Characterization of Laser-Resistant Port Wine Stain Blood Vessels Using In Vivo Reflectance Confocal Microscopy.

Background and objectivesPort wine stain (PWS) is a congenital vascular malformation of the human skin. Laser is the treatment of choice for PWS. Laser-resistant PWS is one crucial factor accounting for inadequate treatment outcome, which needs to be fully characterized. This study aims to quantitatively characterize the morphology of laser-resistant PWS blood vessels in the upper papillary dermis using in vivo reflectance confocal microscopy (RCM).Study design/materials and methodsA total of 42 PWS subjects receiving laser treatment from August 2016 through July 2018 were enrolled into this study. Thirty-three subjects had facial PWS; nine had extremity PWS. All subject's PWS received multiplex 585/1,064 nm laser treatment. RCM images were taken before and after treatment. The density, diameter, blood flow, and depth of PWS blood vessels were analyzed.ResultsWe found 44.4% PWS on the extremities (four out of nine subjects) were laser-resistant, which was significantly higher (P < 0.001) when compared with those PWS on the face (15.2%, 5 out of 33 subjects). The laser-resistant facial PWS blood vessels had significantly higher blood flow (1.35 ± 0.26 U vs. 0.89 ± 0.22 U, P < 0.001), larger blood vessel diameters (109.60 ± 18.24 µm vs. 84.36 ± 24.04 µm, P = 0.033) and were located deeper in the skin (106.01 ± 13.87 µm vs. 87.82 ± 12.57 µm, P < 0.001) in the skin when compared with laser-responsive PWS on the face. The average PWS blood vessel density (17.01 ± 4.63/mm2 vs. 16.61 ± 4.44/mm2 , P = 0.857) was not correlated to the laser resistance.ConclusionsLaser-resistant PWS blood vessels had significantly higher blood flow, larger diameters, and were located deeper in the skin. RCM can be a valuable tool for a prognostic evaluation on laser-resistant lesions before treatment, thereby providing guidance for tailored laser treatment protocols, which may improve the therapeutic outcome. The limitations for this study include relative small sample size and acquisitions of different blood vessels before and after 2 months of treatment. Lasers Surg. Med. © 2019 Wiley Periodicals, Inc

Unexpected Diversity of Magnetococci in Intertidal Sediments of Xiaoshi Island in the North Yellow Sea

Magnetotactic bacteria (MTB) are a group of prokaryotes that, despite their high morphological, phylogenetic, and ecological diversity, share a common capability of forming intracellular nanocrystals of magnetite (Fe3O4) or greigite (Fe3S4), called magnetosomes, and swimming along geomagnetic field lines in a process called magnetotaxis. In this study, we investigated the MTB diversity within the intertidal sediments near Xiaoshi Island (Weihai) in the North Yellow Sea using a combination of molecular ecology techniques and transmission electron microscopy (TEM). The combination of restriction fragment length polymorphism (RFLP) analysis and 16S rRNA gene sequencing revealed seven new MTB genera affiliated with the Alphaproteobacteria class. Fluorescence in situ hybridization (FISH) analyses suggested that one magnetotactic coccus (designated as WHI-2) is the dominant species. TEM observations and energy dispersive X-ray analyses revealed that MTB cells mainly form magnetite magnetosomes that are organized into two chains of magnetosomes composed of e-prismatic magnetite crystals. This finding suggests the adaptation of a magnetotactic bacterial population to the marine tide. This is the first report of magnetotactic bacteria near Xiaoshi Island, which should be useful for studies of biogeochemical cycling and the geohistory of this area

Multi-parametric quantitative microvascular imaging with optical-resolution photoacoustic microscopy in vivo

