Diverse Roles of ScSERF in Modifying the Fibril Growth of Amyloidogenic Proteins.

The aggregation of amyloidogenic proteins is often related to the occurrence of neurodegenerative diseases, including fused in sarcoma protein (FUS) in frontotemporal lobar degeneration and amyotrophic lateral sclerosis diseases. Recently, the SERF protein family has been reported to have a significant regulatory effect on amyloid formation, but it is still unclear about the detailed mechanisms of SERF acting on different amyloidogenic proteins. Herein, nuclear magnetic resonance (NMR) spectroscopy and fluorescence spectroscopy were used to explore interactions of ScSERF with three amyloidogenic proteins FUS-LC, FUS-Core, and α-Synuclein. NMR chemical shift perturbations reveal them sharing similar interaction sites on the N-terminal region of ScSERF. However, the amyloid formation of α-Synuclein protein is accelerated by ScSERF, while ScSERF inhibits fibrosis of FUS-Core and FUS-LC proteins. Both the primary nucleation and the total amount of fibrils produced are detained. Our results suggest a diverse role of ScSERF in regulating the fibril growth of amyloidogenic proteins.

High-order mode erbium-doped fiber laser based on cavity LPFG converters.

We experimentally investigate high-order mode (HOM) generation at a wavelength of 1.5 µm in an all-fiber erbium-doped laser based on a long-period fiber grating (LPFG). The CW laser emission is achieved when the pump power is above the threshold of 10 mW. An LPFG with a 15 dB bandwidth of 147.76 nm from 1502.76 nm to 1650.52 nm is used as a mode converter inside the cavity. The generation of the broadband L P 11 mode is ultimately obtained. By using a few-mode output coupler, we can obtain the intracavity conversion of the linear polarization mode. Single-, dual-, triple-, and quadruple-wavelength operations can be achieved by changing the polarization state of the polarization controllers in the cavity. The tunable range of the output wavelengths is up to ∼23.20n m. The output power and slope efficiency of the HOMs are presented and discussed. We believe our work might benefit the investigation of HOM fiber lasers, and might be further applied to the intracavity conversion of the linear polarization mode or orbital angular momentum beams.

Demethylase FTO promotes mechanical stress induced osteogenic differentiation of BMSCs with up-regulation of HIF-1α.

BACKGROUND: In orthodontics, mechanical stress plays an important role in the process of bone remodeling. Mechanical stress has an effect on osteogenic differentiation of bone marrow-derived mesenchymal stem cells (BMSCs). However, the mechanism remains to be studied. The aim of this study is to investigate the effects of demethyltransferase fat mass and obesity-associated (FTO) on osteogenic differentiation of BMSCs under mechanical stress condition. METHODS AND RESULTS: The rat BMSCs were cultured in vitro, followed by flow cytometry to identify the cell surface antigens. Osteogenic differentiation of BMSCs was induced by mechanical stress by using the flexcell tension system for 6 h every day and 3 days in total. BMSCs were transfected by using plasmid for FTO knockdown. The expression level of FTO, hypoxia-inducible factor (HIF)-1α, runt-related transcription factor 2 (RUNX2), bone morphogenetic proteins (BMPs) and alkaline phosphatase (ALP) were measured by real-time qPCR, western blotting. ALP activity were determined by ALP staining assays. The expression of FTO and HIF-1α in BMSCs with mechanical stress were significantly higher than BMSCs without mechanical stress, also, the expression of osteogenic differentiation markers were higher in BMSCs with mechanical stress. Knockdown of FTO decreased expression of osteogenic differentiation marker and ALP activity in stretched BMSCs. In addition, the expression of HIF-1α was decreased after knocking down FTO. CONCLUSIONS: FTO promotes the expression of HIF-1α and osteogenic differentiation under the condition of mechanical stress. This finding may facilitate the clinical application of orthodontics and the mechanism research of mechanical stress-induced osteogenesis.

