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Bioactive polyethylene incorporating hydrophobic PE-bearing macromonomers and hydrophilic PEGylated-peptide macromonomers was synthesized via ROMP. 3D-printed sheets of it with UHMWPE showed enhanced osteogenic activity for potential orthopaedic applications.

Targeting protein kinase C (PKC) family was found to repress the migration and resistance of non-small cell lung cancer cells to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs). However, none of the PKC inhibitors has been approved for anticancer therapy yet due to the limited efficacy in clinical trials, and the underlying mechanisms remain unclear. l-lactic acidosis, a common condition comprising high l-lactate concentration and acidic pH in the tumor microenvironment, has been known to induce tumor metastasis and drug resistance. In this study, l-lactic acid was found to reverse the inhibitory effects of pan-PKC inhibitors GO6983 on PKC activity, cell migration, and EGFR-TKI resistance, but these effects were not affected by the modulators of lactate receptor GPR81. Interestingly, blockade of lactate transporters, monocarboxylate transporter-1 and -4 (MCT1 and MCT4), attenuated the intracellular level of GO6983, and its inhibitory effect on PKC activity, suggesting that lactic acid promotes the resistance to PKC inhibitors by competing for the uptake through these transporters rather than by activating its receptor, GPR81. Our findings explain the underlying mechanisms of the limited response of PKC inhibitors in clinical trials.

Cutting force is a vital parameter that affects product quality. Proper control of the cutting force helps optimize the production process as it improves productivity and product quality. This paper assesses the influence of machining parameters, such as alloy steel hardness and workpiece diameters, to cutting forces when external cylindrical grinding by experimental methods. The cutting force was measured using a workpiece shaft-mounted sensor with a balanced bridge-type resistor sensor. Steel for testing: 40Cr, 9CrSi, 65Mn, and W18Cr4V, which were heat-treated at three different hardness levels: 40, 50, and 60 HRC. The Taguchi method's experimental results show that the main parameters affecting cutting forces are: Feed rate of the grinding wheel Sd, cutting depth t, and hardness of workpiece material on the HRC scale. Since then, we built a mathematical model of the normal cutting force function Fn and tangent cutting force function Ft according to Sd, t, and HRC of 9CrSi steel then tested again with three steel types: 40Cr, 65Mn, and W18Cr4V for quite similar results. The cutting force is controlled through cutting parameters suitable for different hardness and workpiece material based on this model.

Chronic heart failure (CHF) occurs in 4.3-28% of patients with diabetes mellitus and is most often associated with the presence of coronary heart disease, arterial hypertension and the direct adverse effects of insulin-resistance, hyperinsulinemia and hyperglycemia on the myocardium. Diabetes mellitus occurs in 12-47% of patients with CHF and can develop within several years after a diagnosis of HF in 22% of patients due to insulin-resistance of failure tissues. The presence of diabetes mellitus leads to a greater severity of clinical symptoms and hospitalization rate, worsening of quality of life and prognosis in CHF. A decreased left ventricular ejection fraction is an independent predictor of the poor prognosis in the patients with diabetes mellitus. The algorithm of the treatment of CHF in the patients with and without diabetes mellitus is not fundamentally different, but it requires taking into account the metabolic effects of the prescribed drugs. Angiotensin receptor-neprilysin inhibitor are increasingly used in clinical practice and are gradually replacing angiotensin-converting enzyme inhibitors and sartans in CHF both without diabetes mellitus and in its presence. Recently, the effectiveness of type 2 sodium glucose cotransporter inhibitors has been proven in patients with CHF with and without diabetes mellitus. This review is devoted to the relationship of diabetes mellitus and CHF, as well as the approaches to the management of such comorbid patients.

