Imidazolium-based zwitterionic liquid-modified PEG-PLGA nanoparticles as a potential intravenous drug delivery carrier.

Zwitterionic-based systems offer promise as next-generation drug delivery biomaterials capable of enhancing nanoparticle (NP) stimuli-responsiveness, biorecognition, and biocompatibility. Further, imidazole-functionalized amphiphilic zwitterions are able to readily bind to various biological macromolecules, enabling antifouling properties for enhanced drug delivery efficacy and bio-targeting. Herein, we describe structurally tuned zwitterionic imidazole-based ionic liquid (ZIL)-coated PEG-PLGA nanoparticles made with sonicated nanoprecipitation. Upon ZIL surface modification, the hydrodynamic radius increased by nearly 20 nm, and the surface charge significantly shifted closer to neutral. 1H NMR spectra suggests that the amount of ZIL on the nanoparticle surface is controlled by the structure of the ZIL and that the assembly occurs as a result of non-covalent interactions of ZIL-coated nanoparticle with the polymer surface. These nanoparticle-zwitterionic liquid (ZIL) constructs demonstrate selective affinity towards red blood cells in whole mouse blood and show relatively low human hemolysis at ∼5%. Additionally, we observe higher nanoparticle accumulation of ZIL-NPs compared with unmodified NP controls in human triple-negative breast cancer cells (MDA-MB-231). Furthermore, although the ZIL shows similar protein adsorption by SDS-PAGE, LC-MS/MS protein analysis data demonstrate a difference in the relative abundance and depletion of proteins in mouse and human serum. Hence, we show that ZIL-coated nanoparticles provide a new potential platform to enhance RBC-based drug delivery systems for cancer treatments.

Structure-Dependence and Mechanistic Insights into the Piezoelectric Effect in Ionic Liquids.

We reported recently that two imidazolium room-temperature ionic liquids (RTILs) exhibit the direct piezoelectric effect (J. Phys. Chem. Lett., 2023, 14, 2731-2735). We have subsequently investigated several other RTILs with pyrrolidinium and imidazolium cations and tetrafluoroborate and bis(trifluoromethylsulfonyl)imide anions in an effort to gain insight into the generality and mechanism of the effect. All the RTILs studied exhibit the direct piezoelectric effect, with a magnitude (d33) and threshold force that depend on the structures of both the cation and anion. The structure-dependence and existence of a threshold force for the piezoelectric effect are consistent with a pressure-induced liquid-to-crystalline solid phase transition in the RTILs, and this is consistent with experimental X-ray diffraction data.

Internet Addiction and Its Associated Factors among Undergraduate Students in Kathmandu, Nepal.

Background: Internet has penetrated all processes of life and has become an unavoidable part of people's daily life. This widespread use of the Internet has resulted in significant concerns with regard to problematic Internet behaviours and related conditions. The aim of the study was to find out the prevalence of Internet addiction and its associated factors among undergraduate students in Kathmandu. Materials and Methods: We included all together 344 undergraduate students from different colleges affiliated to Pokhara University for this cross-sectional study. We used self-administered questionnaire consisting of the Internet Addiction Test scale to assess the Internet addiction. We coded the data, entered it in Epi-Data 3.1 and transferred to IBM SPSS 25 for analysis. We applied bivariate and multivariate logistic regression analysis to identify factors associated with Internet addiction, and p value <0.05 was considered as statistically significantt. Results: The prevalence of Internet addiction was found to be 29.90% (95% CI: 25.0-34.9). In the chi-squared test relationship with parents, parental control over the Internet use, perceived feeling of loneliness, and time spent on internet per day were found to be statistically associated (p < 0.05) with Internet addiction. Conclusion: This study revealed nearly one-third of the Internet addiction among undergraduate students. Relationship with parents, parental control over the internet use, perceived loneliness feelings, and time spent on internet per day were significantly associated with Internet addiction along other factors. Therefore, it is important to raise awareness among young generation, parents, and teachers towards risk of Internet addiction.

