In vivo study on osteogenic efficiency of nHA/ gel porous scaffold with nacre water-soluble matrix.

BACKGROUND/PURPOSE: Nano-hydroxyapatite (nHA)/ gel porous scaffolds loaded with WSM carriers are promising bone replacement materials that can improve osseointegration ability. This investigation aimed to evaluate the osteoinductive activity by implanting the composition of nano-hydroxyapatite (nHA)/ Gel porous scaffolds as a carrier of WSM via an animal model. MATERIALS AND METHODS: WSM was extracted and nHA was added to the matrix to construct porous composite scaffolds. The dose-effect curve of WSM concentration and alkaline phosphatase (ALP) activity was made by culturing rat osteoblasts and examining the absorbance. Three different materials were implanted into critical size defects (CSD) in the skulls of rats, which were further divided into four groups: WSM nHA /Gel group, n-WSM nHA /Gel group, HA powder group, and control group. RESULTS: WSM (150 µg/mL-250µg/mL) effectively improved the activity of ALP in rat osteoblasts. All rats in each group had normal healing. WSM-loaded nHA /Gel group showed better performance on newly-formed bone tissue of rat skull and back at 4th week and 8th week, respectively. At the 4th week, the network of woven bone formed in the WSM-loaded nHA/Gel scaffold material. At 8th week, the reticular trabecular bone in the WSM-loaded scaffold material became dense lamellar bone, and the defect was mature lamellar bone. In the subcutaneous implantation experiment, WSM-loaded nHA/Gel scaffold material showed a better performance of heterotopic ossification than the pure nHA/Gel scaffold material. CONCLUSION: WSM promotes osteoblast differentiation and bone mineralization. The results confirm that the nHA/ Gel Porous Scaffold with Nacre Water-Soluble Matrix has a significant bone promoting effect and can be used as a choice for tissue engineering to repair bone defects.

A long-term experiment reveals no trade-off between seed persistence and seedling emergence.

Information on seed persistence and seedling emergence from the soil seed bank is critical for understanding species coexistence and predicting community dynamics. However, quantifying seed persistence in the soil is challenging; thus, its association with other life-history traits is poorly known on a broad scale. Using germination phenology for 349 species in a 42-yr experiment, we quantified the persistence-emergence correlations and their associations with intrinsic regeneration traits using Bayesian phylogenetic multilevel models. We showed no trade-off between seed persistence and seedling emergence. Physically dormant seeds were more persistent but exhibited lower emergence than nondormant seeds. Monocarpic species had both higher persistence and emergence than polycarpic species. Seed mass posed a marginal proxy for persistence, while emergence almost doubled from the smallest to the largest seeds. This study challenges the traditional assumption and is the first demonstration of noncorrelation between persistence and emergence, probably owing to the complexity of regenerative strategies. Species with short persistence and low emergence would be the most vulnerable for in situ conservation. Our analyses of this unique, long-term dataset provide a strong incentive for further experimental studies and a rich data resource for future syntheses.

Immunogenicity and safety of an Escherichia coli-produced human papillomavirus (types 6/11/16/18/31/33/45/52/58) L1 virus-like-particle vaccine: a phase 2 double-blind, randomized, controlled trial.

The Escherichia coli-produced human papillomavirus (HPV) 16/18 bivalent vaccine (Cecolin) has received prequalification by the World Health Organization based on its high efficacy and good safety profile. We aimed to evaluate the immunogenicity and safety of the second-generation nonavalent HPV 6/11/16/18/31/33/45/52/58 vaccine (Cecolin 9) through the randomized, blinded phase 2 clinical trial. Eligible healthy women aged 18-45 years were randomly (1:1) allocated to receive three doses of 1.0 mL (270 µg) of Cecolin 9 or placebo with a 0-1-6-month schedule. The primary endpoint was the seroconversion rate and geometric mean titer of neutralizing antibodies (nAbs) one month after the full vaccination course (month 7). The secondary endpoint was the safety profile including solicited adverse reactions occurring within 7 d, adverse events (AEs) occurring within 30 d after each dose, and serious adverse events (SAEs) occurring during the 7-month follow-up period. In total, 627 volunteers were enrolled and randomly assigned to Cecolin 9 (n = 313) or placebo (n = 314) group in Jiangsu Province, China. Almost all participants in the per-protocol set for immunogenicity (PPS-I) seroconverted for nAbs against all the nine HPV types at month 7, while two failed to seroconvert for HPV 11 and one did not seroconvert for HPV 52. The incidence rates of total AEs in the Cecolin 9 and placebo groups were 80.8% and 72.9%, respectively, with the majority of them being mild and recovering shortly. None of the SAEs were considered related to vaccination. In conclusion, the E. coli-produced 9-valent HPV (9vHPV) vaccine candidate was well tolerated and immunogenic, which warrants further efficacy studies in larger populations.

