï¼1.9 ±0.4ï¼×108 copies per 1 µmol Cl- releasedï¼ after dechlorinating 222.8 µmol of TCE to ethylene. The 16S rRNA gene sequence of Dehalococcoides LWT1ï¼ the main functional dehalogenating bacterium in enrichment culture W-1ï¼ was obtained using PCR and Sanger sequencingï¼ and it showed 100% similarity with the 16S rRNA gene sequence of D. mccartyi strain 195. The anaerobic microbial consortium W-1 was also bioaugmented into the groundwater contaminated by TCE at a concentration of 418.7 µmol·L-1. The results showed that ï¼69.2 ±9.8ï¼% of TCE could be completely detoxified to ethylene within 28 days with a dechlorination rate of ï¼10.3 ±1.5ï¼ µmol·ï¼L·dï¼-1. This study can provide the microbial resource and theoretical guidance for the anaerobic microbial remediation in PCE or TCE-contaminated groundwater.
Subject(s)
Chloroflexi , Ethylene Dichlorides , Tetrachloroethylene , Trichloroethylene , Humans , Anaerobiosis , RNA, Ribosomal, 16S/genetics , Ethylenes , Dichloroethylenes , Biodegradation, Environmental , Chloroflexi/geneticsABSTRACT
Physical exercise is known to reduce anxiety, but the underlying brain mechanisms remain unclear. Here, we explore a hypothalamo-cerebello-amygdalar circuit that may mediate motor-dependent alleviation of anxiety. This three-neuron loop, in which the cerebellar dentate nucleus takes center stage, bridges the motor system with the emotional system. Subjecting animals to a constant rotarod engages glutamatergic cerebellar dentate neurons that drive PKCδ+ amygdalar neurons to elicit an anxiolytic effect. Moreover, challenging animals on an accelerated rather than a constant rotarod engages hypothalamic neurons that provide a superimposed anxiolytic effect via an orexinergic projection to the dentate neurons that activate the amygdala. Our findings reveal a cerebello-limbic pathway that may contribute to motor-triggered alleviation of anxiety and that may be optimally exploited during challenging physical exercise.
Subject(s)
Anti-Anxiety Agents , Animals , Anxiety/metabolism , Hypothalamus , Cerebellum , Anxiety DisordersABSTRACT
Although more than 30 different types of neuropeptides have been identified in various cell types and circuits of the cerebellum, their unique functions in the cerebellum remain poorly understood. Given the nature of their diffuse distribution, peptidergic systems are generally assumed to exert a modulatory effect on the cerebellum via adaptively tuning neuronal excitability, synaptic transmission, and synaptic plasticity within cerebellar circuits. Moreover, cerebellar neuropeptides have also been revealed to be involved in the neurogenetic and developmental regulation of the developing cerebellum, including survival, migration, differentiation, and maturation of the Purkinje cells and granule cells in the cerebellar cortex. On the other hand, cerebellar neuropeptides hold a critical position in the pathophysiology and pathogenesis of many cerebellar-related motor and psychiatric disorders, such as cerebellar ataxias and autism. Over the past two decades, a growing body of evidence has indicated neuropeptides as potential therapeutic targets to ameliorate these diseases effectively. Therefore, this review focuses on eight cerebellar neuropeptides that have attracted more attention in recent years and have significant potential for clinical application associated with neurodegenerative and/or neuropsychiatric disorders, including brain-derived neurotrophic factor, corticotropin-releasing factor, angiotensin II, neuropeptide Y, orexin, thyrotropin-releasing hormone, oxytocin, and secretin, which may provide novel insights and a framework for our understanding of cerebellar-related disorders and have implications for novel treatments targeting neuropeptide systems.
