Using Arterial Pulse and Laser Doppler Analyses to Discriminate between the Cardiovascular Effects of Different Running Levels.

BACKGROUND AND AIMS: Running can induce advantageous cardiovascular effects such as improved arterial stiffness and blood-supply perfusion. However, the differences between the vascular and blood-flow perfusion conditions under different levels of endurance-running performance remains unclear. The present study aimed to assess the vascular and blood-flow perfusion conditions among 3 groups (44 male volunteers) according to the time taken to run 3 km: Level 1, Level 2, and Level 3. METHODS: The radial blood pressure waveform (BPW), finger photoplethygraphy (PPG), and skin-surface laser-Doppler flowmetry (LDF) signals of the subjects were measured. Frequency-domain analysis was applied to BPW and PPG signals; time- and frequency-domain analyses were applied to LDF signals. RESULTS: Pulse waveform and LDF indices differed significantly among the three groups. These could be used to evaluate the advantageous cardiovascular effects provided by long-term endurance-running training, such as vessel relaxation (pulse waveform indices), improvement in blood supply perfusion (LDF indices), and changes in cardiovascular regulation activities (pulse and LDF variability indices). Using the relative changes in pulse-effect indices, we achieved almost perfect discrimination between Level 3 and Level 2 (AUC = 0.878). Furthermore, the present pulse waveform analysis could also be used to discriminate between the Level-1 and Level-2 groups. CONCLUSIONS: The present findings contribute to the development of a noninvasive, easy-to-use, and objective evaluation technique for the cardiovascular benefits of prolonged endurance-running training.

Out of Asia: Intercontinental dispersals after the Eocene-Oligocene transition shaped the zoogeography of Limenitidinae butterflies (Lepidoptera: Nymphalidae).

Most members of the nymphalid subfamily Limenitidinae are distributed in tropical regions of Africa, Asia, and the Americas. Previous studies have inferred their higher-level phylogeny and found that Southeast Asia seems to be the center of origin, with numerous dispersal events to other continents. However, the complete biogeographic history of Limenitidinae butterflies is still largely unknown. We sampled 181 taxa from 164 species and used a metagenomic method to obtain 40 genes (mitogenomes and three nuclear ribosomal loci) for inferring the historical biogeography of the group. We find that Limenitidinae originated in eastern Asia during the early Eocene (ca. 52 Ma) and started to diversify and disperse into Africa before the end of Eocene. Intercontinental exchanges between Africa and eastern Asia continued in the early Miocene: Asian Adoliadini and Asian endemic taxa Bhagadatta had African origins in the Oligocene, whereas African Neptini dispersed in the opposite direction from Asia in the early Miocene. In addition, ancestors of the tribes Limenitidini and Adoliadini dispersed into the Neotropics and Australasia multiple times during the early-to-middle Miocene. Eastern Asia is the center of origin of the tribe Limenitidini, with several taxa disjunctly distributed in eastern Asia and the Americas. Our work provides a robust phylogenetic hypothesis of relationships in the tribe Limenitidini and suggests that the alala-species group of Adelpha should be placed in the genus Limenitis. Renamed taxa comb. nov. based on our findings are listed in the text.

Machine-Learning Classification of Pulse Waveform Quality.

