DNN-BP: a novel framework for cuffless blood pressure measurement from optimal PPG features using deep learning model.

Continuous blood pressure (BP) provides essential information for monitoring one's health condition. However, BP is currently monitored using uncomfortable cuff-based devices, which does not support continuous BP monitoring. This paper aims to introduce a blood pressure monitoring algorithm based on only photoplethysmography (PPG) signals using the deep neural network (DNN). The PPG signals are obtained from 125 unique subjects with 218 records and filtered using signal processing algorithms to reduce the effects of noise, such as baseline wandering, and motion artifacts. The proposed algorithm is based on pulse wave analysis of PPG signals, extracted various domain features from PPG signals, and mapped them to BP values. Four feature selection methods are applied and yielded four feature subsets. Therefore, an ensemble feature selection technique is proposed to obtain the optimal feature set based on major voting scores from four feature subsets. DNN models, along with the ensemble feature selection technique, outperformed in estimating the systolic blood pressure (SBP) and diastolic blood pressure (DBP) compared to previously reported approaches that rely only on the PPG signal. The coefficient of determination ( R 2 ) and mean absolute error (MAE) of the proposed algorithm are 0.962 and 2.480 mmHg, respectively, for SBP and 0.955 and 1.499 mmHg, respectively, for DBP. The proposed approach meets the Advancement of Medical Instrumentation standard for SBP and DBP estimations. Additionally, according to the British Hypertension Society standard, the results attained Grade A for both SBP and DBP estimations. It concludes that BP can be estimated more accurately using the optimal feature set and DNN models. The proposed algorithm has the potential ability to facilitate mobile healthcare devices to monitor continuous BP.

Pharmacological insight of rutin as a potential candidate against peptic ulcer.

Peptic ulcer is a sore on the stomach lining that results from the erosion of the gastrointestinal tract mucosa due to various influencing factors. Of these, Helicobacter pylori infection and non-steroidal anti-inflammatory drugs (NSAIDs) stand out as the most prominent causes. This condition poses a significant global health concern due to its widespread impact on individuals worldwide. While various treatment strategies have been employed, including proton pump inhibitors and histamine-2 receptor antagonists, these have notable side effects and limitations. Thus, there is a pressing need for new treatments to address this global health issue. Rutin, a natural flavonoid, exhibits a range of biological activities, including anti-inflammatory, anticancer, and antioxidant properties. This review explores the potential anti-ulcer effect of rutin in experimental models and how rutin can be a better alternative for treating peptic ulcers. We used published literature from different online databases such as PubMed, Google Scholar, and Scopus. This work highlights the abundance of rutin in various natural sources and its potential as a promising option for peptic ulcer treatment. Notably, the anti-inflammatory properties of rutin, which involve inhibiting inflammatory mediators and the COX-2 enzyme, are emphasized. While acknowledging the potential of rutin, it is important to underscore the necessity for further research to fully delineate its therapeutic potential and clinical applicability in managing peptic ulcers and ultimately improving patient outcomes. This review on the anti-ulcer potential of rutin opened a new door for further study in the field of alternative medicine in peptic ulcer management.

Decision support system for community managed rainwater harvesting: A case study in the salinity-prone coastal region of Bangladesh.

Climate change-induced saline intrusion into both surface and groundwater, extreme weather events, and unregulated water usage are serious threats to the drinking water supply in coastal areas worldwide, especially in least-developed countries. This research developed a data-driven decision-making methodology to evaluate the performance of rainwater harvesting (RWH) systems in the saline-prone southwestern coastal region of Bangladesh. Twenty-five community managed RWH systems, recently piloted in two major coastal districts, were considered the case study to develop and validate this evaluation tool. The evaluation methodology integrates daily water models, lifetime cost analysis, Geographic Information System (GIS)-based parameters supported by the Analytical Hierarchy Process (AHP), and field observation. While the meteorological parameters as well as the hydrological and economic performance were found to be highly suitable, 36 % of the systems showed moderate performance, as challenges remain in ensuring proper operation and maintenance practices at the community level. However, 40 % of the systems showed high performance, with two systems showing very high suitability, which suggests community managed RWH systems as a sustainable adaptation for coastal water supply.

