A kinetic and mechanistic study of the self-reaction between two propargyl radicals.

CONTEXT: The propargyl radical plays a critical role in various chemical processes, including hydrocarbon combustion, flame synthesis, and interstellar chemistry. Its unique stability arises from the delocalization of π-electrons, allowing it to participate in a wide range of reactions despite being a radical. The self-reaction of propargyl radicals is a fundamental step in synthesizing polycyclic aromatic hydrocarbons. In this work, therefore, a computational study into the C3H3 + C3H3 potential energy surface has been carefully characterized. The calculated results indicate that the reaction can occur by H-abstraction or addition of two propargyl radicals together. The H-abstraction mechanism can create the products P3 (H2CCC + H3CCCH) and P4 (H2CCCH2 + HCCCH) but the energy barriers of the two H-abstraction channels are very high (from 12 to 22 kcal/mol). In contrast, the addition mechanism of two propargyl radicals forming the intermediates (I1, I5, I12) and the bimolecular products (P1, P2, P7, P11, P12) are dominant. Among the bimolecular products, the P11 (C6H4 + H2) product is the most energetically favorable, and the channel leading to this product is also the most preferred path compared to all other paths throughout the PES. The calculated enthalpy changes of various reaction paths in this study are in good agreement with the available literature data, indicating that the CCSD(T) method is suitable for the title reaction. The overall rate constant of the reaction depends on both temperature and pressure, reducing with temperature but rising with pressure. The calculated results agree closely with the available experimental values ​​and previous calculated data. Thus, it can be affirmed that in addition to the CASPT2 method as applied in the study of Georgievskii et al. (Phys. Chem. Chem. Phys., 2007, 9, 4259-4268), the CCSD(T) method is also very good for the self-reaction of two propargyl radicals. METHODS: The M06-2X and CCSD(T) methods with the aug-cc-pVTZ basis set were used to optimize and calculate single-point energies for all species of the reaction. The bimolecular rate constants of the dominant reaction paths were predicted in the temperature and pressure ranges of 300-1800 K and 0 - 76,000 Torr, respectively, using the VTST and RRKM models with Eckart tunneling correction for the H-shift steps.

Health-related quality of life of people with depression: pre-post intervention compared with age-matched general population in Vietnam.

BACKGROUND: In Vietnam, there is a paucity of health-related quality of life (HRQoL) research on people with depression as well as a lack of evidence on supported self-management (SSM) intervention for depression on HRQoL. This study aimed to compare the HRQoL of people with depression and age-matched people in the Vietnamese population, evaluate the effects of Tele-SSM intervention on HRQoL, and examine the association between the changes in HRQoL score and mental health well-being (depression, anxiety, and stress). METHODS: This study was a pre- and post-study involving Vietnamese adults aged 18-64 who had depression symptoms (score ≥ 5 points in the PHQ-9). Participants (N = 58) completed Tele-SSM-a supported self-management intervention incorporating cognitive behavioral therapy and non-violent communication and using a task-shifting approach. To compare with the general population, we conducted a 1-to-1 matching by age with an EQ-5D-5L valuation study with a nationally representative sample of the Vietnamese general population. RESULTS: HRQoL was significantly impaired in people with depression compared to the age-matched general population. Regarding health profile, participants reported the most difficulties in usual activities, pain/discomfort, and anxiety/depression dimensions. Significant improvements were observed in HRQoL scores post-intervention compared to pre-intervention in both EQ-VAS scores (from 59.84 to 79.48) and utility scores (from 0.79 to 0.90). These results remained lower than the age-matched general population (EQ-VAS score = 83.28, utility score = 0.96). Depression was associated with lower HRQoL while controlling for stress, anxiety symptoms and sociodemographic characteristics. CONCLUSIONS: These results indicate that HRQoL is significantly impaired in people with depression and contribute to providing empirical evidence of Tele-SSM intervention in improving HRQoL. Further randomized controlled trials should be conducted to evaluate the effectiveness and cost-effectiveness of the Tele-SSM intervention.

Exploring key factors influencing depressive symptoms among middle-aged and elderly adult population: A machine learning-based method.

