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We provide an in silico study of stochastic viral infection extinction from a pharmacokinetical viewpoint. Our work considers a non-specific antiviral drug that increases the virus clearance rate, and we investigate the effect of this drug on early infection extinction. Infection extinction data are generated by a hybrid multiscale framework that applies both continuous and discrete mathematical approaches. The central result of our paper is the observation, analysis and explanation of a linear relationship between the virus clearance rate and the probability of early infection extinction. The derivation behind this simple relationship is given by merging different mathematical toolboxes.

Abstract Background Participatory surveillance of self-reported symptoms and vaccination status can be used to supplement traditional public health surveillance and provide insights into vaccine effectiveness and changes in the symptoms produced by an infectious disease. The University of Maryland COVID Trends and Impact Survey provides an example of participatory surveillance that leveraged Facebook’s active user base to provide self-reported symptom and vaccination data in near real-time. Methods Here, we develop a methodology for identifying changes in vaccine effectiveness and COVID-19 symptomatology using the University of Maryland COVID Trends and Impact Survey data from three middle-income countries (Guatemala, Mexico, and South Africa). We implement conditional logistic regression to develop estimates of vaccine effectiveness conditioned on the prevalence of various definitions of self-reported COVID-like illness in lieu of confirmed diagnostic test results. Results We highlight a reduction in vaccine effectiveness during Omicron-dominated waves of infections when compared to periods dominated by the Delta variant (median change across COVID-like illness definitions: −0.40, IQR[−0.45, −0.35]. Further, we identify a shift in COVID-19 symptomatology towards upper respiratory type symptoms (i.e., cough and sore throat) during Omicron periods of infections. Stratifying COVID-like illness by the National Institutes of Health’s (NIH) description of mild and severe COVID-19 symptoms reveals a similar level of vaccine protection across different levels of COVID-19 severity during the Omicron period. Conclusions Participatory surveillance data alongside methodologies described in this study are particularly useful for resource-constrained settings where diagnostic testing results may be delayed or limited.

Abstract In recent decades, the role of tumor biomechanics on cancer cell behavior at the primary site has been increasingly appreciated. However, the effect of primary tumor biomechanics on the latter stages of the metastatic cascade, such as metastatic seeding of secondary sites and outgrowth remains underappreciated. This work sought to address this in the context of triple negative breast cancer (TNBC), a cancer type known to aggressively disseminate at all stages of disease progression. Using mechanically tuneable model systems, mimicking the range of stiffness's typically found within breast tumors, it is found that, contrary to expectations, cancer cells exposed to softer microenvironments are more able to colonize secondary tissues. It is shown that heightened cell survival is driven by enhanced metabolism of fatty acids within TNBC cells exposed to softer microenvironments. It is demonstrated that uncoupling cellular mechanosensing through integrin β1 blocking antibody effectively causes stiff primed TNBC cells to behave like their soft counterparts, both in vitro and in vivo. This work is the first to show that softer tumor microenvironments may be contributing to changes in disease outcome by imprinting on TNBC cells a greater metabolic flexibility and conferring discrete cell survival advantages.

As a kind of new material, nanomagnetic Fe3O4 (NMF) has many advantages in water and wastewater treatment. In this paper, the adsorption characteristic for arsenic(III) (As) by NMF was studied, and the adsorption was compared with the traditional adsorbent of activated carbon (AC) and modified activated carbon (MAC). The results showed that the NMF had high adsorption performance for As, and the adsorption performance of modified activated carbon and activated carbon were far lower than that of magnetic nanomagnetic Fe3O4. The adsorption capacity for As with NMF, MAC, and AC was 0.189 mg.g-1, 0.023 mg.g-1 and 0.013 mg.g-1 in 0.25 mg.L-1 As solution, respectively. The adsorption rate for As was different from the three adsorbents. For NMF, it needs only 10 minutes to reach an adsorption balance, while the time to balance was 20 minutes for MAC and more than 120 minutes for AC. The adsorption for As by the three adsorbents all conform to Langmuir adsorption isotherm, and the adsorption kinetics for As by the three adsorbents were in accordance with the pseudo-second-order kinetics model. The adsorption efficiency of MAC and AC was lower than nanomagnetic Fe3O4. The nanomagnetic Fe3O4 was an effective adsorbent for arsenic.

