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In this project, we attempt to study the effects of self-focused happiness and other-focused happiness on employee creativity, with vigor as a mediating mechanism, and job resources as a moderator variable. Based on existing research, we anticipate that both kinds of happiness motivation will increase employee vigor and thus increase employee creativity. In addition, when job resources are higher, other-focused happiness has a stronger indirect effect on employee creativity than self-focused happiness. In contrast, when job resources are lower, self-focused happiness has a stronger indirect effect on employee creativity than other-focused happiness.

In recent years, chimeric antigen receptor T (CAR T)‐cell therapy has shown great potential in treating haematologic disease, but no breakthrough has been achieved in solid tumours. In order to clarify the antitumour mechanism of CAR T cell in solid tumours, the pharmacokinetic (PK) and pharmacodynamic (PD) investigations of CD19 CAR T cell were performed in human leukaemic xenograft mouse models. For PK investigation, we radiolabelled CD19 CAR T cell with 89Zr and used PET imaging in the CD19‐positive and the CD19‐negative K562‐luc animal models. For PD evaluation, optical imaging, tumour volume measurement and DNA copy‐number detection were performed. Unfortunately, the qPCR results of the DNA copy number in the blood were below the detection limit. The tumour‐specific uptake was higher in the CD19‐positive model than in the CD19‐negative model, and this was consistent with the PD results. The preliminary PK and PD studies of CD19 CAR T cell in solid tumours are instructive. Considering the less efficiency of CAR T‐cell therapy of solid tumours with the limited number of CAR T cells entering the interior of solid tumours, this study is suggestive for the subsequent CAR T‐cell design and evaluation of solid tumour therapy.

There is a belief that leader narcissism plays a key role in the development of groups’ radical creative capability, but no empirical study has tested this effect. Theoretically, there are conflicting arguments regarding the effect of leader narcissism on team radical creativity. Therefore, we will conduct a filed study to examine when and how leader narcissism promotes team radical creativity

In today's competitive marketplace, organizations largely rely on team radical innovation to gain and maintain competitive advantages. Although scholars have studied the formation mechanism of team radical innovation from different perspectives, few studies focus on the potential impact of innovation expectation discrepancy and team leader’s self-regulation process. By drawing on self-regulation theory, the current study investigated leader creative process engagement as a vital mechanism through which innovation expectation discrepancy impacts team radical innovation.

Additional file 1: Table S1. Primers Used for Amplification and Verification of SLO3 Mutations. Table S2. Primers Used for qRT-PCR Assays Primer.

Clinical tracking of chimeric antigen receptor (CAR) T cells in vivo by positron emission tomography (PET) imaging is an area of intense interest. But the long-lived positron emitter-labeled CAR T cells stay in the liver and spleen for days or even weeks. Thus, the excessive absorbed effective dose becomes a major biosafety issue leading it difficult for clinical translation. In this study we used 68Ga, a commercially available short-lived positron emitter, to label CAR T cells for noninvasive cell tracking in vivo. CAR T cells could be tracked in vivo by 68Ga-PET imaging for at least 6 h. We showed a significant correlation between the distribution of 89Zr and 68Ga-labeled CAR T cells in the same tissues (lungs, liver, and spleen). The distribution and homing behavior of CAR T cells at the early period is highly correlated with the long-term fate of CAR T cells in vivo. And the effective absorbed dose of 68Ga-labeled CAR T cells is only one twenty-fourth of 89Zr-labeled CAR T cells, which was safe for clinical translation. We conclude the feasibility of 68Ga instead of 89Zr directly labeling CAR T cells for noninvasive tracking of the cells in vivo at an early stage based on PET imaging. This method provides a potential solution to the emerging need for safe and practical PET tracer for cell tracking clinically.

Purpose: Radiolabeled FSH1 peptides are potential specific probes for FSHR imaging. However, moderate uptakes and fast washout from the tumors may limit its widespread use. In this study, 68Ga labeled modified FSH1 analogs was prepared and the imaging properties were determined in the prostate cancer model with or without aprotinin.Methods: NOTA-MAL-FSH4 was synthesized and labeled with 68Ga. The pharmacokinetic profile of the peptide after co-administration with aprotinin was determined through metabolism analyses and microPET imaging.Results: 68Ga-NOTA-MAL-FSH4 was successfully prepared. The IC50 value of displacement 68Ga-NOTA-MAL-FSH4 with FSH1 was 139.4±1.16 nM. The PC-3 prostate tumor was visible after administration of the 68Ga labeled tracer. In vitro RP-HPLC analysis revealed that the average percentage of intact peptide in the plasma, liver and tumor was 8.30, 9.57 and 7.06 % respectively. In presence of aprotinin, the amounts of intact peptide increased to 34.32%, 20.63 % and 15.39 % in the counterparts respectively. MicroPET imaging showed that the uptakes of PC-3 tumors at 60mins after co-administration of 100μg, 200μg or 400μg enzyme inhibitors were 2.91±0.21%ID/g, 3.89±0.16%ID/g and 9.21±0.22%ID/g respectively.Conclusion: With the aid of a serine protease inhibitor, the performance of the 68Ga labeled peptide was optimized, which may benefit further clinical application.