Pulse measurements made using wearable devices can aid the monitoring of human physiological condition. Accurate estimation of waveforms is often difficult for nonexperts; motion artifacts may occur during tonometry measurements when the skin-sensor contact pressure is insufficient. An alternative approach is to extract only high-quality pulses for use in index calculations. The present study aimed to determine the effectiveness of using machine-learning analysis in discriminating between high-quality and low-quality pulse waveforms induced by applying different contact pressures. Radial blood pressure waveform (BPW) signals were measured noninvasively in healthy young subjects using a strain-gauge transducer. One-minute-long trains of pulse data were measured when applying the appropriate contact pressure (67.80 ± 1.55 mmHg) and a higher contact pressure (151.80 ± 3.19 mmHg). Eight machine-learning algorithms were employed to evaluate the following 40 harmonic pulse indices: amplitude proportions and their coefficients of variation and phase angles and their standard deviations. Significant differences were noted in BPW indices between applying appropriate and higher skin-surface contact pressures. The present appropriate contact pressure could not only provide a suitable holding force for the wearable device but also helped to maintain the physiological stability of the underlying tissues. Machine-learning analysis provides an effective method for distinguishing between the high-quality and low-quality pulses with excellent discrimination performance (leave-one-subject-out test: random-forest AUC = 0.96). This approach will aid the development of an automatic screening method for waveform quality and thereby improve the noninvasive acquisition reliability. Other possible interfering factors in practical applications can also be systematically studied using a similar procedure.

Relationship between ideal cardiovascular health metrics and hearing loss: A 10-year retrospective cohort study.

OBJECTIVE: The role of ideal cardiovascular health (CVH) metrics in developing hearing loss remains uncertain. Thus, our objective was to analyse the connection between hearing loss and ideal CVH metrics in a 10-year retrospective cohort. STUDY DESIGN: Retrospective cohort study. SETTING: A health management centre in Taiwan. PARTICIPANTS: Participants who underwent the first annual health check-up between 2000 and 2006 and with a follow-up check-up more than ten years later. MAIN OUTCOME MEASURES: Hearing thresholds were measured at 500 Hz, 1000 Hz, 2000 Hz and 4000 Hz. Individuals with a best ear pure-tone audiometry four-frequency average of >25 dB HL were defined as having hearing loss. The ideal CVH metrics were classified into 7 categories based on the American Heart Association's definition. The associations of hearing loss with the sum of the ideal CVH metrics and each ideal CVH metric were examined by multiple logistic regression analysis. RESULTS: The present study consisted of 6974 participants. The 10-year follow-up showed that the odds ratio (OR) of hearing loss was .74 for participants with 5-7 ideal CVH metrics (95% CI, .59-.93, p = .01) compared with those with 0-2 ideal CVH metrics. Among the CVH metrics, participants with an ideal smoking status might have reduced odds of developing hearing loss; the OR was .72 (95% CI, .58-.89, p = .003). CONCLUSIONS: Participants with an increased number of ideal CVH metrics and better performance on the smoking metric had a significantly protective effect regarding hearing loss development.

Associations between different measurements of sarcopenic obesity and health outcomes among non-frail community-dwelling older adults in Taiwan.

The most important issue for the clinical application of sarcopenic obesity (SO) is the lack of a consensus definition. The aim of the present study was to determine the best measurement for SO by estimating the association between various definitions and the risk of falls and metabolic syndrome (MS). We studied a community of 765 adults aged 65 years and older in 2015-2017. Sarcopenia obesity was measured by sarcopenia (defined by low muscle mass with either low handgrip strength or low gait speed or both) plus obesity (defined by waist circumference, body fat percentage and BMI). The MS was defined according to the National Cholesterol Education Program ATP III. Logistic regression models were constructed to examine the relationships between sarcopenia obesity and risk of fall and MS. In the analysis of the fall risk with SO defined by waist circumference, the participants with non-sarcopenia/non-obesity were treated as the reference group. The OR to fall in participants with SO was 10·16 (95 % CI 2·71, 38·13) after adjusting for confounding covariates. In the analysis of the risk of the MS between participants with individual components of sarcopenia coupled with obesity defined by waist circumference, the risk was statistically significant for low gait speed (OR: 7·19; 95 % CI 3·61, 14·30) and low grip strength (OR: 9·19; 95 % CI 5·00, 16·91). A combination of low grip strength and abdominal obesity for identifying SO may be a more precise and practical method for predicting target populations with unfavourable health risks, such as falls risk and MS.

Fucoidan and Fucoxanthin Attenuate Hepatic Steatosis and Inflammation of NAFLD through Modulation of Leptin/Adiponectin Axis.

