Search

Abstract To date, earlier diagnosis of Alzheimer’s disease (AD) is still challenging. Recent studies revealed the elevated expression of connective tissue growth factor (CTGF) in AD brain is an upstream regulator of amyloid-beta (Aβ) plaque, thus CTGF could be an earlier diagnostic biomarker of AD than Aβ plaque. Herein, we develop a peptide-coated gold nanocluster that specifically targets CTGF with high affinity (KD ~ 21.9 nM). The probe can well penetrate the blood-brain-barrier (BBB) of APP/PS1 transgenic mice at early-stage (earlier than 3-month-old) in vivo, allowing non-invasive NIR-II imaging of CTGF when there is no appearance of Aβ plaque deposition. Notably, this probe can also be applied to measuring CTGF on postmortem brain sections by multimodal analysis, including fluorescence imaging, peroxidase-like chromogenic imaging, and ICP-MS quantitation, which enables distinguishment between the brains of AD patients and healthy people. This probe possesses great potential for precise diagnosis of earlier AD before Aβ plaque formation.

The nitrogen and phosphorus in electroplating wastewater were recovered using struvite crystallization method. The effects of pH, concentration of heavy metal ions and mass concentration of fluoride ions on the removal of nitrogen and phosphorus in electroplating wastewater were investigated. The results showed that pH and concentration of heavy metal ions had significantly affect on the process of struvite crystallization, while the effect of low mass concentration（0-40 mg/L） of fluoride ions on the structure of struvite could be ignored. XRD, SEM and XPS characterization were conducted on struvite formed under different conditions, and the influence mechanism of heavy metal ions and fluorine ions on the crystallization process of struvite was analyzed. Heavy metal ions could co-precipitate with struvite and interfere with the formation of struvite crystals. When fluoride ions coexisted with heavy metal ions, fluoride ions would interfere the adsorption of heavy metal ions on the crystal, and generate amorphous phase coprecipitates, changing the crystal morphology of struvite. This study provides a theoretical basis for the recovery of nitrogen and phosphorus from electroplating wastewater by the struvite crystallization method.

Aiming at the problem of insufficient primary frequency regulation resources of power grid in the future, an adaptive control strategy based on charging and discharging margin is proposed for virtual energy storage of electric vehicle aggregation to participate in primary frequency regulation of power grid. Firstly, regulatory and operating range of the electric vehicle is analyzed. Secondly, the primary frequency regulation method of electric vehicle aggregation participating in the power grid is studied. Considering the margin of charging and discharging time and state of charge (SOC), charging and discharging margin index of electric vehicles is designed. Then, an adaptive primary frequency regulation control strategy based on charging and discharging margin is proposed to optimize the droop power of electric vehicles participating in primary frequency regulation, which considers both requirements of primary frequency regulation of power grid and charging, discharging of electric vehicles. Then, the primary frequency regulation capability of virtual energy storage in electric vehicle aggregation is evaluated by regular update, and the evaluation index of primary frequency regulation effect is proposed. Finally, through the simulation analysis of regional power grid cases, the effectiveness of the proposed strategy in reducing the system frequency deviation and optimizing the primary frequency regulation output of electric vehicles is verified.

BackgroundMicro-reactors can be used as a lunar surface power or spacecraft power source for space exploration. Before launching the reactor, a safety analysis should be conducted to prevent a launch accident. Currently, the safety analysis of the radioactive isotope power system does not fully include the safety analysis of the reactor. The main critical safety analysis scenario is that the reactor falls and hits the concrete ground from a high altitude. The reactor may return to criticality after high-speed impact.PurposeThis study aims to investigate the nuclear safety characteristics of a space reactor subjected to dynamic shock under high-speed impact conditions.MethodsFirst of all, based on internal and surface unstructured grids, two simplified reactor models corresponding to two high-speed impact scenarios, i.e., pure fuel reactor vertical impact with ground, and cylinder reactor with a reflector layer and shielding layer impact the ground at a 30° angle were established. Then, the ABAQUS finite element method and unstructured mesh Monte Carlo method of particle transport were combined to predict the criticality properties of the pure fuel and cylindrical reactor during high-speed impact. Based on the surface and internal unstructured mesh Monte Carlo transport technology, the criticality safety analysis platform of micro-reactor under high speed impact was established.ResultsThe results show that the keff induced by the deformation may increase with time for the above mentioned two simplified reactors. The maximum increase in the keff of the pure fuel reactor can reach 1 000×10-5, whereas for the cylinder reactor, the keff is improved to a maximum of 200×10-5. Considering the non-uniform density effect, reactivities of -666×10-5 and -132×10-5 are introduced into the two reactors.ConclusionsThe critical safety characteristics of the reactor under different impact conditions should be evaluated to ensure sufficient safety margins under such accident conditions.