Pyrrolizidine alkaloids and health risk of three Boraginaceae used in TCM.

Objective: The aim of this study was to systematically explore the pyrrolizidine alkaloids (PAs) type, content and risk assessment in the three Boraginaceae used in TCM, involving Arnebia euchroma (AE), A. guttata (AG), and Lithospermum erythrorhizon (LE). Method: A UHPLC-MS/MS method was established to simultaneously determine eight pyrrolizidine alkaloids (PAs), namely intermedine, lycopsamine, intermedine N-oxide, lycopsamine N-oxide, 7-acetyllycopsamine, 7-acetyllycopsamine N-oxide, echimidine N-oxide, and echimidine in the three herbs. Based on these results, the risk assessment was explored using the routine margin of exposure (MOE) combined with relative potency (REP) for oral and external usage, respectively. Results and Conclusion: Imermedine and imermedine N-oxide were common components in the eight tested PAs. 7-acetyllycopsamine and its N-oxide were not detected in AE; echimidine and its N-oxide were not detected in AG; lycopsamine and its N-oxide, 7-acetyllycopsamine and its N-oxide were not detected in LE. The total contents of 8 PAs in 11 batches of AG was341.56-519.51 µg/g; the content in 15 batches of LE was 71.16-515.73 µg/g, and the content in 11 batches of AE was 23.35-207.13 µg/g. Based on these results, the risk assessment was explored using MOE combined with REP for oral and external usage, respectively. The findings of the risk assessment method of PAs based on MOE combined with the REP factor were consistent with the clinical toxicity results. As an oral herb, AE had low risk or no risk due to its low PA contents, and individual batches of LE were medium risk, while attention should be paid to their clinical use.AG was also low risk. The external use of the three Boraginaceae used in TCM was not associated with any risk. This study systematically explored the PA type and content of the three Boraginaceae used in TCM. Additionally, the refined risk assessment of PAs based on REP provided a more scientific basis for quality evaluation and rational use of the medicinal Boraginaceae used in TCM to improve public health.

Care Endpoints in Adults With Type 2 Diabetes: Screening and Therapeutic Targets at a Canadian Tertiary Diabetes Care Centre.

OBJECTIVES: Although national diabetes guidelines recommend targets for various health parameters, studies have demonstrated a gap between recommendations and real-life practice. The objectives of the present study were to 1) assess measurements in type 2 diabetes (T2DM) care performed by diabetologists in tertiary care, 2) determine whether these measurements were within recommended targets by Canadian guidelines, and 3) identify how these measurements compare with previously published Canadian studies. METHODS: A retrospective chart review analyzed electronic medical records of patients seen by diabetes specialists at the McGill University Health Centre (MUHC). Patients 18 to 75 years of age and diagnosed with T2DM were assessed for blood pressure <130/80 mmHg, low-density lipoprotein cholesterol (LDL-C) ≤2 mmol/L and glycated hemoglobin (A1C) ≤7%. Urinary albumin:creatinine ratio (uACR) was also assessed. Comparisons were made with existing literature data. RESULTS: The percentages of patients with recent screening of A1C, LDL-C, blood pressure and uACR were higher compared with the earlier studies. The calculated means for A1C, LDL-C and blood pressure were comparable with those studies. The percentage of measurements achieving target was comparable with subspecialty care data but differed from primary care data. CONCLUSIONS: Patients with T2DM at the MUHC receive guideline-based measurements of health parameters more frequently than at other institutions. Achievement of target values was closer to that seen by Canadian specialists than by primary care. Although further analyses are necessary to help implement effective strategies for improvement, quality assurance is nonetheless an essential part of ensuring the standards of tertiary care.

Nonlinear Bloch dynamics and spin-wave generation in a Bose-Hubbard ladder subject to effective magnetic field.