Silencing of B7H4 Represses the Development of Oral Squamous Cell Carcinoma Through Promotion of M1 Macrophage Polarization.

PURPOSE: Tumor-associated macrophages can support oral squamous cell carcinoma (OSCC) progression, and overexpression of the immunomodulator B7H4 correlates with poor prognosis of OSCC patients. We performed this study to assess the effect of B7H4 silencing on macrophage polarization and explore the potential mechanism of B7H4 during OSCC progression. METHODS: Short hairpin RNA targeting B7H4 was used to knock down B7H4. The predictor variable was B7H4 expression level, and the outcome variables were SCC9 cell growth and metastasis, M1/M2 macrophage ratio, and anti-programmed death-1 (PD-1)/STAT3 pathway-related protein levels. These were measured through real-time qPCR, Western blot analysis, 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H tetrazolium bromide (MTT), 5-ethynyl-2'-deoxyuridine assay, and transwell assay. In addition, a tumor xenograft mouse model was used to examine the effect of B7H4 silencing (+/- Colivelin, an activator of STAT3) on tumor growth and macrophage polarization. RESULTS: The expression of B7H4 in OSCC cell lines was more than 2-fold compared with that in human normal oral keratinocytes via real-time qPCR and Western blot analysis. Knockdown of B7H4 repressed the proliferation, migration, and invasion of SCC9 cells, which were detected by 5-ethynyl-2'-deoxyuridine and transwell assay, as well as reduced PD-1/STAT3 pathway-related protein levels, promoted M1 macrophage polarization, and inhibited M2 polarization. In vivo research demonstrated that B7H4 silencing also inhibited the growth of tumor xenograft and increased the M1/M2 ratio in an OSCC mouse model. Colivelin reversed the inhibitory effects of B7H4 knockdown on OSCC progression and reversed macrophage polarization both in vitro and in vivo. CONCLUSIONS: B7H4 is upregulated during OSCC progression. Its downregulation may promote M1 macrophage polarization and inhibit M2 macrophage polarization via deactivating the PD-1/STAT3 pathway, thus restraining OSCC development.

How has the COVID-19 pandemic affected the use of ride-sourcing services? An empirical evidence-based investigation for the Greater Toronto Area.

The ongoing COVID-19 pandemic has fundamentally changed the nature of day-to-day life in cities worldwide. In the transportation sector, COVID-19 appears to have impacted modal preferences. In particular, people seem to be less willing to use modes where they may encounter strangers (such as public transit) and modes that involve coming into contact with shared surfaces (such as ride-sourcing). Given the transformative impact that ride-sourcing services had on urban mobility before the pandemic, it is crucial to understand the effects of COVID-19 on the use of ride-sourcing moving forward. Using data from a web-based survey, this study combines descriptive analysis with the application of a two-stage ordered logit model framework to investigate the impacts of COVID-19 on the utilization of ride-sourcing services in the Greater Toronto Area, including how often ride-sourcing is used and the earliest stage of the pandemic that a person would consider using ride-sourcing. Generally speaking, the use of ride-sourcing has decreased since the start of the pandemic, however, there are also people who are using ride-sourcing more often than they did before the pandemic. The results indicate that the perception of risk, the tendency to take precautions when leaving home, and socio-economic factors influence the earliest stage of the pandemic where a person would consider using ride-sourcing. Overall, it appears that ride-sourcing usage will gradually increase as restrictions are lifted; however, it is unlikely to return to pre-pandemic levels until COVID-19 is no longer considered a public health threat.

Receptor for advanced glycation end products up-regulation in cerebral endothelial cells mediates cerebrovascular-related amyloid ß accumulation after Porphyromonas gingivalis infection.

