Altered replication stress response due to CARD14 mutations promotes recombination-induced revertant mosaicism.

Revertant mosaicism, or "natural gene therapy," refers to the spontaneous in vivo reversion of an inherited mutation in a somatic cell. Only approximately 50 human genetic disorders exhibit revertant mosaicism, implicating a distinctive role played by mutant proteins in somatic correction of a pathogenic germline mutation. However, the process by which mutant proteins induce somatic genetic reversion in these diseases remains unknown. Here we show that heterozygous pathogenic CARD14 mutations causing autoinflammatory skin diseases, including psoriasis and pityriasis rubra pilaris, are repaired mainly via homologous recombination. Rather than altering the DNA damage response to exogenous stimuli, such as X-irradiation or etoposide treatment, mutant CARD14 increased DNA double-strand breaks under conditions of replication stress. Furthermore, mutant CARD14 suppressed new origin firings without promoting crossover events in the replication stress state. Together, these results suggest that mutant CARD14 alters the replication stress response and preferentially drives break-induced replication (BIR), which is generally suppressed in eukaryotes. Our results highlight the involvement of BIR in reversion events, thus revealing a previously undescribed role of BIR that could potentially be exploited to develop therapeutics for currently intractable genetic diseases.

Total Synthesis of (+)-Haperforin G.

(+)-Haperforin G was synthesized in 20 steps from commercially available starting materials. A Co-catalyzed intramolecular Pauson-Khand reaction was used for stereoselective construction of cyclopentanone bearing an all-carbon quaternary stereogenic center at the bridge-head position. Light-initiated photocatalysis was used for convergent and asymmetric cross-coupling of the unstabilized C(sp3) radical with an enone. The developed chemistry paves the way to the synthesis of structurally diverse analogs of haperforin G (6).

Effect of high-flow nasal cannula on patients' recovery after inhalation general anesthesia.

Objective: To investigate the effect of high-flow nasal cannula (HFNC) and Oxygen Nebuliser mask (ONM) on patients recovering from inhalation anesthesia. Methods: A retrospective analysis was performed on 128 patients after inhalation of general anesthesia in the recovery room of the Anesthesiology Department of The Fourth Hospital of Hebei Medical University from September 2019 to September 2021. All patients received the same anesthesia induction and analgesia methods, inhalation anesthesia or intravenous-inhalation anesthesia maintenance, recovered spontaneous breathing and removed endotracheal intubation after surgery, then were divided into HFNC group and ONM group for oxygen therapy. HFNC setting mode: flow rate: 20-60 L/minutes, humidification temperature: 37°C, the oxygen concentration was adjusted to maintain finger pulse oxygen saturation SPO2>90%; ONM group, the oxygen flow rate was adjusted to maintain finger pulse oxygen saturation SPO2>90%. All patients in the two groups were compared immediately after they entered the recovery room for 0 minutes,, 10 minutes, and 20 minutes,, including tidal volume, blood gas, Richmond Agitation-Sedation Scale (RASS) score and time from sedation to awakening. Results: The changes in tidal volume, oxygenation index and RASS score over time in the HFNC group were higher than those in the ONM group (p<0.05), and the awakening time in the HFNC group was faster than that in the ONM group (p<0.01), with significant statistical differences. Conclusions: Compared with ONM, HFNC can shorten postoperative recovery time, reduce the incidence of agitation and improve lung function and oxygenation state during recovery from anesthesia.

Activation of peripheral group III metabotropic glutamate receptors suppressed formalin-induced nociception.

Intraplantar injection of formalin produces persistent spontaneous nociception and hyperalgesia. The underlying mechanism, however, remains unclear. The present study was, therefore, designed to determine the roles of peripheral group III metabotropic glutamate receptors (mGluRs) in formalin-evoked spontaneous nociception. Pre-treatment with intraplantar injections of L-serine-O-phosphate (L-SOP), a group III mGluRs agonist, significantly inhibited formalin-induced nociceptive behaviours and decreased Fos production in the spinal dorsal horn. The inhibitory effects of L-SOP were abolished completely by pre-treatment with the group III mGluR antagonist (RS)-a-methylserine-O-phosphate (M-SOP). These data suggest that the activation of group III mGluRs in the periphery may play a differential role in formalin-induced nociception. In addition, L-SOP decreased the formalin-induced upregulation of tumour necrosis factor-α (TNF-α) as well as interleukine-1ß (IL-1ß) expression in the spinal cord, suggesting that activation of peripheral group III mGluRs reduces formalin-induced nociception through inhibition of the pro-inflammatory cytokines in the spinal cord. Therefore, the agonists acting peripheral group III mGluRs possess therapeutic effectiveness in chronic pain.