Many diseases involve either the formation of new blood vessels (e.g., tumor angiogenesis) or the damage of existing ones (e.g., diabetic retinopathy) at the microcirculation level. Optical-resolution photoacoustic microscopy (OR-PAM), capable of imaging microvessels in 3D in vivo down to individual capillaries using endogenous contrast, has the potential to reveal microvascular information critical to the diagnosis and staging of microcirculation-related diseases. In this study, we have developed a dedicated microvascular quantification (MQ) algorithm for OR-PAM to automatically quantify multiple microvascular morphological parameters in parallel, including the vessel diameter distribution, the microvessel density, the vascular tortuosity, and the fractal dimension. The algorithm has been tested on in vivo OR-PAM images of a healthy mouse, demonstrating high accuracy for microvascular segmentation and quantification. The developed MQ algorithm for OR-PAM may greatly facilitate quantitative imaging of tumor angiogenesis and many other microcirculation related diseases in vivo

Ethnicity and smoking-associated DNA methylation changes at HIV co-receptor GPR15

Smoking is associated with poorer health outcomes for both African and European Americans. In order to better understand whether ethnic-specific genetic variation may underlie some of these differences, we compared the smoking-associated genome-wide methylation signatures of African Americans with those of European Americans, and followed up this analysis with a focused examination of the most ethnically divergent locus, cg19859270, at the GPR15 gene. We examined the association of methylation at this locus to the rs2230344 SNP and GPR15 gene and protein expression. Consistent with prior analyses, AHRR residue cg05575921 was the most differentially methylated residue in both African Americans and European Americans. However, the second most differentially methylated locus in African Americans, cg19859270, was only modestly differentially methylated in European Americans. Interrogation of the methylation status of this CpG residue found in GPR15, a chemokine receptor involved in HIV pathogenesis, showed a significant interaction of ethnicity with smoking as well as a marginal effect of genotype at rs2230344, a neighboring non-synonymous SNP, but only among African Americans. Gene and protein expression analyses showed that demethylation at cg19859270 was associated with an increase in both mRNA and protein levels. Since GPR15 is involved in the early stages of viral replication for some HIV-1 and HIV-2 isolates, and the prevalence of HIV is increased in African Americans and smokers, these data support a possible role for GPR15 in the ethnically dependent differential prevalence of HIV

Reference ranges of handgrip strength from 125,462 healthy adults in 21 countries: a prospective urban rural epidemiologic (PURE) study.

BACKGROUND: The measurement of handgrip strength (HGS) has prognostic value with respect to all-cause mortality, cardiovascular mortality and cardiovascular disease, and is an important part of the evaluation of frailty. Published reference ranges for HGS are mostly derived from Caucasian populations in high-income countries. There is a paucity of information on normative HGS values in non-Caucasian populations from low- or middle-income countries. The objective of this study was to develop reference HGS ranges for healthy adults from a broad range of ethnicities and socioeconomically diverse geographic regions. METHODS: HGS was measured using a Jamar dynamometer in 125,462 healthy adults aged 35-70 years from 21 countries in the Prospective Urban Rural Epidemiology (PURE) study. RESULTS: HGS values differed among individuals from different geographic regions. HGS values were highest among those from Europe/North America, lowest among those from South Asia, South East Asia and Africa, and intermediate among those from China, South America, and the Middle East. Reference ranges stratified by geographic region, age, and sex are presented. These ranges varied from a median (25th-75th percentile) 50 kg (43-56 kg) in men \u3c40 years from Europe/North America to 18 kg (14-20 kg) in women \u3e60 years from South East Asia. Reference ranges by ethnicity and body-mass index are also reported. CONCLUSIONS: Individual HGS measurements should be interpreted using region/ethnic-specific reference ranges

Magnetic domain state diagnosis using hysteresis reversal curves

We present results for a series of hysteresis measurements that provide information about remanent, induced, transient-free, and transient magnetization components. These measurements, and differences between measurement types, enable production of six types of first-order reversal curve (FORC)-like diagrams which only double the number of measurements involved in a conventional FORC measurement. These diagrams can be used to distinguish magnetic signatures associated with each domain state. When analyzing samples with complex magnetic mineral mixtures, the contrasting domain state signatures are mixed together in a traditional FORC diagram, but these signatures can be identified individually when using the various FORC diagrams discussed here. The ability to make different FORC measurements and to identify separately each magnetic component by investigating different magnetization types can provide much-improved understanding of the information provided by FORC diagrams. In particular, the transient hysteresis FORC diagram provides a method to measure the nucleation field of magnetic vortices and domain walls. We provide a simple explanation for FORC results from natural multidomain samples that are not explained by conventional domain wall pinning models. We also provide software for processing the different types of FORC data.This work was supported by the Australian Research Council (grant DP160100805) and the National Natural Science Foundation of China (grants 41522402, 41374004, 41374072, and 41574063)