The portrayal of antimicrobial resistance in Bangladeshi newspapers during 2010-2021: Toward understanding the narrative.

BACKGROUND: Antimicrobial resistance (AMR) is a major global public health crisis and around the last decade, newspapers were one of the main sources of public dissemination of information for so. This study highlights how Bangladeshi mainstream newspapers represented AMR-related news and how they created the narrative of AMR in Bangladesh. METHODS: We conducted both quantitative and qualitative content analysis on 275 AMR-related news articles published in the twelve highest circulated dailies (January 2010 to September 2021). We divided the articles into report, opinion, and editorials and analyzed how their contents built the narrative of AMR in Bangladesh. RESULTS: Bangladeshi newspapers reported misuse of antibiotics by the consumers the most (32.2%), followed by selling without prescriptions (29%), and over-prescription by the health providers (26.1%). There were hardly any news reports describing the impact of pharmaceutical companies in prescribing and selling antibiotics. Around 45% of the news articles were event-oriented. Moreover, they suggested inadequate recommendations to battle AMR. CONCLUSION: Valid, consistent, and reliable AMR news coverage can play a crucial role in creating mass awareness, making providers accountable, and supporting national action plan in mitigating AMR threat. The Bangladeshi journalists interested in reporting AMR-issues should focus on disseminating more Bangla articles with scientific information, and reporting causes and recommendations responsibly.

A continuous cuffless blood pressure measurement from optimal PPG characteristic features using machine learning algorithms.

Background and objective: Hypertension is a potentially dangerous health condition that can be detected by measuring blood pressure (BP). Blood pressure monitoring and measurement are essential for preventing and treating cardiovascular diseases. Cuff-based devices, on the other hand, are uncomfortable and prevent continuous BP measurement. Methods: In this study, a new non-invasive and cuff-less method for estimating Systolic Blood Pressure (SBP), Mean Arterial Pressure (MAP), and Diastolic Blood Pressure (DBP) has been proposed using characteristic features of photoplethysmogram (PPG) signals and nonlinear regression algorithms. PPG signals were collected from 219 participants, which were then subjected to preprocessing and feature extraction steps. Analyzing PPG and its derivative signals, a total of 46 time, frequency, and time-frequency domain features were extracted. In addition, the age and gender of each subject were also included as features. Further, correlation-based feature selection (CFS) and Relief F feature selection (ReliefF) techniques were used to select the relevant features and reduce the possibility of over-fitting the models. Finally, support vector regression (SVR), K-nearest neighbour regression (KNR), decision tree regression (DTR), and random forest regression (RFR) were established to develop the BP estimation model. Regression models were trained and evaluated on all features as well as selected features. The best regression models for SBP, MAP, and DBP estimations were selected separately. Results: The SVR model, along with the ReliefF-based feature selection algorithm, outperforms other algorithms in estimating the SBP, MAP, and DBP with the mean absolute error of 2.49, 1.62 and 1.43 mmHg, respectively. The proposed method meets the Advancement of Medical Instrumentation standard for BP estimations. Based on the British Hypertension Society standard, the results also fall within Grade A for SBP, MAP, and DBP. Conclusion: The findings show that the method can be used to estimate blood pressure non-invasively, without using a cuff or calibration, and only by utilizing the PPG signal characteristic features.

Investigating the role of hypothetical protein (AAB33144.1) in HIV-1 virus pathogenicity: A comparative study with FDA-Approved inhibitor compounds through In silico analysis and molecular docking.