OBJECTIVE: This paper aims to investigate the key factors, including demographics, socioeconomics, physical well-being, lifestyle, daily activities and loneliness that can impact depressive symptoms in the middle-aged and elderly population using machine learning techniques. By identifying the most important predictors of depressive symptoms through the analysis, the findings can have important implications for early depression detection and intervention. PARTICIPANTS: For our cross-sectional study, we recruited a total of 976 volunteers, with a specific focus on individuals aged 50 and above. Each participant was requested to provide their demographic, socioeconomic information and undergo several physical health tests. Additionally, they were asked to respond to questionnaires that assessed their mental well-being. Furthermore, participants were requested to maintain an activity log for a continuous 14-day period, starting from the day after they signed up. They had the option to use either a provided mobile application or paper to record their activities. METHODS: We evaluated multiple machine learning models to find the best-performing one. Subsequently, we conducted post-hoc analysis to extract the variable significance from the selected model to gain deeper insights into the factors influencing depression. RESULTS: Logistic Regression was chosen as it exhibited superior performance across other models, with AUC of 0.807 ± 0.038, accuracy of 0.798 ± 0.048, specificity of 0.795 ± 0.061, sensitivity of 0.819 ± 0.097, NPV of 0.972 ± 0.013 and PPV of 0.359 ± 0.064. The top influential predictors identified in the model included loneliness, health indicator (i.e. frailty, eyesight, functional mobility), time spent on activities (i.e. staying home, doing exercises and visiting friends) and perceived income adequacy. CONCLUSION: These findings have the potential to identify individuals at risk of depression and prioritize interventions based on the influential factors. The amount of time dedicated to daily activities emerges as a significant indicator of depression risk among middle-aged and elderly individuals, along with loneliness, physical health indicators and perceived income adequacy.

A non-classical synthetic strategy for organic mesocrystals.

Mesocrystals are ordered nanoparticle superstructures, often with internal porosity, which receive much recent research interest in catalysis, energy storage, sensors, and biomedicine area. Understanding the mechanism of synthetic routes is essential for precise control of size and structure that affect the function of mesocrystals. The classical synthetic strategy of mesocrystal was formed via self-assembly of nanoparticles with a faceted inorganic core but a denser (or thicker) shell of organic molecules. However, the potential materials and synthetic handles still need to be explored to meet new applications. In this work, we develop a non-classical synthetic strategy for organic molecules, such as tetrakis (4-hydroxyphenyl) ethylene (TPE-4OH), tetrakis (4-bromophenyl) ethylene (TPE-4Br), and benzopinacole, to produce mesocrystals with composed of microrod arrays via co-solvent-induced crystal transformation. The aligned nanorods are grown epitaxially onto organic microplates, directed by small lattice mismatch between plates and rods. Thus, the present work offers general synthetic handle for establishing well-organized organic mesocrystals.

Dehydroepiandrosterone suppresses human colorectal cancer progression through ER stress-mediated autophagy and apoptosis in a p53-independent manner.

Colorectal cancer (CRC) is one of the primary contributors to cancer-related fatalities, with up to 80% of advanced CRC cases exhibiting mutations in the p53 gene. Unfortunately, the development of new compounds targeting mutant p53 is quite limited. The anticancer effects of Dehydroepiandrosterone (DHEA) on various cancers have been reported. However, the suppressive effect of DHEA on CRC cells harboring wild-type or mutant p53 gene remains controversial. This study emphasized revealing the suppressive mechanism and the effect of DHEA on CRC cell tumorigenesis in the presence of wild-type or mutant p53 gene. We demonstrate that DHEA causes CRC cell death and cell cycle arrest in a dose and time-dependent manner. Notably, DHEA exhibits similar inhibitory effects on CRC cells regardless of the p53 gene status. Further study reveals that DHEA induces endoplasmic reticulum (ER) stress and triggers PERK/eIF2/ATF4/CHOP UPR signaling pathway to activate autophagy followed by apoptosis, which was confirmed by suppression of 4-phenylbutyric acid (an ER stress inhibitor) or knockdown either ATF4 or CHOP. DHEA-induced apoptosis was attenuated by silencing ATG5 gene in either p53+/+ or p53-/- CRC cells, indicating autophagy regulation of apoptosis. Furthermore, DHEA treatment accompanied by bafilomycin A1 (a blocker of autophagosome degradation) leads to the accumulation of ATF4, CHOP, DR5, and p21 levels in CRC cells, implying that the degradative autophagy machinery regulates these four molecules. Consistently, DHEA demonstrates its inhibitory effect by suppressing CRC tumor formation in vivo. Altogether, we provide compelling evidence that DHEA is a potential therapeutic candidate for CRC patient treatment regardless of the p53 status through ER stress-PERK-autophagy-apoptosis axis.

Antibacterial efficacy of low-dosage silver nanoparticle-sodium alginate-chitosan nanocomposite films against pure and clinical acne strains.

