Search

Yb/Er/Ho-engineered rare earth fluoride nanoparticles with synergistic three-modal imaging abilities are presented, which can provide an alternative approach for in vivo disease diagnosis and supervision.

The construction of nanoplatforms with combined photothermal property and cascade enzymatic activities has become one of hot spots in anticancer research. However, the overheat of photothermal therapy (PTT) and the specific properties of tumor microenvironment (TME) greatly impaired the therapeutic efficiency. Herein, we rationally fabricated a virus-like SiOx/CeO2/VOx (SCV) nanoplatform for 1064 nm near-infrared (NIR) triggered mild-temperature PTT and nanozyme catalytic therapy. Firstly, the virus-like shape of SiOx/CeO2/VOx made it favorable for cell adhesion and had a better phagocytosis in cells, and the SCV generated effective PTT effect upon 1064 nm laser irradiation. Particularly, the produced VO2+ in TME could be used as a heat shock protein inhibitor to inhibit the expression of heat shock protein 60 (HSP60) to enhance the PTT efficiency. Moreover, SCV nanozyme exhibited obvious peroxidase-mimic (POD) catalytic activity, which could generate highly toxic free radical ion (•OH) under acidic conditions. The mild-temperature heat and •OH produced by enzymatic catalysis effectively blocked the tumor growth, verified firmly by the in vitro and in vivo tests. Our designed virus-like SCV nanozyme with POD mimic enzyme activity and mild photothermal effect may provide a new way of thinking for the combination therapy model.

The present study aimed to investigate the relationship of follower’s strengths-based leadership (FSBL) with follower work engagement. Additionally, this study also examined the mediational effect of employee strengths use and the moderating effect of core self-evaluation (CSE) on the relationship between FSBL and follower work engagement. Data were garnered at two points in time with a time lag of 2 months. Moderated-mediation path analysis with a total of 238 employees working in a research and design institute in Beijing was deployed to examine our hypotheses. As hypothesized, FSBL was a statistically significant predictor of work engagement, and strengths use acted as a mediator in the FSBL-work engagement relationship. In addition, we also found that CSE significantly and negatively moderates the direct effect of FSBL on strengths use and the indirect effect of FSBL on work engagement through strengths use. This study advances the FSBL theory and research and provides a new insight into the driving force of work engagement.

Therapeutic nanosystems triggered by a specific tumor microenvironment (TME) offer excellent safety and selectivity in the treatment of cancer by in situ conversion of a less toxic substance into effective anticarcinogens. However, the inherent antioxidant systems, hypoxic environment, and insufficient hydrogen peroxide (H2O2) in tumor cells severely limit their efficacy. Herein, a new strategy has been developed by loading the chemotherapy prodrug disulfiram (DSF) and coating glucose oxidase (GOD) on the surface of Cu/ZIF-8 nanospheres and finally encapsulating manganese dioxide (MnO2) nanoshells to achieve efficient DSF-based cancer chemotherapy and dual-enhanced chemodynamic therapy (CDT). In an acidic TME, the nanocatalyst can biodegrade rapidly and accelerate the release of internal active substances. The outer layer of MnO2 depletes glutathione (GSH) to destroy the reactive oxygen defensive mechanisms and achieves continuous oxygen generation, thus enhancing the catalytic efficiency of GOD to burst H2O2. Benefiting from the chelation reaction between the released Cu2+ and DSF, a large amount of cytotoxic CuET products is generated, and the Cu+ are concurrently released, thereby achieving efficient chemotherapy and satisfactory CDT efficacy. Furthermore, the release of Mn2+ can initiate magnetic resonance imaging signals for the tracking of the nanocatalyst.

Although extant literature has highlighted the importance of human resource system to thriving at work, we have yet to know whether perceived strengths-based human resource (HR) system has a significant relationship with employee thriving at work. Drawing upon conservation of resources theory, the current study sought to investigate the relationship of perceived strengths-based HR system with employee thriving at work and the mediating role of general self-esteem and the moderating role of emotional exhaustion in this relationship. Research data were gathered at three points in time from employees working in various organizations in China. Results of structural equation modeling analyses demonstrated that perceived strengths-based HR system is positively related to thriving at work even after controlling for perceived high performance work system, and general self-esteem partially mediates the positive relationship of perceived strengths-based HR system with thriving at work. In addition, emotional exhaustion negatively moderated the direct relationship of general self-esteem with thriving and the indirect relationship of perceived strengths-based HR system with thriving at work through general self-esteem. The current study is the first to empirically investigate the perceived strengths-based HR system and thriving at work linkage, which advances HR system and thriving at work theories and research.