Aim and objective: Due to the a lot of unexplored proteins in HIV-1, this research aimed to explore the functional roles of a hypothetical protein (AAB33144.1) that might play a key role in HIV-1 pathogenicity. Methods: The homologous protein was identified along with building and validating the 3D structure by searching several bioinformatics tools. Results: Retroviral aspartyl protease and retropepsin like functional domains and motifs, folding pattern (cupredoxins), and subcellular localization in cytoplasmic membrane were determined as biological activity. Besides, the functional annotation revealed that the chosen hypothetical protein possessed protease-like activity. To validate our generated protein 3D structure, molecular docking was performed with five compounds where nelfinavir showed (-8.2 kcal/mol) best binding affinity against HXB2 viral protease (PDB ID: 7SJX) and main protease (PDB ID: 4EYR) protein. Conclusions: This study suggests that the annotated hypothetical protein related to protease action, which may be useful in viral genetics and drug discovery.

Evaluating Gut Microbiota Modification as a Next-Generation Therapy for Obesity and Diabetes.

The human body is a complex ecosystem that thrives on symbiosis. It is estimated that around 10^14 commensal microorganisms inhabit the human body, with the gut microbiota being one of the most diverse and complex populations of bacteria. This community is thought to comprise over a thousand different species that play a crucial role in the development of critical human diseases such as cancer, obesity, diabetes, mental depression, hypertension, and others. The gut microbiota has been identified as one of the most recent contributors to these metabolic disorders. With the emergence of inexpensive and high-performance sequence technology, our understanding of the function of the intestinal microbiome in host metabolism regulation and the development of (cardio) metabolic diseases has increased significantly. The symbiotic relationship between the gut microbiota and the host is essential for properly developing the human metabolic system. However, if this balance is disrupted by various factors such as infection, diet, exercise, sleep patterns, or exposure to antibiotics, it can lead to the development of various diseases in the body, including obesity and diabetes type 1 and 2. While many approaches and medications have been developed globally to treat these diseases, none have proven to be entirely effective, and many show side effects. Therefore, scientists believe that treating the gut microbiota using tried-and-true methods is the best option for combating obesity and diabetes. In this study, we aim to identify several feasible ways and prospects for gut microbiota therapy that can shape a new format for the treatment of obesity and diabetes.

Gold Nanorod Density-Dependent Label-Free Bacteria Sensing on a Flake-like 3D Graphene-Based Device by SERS.

Surface-enhanced Raman spectroscopy (SERS) is an effective technique for biosensing, enabling label-free detection of biomolecules with enhanced sensitivity. There is a tremendous probability of signal failure in Raman frequencies because of the scattering of the Raman radiation in liquids, effective SERS improvement is required to reduce this issue when considering liquid specimens. We examined a liquid bacterial sample, investigating the electrostatic interactions of the bacterial samples with gold nanorods (AuNRs) and graphene. We established a voltage-gated 3D graphene functionalized with an AuNR-based device on the silicon substrate for SERS measurements when the applied voltage ranges from 0 to 3 V. Moreover, AuNRs density-susceptible bacterial sample analysis with varied concentrations of bacterial samples has also been described. Using bacterial SERS analysis, the bacterial components amide II (1555-1565 cm-1) and amide III (1250-1350 cm-1) have been discovered for both bacteria, Gram-positive, Listeria monocytogenes and Gram-negative, Salmonella typhi. Our fabricated device affords an interesting label-free, rapid, and reproducible bacterial sample analysis based on the density of the AuNRs when functionalizing flake-like 3D graphene, which can help facilitate label-free bacteria sensing platforms.

Anxiolytic-like Effects by trans-Ferulic Acid Possibly Occur through GABAergic Interaction Pathways.

Numerous previous studies reported that ferulic acid exerts anxiolytic activity. However, the mechanisms have yet to be elucidated. The current study aimed to investigate the anxiolytic effect of trans-ferulic acid (TFA), a stereoisomer of ferulic acid, and evaluated its underlying mechanism using in vivo and computational studies. For this, different experimental doses of TFA (25, 50, and 75 mg/kg) were administered orally to Swiss albino mice, and various behavioral methods of open field, hole board, swing box, and light-dark tests were carried out. Diazepam (DZP), a positive allosteric modulator of the GABAA receptor, was employed as a positive control at a dose of 2 mg/kg, and distilled water served as a vehicle. Additionally, molecular docking was performed to estimate the binding affinities of the TFA and DZP toward the GABAA receptor subunits of α2 and α3, which are associated with the anxiolytic effect; visualizations of the ligand-receptor interaction were carried out using various computational tools. Our findings indicate that TFA dose-dependently reduces the locomotor activity of the animals in comparison with the controls, calming their behaviors. In addition, TFA exerted the highest binding affinity (-5.8 kcal/mol) to the α2 subunit of the GABAA receptor by forming several hydrogen and hydrophobic bonds. Taken together, our findings suggest that TFA exerts a similar effect to DZP, and the compound exerts moderate anxiolytic activity through the GABAergic interaction pathway. We suggest further clinical studies to develop TFA as a reliable anxiolytic agent.

