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1.
Calcif Tissue Int ; 2021 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-34480200

RESUMO

Gut microbiota (GM) dysbiosis is closely related to several metabolic diseases such as hypertension, obesity, and Alzheimer's disease. However, little is known about the causal relationship between GM dysbiosis and osteoporosis. In our work, 32 3-month-old female SD rats were randomly divided into two groups: the fecal microbiota transplantation (FMT) group and the control group. The supernatant of feces from senile osteoporotic rats was transplanted to the FMT group and the same amount of sterile saline was given to the control rats. After 12 and 24 weeks, all rats were sacrificed, and the serum, bone, fecal feces, and intestine tissue were collected for the subsequent analysis. The osteocalcin (OC), CTX, and P1NP of the FMT group increased significantly at 12 and 24 weeks compared with the control group (P < 0.05). Furthermore, the BV, BV/TV, Tb.N, and Tb.Th decreased significantly in the FMT group (P < 0.05). The alpha diversity (ACE, Chao) of the FMT group was higher than the control at 24 weeks (P < 0.05). The beta diversity was close between the FMT rats and the donor rats. In addition, GM from donor rats changed the GM composition and function of the FMT rats, which was similar to that of the donor rats at 24 weeks. The impaired intestinal structure and the decreased expression of occludin, claudin, and ZO-1 were found in FMT rats. In conclusion, GM dysbiosis by transferring the feces from senile osteoporotic rats to young rats could induce osteoporosis. The changed GM and the impaired intestinal barrier contributed to the pathogenesis of osteoporosis.

2.
Nanoscale ; 13(32): 13624-13630, 2021 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-34477637

RESUMO

Twistronics has emerged as one of the most attractive playgrounds for manipulating the interfacial structures and electronic properties of two-dimensional materials. However, the layer-dependent lattice reconstruction and resulted strain distribution in marginally twisted transition metal dichalcogenides still remain elusive. Here we report a systematic study by both electron diffraction quantification and atomic-resolution imaging on the interface reconstruction of twisted WSe2, which shows a strong dependence on the constituent layer numbers and twist angles. The competition between the interlayer interaction, which varies with local atomic configurations, and the intralayer elastic deformation, related to the layer thickness, leads to rich superlattice motifs and strain modulation patterns, i.e. triangular for odd and kagome-like textures for even layer numbers, against the rigid stacking moiré model. The strain effects of small twist angles are further demonstrated by electrical transport measurements, manifesting intriguing conducting states at low temperatures beyond the flat band features of large twist angles. Our work not only provides a comprehensive understanding of layer-dependent twist structures, but also may shed light on the future design of twistronic devices.

3.
Adv Mater ; : e2102811, 2021 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-34486181

RESUMO

Currently, organic semiconductors (OSs) are widely used as active components in practical devices related to energy storage and conversion, optoelectronics, catalysis, and biological sensors, etc. To satisfy the actual requirements of different types of devices, chemical structure design and self-assembly process control have been synergistically performed. The morphology and other basic properties of multiscale OS components are governed on a broad scale from nanometers to macroscopic micrometers. Herein, the up-to-date design strategies for fabricating multiscale OSs are comprehensively reviewed. Related representative works are introduced, applications in practical devices are discussed, and future research directions are presented. Design strategies combining the advances in organic synthetic chemistry and supramolecular assembly technology perform an integral role in the development of a new generation of multiscale OSs.