Cerebrovascular-related amyloidogenesis is found in over 80% of Alzheimer's disease (AD) cases, and amyloid ß (Aß) generation is increased in the peripheral macrophages during infection of Porphyromonas gingivalis (P. gingivalis), a causal bacterium for periodontitis. In this study, we focused on receptor for advanced glycation end products (RAGE), the key molecule involves in Aß influx after P. gingivalis infection to test our hypothesis that Aß transportation from periphery into the brain, known as "Aß influx," is enhanced by P. gingivalis infection. Using cultured hCMEC/D3 cell line, in comparison to uninfected cells, directly infection with P. gingivalis (multiplicity of infection, MOI = 5) significantly increased a time-dependent RAGE expression resulting in a dramatic increase in Aß influx in the hCMEC/D3 cells; the P. gingivalis-up-regulated RAGE expression was significantly decreased by NF-κB and Cathepsin B (CatB)-specific inhibitors, and the P.gingivalis-increased IκBα degradation was significantly decreased by CatB-specific inhibitor. Furthermore, the P. gingivalis-increased Aß influx was significantly reduced by RAGE-specific inhibitor. Using 15-month-old mice (C57BL/6JJmsSlc, female), in comparison to non-infection mice, systemic P. gingivalis infection for three consecutive weeks (1 × 108  CFU/mouse, every 3 days, intraperitoneally) significantly increased the RAGE expression in the CD31-positive endothelial cells and the Aß loads around the CD31-positive cells in the mice's brains. The RAGE expression in the CD31-positive cells was positively correlated with the Aß loads. These observations demonstrate that the up-regulated RAGE expression in cerebral endothelial cells mediates the Aß influx after P. gingivalis infection, and CatB plays a critical role in regulating the NF-κB/RAGE expression. Cover Image for this issue: https://doi.org/10.1111/jnc.15073.

Awareness of and barriers to using non-occupational post-exposure prophylaxis among male clients of female sex workers in two cities of China: a qualitative study.

Background Male clients of female sex workers ('clients' hereafter) are considered high-risk and potentially a bridge population in the HIV epidemic. Non-occupational post-exposure prophylaxis (nPEP) is a safe and effective but under-utilised public health intervention to prevent HIV transmission. This study aims to explore clients' awareness of nPEP, intention of uptake, potential barriers to nPEP uptake and adherence, and suggestions for nPEP promotion in China. METHODS: We conducted semi-structured in-depth interviews with 20 clients in two Chinese cities in 2018. Participants were recruited through purposive sampling. The content of the interviews was analysed using thematic content analysis in ATLAS.ti. RESULTS: Overall, just a minority of participants were aware of nPEP. A majority expressed willingness to use nPEP. Potential barriers to nPEP uptake and adherence included adverse drug reactions, price, concerns of drug efficacy, privacy issues, and forgetting to take the drugs. Almost all participants expressed the need to promote nPEP among clients. Participants suggested that the promotion of nPEP should be at hospitals, online, and be integrated with HIV/AIDS health education. CONCLUSIONS: Our findings suggested that nPEP guidelines should be formulated and implementation strategies should be developed to address barriers to uptake and adherence in order to successfully tap into the potential of nPEP as an effective HIV prevention tool.

COVid-19 influenced households' Interrupted Travel Schedules (COVHITS) survey: Lessons from the fall 2020 cycle.

The spread of the novel coronavirus disease-2019 (COVID-19) since early in 2020 has affected every aspect of daily life, including urban passenger travel patterns. Lockdowns to control the spread of COVID-19 created unprecedented travel demand contexts that have never been seen in modern history. So, it is essential to benchmark trends of travel behaviour, especially people's daily travel patterns that are necessary to develop a comprehensive understanding of the impacts of COVID-19. A multi-cycle benchmarking household travel study: the COVid-19 influenced Households' Interrupted Travel Schedules (COVHITS) Survey was implemented in the Greater Toronto Area with a random sample of over 4000 households. The results indicated a stark alteration in people's daily activity-travel patterns due to COVID-19. The pandemic caused a substantial decline in mobility in the study area. The average weekday household trip rate dropped from 5.2 to 2.0 trips. Transit modal shares suffered severely during the paramedic, while private car dependency was enhanced. Overall, transit modal share dropped from 17.3% to 8.1% in the study area, while the modal share of private cars increased from 70.8% to 74.1%. Factors such as having to work from home, ownership of private cars, and household incomes influenced mobility levels of the people in the study area during the pandemic. While overlooked, travel demand analysis can reveal effective strategies to curb the spread of such contagious diseases. An econometric model and analysis of sample data reveal several potential strategies. These include: (1) working/learning from home should be implemented until the end of the pandemic; (2) transit agencies should provide as much transit frequency as possible (particularly for bus routes) during peak hours to avoid crowding inside transit vehicles and project a positive image of public transit; and (3) strict restrictions should be implemented in regions with lower confirmed COVID-19 cases, as they became attractive destinations during the pandemic.