Deep Learning for Detecting Cerebral Aneurysms with CT Angiography.

Background Cerebral aneurysm detection is a challenging task. Deep learning may become a supportive tool for more accurate interpretation. Purpose To develop a highly sensitive deep learning-based algorithm that assists in the detection of cerebral aneurysms on CT angiography images. Materials and Methods Head CT angiography images were retrospectively retrieved from two hospital databases acquired across four different scanners between January 2015 and June 2019. The data were divided into training and validation sets; 400 additional independent CT angiograms acquired between July and December 2019 were used for external validation. A deep learning-based algorithm was constructed and assessed. Both internal and external validation were performed. Jackknife alternative free-response receiver operating characteristic analysis was performed. Results A total of 1068 patients (mean age, 57 years ± 11 [standard deviation]; 660 women) were evaluated for a total of 1068 CT angiograms encompassing 1337 cerebral aneurysms. Of these, 534 CT angiograms (688 aneurysms) were assigned to the training set, and the remaining 534 CT angiograms (649 aneurysms) constituted the validation set. The sensitivity of the proposed algorithm for detecting cerebral aneurysms was 97.5% (633 of 649; 95% CI: 96.0, 98.6). Moreover, eight new aneurysms that had been overlooked in the initial reports were detected (1.2%, eight of 649). With the aid of the algorithm, the overall performance of radiologists in terms of area under the weighted alternative free-response receiver operating characteristic curve was higher by 0.01 (95% CI: 0.00, 0.03). Conclusion The proposed deep learning algorithm assisted radiologists in detecting cerebral aneurysms on CT angiography images, resulting in a higher detection rate. © RSNA, 2020 Online supplemental material is available for this article. See also the editorial by Kallmes and Erickson in this issue.

Enhancement degree of brain metastases: correlation analysis between enhanced T2 FLAIR and vascular permeability parameters of dynamic contrast-enhanced MRI.

OBJECTIVES: To investigate the correlation between enhancement degrees of brain metastases on contrast-enhanced T2-fluid-attenuated inversion recovery (CE-T2 FLAIR) and vascular permeability parameters of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI). METHODS: Thirty-nine patients with brain metastases were prospectively collected. They underwent non-enhanced T2 FLAIR, DCE-MRI, CE-T2 FLAIR, and contrast-enhanced three-dimensional brain volume imaging (CE-BRAVO). Quantitative parameters of DCE-MRI were evaluated for all lesions, which included volume transfer constant (Ktrans), rate constant (Kep), and fractional volume of the extracellular extravascular space (Ve). Contrast ratio (CR) and percentage increase (PI) values of all lesions on CE-T2 FLAIR were also measured. The tumor enhancement degree on CE-T2 FLAIR in relation to CE-BRAVO was visually classified as higher (group A), equal (group B), and lower (group C). RESULTS: A total of 82 brain metastases were evaluated, including 31 in group A, 19 in group B, and 32 in group C. The Ktrans and Kep were negatively correlated with the CR (ρ = - 0.551, p < 0.001 and ρ = - 0.708, p < 0.001, respectively) and PI (ρ = - 0.511, p < 0.001 and ρ = - 0.621, p < 0.001, respectively). The Ktrans and Kep of group A were significantly lower than those of group C (both p < 0.001). No significant difference was found in Ve among the groups (p = 0.327). CONCLUSIONS: The enhancement degree of brain metastases on CE-T2 FLAIR is negatively correlated with Ktrans and Kep values, which indicate that vascular permeability parameters may play an important role in explaining the difference in enhancement between CE-T2 FLAIR and CE-BRAVO. KEY POINTS: • The enhancement degree on CE-T2 FLAIR was negatively correlated with Ktrans and Kep values. • The vascular permeability of brain metastasis accounted for the difference in enhancement degree between CE-T2 FLAIR and CE-BRAVO. • CE-T2 FLAIR is useful for detecting brain metastases with mild disruption of the blood-brain barrier.