Role of FOXO3 Activated by HIV-1 Tat in HIV-Associated Neurocognitive Disorder Neuronal Apoptosis

There are numerous types of pathological changes in human immunodeficiency virus (HIV)-associated neurocognitive disorder (HAND), including apoptosis of neurons. HIV-1 transactivator of transcription (Tat) protein, which is encoded by HIV-1, may promote apoptosis in HAND. Forkhead box O3 (FOXO3) is a multispecific transcription factor that has roles in many biological processes, including cellular apoptosis. The aim of this study was to determine whether FOXO3 is activated by HIV-1 Tat and to investigate its role in neuronal apoptosis in HAND. We employed tissue staining and related molecular biological experimental methods to confirm our hypothesis. The in vivo experimental results demonstrated that the expression of nuclear FOXO3 increased in the apoptotic neurons of the cerebral cortexes of rhesus macaques infected with simian human immunodeficiency virus (SHIV). The in vitro investigation showed that HIV-1 Tat activated FOXO3, causing it to move from the cytoplasm to the nucleus via the c-Jun N-terminal kinase (JNK) signaling pathway in SH-SY5Y cells. Moreover, FOXO3 down-regulated expression of the anti-apoptosis gene B-cell lymphoma 2 (Bcl-2) and up-regulated the expression of the pro-apoptosis gene Bcl-2-like 11 (Bim) after entering the nucleus, eventually causing cellular apoptosis. Finally, reduction of nuclear FOXO3 reversed cellular apoptosis. Our results suggest that HIV-1 Tat induces FOXO3 to translocate from the cytoplasm to the nucleus via the JNK signaling pathway, leading to neuronal apoptosis. Agents targeting FOXO3 may provide approaches for restoring neuronal function in HAND

Comprehensive analysis of lactate-related gene profiles and immune characteristics in lupus nephritis

ObjectivesThe most frequent cause of kidney damage in systemic lupus erythematosus (SLE) is lupus nephritis (LN), which is also a significant risk factor for morbidity and mortality. Lactate metabolism and protein lactylation might be related to the development of LN. However, there is still a lack of relative research to prove the hypothesis. Hence, this study was conducted to screen the lactate-related biomarkers for LN and analyze the underlying mechanism.MethodsTo identify differentially expressed genes (DEGs) in the training set (GSE32591, GSE127797), we conducted a differential expression analysis (LN samples versus normal samples). Then, module genes were mined using WGCNA concerning LN. The overlapping of DEGs, critical module genes, and lactate-related genes (LRGs) was used to create the lactate-related differentially expressed genes (LR-DEGs). By using a machine-learning algorithm, ROC, and expression levels, biomarkers were discovered. We also carried out an immune infiltration study based on biomarkers and GSEA.ResultsA sum of 1259 DEGs was obtained between LN and normal groups. Then, 3800 module genes in reference to LN were procured. 19 LR-DEGs were screened out by the intersection of DEGs, key module genes, and LRGs. Moreover, 8 pivotal genes were acquired via two machine-learning algorithms. Subsequently, 3 biomarkers related to lactate metabolism were obtained, including COQ2, COQ4, and NDUFV1. And these three biomarkers were enriched in pathways ‘antigen processing and presentation’ and ‘NOD-like receptor signaling pathway’. We found that Macrophages M0 and T cells regulatory (Tregs) were associated with these three biomarkers as well.ConclusionOverall, the results indicated that lactate-related biomarkers COQ2, COQ4, and NDUFV1 were associated with LN, which laid a theoretical foundation for the diagnosis and treatment of LN