The HEAT repeat protein HPO-27 is a lysosome fission factor.

Lysosomes are degradation and signalling centres crucial for homeostasis, development and ageing1. To meet diverse cellular demands, lysosomes remodel their morphology and function through constant fusion and fission2,3. Little is known about the molecular basis of fission. Here we identify HPO-27, a conserved HEAT repeat protein, as a lysosome scission factor in Caenorhabditis elegans. Loss of HPO-27 impairs lysosome fission and leads to an excessive tubular network that ultimately collapses. HPO-27 and its human homologue MROH1 are recruited to lysosomes by RAB-7 and enriched at scission sites. Super-resolution imaging, negative-staining electron microscopy and in vitro reconstitution assays reveal that HPO-27 and MROH1 self-assemble to mediate the constriction and scission of lysosomal tubules in worms and mammalian cells, respectively, and assemble to sever supported membrane tubes in vitro. Loss of HPO-27 affects lysosomal morphology, integrity and degradation activity, which impairs animal development and longevity. Thus, HPO-27 and MROH1 act as self-assembling scission factors to maintain lysosomal homeostasis and function.

Direct growth of single-chiral-angle tungsten disulfide nanotubes using gold nanoparticle catalysts.

Transition metal dichalcogenide (TMD) nanotubes offer a unique platform to explore the properties of TMD materials at the one-dimensional limit. Despite considerable efforts thus far, the direct growth of TMD nanotubes with controllable chirality remains challenging. Here we demonstrate the direct and facile growth of high-quality WS2 and WSe2 nanotubes on Si substrates using catalytic chemical vapour deposition with Au nanoparticles. The Au nanoparticles provide unique accommodation sites for the nucleation of WS2 or WSe2 shells on their surfaces and seed the subsequent growth of nanotubes. We find that the growth mode of nanotubes is sensitive to the temperature. With careful temperature control, we realize ~79% WS2 nanotubes with single chiral angles, with a preference of 30° (~37%) and 0° (~12%). Moreover, we demonstrate how the geometric, electronic and optical properties of the synthesized WS2 nanotubes can be modulated by the chirality. We anticipate that this approach using Au nanoparticles as catalysts will facilitate the growth of TMD nanotubes with controllable chirality and promote the study of their interesting properties and applications.

The association between sleep duration and lung cancer: a meta-analysis.

PURPOSE: The link between sleep duration and lung cancer risk has been suggested by some epidemiological studies. This meta-analysis was performed to further understand this relationship. METHODS: MEDLINE and EMBASE entries up to December 2022 were searched for eligible publications. A random effects model was used to calculate pooled relative risks (RRs) with 95% confidence intervals (95% CIs). Publication bias was estimated using Begg's and Egger's regression asymmetry test. RESULTS: The meta-analysis included 11 studies (including 10 cohort studies and 1 case-control study). The pooled adjusted RRs were 1.13 (95% CI: 1.03-1.24) for short sleep duration and 1.21 (95% CI: 1.07-1.37) for long sleep duration. CONCLUSION: The findings of this meta-analysis suggested that both short and long sleep duration are associated with an increase in lung cancer risk. These findings need to be corroborated through large-scale prospective studies.

Factors associated with dysmenorrhoea and menorrhagia improvement in patients with adenomyosis after uterine artery embolisation.

BACKGROUND: This study examined the improvement of dysmenorrhoea and menorrhagia after uterine artery embolisation (UAE) in women with symptomatic adenomyosis and identified factors that could predict the improvement of dysmenorrhoea and menorrhagia. METHODS: This retrospective study included women with adenomyosis who underwent bilateral UAE between December 2014 and December 2016. The percentage of the volume of the absence of contrast enhancement on T1-weighted images was evaluated 5-7 days after UAE. A receiver operating characteristic (ROC) analysis was used to determine a cut-off point and predict the improvement of dysmenorrhoea and menorrhagia. RESULTS: Forty-eight patients were included. At 24 and 36 months after UAE, the improvement rates for dysmenorrhoea and menorrhagia were 60.4% (29/48) and 85.7% (30/35), and the recurrence rates were 19.4% (7/36) and 9.1% (3/33), respectively. Only the percentage of the volume of the absence of contrast enhancement on T1-weighted images was associated with the improvement of dysmenorrhoea (p = 0.001, OR = 1.051; 95% CI: 1.02-1.08) and menorrhagia (p = 0.006, OR = 1.077; 95% CI: 1.021-1.136). When the cut-off value of the ROC analysis was 73.1%, sensitivity, specificity, positive predictive value, and negative predictive value for the improvement of dysmenorrhoea were 58.6%, 94.7%, 94.4%, and 60%, while they were 58.9%, 80%, 100%, 100%, and 45.5% for the improvement of dysmenorrhoea. CONCLUSION: Bilateral UAE for symptomatic adenomyosis led to good improvement of dysmenorrhoea and menorrhagia. The percentage of the volume of the absence of contrast enhancement on T1-weighted images of the uterus in postoperative magnetic resonance imaging might be associated with the improvement of dysmenorrhoea and menorrhagia.