BackgroundThe third most severe COVID-19 wave in the middle of 2021 coincided with the dual challenges of limited vaccine supply and lagging acceptance in Bangkok, Thailand. Understanding of persistent vaccine hesitancy during the “608” campaign to vaccinate those aged over 60 years and 8 medical risk groups was needed. On-the-ground surveys place further demands on resources and are scale limited. We leveraged the University of Maryland COVID-19 Trends and Impact Survey (UMD-CTIS), a digital health survey conducted among daily Facebook user samples, to fill this need and inform regional vaccine rollout policy. ObjectiveThe aims of this study were to characterize COVID-19 vaccine hesitancy, frequent reasons for hesitancy, mitigating risk behaviors, and the most trusted sources of COVID-19 information through which to combat vaccine hesitancy in Bangkok, Thailand during the 608 vaccine campaign. MethodsWe analyzed 34,423 Bangkok UMD-CTIS responses between June and October 2021, coinciding with the third COVID-19 wave. Sampling consistency and representativeness of the UMD-CTIS respondents were evaluated by comparing distributions of demographics, 608 priority groups, and vaccine uptake over time with source population data. Estimates of vaccine hesitancy in Bangkok and 608 priority groups were tracked over time. Frequently cited hesitancy reasons and trusted information sources were identified according to the 608 group and degree of hesitancy. Kendall tau was used to test statistical associations between vaccine acceptance and vaccine hesitancy. ResultsThe Bangkok UMD-CTIS respondents had similar demographics over weekly samples and compared to the Bangkok source population. Respondents self-reported fewer pre-existing health conditions compared to census data overall but had a similar prevalence of the important COVID-19 risk factor diabetes. UMD-CTIS vaccine uptake rose in parallel with national vaccination statistics, while vaccine hesitancy and degree of hesitancy declined (−7% hesitant per week). Concerns about vaccination side effects (2334/3883, 60.1%) and wanting to wait and see (2410/3883, 62.1%) were selected most frequently, while “not liking vaccines” (281/3883, 7.2%) and “religious objections” (52/3883, 1.3%) were selected least frequently. Greater vaccine acceptance was associated positively with wanting to “wait and see” and negatively with “don’t believe I need (the vaccine)” (Kendall tau 0.21 and −0.22, respectively; adjusted P

Two nearly degenerate positive-parity bands with the πg9/22⊗νg9/2−1 configuration and three nearly degenerate negative-parity bands with the πg9/2(p3/2,f5/2)⊗νg9/2−1 configuration have been identified in 81Kr. They are interpreted as chiral doublet bands and pseudospin-chiral triplet bands, which is supported by the constrained covariant density functional theory and the multiparticle plus rotor model calculations. The present work reports two new chiral configurations πg9/22⊗νg9/2−1 and πg9/2(p3/2,f5/2)⊗νg9/2−1, and the first example of pseudospin-chiral triplet bands involving the π(p3/2,f5/2) pseudospin doublet.

Abstract Plants adjust their shoot growth to acclimate to changing environmental factors, such as to enhanced Ultraviolet-B (UV-B) radiation. However, people have ignored that plant roots can also respond to UV-B light. Here, we find the morphology curled wheat roots under UV-B radiation, that we call, “bending roots.” The curly region is the transition zone of the root after observed at the cellular level. After exposed to enhanced UV-B radiation for 2 d (10.08 KJ/m2/d), cell size decreased and actin filaments gathered in wheat roots. We also find that H2O2 production increased and that content of the indole-3-acetic acid (IAA) increased remarkably. The pharmacological experiment revealed that actin filaments gathered and polymerized into bundles in the wheat root cells after irrigated H2O2 and IAA. These results indicated that actin filaments changed their distribution and formed the “bending root,” which was related to H2O2 production and increase in IAA. Overall, actin filaments in wheat root cells could be a subcellular target of UV-B radiation, and its disruption determines root morphology.