Non-alcoholic fatty liver disease (NAFLD) is the emerging cause of chronic liver disease globally and lack of approved therapies. Here, we investigated the feasibility of combinatorial effects of low molecular weight fucoidan and high stability fucoxanthin (LMF-HSFx) as a therapeutic approach against NAFLD. We evaluated the inhibitory effects of LMF-HSFx or placebo in 42 NAFLD patients for 24 weeks and related mechanism in high fat diet (HFD) mice model and HepaRGTM cell line. We found that LMF-HSFx reduces the relative values of alanine aminotransferase, aspartate aminotransferase, total cholesterol, triglyceride, fasting blood glucose and hemoglobin A1c in NAFLD patients. For lipid metabolism, LMF-HSFx reduces the scores of controlled attenuation parameter (CAP) and increases adiponectin and leptin expression. Interestingly, it reduces liver fibrosis in NAFLD patients, either. The proinflammatory cytokines interleukin (IL)-6 and interferon-γ are reduced in LMF-HSFx group. In HFD mice, LMF-HSFx attenuates hepatic lipotoxicity and modulates adipogenesis. Additionally, LMF-HSFx modulates SIRI-PGC-1 pathway in HepaRG cells under palmitic acid-induced lipotoxicity environment. Here, we describe that LMF-HSFx ameliorated hepatic steatosis, inflammation, fibrosis and insulin resistance in NAFLD patients. LMF-HSFx may modulate leptin-adiponectin axis in adipocytes and hepatocytes, then regulate lipid and glycogen metabolism, decrease insulin resistance and is against NAFLD.

Hypermethylation of SHISA3 DNA as a blood-based biomarker for colorectal cancer.

In Taiwan, colorectal cancer (CRC) is the second most common cancer and the cancer with the third highest mortality rate. This may be because of the difficulty of detecting the disease in the early stages, as well as the fact that colonoscopy, a typical method used in screening for CRC, causes discomfort to the recipient and is prone to technical interference. For the earlier detection of CRC, finding an easier screening method with a simpler collection procedure is essential. Thus, in the present study, plasma samples from patients with CRC were analyzed to determine the extent of methylation in SHISA3 DNA. Studies have suggested that SHISA3, a newly identified tumor suppressor, can regulate tumor growth, and that the inactivation of its DNA can be traced to epigenomic alterations in CRC. Another study reported the presence of hypermethylated SHISA3 DNA in CRC biopsy specimens. In the present study, the plasma of 30 patients with CRC and nine healthy controls was collected and analyzed for the concentration of cell-free DNA through bisulfite sequencing. The methylation rates were determined. Our results have shown that an increasing amount of cell-free DNA in the group of CRC patient's plasma compared to the healthy group. Moreover, patients with later stages of CRC had higher concentrations of cell-free DNA. Notably, the methylation rate of SHISA3 was higher in the plasma of the CRC group than in that of the healthy group. The results indicated that the presence of tumor cells does not reduce the degree of SHISA3 DNA in the peripheral blood of patients with CRC. In other words, the hypermethylation of SHISA3, which inactivates the gene, is a potential cause of tumorigenesis. Furthermore, the methylation rate of SHISA3 DNA was higher in the plasma of patients with stage II CRC than in that of those with stage I CRC. In conclusion, the combination of conventional testing and screening for SHISA3 hypermethylation in plasma could improve the rate at which CRC is detected.

Platelet-derived growth factor-AA is a substantial factor in the ability of adipose-derived stem cells and endothelial progenitor cells to enhance wound healing.