This study examined the improvement of dysmenorrhoea and menorrhagia after uterine artery embolisation in women with symptomatic adenomyosis and identified factors that could predict the improvement of dysmenorrhoea and menorrhagia. This retrospective study included women with adenomyosis who underwent uterine artery embolisation. A total of 48 patients were included. Only the percentage of the volume of the absence of contrast enhancement on T1-weighted images was associated with improvement of dysmenorrhoea and menorrhagia. Bilateral uterine artery embolisation for symptomatic adenomyosis led to good improvement. The percentage of the volume of the absence of contrast enhancement on images in postoperative T1-weighted magnetic resonance imaging of the uterus might be associated with the improvement of dysmenorrhoea and menorrhagia.

Uncovering the first complete chloroplast genomics, comparative analysis, and phylogenetic relationships of the medicinal plants Rhamnus cathartica and Frangula alnus (Rhamnaceae).

Rhamnus cathartica and Frangula alnus are economically valuable medicinal plants from the Rhamnaceae family. However, their chloroplast genome structure, phylogenetic position, relationships, and evolution remain poorly understood. Herein, the complete chloroplast genome resources of R. cathartica and F. alnus have been added. The first comparative analysis of the Rhamnus and Frangula species based on complete chloroplast genomes was provided. The chloroplast genomes of R. cathartica and F. alnus exhibited a quadripartite structure, with total lengths of 161,149 bp and 161,255 bp, respectively. The lack of the infA and psbL genes does not negatively impact the normal functioning of Rhamnus and Frangula species. The rpl20 and rpl33 genes are undergoing rapid evolution. Rhamnus and Frangula species prefer amino acids with A/U-terminal codons. There were between 100 and 126 simple sequence repeats and between 38 and 100 long repeats. Several highly divergent intergenic regions (trnK-UUU-trnQ-UUG, atpH-atpI, trnY-GUA-trnE-UUC, trnG-GCC-trnfM-CAU, trnT-UGU-trnF-GAA, rpl20-rps12, and rpl22-rps19) and highly divergent genes (ycf3, ndhA, rpl32, and ycf1) were identified, which could serve as potential phylogenetic markers due to their variability. We reconstructed the phylogenetic relationships among Rhamnus species and F. alnus using complete chloroplast genomes. There is no significant correlation between the medicinal value of the species analyzed and their phylogenetic relationships. These results provide valuable insights for understanding the phylogenetic relationship and evolution of Rhamnus and Frangula species. These findings could serve as a foundation for future studies on the Rhamnaceae. Supplementary Information: The online version contains supplementary material available at 10.1007/s12298-023-01331-7.

Determination of Nanoplastics Using a Novel Contactless Conductivity Detector with Controllable Geometric Parameters.

Plastic waste in the environment is continuously degraded to form nanoplastic particles, and its harm has attracted widespread attention. At present, the identification and quantification of nanoplastics are performed by visual observation and using some spectroscopy methods, which are time-consuming and lack accuracy. Therefore, this study proposes a contactless conductivity detector (C4D) based on a glass microfluidic chip with controllable geometric parameters to quantify nanoplastics. We found that when the insulating layer thickness was 15 µm, the electrode spacing was 1 mm, and the shielding method was on-chip shielding, the detector displayed the best performance. The detector possesses a simple structure with high sensitivity and outstanding reproducibility, that is, the limit of detection of KCl solutions can reach the micromolar level, and the intraday RSD is 0.2% (n = 5). This work uses a microfluidic chip C4D to study nanoplastics for the first time, and the limit of detection is 0.25 µg/mL and the quantitative limit is 0.8 µg/mL. In addition, plant experiments have verified that terrestrial plants can absorb nanoplastics in water, expanding the application of contactless conductivity detectors and providing a new method for the quantitative analysis of nanoplastics.