How basal cell carcinoma (BCC) interacts with its tumor microenvironment to promote growth is unclear. We use singe-cell RNA sequencing to define the human BCC ecosystem and discriminate between normal and malignant epithelial cells. We identify spatial biomarkers of tumors and their surrounding stroma that reinforce the heterogeneity of each tissue type. Combining pseudotime, RNA velocity–PAGA, cellular entropy, and regulon analysis in stromal cells reveals a cancer-specific rewiring of fibroblasts, where STAT1, TGF-β, and inflammatory signals induce a noncanonical WNT5A program that maintains the stromal inflammatory state. Cell-cell communication modeling suggests that tumors respond to the sudden burst of fibroblast-specific inflammatory signaling pathways by producing heat shock proteins, whose expression we validated in situ. Last, dose-dependent treatment with an HSP70 inhibitor suppresses in vitro vismodegib-resistant BCC cell growth, Hedgehog signaling, and in vivo tumor growth in a BCC mouse model, validating HSP70’s essential role in tumor growth and reinforcing the critical nature of tumor microenvironment cross-talk in BCC progression.

Thanh D Dinh,1,2 Hung N Nguyen,1 Ba Hai Le,1 Thuy TT Nguyen,1 Huong TL Nguyen1 1Department of Clinical Pharmacy, Hanoi University of Pharmacy, Hanoi, Vietnam; 2Phu Tho General Hospital, Việt Trì, Phu Tho Province, VietnamCorrespondence: Huong TL Nguyen, Department of Clinical Pharmacy, Hanoi University of Pharmacy, 13, 15 – Lê Thánh Tông, Hoà n Kiếm, Hà Nội, 100000, Vietnam, Tel +84904308406, Email huongntl@hup.edu.vnPurpose: The purpose of this study was to characterize the population-based pharmacokinetic (POP-PK) profile of imipenem in Vietnamese adult patients and to assess the probability of target attainment (PTA) of the pharmacokinetic/pharmacodynamic (PK/PD) parameter to determine the optimal dose.Patients and Methods: A POP-PK model of imipenem was developed in patients with severe infection from a 1500-bed general hospital in Vietnam, using MONOLIX 2019. After the initial dose infusion, 6 blood samples per patient were collected to measure plasma imipenem levels. Eight covariates (eg, age, weight) were investigated to ascertain their influence on imipenem’s PK. Monte Carlo simulations were performed to determine the PTA for the time in which the total steady-state imipenem concentrations remained above the MIC (T>MIC) for 40% and 100% of the dosing interval.Results: The best fit to the PK data was a two-compartment model with inter-individual variability (IIV) in clearance (CL), central volume of distribution (Vc), intercompartmental clearance (Q), and peripheral volume of distribution (Vp). Only creatinine clearance was retained as a covariate on CL in the final model. The typical value of CL and Vc were estimated to be 4.79 L/h and 11.1 L, respectively. The between-subject variability in this population was noted to be high (> 38%, especially for IIV on Q at 110%). Prolonged or continuous infusion demonstrated efficacy (40% T>MIC) against bacteria with a MIC of 4mg/L. To achieve 100% T>MIC or bacteria with MIC> 4 mg/L, however, the number of doses must be increased while maintaining the same daily dose for the 3-hour prolonged infusion regimen.Conclusion: A population pharmacokinetic model of imipenem was developed for Vietnamese adult patients with severe illness. By using Monte Carlo simulation, the appropriate dose has been suggested based on the bacterial MIC value and the targeted PK/PD goal.Keywords: imipenem, pharmacokinetic modeling, PK/PD, Monte Carlo, carbapenem

The reaction of carboxamides with phosphorus trichloride under heating at 75–80°C for 1 h in the presence of a 4-dimethylaminopyridine catalyst was used to synthesize imidoyl chlorides in yields of 63–99%.

Cubic magnetic nanoparticles with average sizes of 16.1 ± 2.2, 22.3 ± 3.5, and 37.4 ± 5.2 nm are obtained by a variety of means. The magnetic characteristics of these nanoparticles are studied as well. The samples are probed via X-ray diffraction to establish structural features, and the specific absorption rate (SAR) is analyzed as a function of the frequency and induction of an alternating magnetic field.