Optimization of Contrast Agent Dosage on Contrast-Enhanced T2 Fluid-Attenuated Inversion Recovery: An In Vitro and In Vivo Study.

OBJECTIVE: This study aimed to ascertain the minimum gadolinium dosage on contrast-enhanced (CE) T2 fluid-attenuated inversion recovery (FLAIR) at appropriate imaging time. METHODS: Different dosages of gadodiamide were imaged with a 3.0-T magnetic resonance scanner for T2-FLAIR and T1WI. Twenty glioma-induced rat models were randomly assigned into 4 groups (1/2, 1/4, 1/6, 1/8 of routine dosage) and imaged for T2-FLAIR and T1WI preinjection and postinjection of gadodiamide. Contrast-enhanced T2-FLAIR was acquired for 8 repetitions postinjection. Enhancement effects were assessed by calculating contrast-noise ratio and contrast ratio using Kruskal-Wallis and Mann-Whitney rank sum test. RESULTS: The in vitro experiment showed that gadodiamide at 1/4 of the T1WI dosage presented the best contrast on CE-T2-FLAIR. For in vivo study, the best enhancement effect on CE-T2-FLAIR was achieved at 1/2 of the routine dosage at 8 to 12 minutes of delayed scanning. Compared with CE-T1WI at routine dosage, CE-T2-FLAIR at 1/2 gadodiamide dosage presented similar enhancement effects with no statistical difference (P = 0.244 and 0.090 for contrast-noise ratio and contrast ratio, respectively). CONCLUSIONS: Contrast-enhanced T2-FLAIR imaging with half of T1WI routine gadodiamide dosage can produce similar enhancement effects to CE-T1WI when characterizing brain gliomas. The cut-down of contrast agent dosage may help reduce gadolinium accumulation in certain tissues.

Total Synthesis of (+)-Haperforin G.

A concise chemical synthesis of (+)-haperforin G in 20 steps from commercially available starting materials is achieved with the integration of the Co-catalyzed intramolecular Pauson-Khand reaction for the stereoselective construction of cyclopentanone bearing an all-carbon quaternary stereogenic center at the bridge-head position and the light-initiated photocatalysis for convergent and asymmetric cross-coupling of the unstabilized C(sp3)-radical with an enone. The developed chemistry paves the way to synthesizing structurally diverse analogs of haperforin G (6).

A comprehensive analysis of the allergenicity and IgE epitopes of myosinogen allergens in Scylla paramamosain.

BACKGROUND: Scylla paramamosain is one of the most common and serious food allergens in Asia. Therefore, research on its prevalence, accurate diagnosis, and IgE-binding pattern of the allergens is crucial. OBJECTIVE: To identify the IgE epitopes of the myosinogen allergens in S. paramamosain using phage peptide library. METHODS: The prevalence of allergy to crabs (AC) and of sensitization was analysed using a questionnaire and a serological assay. BAT was performed by flow cytometry, and its diagnostic performance was evaluated in relation to allergens purified from crab myosinogen. IgE-binding epitopes were identified by phage display using the IgE from patients with AC. Sequence- and structure-based bioinformatics analyses were performed to identify allergenic epitopes. RESULTS: Crab was the most common cause of food allergies in this study. Subjects with AC (n = 30) with clear clinical symptoms were identified by immunoblotting and BAT. All of the myosinogen allergens triggered basophil activation; surface expression of CD63 and CD203c was higher in patients allergic to AK and FLN c than in patients allergic to SCP and TIM. In addition to six conformational epitopes of SCP, six linear epitopes and eight conformational epitopes of AK were identified. Five linear epitopes and three conformational epitopes of TIM, nine linear and ten conformational epitopes of FLN c were also identified, and the sequence VH(I/T) L was appeared in epitopes of both TIM and FLN c. The number of epitopes showed consistency with the value of BAT. CONCLUSIONS AND CLINICAL RELEVANCE: BAT can be used for accurate diagnosis of AC. Identification of particular allergenic motifs could be a valuable tool for prevention, diagnosis, and treatment of food allergies.