This paper first reports a liquid-core hydrogel optical fiber fluorescence probe. It is composed of a liquid core, a high-refractive-index hydrogel fiber core, and a low-refractive-index hydrogel fiber cladding, which is completely different from many existing optical fiber fluorescence probes. The sensing solution with sensitive materials is sealed as a liquid core, and it can sufficiently react with small-molecule targets penetrating through the hydrogel fiber cladding and core, thus inducing variations in the fluorescence signals. These fluorescence signals can be localized and transmitted within the probe and finally collected and quantified for target detection. This proposed probe can be simply and rapidly fabricated and reused, and it was proven to have high sensitivity, accuracy, and selectivity in practical applications. Therefore, this liquid-core hydrogel optical fiber fluorescence probe will enable a novel sensing platform for small-molecule analyte detection that faces on-site detection challenges.

Argonaute small-RNA pathways engage heterochromatin-silencing co-factors to promote transgenerational inheritance in animals. However, little is known about how heterochromatin and small-RNA pathways interact to transmit silencing. Here we show that the induction of heterochromatin silencing in C. elegans by RNAi or by artificially tethering pathway components to target RNA correlates with the co-localization of the target alleles in pachytene nuclei. Tethering the nuclear Argonaute WAGO-9/HRDE-1 induces heterochromatin formation, but also functions independently to induce small-RNA amplification. We show that HRDE-1 shuttles to nuage domains called mutator foci where amplification is thought to occur. Tethering a heterochromatin-silencing factor, NRDE-2, induces heterochromatin silencing and also induces the de-novo synthesis of HRDE-1 guide RNAs, and through HRDE-1 acts to further amplify downstream small-RNA silencing. Our findings support a model in which HRDE-1 functions both upstream, to initiate heterochromatin silencing, and downstream, to stimulate small-RNA amplification, establishing a self-enforcing mechanism that propagates silencing to offspring.

Nanozymes with the merits of effective enzyme-mimic activities, tunable catalytic properties, pH/temperature tolerance, and high stability have been consumingly researched for nanocatalytic therapy. Herein, the union nanozymes and a natural enzyme nanoplatform (DMSN@CoFe

PurposeThe purpose of the current article was to propose the strengths-based human resource (HR) system construct as well as develop and validate the perceived strengths-based HR system scale by using three independent studies.Design/methodology/approachStudy 1 mainly adopted exploratory factor analysis to test whether fifteen items proposed by the authors can represent the perceived strengths-based HR system construct. The aim of Study 2 was to examine the discriminant validity and criteria validity of the fifteen-item perceived strengths-based HR system scale and reliability of this scale. By structural equation modeling analysis, Study 3 primarily tested the incremental predictive validity of the perceived strengths-based HR system for employee performance (i.e. task performance and innovative behavior) after controlling for the perceived high-performance work system (HPWS) and perceived high-commitment work system (HCWS).FindingsStudy 1 showed that initial fifteen items of the perceived strengths-based HR system appropriately are loaded on one factor and exhibit a good reliability. Study 2 found that there is good discriminant validity between the perceived strengths-based HR system, perceived organizational support, perceived supervisory career support, and work engagement, and the perceived strengths-based HR system exhibits better convergent validity and criteria validity. Study 3 demonstrated that the perceived strengths-based HR system could significantly predict employee performance (i.e. task performance and innovative behavior) even after controlling for perceived HPWS and HCWS.Originality/valueThe current article contributes to advancing HR theory and research and provides a valuable tool for future empirical research on the strengths-based HR system.