The silver nanoparticles-sodium alginate-chitosan (AgNPs-Alg-Chi) nanocomposite film is a compelling material with demonstrated antibacterial efficacy against various pure bacterial strains. However, its potential cytotoxicity at elevated Ag doses warrants investigation. There is a notable dearth of studies assessing its antibacterial effectiveness against clinically relevant bacterial strains, notably Cutibacterium acnes. This study aims to assess the antibacterial efficacy of the low-dose AgNPs-Alg-Chi nanocomposite films on both pure bacterial strains and strains isolated from clinical samples obtained from 65 acne patients. The films were synthesized using green methods, incorporating kumquat (Citrus japonica) extract as a silver ion-reducing agent. The material characterization methods include UV-Vis and FTIR spectroscopies, SEM-EDS, XPS, cell culture, and MTT assay. We successfully fabricated the AgNPs-Alg-Chi nanocomposite films with a low-loading dose of Ag NPs (≤11 µg mL-1, and 37.8 ± 11.5 nm in size). The AgNPs-Alg-Chi nanocomposite film demonstrated comparable antibacterial efficacy to the AgNPs-Chi solution, with MIC values ranging from 3.67 to 5.50 µg mL-1 (p > 0.05) across all strains. Importantly, the AgNPs-Alg-Chi films demonstrated excellent biocompatibility with human keratinocytes (HaCaT cells), maintaining cell viability above 70%. The present AgNPs-Alg-Chi nanocomposite films synthesized by a green approach demonstrated potent antibacterial activity, making them promising for further development into suitable products for human use.

Pharmacomicrobiomics in precision cancer therapy: bench to bedside.

The burgeoning field of pharmacomicrobiomics offers promising insights into the intricate interplay between the microbiome and cancer, shaping responses to diverse treatment modalities. This review aims to analyze the molecular mechanisms underlying interactions between distinct microbiota types and cancer, as well as their influence on treatment outcomes. We explore how the microbiome impacts antitumor immunity, and response to chemotherapy, immunotherapy, and radiation therapy, unveiling its multifaceted roles in cancer progression and therapy resistance. Moreover, we discuss the challenges hindering the development of microbiome-based interventions in cancer therapy, including standardization, validation, and clinical translation. By synthesizing clinical evidence, we underscore the transformative potential of harnessing pharmacomicrobiomics in guiding cancer treatment decisions, paving the way for improved patient outcomes in clinical practice.

KRN5b regulates maize kernel row number through mediating phosphoinositol signalling.

Kernel row number (KRN) is a major yield related trait for maize (Zea mays L.) and is also a major goal of breeders, as it can increase the number of kernels per plant. Thus, identifying new genetic factors involving in KRN formation may accelerate improving yield-related traits genetically. We herein describe a new kernel number-related gene (KRN5b) identified from KRN QTL qKRN5b and encoding an inositol polyphosphate 5-phosphatase (5PTase). KRN5b has phosphatase activity towards PI(4,5)P2, PI(3,4,5)P3, and Ins(1,4,5)P3 in vitro. Knocking out KRN5b caused accumulation of PI(4,5)P2 and Ins(1,4,5)P3, resulting in disordered kernel rows and a decrease in the number of kernels and tassel branches. The introgression of the allele with higher expression abundance into different inbred lines could increase the ear weight of the inbred lines and the corresponding hybrids by 10.1%-12.2% via increasing KRN, with no adverse effects on other agronomic traits. Further analyses showed that KRN5b regulates inflorescence development through affecting the synthesis and distribution of hormones. Together, KRN5b contributes to spikelet pair meristem development through inositol phosphate and phosphatidylinositols, making it a selecting target for yield improvement.

High photocatalytic efficiency of a ZnO nanoplate/Fe2O3 nanospindle hybrid using visible light for methylene blue degradation.