Exploring the impacts of the COVID-19 pandemic on modality profiles for non-mandatory trips in the Greater Toronto Area.

The ongoing COVID-19 pandemic has drastically altered daily life in cities across the world. To slow the spread of COVID-19, many countries have introduced mobility restrictions, ordered the temporary closure of businesses, and encouraged social distancing. These policies have directly and indirectly influenced travel behaviour, particularly modal preferences. The purpose of this paper to explore modality profiles for non-mandatory trips and analyze how they have changed in response to the pandemic and pandemic-related public health policies. The data used for this study were collected from web-based surveys conducted in the Greater Toronto Area. Modality profiles were identified through the application of latent class cluster analysis, with six modality profiles being identified for both the pre-pandemic and pandemic periods. The results indicate that the importance of public transit has declined during the pandemic, while the roles of private vehicles and active modes have become more prominent. However, individuals' changes in modal preferences vary based on their pre-pandemic modality profile. In particular, it appears that pre-pandemic transit users with access to a private vehicle have substituted public transit for travel by private vehicle, while those without private vehicle access are continuing to use public transit for non-mandatory trips. Consequently, pandemic-related transportation policies should consider those who do not have access to a private vehicle and aim to help those making non-mandatory trips using transit or active modes comply with local public health guidelines while travelling. The results highlight how the changes in modal preferences that occurred due to the pandemic differ among different segments of the population.

Cathepsin B plays a critical role in inducing Alzheimer's disease-like phenotypes following chronic systemic exposure to lipopolysaccharide from Porphyromonas gingivalis in mice.

A number of clinical and experimental studies have revealed a strong association between periodontitis and accelerated cognitive decline in Alzheimer's disease (AD); however, the mechanism of the association is unknown. In the present study, we tested the hypothesis that cathepsin (Cat) B plays a critical role in the initiation of neuroinflammation and neural dysfunction following chronic systemic exposure to lipopolysaccharide from Porphyromonas gingivalis (PgLPS) in mice (1mg/kg, daily, intraperitoneally). Young (2months old) and middle-aged (12months old) wild-type (WT; C57BL/6N) or CatB-deficient (CatB-/-) mice were exposed to PgLPS daily for 5 consecutive weeks. The learning and memory function were assessed using the passive avoidance test, and the expression of amyloid precursor protein (APP), CatB, TLR2 and IL-1ß was analyzed in brain tissues by immunohistochemistry and Western blotting. We found that chronic systemic exposure to PgLPS for five consecutive weeks induced learning and memory deficits with the intracellular accumulation of Aß in neurons in the middle-aged WT mice, but not in young WT or middle-aged CatB-/- mice. PgLPS significantly increased the expression of CatB in both microglia and neurons in middle-aged WT mice, while increased expression of mature IL-1ß and TLR2 was restricted to microglia in the hippocampus of middle-aged WT mice, but not in that of the middle-aged CatB-/- ones. In in vitro studies, PgLPS (1µg/ml) stimulation upregulated the mean mRNA expression of IL-1ß, TLR2 and downregulated the protein levels of IκBα in the cultured MG6 microglia as well as in the primary microglia from WT mice, which were significantly inhibited by the CatB-specific inhibitor CA-074Me as well as by the primary microglia from CatB-/- mice. Furthermore, the mean mRNA expression of APP and CatB were significantly increased in the primary cultured hippocampal neurons after treatment with conditioned medium from PgLPS-treated WT primary microglia, but not after treatment with conditioned medium neutralized with anti-IL-1beta, and not after treatment with conditioned medium from PgLPS-treated CatB-/- primary microglia or with PgLPS directly. Taken together, these findings indicate that chronic systemic exposure to PgLPS induces AD-like phenotypes, including microglia-mediated neuroinflammation, intracellular Aß accumulation in neurons and impairment of the learning and memory functions in the middle-aged mice in a CatB-dependent manner. We propose that CatB may be a therapeutic target for preventing periodontitis-associated cognitive decline in AD.