Comparative safety analysis of newly prepackaged backed food products and those approaching the expiry date in Bangladesh.

PURPOSE: The enrichment of microbial growth in prepackaged, frozen food goods from the day of manufacturing to the day of expiration has been the subject of recurrent concerns. These fortified foods are widely consumed by individuals of all ages in poor nations due to their ability to satisfy even the smallest of appetites. People often disregard the expiration dates printed on food packaging despite the fact that manufacturers are required by law to do so. This research looked into whether or not it was safe to consume packaged foods that were getting close to their expiration date. Finding out if people are exposed to hazardous microorganisms and how much bacteria is created daily on them. MATERIALS AND METHODS: We collected six prepackaged backed food products samples of three types separately, where three were collected around manufacturing days and three were nearly expired days from different companies. We have assayed and identified the foodborne microbial communities among the samples by morphological study and different types of biochemical tests. After that, we tested how well various popular antibiotics worked against those isolates. RESULTS: It showed that there are more bacterial communities that grow gradually day by day on prepackaged backed food products and nearly expired products that contain a large number of food-borne disease-causing bacteria that show mostly resistance against commonly used antibiotics. CONCLUSION: Although nowadays the demand for prepackaged backed food products is increasing as ready-to-eat processed foods, mostly in developing countries, there's a serious health risk if we take the products that were produced a long time ago.

Toxicity Analysis of Some Frequently Used Food Processing Chemicals Using Allium cepa Biomonitoring System.

Frequent use of various food processing chemical agents sometimes causes damage to our bodies by inducing cytotoxicity, genotoxicity, and mutagenesis. In Bangladesh, among various chemical agents, formalin, saccharin, and urea are vastly used for processing foodstuffs by industry and local people. This study is focused to assess the toxic effects of formalin, saccharin, and urea on the popularly used eukaryotic test model, Allium cepa L. The assay was carried out by exposing different concentrations of test samples to A. cepa at 24, 48, and 72 h, where distilled water and CuSO4·5H2O (0.6 µg/mL) were utilized as the vehicle and positive control, respectively. The root length of the onions was measured in mm, and the results propose that all the chemical agents demonstrated toxicity in onions in a concentration- and exposure-time-dependent manner. The highest root length was examined at the lower concentrations, and with the increase in the concentration of the test sample and exposure time, the RG (root growth) was inhibited due to the deposition of chemicals and hampering of cell division in the root meristematic region of A. cepa. All the chemical agents also revealed a concentration- and time-dependent adaptive effect up to 72 h inspection of 24 h and a depletion of % root growth at 72 h inspection of 48 h. Our study suggests that sufficient precautions should be confirmed during its industrial and traditional usage as a toxicological response to the chemical agents observed in the A. cepa assay.

Prevalence and predictors of musculoskeletal health complaints among sedentary, monotonous urban workers: A survey in Bangladesh.