Multi-parameter influenced acquisition model with an in-orbit jitter for inter-satellite laser communication of the LCES system.

With the development of large low earth orbit (LEO) communication constellations, the efficiency of laser inter-satellite link (ISL) establishing become the bottleneck for subsequent large-scale launch and rapid networking applications of LEO communication constellations. Hence, we establish the pointing jitter error structure of LEO communication experiment satellites (LCES) system. The error structure can be used to trace the source of errors and evaluate the in-orbit jitter. And we derive an analytical expression of the acquisition probability density function (PDF) which comprehensively considering the influence of the scanning region, the pointing jitter error, the overlap factor and the in-orbit jitter error. The multi-parameter influenced acquisition model is validated by Monte Carlo (MC) simulations and semi-physical tests. The results reveals that the multi-parameter influenced acquisition model can be used to guide the in-orbit ISL establishing.

Machine learning-based prediction of invisible intraprostatic prostate cancer lesions on 68 Ga-PSMA-11 PET/CT in patients with primary prostate cancer.

PURPOSE: 68 Ga-PSMA PET/CT has high specificity and sensitivity for the detection of both intraprostatic tumor focal lesions and metastasis. However, approximately 10% of primary prostate cancer are invisible on PSMA-PET (exhibit no or minimal uptake). In this work, we investigated whether machine learning-based radiomics models derived from PSMA-PET images could predict invisible intraprostatic lesions on 68 Ga-PSMA-11 PET in patients with primary prostate cancer. METHODS: In this retrospective study, patients with or without prostate cancer who underwent 68 Ga-PSMA PET/CT and presented negative on PSMA-PET image at either of two different institutions were included: institution 1 (between 2017 and 2020) for the training set and institution 2 (between 2019 and 2020) for the external test set. Three random forest (RF) models were built using selected features extracted from standard PET images, delayed PET images, and both standard and delayed PET images. Then, subsequent tenfold cross-validation was performed. In the test phase, the three RF models and PSA density (PSAD, cut-off value: 0.15 ng/ml/ml) were tested with the external test set. The area under the receiver operating characteristic curve (AUC) was calculated for the models and PSAD. The AUCs of the radiomics model and PSAD were compared. RESULTS: A total of 64 patients (39 with prostate cancer and 25 with benign prostate disease) were in the training set, and 36 (21 with prostate cancer and 15 with benign prostate disease) were in the test set. The average AUCs of the three RF models from tenfold cross-validation were 0.87 (95% CI: 0.72, 1.00), 0.86 (95% CI: 0.63, 1.00), and 0.91 (95% CI: 0.69, 1.00), respectively. In the test set, the AUCs of the three trained RF models and PSAD were 0.903 (95% CI: 0.830, 0.975), 0.856 (95% CI: 0.748, 0.964), 0.925 (95% CI:0.838, 1.00), and 0.662 (95% CI: 0.510, 0.813). The AUCs of the three radiomics models were higher than that of PSAD (0.903, 0.856, and 0.925 vs. 0.662, respectively; P = .007, P = .045, and P = .005, respectively). CONCLUSION: Random forest models developed by 68 Ga-PSMA-11 PET-based radiomics features were proven useful for accurate prediction of invisible intraprostatic lesion on 68 Ga-PSMA-11 PET in patients with primary prostate cancer and showed better diagnostic performance compared with PSAD.

The loss of histone deacetylase 4 in macrophages exacerbates hepatic and adipose tissue inflammation in male but not in female mice with diet-induced non-alcoholic steatohepatitis.