Mitochondria are the "power plant" of the cell, providing a constant source of energy, and are involved in a variety of intracellular signaling pathways. Among these pathways, Ca2+ homeostasis is closely related to the normal function of mitochondria. By destroying the Ca2+ steady state of mitochondria and disrupting their multiple cellular activities, tumor cell killing can be achieved. In addition, the presence of an intracellular oxidative stress state triggers the closure of cellular calcium channels, which leads to intracellular Ca2+ retention and enrichment. We designed a targeted and tumor microenvironment (TME)-responsive CaO2-based nanosystem that can selectively target cancer cells for pH-controlled degradation and drug release, alter cellular physiological mechanisms by disrupting Ca2+ homeostasis in an artificial manner, and introduce mitochondrial Ca2+ excess-mediated apoptosis. Meanwhile, the production of Ca(OH)2 will raise the pH of the microenvironment and subsequently promote the oxidation process of glutathione by H2O2 released from CaO2 degradation, achieving the goal of remodeling TME. Moreover, calcium overload of tumor cells and calcification of tissues can both inhibit tumor growth and act as a contrast agent for computed tomography imaging.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is a serious infection caused by the new coronavirus severe acute respiratory syndrome coronavirus 2. The disease was first identified in December 2019 and has caused significant morbidity and mortality worldwide. AIM: To explore the clinical characteristics and treatments for COVID-19 in the Qinghai-Tibetan Plateau Area in China. METHODS: We retrospectively analyzed the blood cell counts (neutrophils and lymphocytes), blood gas analysis, and thoracic computed tomography changes of patients from Qinghai Province before, during, and after treatment (January 23, 2020 to February 21, 2020). In addition, we summarized and analyzed the information of critical patients. All data were analyzed using SPSS 17.0 (SPSS Inc., Chicago, IL, United States). The quantitative and count variables are represented as the mean ± SD and n (%), respectively. RESULTS: The main symptoms and signs of patients with COVID-19 were fever, dry cough, cough with phlegm, difficulty breathing, and respiratory distress with a respiration rate ≥ 30 times/min, finger oxygen saturation ≤ 93% in the resting state, and oxygenation index less than 200 but greater than 100 (after altitude correction). Eighteen patients with COVID-19, of whom three were critical, and the others were in a mild condition, were included. The main manifestations included fever, dry cough, and fatigue. Three patients developed difficulty breathing and had a fever. They were eventually cured and discharged. Adjuvant examinations showed one case with reduced white cell count (6%) (< 4 × 109/L), six with reduced count of lymphocytes (33%) (< 0.8 × 109/L), and one with abnormal blood glucose level. All 18 patients were discharged, and no death occurred. CONCLUSION: Our findings provide critical insight into assessing the clinical diagnosis and treatment for COVID-19 in the Tibetan plateau area.

Background: Toxoplasma gondii is capable of infecting a wide range of warm-blooded animals, causing a worldwide epidemic of zoonotic toxoplasmosis. SAG1 protein is expressed at the proliferative tachyzoite stage, whereas MAG1 is expressed at the bradyzoite and tachyzoite stages. These two proteins display protective roles in previous studies, however, there synergetic protective efficacy as a DNA vaccine against toxoplasmosis has not been clarified.Methods: In this study, we amplified TgMAG1 and TgSAG1 genes and inserted into eukaryotic expression vector pcDNA3.1(+). The pcDNA3.1(+)-TgMAG1 (pMAG1), pcDNA3.1(+)-TgSAG1 (pSAG1), pcDNA3.1(+)-TgMAG1-TgSAG1 (pMAG1-SAG1) plasmids were transfected into HEK-293 cells and each protein was verified in vitro through western blot. Then, mice were intramuscularly immunized with pMAG1, pSGA1 or pMAG1-SGA1, and anti-T. gondii IgG levels were measured in the serum. Cytokines levels of IL-4, IL-10 and IFN-γ in mice splenocytes culturing supernatants were measured using commercial ELISA kits. Immunized mice were challenged with T. gondii tachyzoites with lethal doses followed by determination of mortality, whereas mice infected with low dose tachyzoites followed by monitoring the parameters of survival rate and parasites burden analysis of brains and livers.Results: The pMAG1, pSGA1 or pMAG1-SGA1 exhibited well reactogenicity with expected band sizes of 17.843 kDa, 15.572 kDa, 33.415 kDa, respectively. The immunized mice triggered significantly high levels of anti-T. gondii IgG antibodies in comparison with that in the negative control groups, moreover pMAG1-SGA1 immune achieved the highest levels. The DNA vaccines also led to obvious IFN-γ release from splenocytes culturing supernatants, whereas had no role in the IL-4 and IL-10. The protective efficacy results showed that DNA vaccines immunization prolonged the acute infection mice survival time to 14 d, 16 d, 32 d. Consistently, the liver and brain parasites in each immunization group were significantly reduced comparing with PBS control group.Conclusions: This study revealed that bivalent TgMAG1 and TgSAG1 DNA vaccine displayed excellent protective immunity against toxoplasmosis in mice. These data provide new sight into the development of Toxoplasma gondii vaccines.

