This report describes a clinically rare and atypical case of 46,X,idic(X)(q21.32)/45,X-type Turner syndrome with rapidly progressive puberty development. After 11 months of treatment with recombinant ...human growth hormone (rhGH), the child’s height increased. After 18 months of treatment with rhGH, the child showed secondary sex characteristics. The child was followed up for 1 year after the appearance of the secondary sex characteristics, and regular menses were still present. This case indicates that modern molecular biology techniques should be used rationally to further investigate the existence of X-chromosome translocations and occult chimeras to prevent misdiagnosis.
•Ten kinds of Trombe wall systems integrated with PCMs were proposed.•The effect on thermal comfort of PCM temperature and location was analyzed.•The integrated indoor discomfort hour and discomfort ...degree-hour were calculated.•An optimal wall structure was obtained for the hot summer and cold winter region.
Trombe wall and phase change materials (PCMs) are two effective ways to regulate indoor thermal comfort. However, Trombe wall surfers from overheating in summer and PCMs suffer from low heat transfer rate caused by the limited thermal conductivity. To compensate the shortcomings of the two methods, this paper proposed a Trombe wall system integrated with PCMs. Based on a light-weight building envelope in Changsha, China, the thermal comfort of 10 kinds of Trombe wall systems with PCMs with a melting temperature of 18–28 ℃ were studied. Taking the integrated indoor discomfort duration (ID), integrated indoor discomfort degree-hour (IDH), indoor air temperature (Tin), PCM liquid fraction (γ) and heat flux across wall (q) as evaluation indexes, the indoor thermal comfort was assessed in hot summer and cold winter region. Results show that the Trombe wall helped PCMs complete the phase change process effectively. Trombe wall with PCM25 next to the wall inner surface possessed the lowest annual ID and IDH, as 2877 h and 12,974 ℃· h, respectively. Compared with the values in a traditional building, the ID and IDH were reduced by 7.01% and 14.14%. In order to give full play to the heat storage and heat release of the Trombe wall with PCMs, PCMs with phase change temperature 7℃ lower than the peak ambient temperature in summer or 8℃ higher than the winter night temperature was recommended according to regional climate conditions.
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Injectable hydrogels have great promise in the treatment of myocardial infarction (MI); however, the lack of electromechanical coupling of the hydrogel to the host myocardial tissue and the inability ...to monitor the implantation may compromise a successful treatment. The introduction of conductive biomaterials and mesenchymal stem cells (MSCs) may solve the problem of electromechanical coupling and they have been used to treat MI. In this study, we developed an injectable conductive nanocomposite hydrogel (GNR@SN/Gel) fabricated by gold nanorods (GNRs), synthetic silicate nanoplatelets (SNs), and poly(lactide-co-glycolide)-b-poly (ethylene glycol)-b-poly(lactide-co-glycolide) (PLGA-PEG-PLGA). The hydrogel was used to encapsulate MSCs and
Ga
cations, and was then injected into the myocardium of MI rats to monitor the initial hydrogel placement and to study the therapeutic effect via
F-FDG myocardial PET imaging.
Our data showed that SNs can act as a sterically stabilized protective shield for GNRs, and that mixing SNs with GNRs yields uniformly dispersed and stabilized GNR dispersions (GNR@SN) that meet the requirements of conductive nanofillers. We successfully constructed a thermosensitive conductive nanocomposite hydrogel by crosslinking GNR@SN with PLGA
-PEG
-PLGA
, where SNs support the proliferation of MSCs. The cation-exchange capability of SNs was used to adsorb
Ga
to locate the implanted hydrogel in myocardium via PET/CT. The combination of MSCs and the conductive hydrogel had a protective effect on both myocardial viability and cardiac function in MI rats compared with controls, as revealed by
F-FDG myocardial PET imaging in early and late stages and ultrasound; this was further validated by histopathological investigations.
The combination of MSCs and the GNR@SN/Gel conductive nanocomposite hydrogel offers a promising strategy for MI treatment.