miR-483-3p regulates hyperglycaemia-induced cardiomyocyte apoptosis in transgenic mice.

Diabetic cardiomyopathy represents severe heart complications, and is the leading cause of morbidity and mortality among patients with diabetes. Although a few microRNAs (miRNAs) have been implicated in diabetes-related complications, a functional association between miRNAs and cardiac dysfunction in diabetic cardiomyopathy remains to be demonstrated. Our results show that miR-483-3p is upregulated in streptozotocin-induced diabetic mice, and cultured cardiomyocytes mimicking hyperglycemia. Overexpressing miR-483-3p in transgenic mice with diabetes mellitus (DM) exacerbated cardiomyocyte apoptosis by transcriptionally repressing insulin growth factor 1 (IGF1). Therefore, we have uncovered a novel signaling pathway, involving miR-483-3p-IGF1, that promotes myocardial cell apoptosis under high blood-glucose condition. Further, our study indicates that miR-483-3p could be a potential therapeutic target for managing diabetes-associated heart complications.

MiR-214 increases the sensitivity of breast cancer cells to tamoxifen and fulvestrant through inhibition of autophagy.

BACKGROUND: Tamoxifen (TAM) and fulvestrant (FUL) are the major drugs for patients with estrogen receptor-positive (ER(+)) breast cancers. However, the development of endocrine resistance is the impediment for successful treatment. We aimed to explore the mechanisms of endocrine resistance and therapeutic strategy for overcoming resistance against TAM and FUL. METHODS: Experiments were performed in ER(+) and estrogen/TAM-sensitive MCF7 cells and antiestrogen-resistant MCF7/LCC9 cells. The expression of miR-214 and uncoupling protein 2 (UCP2) was determined by RT-qPCR and Western blot in breast cancer cells and human breast cancer tissue specimens. Cell autophagy was examined by fluorescent probe monodansyl cadaverine (MDC) and GFP-LC3-II-positive punctate identified by confocal microscopy. Apoptotic cells were determined by Annexin V-FITC/PI staining. The potential regulatory target of miR-214 was determined by prediction tool, target protein expression and luciferase reporter assay. RESULTS: 4-OHT/FUL treatment resulted in induction of apoptosis as well as autophagy in breast cancer cells. Autophagy might be the major cause of endocrine resistance to 4-OHT or FUL. MiR-214 increased the sensitivity of breast cancer cells to the 4-OHT/FUL-induced apoptosis through inhibition of autophagy. Importantly, a negative correlation was established between miR-214 and UCP2 in human breast cancer tissue specimens assayed by RT-qPCR. UCP2 was identified to be a direct target of miR-214. Further study in MCF7/LCC9 cells indicated that endocrine resistance might arise from activation of the PI3K-Akt-mTOR pathway, thereby inducing autophagy by overexpression of UCP2. CONCLUSION: MiR-214 increased the sensitivity of breast cancer cells to TAM and FUL through inhibition of autophagy by targeting UCP2. MiR-214 shows potential as a novel therapeutic strategy for overcoming endocrine resistance in ER(+) breast cancers.