The two-leg magnetic ladder is the simplest and ideal model to reflect the coupling effects of lattice and magnetic field. It is of great significance to study some novel phases, topological characteristics, and chiral characteristics in condensed matter physics. In particular, the left-right leg degree of freedom can be regarded as a pseudospin, and the two-leg magnetic ladder also provides an ideal platform for the study of spin dynamics. Here the ground state, Bloch oscillations (BOs), and spin dynamics of the interacting two-leg magnetic ladder subject to an external linear force are studied by using variational approach and numerical simulation. In the absence of the external linear force, the critical condition of transition between the zero-momentum state and plane-wave state is obtained analytically, and the physical mechanism of the ground-state transition is revealed. When the external linear force presents, the occurrence of BOs excites the spin dynamics, and we reveal the chiral BOs and the accompanied spin dynamics of the system in different ground states. In particular, we further study the influence of periodically modulated linear force on BOs and spin dynamics. The frequencies of the linear force corresponding to the resonances and pseudoresonances are obtained analytically, which result in rich nonlinear dynamics. In resonances, stable and strong BOs (with larger amplitude) are observed. In pseudoresonances, because the pseudoresonance frequencies are related to the initial momentum and phase of the wave packet, a dispersion effect takes place and strong diffusion of wave packet occurs. When the frequency is nonresonant, drift and weak dispersion of wave packet occur simultaneously with the wave-packet oscillation. In all cases, the wave-packet dynamics is accompanied with periodic but anharmonic pseudospin oscillation. The BOs and spin dynamics are effectively controlled by periodically modulating the linear force.

GOx-encapsulated iron-phenolic networks power catalytic cascade to eradicate bacterial biofilms.

Bacterial biofilms, especially ones caused by multi-drug resistant strains, are increasingly posing a significant threat to human health. Inspired by nature, we report the fabrication of glucose oxidase-loaded iron-phenolic networks that can power the cascade reaction to generate free radicals to eradicate bacterial biofilms. A soft template, sodium deoxycholate, is employed to guarantee glucose oxidase activity during encapsulation, yielding the porous nanocomplexes after removing the template. The porous nature of nanocomplexes, characterized via transmission electron microscopy, N2 adsorption isotherms, and thermogravimetric analysis, facilitates the diffusion of substrates and products during the cascade reaction and protects glucose oxidase from protease attack. Our optimized nanocomplexes (Fe-GA/GOx) could efficiently kill drug-resistant ESKAPE pathogens, including the clinically isolated strains and eradicate their biofilms. In this regard, Fe-GA/GOx could induce over 90% of the biomass of Klebsiella pneumoniae and Staphylococcus aureus biofilms. In the murine peritonitis infection model induced by Staphylococcus aureus and pneumonia model induced by Klebsiella pneumoniae, our Fe-GA/GOx nanocomplexes could efficiently eradicate the bacteria (over 3-log reduction in colony-forming units) and alleviate the inflammatory response without notable side effects on normal tissues. Therefore, our strategy may provide an efficient alternative treatment to combat bacterial biofilms and address the emergence of drug resistance.

Optical characteristics of bilayer decoupling MoS2 grown by the CVD method.

Study of exciton recombination process is of great significance for the optoelectronic device applications of two-dimensional transition metal chalcogenides (TMDCs). This research investigated the decoupling MoS2 structures by photoluminescence (PL) measurements. First, PL intensity of the bilayer MoS2 (BLM) is about twice of that of the single layer MoS2 (SLM) at low temperature, indicating no transition from direct bandgap to indirect bandgap for BLM due to the decrease of interlayer coupling which can be shown by Raman spectra. Then, the localized exciton emission appears for SLM at 7 K but none for BLM, showing different exciton localization characteristics. The PL evolution with respect to the excitation intensity and the temperature further reveal the filling, interaction, and the redistribution among free exciton states and localized exciton states. These results provide very useful information for understanding the localized states and carrier dynamics in BLM and SLM.

Seed Germination and Seed Bank Dynamics of Eruca sativa (Brassicaceae): A Weed on the Northeastern Edge of Tibetan Plateau.