The proliferation of chimeric antigen receptor (CAR) T cells is closely related to their efficacy, but it is still a great challenge to monitor and quantify CAR T cells in vivo. Based on the high affinity (Kd ≈ 10−15 M) of streptavidin (SA) and biotin, radiolabeled biotin may be used to quantify SA-transduced CAR T cells (SA-CAR T cells). Radio-thin-layer chromatography (radio-TLC) and positron emission tomography (PET) are highly sensitive for trace analysis. Our aim was to develop radio-TLC and PET methods to quantify SA-CAR T cells in vitro and in vivo. First, we developed [68Ga]-DOTA-biotin. Commercially available SA was used as a standard, and quantitative standard curves were established in vitro and in vivo by radio-TLC and PET. Furthermore, the feasibility of the method was verified in Raji model mice. The linear range of radio-TLC was 0.02 ∼ 0.15 pmol/μL with R2 = 0.9993 in vitro. The linear range of PET was 0.02 ∼ 0.76 pmol/μL with R2 = 0.9986 in vivo. SA in CAR T cells can also be accurately quantified in a Raji leukemia model according to PET imaging. The radio-TLC/PET method established in this study is promising for using in the dynamic monitoring and analysis of SA-CAR T cells during therapy.

Context Adult growth hormone deficiency (AGHD) is characterized by low bone density and increased risk of fracture. Bone microarchitecture is insufficiently evaluated in patients with childhood-onset AGHD (CO AGHD). Objective To assess volumetric bone density (vBMD) and bone microarchitecture in CO AGHD in early adulthood after cessation of recombinant growth hormone (rhGH) treatment. Design and subjects Case–control study in a major academic medical center in Beijing, including 20 young male adults with CO AGHD and 30 age- and weight-matched non-athletic healthy men. High-resolution peripheral quantitative computerized tomography (HR-pQCT) of distal radius and tibia was performed. Outcomes The main outcomes were vBMD and morphometry parameters from HR-pQCT. Results Compared with healthy controls, CO AGHD group had significantly decreased insulin-like growth factor 1 (IGF-1) level and IGF-1 SDS (P P P P = 0.001). At both tibia and radius, by finite element analysis, bone stiffness and failure load of the CO AGHD patients were significantly decreased (P Conclusions Young adult male patients with childhood-onset adult growth hormone deficiency who are no longer receiving growth hormone replacement have prominently impaired volumetric bone density and bone microarchitecture and lower estimated bone strength.

Background Positron emission tomography (PET) has the potential for visualization and quantification of gastric emptying (GE). The traditional Chinese medicine (TCM) has been recognized promising for constipation. This study aimed to establish a PET imaging method for noninvasive GE measurement and to evaluate the efficacy of a TCM on delayed GE caused by constipation using PET imaging. Methods [68Ga]Ga-NOTA was synthesized as the tracer and sesame paste with different viscosity were selected as test meals. The dynamic PET scans were performed after [68Ga]Ga-NOTA mixed with test meals were administered to normal mice. Two methods were utilized for the quantification of PET imaging. A constipation mouse model was treated with maren chengqi decoction (MCD), and the established PET imaging scans were performed after the treatment. Results [68Ga]Ga-NOTA was synthesized within 20 min, and its radiochemical purity was > 95%. PET images showed the dynamic process of GE. %ID/g, volume, and total activity correlated well with each other. Among which, the half of GE time derived from %ID/g for 4 test meals were 3.92 ± 0.87 min, 13.1 ± 1.25 min, 17.8 ± 1.31 min, and 59.7 ± 3.11 min, respectively. Constipation mice treated with MCD showed improved body weight and fecal conditions as well as ameliorated GE measured by [68Ga]Ga-NOTA PET. Conclusions A PET imaging method for noninvasive GE measurement was established with stable radiotracer, high image quality, and reliable quantification methods. The efficacy of MCD on delayed GE was demonstrated using PET.