Testing for treatment-biomarker interaction based on local partial-likelihood.

In clinical trials, patients with different biomarker features may respond differently to the new treatments or drugs. In personalized medicine, it is important to study the interaction between treatment and biomarkers in order to clearly identify patients that benefit from the treatment. With the local partial-likelihood estimation (LPLE) method proposed by Fan J, Lin H, Zhou Y. Local partial-likelihood estimation for lifetime data. The Annals of Statistics 2006; 34(1):290U325, the treatment effect can be modeled as a flexible function of the biomarker. In this paper, we propose a bootstrap test method for survival outcome data based on the LPLE, for assessing whether the treatment effect is a constant among all patients or varies as a function of the biomarker. The test method is called local partial-likelihood bootstrap (LPLB) and is developed by bootstrapping the martingale residuals. The test statistic measures the amount of change in treatment effects across the entire range of the biomarker and is derived based on asymptotic theories for martingales. The LPLB method is nonparametric and is shown in simulations and data analysis examples to be flexible enough to identify treatment effects in a biomarker-defined subset and more powerful to detect treatment-biomarker interaction of complex forms than the Cox regression model with a simple interaction. We use data from a breast cancer and a prostate cancer clinical trial to illustrate the proposed LPLB test.

Spectral Decomposition and Transformation for Cross-domain Few-shot Learning.

Cross-domain few-shot Learning (CDFSL) is proposed to first pre-train deep models on a source domain dataset where sufficient data is available, and then generalize models to target domains to learn from only limited data. However, the gap between the source and target domains greatly hampers the generalization and target-domain few-shot finetuning. To address this problem, we analyze the domain gap from the aspect of frequency-domain analysis. We find the domain gap could be reflected by the compositions of source-domain spectra, and the lack of compositions in the source datasets limits the generalization. Therefore, we aim to expand the coverage of spectra composition in the source datasets to help the source domain cover a larger range of possible target-domain information, to mitigate the domain gap. To achieve this goal, we propose the Spectral Decomposition and Transformation (SDT) method, which first randomly decomposes the spectrogram of the source datasets into orthogonal bases, and then randomly samples different coordinates in the space formed by these bases. We integrate the above process into a data augmentation module, and further design a two-stream network to handle augmented images and original images respectively. Experimental results show that our method achieves state-of-the-art performance in the CDFSL benchmark dataset.

The impact of skeletal muscle index at the third lumbar spine on nosocomial deterioration and short-term prognosis in acute pancreatitis: a retrospective observational study.

Objective: To investigate the impact of the third lumbar skeletal muscle index (L3-SMI) assessed by CT on the in-hospital severity and short-term prognosis of acute pancreatitis. Methods: A total of 224 patients with severe acute pancreatitis admitted to Yantaishan Hospital from January 2021 to June 2022 were selected as the subjects. Based on the in-hospital treatment outcomes, they were divided into a mortality group of 59 cases as well as a survival group of 165 cases. Upon admission, general information such as the Acute Physiology and Chronic Health Evaluation II (APACHE II) score, along with the abdominal CT images of each patient, were analyzed. The L3-SMI was calculated, and the Modified CT Severity Index (MCTSI) and Balthazar CT grade were used to assess the severity of in-hospital complications of acute pancreatitis. The evaluation value of L3-SMI for the prognosis of severe acute pancreatitis was analyzed, as well as the factors influencing the prognosis of severe acute pancreatitis. Results: No statistically significant differences in gender, age, BMI, etiology, duration of anti-inflammatory drug use, and proportion of surgical patients between the survival and mortality groups were observed. But the mortality group showed higher proportions of patients with an elevated APACHE II score upon admission, mechanical ventilation, and renal replacement therapy, compared to the survival group, with statistically significant differences (P < 0.001). Furthermore, the mortality group had higher MCTSI scores (6.42 ± 0.69) and Balthazar CT grades (3.78 ± 0.45) than the survival group, with statistically significant differences (P < 0.001). The mortality group also had a lower L3-SMI (39.68 ± 3.25) compared to the survival group (42.71 ± 4.28), with statistically significant differences (P < 0.001). L3-SMI exhibited a negative correlation with MCTSI scores and Balthazar CT grades (r = -0.889, -0.790, P < 0.001). Logistic regression analysis, with mortality of acute pancreatitis patients as the dependent variable and MCTSI scores, Balthazar CT grades, L3-SMI, APACHE II score upon admission, mechanical ventilation, and renal replacement therapy as independent variables, revealed that MCTSI scores and L3-SMI were risk factors for mortality in acute pancreatitis patients (P < 0.001). Logistic regression analysis using the same variables confirmed that all these factors were risk factors for mortality in acute pancreatitis patients. Conclusion: This study confirmed that diagnosing muscle depletion using L3-SMI is a valuable radiological parameter for predicting in-hospital severity and short-term prognosis in patients with acute pancreatitis.