Noninvasive Prediction of IDH1 Mutation and ATRX Expression Loss in Low-Grade Gliomas Using Multiparametric MR Radiomic Features.

BACKGROUND: Noninvasive detection of isocitrate dehydrogenase 1 mutation (IDH1(+)) and loss of nuclear alpha thalassemia/mental retardation syndrome X-linked expression ((ATRX(-)) are clinically meaningful for molecular stratification of low-grade gliomas (LGGs). PURPOSE: To study a radiomic approach based on multiparametric MR for noninvasively determining molecular status of IDH1(+) and ATRX(-) in patients with LGG. STUDY TYPE: Retrospective, radiomics. POPULATION: Fifty-seven LGG patients with IDH1(+) (n = 36 with 19 ATRX(-) and 17 ATRX(+) patients) and IDH1(-) (n = 21). FIELD STRENGTH/SEQUENCE: 3.0T MRI / 3D arterial spin labeling (3D-ASL), T2 /fluid-attenuated inversion recovery (T2 FLAIR), and diffusion-weighted imaging (DWI). ASSESSMENT: In all, 265 high-throughput radiomic features were extracted on each tumor volume of interest from T2 FLAIR and the other three parametric maps of ASL-derived cerebral blood flow (CBF), DWI-derived apparent diffusion coefficient (ADC), and exponential ADC (eADC). Optimal feature subsets were selected as using the support vector machine with a recursive feature elimination algorithm (SVM-RFE). Receiver operating characteristic curve (ROC) analysis was employed to assess the efficiency for identifying the IDH1(+) and ATRX(-) status. STATISTICAL TESTS: Student's t-test, chi-square test, and Fisher's exact test were applied to confirm whether intergroup significant differences exist between molecular subtypes decided by IDH1 and ATRX. RESULTS: Optimal SVM predictive models of IDH1(+) and ATRX(-) were established using 28 features from T2 Flair, ADC, eADC, and CBF and six features from T2 Flair, ADC, and CBF. The accuracies/AUCs/sensitivity/specifity/PPV/NPV of predicting IDH1(+) in LGG were 94.74%/0.931/100%/85.71%/92.31%/100%, and those of predicting ATRX(-) in LGG with IDH1(+) were 91.67%/0.926/94.74%/88.24%/90.00%/93.75%, respectively. DATA CONCLUSION: Using the optimal texture features extracted from multiple MR sequences or parametric maps, a promising stratifying strategy was acquired for predicting molecular subtypes of IDH1 and ATRX in LGGs. LEVEL OF EVIDENCE: 3 Technical Efficacy Stage: 2 J. Magn. Reson. Imaging 2019;49:808-817.

Nucleus-translocated matrix metalloprotease 1 regulates innate immune response in Pacific abalone (Haliotis discus hannai).

As an important economical shellfish in coastal area of China, abalone is susceptible to bacterial infection, especially Vibiro parahemolyticus (V. parahemolyticus). Matrix metalloproteinases (MMPs) have been extensively investigated in the immune response of mammals. However, little is known about the involvement of MMP in abalone innate immune system against pathogen infection. In this study, the role of MMP-1 in the immune response of Pacific abalone (Haliotis discus hannai) was explored. The results showed that V. parahemolyticus infection induced significantly elevated expression of MMP-1 as well as immune related genes including allograft inflammatory factor 1 (AIF-1), macrophage expressed gene 1 (MPEG-1) and TPA-inducible sequence 11 family protein (Tis11FP). Notably, silencing of MMP-1 reduced the expression of these genes, suggesting that MMP-1 was an upstream regulatory factor in V. parahemolyticus infection. Further analysis showed that MMP-1 was engaged in the regulation of cellular (phagocytosis, apoptosis) and humoral [superoxide dismutase (SOD), alkaline phosphatase (ALP), acid phosphatase (ACP)] immunity. Interestingly, the extracellularly distributed MMP-1 could be translocated to the nuclei of hemocytes, thereby functioning as a transcriptional regulator or by selectively activating or inactivating other components through proteolysis. Hence, our study established an important role of MMP-1 in abalone innate immunity against V. parahemolyticus infection and it represented the first report on the investigation of MMP in abalone.