Drawing upon ability-motivation-opportunity model, the present study attempts to inspect the association of strengths-based leadership with employee psychological well-being and the mediational role of employee strengths use and the moderating role of job autonomy in the linkage. Data were gathered using a three-wave survey from a sample of 308 employees working in a wide variety of organizations in China. Results of multiple regression analyses with bootstrapping procedure revealed that strengths-based leadership positively relates to employee psychological well-being even after controlling for employee core self-evaluation. In addition, employee strengths use was found to partially mediate the relationship of strengths-based leadership with employee psychological well-being, and this study demonstrated job autonomy to positively moderate the direct relationship of strengths-based leadership with strengths use of employee and the indirect association of strengths-based leadership with employee psychological well-being through employee strengths use. The present study advances strengths-based leadership and psychological well-being theories and research.

Nanosystem-mediated tumor radiosensitization strategy combining the features of X-ray with infinite penetration depth and high atomic number elements shows considerable application potential in clinical cancer therapy. However, it is difficult to achieve satisfactory anticancer efficacy using clinical radiotherapy for the majority of solid tumors due to the restrictions brought about by the tumor hypoxia, insufficient DNA damage, and rapid DNA repair during and after treatment. Inspired by the complementary advantages of nitric oxide (NO) and X-ray-induced photodynamic therapy, we herein report a two-dimensional nanoplatform by the integration of the NO donor-modified LiYF4:Ce scintillator and graphitic carbon nitride nanosheets for on-demand generation of highly cytotoxic peroxynitrite (ONOO–). By simply adjusting the Ce3+ doping content, the obtained nanoscintillator can realize high radioluminescence, activating photosensitive materials to simultaneously generate NO and superoxide radical for the formation of ONOO– in the tumor. Obtained ONOO– effectively amplifies therapeutic efficacy of radiotherapy by directly inducing mitochondrial and DNA damage, overcoming hypoxia-associated radiation resistance. The level of glutamine synthetase (GS) is downregulated by ONOO–, and the inhibition of GS delays DNA damage repair, further enhancing radiosensitivity. This work establishes a combinatorial strategy of ONOO– to overcome the major limitations of radiotherapy and provides insightful guidance to clinical radiotherapy. Agency for Science, Technology and Research (A*STAR) Submitted/Accepted version Financial support from the National Natural Science Foundation of China (51972075, 51972076, and 51772059), the Natural Science Foundation of Shandong Province (ZR2019ZD29), the Natural Science Foundation of Heilongjiang Province (YQ2019E014), the Postdoctoral Scientific Research Developmental Fund (LBH-Q18034), and the Ph.D. Student Research and Innovation Fund of the Fundamental Research Funds for the Central Universities (3072020GIP1016) are greatly acknowledged. This research is also supported by the Singapore Agency for Science, Technology and Research (A*STAR) AME IRG grant (A20E5c0081).

Thin-film microscale light-emitting diodes (LEDs) are efficient light sources and their integrated applications offer robust capabilities and potential strategies in biomedical science. By leveraging innovations in the design of optoelectronic semiconductor structures, advanced fabrication techniques, biocompatible encapsulation, remote control circuits, wireless power supply strategies, etc., these emerging applications provide implantable probes that differ from conventional tethering techniques such as optical fibers. This review introduces the recent advancements of thin-film microscale LEDs for biomedical applications, covering the device lift-off and transfer printing fabrication processes and the representative biomedical applications for light stimulation, therapy, and photometric biosensing. Wireless power delivery systems have been outlined and discussed to facilitate the operation of implantable probes. With such wireless, battery-free, and minimally invasive implantable light-source probes, these biomedical applications offer excellent opportunities and instruments for both biomedical sciences research and clinical diagnosis and therapy.

Thermometric detectors are crucial in evaluating the condition of target objects spanning from environments to the human body. Optical-based thermal sensing tools have received extensive attention, in which the photon upconversion process with low autofluorescence and high tissue penetration depth is considered as a competent method for temperature monitoring, particularly in biomedical fields. Here, we present an optoelectronic thermometer via infrared-to-visible upconversion, accomplished by integrated light receiving and emission devices. Fully fabricated thin-film, microscale devices present temperature-dependent light emission with an intensity change of 1.5% °C−1 and a spectral shift of 0.18 nm °C−1. The sensing mechanism is systematically characterized and ascribed to temperature dependent optoelectronic properties of the semiconductor band structure and the circuit operation condition. Patterned device arrays showcase the capability for spatially resolved temperature mapping. Finally, in vitro and in vivo experiments implemented with integrated fiber-optic sensors demonstrate real-time thermal detection of dynamic human activity and in the deep brain of animals, respectively.