Relating the Induced Free Charge Density Gradient in a Room-Temperature Ionic Liquid to Molecular-Scale Organization.

We report on dilution-dependent changes in the local environments of chromophores incorporated into room-temperature ionic liquid (RTIL)-molecular solvent binary systems where the ionic liquid cation and molecular solvent possess the same alkyl chain length. We have used the RTIL 1-decyl-1-methylpyrrolidinium bis(trifluoromethanesulfonyl)imide (DMPyrr+TFSI-) and the molecular solvent 1-decanol. Perylene was used as a non-polar probe, and cresyl violet (CV+) was used as a polar probe chromophore. We observe that in both regions there is a change in the chromophore local environments with increasing 1-decanol content. The changes in the nonpolar regions of the binary RTIL-molecular solvent system occur at a lower 1-decanol concentration than changes in the polar regions. Both chromophores reorient as oblate rotors in this binary system, allowing detailed information on the relative values of the Cartesian components of the rotational diffusion constants to be extracted from the experimental data. The induced free charge density gradient, ρf, known to exist in RTILs, persists to high 1-decanol content (1-decanol mole fraction of 0.75), with the structural details of the gradient being reflected in depth-dependent changes in the Cartesian components of the rotational diffusion constants of CV+. This is the first time that changes in molecular organization have been correlated with ρf.

Cation structure-dependence of the induced free charge density gradient in imidazolium and pyrrolidinium ionic liquids.

We report on the structure-dependence and magnitude of the induced free charge density gradient (ρf) seen in room-temperature ionic liquids (RTILs) with imidazolium and pyrrolidinium cations. We characterize the spatially-resolved rotational diffusion dynamics of a trace-level cationic chromophore to characterize ρf in three different pyrrolidinium RTILs and two imidazolium RTILs. Our data show that the magnitude of ρf depends primarily on the alkyl chain length of RTIL cation and the persistence length of ρf is independent of RTILs' cation structure. These findings collectively suggest that mesoscopic structure in RTILs plays a significant role in allowing charge density gradients to form.

Cation structure-dependence of the Pockels effect in aprotic ionic liquids.

We report on the dependence of surface charge-induced birefringence (the Pockels effect) in room temperature ionic liquids (RTILs) with different cation constituents. The induced birefringence is related to the induced free charge density gradient (ρf) in the RTIL. The RTILs are confined in a lens-shaped cell and the surface charge density of the concave cell surface is controlled by the current passed through the surface ITO film. We find that, in all cases, the induced birefringence is proportional to the surface charge density and that the change in refractive index nearest the ITO surface can be on the order of 20%. Our findings indicate that the induced birefringence depends more sensitively on the cation aliphatic substituent length than on the identity of the charge-carrying headgroup.

Mental Health Status of Migrant Nepalese Workers Rescued By Government of Nepal During the Corona Virus disease -19 Pandemic.

BACKGROUND: The corona virus pandemic rapidly sweeps across the world; it is inducing a considerable degree of depression, stress and anxiety concern in the population at large and among certain groups in particular, such as migrant workers. The aim of the study is to find out mental health status of migrant workers rescued by Nepal Government from different countries during corona virus disease -19-19 pandemic. METHODS: Cross-sectional descriptive study involving 427 returned migrant workers was conducted using the depression, anxiety and stress scale -21(DASS-21). Association between socio-demographic variables to mental health status was performed using chi-square test and p-value <0.05 was considered as significant level. RESULTS: Out of 427 participants, 4 % of respondents found to have extremely severe level of stress followed by 1.9 % extremely severe level of depression and 2.3% extremely severe level of anxiety. The association between mental health status and covariates showed that depression, anxiety and stress were associated with the place of residence, educational status of the respondents, and their perception of corona virus disease -19 risk at workplace, and test for COVID-19 after arrival to Nepal. CONCLUSIONS: The study revealed that job loss, visa and employment contract expiry were the main reasons for migrant workers to return Nepal. Nearly one fourth of the respondents had suffered from depression, nearly one third from stress and 17% from anxiety. Necessary psychosocial interventions should be formulated and implemented for addressing the mental health problems of migrant workers during the corona virus disease -19-19 pandemic.