Epigenetic regulation in macrophages plays a crucial role in the inflammatory response of cells. We investigated the role of macrophage histone deacetylase 4 (HDAC4) in diet-induced obesity and non-alcoholic steatohepatitis using macrophage-specific Hdac4 knockout mice (Hdac4MKO ). Hdac4 floxed control (Hdac4fl/fl ) and Hdac4MKO mice were fed a regular chow diet or an obesogenic high-fat/high-sucrose/high-cholesterol (HF/HS/HC) diet for 12 weeks. The loss of macrophage Hdac4, compared with Hdac4fl/fl control, aggravated the diet-induced inflammation in the liver and white adipose tissue only in male mice. Splenic monocytes isolated from male mice fed the HF/HS/HC diet showed increased lipopolysaccharide (LPS) sensitivity and decreased Ly6C-/Ly6C+ ratios in male Hdac4MKO mice, but not in females. Bone marrow-derived macrophages (BMMs) from male Hdac4MKO mice had a lesser efferocytotic capacity but higher proinflammatory gene expression upon LPS stimulation than male Hdac4fl/fl mice. However, female Hdac4MKO BMMs exhibited the opposite responses. The induction of estrogen receptor α (ERα, Esr1) expression by LPS was less in male but more in female Hdac4MKO BMMs than Hdac4fl/fl BMMs. Moreover, overexpression of human HDAC4 decreased basal expression of Esr1 and abolished its induction by LPS. Inhibition of ERα increased Hdac4 with induction of inflammatory genes, whereas activation of ERα decreased Hdac4 with reduction of inflammatory genes in male and female Hdac4fl/fl BMMs treated with LPS. However, regardless of the inhibition or activation of ERα, proinflammatory genes were induced by LPS more in male Hdac4MKO BMMs than Hdac4fl/fl cells, whereas cells in females showed opposite responses. In conclusion, this study suggests that the lack of macrophage Hdac4 aggravates hepatic and white adipose inflammation in male mice with diet-induced obesity and non-alcoholic steatohepatitis, and not in female mice. HDAC4 and ERα appear to counteract each other, but ERα may not be a major player in sex-dependent inflammatory responses in macrophages deficient in HDAC4. © 2021 The Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Small-scale spatiotemporal epidemiology of notifiable infectious diseases in China: a systematic review.

BACKGROUND: The prevalence of infectious diseases remains one of the major challenges faced by the Chinese health sector. Policymakers have a tremendous interest in investigating the spatiotemporal epidemiology of infectious diseases. We aimed to review the small-scale (city level, county level, or below) spatiotemporal epidemiology of notifiable infectious diseases in China through a systematic review, thus summarizing the evidence to facilitate more effective prevention and control of the diseases. METHODS: We searched four English language databases (PubMed, EMBASE, Cochrane Library, and Web of Science) and three Chinese databases (CNKI, WanFang, and SinoMed), for studies published between January 1, 2004 (the year in which China's Internet-based disease reporting system was established) and December 31, 2021. Eligible works were small-scale spatial or spatiotemporal studies focusing on at least one notifiable infectious disease, with the entire territory of mainland China as the study area. Two independent reviewers completed the review process based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. RESULTS: A total of 18,195 articles were identified, with 71 eligible for inclusion, focusing on 22 diseases. Thirty-one studies (43.66%) were analyzed using city-level data, 34 (47.89%) were analyzed using county-level data, and six (8.45%) used community or individual data. Approximately four-fifths (80.28%) of the studies visualized incidence using rate maps. Of these, 76.06% employed various spatial clustering methods to explore the spatial variations in the burden, with Moran's I statistic being the most common. Of the studies, 40.85% explored risk factors, in which the geographically weighted regression model was the most commonly used method. Climate, socioeconomic factors, and population density were the three most considered factors. CONCLUSIONS: Small-scale spatiotemporal epidemiology has been applied in studies on notifiable infectious diseases in China, involving spatiotemporal distribution and risk factors. Health authorities should improve prevention strategies and clarify the direction of future work in the field of infectious disease research in China.

Short-Term HRV Detection and Human Fatigue State Analysis Based on Optical Fiber Sensing Technology.

Mental fatigue is a key cause of chronic diseases and traffic accidents, which is difficult to be quantitatively evaluated. In order to non-intrusively detect fatigue state, an optical fiber sensing system is proposed, which is non-invasive and does not require direct contact with skin. The fiber sensor was fabricated through phase mask exposure method and packaged by sensitivity-enhanced structure, which can suppress transverse force and increase signal amplitude by 5%. A fatigue-inducing experiment was carried out, and the heartbeat signals of 20 subjects under different fatigue states were collected by the proposed sensing system. A series of heart rate variability indicators were calculated from the sensing signals, and their statistical significance for fatigue was analyzed. The experiment results showed that the values of SDNN and LF/HF increased significantly with subjects' fatigue level. This study shows that the proposed fiber optic sensing system has practical value in fatigue state monitoring.