BACKGROUND: Monotonous and sedentary work is significantly associated with the worst health of workers. There is a scarcity of data investigating the musculoskeletal health of sedentary workers working in low-income and middle-income settings. This study aimed to measure the prevalence and predictors of musculoskeletal health complaints (MHC) among Bangladeshi shopkeepers. METHODS: This cross-sectional study was conducted in Dhaka, Bangladesh. Data from 1553 Bangladeshi shopkeepers aged 18 years and above were analyzed. MHC was measured using the musculoskeletal subscale of the subjective health complaints scale. The descriptive analysis helped to compute MHC prevalence and compare the prevalence across groups. Regression analysis revealed the predictors of MHC for the shopkeepers. RESULTS: The prevalence of MHC among shopkeepers was 58.0%. The prevalence of low back pain was the highest (55.5%), followed by neck pain (48.0%) and upper back pain (43.5%). Regression analysis identified sex (aOR 1.301, CI 0.996 to 1.700), age (aOR 1.405, CI 1.047 to 1.886), body mass index (aOR 0.495, CI 0.397 to 0.617), and substance abuse (aOR 1.998, CI 1.136 to 3.514) as independent predictors of MHC among the shopkeepers. Furthermore, significantly higher odds of MHC have been found among tobacco users (OR 1.234, CI 1.009 to 1.510). CONCLUSION: This study revealed a high prevalence of MHC and unhealthy lifestyles among shopkeepers in Bangladesh. Shopkeepers should be provided with better health literacy to follow healthy lifestyles and prevent MHC among this cohort.

Modulatory effects of phytol on the antiemetic property of domperidone, possibly through the D2 receptor interaction pathway: in vivo and in silico studies.

The current study is designed to evaluate the antiemetic effect of the diterpenoid phytol (PHY) using in vivo and in silico studies. For this, emesis was induced in 4-day-old chicks by the oral administration of copper sulfate (CuSO4.5H2O) at 50 mg/kg. To see the possible antiemetic mechanism of PHY, we used a number of reference drugs such as domperidone (80 mg/kg), ondansetron (24 mg/kg) and hyoscine (100 mg/kg) as positive controls, while the vehicle served as a negative control group. PHY was administered orally at the doses of 50 and 75 mg/kg. Both PHY and reference drugs were given alone or in combined groups to evaluate their synergistic or antagonistic effects on the chicks. Molecular docking of PHY and reference drugs was carried out against 5HT3, D2, D3, H1, NK1, and mAChRs (M1-M5) receptors for estimating binding affinity to the receptors. Drug-receptor interactions and active sites of the receptors were observed with the aid of different computational tools. The drug-likeness and pharmacokinetics of all the drugs were predicted through the SwissADME online database. The results suggest that PHY reduces the mean number of retches and increases latency dose-dependently in the birds. In the combination groups, PHY75 showed better antiemetic effects with domperidone and ondansetron. In addition, PHY exhibited the highest binding affinity with the D2 receptor (6CM4) (- 7.3 kcal/mol). In conclusion, PHY showed an antiemetic activity in chicks, possibly through the D2 receptor interaction pathway.

Biohydrogen production from Euglena acus microalgae available in Bangladesh.

Hydrogen is generally considered as an ideal non-polluting future energy carrier because it releases energy and water as a byproduct on combustion. Besides, hydrogen possesses the highest energy density on mass basis compared to any other fuel. However, hydrogen production in a sustainable and environmentally friendly way still remains a challenge. Recently, biohydrogen production from green microalgae has gained significant attention due to availability of the feedstock, which are environmentally friendly and renewable. Biohydrogen production from photosynthetic microalgae is attractive, however in the current context, it has a low yield, and an optimization of the affecting parameters including algae concentration, light intensity, culture medium, etc. is critical. In this study, biohydrogen was produced in laboratory from Euglena acus microalgae as it was locally available in Bangladesh.•The effect of two different culture mediums (i.e. sulfur-rich and sulfur-deprived TAP mediums) for microalgae cultivation and biohydrogen yield were studied.•Depending on the concentration of microalgae (50% and 75% by weight) in the medium solution ∼3 ml to 5 ml biohydrogen was obtained.

Synthesis and biological evaluation of tert-butyl ester and ethyl ester prodrugs of L-γ-methyleneglutamic acid amides for cancer.