Nonhealing wounds with various forms of complications have been a major challenge for patients with different diseases, and few data are available regarding the clinical significance of platelet-derived growth factor-AA (PDGF-AA) in the enhanced wound healing with stem cells, and the precise molecular mechanism remains unclear. The study aims to investigate the role of PDGF-AA in adipose-derived stem cells (ASCs) and endothelial progenitor cells (EPCs) enhancing wound healing. In this study, ASCs and EPCs were applied to treat wounds in an animal wound model with a wound-healing assay. We knocked down PDGF-AA expression in ASCs using the PDGF-AA short hairpin RNA technique and investigated the related molecular mechanism. The wound model and wound-healing assay of the study showed that transplantation of ASCs could enhance wound healing. The results showed that the PDGF-AA knockdown ASC group had much less improvement of wound healing than other groups treated with wild-type ASCs in wound tissues. The regulation of PDGF-AA in ASCs may contribute to improve wound healing through the PI3K/Akt/eNOS signaling pathway. The data indicated that PDGF-AA might play a vital role in ASCs and EPCs enhancing wound healing, possibly by its effects on angiogenesis. It would be a potential approach using PDGF-AA for clinical treatment of chronic wounds.-Wu, L.-W., Chen, W.-L., Huang, S.-M., Chan, J. Y.-H. Platelet-derived growth factor AA is a substantial factor in the ability of adipose-derived stem cells and endothelial progenitor cells to enhance wound healing.

Unravelling relationships among the shared stripes of sailors: Mitogenomic phylogeny of Limenitidini butterflies (Lepidoptera, Nymphalidae, Limenitidinae), focusing on the genera Athyma and Limenitis.

The phylogenetic relationships of the nymphalid butterfly tribe Limenitidini are best known for the genera Limenitis and Adelpha, model taxa for evolutionary processes such as Batesian mimicry and rapid adaptive radiations. Whereas these American limenitidines have received the most attention, phylogenetic relationships of their Asian relatives are still controversial and largely unexplored. Even one of the largest genera in Asia, Athyma, is polyphyletic. To clarify the phylogenetic relationships of these Asian Limenitidini, a total of 53 representatives were sampled; 37 have their mitogenomes sequenced for the first time. Our phylogenetic results confirm that mitogenomic data provides well-resolved relationships at most major levels of the phylogeny, even using different partition schemes or different inference methods. Interestingly, our results show that some Athyma taxa are embedded within the genus Limenitis, whereas the genus Tacola, previously considered to be a synonym of Athyma, needs to be recognized as a valid clade. Additionally, the other Limenitidini genera in Asia (namely Tarattia, Litinga, Sumalia, Pandita and Patsuia) are now grouped either within Athyma or Limenitis, so these genera need to be sunk. Importantly, we also show that the mainly Old World Limenitis and entirely New World Adelpha are sister groups, confirming the relevance of Asian lineages to global studies of Limenitis evolution.

Improving Interlaminar Fracture Toughness and Impact Performance of Carbon Fiber/Epoxy Laminated Composite by Using Thermoplastic Fibers.

The effects of thermoplastic polyimide (PI) and polypropylene (PP) fibers and areal density of toughened layer on interlaminar fracture toughness and impact performance of carbon fiber/epoxy (CF/EP) laminated composites were studied. Mode I interlaminar fracture toughness (GIC) was analyzed via double cantilever beam (DCB) tests. When comparing for the toughener type, PI played a positive role in enhancing the mode-I fracture toughness, while PP was not effective due to the less fiber bridge formed during composite curing. The toughening effects of areal density of PI were further investigated by end notched flexure (ENF) testing and low velocity impact testing to better understand the toughening mechanisms. The results revealed that the toughening effect reached its best effectiveness when the areal density of toughened layer was 30 g/m2. Compared with the control group, GIC and GIIC of CF/EP laminated composite were increased by 98.49% and 84.07%, and Fmax and Ee were enhanced by 92.38% and 299.08% under low velocity impact. There is no obvious delamination phenomenon on the surface of laminates after low velocity impact, indicating the improved interlaminar and impact performance of laminated composite.

[Cloning and expression analysis of F3'H and quantification of downstream products in Chrysanthemum morifolium under flooding stress].