4.
Ecotoxicol Environ Saf ; 225: 112772, 2021 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-34530262

RESUMO

With rapid economic growth, urbanization and industrialization, fine particulate matter with aerodynamic diameters ≤ 2.5 µm (PM2.5) has become a major pollutant and shows adverse effects on both human health and the atmospheric environment. Many studies on estimating PM2.5 concentrations have been performed using statistical regression models and satellite remote sensing. However, the accuracy of PM2.5 concentration estimates is limited by traditional regression models; machine learning methods have high predictive power, but fewer studies have been performed on the complementary advantages of different approaches. This study estimates PM2.5 concentrations from satellite remote sensing-derived aerosol optical depth (AOD) products, meteorological data, terrain data and other predictors in 2015 in Shaanxi, China, using a combined genetic algorithm-support vector machine (GA-SVM) method, after which the spatial clustering pattern was explored at the season and year levels. The results indicated that temperature (r = -0.684), precipitation (r = -0.602) and normalized difference vegetation index (NDVI) (r = -0.523) were significantly negatively correlated with the PM2.5 concentration, while AOD (r = 0.337) was significantly positively correlated with the PM2.5 concentration. Compared to conventional land use regression (LUR) and SVM models and previous related studies, the GA-SVM method demonstrated a significantly better prediction accuracy of PM2.5 concentration, with a higher 10-fold cross-validation coefficient of determination (R2) of 0.84 and lower root mean square error (RMSE) and mean absolute error (MAE) of 12.1 µg/m3 and 10.07 µg/m3, respectively. Y-scrambling test shows that the models have no chance correlation. The central and southern parts of Shaanxi have high PM2.5 concentrations, which are mainly due to the pollutant emissions and meteorological and topographical conditions in those areas. There was a positive spatial agglomeration characteristic of regional PM2.5 pollution, and the spatial spillover effect of PM2.5 pollution for seasonal and annual variations does exist. In general, the GA-SVM method is robust and accurately estimates PM2.5 concentrations via a novel modeling framework application and high-quality spatiotemporal information. It also has great significance for the exploration of PM2.5 pollution estimation and high-precision mapping methods, especially early warning in high-risk areas. Finally, the prevention and control of atmospheric pollution should take pollution control measures from major cities and surrounding cities, and focus on the joint pollution control measures for plain cities.

5.
Eur J Pharmacol ; 910: 174470, 2021 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-34478691

RESUMO

Myocardial fibrosis in post-myocardial infarction is a self-healing process of the myocardium, making ventricular remodelling difficult to reverse and develop continuously. Fibroblast growth factor 21 (FGF21) plays an essential role in cardiovascular and metabolic diseases. However, the effect and mechanism of FGF21 action on cardiac inflammation and fibrosis caused by myocardial injury have rarely been reported. Adult male Sprague-Dawley rats administered with or without recombinant human basic FGF21 (rhbFGF21) were assessed using echocardiography and haematoxylin-eosin and Masson's trichrome staining to determine the cardiac function and cardiac inflammation and fibrosis levels. FGF21 might improve cardiac remodelling, as characterised by a decrease in the expression of a series of inflammatory and fibrosis-related factors. Moreover, when FGF receptors (FGFRs) were blocked, the effects of FGF21 disappeared. Mechanistically, we found that oxidative stress induced the downregulation of early growth response protein 1 (EGR1), which contributed to inflammatory factors and fibrosis reduction in cardiomyocytes treated with H2O2. Collectively, FGF21 effectively suppressed the inflammation and fibrosis in post-infarcted hearts by regulating FGFR-EGR1.

6.
Biomed Pharmacother ; 143: 112128, 2021 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-34492424

RESUMO

Gender differences have important biological significance for medical research. In this study, a bias towards males was identified in animal experiments of Damp-Heat Syndrome in traditional Chinese medicine, as was first proposed by a data mining method. Combined with the correlation between Damp-Heat Syndrome in traditional Chinese medicine and Gender differences, it was considered that Gender-related factors have a significant influence on the development of Damp-Heat Syndrome in traditional Chinese medicine. However, most traditional Chinese medicine studies ignore the key significance of Gender-related factors. This study emphasises that the development of modern traditional Chinese medicine research needs to pay full attention to the biological significance of Gender-related factors and to apply this concept to the research on the Gender equivalence strategy in basic research and the practice of personalised medical diagnosis and clinical treatment.

7.
Vet Microbiol ; 262: 109223, 2021 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-34507016

RESUMO

Senecavirus A (SVA), formerly known as Seneca Valley virus, is classified into the genus Senecavirus in the family Picornaviridae. Mature virion harbors an approximately 7 300-nt-long, positive-sense, and single-stranded RNA genome, which contains 5' and 3' untranslated regions (UTRs). Internal ribosome entry site (IRES) is identified in the SVA 5' UTR, and includes a RNA pseudoknot upstream of the start codon. This pseudoknot contains two stem structures, pseudoknot stem I and II (PKS-I and -II). The PKS-I is composed of two base-paired motifs (PKS-Ia and -Ib), between which there is an unpaired spacing (UpS). We reported previously that motif mutation in the PKS-II did not abolish the IRES activity, but interfered with SVA recovery from cDNA clone. In this study, we constructed five SVA minigenomes with point mutations in the PKS-I motif. Dual-luciferase reporter assay showed that motif mutations in PKS-I did not significantly interfere with the IRES activity to initiate protein expression. Correspondingly, we constructed five SVA cDNA clones with point mutations in the PKS-I motif. These genetically modified cDNA clones were separately transfected into BSR-T7/5 cells in attempting to rescue competent SVAs. However, only two viruses, namely PKS-Ia- and UpS-mutated recombinants, could be recovered from their individual cDNA clones. It can be concluded that the PKS-Ib is indispensable for viral growth.