Subject(s)
Cerebellar Diseases , Neuropeptides , Humans , Cerebellum/metabolism , Purkinje Cells/metabolism , Neurons/metabolism , Cerebellar Cortex/metabolism , Neuropeptides/metabolism , Cerebellar Diseases/pathologyABSTRACT
Pyroptosis, a new mode of regulatory cell death, holds a promising prospect in tumor therapy. The occurrence of pyroptosis can trigger the release of damage-associated molecular patterns (DAMPs) and activate the antitumor immune response. Moreover, enhancing intracellular reactive oxygen species (ROS) generation can effectively induce pyroptosis. Herein, an integrated nanoplatform (hCZAG) based on zeolitic imidazolate framework-8 (ZIF-8) with Cu2+ and Zn2+ as active nodes and glucose oxidase (GOx) loading is constructed to evoke pyroptosis. GOx can effectively elevate intracellular hydrogen peroxide (H2O2) levels to regulate the unfavorable tumor microenvironment (TME). Cu2+ can be reduced to Cu+ by endogenous overexpressed GSH and both Cu2+ and Cu+ can exert Fenton-like activity to promote ROS generation and amplify oxidative stress. In addition, the accumulation of Cu2+ leads to the aggregation of lipoylated dihydrolipoamide S-acetyltransferase (DLAT), thus resulting in cuproptosis. Notably, the outburst of ROS induced by hCZAG activates Caspase-1 proteins, leads to the cleavage of gasdermin D (GSDMD), and induces pyroptosis. Pyroptosis further elicits an adaptive immune response, leading to immunogenic cell death (ICD). This study provides effective strategies for triggering pyroptosis-mediated immunotherapy and achieving improved therapeutic effects.
Subject(s)
Glucose Oxidase , Pyroptosis , Reactive Oxygen Species , Tumor Microenvironment , Pyroptosis/drug effects , Reactive Oxygen Species/metabolism , Tumor Microenvironment/drug effects , Animals , Glucose Oxidase/metabolism , Glucose Oxidase/chemistry , Humans , Mice , Copper/chemistry , Hydrogen Peroxide/chemistry , Cell Line, Tumor , Metal-Organic Frameworks/chemistry , Metal-Organic Frameworks/pharmacology , Nanoparticles/chemistry , Immunity/drug effects , Oxidative Stress/drug effects , ImidazolesABSTRACT
ProBDNF is the precursor protein of brain-derived neurotrophic factor (BDNF) expressed in the central nervous system and peripheral tissues. Previous studies showed that the blood levels of both proBDNF and p75 neurotrophic receptors (p75NTR) in major depressive disorder (MDD) were increased, but which blood cell types express proBDNF and its receptors is not known. Furthermore, the relationship between proBDNF/p75NTR and inflammatory cytokines in peripheral blood of MDD is unclear. Peripheral blood mononuclear cells (PBMCs) and serum were obtained from depressive patients (n = 32) and normal donors (n = 20). We examined the expression of proBDNF and inflammatory markers and their correlative relationship in patients with major depression. Using flow cytometry analysis, we examined which blood cells express proBDNF and its receptors. Finally, the role of proBDNF/p75NTR signal in inflammatory immune activity of PBMCs was verified in vitro experiments. Inflammatory cytokines in PBMC from MDD patients were increased and correlated with the major depression scores. The levels of IL-1ß and IL-10 were also positively correlated with the major depression scores, while the levels of TNF-α and IL-6 were negatively correlated with the major depression scores. Intriguingly, the levels of sortilin were positively correlated with IL-1ß. Q-PCR and Western blots showed proBDNF, p75NTR, and sortilin levels were significantly increased in PBMCs from MDD patients compared with that from the normal donors. Flow cytometry studies showed that proBDNF and p75NTR were present mainly in CD4+ and CD8+ T cells. The number of proBDNF and p75NTR positive CD4+ and CD8+ T cells from MDD patients was increased and subsequently reversed after therapeutic management. Exogenous proBDNF protein or p75ECD-Fc treatment of cultured PBMC affected the release of inflammatory cytokines in vitro. ProBDNF promoted the expression of inflammatory cytokines, while p75ECD-Fc inhibited the expression of inflammatory cytokines. Given there was an inflammatory response of lymphocytes to proBDNF, it is suggested that proBDNF/p75NTR signaling may upstream inflammatory cytokines in MDD. Our data suggest that proBDNF/p75NTR signaling may not only serve as biomarkers but also may be a potential therapeutic target for MDD.