Peptide-protected gold nanoclusters (AuNCs), possessing exceptional biocompatibility and remarkable physicochemical properties, have demonstrated intrinsic pharmaceutical activity in immunomodulation, making them a highly attractive frontier in the field of nanomedicine exploration. Autoimmune hepatitis (AIH) is a serious autoimmune liver disease caused by the disruption of immune balance, for which effective treatment options are still lacking. In this study, we initially identified glutathione (GSH)-protected AuNCs as a promising nanodrug candidate for AIH alleviating in a Concanavalin A (Con A)-induced mice model. However, to enhance treatment efficiency, liver-targeted delivery needs to be improved. Therefore, human serum albumin (HSA)-encapsulated AuNCs were constructed to achieve enhanced liver targeting and more potent mitigation of Con A-induced elevations in plasma aspartate transaminase (AST), alanine transaminase (ALT), and liver injury in mice. In vivo and in vitro mechanism studies indicated that AuNCs could suppress the secretion of IFN-γ by Con A-stimulated T cells and subsequently inhibit the activation of the JAK2/STAT1 pathway and eventual hepatocyte apoptosis induced by IFN-γ. These actions ultimately protect the liver from immune cell infiltration and damage caused by Con A. These findings suggest that bio-protected AuNCs hold promise as nanodrugs for AIH therapy, with their liver targeting capabilities and therapeutic efficiency being further improved via rational surface ligand engineering.

BackgroundThe benefits of virtual reality (VR)-based rehabilitation were reported in patients after stroke, but there is insufficient evidence about how VR promotes brain activation in the central nervous system. Hence, we designed this study to explore the effects of VR-based intervention on upper extremity motor function and associated brain activation in stroke patients.Methods/designIn this single-center, randomized, parallel-group clinical trial with a blinded assessment of outcomes, a total of 78 stroke patients will be assigned randomly to either the VR group or the control group. All stroke patients who have upper extremity motor deficits will be tested with functional magnetic resonance imaging (fMRI), electroencephalography (EEG), and clinical evaluation. Clinical assessment and fMRI will be performed three times on each subject. The primary outcome is the change in performance on the Fugl-Meyer Assessment Upper Extremity Scale (FMA-UE). Secondary outcomes are functional independence measure (FIM), Barthel Index (BI), grip strength, and changes in the blood oxygenation level-dependent (BOLD) effect in the ipsilesional and contralesional primary motor cortex (M1) on the left and right hemispheres assessed with resting-state fMRI (rs-fMRI), task-state fMRI (ts-fMRI), and changes in EEG at the baseline and weeks 4 and 8.DiscussionThis study aims to provide high-quality evidence for the relationship between upper extremity motor function and brain activation in stroke. In addition, this is the first multimodal neuroimaging study that explores the evidence for neuroplasticity and associated upper motor function recovery after VR in stroke patients.Clinical trial registrationChinese Clinical Trial Registry, identifier: ChiCTR2200063425.

There are various geometric fuels in reactors, including cylindrical fuel such as SPERT test reactor, plate fuel such as JRR3 research reactor, annular fuel such as Xi’an Pulse Reactor, and other geometric fuel such as advanced test reactor, etc. Many researchers made efforts for the resonance calculation of these geometric kinds of fuels and several methods were proposed, such as the equivalence theory, the ultrafine group method, the subgroup method, and the globallocal method. At the beginning of the equivalence theory and the ultrafine group method, only cylindrical fuels and plate fuels are supported. Thus, some improvements were proposed in the following years, such as trinomial rational approximation for the equivalence theory and the MOC (method of characteristics) based ultrafine group method. However, these methods have some accuracy and efficiency problems. As for the subgroup method, although arbitrary geometry fuel can be treated since the subgroup fixed source equation can be solved by the MOC, the geometry processing capability of the subgroup method is limited by the resonance integral table. As for the uniformity problembased resonance integral table, the accuracy is not enough. While for the nonuniformity problembased resonance integral table, the arbitrary geometric ability will be lost. For the globallocal method, only cylindrical fuel and plate fuel can be solved. Thus, in this paper, based on the globallocal coupling strategy, a resonance calculation method based on the equivalent geometry method for complex geometric fuels was proposed. First, for the isolated system of complex geometry fuel, based on the conservation of escape probability, an equivalent onedimensional (1D) cylindrical (or plate) fuel model of the complex geometry fuel was established. Secondly, based on the conservation of the collision probability of the fuel to the outer structure material, the equivalent size of the fuel outer structure material was obtained. Then, based on the Dancoff factor conservation of the complex geometry fuel, the equivalent moderator of 1D cylindrical (or plate) fuel model was established. And finally, for the equivalent 1D cylindrical (or plate) model, the pseudoresonantnuclide subgroup method was used to calculate the selfshielding crosssection. The method was applied to the resonance calculation of noncylindrical geometry fuel. As for the pin cases and assembly cases, the deviation of the microscopic absorption section is less than 320%, and the deviation of the eigenvalue is less than 150 pcm. The power deviation is less than 0128%. Compared with the MOCbased pseudoresonantnuclide subgroup resonance calculation method, under the comparable calculation accuracy, the calculation efficiency increases by more than two orders of magnitude. For the core level case, the eigenvalue difference is 338 pcm, the maximum deviation of assembly power is 1182%. The results show geometry flexibility, high accuracy, and high efficiency of this method.