Mild photothermal therapy (PTT,45 °C) can prevent tumor metastasis and heat damage to normal tissue, compared with traditional PTT (50 °C). However, its therapeutic efficacy is limited owing to the hypoxic tumor environment and tumor thermoresistance owing to the overproduction of heat shock proteins (HSPs). Herein, a near-infrared (NIR)-triggered theranostic nanoplatform (GA-PB@MONs@LA) is designed for synergistic mild PTT and enhanced Fenton nanocatalytic therapy against hypoxic tumors. The nanoplatform is fabricated by the confined formation of Prussian blue (PB) nanoparticles in mesoporous organosilica nanoparticles (MONs), followed by the loading of gambogic acid (GA), an HSP90 inhibitor, and coating with thermo-sensitive lauric acid (LA). Upon NIR irradiation, the photothermal effect (44 °C) of PB not only induces apoptosis of tumor cells but also triggers the on-demand release of GA, inhibiting the production of HSP90. Moreover, the delivered heat simultaneously enhances the catalase-like and Fenton activity of PB@MONs@LA in an acidic tumor microenvironment, relieving the tumor hypoxia and promoting the generation of highly toxic •OH. In addition, the nanoplatform enables magnetic resonance/photoacoustic dual-modal imaging. Thus, this study describes a distinctive paradigm for the development of NIR-triggered theranostic nanoplatforms for enhanced cancer therapy.

To explore the effect of CXCR4 on the treatment response and prognosis of Carfilzomib (CFZ) in multiple myeloma.Dataset GSE69078 based on microarray data from two CFZ-resistant MM cell lines and their corresponding parental cell lines (KMS11-KMS11/CFZ and KMS34-KMS34/CFZ) were downloaded from Gene Expression Omnibus (GEO). Differentially expressed genes (DEGs) were identified, and Protein-protein interaction (PPI) network was established to identify the key genes involved in CFZ resistance acquisition. Finally, the prognostic roles of the CFZ risistance key genes in MM using MMRF-CoMMpass data study was verified.44 up-regulated and 46 down-regulated DEGs were identified. Top 10 hub genes (CCND1, CXCR4, HGF, PECAM1, ID1, HEY1, TCF4, HIST1H4J, HIST1H2BD and HIST1H2BH) were identified via Protein-protein interaction (PPI) network analysis. The CoMMpass data showed that high CXCR4 expression showed correlation to relative higher relapse and progress rates and the overall survival was significant decreased in high CXCR4 patients (P=0.013).CXCR4 perhaps plays a crucial role in CFZ acquired resistance, which might help identifying potential CFZ-sensitive patients before treatment and providing a new therapeutic target in CFZ-resistant MM.CXCR4在多发性骨髓瘤中对卡菲佐米疗效及预后的影响.探讨CXCR4对卡菲佐米（CFZ）治疗多发性骨髓瘤(MM)患者的效果及预后的影响.下载在线数据库Gene Expression Omnibus（GEO）中含两种耐CFZ的MM细胞株（KMS11/CFZ及KMS34/CFZ）以及相对应的亲本株KMS11和KMS34基因表达谱数据的数据集GSE69078。分析差异表达基因（DEGs）并构建蛋白-蛋白互作（PPI）网络，获得CFZ耐药关键基因。最终，以MMRF-CoMMpass研究数据作为验证数据集探讨CFZ耐药关键基因的临床意义.共鉴定出44个上调DEGs和46个下调DEGs，通过PPI网络分析筛选出前10位关键基因（CCND1、CXCR4、HGF、PECAM1、ID1、HEY1、TCF4、HIST1H4J、HIST1H2BD及HIST1H2BH）。MMRF-CoMMpass数据显示，C-X-C基序趋化因子受体4（CXCR4）高表达与较高的复发/进展率相关，且CXCR4高表达患者的总生存（OS）率显著降低（P=0.013）.CXCR4高表达可能与MM患者CFZ获得性耐药相关，有助于在治疗前筛选潜在的CFZ敏感患者，并有望为CFZ耐药MM提供新的治疗靶点.

Cadmium (Cd) is a common environmental heavy metal contaminant of reproduction toxicity. Cd accumulation in animals leads to the damage of granulosa cells. However, its mechanism needs to be elucidated. This research found that treating granulosa cells with Cd resulted in reduced cell viability. The flow cytometry results showed that Cd increased the degree of apoptosis and level of superoxide anion (O