To investigate the effects of the expression of flavonoid 3' hydroxylase gene (F3'H) and active ingredients in Chrysanthemum morifolium under flooding stress, we cloned F3'H from Hangju (temporarily named CmF3'H) and conducted bioinformatics analysis. During the flower bud differentiation stage, we flooded the Ch. morifolium and then used the Real-time PCR to detect the relative expression of CmF3'H; Finally, active ingredients of the inflorescence were measured by HPLC.The sequencing results showed that 1 562 bp sequence was acquired with the largest open reading frame of 1 527 bp, which encoded 508 amino acids. The phylogenetic tree found that CmF3'H was highly homologous to other species of Compositae. Real-time PCR results showed that CmF3'H had a significant response to flooding stress and had the highest expression level after flooding for 24 h, which was about 9 times as that of the control group. The results of HPLC showed that luteolin and luteoloside, the downstream products catalyzed by the F3'H, were significantly higher than those in the control group. It was also found that the contents of chlorogenic acid and 3,5-O-di-caffeoylquinic acid were also significantly higher than those of the control group. Therefore, Ch. morifolium regulates the synthesis of downstream products by regulating the expression of CmF3'H in the flavonoid synthesis pathway under flooding stress, thereby responding to flooding stress. The flooding stress during flower bud differentiation can significantly enhance the accumulation of active ingredients.

Does Serum Homocysteine Explain the Connection Between Sexual Frequency and Cardiovascular Risk?

BACKGROUND: Sexual activity correlates with various health issues, and homocysteine is considered an independent risk factor for cardiovascular events and atherosclerosis. Research on the relation of sexual activity to sexual frequency and homocysteine is sparse. AIM: To examine the association between sexual frequency and homocysteine in the general population in the United States. METHODS: In total, 2,267 eligible participants 20 to 59 years old who had serum homocysteine data and completed a sexual behavior questionnaire were enrolled from the National Health and Nutrition Examination Survey of 2005 to 2006. The correlation between sexual frequency and serum homocysteine levels was analyzed using a linear regression model and an extended-model approach was performed for covariate adjustment. OUTCOMES: Individuals, especially men, in the lower quartiles of sexual frequency had significantly higher serum homocysteine levels, and a sex difference was identified in subgroup analysis. RESULTS: In a model of quartile-based analysis after adjustment for age, sex, and race and ethnicity, the regression coefficient of the highest quartile of sexual frequency compared with the lowest quartile was -1.326 (P = .012). After further adjustment for multiple covariates, the inverse association between sexual frequency and serum homocysteine levels remained unchanged. Negative trends maintained statistical significance (P for trend < .05). In subgroup analysis by sex, a negative association between sexual frequency and serum homocysteine levels remained unchanged in men even after adjusting for multiple covariates, but not in women. CLINICAL IMPLICATIONS: Clinical physicians in primary care should support patients' sexual activity, and there are implications for health promotion programs. STRENGTHS AND LIMITATIONS: This is the first observational investigation stratified by sex to evaluate the correlation between sexual frequency and serum homocysteine levels. The study was a cross-sectional observational investigation and the causal relation should be evaluated in a follow-up study. CONCLUSION: Decreased sexual frequency correlated with higher homocysteine levels in a nationally representative sample of US adults, especially men; this might increase the risk of cardiovascular disease or other atherothrombotic events. Yang H-F, Kao T-W, Lin Y-Y, et al. Does Serum Homocysteine Explain the Connection Between Sexual Frequency and Cardiovascular Risk? J Sex Med 2017;14:910-917.

Ancient Neotropical origin and recent recolonisation: Phylogeny, biogeography and diversification of the Riodinidae (Lepidoptera: Papilionoidea).