Application of MRS- and ASL-guided navigation for biopsy of intracranial tumors.

BACKGROUND: The diagnosis of a tumor depends on accurate identification of the target area for biopsy. However, tumor heterogeneity and the inability of conventional structural data for identifying the most malignant areas can reduce this accuracy. PURPOSE: To evaluate the feasibility and practicality of magnetic resonance spectroscopy (MRS)- and arterial spin labeling (ASL)-guided MRI navigation for needle biopsy of intracranial tumors. MATERIAL AND METHODS: Thirty patients with intracranial tumors who underwent intraoperative stereotactic biopsy were retrospectively analyzed. Contrast-enhanced 3D-BRAVO or 3D-T2FLAIR structural data, combined with MRS and ASL data, were used to identify the target area for biopsy. High-choline or high-perfusion sites were chosen preferentially, and then the puncture trajectory was optimized to obtain specimens for histopathologic examination. RESULTS: Twenty-two specimens were collected from 20 glioma patients (two specimens each were collected from two patients) and ten specimens were collected from ten lymphoma patients. The diagnosis rate after the biopsy was 93.3% (28/30). Two gliomas were initially diagnosed as gliosis and subsequently diagnosed correctly after the collection of a second biopsy specimen. Combined MRS and ASL helped target selection in 23 cases (76.7%), including three cases each of low-enhancing and non-enhancing gliomas. In two cases, the target selection decision was changed because the areas initially chosen on the basis of positron emission tomography data did not match the high-perfusion areas identified with ASL. CONCLUSION: Compared with conventional MRI, combined MRS and ASL improved the accuracy of target selection for the stereotactic biopsy of intracranial tumors.

In Vivo MR Imaging of Glioma Recruitment of Adoptive T-Cells Labeled with NaGdF4 -TAT Nanoprobes.

Adoptive T lymphocyte immunotherapy is one of the most promising methods to treat residual lesions after glioma surgery. However, the fate of the adoptively transferred T-cells in vivo is unclear, hampering the understanding of this emerging therapy. Thus, it is highly desirable to develop noninvasive and quantitative in vivo tracking of these T-cells to glioma for better identification of the migratory fate and to provide objective evaluation of outcomes of adoptive T-cell immunotherapy targeting glioma. In this work, ultrasmall T1 MR-based nanoprobes, NaGdF4 -TAT, as molecular probes with high longitudinal relaxivity (8.93 mm-1 s-1 ) are designed. By means of HIV-1 transactivator (TAT) peptides, nearly 95% of the adoptive T-cells are labeled with the NaGdF4 -TAT nanoprobes without any measurable side effects on the labeled T-cells, which is remarkably superior to that of the control fluorescein isothiocyanate-NaGdF4 concerning labeling efficacy. Labeled adoptive T-cell clusters can be sensitively tracked in an orthotopic GL261-glioma model 24 h after intravenous infusion of 107 labeled T-cells by T1 -weighted MR imaging. Both in vitro and in vivo experiments show that the NaGdF4 -TAT nanoprobes labeling of T-cells may be a promising method to track adoptive T-cells to improve our understanding of the pathophysiology in adoptive immunotherapy for gliomas.

Involvement of clip-domain serine protease in the anti-Vibrio immune response of abalone (Haliotis discus hannai)-Molecular cloning, characterization and functional analysis.

Vibrio parahemolyticus (V. parahemolyticus) is a major pathogen for abalone, an important economical shellfish in coastal area of China. There is little known about the abalone innate immune system against pathogen infection. Clip-domain serine proteases (cSPs) are increasingly recognized to play important roles in host immune defense in invertebrates. In this study, we cloned a cSP (Hdh-cSP) from abalone (Haliotis discus hannai). We found out that Hdh-cSP was widely expressed in multiple tissues of abalone, with highest level in the immune-like organ, hepatopancreas. V. parahemolyticus infection induced significantly elevated expression of Hdh-cSP in addition to better-characterized innate immune component genes including Rel/NF-κB, allograft inflammatory factor (ALInFa), macrophage expressed protein (MEP) and caspase-8. Importantly, the silencing of Hdh-cSP reduced the expression of these genes, suggesting that Hdh-cSP was an upstream regulatory factor in V. parahemolyticus infection. Further analysis showed that apoptosis of hemocytes was inhibited when the transcription of Hdh-cSP was knocked down, suggesting that Hdh-cSP participated in cell apoptosis by regulation of caspase 8 expression in V. parahemolyticus infection. Therefore, our study established an important role of cSP in the innate immunity against V. parahemolyticus infection in abalone.