Association between short-term exposure to air pollution and respiratory diseases among children in China: a systematic review and meta-analysis.

OBJECTIVE: To assess the quantitative association between short-term exposure to air pollution and respiratory disease outpatient visits among children in China. METHODS: We searched articles from 1 January 2000 to 31 December 2020 in six peer-reviewed literature databases following PRISMA guidelines. RESULTS: Of 2668 records, 33 were included in meta-analysis. The pooled excess risks of respiratory disease outpatient visits among children in China per 10 µg/m3 increase were 0.75% (95% CI: 0.54%, 0.96%) for PM2.5, 0.70% (95% CI: 0.50%, 0.89%) for PM10, 0.82% (95% CI: 0.58%, 1.05%) for SO2, 1.61% (95% CI: 1.25%, 1.98%) for NO2 and 0.74% (95% CI: 0.01%, 1.46%) for O3. In subgroup analysis, air pollution had a greater impact in southern or central cities, cold seasons, and areas with high relative humidity. CONCLUSIONS: Short-term exposure to air pollution was significantly associated with an increased excess risk of respiratory disease outpatient visits among children in China.

Pro-515 of the dynamin-like GTPase MxB contributes to HIV-1 inhibition by regulating MxB oligomerization and binding to HIV-1 capsid.

Interferon-regulated myxovirus resistance protein B (MxB) is an interferon-induced GTPase belonging to the dynamin superfamily. It inhibits infection with a wide range of different viruses, including HIV-1, by impairing viral DNA entry into the nucleus. Unlike the related antiviral GTPase MxA, MxB possesses an N-terminal region that contains a nuclear localization signal and is crucial for inhibiting HIV-1. Because MxB previously has been shown to reside in both the nuclear envelope and the cytoplasm, here we used bioinformatics and biochemical approaches to identify a nuclear export signal (NES) responsible for MxB's cytoplasmic location. Using the online computational tool LocNES (Locating Nuclear Export Signals or NESs), we identified five putative NES candidates in MxB and investigated whether their deletion caused nuclear localization of MxB. Our results revealed that none of the five deletion variants relocates to the nucleus, suggesting that these five predicted NES sequences do not confer NES activity. Interestingly, deletion of one sequence, encompassing amino acids 505-527, abrogated the anti-HIV-1 activity of MxB. Further mutation experiments disclosed that amino acids 515-519, and Pro-515 in particular, regulate MxB oligomerization and its binding to HIV-1 capsid, thereby playing an important role in MxB-mediated restriction of HIV-1 infection. In summary, our results indicate that none of the five predicted NES sequences in MxB appears to be required for its nuclear export. Our findings also reveal several residues in MxB, including Pro-515, critical for its oligomerization and anti-HIV-1 function.

The effect of cranberry consumption on lipid metabolism and inflammation in human apo A-I transgenic mice fed a high-fat and high-cholesterol diet.

Lipid metabolism and inflammation contribute to CVD development. This study investigated whether the consumption of cranberries (CR; Vaccinium macrocarpon) can alter HDL metabolism and prevent inflammation in mice expressing human apo A-I transgene (hApoAITg), which have similar HDL profiles to those of humans. Male hApoAITg mice were fed a modified American Institute of Nutrition-93M high-fat/high-cholesterol diet (16 % fat, 0·25 % cholesterol, w/w; n 15) or the high-fat/high-cholesterol diet containing CR (5 % dried CR powder, w/w, n 16) for 8 weeks. There were no significant differences in body weight between the groups. Serum total cholesterol, non-HDL-cholesterol and TAG concentrations were significantly lower in the control than CR group with no significant differences in serum HDL-cholesterol and apoA-I. Mice fed CR showed significantly lower serum lecithin-cholesterol acyltransferase activity than the control. Liver weight and steatosis were not significantly different between the groups, but hepatic expression of genes involved in cholesterol metabolism was significantly lower in the CR group. In the epididymal white adipose tissue (eWAT), the CR group showed higher weights with decreased expression of genes for lipogenesis and fatty acid oxidation. The mRNA abundance of F4/80, a macrophage marker and the numbers of crown-like structures were less in the CR group. In the soleus muscle, the CR group also demonstrated higher expression of genes for fatty acid ß-oxidation and mitochondrial biogenesis than those of the control. In conclusion, although CR consumption elicited minor effects on HDL metabolism, it prevented obesity-induced inflammation in eWAT with concomitant alterations in soleus muscle energy metabolism.