How basal cell carcinoma (BCC) interacts with its tumor microenvironment to promote growth is unclear. Here we use singe-cell RNA sequencing to define the human BCC ecosystem and discriminate between normal and malignant epithelial cells. We identify spatial biomarkers of both tumors and their surrounding stroma that reinforce the heterogeneity of each tissue type. Combining pseudotime, RNA velocity, cellular entropy, and regulon analysis in stromal cells reveal a cancer-specific rewiring of fibroblasts where STAT1, TGF-β, and inflammatory signals induce a non-canonical WNT5A program that maintains the stromal inflammatory state. Cell-cell communication modeling suggests that tumors respond to the sudden burst of fibroblast-specific inflammatory signaling pathways by producing heat shock proteins, which we validated in situ. Finally, dose-dependent treatment with an HSP70 inhibitor suppresses in vitro BCC cell growth and Hedgehog signaling and in vivo tumor growth in a BCC mouse model, validating HSP70’s essential role in tumor growth and reinforcing the critical nature of tumor microenvironment crosstalk in BCC progression.

N-Aryl(benzyl)adamantane-1-carboxamides were synthesized in 54–87% yields by reaction of adamantane-1-carboxylic acid with aromatic amines in the presence of phosphorus trichloride, 4-dimethylaminopyridine, and triethylamine on heating at 80°C for 8 h.

The article discusses the role of child interaction with a significant adult (parent, kindergarten teacher, caregiver) in child’s neurocognitive development within socio-cultural contexts of Russia and Vietnam. The article presents the results of a pilot study that included focus group interviews with kindergarten specialists from Russia and Vietnam. The pilot study sample consisted of 74 participants (72 women, 2 men), aged 32 to 54 years (M = 43.04; SD = 6.61). Of these, Russian participants (10 cities) — 42 people (40 women and 2 men) aged 32 to 50 (M = 40.19; SD = 6.28) and Vietnamese participants (1 city) — 32 people (32 women) aged 38 to 54 years (M = 46.67; SD = 5.12). The interviews followed the questionnaire developed by the authors. It consisted of 21 open-ended questions grouped in 3 blocks: Block 1. What characteristics and skills should be developed during early childhood? Where and how should these be developed? Block 2. How are children under 3 years of age developed? Block 3. Who is involved in the development of a child under 3 years of age? A comparative analysis of the responses of the Russian and Vietnamese kindergarten specialists revealed no significant differences between the groups, which suggests similarities in educational and developmental strategies of young children in a kindergarten environment. © 2019 Moscow State University of Psychology& Education. The reported study was funded by RFBR and VASS, project number 19-513-92001.

Graphene oxide (GO) is an oxygenated functionalized form of graphene that has received considerable attention because of its unique physical and chemical properties that are suitable for a large number of industrial applications. Herein, GO is rapidly obtained directly from the oxidation of graphene using an environmentally friendly modified Hummers method. As the starting material consists of graphene flakes, intercalant agents are not needed and the oxidation reaction is enhanced, leading to orders of magnitude reduction in the reaction time compared to the conventional methods of graphite oxidation. With a superior surface area, the graphene flakes are quickly and more homogeneously oxidized since the flakes are exposed at the same extension to the chemical agents, excluding the necessity of sonication to separate the stacked layers of graphite. This strategy shows an alternative approach to quickly producing GO with different degrees of oxidation that can be potentially used in distinct areas ranging from biomedical to energy storage applications.