Several satellites have been launched to monitor the increasing concentrations of greenhouse gases, especially CO2 and CH4 in the atmosphere, through backscattered hyperspectral radiance in the shortwave infrared (SWIR) band. The vertical profiles of greenhouse gases and aerosols could strongly affect the results from these instruments. To investigate the effects of the vertical distribution of CO2 on the uncertainty of SWIR satellite retrieval results, we conducted observations of the vertical profiles of CO2, CH4 and aerosol particles at 0.6–7 km above sea level using a Beechcraft King Air 350ER in Jiansanjiang (46.77∘ N, 131.99∘ E), Heilongjiang Province, northeast China, on 7–12 August 2018. The profiles from this aircraft captured a decrease in CO2 from 2 km to the minimum altitude due to the absorption of vegetation at the surface in summer. CH4 measurements showed about a 0.2 ppm increase from 2.0 to 0.6 km on 10 August, which may result from emissions from the large area of paddy fields below, and a constant mole fraction between 1.951 and 1.976 ppm was recorded at 2 km and above. Comparison of CO2 profiles from a new version of the carbon cycle data assimilation system Tan-Tracker (v1), retrievals from OCO-2 and aircraft measurements was conducted. The results from OCO-2 and the assimilation model system Tan-Tracker captured the vertical structure of CO2 above 3 km, whereas below 3 km the values from OCO-2 and the Tan-Tracker model were lower than those from in situ measurements. Column-averaged CO2 volume mole fractions calculated from in situ measurements showed biases of -4.68±0.44 ppm (-1.18±0.11%) compared to OCO-2 retrievals.

The solid-phase peptide synthesis (SPPS) strategy, as the main procedure of peptide manufacturing, has a profound impact on the research of peptides. The rapid development of nanotechnology is expected to promote the evolution of the solid phase to miniaturization, convenience and multi-function. In this work, silica-coated magnetic ferriferous oxide (Fe3O4) nanoparticles (MNP/SiO2) were used as new generation of solid phase for SPPS in Fmoc chemistry. The superparamagnetic solid phase facilitated a multi-step synthesis reaction due to its magnetic maneuverability, which could efficiently separate reaction intermediates, and were then redispersed in the next-step synthetic solution for peptide elongation. In addition, this strategy further allowed the simultaneous acquisition of magnetic nanoparticle–peptide conjugates as available bioprobes to examine the biological function of synthesized peptides. The feasibility of this novel magnetic nanoparticle-based solid phase peptide synthesis (MNP-SPPS) strategy was confirmed by the synthesis of arginine-glycine-aspartic acid-glycine-glycine (RGDGG) as a model pentapeptide. The simultaneously acquired magnetic nanoparticle–peptide conjugates (RGDGG-MNP/SiO2), possessing excellent biological functions, could be recognized and further internalized by tumor cells through receptor-mediated endocytosis, thereby achieving the extraction and removal of malignant cells in vitro under an external magnetic field. The RGDGG-MNP/SiO2 could further be used as a contrasting agent for tumor-targeting T2 magnetic resonance imaging in vivo. This study developed a novel MNP-SPPS strategy that could realize the simple synthesis of peptides, and the synchronously obtained nanoprobes could quickly detect the biological activity of the target synthetic sequence. This strategy may have broad application prospects in combinatorial chemistry and the construction of peptide libraries in the future.