Subject(s)
Depressive Disorder, Major , Humans , Depressive Disorder, Major/metabolism , Leukocytes, Mononuclear/metabolism , Receptors, Nerve Growth Factor/genetics , Receptors, Nerve Growth Factor/metabolism , Up-Regulation , CD8-Positive T-Lymphocytes/metabolism , Depression , Brain-Derived Neurotrophic Factor/metabolism , Cytokines/metabolismABSTRACT
Nanocatalytic therapy (NCT) has made great achievements in tumor treatments due to its remarkable enzyme-like activities and high specificity. Nevertheless, the limited types of nanozymes and undesirable tumor microenvironments (TME) greatly weaken the therapeutic efficiency. Developing a combination therapy integrating NCT and other strategies is of great significance for optimal treatment outcomes. Herein, a AuPt-loaded Cu-doped polydopamine nanocomposite (AuPt@Cu-PDA) with multiple enzyme-like activities was rationally designed, which integrated photothermal therapy (PTT) and NCT. The peroxidase (POD)-like activity of AuPt@Cu-PDA can catalyze hydrogen peroxide (H2O2) into ·OH, and the catalase (CAT)-mimic activity can decompose H2O2 into O2 to alleviate hypoxia of TME, and O2 can be further converted into toxic ·O2- by its oxidase (OXD)-mimic activity. In addition, Cu2+ in AuPt@Cu-PDA can effectively consume GSH overexpressed in tumor cells. The boosting of reactive oxygen species (ROS) and glutathione (GSH) depletion can lead to severe oxidative stress, which can be enhanced by its excellent photothermal performance. Most importantly, the accumulation of Cu2+ can disrupt copper homeostasis, promote the aggregation of lipoylated dihydrolipoamide S-acetyltransferase (DLAT), disrupt the mitochondrial tricarboxylic acid (TCA) cycle, and finally result in cuproptosis. Collectively, photothermal and photoacoustic imaging (PTI/PAI)-guided cuproptosis-enhanced NCT/PTT can be achieved. This work may expand the application of nanozymes in synergistic therapy and provide new insights into cuproptosis-related therapeutic strategies.
Subject(s)
Apoptosis , Copper , Hydrogen Peroxide , Diagnostic Imaging , Glutathione , Photothermal Therapy , Tumor Microenvironment , Cell Line, TumorABSTRACT
The cumulative evidence suggests that oxytocin is involved in the male sexual behaviors. However, no significant sexual impairments were observed in oxytocin gene knock-out (KO) mice, suggesting that oxytocin is not necessary for sexual behavior in male mice. To better understand the role of oxytocin in male erection, two types of oxytocin gene KO mice were created. In the first type, the oxytocin gene was deleted in the zygote, while in the second type, the oxytocin gene was mutated in adulthood by injecting the CRISPR/Cas9 AAVs. The results showed that disrupting the oxytocin gene at either the embryonic or adult stage did not affect erection, indicating that oxytocin is not necessary for penile erection. Pharmacologically, injecting oxytocin receptor agonist Carbetocin into the VTA of the oxytocin gene KO mice still evoked penile erection. By employing the Oxt-Ires-Cre mice, we found that specifically activating oxytocinergic neurons through chemogenetics strongly induced penile erection, while inhibiting these neurons blocked the erection responses. Furthermore, ablating PVN oxytocinergic neurons abolished the male erection response. In conclusion, although the neuropeptide oxytocin is not essential for male erection, the activity of oxytocinergic neurons is required. Our results might reflect the redundancy in the central nerve system in the sense that many signals contribute to the activation of oxytocinergic neurons to evoke penile erection during sexual behaviors.