In-situ dual-channel surface plasmon resonance fiber sensor for temperature-compensated detection of glucose concentration.

External temperature variations inevitably affect the accuracy of surface plasmon resonance (SPR) biosensors. To that end, we propose an ultra-compact label-free dual-channel SPR fiber sensor (DSPRFS) that can simultaneously measure the glucose concentration and ambient temperature in real-time. The proposed sensor is based on a unique dual-channel structure fabricated by etching a side-hole fiber (SHF), and has significantly higher spatial sensitivity than traditional SPR biosensors. After coating with silver and zinc oxide films, one channel was filled with polydimethylsiloxane (PDMS) to sense the ambient temperature, and the other channel was immobilized with glucose oxidase (GOx) enzyme for glucose sensing. The proposed sensor is analyzed theoretically, fabricated and characterized. Glucose concentration sensitivity and temperature sensitivity of the manufactured sensor sample were found to be as high as 6.156 nm/mMand -1.604 nm/°C with limits of detection (LOD) of 16.24 µM and 0.06 °C, respectively. The proposed sensor has an extremely compact structure, enables temperature compensation, and is suitable for in-situ monitoring and high-precision sensing of glucose and other biological analytes.

Co-circulation of coxsackieviruses A-6, A-10, and A-16 causes hand, foot, and mouth disease in Guangzhou city, China.

BACKGROUND: Hand, foot, and mouth disease (HFMD) is a common infectious disease occurring in children under 5 years of age worldwide, and Enterovirus A71 (EV-A71) and Coxsackievirus A16 (CVA-16) are identified as the predominant pathogens. In recent years, Coxsackievirus A6 (CVA-6) and Coxsackievirus A10 (CVA-10) have played more and more important role in a series of HFMD outbreaks. This study aimed to understand the epidemic characteristics associated with HFMD outbreak in Guangzhou, 2018. METHODS: The clinical and laboratory data of 1220 enterovirus-associated HFMD patients in 2018 were analysed in this study. Molecular diagnostic methods were performed to identify its serotypes. Phylogenetic analyses were depicted based on the complete VP1 gene. RESULTS: There were 21 enterovirus serotypes detected in Guangzhou in 2018. Three serotypes of enterovirus, CVA-6 (364/1220, 29.8%), CVA-10 (305/1220, 25.0%), and CVA-16 (397/1220, 32.5%), were identified as the causative pathogens and accounted for 87.3% among all 1220 HFMD patients. In different seasons, CVA-6 was the predominant pathogen of HFMD during autumn, and CVA-10 as well as CVA-16 were more prevalent in summer. Patients infected by CVA-6, CVA-10 or CVA-16 showed similar clinical features and laboratory characteristics, and the ratios of severe HFMD were 5.8, 5.9, and 1.5% in the three serotypes. Phylogenetic analyses of VP1 sequences showed that the CVA-6, CVA-10, and CVA-16 sequences belonged to the sub-genogroup E2, genogroup E, and genogroup B1, respectively. CONCLUSIONS: CVA-6, CVA-10, and CVA-16 were the predominant and co-circulated serotypes in Guangzhou China, 2018, which should be the new target for prevention and control of HFMD. Our findings provide useful information for diagnosis, treatment, and prevention of HFMD.

MOV10 sequesters the RNP of influenza A virus in the cytoplasm and is antagonized by viral NS1 protein.

MOV10 has emerged as an important host antiviral factor. MOV10 not only inhibits various viruses, including human immunodeficiency virus type 1, hepatitis C virus and vesicular stomatitis virus, but also restricts the activity of retroelements long interspersed nucleotide element-1, Alu, SVA and intracisternal A particles. Here, we report that MOV10 suppresses influenza A virus infection through interacting with viral nucleoprotein (NP), sequestering viral RNP in the cytoplasm and causing the degradation of viral vRNA. The antiviral activity of MOV10 depends on the integrity of P-bodies. We also found that the antiviral activity of MOV10 is partially countered by viral NS1 protein that interferes with the interaction of MOV10 with viral NP and causes MOV10 degradation through the lysosomal pathway. Moreover, NS1-defective influenza A virus is more susceptible to MOV10 restriction. Our data not only expand the antiviral spectrum of MOV10 but also reveal the NS1 protein as the first viral antagonist of MOV10.