Abstract Background Obstetric dfficult airway is a leading cause of maternal morbidity and mortality. The laryngeal mask airway (LMA) is often used as a rescue airway device after failed intubation, however, little is known about predictors of difficult LMA insertion, particularly in obstetrics. Since Mallampati scores of III/IV has been associated with difficult tracheal intubation, our present study aims to investigate if Mallampati score (MP) could predict airway outcomes for LMA use in obstetrics. Methods This prospective cohort study was performed at a single-center: Quanzhou Women’s and Children’s Hospital, Fujian Province, China. Five hundred and eighty-four parturients undergoing elective cesarean section under general anesthesia were recruited. The primary outcome was time to effective ventilation, and secondary outcomes included first attempt insertion success, seal pressure, ventilation and hemodynamic parameters, occurrence of clinical aspiration, and maternal and fetal outcomes. Results The parturients were classified into two groups based on MP of III/IV (High MP: 61) versus I/II (Low MP: 523). BMI was higher in the High MP group than in the Low MP group (mean (SD) 29.3 (7.0) vs 26.8 (3.1), p

Abstract Background The obstetric airway is a significant cause of maternal morbidity and mortality. Endotracheal intubation is considered the standard of care but the laryngeal mask airway (LMA) has gained acceptance as a rescue airway and has been incorporated into the obstetric airway management guidelines. In this randomized controlled equivalence trial, we compared the Supreme LMA (SLMA) with endotracheal intubation (ETT) in managing the obstetric airway during cesarean section. Methods Parturients who underwent elective cesarean section under general anesthesia were randomized to receive either an SLMA or ETT as their airway device. Our primary outcome was first-attempt insertion success. Successful insertion was defined as adequate bilateral air entry with auscultation and the presence of end-tidal carbon dioxide on the capnogram. The first-attempt insertion success rate was compared using the Chi-Square test. Secondary outcomes included time-to-ventilation, seal pressure, ventilation/hemodynamic parameters, occurrence of clinical aspiration, fetal outcomes, and maternal side effects associated with the airway device. Results We recruited 920 parturients (460 SLMA, 460 ETT) who underwent elective cesarean section under general anesthesia. Patient characteristics were similar between the groups. First attempt success was similar (Odds Ratio--ORSLMA/ETT: 1.00 (95%CI: 0.25, 4.02), p = 1.0000). SLMA was associated with reduced time to effective ventilation (Mean Difference--MD -22.96; 95%CI: − 23.71, − 22.21 s) compared to ETT group (p

Abstract Background The oncogenic receptor tyrosine kinase (RTK) ERBB2 is known to dimerize with other EGFR family members, particularly ERBB3, through which it potently activates PI3K signalling. Antibody-mediated inhibition of this ERBB2/ERBB3/PI3K axis has been a cornerstone of treatment for ERBB2-amplified breast cancer patients for two decades. However, the lack of response and the rapid onset of relapse in many patients now question the assumption that the ERBB2/ERBB3 heterodimer is the sole relevant effector target of these therapies. Methods Through a systematic protein-protein interaction screen, we have identified and validated alternative RTKs that interact with ERBB2. Using quantitative readouts of signalling pathway activation and cell proliferation, we have examined their influence upon the mechanism of trastuzumab- and pertuzumab-mediated inhibition of cell growth in ERBB2-amplified breast cancer cell lines and a patient-derived xenograft model. Results We now demonstrate that inactivation of ERBB3/PI3K by these therapeutic antibodies is insufficient to inhibit the growth of ERBB2-amplified breast cancer cells. Instead, we show extensive promiscuity between ERBB2 and an array of RTKs from outside of the EGFR family. Paradoxically, pertuzumab also acts as an artificial ligand to promote ERBB2 activation and ERK signalling, through allosteric activation by a subset of these non-canonical RTKs. However, this unexpected activation mechanism also increases the sensitivity of the receptor network to the ERBB2 kinase inhibitor lapatinib, which in combination with pertuzumab, displays a synergistic effect in single-agent resistant cell lines and PDX models. Conclusions The interaction of ERBB2 with a number of non-canonical RTKs activates a compensatory signalling response following treatment with pertuzumab, although a counter-intuitive combination of ERBB2 antibody therapy and a kinase inhibitor can overcome this innate therapeutic resistance.