As a versatile cruciferous species, Eruca sativa is widely cultivated, but in some areas, it has become an invasive weed. There are few studies on its seed dormancy and soil seed bank. This research examined seed dormancy, germination, and dynamics of the soil seed bank of E. sativa, with a view to provide support for its prevention and control. We tested the effects of temperature, light, storage, water, and salinity stress on seed germination and burial depth on seedling emergence of E. sativa. Dynamics of the soil seed bank were determined with a 24 month in situ seed-burial study. Seeds of E. sativa can germinate in a temperature range of 5-35°C; moreover, they exhibited non-deep physiological dormancy (NDPD) at maturity, which can be broken by dry storage or exposure to low temperature in winter. Germination of E. sativa seeds was sensitive to water and salinity stress, and most seeds did not germinate at -0.3 MPa. When buried in soil in the field, seeds exhibited an annual dormancy/non-dormancy cycle and formed at least a short-term persistent soil seed bank. Seeds buried deeper than 5 cm can hardly emerge. Seeds of E. sativa have a wide germination temperature range and exhibited dormancy cycling, which promotes the formation of a persistent soil seed bank and enables it to better adapt to the harsh low-temperature climate of the Qinghai-Tibet Plateau. No-tillage would be a good management strategy for this species.

Phonon and Exciton Properties between WS2 and MoS2 Layers via Inversion Heterostructure Engineering.

Recently, two-dimensional (2D) van der Waals heterostructures (vdWHs) have exhibited emergent electronic and optical properties due to their peculiar phonons and excitons, which lay the foundation for the development of photoelectronic devices. The dielectric environment plays an important role in the interlayer coupling of vdWHs. Here, we studied the interlayer and extra-layer dielectric effects on phonon and exciton properties in WS2/MoS2 and MoS2/WS2 vdWHs by Raman and photoluminescence (PL) spectroscopy. The ultralow frequency (ULF) Raman modes are insensitive to atomic arrangement at the interface between 1LW and 1LM and dielectric environments of neighboring materials, and the layer breathing mode (LBM) frequency follows that of WS2. The shift of high-frequency (HF) Raman modes is attributable to interlayer dielectric screening and charge transfer effects. Furthermore, the energy of interlayer coupling exciton peak I is insensitive to atomic arrangement at the interface between 1LW and 1LM and its energy follows that of MoS2, but the slight intensity difference in inversion vdWHs means that the substrate's dielectric properties may induce doping on the bottom layer. This paper provides fundamental understanding of phonon and exciton properties of such artificially formed vdWHs structures, which is important for new insights into manipulating the performances of potential devices.

Prognosis assessment model based on low serum calcium in patients with acute pulmonary thromboembolism.

BACKGROUND AND OBJECTIVE: The pulmonary embolism severity index (PESI) and simplified PESI (sPESI) are recommended to recognize patients with acute pulmonary thromboembolism (PTE) with low prognosis risk, which is of great significance for treatment. This study aims to verify the influence of hypocalcaemia on the prognosis of patients with PTE and to establish a new prognosis assessment model. METHODS: This is an observational, multicentre study enrolling patients with PTE from February 2010 to June 2020 across 12 Chinese hospitals. Variables in PESI, serum calcium levels and patient survival status as of 5 July 2020 were collected. The area under the curve of the receiver operating characteristic curve, sensitivity, specificity and Youden index were used to evaluate model performance. RESULTS: In the cohort of 4196 patients with PTE, independent associations existed between hypocalcaemia and mid- and long-term mortalities (p <0.05). By including hypocalcaemia, the new 30-day death risk prediction rule, Peking Union Medical College Hospital rule (PUMCH rule), showed significantly higher specificity (0.622 [0.582, 0.661]; p <0.001) than the PESI (0.514 [0.473, 0.554]) and sPESI (0.484 [0.444, 0.525]) and similar sensitivity (0.963 [0.810, 0.999]; p = 0.161) with PESI (0.889 [0.708, 0.976]) and sPESI (0.963 [0.810, 0.999]) in the internal validation cohort. Well-performing predictive validity was also verified on a constructed external validation cohort. CONCLUSION: Hypocalcaemia is independently associated with mid- and long-term PTE mortalities. The PUMCH rule showed significantly higher specificity than the PESI and sPESI and similar sensitivity, which may be used as a prognostic assessment tool for patients with acute PTE.

Acute Respiratory Distress Syndrome Caused by Occupational Exposure to Waterproofing Spray: A Case Report and Literature Review.