Developmental delay and its associated factors among children under five years in urban slums of Nepal.

INTRODUCTION: Children from low-resource settings are more likely to encounter those factors that adversely influence their ability to acquire developmental potential. This study was conducted to assess the developmental status and its associated factors among children under five years of slum areas of Butwal Sub Metropolitan City, Rupandehi, Nepal. METHODS AND FINDINGS: We conducted a community-based cross-sectional descriptive study using Developmental Milestone Chart (DMC) among 165 children under five years. Ethical approval was obtained from Ethical Review Board of Nepal Health Research Council. R software was used for data analysis. The association between developmental status and associated factors were examined with Chi-square and followed by logistic regression. Notably, more than half of the children (56.4%) had delayed development across two or more domains of gross motor, fine motor, language/ speech, and social development. Age, sex, socio-economic status, availability of learning materials, the occurrence of infectious diseases, and height-for-age of children were found to be significantly associated with the developmental status of children under study (p<0.05). CONCLUSIONS: More than half of the children taken under the study had delayed development on different four domains. Findings from the study suggest that there should be similar studies conducted among children living in slum-like conditions. Additionally, programs should be designed as such which aims to mitigate the effect of socio-economic status on child development and has learning and nutritional aspects embedded central to its deliverance.

Deep eutectic solvents comprising creatine and citric acid and their hydrated mixtures.

We report the phase diagram for the binary creatine-citric acid mixture which features a stable and broad eutectic region. Combinations containing 10-60 mol% creatine yield a deep eutectic solvent with a glass transition temperature at 270 K. Addition of up to 70 mol% water to the binary mixture affords retention of the eutectic nature and a handle to vary solvent viscosity and polarity.

Laser-induced sound pinging for the rapid determination of total sugar or sweetener content in commercial beverages.

We recently reported on fixed-path length laser-induced sound pinging (FPL-LISP) as a rapid photoacoustic technique employing an inexpensive benchtop tattoo-removal laser for reliably determining the speed of sound in low-volume fluids. In this contribution, we demonstrate the capacity of FPL-LISP to analyze representative commercial beverages for their natural or artificial sweetener contents. As a benchmark, the speed of sound was determined for solutions of sugars (glucose, fructose, sucrose), mock high fructose corn syrup (HFCS-55), and 12 household sweeteners (culinary sugars, syrups, honey, molasses) across the concentration range of 1-20% w/v in water, simulating the typical sweetener range found in commercial soft drinks. The setup was then employed to estimate sweetener contents of 26 popular commercial beverages using the HFCS-55 standard curve as a training data set. Our results are remarkably consistent with the label values for these representative commercial beverages, in spite of the fact that some beverages clearly employ a sweetener other than HFCS-55 or a proprietary blend, suggesting the excellent potential of the FPL-LISP setup as a quick screening tool well-suited to quality control and real-time assessment in the beverage and fermentation industrial sectors. The proposed approach represents a significant improvement over many existing methods on the basis of measurement time (down to 1 s, which can be considered real time for many applications), lenient sample requirements (tens of microliters to 1 mL), robust and user-friendly analysis, practical considerations (e.g., economical, minimal service and maintenance concerns), and prospects for advancing both online monitoring and fully portable versions of this instrumentation.

Analytical similarity assessment of MYL-1402O to reference Bevacizumab.