BackgroundRecently, the Age–Bleeding–Organ Dysfunction (ABO) algorithm was recommended by the Asian Pacific Society of Cardiology Consensus as a binary approach to evaluate bleeding risk. This analysis made comparison of the predictive performances between the PRECISE-DAPT and ABO bleeding score in identifying the risk of 12-months major bleeding in Chinese elderly patients over 65 years old patients who underwent percutaneous coronary intervention (PCI) during dual-antiplatelet therapy period.MethodsA total of 2,037 elderly coronary artery disease (CAD) patients (≥65 years) receiving dual antiplatelet therapy (DAPT) after PCI were enrolled in the study. The predictive accuracy of the two bleeding risk scores (PRECISE-DAPT and ABO) was compared for identifying the risk of bleeding during the dual-antiplatelet therapy in patients who underwent PCI. Major clinically relevant bleeding events were defined according to the Bleeding Academic Research Consortium (BARC) criteria.ResultsThe PRECISE-DAPT score in the no bleeding, BARC = 1 bleeding, BARC ≥ 2 bleeding patients was 23.55 ± 10.46, 23.23 ± 10.03, and 33.54 ± 14.33 (p < 0.001), respectively. Meanwhile, the ABO score in the three groups was 0.72 ± 0.80, 0.69 ± 0.81, and 1.49 ± 0.99 (p < 0.001), respectively. The C-statistic of the PRECISE-DAPT model for prediction of BARC ≥ 2 bleeding in overall patients was 0.717 (95% CI, 0.656–0.777) and 0.720 (95% CI, 0.656–0.784) in acute coronary syndrome (ACS) patients. Similar discriminatory capacity was demonstrated in the ABO risk score [overall, patients, AUC: 0.712 (95% CI, 0.650–0.774); ACS patients, AUC: 0.703 (95% CI, 0.634–0.772)]. No differences were observed when the ABO model was in comparison with the PRECISE-DAPT model, regardless in overall patients (z = −0.199, p = 0.842) or ACS patients (z = −0.605, p = 0.545). The calibration for BARC ≥ 2 bleeding of the PRECISE-DAPT and ABO score were acceptable, regardless in overall patients [goodness-of-fit (GOF) Chi-square = 0.432 and 0.001, respectively; p-value = 0.806 and 0.999, respectively] or ACS patients (GOF Chi-square = 0.008 and 0.580, respectively; p-value = 0.996 and 0.748, respectively).ConclusionNo matter of clinical presentation in Asian 65-years older patients with DAPT, the PRECISE-DAPT, and ABO scores had the similar discriminative ability for 12-months BARC ≥ 2 bleeding. Considering the simplicity and reliability, the PRECISE-DAPT score might be more clinically applicable in the overall population and ACS patients in bleeding prediction.

Immune-mediated skin diseases have a high prevalence and seriously affect patients’ quality of life. Gold compounds have been considered promising therapeutic agents in dermatology, but the high incidence of adverse reactions have limited their clinical application. There is a great need to develop more effective and less toxic gold-based drugs. Gold nanoclusters fabricated by using peptides (pep-AuNCs) have appeared as potential biomedical nanomaterials because of their excellent biocompatibility, ease of fabrication and unique physicochemical properties. Glutathione (GSH) is an endogenous tripeptide and has been used for lightening the skin color. Therefore, we fabricated a well-defined gold nanocluster with GSH as an example to explore the immunomodulatory effect of AuNCs on a TNF-α-treated human keratinocyte cell line (HaCaT) in vitro, the 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced irritant contact dermatitis (ICD) model and the oxazolone (OXA)-induced psoriatic model in vivo. The results indicated that topically applied AuNCs successfully attenuated the severity of ICD and psoriasis-like lesions. In vitro and in vivo, AuNCs effectively inhibited the abnormal activation of the NF-κB pathway and the consequent overexpression of proinflammatory cytokines in keratinocytes. In particular, the transactivation of IL-17A, the most important cytokine in psoriasis pathology, was effectively inhibited by AuNCs treatment. In addition, AuNCs did not show any obvious cytotoxicity in HaCaT cells at doses even up to 100 µM and did not induce any irritation in the healthy skin and major organs, which indicated their favorable biosafety. These results indicate that biocompatible pep-AuNCs might be a promising gold-based nanomedicine for the treatment of inflammatory skin diseases.