We present the first dated higher-level phylogenetic and biogeographic analysis of the butterfly family Riodinidae. This family is distributed worldwide, but more than 90% of the c. 1500 species are found in the Neotropics, while the c. 120 Old World species are concentrated in the Southeast Asian tropics, with minor Afrotropical and Australasian tropical radiations, and few temperate species. Morphologically based higher classification is partly unresolved, with genera incompletely assigned to tribes. Using 3666bp from one mitochondrial and four nuclear markers for each of 23 outgroups and 178 riodinid taxa representing all subfamilies, tribes and subtribes, and 98 out of 145 described genera of riodinids, we estimate that Riodinidae split from Lycaenidae about 96Mya in the mid-Cretaceous and started to diversify about 81Mya. The Riodinidae are monophyletic and originated in the Neotropics, most likely in lowland proto-Amazonia. Neither the subfamily Euselasiinae nor the Nemeobiinae are monophyletic as currently constituted. The enigmatic, monotypic Neotropical genera Styx and Corrachia (most recently treated in Euselasiinae: Corrachiini) are highly supported as derived taxa in the Old World Nemeobiinae, with dispersal most likely occurring across the Beringia land bridge during the Oligocene. Styx and Corrachia, together with all other nemeobiines, are the only exclusively Primulaceae-feeding riodinids. The steadily increasing proliferation of the Neotropical Riodininae subfamily contrasts with the decrease in diversification in the Old World, and may provide insights into factors influencing the diversification rate of this relatively ancient clade of Neotropical insects.

Mitogenomic sequences effectively recover relationships within brush-footed butterflies (Lepidoptera: Nymphalidae).

BACKGROUND: Mitogenomic phylogenies have revealed well-supported relationships for many eukaryote groups. In the order Lepidoptera, 113 species mitogenomes had been sequenced (May 14, 2014). However, these data are restricted to ten of the forty-three recognised superfamilies, while it has been challenging to recover large numbers of mitogenomes due to the time and cost required for primer design and sequencing. Nuclear rather than mitochondrial genes have been preferred to reconstruct deep-level lepidopteran phylogenies, without seriously evaluating the potential of entire mitogenomes. Next-generation sequencing methods remove these limitations by providing efficiently massive amounts of sequence data. In the present study, we simultaneously obtained a large number of nymphalid butterfly mitogenomes to evaluate the utility of mitogenomic phylogenies by comparing reconstructions to the now quite well established phylogeny of Nymphalidae. RESULTS: We newly obtained 30 nymphalid mitogenomes via pyrosequencing on the Roche 454 GS Junior system, and combined these sequences with publicly accessible data to provide a 70-taxa dataset covering 37 genes for a 15,495 bp alignment. Polymorphic sites were not homogeneously distributed across the gene. Two gene regions, nad6 and 3' end of nad5, were most variable, whereas the cox1 and 5' ends of rrnL were most conserved. Phylogenetic relationships inferred by two likelihood methods were congruent and strongly supported (>0.95 posterior probability; ML bootstrap >85%), across the majority of nodes for multiple partitioning strategies and substitution models. Bayes factor results showed that the most highly partitioned dataset is the preferred strategy among different partitioning schemes. The most striking phylogenetic findings were that the subfamily Danainae not Libytheinae was sister of the remaining brush-footed butterflies and that, within Limenitidini, the genus Athyma was clearly polyphyletic. None of the single-gene phylogenies recovered the highly supported topologies generated on the basis of the whole mitogenomic data. CONCLUSIONS: Thirty mitogenomes were assembled with 89% completeness from the contigs of pyrosequencing-derived reads. Entire mitogenomes or higher-quality sequences could be obtained by increasing pyrosequencing read coverage or by additional Sanger sequencing. Our mitogenomic phylogenies provide robust nodal support at a range of levels, demonstrating that mitogenomes are both accurate and efficient molecular markers for inferring butterfly phylogeny.

Corrigendum: Identification of ACKR4 as an immune checkpoint in pulmonary arterial hypertension.

[This corrects the article DOI: 10.3389/fimmu.2023.1153573.].

Prevalence of Ideal Cardiovascular Health Metrics among Young Asian Adults over 5 Years of Follow-Up.