In cancer cells, glutaminolysis is the primary source of biosynthetic precursors. Recent efforts to develop amino acid analogues to inhibit glutamine metabolism in cancer have been extensive. Our lab recently discovered many L-γ-methyleneglutamic acid amides that were shown to be as efficacious as tamoxifen or olaparib in inhibiting the cell growth of MCF-7, SK-BR-3, and MDA-MB-231 breast cancer cells after 24 or 72 h of treatment. None of these compounds inhibited the cell growth of nonmalignant MCF-10A breast cells. These L-γ-methyleneglutamic acid amides hold promise as novel therapeutics for the treatment of multiple subtypes of breast cancer. Herein, we report our synthesis and evaluation of two series of tert-butyl ester and ethyl ester prodrugs of these L-γ-methyleneglutamic acid amides and the cyclic metabolite and its tert-butyl esters and ethyl esters on the three breast cancer cell lines MCF-7, SK-BR-3, and MDA-MB-231 and the nonmalignant MCF-10A breast cell line. These esters were found to suppress the growth of the breast cancer cells, but they were less potent compared to the L-γ-methyleneglutamic acid amides. Pharmacokinetic (PK) studies were carried out on the lead L-γ-methyleneglutamic acid amide to establish tissue-specific distribution and other PK parameters. Notably, this lead compound showed moderate exposure to the brain with a half-life of 0.74 h and good tissue distribution, such as in the kidney and liver. Therefore, the L-γ-methyleneglutamic acid amides were then tested on glioblastoma cell lines BNC3 and BNC6 and head and neck cancer cell lines HN30 and HN31. They were found to effectively suppress the growth of these cancer cell lines after 24 or 72 h of treatment in a concentration-dependent manner. These results suggest broad applications of the L-γ-methyleneglutamic acid amides in anticancer therapy.

Musculoskeletal health complaints: A growing concern that should be investigated elaborately in Bangladesh.

Evidence from the past few decades suggests that the most increases in disability-related musculoskeletal health complaints (MHC) have occurred in low-income and middle-income countries (LMICs). Past studies identified long sitting, higher commute time to the office, and traffic congestion predictors of MHC in Bangladesh. Additionally, post-acute COVID-19 patients reported MHC at a higher rate in Bangladesh. Further studies are needed to recommend exclusive initiatives from authorities to tackle the upcoming tsunami of MHC in LMICs, for example, in Bangladesh.

Recent Insights into NIR-Light-Responsive Materials for Photothermal Cell Treatments.

Controlling cells using photo-responsive materials is highly indispensable in the current biomedical sector. Considering the potential side effects of nanoparticles, it has become a challenge to control cells with photo-responsive materials. Recent studies have described several methods for controlling cell behavior using nanoparticles subjected to the near-infrared (NIR) laser light operating at the wavelength of 808 nm to 980 nm and at the power densities of 0.33 to 0.72 W·cm-2. The challenge here is the preparation of biocompatible nanoparticles for both in vivo and in vitro studies and understanding cell behavior with an external light source recommended for biological application. Earlier studies have well documented many approaches and associated mechanisms for controlling cell behavior and the interaction between nanoparticles, cells, and appropriate external light sources. In this review, various nanomaterials such as metal nanomaterials and carbon-based nanomaterials are compared systematically regarding the effects of controlling cell behavior and inflammation by studying their mechanisms, route of administration, dose, and adverse effects such as toxicity and the interaction of nanoparticles with a specific wavelength of the light. Future directions should focus on stable and efficient light-responsive materials with minimal cytotoxicity.

Corrigendum to: GSK-3 Inhibitors in the Regulation and Control of Colon Carcinoma.