Background: Acute respiratory distress syndrome (ARDS) is a serious respiratory disease, caused by severe infection, trauma, shock, inhalation of harmful gases and poisons and presented with acute-onset and high mortality. Timely and accurate identification will be helpful to the treatment and prognosis of ARDS cases. Herein, we report a case of ARDS caused by occupational exposure to waterproofing spray. To our knowledge, inhalation of waterproofing spray is an uncommon cause of ARDS, and what makes our case special is that we ruled out concurrent infections with some pathogens by using metagenomic next-generation sequencing (mNGS) as an auxiliary diagnosis, which presents the most comprehensive etiological examination of similar reports. Case Presentation: A previously healthy 25 years old delivery man developed hyperpyrexia, chest tightness, cough and expectoration. The symptoms occurred and gradually exacerbated after exposure to a waterproofing spray. The chest computed tomography (CT) finding showed diffuse ground glass and infiltrative shadows in both lungs. The diagnosis of ARDS related to waterproofing spray was established on the basis of comprehensive differential diagnosis and etiological examination. The patient achieved good curative effect after proper systemic glucocorticoid therapy. Conclusions: The diagnosis and differential diagnosis of acute respiratory failure for outdoor workers, such as delivery drivers or hikers, should be considered whether toxic aerosol exposure exists from daily contacts. The case can educate the public that more attention should be paid to avoid exposure to these chemicals by aerosols/ingestion mode and some preventive strategies should be taken in occupational environment. The treatment effect of glucocorticoids is significant in ARDS patients with general chemical damage caused by inhaling toxic gases and substances.

UHPLC-QQQ-MS/MS assay for the quantification of dianthrones as potential toxic markers of Polygonum multiflorum Thunb: applications for the standardization of traditional Chinese medicines (TCMs) with endogenous toxicity.

BACKGROUND: The raw and processed roots of Polygonum multiflorum Thunb (PM) are commonly used in clinical practice to treat diverse diseases; however, reports of hepatotoxicity induced by Polygoni Multiflori Radix (PMR) and Polygoni Multiflori Radix Praeparata (PMRP) have emerged worldwide. Thus, it is necessary for researchers to explore methods to improve quality standards to ensure their quality and treatment effects. METHODS: In the present study, an ultra-high performance liquid chromatography triple quadrupole mass spectrometry (UHPLC-QQQ-MS/MS) method was optimized and validated for the determination of dianthrones in PMR and PMRP using bianthronyl as the internal standard. Chromatographic separation with a gradient mobile phase [A: acetonitrile and B: water containing 0.1% formic acid (v/v)] at a flow rate of 0.25 mL/min was achieved on an Agilent ZORBAX SB-C18 column (2.1 mm × 50 mm, 1.8 µm). The triple quadrupole mass spectrometer (TQMS) was operated in negative ionization mode with multiple reaction monitoring for the quantitative analysis of six dianthrones. Moreover, compounds 5 and 6 were further evaluated for their cytotoxicity in HepaRG cells by CCK-8 assay. RESULTS: The UHPLC-QQQ-MS/MS method was first developed to simultaneously determine six dianthrones in PMR and PMRP, namely, polygonumnolides C1-C4 (1-4), trans-emodin dianthrones (5), and cis-emodin dianthrones (6). The contents of 1-6 in 90 batches of PMR were in the ranges of 0.027-19.04, 0.022-13.86, 0.073-15.53, 0.034-23.35, 0.38-83.67 and 0.29-67.00 µg/g, respectively. The contents of 1-6 in 86 batches of commercial PMRP were in the ranges of 0.020-13.03, 0.051-8.94, 0.022-7.23, 0.030-12.75, 0.098-28.54 and 0.14-27.79 µg/g, respectively. Compounds 1-4 were almost completely eliminated after reasonable processing for 24 h and the contents of compounds 5 and 6 significantly decreased. Additionally, compounds 5 and 6 showed inhibitory activity in HepaRG cells with IC50 values of 10.98 and 15.45 µM, respectively. Furthermore, a systematic five-step strategy to standardize TCMs with endogenous toxicity was proposed for the first time, which involved the establishment of determination methods, the identification of potentially toxic markers, the standardization of processing methods, the development of limit standards and a risk-benefit assessment. CONCLUSION: The results of the cytotoxicity evaluation of the dianthrones indicated that trans-emodin dianthrones (5) and cis-emodin dianthrones (6) could be selected as toxic markers of PMRP. Taking PMR and PMRP as examples, we hope this study provides insight into the standardization and internationalization of endogenous toxic TCMs, with the main purpose of improving public health by scientifically using TCMs to treat diverse complex diseases in the future.

Attenuated and delayed niacin skin flushing in schizophrenia and affective disorders: A potential clinical auxiliary diagnostic marker.