BACKGROUND: Ideal cardiovascular health (CVH) metrics play an important role in preventing cardiovascular disease (CVD). However, there is a lack of cohort studies on CVH metrics among young Asian adults. The aims of this study were to describe early changes in CVH among young Asian adults and to investigate the association between CVH metrics and sociodemographic variables. METHODS: A total of 10,000 young adults (aged 21-30 years) were recruited between 2000 and 2016. There were two CVH measurements taken from these participants over the study period. One measurement was taken at the beginning, and the other was taken five years later. Subgroup analysis of the changes in CVH metrics was divided by education level and marital status. RESULTS: The mean age of the participants was 26.8 years. The initial prevalence of ideal CVH metrics was 52.3% and 86.8% and decreased to 43.8% and 81.2% after five years for males and females, respectively. In the subgroup analysis, males with less than a university education had a smaller ideal CVH metric decrease (6.2%) than males with more than a university education (8.9%), while females with more than a university education had a smaller ideal CVH metric decrease (5.4%) than females with less than a university education (7.3%). Married males had a smaller ideal CVH metric decrease (6.1%) than single males (9.1%), while single females had a smaller ideal CVH metric decrease (5.3%) than married females (6.2%). CONCLUSIONS: The prevalence of ideal CVH metrics among young adults gradually decreased as age increased. Higher educational attainment and unmarried status were associated with a greater prevalence of ideal CVH metrics regardless of sex, but early CVH changes differed by sex, education level, and marital status. The prevalence of CVH changes found early among young adults can be used to monitor CVH changes quickly. Effective health promotion programs are needed to maintain CVH metrics among young adults.

Identification of ACKR4 as an immune checkpoint in pulmonary arterial hypertension.

Objective: Inflammation is recognized as a contributor in the development of pulmonary arterial hypertension (PAH), and the recruitment and functional capacity of immune cells are well-orchestrated by chemokines and their receptors. This study is aimed at identification of critical chemokines in the progression of PAH via transcriptomic analysis. Methods: Differentially expressed genes (DEGs) from lungs of PAH patients were achieved compared to controls based on Gene Expression Omnibus (GEO) database. Gene set enrichment analysis (GSEA) was applied for functional annotation and pathway enrichement. The abundance of immune cells was estimated by the xCell algorithm. Weighted correlation network analysis (WGCNA) was used to construct a gene expression network, based on which a diagnostic model was generated to determine its accuracy to distinguish PAH from control subjects. Target genes were then validated in lung of hypoxia-induce pulmonary hypertension (PH) mouse model. Results: ACKR4 (atypical chemokine receptor 4) was downregulated in PAH lung tissues in multiple datasets. PAH relevant biological functions and pathways were enriched in patients with low-ACKR4 level according to GSEA enrichment analysis. Immuno-infiltration analysis revealed a negative correlation of activated dendritic cells, Th1 and macrophage infiltration with ACKR4 expression. Three gene modules were associated with PAH via WGCNA analysis, and a model for PAH diagnosis was generated using CXCL12, COL18A1 and TSHZ2, all of which correlated with ACKR4. The ACKR4 expression was also downregulated in lung tissues of our experimental PH mice compared to that of controls. Conclusions: The reduction of ACKR4 in lung tissues of human PAH based on transcriptomic data is consistent with the alteration observed in our rodent PH. The correlation with immune cell infiltration and functional annotation indicated that ACKR4 might serve as a protective immune checkpoint for PAH.

Gender-specific impacts of thigh skinfold thickness and grip strength for predicting osteoporosis in type 2 diabetes.