We propose and implement a novel scheme for dissipatively pumping two qubits into a singlet Bell state. The method relies on a process of collective optical pumping to an excited level, to which all states apart from the singlet are coupled. We apply the method to deterministically entangle two trapped 40Ca+ ions. Within 16 pumping cycles, an initially separable state is transformed into one with 83(1)% singlet fidelity, and states with initial fidelity of ⪆70% converge onto a fidelity of 93(1)%. We theoretically analyze the performance and error susceptibility of the scheme and find it to be insensitive to a large class of experimentally relevant noise sources., Physical Review Letters, 128 (8), ISSN:0031-9007, ISSN:1079-7114

Background and Aims: A panel of experts (the Poseidon Group) introduced a new and more detailed stratification for poor ovarian responders in order to predict the prognosis of IVF outcome according to the sensitivity to FSH. However, various arguments about the management strategy of these patients still remain, including the convenience and the cost. Therefore, this study was conducted to compare the efficacy of mild and conventional GnRH antagonist ovarian stimulation prescribed in patients classified in Poseidon Group 4.Methods: This retrospective cohort study included 359 poor responder patients (Poseidon Group 4) treated with mild or conventional GnRH antagonist stimulation regimens from 8/2017 to 7/2019 at Tam Anh Hospital ART Center. The main outcomes were the index of Follicular Output Rate (FORT) or Follicle to Oocyte Index (FOI), the number of day-2 embryos and top-quality embryos obtained. The t-test and Mann–Whitney U test in SPSS v25.0 was used to analyze the continuous data and Chi-squared/Exact test was used for binary variables. Multiple linear regression analysis was done by using Stata versions 15.0 to measure association between primary endpoints with stimulation regimen controlled for covariates and possible confounding factors.Results: In the overall group of poor responders, the conventional GnRH antagonist protocol performed better than the mild protocol. Subsequently, data were analyzed according to the AFC. In women with AFC < 3, no significant differences were observed between the 2 regimens regarding FORT (p = 0.71), FOI (p = 0.12), the number of day-2-embryos (p = 0.052) and the number of top-quality embryos (p = 0.26). In contrast, in women with AFC ≥ 3, mild stimulation regimen resulted in significantly poorer outcome compared to the conventional GnRH antagonist regimen, regarding FORT (p < 0.01), FOI (p < 0.01), the number of day-2-embryos (p < 0.01) and top-quality embryos (p = 0.01).Conclusions: Considering poor responders classified in Poseidon Group 4, both ovarian stimulation regimens resulted in similar outcome for patients with a very low ovarian reserve (AFC < 3). In contrast, the GnRH conventional antagonist protocol with maximum initial FSH dose (300–375 IU/day) and supplementary LH (75–150 IU/day) was more effective than the mild one for patients whose ovarian reserve was less reduced. The Clinical Trial was approved by the Ethnical Biomedical Research Committee Tam Anh General Hospital.

Plastic microbeads are commonly used in many personal care products and can cause adverse impacts to the environment and ecosystem. The toxicological problem with these pollutants are due to their non-biodegradable materials, which washed down the drain; end up accumulating in the aquatic system causing increased frequency and quantity of items ingested by biota. Several polymers (e.g. Polyethylene) especially those found in plastic microbeads have been reported to be in tandem with other toxic contaminants serving as a vector for their transports in the environment. Thus, the legislative ban for plastic microbeads is used in some developed countries, but many countries including Vietnam do not take any legal action. This present study aimed at potential microbead’s existence in the cosmetic market of Ho Chi Minh City (HCMC). The list and ingredients of microbeads containing personal care products (toothpaste, facial cleanser/scrubs and body wash/scrubs) have been checked. The microbeads containing PCPs are common for all explored categories, especially in toothpaste. Data from the online questionnaire survey have shown that 98% of respondents have frequently used at least one microbead containing product. Four polymers (Polyethylene, Acrylates Copolymer Styrene/Acrylates Copolymer and Acrylates/C10-30 Alkyl Acrylate Crosspolymer) have been observed in the product package of several facial cleansers and body scrubs. Thus, the potential negative impacts of this contaminant should not be ignored.