In this work, ZnO nanoplates and Fe2O3 nanospindles were successfully fabricated via a simple hydrothermal method using inorganic salts as precursors. The ZnO/Fe2O3 hybrid was fabricated using a mechanical mixture of two different ZnO : Fe2O3 weight ratios to investigate the effect of weight ratio on catalytic properties. Scanning electron microscopy (SEM) and transmission electron microscopy (TEM) images showed that ZnO nanoplates (NPls) are about 20 nm thick with lateral dimensions of 100 × 200 nm, and Fe2O3 nanospindles (NSs) are about 500 nm long and 50 nm wide. X-ray diffraction (XRD) patterns revealed the successful formation of the ZnO, Fe2O3, and ZnO/Fe2O3 samples and indicated that their crystallite sizes varied from 20 to 29 nm depending on the ZnO : Fe2O3 weight ratio. Ultraviolet-visible (UV-vis) spectra showed that the bandgap energies of ZnO and Fe2O3 were 3.15 eV and 2.1 eV, respectively. Energy dispersive X-ray spectroscopy (EDS) results revealed the successful combination of ZnO and Fe2O3. Photocatalytic activity of the materials was evaluated through the degradation of methylene blue (MB) in aqueous solution under green light-emitting diode (GLED) irradiation. The results indicated that the ZnO/Fe2O3 composite showed a remarkable enhanced degradation capacity compared to bare ZnO NPls and Fe2O3 NSs. The ZnO : Fe2O3 = 3 : 2 sample demonstrated the best performance among all samples under identical conditions with a degradation efficiency of 99.3% for MB after 85 min. The optimum photocatalytic activity of the sample with ZnO : Fe2O3 = 3 : 2 was nearly 3.6% higher than that of the pure ZnO sample and 1.12 times more than that of the pristine Fe2O3 sample. Moreover, the highest photo-degradation was obtained at a photocatalyst dosage of 0.25 g l-1 in dye solution.

New Cytotoxic Sesquiterpene Lactones from the Leaves of Tithonia Diversifolia and their Apoptosis Effect Evaluation in KB Cancer Cells.

From the leaves of Tithonia diversifolia, nine sesquiterpenoids (1-9), including two new ones (tagitinin J (1) and tagitinin K (2)) were isolated and structurally determined. Their chemical structures were elucidated by extensive analyses of the HRESIMS and NMR spectral data, as well as comparison with the literature. All of the isolated compounds (except compounds 7-9) significantly exhibited cytotoxic activity against four human cancer cell lines (KB, HepG2, A549 and MCF7), with IC50 values ranging from 0.29-17.0 µM, which were in the same range as the positive control ellipticine or even lower. Further, the apoptosis induction effects of two new compounds 1 and 2 were also investigated and reported. While compound 2 did not induce the apoptosis in KB cells at test concentrations, compound 1 was found to possess anti-proliferative activity through concentration-dependently inducing cell cycle arrest at S phase, morphological changes, activation of caspase 3, and an increase in the early-stage apoptosis of KB cells at a concentration of 7.26 µM.

In Vitro and in Silico Study of New Biscoumarin Glycosides from Paramignya trimera against Angiotensin-Converting Enzyme 2 (ACE-2) for Preventing SARS-CoV-2 Infection.

In Vietnam, the stems and roots of the Rutaceous plant Paramignya trimera (Oliv.) Burkill (known locally as "Xáo tam phân") are widely used to treat liver diseases such as viral hepatitis and acute and chronic cirrhosis. In an effort to search for Vietnamese natural compounds capable of inhibiting coronavirus based on molecular docking screening, two new dimeric coumarin glycosides, namely cis-paratrimerin B (1) and cis-paratrimerin A (2), and two previously identified coumarins, the trans-isomers paratrimerin B (3) and paratrimerin A (4), were isolated from the roots of P. trimera and tested for their anti-angiotensin-converting enzyme 2 (ACE-2) inhibitory properties in vitro. It was discovered that ACE-2 enzyme was inhibited by cis-paratrimerin B (1), cis-paratrimerin A (2), and trans-paratrimerin B (3), with IC50 values of 28.9, 68, and 77 µM, respectively. Docking simulations revealed that four biscoumarin glycosides had good binding energies (∆G values ranging from -10.6 to -14.7 kcal/mol) and mostly bound to the S1' subsite of the ACE-2 protein. The key interactions of these natural ligands include metal chelation with zinc ions and multiple H-bonds with Ser128, Glu145, His345, Lys363, Thr371, Glu406, and Tyr803. Our findings demonstrated that biscoumarin glycosides from P. trimera roots occur naturally in both cis- and trans-diastereomeric forms. The biscoumarin glycosides Lys363, Thr371, Glu406, and Tyr803. Our findings demonstrated that biscoumarin glycosides from P. trimera roots hold potential for further studies as natural ACE-2 inhibitors for preventing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection.

Evaluation of Dihydroartemisinin-Piperaquine Efficacy and Molecular Markers in Uncomplicated Falciparum Patients: A Study across Binh Phuoc and Dak Nong, Vietnam.