BACKGROUND: Diabetes with co-existing bone fragility or osteoporosis is common in elderly patients, whereas is frequently underestimated. METHODS: We conducted dual-energy x-ray absorptiometry (DXA) with 7-site skinfold (SF) and dominant hand grip strength measurements among patients with type 2 diabetes (T2DM) to assess their gender-specific associations. A total of 103 patients with T2DM (60 females and 43 males), aged between 50 and 80 years (median 68.0 years) were enrolled and 45 non-DM females were also included to compare with T2DM females. RESULTS: Our results revealed osteoporosis was negatively correlated with grip strength in both genders, negatively correlated with lean mass solely in males and negatively correlated with fat mass (particular the gynoid fat mass and thigh SF thickness) in females. Via performing multivariable stepwise logistic regression, we identified grip strength in both genders and thigh SF thickness in females as predictors for osteoporosis. Receiver operating characteristic curve analysis further disclosed 20.5 mm female thigh skinfold thickness, 18.1 kg female grip strength and 29.0 kg male grip strength as reasonable cutoff levels for predicting osteoporosis in the Taiwanese patients with T2DM. CONCLUSIONS: Patients with T2DM presented gender-specific associations between osteoporosis, body composition and grip strength. Grip strength and thigh SF thickness might serve as predictors for detection of osteoporosis in patients with T2DM.

Proteinuria as a Nascent Predictor of Frailty Among People With Metabolic Syndrome: A Retrospective Observational Study.

Frailty is a commonly occurring geriatric condition that increases the risk of adverse health outcomes. The factors and predictors behind frailty are not yet well understood. A better understanding of these factors can enable prevention of frailty in elderly patients. The objective of this study was to determine the association between proteinuria and frailty in US individuals with metabolic syndrome (MetS). Data from the National Health and Nutrition Examination Survey III (NHANES III, 1988-1994) conducted by the National Center for Health Statistics of the Centers for Disease Control and Prevention. This is a cross-sectional study, and proteinuria and frailty were measured only once at enrollment. The study included 2,272 participants with MetS aged 40-90 years from the NHANES III. The participants underwent assessments to evaluate frailty and frailty components (low body weight, weakness, exhaustion, low physical activity, and slow walking). Proteinuria was represented as albumin-to-creatinine ratio (ACR) (mg/g) and divided into tertiles: T1-normal range (ACR <30 mg/g), T2-microalbuminuria (ACR 30-299 mg/g), and T3-macroalbuminuria (ACR ≥ 300 mg/g). We applied multiple logistic regression to determine the odds ratios (ORs) of frailty for T2 vs. T1 and T3 vs. T1 in both sexes. In the adjusted analysis for male participants, the ORs of frailty for T2 and T3 vs. T1 were 3.106 (95% confidence interval [CI] = 1.078-8.948, P = 0.036) and 14.428 (95% CI = 4.231-49.193, P < 0.001), respectively. For female participants, the ORs of frailty for T2 and T3 vs. T1 were 1.811 (95% CI = 1.071-3.063, P = 0.027) and 2.926 (95% CI = 1.202-7.124, P = 0.018), respectively. The positive association between T2 and T3 vs. T1, and frailty were statistically significant. The trends of higher likelihood of every frailty component were also statistically significant across increasing tertiles of proteinuria after multiple levels of adjustment for covariates (P < 0.05). Increased proteinuria levels were positively associated with frailty and each frailty component. Proteinuria might be a useful maker for frailty in individuals with MetS.

Phylogenetic position and morphological polymorphism of the chafer, Clinterocera nigra (Coleoptera: Scarabaeidae: Cetoniinae) from Taiwan.

Three mitochondrial genomes of the cetoniine beetle, Clinterocera nigra (Kano, 1931) were assembled via next-generation sequencing. The newly sequenced mitogenomes all have 37 genes, showing standard gene order and annotation as the other insects. To examine their phylogenetic positions and relationships between their elytral color (red-spot and melanistic forms) and sequence variation, a total of 118 public mitogenomes of Scarabaeidae were used to infer a maximum-likelihood (ML) tree. Our results show that the melanistic form is grouped within red-spot ones, revealing a population level variation on the elytra color. Our work also provides the first mitogenomic reference of myrmecophilous chafers.