Evaluation of vascular invasion in patients with musculoskeletal tumors of lower extremities: use of time-resolved 3D MR angiography at 3-T.

Background Time-resolved angiography with stochastic trajectories (TWIST) sequence makes considerable progress in temporal and spatial resolution, which presents high potential in evaluation of vascular diseases. Purpose To assess magnetic resonance imaging (MRI) using TWIST MR angiography (MRA) sequence in the assessment of vascular invasion for bone and soft-tissue tumors in comparison to computed tomography angiography (CTA) as the reference standard. Material and Methods Thirty-three patients with lower extremity musculoskeletal tumors were imaged with conventional MR and TWIST MRA. CTA was performed 48 h later. The signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) of the femoral artery were calculated. Vascular invasion as determined by MRA and CTA was separately analyzed. Vascular invasion by MRA and CTA were analyzed with kappa coefficients to determine agreement between the imaging methods. Results Seven cases of bone and 26 cases of soft tissue tumors were examined. SNR and CNR of the femoral artery were excellent for TWIST MRA (mean ± SD values of 317 ± 80 and 276 ± 76, respectively). Based on the TWIST sequence, the vessels were free of tumor in 16 cases. Vascular displacement was found in 11 cases and vascular stenosis in six cases. The MRA findings conflicted with CTA findings in only one case. The kappa value was 0.953 ( P < 0.01). In five cases, vascular malformations were found with TWIST MRA but not CTA. Conclusion TWIST MRA enables accurate delineation of anatomical structures and tumor arterial involvement, providing reliable preoperative imaging information with respect to lower extremity musculoskeletal tumors.

Low-temperature vaterite-type LuBO3, a vacancy-stabilized phase synthesized at high temperature.

Low-temperature vaterite-type LuBO(3) (π-LBO) was prepared by a solid-state reaction method at high temperature. The reasoning of the existence of vacancy-stabilized π-LBO was investigated for the first time using neutron diffraction patterns, Fourier transform infrared (FT-IR) spectra, and high-resolution transmission electron microscopy. The results clearly demonstrated that the B and O vacancies in π-LBO came into being during the heating process. The existence of an open B(3)O(9) ring consisting of BO(3) and BO(4) units in π-LBO due to the B and O vacancies was demonstrated by FT-IR. The vacuum ultraviolet-ultraviolet spectroscopic properties of π-LBO were studied in detail. In addition, the luminescence mechanism of Ce(3+) in π-LBO was put forward and discussed with that of calcite-type LuBO(3) (ß-LBO).

Self-adjuvanted L-arginine-modified dextran-based nanogels for sustained local antigenic protein delivery to antigen-presenting cells and enhanced cellular and humoral immune responses.