AIM: Schizophrenia and affective disorders all show high heterogeneity in clinical manifestations. A lack of objective biomarkers has long been a challenge in the clinical diagnosis of these diseases. In this study, we aimed to investigate the performance of niacin skin flushing in schizophrenia and affective disorders and determine its clinical potential as an auxiliary diagnostic marker. METHODS: In this case-control study, niacin skin-flushing tests were conducted in 613 patients (including 307 schizophrenia patients, 179 bipolar disorder patients, and 127 unipolar depression patients) and 148 healthy controls (HCs) with a modified method. Differences in niacin skin-flushing responses were compared with adjustment for gender, BMI, age, nicotine dependence, alcohol consumption and educational status. A diagnostic model was established based on a bivariate cut-off. RESULTS: Schizophrenia and affective disorders showed similar performance of niacin bluntness, characterized by attenuated flushing extent and reduced flushing rate. An innovative bivariate cut-off was established according to these two features, by which we could identify -patients with either schizophrenia or affective disorders from HCs with a sensitivity of 55.28%, a specificity of 83.56% and a positive predictive value of 93.66%. CONCLUSIONS: The niacin-induced skin flushing was prevalently blunted in patients with schizophrenia or affective disorders, indicating a promising potential as an auxiliary diagnostic marker in risk prediction and clinical management of these disorders. Additionally, the niacin-blunted subgroup implies a common biological basis in the investigated disorders, which provokes new thoughts in elucidating the pathological mechanisms.

Localization and spin dynamics of spin-orbit-coupled Bose-Einstein condensates in deep optical lattices.

We analytically and numerically discuss the dynamics of two pseudospin components Bose-Einstein condensates (BECs) with spin-orbit coupling (SOC) in deep optical lattices. Rich localized phenomena, such as breathers, solitons, self-trapping, and diffusion, are revealed and strongly depend on the strength of the atomic interaction, SOC, Raman detuning, and the spin polarization (i.e., the initial population difference of atoms between the two pseudospin components of BECs). The critical conditions for the transition of localized states are derived analytically. Based on the critical conditions, the detailed dynamical phase diagram describing the different dynamical regimes is derived. When the Raman detuning satisfies a critical condition, localized states with a fixed initial spin polarization can be observed. When the critical condition is not satisfied, we use two quenching methods, i.e., suddenly and linearly quenching Raman detuning from the soliton or breather state, to discuss the spin dynamics, phase transition, and wave packet dynamics by numerical simulation. The sudden quenching results in a damped oscillation of spin polarization and transforms the system to a new polarized state. Interestingly, the linear quenching of Raman detuning induces a controllable phase transition from an unpolarized phase to an expected polarized phase, while the soliton or breather dynamics is maintained.

Seed dormancy release of Halenia elliptica in response to stratification temperature, duration and soil moisture content.

BACKGROUND: Although the effect of cold stratification on seed dormancy release has been extensively studied for many species, knowledge of the role of stratifying temperature, soil moisture content and duration of stratification on seed dormancy release at the population level is limited. Here, we aimed to determine the response of seed dormancy release to these factors in six populations of Halenia elliptica. RESULTS: Seed dormancy release was more responsive to low than high temperatures, and no dormancy break occurred at 8 °C. Seed germination percentage increased first and then remained unchanged as stratifying soil moisture content increased from 0 to 24%. Seed dormancy release of populations from low altitude was more sensitive to increased stratifying temperature and decreased soil moisture content than those from high altitudes. CONCLUSIONS: Temperature and soil moisture changes resulting from global warming could affect seed dormancy release and consequently seedling establishment. Thus, incorporating data on seed dormancy release involving temperature, soil moisture content and stratification duration is beneficial for predicting plant species regeneration, migration and coexistence in a scenario of climate change.

Identification of common and severe COVID-19: the value of CT texture analysis and correlation with clinical characteristics.