8.
J Colloid Interface Sci ; 606(Pt 2): 1111-1119, 2021 Aug 18.
Artigo em Inglês | MEDLINE | ID: mdl-34487931

RESUMO

Lithium-sulfur (Li-S) batteries are considered to be promising candidates for next-generation storage systems. However, the practical applications are still hindered by the severe capacity decay, mainly caused by the large volume change, polysulfide shuttle and sluggish sulfur conversion kinetics. Herein, hollow urchin-like Mn3O4 (HU-Mn3O4) microspheres as sulfur hosts have been synthesized by the hydrothermal method and calcination treatment, aiming to prevent the polysulfide dissolution (benefiting from the strong polysulfide anchoring effect of Mn3O4) and alleviate the volume expansion of sulfur (benefiting from the special hollow structure). Meanwhile, the urchin-like thorny surface also facilitates the rapid ion/electron transfer and the abundant active sites for the fast sulfur redox kinetics. When used as the sulfur host in Li-S batteries, the S@HU-Mn3O4 cathode delivers a high initial capacity of 1137.4 mAh g-1 with a slow capacity decay of 0.042% after 200 cycles at 0.2 C. Even under the conditions of lean electrolyte (E/S = 7 mL g-1) and low N/P ratio (N/P = 2.1), the S@HU-Mn3O4 cathode still enables a stable cycling performance with a high gravimetric energy density (202 Wh kg cell-1), demonstrating its great potential in the development of future practical Li-S battery materials.

9.
J Appl Toxicol ; 2021 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-34550611

RESUMO

The effects of low-dose radiation (LDR, ≤0.1 Gy) on living organisms have been the hot areas of radiation biology but do not reach a definitive conclusion yet. So far, few studies have adequately accounted for the male reproductive system responses to LDR, particularly the regulation of testosterone content. Hence, this study was designed to evaluate the effects of LDR on Leydig cells and testicular tissue, especially the ability to synthesize testosterone. We found that less than 0.2-Gy 60 Co gamma rays did not cause significant changes in the hemogram index and the body weight; also, pathological examination did not find obvious structural alterations in testis, epididymis, and other radiation-sensitive organs. Consistently, the results from in vitro showed that only more than 0.5-Gy gamma rays could induce remarkable DNA damage, cycle arrest, and apoptosis. Notably, LDR disturbed the contents of testosterone in mice serums and culture supernatants of TM3 cells and dose dependently increased the expression of 3ß-HSD. After cotreatment with trilostane (Tril), the inhibitor of 3ß-HSD, increased testosterone could be partially reversed. Besides, DNA damage repair-related enzymes, including DNMT1, DNMT3B, and Sirt1, were increased in irradiated TM3 cells, accompanying by evident demethylation in the gene body of 3ß-HSD. In conclusion, our results strongly suggest that LDR could induce obvious perturbation in the synthesis of testosterone without causing organic damage, during which DNA demethylation modification of 3ß-HSD might play a crucial role and would be a potential target to prevent LDR-induced male reproductive damage.

10.
Virology ; 563: 126-133, 2021 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-34530232

RESUMO

The 5' untranslated region (UTR) of Senecavirus A (SVA) harbors an internal ribosome entry site (IRES), in which a pseudoknot structure is upstream of start codon AUG. Wild-type SVAs have a highly conserved 13-nt-sequence between the pseudoknot stem II (PKS-II)-forming motif and the AUG. In this study, a single nucleotide was deleted one by one from the 13-nt-sequence within a wild-type SVA minigenome. The result showed that neither mono- nor multi-nucleotide deletions abolished the IRES activity. Furthermore, a single nucleotide was deleted one by one from the 13-nt-sequence within a full-length SVA cDNA clone. The result indicated that nucleotide-deleting SVAs could be rescued from 1- to 5-nt-deleting cDNA clones, whereas only the 1- and 2-nt-deleting viruses were genetically stable during nine serial passages in vitro. Additionally, only the 1-nt-deleting SVA showed similar growth kinetics to that of the wild-type virus, suggesting that the pseudoknot-AUG distance was crucial for SVA replication.