Nitrous acid (HONO) can strongly affect atmospheric photochemistry in polluted regions through the production of hydroxyl radicals (OHs). In January 2017, a severe pollution episode occurred in the Pearl River Delta (PRD) of China, with maximum hourly PM2.5, ozone, and HONO levels reaching 400 µg m−3, 150 ppb, and 8 ppb, respectively, at a suburban site. The present study investigated the sources and processes generating such high HONO concentrations and the role of HONO chemistry in this severe winter episode. Four recently reported HONO sources were added to the Community Multiscale Air Quality (CMAQ) model, including RH-dependent (relative humidity) and light-enhancing effects on heterogeneous reactions, photolysis of particulate nitrate in the atmosphere, and photolysis of HNO3 and nitrate on surfaces. The revised model reproduced the observed HONO and significantly improved its performance for O3 and PM2.5. The model simulations showed that the heterogeneous generation on surfaces (with RH and light effects) was the largest contributor (72 %) to the predicted HONO concentrations, with the RH-enhancing effects more significant at nighttime and the light-enhancing effects more important in the daytime. The photolysis of total nitrate in the atmosphere and deposited on surfaces was the dominant HONO source during noon and afternoon, contributing above 50 % of the simulated HONO. The HONO photolysis was the dominant contributor to HOx production in this episode. With all HONO sources, the daytime average O3 at the Heshan site was increased by 24 ppb (or 70 %), compared to the simulation results without any HONO sources. Moreover, the simulated mean concentrations of TNO3 (HNO3+ fine particle NO3−) at the Heshan site, which was the key species for this haze formation, increased by about 17 µg m−3 (67 %) due to the HONO chemistry, and the peak enhancement reached 55 µg m−3. This study highlights the key role of HONO chemistry in the formation of winter haze in a subtropical environment.

Histone deacetylases (HDACs) are enzymes that play a key role in regulating gene expression by remodeling chromatin structure. An imbalance of histone acetylation caused by deregulated HDAC expression and activity is known to promote tumor progression in a number of tumor types, including neuroblastoma, the most common solid tumor in children. Consequently, the inhibition of HDACs has emerged as a potential strategy to reverse these aberrant epigenetic changes, and several classes of HDAC inhibitors (HDACi) have been shown to inhibit tumor proliferation, or induce differentiation, apoptosis and cell cycle arrest in neuroblastoma. Further, the combined use of HDACi with other chemotherapy agents, or radiotherapy, has shown promising pre-clinical results and various HDACi have progressed to different stages in clinical trials. Despite this, the effects of HDACi are multifaceted and more work needs to be done to unravel their specific mechanisms of actions. In this review, we discuss the functional role of HDACs in neuroblastoma and the potential of HDACi to be optimized for development and use in the clinic for treatment of patients with neuroblastoma.

Abstract Background The mechanism of maternal immune tolerance of the semi‐allogenic fetus has been explored extensively. The immune reaction to defend from invasion by pathogenic microorganisms should be maintained during pregnancy. An imbalance between the immune tolerance to the fetus and immune activation to the pathogenic organisms is associated with poor pregnancy outcomes. This emphasizes that the immune mechanism of successful reproduction is not just immune suppression, but adequate immune modulation. Methods In this review, the action of i.v. immunoglobulin G (IVIg) on the immune system and its efficacy in reproductive failure (RF) was summarized. Also suggested is the indication of IVIg therapy for women with RF. Main findings (Results) Based on the mechanism of the immune regulation of IVIg and following confirmation of the immune modulation effects of it in various aberrant immune parameters in patients with RF, it is obvious that IVIg is effective in recurrent pregnancy losses and repeated implantation failures with immunologic disturbances. Conclusion The authors recommend IVIg therapy in patients with RF with aberrant cellular immunologic parameters, including a high natural killer cell proportion and its cytotoxicity or elevated T helper 1 to T helper 2 ratio, based on each clinic's cut‐off values. Further clinical studies about the safety of IVIg in the fetus and its efficacy in other immunologic abnormalities of RF are needed.