BACKGROUND: Bevacizumab (BEV) is a recombinant humanized monoclonal immunoglobulin G1 antibody that binds to vascular endothelial growth factor (VEGF)-A and acts as an antiangiogenic agent. It is approved for treatment of many cancer indications, including metastatic colorectal cancer and nonsquamous non-small cell lung cancer. RESEARCH DESIGN AND METHODS: The analytical similarity of the BEV biosimilar MYL-1402O to reference BEV sourced from the European Union and United States was assessed using physicochemical and functional tests to support the clinical development of MYL-1402O. Assessment of physicochemical and analytical similarity showed that MYL-1402O has the same amino acid sequence and similar posttranslational modification profile as the reference BEV products. RESULTS: The functional and biologic activity of MYL-1402O assessed using inhibition of VEGF-induced cell proliferation in human umbilical vein endothelial cells, inhibition of VEGF-induced VEGF receptor 2 phosphorylation, and fragment antigen and fragment crystallizable receptor binding, was comparable to reference BEV products. CONCLUSIONS: The totality of the data assessment confirms the high degree of similarity of MYL-1402O to reference BEV with respect to physicochemical and in vitro functional properties. The product quality data presented here, along with data from phase 1 clinical studies, demonstrate the similarity of MYL-1402O to reference BEV products, supporting further clinical development of this BEV biosimilar.

Deep Eutectic Solvents: A Review of Fundamentals and Applications.

Deep eutectic solvents (DESs) are an emerging class of mixtures characterized by significant depressions in melting points compared to those of the neat constituent components. These materials are promising for applications as inexpensive "designer" solvents exhibiting a host of tunable physicochemical properties. A detailed review of the current literature reveals the lack of predictive understanding of the microscopic mechanisms that govern the structure-property relationships in this class of solvents. Complex hydrogen bonding is postulated as the root cause of their melting point depressions and physicochemical properties; to understand these hydrogen bonded networks, it is imperative to study these systems as dynamic entities using both simulations and experiments. This review emphasizes recent research efforts in order to elucidate the next steps needed to develop a fundamental framework needed for a deeper understanding of DESs. It covers recent developments in DES research, frames outstanding scientific questions, and identifies promising research thrusts aligned with the advancement of the field toward predictive models and fundamental understanding of these solvents.

Menopausal Symptoms among Postmenopausal Women of a Selected Municipality: A Cross-sectional Survey.

INTRODUCTION: Postmenopausal women experience various menopause-specific somatic, psychological, and urogenital symptoms which tend to affect their overall well-being. However, there is a scant focus on menopausal health problems of postmenopausal women in Nepal. The aim of the study was to find out the prevalence of menopausal symptoms among postmenopausal women of a Municipality. METHODS: A cross-sectional survey was conducted in selected wards of Tokha Municipality of Kathmandu district among postmenopausal women aged 45-60 years from September to October 2019. Ethical approval was taken from the Ethical Review Board, Nepal Health Research Council (reference number 694). Random sampling was used as the sampling technique. Face-to-face interview was used for data collection while a semi-structured interview schedule including the Nepali version of Menopause Rating Scale was used as a tool for measuring menopausal symptoms. EpiData version 3.1 was used for data entry while data analysis was performed using Statistical Packages for the Social Sciences version 20. RESULTS: Amongst the postmenopausal women, all 203 (100%) had menopausal symptoms with majority reporting milder symptoms as found in 143 (70.4%). The mean Menopause Rating Scale (MRS) score was obtained as 13.21±5.1. The most prevalent moderate and mild symptoms were vaginal dryness 94 (46.3%), and depressive mood 71 (35%) respectively while physical and mental exhaustion 175 (86.2%) was the most common in all forms. Over half 102 (50.2%) of the respondents were unaware of menopausal symptoms and almost three-fifth 121 (59.6%) reported menopause related symptoms affected their daily work activities. CONCLUSIONS: The majority of postmenopausal women in this study had milder menopausal symptoms, which parallels findings from other national studies.

Factors Associated with Postnatal Depression among Mothers Attending at Bharatpur Hospital, Chitwan.