Primary cilia loss is a common feature of advanced cancers. While primary cilia are necessary to initiate Hedgehog (HH)-driven cancers, how HH pathway activity is maintained in advanced cancers devoid of primary cilia is unclear. Here, we find that HH-driven basal cell carcinoma (BCC) accumulate mutations in the Alström and Usher syndrome genes in advanced and SMO inhibitorresistant tumors. Loss of Alström and Usher syndrome gene expression, which are common underlying causes of deafness and blindness, suppresses ciliogenesis and HH signaling. Atypical protein kinase C iota/lambda (aPKC) is a GLI1 kinase with higher expression in advanced BCCs and we show that a constitutively active isoform drives HH pathway activity and mutually antagonizes primary cilia. Overexpression of the constitutively active aPKC variant can maintain HH pathway activity in the absence of primary cilia and can drive resistance to the SMO antagonist vismodegib regardless of cilia status. Finally, superficial BCCs display less primary cilia and higher aPKC expression, which is inversely correlated in nodular BCC subtypes. Our results suggest aPKC may serve as a biomarker for SMO inhibitor sensitivity and a target for clinical application.

Results are presented from synthesizing and characterizing magnetite nanoparticles with spherical, cubic and octahedral geometry. Magnetic properties (saturation magnetization, residual magnetization, and coercive force), cytotoxicity, and T2 relaxivity are measured for the synthesized nanoparticles. They are characterized via X-ray diffraction and dynamic light scattering (hydrodynamic size and zeta potential). The effect the shape of the nanoparticles have on the values of T2 relaxivity is analyzed. Nontoxic magnetite nanoparticles coated with copolymer are excellent contrast agents for magnetic resonance imaging (MRI) and show better contrast properties than their commercial analogs (Rezovist, Ferumoxytol, Feridex).

Nb-doped TiO2 (TNO) is known as a multifunctional thin film. In this study, Ag was added to TNO thin films via a co-sputtering methodology to improve the properties of the films. X-ray diffraction, scanning electron microscopy and Raman spectroscopy were used to characterize the samples. The UV–Vis spectra indicated that the transparency of the samples decreased as the Ag content increased. The photocatalytic properties of the co-sputtered films were evaluated by photodegrading a methylene blue (MB) solution under ultraviolet (UV) radiation using back-side illumination; i.e., the UV light reaches the thin film through the Corning glass instead of the MB solution. By adding Ag into TNO films, their photocatalytic property significantly improved. The 2-min Ag-TNO film showed a maximum photocatalytic efficiency (k = 0.034 min−1) and good transparency of 70% in the visible range. Nevertheless, adding too much Ag led to a negative photocatalytic performance. The results suggested that the co-sputtering process is an efficient method to combine Ag with TNO thin films to improve their photocatalytic performance.

Actin polymerization is important to generate primary cilia. Drummond et al. show that upstream actin regulators are necessary for this process by controlling aPKC and Src kinase activity to promote Hedgehog signaling and restrict primary cilia., Primary cilia are polarized organelles that allow detection of extracellular signals such as Hedgehog (Hh). How the cytoskeleton supporting the cilium generates and maintains a structure that finely tunes cellular response remains unclear. Here, we find that regulation of actin polymerization controls primary cilia and Hh signaling. Disrupting actin polymerization, or knockdown of N-WASp/Arp3, increases ciliation frequency, axoneme length, and Hh signaling. Cdc42, a potent actin regulator, recruits both atypical protein pinase C iota/lambda (aPKC) and Missing-in-Metastasis (MIM) to the basal body to maintain actin polymerization and restrict axoneme length. Transcriptome analysis implicates the Src pathway as a major aPKC effector. aPKC promotes whereas MIM antagonizes Src activity to maintain proper levels of primary cilia, actin polymerization, and Hh signaling. Hh pathway activation requires Smoothened-, Gli-, and Gli1-specific activation by aPKC. Surprisingly, longer axonemes can amplify Hh signaling, except when aPKC is disrupted, reinforcing the importance of the Cdc42–aPKC–Gli axis in actin-dependent regulation of primary cilia signaling.