11.
Am J Chin Med ; : 1-19, 2021 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-34530698

RESUMO

Breast cancer is currently the most common cancer in women, and it accounts for 11.6% of all cancer diagnoses in 2018. Breast cancer patients frequently resort to alternative medicine in addition to conventional Western therapy. This study is to evaluate clinical effectiveness of Chinese herbal medicine (CHM) on breast cancer by conducting meta-analyses on 81 randomized controlled trials (RCTs) with a total of 7215 subjects from eight databases. All RCTs compared patients using Western therapy alone and those using additional CHM therapy to evaluate the difference of primary (tumor response, mean time to progression (mTTP), overall survival (OS) and progression free survival (PFS)) and secondary outcome measures (tumor markers). Results showed that under the RECIST1.1 criteria, 52% patients with additional CHM therapy (67%, under WHO criteria) achieved either a complete response (CR) or a partial response (PR), compared to 38% patients with Western therapy alone (53%, under the WHO criteria). The risk ratio was 1.31 ([Formula: see text]¡ 0.00001, 95% CI = 1.15-1.50) for patients with CHM plus Western therapy and 1.25 ([Formula: see text]¡ 0.00001, 95% CI = 1.18-1.98) for those with Western therapy. Moreover, patients with complementary CHM therapy were associated with an mTTP of 2.79 months longer ([Formula: see text]¡ 0.00001) and an OS of 1.90 months longer ([Formula: see text] ¡ 0.00001); they also had an increase in 3-year PFS ([Formula: see text]= 0.002), 2- ([Formula: see text]= 0.0002) and 5-year ([Formula: see text]= 0.006) OS rates. Therefore, complementary CHM therapy might demonstrate clinical benefits for breast cancer patients in terms of tumor response and survival. Clinical studies with further stratification of tumor stages and intervention types are highly warranted.

12.
Langmuir ; 2021 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-34516132

RESUMO

Nanoengineered capsules encapsulated with functional cargos (e.g., enzymes) are of interest for various applications including catalysis, bioreactions, sensing, and drug delivery. Herein, we report a facile strategy to engineer enzyme-encapsulated metal-phenolic network (MPN) capsules using enzyme-loaded zeolitic imidazolate framework nanoparticles (ZIF-8 NPs) as templates, which can be removed in a mild condition (e.g., ethylenediaminetetraacetic acid (EDTA) solution). The capsule size (from 250 nm to 1 µm) and thickness (from 9.8 to 33.7 nm) are well controlled via varying the template size and coating time, respectively. Importantly, MPN capsules encapsulated with enzymes (i.e., glucose oxidase) can trigger the intracellular cascade reaction via the exhaustion of glucose to produce H2O2 and subsequently generate toxic hydroxyl radicals (•OH) based on the Fenton reaction via the reaction between H2O2 and iron ions in MPN coatings. The intracellular cascade reaction for the generation of •OH is efficient to inhibit cancer cell viability, which is promising for the application in chemodynamic therapy.

13.
Ophthalmic Epidemiol ; : 1-8, 2021 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-34542011

RESUMO

PURPOSE: To assess the distribution and factors related to intraocular pressure (IOP) in a Chinese children population in Northern China. METHODS: 1,238 offspring aged 6 to 18 years, residing in six villages, were recruited for this current study, the Handan Offspring Myopia Study. Participants underwent an interviewer-administered questionnaire and a complete ocular examination, including standardized measurement of IOP with Perkins applanation tonometry. RESULTS: 1,648 eyes of 828 children were included in the analysis. The mean IOP was 13.9 ± 1.6 mmHg. The mean IOP for the study population increased from 13.0 ± 1.5 mmHg for those 6 to 7 years of age to 14.2 ± 1.4 mmHg for those 15 years of age or older (P < .001). The mean central corneal thickness (CCT) was 548.7 ± 32.1 µm, and had no difference among different age groups and gender. In univariate regression analysis, age (0.12 mmHg per 1 year old), height (0.09 mmHg per 5 cm), weight (0.02 mmHg per kg), body mass index (0.07 mmHg per 1 m/kg2), systolic blood pressure (0.06 mmHg per 5 mmHg), CCT (0.06 mmHg per 5 µm), and SE (-0.11 mmHg per 1 D) were correlated with IOP. In multivariate regression analysis, higher IOP was only associated with older ages (p = .002) and thicker CCT (p = .001). CONCLUSION: The mean IOP in healthy rural Chinese children aged 6-18 years is about 14 mmHg, which is lower than in adults in the same locality. The mean IOP is slightly increasing with age during childhood, which is opposite to the result among adults. Age and CCT are the major independent factors associated with IOP.