Subject(s)
Neurons , Oxytocin , Penile Erection , Animals , Male , Mice , Neurons/physiology , Paraventricular Hypothalamic Nucleus , Penile Erection/physiology , Receptors, Oxytocin/genetics , Oxytocin/metabolismABSTRACT
Research on conjugated radiation-conduction (CRC) heat transfer in participating media is of vital scientific and engineering significance due to its extensive applications. Appropriate and practical numerical methods are essential to forecast the temperature distributions during the CRC heat-transfer processes. Here, we established a unified discontinuous Galerkin finite-element (DGFE) framework for solving transient CRC heat-transfer problems in participating media. To overcome the mismatch between the second-order derivative in the energy balance equation (EBE) and the DGFE solution domain, we rewrite the second-order EBE as two first-order equations and then solve both the radiative transfer equation (RTE) and the EBE in the same solution domain, resulting in the unified framework. Comparisons between the DGFE solutions with published data confirm the accuracy of the present framework for transient CRC heat transfer in one- and two-dimensional media. The proposed framework is further extended to CRC heat transfer in two-dimensional anisotropic scattering media. Results indicate that the present DGFE can precisely capture the temperature distribution at high computational efficiency, paving the way for a benchmark numerical tool for CRC heat-transfer problems.
ABSTRACT
The effect of structure of gut microbes on the health of host has attracted increasing attention. Sea bass Lateolabrax japonicus is an important farmed fish in China. The relationship of the dynamic changes of intestinal bacterial communities in L. japonicus and the cultural water environment is very important for healthy culture. Here, the diversity and abundance of the gut microbial communities of L. japonicus were evaluated during the culture using 16S rRNA Illumina sequencing. Both the opportunistic pathogens Aeromonas (1.68%), Vibrio (1.59%), and Acinetobacter (1.22%); and the potential probiotics Lactobacillus (2.27%), Bacillus (1.16%), and Lactococcus (0.37%) were distributed in the gut of L. japonicus. The increasing concentration of nitrogen of water environments with the increase of culture time significantly correlated with shifts in the microbial community structure: 40.04% of gut microbial changes due to nitrogen concentration. Higher concentrations of nitrogen showed a significantly negative correlation with intestinal probiotics in L. japonicus. The results indicate that the abundance of intestinal bacteria of L. japonicus is mainly driven by the changes of environmental factors (e.g., nitrogen), and it's very important that the linking environmental parameters with bacterial data of guts could be used as an early warning indicator in L. japonicus heath culture.
ABSTRACT
Specific medications to combat cerebellar ataxias, a group of debilitating movement disorders characterized by difficulty with walking, balance and coordination, are still lacking. Notably, cerebellar microglial activation appears to be a common feature in different types of ataxic patients and rodent models. However, direct evidence that cerebellar microglial activation in vivo is sufficient to induce ataxia is still lacking. Here, by employing chemogenetic approaches to manipulate cerebellar microglia selectively and directly, we found that specific chemogenetic activation of microglia in the cerebellar vermis directly leads to ataxia symptoms in wild-type mice and aggravated ataxic motor deficits in 3-acetylpyridine (3-AP) mice, a classic mouse model of cerebellar ataxia. Mechanistically, cerebellar microglial proinflammatory activation induced by either chemogenetic M3D(Gq) stimulation or 3-AP modeling hyperexcites Purkinje cells (PCs), which consequently triggers ataxia. Blockade of microglia-derived TNF-α, one of the most important proinflammatory cytokines, attenuates the hyperactivity of PCs driven by microglia. Moreover, chemogenetic inhibition of cerebellar microglial activation or suppression of cerebellar microglial activation by PLX3397 and minocycline reduces the production of proinflammatory cytokines, including TNF-α, to effectively restore the overactivation of PCs and alleviate motor deficits in 3-AP mice. These results suggest that cerebellar microglial activation may aggravate the neuroinflammatory response and subsequently induce dysfunction of PCs, which in turn triggers ataxic motor deficits. Our findings thus reveal a causal relationship between proinflammatory activation of cerebellar microglia and ataxic motor symptoms, which may offer novel evidence for therapeutic intervention for cerebellar ataxias by targeting microglia and microglia-derived inflammatory mediators.