Artemisinin (ART) and dihydroartemisinin (DHA) are first-line antimalarial drugs and have been reported to have anti-obesity effects. Hyperlipidemia is associated with β-cell damage in obese ...subjects, which could contribute to the pathogenesis of type 2 diabetes. In addition to their anti-obesity effects, ART and DHA also have protective roles in some diseases. Thus, we investigated the effects of ART and DHA in palmitate-induced β-cell apoptosis and the underlying mechanism. In this study, the rat pancreatic β-cell line INS-1 and mouse pancreatic β-cell line MIN6 were cultured with palmitate (PA) (0.1 mM) to induce cell apoptosis in the presence or absence of ART or DHA. Cell apoptosis was investigated by using flow cytometry, and the expression of ER stress markers, including CHOP, GRP78 and PDI, was detected by Western blotting and/or qRT-PCR. The results showed that ART and DHA significantly increased the apoptosis of β-cells induced by PA and exacerbated the ER stress caused by PA. An inhibitor of ER stress, 4-phenylbutyric acid (4-PBA), significantly ameliorated cell apoptosis caused by ART and DHA in PA-treated β-cells, consistent with the inhibition of ER stress. Together, the findings from the current study suggested that ART and DHA may promote lipid disorder-associated β-cell injury via enhancing ER stress when they were used to treat obesity.
ØThe effect of PCMs under various climate conditions was investigated.ØA simulated model was developed and verified against experimental data.ØEnergy use intensity (EUI) was used as the index to ...evaluate PCM performance.ØAn economic analysis was conducted using static investment payback period.
The use of phase change materials (PCMs) in building enclosures is an efficient way to reduce the heat gain and/or loss in summer and winter. It was evident that the thermal performance of buildings with PCMs was affected by the outdoor air temperature significantly. However, the influence of humidity, which was serious in the humid subtropical climate was unclear. To explore the effect of PCMs under a humid subtropical climate, the thermal performance of a lightweight building outfitted with PCMs with a melting temperature of 25 °C was investigated. The actual outdoor air temperature with a humidity of 40–90 RH% and wind velocity of 2–6 m/s blowing from the east, west, south, and north was assumed for the performance assessment. A simulated model was developed using EnergyPlus and verified against experimental data. The energy savings by using PCMs was reduced from 3.9% to 2.6% when the outdoor humidity increased from 40 to 90 RH% in summer. However, the savings was not obvious in winter. Annual energy savings decreased from 1.64% to 1.32% with humidity increasing from 40 to 90 RH%. For annual condition, the average energy savings was reduced from 1.43% to 0.92% when the wind speed increased from 2 m/s to 6 m/s. From an economic point of view, the investment payback period was less than 10 years when the PCM price was lower than 18.0 Yuan/kg.
Myocardial infarction (MI) resulting from coronary artery occlusion is the leading global cause of cardiovascular disability and mortality. Anti-inflammatory treatment plays an important role in MI ...treatment. Triptolide (TPL), as a Chinese medicine monomer, has a variety of biological functions, including anti-inflammatory, anti-tumor, and immunoregulation. However, it has been proved that TPL is poorly water soluble, and has clear hepatotoxicity and nephrotoxicity, which seriously limits its clinical application. Herein, we designed a long-acting hydrogel platform (TPL@PLGA@F127) for MI treatment by intramyocardial injection. First, we found that the inflammatory response and immune regulation might be the main mechanisms of TPL against MI by network pharmacology. Subsequently, we prepared the hydrogel platform (TPL@PLGA@F127) and tested its effects and toxicity on normal organs in the early stage of MI (3 days after MI-operation). The results showed that TPL@PLGA@F127 could not only promote "repair" macrophages polarization (to M2 macrophage) by day 3 after MI, but also has a long-lasting anti-inflammatory effect in the later stage of MI (28 days after MI-operation). Additionally, we proved that TPL@PLGA@F127 could attenuate the toxicity of TPL by releasing it more slowly and stably. Finally, we observed the long-term effects of TPL@PLGA@F127 on MI and found that it could improve cardiac function, depress the myocardial fibrosis and protect the cardiomyocytes. In summary, this study indicated that TPL@PLGA@F127 could not only enhance the therapeutic effects of TPL on MI, but also attenuate the hepatotoxicity and nephrotoxicity, which established a strong foundation for the clinical application of TPL for MI.
Tumor cell-derived exosomes (TEx) have emerged as promising nanocarriers for drug delivery. Noninvasive multimodality imaging for tracing the in vivo trafficking of TEx may accelerate their clinical ...translation. In this study, we developed a TEx-based nanoprobe via hydrophobic insertion mechanism and evaluated its performance in dual single-photon emission computed tomography (SPECT) and near-infrared fluorescence (NIRF) imaging of colon cancer.