14.
Sci Total Environ ; 804: 150145, 2021 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-34517326

RESUMO

Poor dewaterability is a bottleneck of the disposal of digestate from food waste (DFW). However, the dewatering mechanism remains unclear due to the complex composition of DFW. Understanding the dewatering mechanism, as well as the transformation of organic/inorganic matters is essential for the DFW management and valorization. In this study, the distribution, transformation, and complex interplay of organic and inorganic matters at different Hydrothermal treatment (HTT) temperatures were comprehensively analyzed to explore the hydrothermal dewatering mechanism of DFW. When HTT was conducted in the temperature range of 120-180 °C, the interstitial water was released as surface or free water because of membrane breaking and size reduction of the solid substrate. Releasing divalent cations increased the Zeta potential of the bulk solution. The weaker electrostatic repulsion between suspended particles made them easier to settle as the centrifugation cake. When the temperature of HTT was above 180 °C, polymerization and aromatization reactions took place gradually for organic matters, and the bound water was further removed. The generated humic substances were more hydrophobic than the raw material. In addition, the humic substance could combine with cationic metals, which decreased the zeta potential of the bulk solution but promoted the aggregation of nanoparticles and enhance the dewaterability of DFW.

15.
Biomater Sci ; 2021 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-34528658

RESUMO

Combination cancer immunotherapy that synergizes the advantages of multiple therapeutic agents has shown great potential in tumor treatment. Herein, we report the one-step assembly of therapeutic nanoparticles (NPs) to co-deliver photosensitizers and adjuvants for combination photodynamic therapy (PDT) and immunotherapy. The NPs are obtained via self-assembly of chlorin e6 (Ce6) and imidazoquinoline-based TLR7 agonists (IMDQ), which results in a high loading efficacy of 72.2% and 27.8% for Ce6 and IMDQ, respectively. Upon laser irradiation, the resulting NPs could not only effectively induce photodynamic immunogenic cancer cell death, but also elicit robust antitumor immunity, leading to significant inhibition of both primary and distant tumors in a bilateral tumor model. This study demonstrates the potential of self-assembled NPs in co-delivering multiple therapeutics for potential immunotherapy to enhance the antitumor efficacy.

16.
Microsc Microanal ; : 1-11, 2021 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-34544517

RESUMO

We present an unsupervised machine learning approach for segmentation of static and dynamic atomic-resolution microscopy data sets in the form of images and video sequences. In our approach, we first extract local features via symmetry operations. Subsequent dimension reduction and clustering analysis are performed in feature space to assign pattern labels to each pixel. Furthermore, we propose the stride and upsampling scheme as well as separability analysis to speed up the segmentation process of image sequences. We apply our approach to static atomic-resolution scanning transmission electron microscopy images and video sequences. Our code is released as a python module that can be used as a standalone program or as a plugin to other microscopy packages.

17.
J Cell Mol Med ; 2021 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-34545688

RESUMO

Hirschsprung disease (HSCR) is an infrequent congenital intestinal dysplasia. The known genetic variations are unable to fully explain the pathogenesis of HSCR. The α/ß-hydratase domain 1 (ABHD1) interferes with the proliferation and migration of intestinal stem cells. Docking protein 6 (DOK6) is involved in neurodevelopment through RET signalling pathway. We examined the association of ABHD1 and DOK6 genetic variants with HSCR using 1470 controls and 1473 HSCR patients from Southern Chinese children. The results clarified that DOK6 rs12968648 G allele significantly increased HSCR susceptibility, in the allelic model (p = 0.034; OR = 1.12, 95%CI = 1.01~1.24) and the dominant model (p = 0.038; OR = 1.12, 95%CI = 1.01~1.25). Clinical stratification analysis showed that rs12968648 G allele was associated with increased risk of short-segment HSCR (S-HSCR), in the allelic model (p = 0.028; OR = 1.14, 95%CI = 1.01~1.28) and the additive model (p = 0.030; OR = 1.14, 95%CI = 1.01~1.28). ABHD1 rs2304678 C allele had higher risk to develop total colonic aganglionosis (TCA) in the allelic model (p = 7.04E-03; OR = 1.67, 95%CI = 1.15~2.43) and the dominant model (p = 4.12E-03; OR = 1.93, 95%CI = 1.23~3.04). DOK6 rs12968648 and ABHD1 rs2304678 had significant intergenic synergistic effect according to logical regression (p = 0.0081; OR = 0.76, 95%CI = 0.63~0.93) and multifactor dimensionality reduction (MDR, p = 0.0045; OR = 1.25, 95%CI = 1.07~1.46). This study verified two susceptible variations of HSCR on ABHD1 and DOK6. Their roles in HSCR should be conducted in further studies.