This paper selected 2006-2016 MODIS NDVI data with a spatial resolution of 500m and time resolution of 16d, got the 11 years’ time series NDVI data of Maowusu sandy land through mosaicking, projection transformation, cutting process in batch. Analysed the spatial and temporal distribution and variation characteristics of vegetation cover in year, season and month time scales by maximum value composite, and unary linear regression analysis. Then, we combined the meteorological data of 33 sites around the sandy area, analysed the response characteristics of vegetation cover change to temperature and precipitation through Pearson correlation coefficient. Studies have shown that: (1) The NDVI value has a stable increase trend, which rate is 0.0075 / a. (2) The vegetation growth have significantly difference in four seasons, the NDVI value of summer > autumn > spring > winter. (3) The NDVI value change trend is conformed to the gauss normal distribution in a year, and it comes to be largest in August, its green season is in April, and yellow season is in the middle of November, the growth period is about 220 d. (4) The vegetation has a decreasing trend from the southeast to the northwest, most part is slightly improved, and Etuokeqianqi improved significantly. (5) The correlation indexes of annual NDVI with temperature and precipitation are −0.2178 and 0.6309, the vegetation growth is mainly affected by precipitation. In this study, a complete vegetation cover analysis and evaluation model for sandy land is established. It has important guiding significance for the sand ecological environment protection.

β-decay studies of neutron-rich nuclei in and around the “island of inversion” have been performed. With a systematic investigation of half-lives for the isotonic chains from N=19 to 22, conspicuous kinks observed at Z=13 provide a clear signature of a boundary on the northern (high-Z) side of the island. Based on the comparison with shell model calculations using Gogny D1S and SDPF-M interactions, a newly determined 22+ state in 34Si at 4519 keV presents an experimental evidence of triaxiality in this region and sheds more light on the structure of the transition across the northern boundary of the island.

The heavy ion fusion–evaporation reaction study for the high-spin spectroscopy of 75As has been performed via the reaction channel 70Zn(9Be, 1p3n)75As at a beam energy of 42 MeV. The collective structure especially a dipole band in 75As is established for the first time. The properties of this dipole band are investigated in terms of the self-consistent tilted axis cranking covariant density functional theory. Based on the theoretical description and the examination of the angular momentum components, this dipole band can be interpreted as a novel stapler band, where the valence neutrons in (1g9/2) orbital rather than the collective core are responsible for the closing of the stapler of angular momentum.

Norovirus (NoV) is a leading cause of epidemic acute non-bacterial gastroenteritis, and replicates through virion protein genome-linked (VPg)-primed or de novo RNA synthesis by RNA-dependent RNA polymerase (RdRp). VPg is a multifunctional protein that plays crucial roles in viral protein translation and genome replication. However, the interaction between the RdRp and this multifunctional VPg in NoV replication has been unknown. In this study, VPg derived from murine NoV (MNV) was found to mediate the formation of higher-order multimers or tubular fibrils of MNV RdRp, which led to significantly enhanced polymerase activity in vitro. The replication of MNV mutants containing a VPg-binding defective RdRp, based on the crystal structure of an RdRp-VPg(1-73) complex, was completely blocked in a cell culture system. Our data suggest that the interaction between RdRp and VPg plays a crucial role in the multimerization-mediated RdRp activity in vivo and consequently in MNV replication, which can provide a new target of therapeutic intervention for NoV outbreaks.