In the development of cancer vaccines, antigens are delivered to elicit potent and specific T-cell responses to eradicate tumour cells. Nonetheless, successful vaccines are often hampered by the poor immunogenicity of tumour antigens, rapid clearance by the innate immunity, and limited cross-presentation on MHC-I to activate CD8+ T-cells arm. To address these issues, we developed dextran-based nanogels to promote antigen uptake, storage, and cross-presentation on MHC-I, while directing immunogenic maturation of the antigen-presenting cells (APCs). To promote the nanocarriers interaction with cells, we modified DX with L-arginine (Arg), whose immunomodulatory activities have been well documented. The ArgDX nanogel performance was compared with the nanogel modified with L-histidine (His) and L-glutamate (Glut). Moreover, we introduced pH-sensitive hydrazone crosslinking during the nanogel formation for the conjugation and controlled release of antigen ovalbumin (OVA). The OVA-laden nanogels have an average size of 325 nm. We demonstrated that the nanogels could rapidly release cargoes upon a pH change from 7 to 5 within 8 days, indicating the controlled release of antigens in the acidic cellular compartments upon internalization. Our results revealed that the ArgDX nanogel could promote greater antigen uptake and storage in DCs in vitro and promoted a stronger immunogenic maturation of DCs and M1 polarization of the macrophages. The OVA signals were co-localized with lysosomal compartments up till 96 hours post-treatment and washing, suggesting the nanogels could facilitate prolonged antigen storage and supply from endo-lysosomal compartments. Furthermore, all the tested nanogel formulations retained antigens at the skin injection sites until day 21. Such delayed clearance could be due to the formation of micron-sized aggregates of OVA-laden nanogels, extending the interactions with the resident DCs. Amongst the amino acid modifications, ArgDX nanogels promoted the highest level of lymph node homing signal CCR7 on DCs. The nanogels also showed higher antigen presentation on both MHC-I and II than DX in vitro. In the in vivo immune studies, ArgDX nanogels were more superior in inducing cellular and humoral immunity than the other treatment groups on day 21 post-treatment. These results suggested that ArgDX nanogel is a promising self-adjuvanted nanocarrier for vaccine delivery.

Effects of open and closed skill exercise interventions on executive function in typical children: a meta-analysis.

BACKGROUND: The effects of open and closed skill exercise interventions for executive function in children and adolescents have received widespread attention. Open skill refers to the skill of performing motor tasks in an unpredictable environment; closed skill refers to the skill of performing motor tasks in a stable environment. However, the results of related studies are currently controversial and Meta-analysis is urgently needed. METHODS: After computer searches of CNKI, Wan-Fang, VIP, WOS, PubMed, and EBSCO databases, two researchers independently screened articles, extracted information, and evaluated the quality of the articles. This study was statistical analyzed using Stata 16.0 software. RESULTS: A total of 31 articles were included, including 2988 typical children. Open, closed, continuous and sequential skills all improved executive function in typical children to varying degrees, but open and sequential skills were more effective in improving executive function, particularly in the former in the working memory (SMD=-0.833, P < 0.001) and in the latter in the inhibitory control (SMD=-0.834, P < 0.001) and cognitive flexibility (SMD=-0.903, P < 0.001). Long-term, moderate- intensity interventions were better than acute, vigorous-intensity interventions for executive function, with long-term interventions reflected in working memory (SMD=-0.579, P < 0.001) and moderate-intensity interventions reflected in all three dimensions of executive function (P < 0.01). Intervention periods, intervention intensity and continuous and sequential skills classified by action structure play a significant moderating role. Better results for long-term, sequential structural action interventions based on open skills (P < 0.001); better results for acute, moderate intensity, sequential structural action interventions based on closed (P < 0.05). Whereas intervention intensity had a non-significant moderating effect in the open skills intervention, both moderate and vigorous intensity had a significant effect on executive function (P < 0.001). CONCLUSION: Open and closed skills have different levels of facilitation effects on executive function in typical children, but open skills are more effective. The facilitation effects of open and closed skills were moderated by the qualitative characteristics and action structure of the intervention.

Three-dimensional image-guided topical photodynamic therapy system with light dosimetry dynamic planning and monitoring.

Photodynamic therapy (PDT) has shown significant potential for skin disease treatment. As a key element, light is critical to influencing its treatment outcome, and light dosimetry is an issue of much concern for researchers. However, because of three-dimensional irregularity in shape and patient's movement during the therapy, irradiance hardly keeps uniform on the lesion and flux measurement remains a challenge. In this work, we report the development of a three-dimensional image-guided PDT system, and the method of dynamic irradiance planning and flux monitoring for lesions in different poses. This system comprises a three-dimensional camera for monitoring patients' movement during therapy, a computer for data analysis and processing, and a homemade LED array for forming uniform irradiance on lesions. Simulations on lesions of the face and arm show that the proposed system significantly increases effective therapy area, enhances irradiance uniformity, is able to visualize flux on the lesion, and reduces risks of burns during PDT. The developed PDT system is promising for optimizing procedures of PDT and providing better treatment outcomes by delivering controllable irradiance and flux on lesions even when a patient is moving.