This study aims to identify the density of TILs in ductal carcinoma in situ (DCIS) in terms of prognostic significance with recurrence and the benefit of whole breast irradiation (WBI). The clinicopathological data of DCIS patients from Jan 2009 to Dec 2016 who received breast-conserving surgery (BCS) were retrospectively reviewed. Cox regression analysis was used to confirm independent prognostic factors of ipsilateral breast tumor recurrence (IBTR). Kaplan–Meier method was utilized to analyze IBTR and values of WBI. Touching-tumor-infiltrating lymphocytes (TILs) were defined by TILs touching or within one lymphocyte cell thickness from the malignant ducts’ basement membrane. In total, 129 patients were enrolled in this analysis with 98 patients who received WBI. After a median follow-up of 53.0 months, there were 16 IBTR events with five invasive IBTRs. Univariate and multivariate analyses showed that touching-TILs >5 were an independent prognostic factor for higher IBTR (HR = 6.17, 95%CI 1.95–19.56, p 5 touching-TILs per duct) and sparse group (≤5 touching-TILs per duct). Dense touching-TILs were associated with unfavorable biologic characteristics. The 5-y rate of IBTR between dense and sparse group was 29.0% versus 4.5% (p

Radiation therapy is one of the important systematic treatment strategies for thoracic neoplasms, but it also can cause a definite cardiac toxicity. With the evolution of main radiotherapeutic technology, the characteristics of heart irradiation dose-volume distribution in patients with thoracic tumor receiving radiotherapy have been changed. The incidence of radiation-related heart diseases (RRHDs) has been significantly decreased. However, precise radiotherapy based on intensity modulated radiation therapy still can not guarantee the absolute cardiac safety currently. This article reviews the effect of heart irradiation dose-volume distribution on potential risks of RRHDs, and the parameters to evaluate heart doses and volume, as well as other techniques affecting the dose-volume distribution of heart irradiation and the detection of RRHDs.

With the development of nuclear reactor, new complicated designs introduce some challenges for the resonance method in the NECP-X code, which is called as the Global-Local method. There are two limitations of the present NECP-X. One is the geometry modeling limitation, and the other one is that the Global-Local resonance method can only deal with the cylindrical fuel rods in the current version. Therefore, some fuels like plate, annular fuels cannot be calculated in the NECP-X code because of these limitations. To overcome above issues, the constructive solid geometry (CSG) method is developed to model the complex problem, and the capability of constructing and solving the equivalent 1D plate and 1D annual fuel pin based on the framework of Global-Local method, is developed. A set of tests are calculated, including multi-annular fuel problems and plate fuel problems. The results show good accuracy of the new developed resonance self-shielding method.

Sepsis-induced acute kidney injury (AKI) with high incidence and mortality rates remains a great challenge in the clinic; thus, novel therapies need to be developed urgently. This complication is associated with an overwhelming systemic inflammatory response. The aim of this study was to evaluate the potential effects and possible mechanisms of gold clusters on septic AKI in vitro. Rat mesangial HBZY-1 cells were treated with peptide-templated gold clusters under lipopolysaccharide (LPS) stimulation. The LPS-induced expression of pro-inflammatory cytokines was measured, including tumor necrosis factor alpha (TNF-α), interleukin-1 beta (IL-1β) and interleukin-6 (IL-6). Our data showed that the LPS-induced transcription and secretion of these cytokines were suppressed by pretreatment of gold clusters in a dose-dependent manner. Cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) also play key roles in septic AKI and both of them are induced upon LPS-stimulation in mesangial cells. Our results further showed that pretreatment with gold clusters dramatically inhibited the LPS-stimulated transcription and expression of COX2 and iNOS, and the subsequent prostaglandin E2 (PGE2) and nitric oxide (NO) production in HBZY-1 cells. Since these factors are involved in the NF-κB pathway upon LPS stimulation, the potential roles of gold clusters on the NF-κB pathway were further determined. We found that LPS-induced NF-κB activation was suppressed in gold clusters-pretreated HBZY-1 cells. These results demonstrated that gold clusters can attenuate LPS-induced inflammation in mesangial cells, probably via inhibiting the activation of the NF-κB pathway, suggesting a potential therapeutic approach for septic AKI.