The health effects of ambient PM 2.5 and its potential mechanisms have generated considerable interest. In vitro cell studies and ex vivo animal experiments may not accurately determine the characteristics of PM 2.5 particles. To better understand their detailed mechanisms, we performed an in vivo study using single photon emission tomography (SPECT) imaging. To mimic the PM 2.5 particles, SiO2 nanoparticles modified by ethylene carbonate or polyvinyl pyrrolidone were labeled with 131I. After administration via inhalation, in vivo SPECT imaging of the radiolabeled particles in sprague dawley rats was performed. It was found that radioactivity accumulated in the lungs and trachea 6 and 24 h after administration. In addition, significant radioactivity was observed in the abdomen, including the liver and kidneys. The results were also confirmed by ex vivo autoradiography. This study revealed that in vivo SPECT imaging could be an effective method for investigating the properties of PM 2.5 particles.

Despite the great progress achieved in nanomedicine, liquid metal (LM) nanodroplets have been mostly implemented as photo-agents for tumor phototherapy. However, in the rational design and construction of LM-based nanoplatforms for chemotherapy, limitations such as low drug-loading efficiency (LE), poor water stability, sterile and sensitive surface chemistry against ligand modification, and difficult morphology control remain to be addressed. Here, a local injectable LM-doxorubicin (LM-DOX) nanoflake-imbedded hydrogel with pH-triggered drug release is developed to achieve an enhanced therapeutic efficacy for the prevention of postoperative tumor relapse. With hyperbranched poly(amido amine) (HPAA) as the ligand, the obtained LM nanodroplets presented excellent aqueous stability and a unique flaky nanomorphology, and chemotherapeutics can be facilely conjugated via Schiff-base reaction as well. Compared to LM-based nanospheres or nanorods (LMNSs or LMNRs), LM nanoflakes (LMNFs) exhibited much higher DOX loading capacity of 63.5%. Further encapsulation of LMNF-DOX within Pluronic F-127 (LMNF-DOX@Gel) was used to diminish burst drug release, achieve long-term antitumor effect, and minimize systemic toxicity. Finally, this nano-formulation was injected into the tumor resection cavity for local chemotherapy to remove the residual tumor, achieving enhanced therapeutic efficacy and biosafety than free drugs. Overall, LMNF-based hydrogel drug delivery system represents a promising candidate for postsurgical cancer treatment.

Molecular imaging is important for early disease diagnosis, personalized therapy guidance, and new drug development. Nuclear scintigraphy using SPECT or PET is the widely used example in the clinic. To achieve functional visualization, specific probes are indispensable. For nuclear probes, radionuclides and targeting ligands (small compounds, peptide, affibody, etc.) are the main contents (Fig. 20.1). Some popular radioisotopes are listed in Table 20.1. In this chapter, we focused on 18F-, 11C-, 68Ga-, 89Zr-, 64Cu-, 90Y-, and 177Lu-labeled probes.

With the aim of developing a new tumor imaging agent, the IFLLWQR (Ile-Phe-Leu–Leu-Trp-Glu-Arg, IF7) was conjugated with 1, 4, 7-triazacyclononane-N, N’, N’’-triacetic acid (NOTA) and labeled with 68Ga. In the optimal conditions, the whole radio-synthesis was accomplished within 20 min. The decay-corrected radiochemical yield was more than 92 %. The radiochemical purity of 68Ga-NOTA-IF7 was more than 95 %. MicroPET studies showed a high tumor uptake at 15 min post-injection with 7.52 ± 0.16 %ID/g. The ratios of tumor to muscle uptake were 20.61 ± 0.31, 13.14 ± 0.21, 2.39 ± 0.12 at 15 min, 30 min and 60 min post-injection, respectively. 68Ga-NOTA-IF7 is a promising radiopharmaceutical for tumor imaging.

Panaxadiol is a novel antitumor agent extracted from the Chinese medical herb Panax ginseng . This agent is being developed for the treatment of tumor diseases. A rapid, selective, and simple method based on ultrafast liquid chromatography-tandem mass spectrometry was established and validated to determine panaxadiol in rat plasma following oral and sublingual intravenous administration of panaxadiol. The plasma samples were pretreated with acetic ether, and chromatographic separation was achieved on a Shim-pack XR-ODS III column using isocratic elution with the mobile phase of 0.1 % formic acid and acetonitrile. Analytes and protopanaxadiol (internal standard) were analyzed and identified using electrospray positive ionization mass spectrometry in the multiple reaction-monitoring mode. The MS/MS detection was carried out by monitoring the fragmentation of m/z 461.45 → m/z 127.1 for panaxadiol and m/z 425.4 → m/z 95.1 for protopanaxadiol (internal standard) on a triple-quadrupole mass spectrometer. The result showed good linearity over a wide concentration range (0.1–20 ng/mL) (R 2 > 0.999) and its lower limit of detection and quantification were 0.03 and 0.1 ng/mL, respectively. The intra- and interday precision (RSD %) was within 15 % and the accuracy ranged from 94.9 % to 112.0 %. The absolute bioavailability was 12.5 %. The method was fully validated and successfully applied to the pharmacokinetic study of a single dose of panaxadiol.