TEx were successfully isolated from HCT116 supernatants, and their membrane vesicle structure was confirmed by TEM. The average hydrodynamic diameter and zeta potential of TEx were 110.87 ± 4.61 nm and -9.20 ± 0.41 mV, respectively. Confocal microscopy and flow cytometry findings confirmed the high tumor binding ability of TEx. The uptake rate of
Tc-TEx-Cy7 by HCT116 cells increased over time, reaching 14.07 ± 1.31% at 6 h of co-incubation. NIRF and SPECT imaging indicated that the most appropriate imaging time was 18 h after the injection of
Tc-TEx-Cy7 when the tumor uptake (1.46% ± 0.06% ID/g) and tumor-to-muscle ratio (8.22 ± 0.65) peaked. Compared with radiolabeled adipose stem cell derived exosomes (
Tc-AEx-Cy7),
Tc-TEx-Cy7 exhibited a significantly higher tumor accumulation in tumor-bearing mice.
Hydrophobic insertion-based engineering of TEx may represent a promising approach to develop and label exosomes for use as nanoprobes in dual SPECT/NIRF imaging. Our findings confirmed that TEx has a higher tumor-targeting ability than AEx and highlight the potential usefulness of exosomes in biomedical applications.
Triple-negative breast cancer (TNBC) is more prone to distant metastasis and visceral recurrence in comparison to other breast cancer subtypes, and is related to dismal prognosis. Nevertheless, TNBC ...has an undesirable response to targeted therapies. Therefore, to tackle the huge challenges in the diagnosis and treatment of TNBC, Nectin-4 was selected as a theranostic target because it was recently found to be highly expressed in TNBC. We developed anti-Nectin-4 monoclonal antibody (mAb
)-based theranostic pair,
Tc-HYNIC-mAb
and mAb
-ICG.
Tc-HYNIC-mAb
was applied to conduct immuno-single photon emission computed tomography (SPECT) for TNBC diagnosis and classification, and mAb
-ICG to mediate photothermal therapy (PTT) for relieving TNBC tumor growth.
Nectin-4 expression levels of breast cancer cells (MDA-MB-468: TNBC cells; and MCF-7, non-TNBC cells) were proved by western blot, flow cytometry, and immunofluorescence imagning. Cell uptake assays, SPECT imaging, and biodistribution were performed to evaluate Nectin-4 targeting of
Tc-HYNIC-mAb
. A photothermal agent (PTA) mAb
-ICG was generated and characterized. In vitro photothermal therapy (PTT) mediated by mAb
-ICG was conducted under an 808 nm laser. Fluorescence (FL) imaging was performed for mAb
-ICG mapping in vivo. In vivo PTT treatment effects on TNBC tumors and corresponding systematic toxicity were evaluated.
Nectin-4 is overexpressed in MDA-MB-468 TNBC cells, which could specifically uptake
Tc-HYNIC-mAb
with high targeting in vitro. The corresponding immunoSPECT imaging demonstrated exceptional performance in TNBC diagnosis and molecular classification. mAb
-ICG exhibited favourable biocompatibility, photothermal effects, and Nectin-4 targeting. FL imaging mapped biodistribution of mAb
-ICG with excellent tumor-targeting and retention in vivo. Moreover, mAb
-ICG-mediated PTT provided advanced TNBC tumor destruction efficiency with low systematic toxicity.
mAb
-based radioimmunoimaging provides visualization tools for the stratification and diagnosis for TNBC, and the corresponding mAb
-mediated PTT shows a powerful anti-tumor effect. Our findings demonstrate that this Nectin-4 targeting strategy offers a simple theranostic platform for TNBC.
Inflammatory regulation induced by macrophage polarization is essential for cardiac repair after myocardial infarction (MI). Berberin (BBR) is an isoquinoline tetrasystemic alkaloid extracted from ...plants. This study analyzes the most likely mechanism of BBR in MI treatment determined via network pharmacology, showing that BBR acts mainly through inflammatory responses. Because platelets (PLTs) can be enriched in the infarcted myocardium, PLT membrane-coated polylactic-co-glycolic acid (PLGA) nanoparticles (BBR@PLGA@PLT NPs) are used, which show enrichment in the infarcted myocardium to deliver BBR sustainably. Compared with PLGA nanoparticles, BBR@PLGA@PLT NPs are more enriched in the infarcted myocardium and exhibit less uptake in the liver. On day three after MI, BBR@PLGA@PLT NPs administration significantly increases the number of repaired macrophages and decreases the number of inflammatory macrophages and apoptotic cells in infarcted rat myocardium. On the 28th day after MI, the BBR@PLGA@PLT group exhibits a protective effect on cardiac function, reduced cardiac collagen deposition, improved scar tissue stiffness, and an excellent angiogenesis effect. In addition, BBR@PLGA@PLT group has no significant impact on major organs either histologically or enzymologically. In summary, the therapeutic effect of BBR@PLGA@PLT NPs on MI is presented in detail from the perspective of the resolution of inflammation, and a new solution for MI treatment is proposed.
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