The assembly of graphene-based materials into nanofibres is of intense technological interest for numerous applications ranging from tissue engineering and drug delivery to fuel cells and space elevators. We demonstrate a composite nanofibre synthesis process using functionalised graphene structures in liquid medium (two-dimensional [2D] electrolytes) as building blocks. The approach consists in simultaneous scrolling and reacting 2D electrolytes, leading to a dimensional reduction of 2D materials into one-dimensional nanostructures. The spontaneous self-assembly and cross-linking processes allow to produce nanofibres without the need of fibrillation techniques, such as wet-spinning or external templates.

A class of compounds sharing the properties of 2D materials and electrolytes, namely 2D electrolytes is described theoretically and demonstrated experimentally. 2D electrolytes dissociate in different solvents, such as water, and become electrically charged. The chemical and physical properties of these compounds can be controlled by external factors, such as pH, temperature, electric permittivity of the medium, and ionic concentration. 2D electrolytes, in analogy with polyelectrolytes, present reversible morphological transitions from 2D to 1D, as a function of pH, due to the interplay of the elastic and Coulomb energies. Since these materials show stimuli-responsive behavior to the environmental conditions, 2D electrolytes can be considered as a novel class of smart materials that expand the functionalities of 2D materials and are promising for applications that require stimuli-responsive demeanor, such as drug delivery, artificial muscles, and energy storage.

We present a numerical simulation of the beam-steering of ultrasonic guided waves in an isotropic and viscoelastic solid plate, which mimics bovine cortex. The excitation was modeled by a group of five finite-size emitters, each exercised a normal force to the bone plate. Beam steering was achieved by delaying the emitters’ firing. The simulation technique was implemented by a semi-analytical finite element scheme to compute the wave fields. At small steering angles, the simulated time-offset signals show mainly two groups of arrivals. The first group is the fast-traveling and high-frequency bulk waves and the second one is slow-traveling and low-frequency guided waves. The fast-traveling waves gradually diminish with increasing steering angles, in agreement with the excitation function of the source influence theory. The frequency-phase velocity dispersion maps also illustrate the phenomenon. The study has demonstrated that the lowest order Lamb asymmetrical mode, A 0, which is useful for bone characterization, can best be excited when the cortical bone thickness is thin, the beam angle is large, and the excited frequency is low.

IntroductionDeclines in mental health among youth in the COVID-19 pandemic have been observed, yet longitudinal studies on how housing may impact these declines are lacking.ObjectivesOur aim was to determine whether changes in mental health among Danish youth were dependent on their housing conditions.MethodsYoung participants from the Danish National Birth Cohort, who had responded to an online questionnaire at 18 years of age, and later during the initial national Danish lockdown, were included. Associations between housing conditions (direct access to outdoor spaces, urbanicity, household density, and household composition) and changes in mental health (mental well-being, quality of life (QoL) and loneliness) were examined in multivariate linear and logistic regression analyses.ResultsWe included 7455 participants. Greater decreases in mental well-being were observed for youth with no access to direct outdoor spaces and those living in denser households (mean difference -0.83 [95 % CI -1.19, -0.48], -0.30 [-0.43, -0.18], respectively). Onset of low mental well-being was associated with no access and living alone (odds ratios (OR) 1.68 [1.15, 2.47] and OR 1.47 [1.05, 2.07], respectively). Household density was negatively associated with QoL (mean difference -0.21 [-0.30, -0.12]). Youth living alone experienced more loneliness (OR 2.12 [95 % CI 1.59, 2.82]).ConclusionsHow youth’s mental health changed from before to during lockdown was associated with housing conditions. Among the Danish youth in our study, greater decreases in mental health during lockdown were observed among youth without access to outdoor spaces, living alone, or living in denser households.DisclosureNo significant relationships.