Subject(s)
Cerebellar Ataxia , Mice , Animals , Cerebellar Ataxia/chemically induced , Purkinje Cells/physiology , Microglia , Tumor Necrosis Factor-alpha/pharmacology , Cerebellum , CytokinesABSTRACT
The classical motor center cerebellum is one of the most consistent structures of abnormality in autism spectrum disorders (ASD), and neuropeptide oxytocin is increasingly explored as a potential pharmacotherapy for ASD. However, whether oxytocin targets the cerebellum for therapeutic effects remains unclear. Here, we report a localization of oxytocin receptor (OXTR) in Purkinje cells (PCs) of cerebellar lobule Crus I, which is functionally connected with ASD-implicated circuits. OXTR activation neither affects firing activities, intrinsic excitability, and synaptic transmission of normal PCs nor improves abnormal intrinsic excitability and synaptic transmission of PCs in maternal immune activation (MIA) mouse model of autism. Furthermore, blockage of OXTR in Crus I in wild-type mice does not induce autistic-like social, stereotypic, cognitive, and anxiety-like behaviors. These results suggest that oxytocin signaling in Crus I PCs seems to be uninvolved in ASD pathophysiology, and contribute to understanding of targets and mechanisms of oxytocin in ASD treatment.
Subject(s)
Autism Spectrum Disorder , Autistic Disorder , Mice , Animals , Receptors, Oxytocin , Oxytocin , Purkinje CellsABSTRACT
Resonant integrated optical gyroscopes (RIOGs) can integrate discrete optical components as a promising candidate for high-performance micro-optical gyroscopes. However, the current RIOG still consists of discrete elements due to the difficulty and complexity of heterogeneous integration of resonator and modulators. This paper presents on-chip integration of optical functional components including modulator, resonator, beam splitter, and coupler for the organic-polymer-based RIOG. Simple integrated optical processes such as spin coating, lithography, and etching can realize RIOG chips with low cost, size, weight, and power (CSWaP) features. Thereinto, the electro-optic modulator (EOM) fabricated by self-synthesized electro-optic (EO) polymer (side chain bonded polyurethane imide) exhibits less than 2 V half-wave voltage, which is half of the lithium niobate (LiNbO3) modulator. With respect to the resonator, a quality factor of approximately million was achieved using low-loss fluorinated polymer. In addition, the angular velocity sensing of RIOG was also investigated. By demonstrating the monolithic integration of the resonator and modulators, such an all-polymer RIOG chip prototype builds the technical foundation for the precision fully integrated optical gyroscope.
ABSTRACT
Cancer is one of the most serious diseases threatening human health, so it is particularly important to develop effective tumor-targeting drugs. As the first CDK4/6 inhibitor, palbociclib effectively inhibits tumor proliferation by blocking the cell cycle to the G1 phase. 10-HCPT is a Topo I inhibitor; however, its clinical application has been greatly limited due to its high toxicity. Based on the successful development of double target inhibitors, three novel palbociclib derivatives (HP-1, HP-2, and HP-3) were designed and synthesized from Palbociclib and 10-HCPT, and their biological activities were investigated. At first, the possible binding sites of the three compounds to Topo I and CDK4/6 were predicted by molecular docking. Then, we evaluated the anti-proliferative effects of the three palbociclib derivatives. In general, human lung cancer cells were more sensitive to HP-1, HP-2, and HP-3, especially NCI-H460. In addition, cell cycle arrest and apoptosis induction were investigated by flow cytometry. The three palbociclib derivatives, especially HP-1, had obvious cell cycle arrest phenomenon on NCI-H460 cells and induced apoptosis of NCI-H460 cells significantly. In the end, it was proved that these three drugs had obvious cyclin-dependent kinase inhibitory activities. In short, all the data showed that HP-1, HP-2, and HP-3 could play anti-cancer roles by acting on dual targets and had the characteristics of high efficiencies and low toxicities, which opened up a new idea for the study of palbociclib derivatives.