18.
J Fluoresc ; 2021 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-34536169

RESUMO

Two coordination polymers, that is [Zn(pdc)(im)(H2O)]n (1) and [Cu(pdc)(im)2]n·n(H2pdc) (2) (H2pdc = terephthalic acid, im = imidazole), were hydrothermally synthesized via the reactions of H2pdc and im in combination with Zn(II) or Cu(II) ions. Compound 1 shows intense blue luminescence and compound 2 shows good photocatalytic activity for the methyl violet degradation under the irradiation of ultraviolet light. In addition, the assessment of the two compounds' application values against Parkinson's disease were carried out and their specific mechanism was tested simultaneously. First of all, the real time RT-PCR was implemented and the relative expression levels of N-methyl-D-aspartic acid receptor receptor on neurons were measured. Besides, the Annexin V-FITC/PI apoptosis assay was utilized for the assessment of the influence of the compounds on the dopaminergic neuron death rate. The hemolysis toxicity detection was conducted to detect the biocompatible of the compounds.

19.
Orphanet J Rare Dis ; 16(1): 391, 2021 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-34538260

RESUMO

BACKGROUND: Aim to identify potential biomarkers to assess therapeutic efficacy for hereditary spastic paraplegias type 5 (SPG5) by investigating the clinical, cerebrospinal fluid (CSF) and magnetic resonance imaging (MRI) features. METHODS: We performed a cross-sectional study to compare SPG5 patients with age- and sex-matched healthy controls who underwent conventional and quantitative MRI techniques of spinal cord (C1-T9) and brain. SPG5 patients also underwent assessment for clinical status and CSF biomarkers (27-hydroxycholesterol, neurofilament light). We identified a set of markers with standardized effect sizes (|t|> 0.5) to estimate sample sizes for disease progression (disease duration > 14 years vs. ≤ 14 years). RESULTS: Seventeen genetically confirmed SPG5 patients (11 men, 6 women; age range, 13-49 years; median disease duration, 14 years) were enrolled. Compared to healthy controls, the total spinal cord area (SCA) of SPG5 patients was reduced particularly at the thoracic levels (cervical levels: 12-27%; thoracic levels 41-60%). Patients did not show significant alterations of brain signal abnormalities or atrophy relative to controls. A total of 10 surrogate markers were selected and a minimum sample size was achieved with the measurement of SCA on T9 (n = 22) much less that what would be required if using clinical disability assessment (n = 124). CONCLUSIONS: SPG5 patients showed distinct MRI features of spinal cord atrophy without significant brain alterations. Our finding supports the measurements of spinal cord on T9 level as potential endpoint for SPG5 clinical trials. Trial registration ClinicalTrials.gov, NCT04006418. Registered 05 July 2019, https://clinicaltrials.gov/ct2/show/NCT04006418?term=NCT04006418&draw=2&rank=1 .

20.
Elife ; 102021 09 20.
Artigo em Inglês | MEDLINE | ID: mdl-34544549

RESUMO

Vaccination strategies for rapid protection against multidrug-resistant bacterial infection are very important, especially for hospitalized patients who have high risk of exposure to these bacteria. However, few such vaccination strategies exist due to a shortage of knowledge supporting their rapid effect. Here, we demonstrated that a single intranasal immunization of inactivated whole cell of Acinetobacter baumannii elicits rapid protection against broad A. baumannii-infected pneumonia via training of innate immune response in Rag1-/- mice. Immunization-trained alveolar macrophages (AMs) showed enhanced TNF-α production upon restimulation. Adoptive transfer of immunization-trained AMs into naive mice mediated rapid protection against infection. Elevated TLR4 expression on vaccination-trained AMs contributed to rapid protection. Moreover, immunization-induced rapid protection was also seen in Pseudomonas aeruginosa and Klebsiella pneumoniae pneumonia models, but not in Staphylococcus aureus and Streptococcus pneumoniae model. Our data reveal that a single intranasal immunization induces rapid and efficient protection against certain Gram-negative bacterial pneumonia via training AMs response, which highlights the importance and the possibility of harnessing trained immunity of AMs to design rapid-effecting vaccine.

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