The author requested to add a co-author after the publication of the original article [1]. In this correction, the author has been added in the article entitled "GSK-3 Inhibitors in the Regulation and Control of Colon Carcinoma" in the journal "Current Drug Targets" 2021; 22(13), 1485-1495. Details of the error and a correction are provided here. The original editorial can be found online at 10.2174/1389450122666210204203950 We regret any errors and apologize to the readers. Original: Sitansu S. Nanda1, Md Imran Hossain1, Heongkyu Ju2 and Dong Kee Yi1,* 1Department of Chemistry, Myongji University, Yongin, 03674, South Korea; 2Department of Physics, Gachon University, Seongnam-si, Gyeonggi-do, South Korea Corrected: Sitansu S. Nanda1, Md Imran Hossain1, Heongkyu Ju2, Georgia C. Papaefthymiou3 and Dong Kee Yi1,* 1Department of Chemistry, Myongji University, Yongin, 03674, South Korea; 2Department of Physics, Gachon University, Seongnam-si, Gyeonggi-do, South Korea 3Department of Physics, Villanova University, Villanova, Pennsylvania19085, USA.

Effects of hydrocarbon chain on the vesicle size distribution, kinetics of average size, bending modulus, and elastic modulus of lipid membranes.

The effects of the hydrocarbon chain of lipids on the size distribution of giant unilamellar vesicles (GUVs), kinetics of average size, bending modulus, and elastic modulus of membranes have been investigated. 1,2-dioleoyl-sn-glycero-3-phosphocholine (18:1 (Δ9-Cis) PC (DOPC)), 1,2-dipalmitoleoyl-sn-glycero-3-phosphocholine (16:1 (Δ9-Cis) PC), and 1,2-ditridecanoyl-sn-glycerol-3-phosphocholine (13:0 PC (DTPC)) lipids were considered. The number of hydrocarbons in a chain of the corresponding lipid was 18, 16, and 13. GUVs were prepared using the natural swelling method under incubation times of 20, 40, 60, 90, 120, and 180 min. The size distribution of vesicles was fitted using the lognormal distribution. The average sizes of DOPC, 16:1 (Δ9-Cis) PC, and DTPC-GUVs increased with the incubation time until 120 min, and then remained steady at 16.7 ± 0.2, 15.2 ± 0.4 and 12.0 ± 0.3 µm for the corresponding lipids. The average size at equilibrium state increased with the number of hydrocarbons. The incubation time-dependent average size was fitted with an exponential growth equation, and then the kinetic constants of 0.028 ± 0.004, 0.036 ± 0.007, and 0.083 ± 0.009 min-1 for DOPC, 16:1 (Δ9-Cis) PC, and DTPC-GUVs, respectively, were obtained. The equilibrium size distribution was fitted by the theoretical equation, and the bending modulus for DOPC, 16:1 (Δ9-Cis) PC, and DTPC membranes were 19.5 ± 0.2, 18.5 ± 0.1 and 14.3 ± 0.1 kBT, respectively. The bending modulus increased with the number of hydrocarbons. The elastic modulus of these membranes was 261 mN/m with a 4% fluctuation. The correlation between the average size and the square root of the bending modulus was supported by theoretical analysis.

Synthesis of 3,4,5-trisubstituted isoxazoles in water via a [3 + 2]-cycloaddition of nitrile oxides and 1,3-diketones, ß-ketoesters, or ß-ketoamides.

Herein we report a method for the synthesis of 3,4,5-trisubstituted isoxazoles in water under mild basic conditions at room temperature via a [3 + 2]-cycloaddition of nitrile oxides and 1,3-diketones, ß-ketoesters, or ß-ketoamides. We optimized the reaction conditions to control the selectivity of the production of isoxazoles and circumvent other competing reactions, such as O-imidoylation or hetero [3 + 2]-cycloaddition. The reaction happens fast in water and completes within 1-2 hours, which provides an environmentally friendly access to 3,4,5-trisubstituted isoxazoles, an important class of structures found in numerous bioactive natural products and pharmaceuticals. Additionally, we optimized the reaction conditions to produce trifluoromethyl-substituted isoxazoles, a prevalent scaffold in biomedical research and drug discovery programs. We also proposed a plausible mechanism for the selectivity of the [3 + 2]-cycloaddition reaction to produce 3,4,5-trisubstituted isoxazoles. Not to be overlooked are our optimized reaction conditions for the dimerization of hydroximoyl chlorides to form furoxans also known as 1,2,5-oxadiazole 2-oxides, a class of structures with important biological activities due to their unique electronic nature and coordination ability.