Evaluation of autoantibodies and immunoglobulin G subclasses in women with suspected macroprolactinemia.

BACKGROUND: Macroprolactin mostly composed of an immunoglobulin G (IgG) and a monomeric prolactin (PRL) represents the major circulating PRL form in the patients with macroprolactinemia that are usually asymptomatic and may not require treatment. In this study, we aimed to evaluate the prevalence of antithyroid and antinuclear antibodies, as well as the IgG subclass distributions in the patients suspected for macroprolactinemia. METHODS: From January to July in 2018, totally 317 patients with elevated PRL were subjected to the polyethylene glycol (PEG) precipitation assay. The patients with recovery rates of ≤60% were subjected for IgG subclass determination and autoantibody testing including thyroid peroxidase antibody (aTPO), antithyroglobulin antibody (aTG), and antinuclear antibodies (ANA). RESULTS: The higher the post-PEG PRL recovery rates, the less typical hyperprolactinemia symptoms and the higher prevalence of autoantibodies were observed. The IgG1 and IgG3 were the predominant subclasses in the PRL-IgG complexes according to the immunoprecipitation experiments. CONCLUSION: The patients with post-PEG PRL recovery rates of <40% and 40%-60% were likely to represent two distinct populations of different clinical presentations. The prevalence of autoantibodies and IgG subclasses distribution suggested their pathogenic significance in the development of macroprolactinemia.

Facile Evaluation of Nanoparticle-Protein Interaction Based on Charge Neutralization with Pulsed Streaming Potential Measurement.

Exploration of simple and universal methods to quantitatively measure nanoparticle (NP)-protein interaction is of great importance. In this work, pulsed streaming potential (SP) measurement has been used to evaluate the interaction between NPs and proteins within microchannels. Graphene oxide (GO) and SiO2 NPs were selected to represent two kinds of NPs. Lysozyme and common blood proteins, including albumin V, γ-globulins, and fibrinogen, were used as model proteins. The linear relationship between the initial adsorption rate (S = dEr/dt) and the concentration of proteins was observed. Combined with the Hill equation, the microscopic dissociation constant (KD) and the Hill coefficient (n) between NPs and proteins were calculated based on the relationship between S and the concentration of each protein. The concentration of free proteins which have not interacted with the NPs in the NPs-protein mixture could also be measured. The influence of pH, conductivity, and ionic strengths of the incubation buffer on the interaction between GO and lysozyme was evaluated based on the constant KD. The interaction intensity between NPs and proteins was defined as charge neutralization efficiency QC, which could be calculated from the value of S. It takes only 150 s to get the whole set of data under the optimized experiment parameters. The measurement solely depends on the surface charge, no intrinsic fluorescence is required for either the NPs or the proteins, and no labeling or immobilization process is involved as well.

Fucoxanthin exerts anti-fibrogenic effects in hepatic stellate cells.

The objective of this study was to evaluate whether fucoxanthin (FCX) have anti-fibrogenic properties in hepatic stellate cells (HSCs). FCX significantly decreased basal and transforming growth factor ß1 (TGFß1)-induced mRNA levels of fibrogenic genes with concomitant decreases in their protein levels in LX-2 cells. The phosphorylation of SMA- and MAD-related protein (SMAD3) was increased by TGFß1, which was attenuated by FCX. Importantly, when LX-2 cells were treated with FCX and SIS3, a SMAD3 inhibitor, there was synergistic repression of fibrogenic gene expression. The anti-fibrogenic effect of FCX was also confirmed in primary human HSCs. FCX prevented TGFß1-induced accumulation of reactive oxygen species by diminishing mRNA level of NADPH oxidase 4 (NOX4) in LX-2 cells. When FCX was present during the activation of quiescent mouse primary HSCs, it decreased the expression of fibrogenic genes while diminishing intracellular lipid droplets. The results suggest that FCX exerts an anti-fibrogenic effect in HSCs primarily by preventing TGFß1-induced pro-fibrogenic genes expression via inhibition of SMAD3 activation and by inhibiting the activation of quiescent HSCs.