Postnatal depression is linked with adverse outcomes for mothers, offspring, and her entire family, which stands as a significant public health problem and is often taken as a neglected issue of maternal and child health in the developing world. Postnatal depression is often falsely interpreted as common consequences related to the recent delivery. The main objective of this study is to find out the status of postnatal depression and the factors associated with it among the postnatal mothers attending at Bharatpur Hospital. Methodology. A total of 242 postnatal women were included in a hospital-based cross-sectional descriptive study. A systematic random sampling technique was done to get the sampling interval. Face to face interview technique was used for data collection, and depressive symptoms were measured by the Edinburgh Postnatal Depression Scale. Data was entered in Epi-Data and imported to SPSS for analysis. The data were summarized in terms of frequency (percentage), mean (SD), or median (IQR) as per necessity for descriptive analysis. The chi-square test and binary logistic regression were performed to find out the association between the covariates and depression status, assuming significance at p value <0.05. Results. The study revealed that the prevalence of postnatal depression was 16.9% by EPDS at cutoff point ≥12. It was found that postnatal depression was associated with current age, smoking, pressure to conceive a child, intent of pregnancy, and delivery-related complications. Conclusion. Postnatal depression within six months of delivery was found among nearly one-fifth of women, where 13.6% also had suicidal thoughts. More than half of the postnatal women had an early marriage. It is recommended that mothers with high risk should be routinely screened for postnatal depression followed by necessary interventions as well as safe motherhood counseling.

Facile, one-pot, in aqua synthesis of catalytically competent gold nanoparticles using pyrogallol[4]arene as the sole reagent.

We report a simple, single-pot, room temperature synthetic route to prepare colloidally-stable pyrogallol[4]arene-capped gold nanoparticles. The number of carbon atoms in the pyrogallol[4]arene pendent alkyl chain and the addition of base (e.g., NaOH) are both found to significantly impact the resulting colloid size, stability, and catalytic activity for nitroarene reduction.

Maturation inhibitors facilitate virus assembly and release of HIV-1 capsid P224 mutant.

HIV-1 Maturation inhibitors (MIs) bind to the C-terminal domain of capsid protein (CA-CTD) and spacer peptide 1 (SP1) in HIV-1 Gag and inhibit the CA-SP1 cleavage by stabilizing the immature Gag. The ß-turn motif, GVGGP in the HIV CA-CTD (residues 220-224) is one of the key determinants of HIV Gag assembly. In the present study, we mutated each residue of HIV-1 ß-turn motif to alanine and observed complete inhibition of virus release of all mutants. This defect in virus release was rescued in the presence of maturation inhibitors; BVM and PF-46396 for P224A mutant. To our knowledge, this is the first report of identification of BVM and PF-46396-dependent capsid mutant. Our results highlight the importance of the core ß-turn motif residues in immature virus assembly and suggest that the presence of MIs enhances Gag membrane binding and multimerization thereby restoring virus release of HIV Gag P224 mutant.

Nanoporous carbon materials with enhanced supercapacitance performance and non-aromatic chemical sensing with C1/C2 alcohol discrimination.

We have investigated the textural properties, electrochemical supercapacitances and vapor sensing performances of bamboo-derived nanoporous carbon materials (NCM). Bamboo, an abundant natural biomaterial, was chemically activated with phosphoric acid at 400 °C and the effect of impregnation ratio of phosphoric acid on the textural properties and electrochemical performances was systematically investigated. Fourier transform-infrared (FTIR) spectroscopy confirmed the presence of various oxygen-containing surface functional groups (i.e. carboxyl, carboxylate, carbonyl and phenolic groups) in NCM. The prepared NCM are amorphous in nature and contain hierarchical micropores and mesopores. Surface areas and pore volumes were found in the range 218-1431 m2 g-1 and 0.26-1.26 cm3 g-1, respectively, and could be controlled by adjusting the impregnation ratio of phosphoric acid and bamboo cane powder. NCM exhibited electrical double-layer supercapacitor behavior giving a high specific capacitance of c.256 F g-1 at a scan rate of 5 mV s-1 together with high cyclic stability with capacitance retention of about 92.6% after 1000 cycles. Furthermore, NCM exhibited excellent vapor sensing performance with high sensitivity for non-aromatic chemicals such as acetic acid. The system would be useful to discriminate C1 and C2 alcohol (methanol and ethanol).