OBJECTIVE: To explore the value of CT texture analysis (CTTA) for determining coronavirus disease 2019 (COVID-19) severity. METHODS: The clinical and CT data of 81 patients with COVID-19 were retrospectively analyzed. The texture features were extracted using LK2.1. The two-sample t test or Mann-Whitney U test was used to find the significant features. Minimum redundancy and maximum relevance (MRMR) method was performed to find the features with maximum correlation and minimum redundancy. These features were then used to construct a radiomics texture model to discriminate the severe patients using multivariate logistic regression method. Besides, a clinical model was also built. ROC analyses were conducted to evaluate the performance of two models. The correlations of clinical features and textural features were analyzed using the Spearman correlation analysis. RESULTS: Of the total cases included, 60 were common and 21 were severe. (1) For textural features, 20 radiomics features selected by MRMR showed good performance in discriminating the two groups (AUC > 70%). (2) For clinical features, chi-square tests or Mann-Whitney U tests identified 16 clinical features as significant, and 12 were discriminative (p < 0.05) between two groups analyzed by univariate logistic analysis. Of these, 10 had an AUC > 70%. (3) Prediction models for textural features and clinical features were established, and both showed high predictive accuracy. The AUC values of textural features and clinical features were 0.93 (0.86-1.00) and 0.95 (0.95-0.99), respectively. (4) The Spearman correlation analysis showed that most textural and clinical features had above-moderate correlations with disease severity (> 0.4). CONCLUSION: Texture analysis can provide reliable and objective information for differential diagnosis of COVID-19. KEY POINTS: • CT texture analysis can well differentiate common and severe COVID-19 patients. • Some textural features showed above-moderate correlations with clinical factors. • CT texture analysis can provide useful information to judge the severity of COVID-19.

Subunit interactions and arrangements in the fission yeast Mis16-Mis18-Mis19 complex.

Centromeric chromatin in fission yeast is distinguished by the presence of nucleosomes containing the histone H3 variant Cnp1CENP-A Cell cycle-specific deposition of Cnp1 requires the Mis16-Mis18-Mis19 complex, which is thought to direct recruitment of Scm3-chaperoned Cnp1/histone H4 dimers to DNA. Here, we present the structure of the essential Mis18 partner protein Mis19 and describe its interaction with Mis16, revealing a bipartite-binding site. We provide data on the stoichiometry and overall architecture of the complex and provide detailed insights into the Mis18-Mis19 interface.

WD40 repeat and FYVE domain containing 3 is essential for cardiac development.

AIMS: WD40 repeat and FYVE domain containing 3 (WDFY3) is an adaptor protein involved in selective degradation of protein aggregates by autophagy. Recent studies have revealed that Wdfy3 is critical in the regulation of brain development and osteoclastogenesis in vivo. However, the function of Wdfy3 in cardiac development remains completely unknown. In this study, we explore the role of Wdfy3 in cardiac morphogenesis using Wdfy3-deficient mice. METHODS AND RESULTS: Wdfy3 was expressed in the developing heart in mice and peaked at embryonic day 12.5 (E12.5). Loss of Wdfy3 in mice led to embryonic and neonatal lethality. Wdfy3-deficient mice displayed various congenital heart defects including membranous ventricular septal defect (VSD), aortic overriding (AO), double outlet right ventricle (DORV), thinning of ventricular wall, ventricular dilation, and disorganized ventricular trabeculation at E14.5. Cell proliferation was reduced in the hearts from Wdfy3-deficient mice at E12.5 and E14.5, which was associated with enhanced p21 expression. Cardiomyocyte differentiation was diminished as demonstrated by reduced Myh6 and MLC2v in Wdfy3-deficient mice at E14.5. In addition, Nkx2-5 and Mef2c, two cardiac transcription factors regulating cardiomyocyte differentiation, were decreased in Wdfy3-deficient mice at E14.5. Apoptotic cell death remained unaltered. These data suggest that reduced cell proliferation and cardiomyocyte differentiation contribute to cardiac defects in Wdfy3-deficient mice. Mechanistically, loss of Wdfy3 led to a reduction in protein levels of Notch 1 intracellular domain and its downstream targets Hes1 and Hey1, which was accompanied with enhanced full-length Notch1 protein levels. In vitro luciferase assay showed that Wdfy3 deficiency induced activity of p21 promoter, while diminished activity of Hes1 promoter through modulation of Notch1 signalling. Moreover, Wdfy3 was co-localized with Notch1 in primary embryonic cardiomyocytes. Endogenous Wdfy3 physically interacted with full-length Notch1 in the developing heart. These results suggest that Notch1 signalling is perturbed in the hearts from Wdfy3-deficient mice. No alteration of autophagy was detected in the hearts from Wdfy3-deficient mice. CONCLUSION: Taken together, our data suggest that Wdfy3 plays an essential role in cardiac development, which may be mediated by modulation of Notch1 signalling.