The solvent-extractable compounds (lipids) of four samples, which were collected from a western suburb of Beijing and in the city of Guiyang, P.R. China, respectively, using a standard high volume air sampler, were investigated to determine the distributions of hydrocarbon compounds. The preliminary results show that all samples contain aliphatic hydrocarbons including n-alkanes, steranes and terpanes, probably derived from either biogenic sources (vascular plant wax input) and/or fossil fuel contamination (coal, crude oil, etc.). However, β-carotane found in the Guiyang aerosol samples may originate from geological or petroleum sources. Polynuclear aromatic hydrocarbons, which are considered to be combustion products from fossil fuels such as petroleum and, especially in this case, coal burning, are also widely distributed in all samples. Furthermore, some apparent fractionation phenomena of organic compounds are observed in samples from different heights above ground.

Glial cells are thought to supply energy for neurotransmission by increasing nonoxidative glycolysis; however, oxidative metabolism in glia may also contribute to increased brain activity. To study glial contribution to cerebral energy metabolism in the unanesthetized state, we measured neuronal and glial metabolic fluxes in the awake rat brain by using a double isotopic-labeling technique and a two-compartment mathematical model of neurotransmitter metabolism. Rats (n = 23) were infused simultaneously with 14C-bicarbonate and [1-13C]glucose for up to 1 hr. The 14C and 13C labeling of glutamate, glutamine, and aspartate was measured at five time points in tissue extracts using scintillation counting and 13C nuclear magnetic resonance of the chromatographically separated amino acids. The isotopic 13C enrichment of glutamate and glutamine was different, suggesting significant rates of glial metabolism compared with the glutamate-glutamine cycle. Modeling the 13C-labeling time courses alone and with 14C confirmed significant glial TCA cycle activity (V(PDH)((g)), approximately 0.5 micromol x gm(-1) x min(-1)) relative to the glutamate-glutamine cycle (V(NT)) (approximately 0.5-0.6 micromol x gm(-1) x min(-1)). The glial TCA cycle rate was approximately 30% of total TCA cycle activity. A high pyruvate carboxylase rate (V(PC), approximately 0.14-0.18 micromol x gm(-1) x min(-1)) contributed to the glial TCA cycle flux. This anaplerotic rate in the awake rat brain was severalfold higher than under deep pentobarbital anesthesia, measured previously in our laboratory using the same 13C-labeling technique. We postulate that the high rate of anaplerosis in awake brain is linked to brain activity by maintaining glial glutamine concentrations during increased neurotransmission.

Some models of brain energy metabolism used to interpret in vivo (13)C nuclear magnetic resonance spectroscopic data assume that intramitochondrial alpha-ketoglutarate is in rapid isotopic equilibrium with total brain glutamate, most of which is cytosolic. If so, the kinetics of changes in (13)C-glutamate can be used to predict citric acid cycle flux. For this to be a valid assumption, the brain mitochondrial transporters of glutamate and alpha-ketoglutarate must operate under physiologic conditions at rates much faster than that of the citric acid cycle. To test the assumption, we incubated brain mitochondria under physiologic conditions, metabolizing both pyruvate and glutamate and measured rates of glutamate, aspartate, and alpha-ketoglutarate transport. Under the conditions employed (66% of maximal O(2) consumption), the rate of synthesis of intramitochondrial alpha-ketoglutarate was 142 nmol/min.mg and the combined initial rate of alpha-ketoglutarate plus glutamate efflux from the mitochondria was 95 nmol/min.mg. It thus seems that much of the alpha-ketoglutarate synthesized within the mitochondria proceeds around the citric acid cycle without equilibrating with cytosolic glutamate. Unless the two pools are in such rapid exchange that they maintain the same percent (13)C enrichment at all points, (13)C enrichment of glutamate alone cannot be used to determine tricarboxylic acid cycle flux. The alpha-ketoglutarate pool is far smaller than the glutamate pool and will therefore approach steady state faster than will glutamate at the metabolite transport rates measured.