A Flexible Skin Bionic Thermally Comfortable Wearable for Machine Learning-Facilitated Ultrasensitive Sensing.

Tremendous popularity is observed for multifunctional flexible electronics with appealing applications in intelligent electronic skins, human-machine interfaces, and healthcare sensing. However, the reported sensing electronics, mostly can hardly provide ultrasensitive sensing sensitivity, wider sensing range, and robust cycling stability simultaneously, and are limited of efficient heat conduction out from the contacted skin interface after wearing flexible electronics on human skin to satisfy thermal comfort of human skin. Inspired from the ultrasensitive tactile perception microstructure (epidermis/spinosum/signal transmission) of human skin, a flexible comfortably wearable ultrasensitive electronics is hereby prepared from thermal conductive boron nitride nanosheets-incorporated polyurethane elastomer matrix with MXene nanosheets-coated surface microdomes as epidermis/spinosum layers assembled with interdigitated electrode as sensing signal transmission layer. It demonstrates appealing sensing performance with ultrasensitive sensitivity (≈288.95 kPa-1), up to 300 kPa sensing range, and up to 20 000 sensing cycles from obvious contact area variation between microdome microstructures and the contact electrode under external compression. Furthermore, the bioinspired electronics present advanced thermal management by timely efficient thermal dissipation out from the contacted skin surface to meet human skin thermal comfort with the incorporated thermal conductive boron nitride nanosheets. Thus, it is vitally promising in wearable artificial electronic skins, intelligent human-interactive sensing, and personal health management.

Eco-evolutionary processes shaping floral nectar sugar composition.

Floral nectar sugar composition is assumed to reflect the nutritional demands and foraging behaviour of pollinators, but the relative contributions of evolutionary and abiotic factors to nectar sugar composition remain largely unknown across the angiosperms. We compiled a comprehensive dataset on nectar sugar composition for 414 insect-pollinated plant species across central Europe, along with phylogeny, paleoclimate, flower morphology, and pollinator dietary demands, to disentangle their relative effects. We found that phylogeny was strongly related with nectar sucrose content, which increased with the phylogenetic age of plant families, but even more strongly with historic global surface temperature. Nectar sugar composition was also defined by floral morphology, though it was not related to our functional measure of pollinator dietary demands. However, specialist pollinators of current plant-pollinator networks predominantly visited plant species with sucrose-rich nectar. Our results suggest that both physiological mechanisms related to plant water balance and evolutionary effects related to paleoclimatic changes have shaped floral nectar sugar composition during the radiation and specialisation of plants and pollinators. As a consequence, the high velocity of current climate change may affect plant-pollinator interaction networks due to a conflicting combination of immediate physiological responses and phylogenetic conservatism.

Leptomeningeal cells transduce peripheral macrophages inflammatory signal to microglia in reponse to Porphyromonas gingivalis LPS.