ABSTRACT
Excitons in two-dimensional (2D) materials have attracted the attention of the community to develop improved photoelectronic devices. Previous reports are based on direct excitation where the out-of-plane illumination projects a uniform single-mode light spot. However, because of the optical diffraction limit, the minimal spot size is a few micrometers, inhibiting the precise manipulation and control of excitons at the nanoscale level. Herein, we introduced the in-plane coherent surface plasmonic interference (SPI) field to excite and modulate excitons remotely. Compared to the out-of-plane light, a uniform in-plane SPI suggests a more compact spatial volume and an abundance of mode selections for a single or an array of device modulation. Our results not only build up a fundamental platform for operating and encoding the exciton states at the nanoscale level but also provide a new avenue toward all-optical integrated valleytronic chips for future quantum computation and information applications.
ABSTRACT
Two-dimensional hybrid lead perovskites have attracted a great deal of attention in white-light-emitting diodes, but the serious toxicity of Pb2+ and the limited photoluminescence quantum yield (PLQY) still restrict further optoelectronic application. To address these issues, a new combining photon strategy was proposed to achieve highly efficient broadband white-light emission in a new family of zero-dimensional (0D) indium halides based on an [InCl6]3- octahedron. Remarkably, these 0D halides display dual-band white-light emission derived from the synergistic work of blue- and yellow-light-emitting bands, which can be ascribed to the radiative recombination of bound excitons in organic cations and self-trapped excitons in inorganic anions, respectively, based on spectroscopy and theoretical studies. In-depth first-principles calculation demonstrates that the increased structural deformability effectively improves the PLQY from 7.01% to 18.56%. As a proof of concept, this work provides a profound understanding for advancing the rational design of novel single-component 0D lead-free halides as high-performance white-light emitters.
ABSTRACT
Betahistine and gastrodin are the first-line medications for vestibular disorders in clinical practice, nevertheless, their amelioration effects on vestibular dysfunctions still lack direct comparison and their unexpected extra-vestibular effects remain elusive. Recent clinical studies have indicated that both of them may have effects on the gastrointestinal (GI) tract. Therefore, we purposed to systematically compare both vestibular and GI effects induced by betahistine and gastrodin and tried to elucidate the mechanisms underlying their GI effects. Our results showed that betahistine and gastrodin indeed had similar therapeutic effects on vestibular-associated motor dysfunction induced by unilateral labyrinthectomy. However, betahistine reduced total GI motility with gastric hypomotility and colonic hypermotility, whereas gastrodin did not influence total GI motility with only slight colonic hypermotility. In addition, betahistine, at normal dosages, induced a slight injury of gastric mucosa. These GI effects may be due to the different effects of betahistine and gastrodin on substance P and vasoactive intestinal peptide secretion in stomach and/or colon, and agonistic/anatgonistic effects of betahistine on histamine H1 and H3 receptors expressed in GI mucosal cells and H3 receptors distributed on nerves within the myenteric and submucosal plexuses. Furthermore, treatment of betahistine and gastrodin had potential effects on gut microbiota composition, which could lead to changes in host-microbiota homeostasis in turn. These results demonstrate that gastrodin has a consistent improvement effect on vestibular functions compared with betahistine but less effect on GI functions and gut microbiota, suggesting that gastrodin may be more suitable for vestibular disease patients with GI dysfunction.