We report here that the leptomeningeal cells transduce inflammatory signals from peripheral macrophages to brain-resident microglia in response to Porphyromonas gingivalis (P.g.) LPS. The expression of Toll-like receptor 2 (TLR2), TLR4, TNF-α, and inducible NO synthase was mainly detected in the gingival macrophages of chronic periodontitis patients. In in vitro studies, P.g. LPS induced the secretion of TNF-α and IL-1ß from THP-1 human monocyte-like cell line and RAW264.7 mouse macrophages. Surprisingly, the mean mRNA levels of TNF-α and IL-1ß in leptomeningeal cells after treatment with the conditioned medium from P.g. LPS-stimulated RAW264.7 macrophages were significantly higher than those after treatment with P.g. LPS alone. Furthermore, the mean mRNA levels of TNF-α and IL-1ß in microglia after treatment with the conditioned medium from P.g. LPS-stimulated leptomeningeal cells were significantly higher than those after P.g. LPS alone. These observations suggest that leptomeninges serve as an important route for transducing inflammatory signals from macrophages to microglia by secretion of proinflammatory mediators during chronic periodontitis. Moreover, propolis significantly reduced the P.g. LPS-induced TNF-α and IL-1ß production by leptomeningeal cells through inhibiting the nuclear factor-κB signaling pathway. Together with the inhibitory effect on microglial activation, propolis may be beneficial in preventing neuroinflammation during chronic periodontitis.

Backbone resonance assignments and dynamics of S. cerevisiae SERF.

Abnormal protein aggregation and precipitation are associated with the perturbation of cellular function and underlie a variety of neurodegenerative diseases. S. cerevisiae SERF (ScSERF), a homolog of modifier of aggregation-4 (MOAG-4) and small EDRK-rich factor protein (SERF1a) is highly conserved and discovered as an enhancer of amyloid formation of Aß40 and α-synuclein both in vitro and in vivo. However, the detailed molecular mechanism whereby ScSERF and its homologs accelerate amyloid formation is not well known yet. Herein, we present the 1 H, 15 N and 13 C NMR assignments of the 68 amino acids long ScSERF. Although ScSERF displays a very high degree of disorder, secondary chemical shifts of Cα, Cß, 15 N{1 H}-NOE values and the residue-specific secondary structure propensity (SSP) scores indicate the segment spanning residues 36E-65 K has a strong helical propensity. This work sets the stage for further detailed structural and dynamic investigations of ScSERF and the molecular mechanism it utilizes in accelerating amyloid formation.

Epidemiology and disease burden of androgenetic alopecia in college freshmen in China: A population-based study.

OBJECTIVE: To evaluate the epidemiology and disease burden of androgenetic alopecia (AGA) in college freshmen in China. METHODS: This population-based cross-sectional survey was carried out among 9227 freshmen of two comprehensive universities in two cities of China (Changsha and Xiamen) from September 2018 to October 2018. Questionnaires covering basic issues, surrounding demographic information, history of diseases, living habits, comorbidities, etc. were completed online in a self-reported manner Dermatological examination was performed by certified dermatologists. The disease burden of AGA, which includes health-related quality of life, symptoms of anxiety, symptoms of depression and quality of sleep, was measured by EQ-5D-3L, PHQ-2, GAD-2 and PSQI, respectively. RESULTS: The prevalence of AGA in college freshmen in China was 5.3/1000. Male was significantly associated with higher prevalence of AGA (7.9/1000, P<0.01) while female with lower risk of AGA (OR = 0.29, P = 0.002). There was no significant association between BMI and AGA, nor predilection of AGA in the Han nationality or the other ethnic minorities. Annual household income or parental highest educational level exerted no significant influence on the prevalence of AGA. Rosacea (OR = 3.22, P = 0.019) was significantly associated with higher prevalence of AGA while acne seemed not to be related to AGA. The scores of EQ-5D, GAD-2, PHQ-2 and PSQI were not significantly different between students with and without AGA. CONCLUSION: The onset of AGA in Chinese college freshmen differ between genders and was significantly associated with rosacea.