Background and Objectives: Malaria continues to be a significant global health challenge. The efficacy of artemisinin-based combination therapies (ACTs) has declined in many parts of the Greater Mekong Subregion, including Vietnam, due to the spread of resistant malaria strains. This study was conducted to assess the efficacy of the Dihydroartemisinin (DHA)-Piperaquine (PPQ) regimen in treating uncomplicated falciparum malaria and to conduct molecular surveillance of antimalarial drug resistance in Binh Phuoc and Dak Nong provinces. Materials and Methods: The study included 63 uncomplicated malaria falciparum patients from therapeutic efficacy studies (TES) treated following the WHO treatment guidelines (2009). Molecular marker analysis was performed on all 63 patients. Methods encompassed Sanger sequencing for pfK13 mutations and quantitative real-time PCR for the pfpm2 gene. Results: This study found a marked decrease in the efficacy of the DHA-PPQ regimen, with an increased rate of treatment failures at two study sites. Genetic analysis revealed a significant presence of pfK13 mutations and pfpm2 amplifications, indicating emerging resistance to artemisinin and its partner drug. Conclusions: The effectiveness of the standard DHA-PPQ regimen has sharply declined, with rising treatment failure rates. This decline necessitates a review and possible revision of national malaria treatment guidelines. Importantly, molecular monitoring and clinical efficacy assessments together provide a robust framework for understanding and addressing detection drug resistance in malaria.

Single-Molecule Investigation of the Binding Interface Stability of SARS-CoV-2 Variants with ACE2.

The SARS-CoV-2 pandemic spurred numerous research endeavors to comprehend the virus and mitigate its global severity. Understanding the binding interface between the virus and human receptors is pivotal to these efforts and paramount to curbing infection and transmission. Here we employ atomic force microscopy and steered molecular dynamics simulation to explore SARS-CoV-2 receptor binding domain (RBD) variants and angiotensin-converting enzyme 2 (ACE2), examining the impact of mutations at key residues upon binding affinity. Our results show that the Omicron and Delta variants possess strengthened binding affinity in comparison to the Mu variant. Further, using sera from individuals either vaccinated or with acquired immunity following Delta strain infection, we assess the impact of immunity upon variant RBD/ACE2 complex formation. Single-molecule force spectroscopy analysis suggests that vaccination before infection may provide stronger protection across variants. These results underscore the need to monitor antigenic changes in order to continue developing innovative and effective SARS-CoV-2 abrogation strategies.

Revealing the high efficiency of fluorescence quenching of rhodamine B by triangular silver nanodisks due to the inner filter effect mechanism.

Performing effective fluorescence quenching based on a metal nanomaterial is essential to construct fluorescence sensors. Silver nanomaterials are well known as an excellent candidate for an absorber in fluorescence sensing systems. Herein, we investigated the fluorescence quenching of rhodamine B (RhB) in the presence of triangular silver nanodisks in which perfect overlap between the absorption of the absorber and the fluorescence of the fluorophore was observed. The fluorescence quenching mechanism of RhB was investigated under various excitation wavelengths, together with measurement of the fluorescence lifetime. The quenching efficiency of RhB was proportional to the wavelength excitation. Remarkably, the highest efficiency of fluorescence quenching of RhB was achieved (∼60%). The quenching mechanism was investigated and revealed to be mostly due to the inner filter effect (IFE) mechanism, without the contribution of energy transfer. This result shows a completely different story from most previous studies based on silver nanoparticles, where energy transfer was reported to play a significant role.

Role of seasonal importation and genetic drift on selection for drug-resistant genotypes of Plasmodium falciparum in high-transmission settings.

Historically Plasmodium falciparum has followed a pattern of drug resistance first appearing in low-transmission settings before spreading to high-transmission settings. Several features of low-transmission regions are hypothesized as explanations: higher chance of symptoms and treatment seeking, better treatment access, less within-host competition among clones and lower rates of recombination. Here, we test whether importation of drug-resistant parasites is more likely to lead to successful emergence and establishment in low-transmission or high-transmission periods of the same epidemiological setting, using a spatial, individual-based stochastic model of malaria and drug-resistance evolution calibrated for Burkina Faso. Upon controlling for the timing of importation of drug-resistant genotypes and examination of key model variables, we found that drug-resistant genotypes imported during the low-transmission season were (i) more susceptible to stochastic extinction due to the action of genetic drift, and (ii) more likely to lead to establishment of drug resistance when parasites are able to survive early stochastic loss due to drift. This implies that rare importation events are more likely to lead to establishment if they occur during a high-transmission season, but that constant importation (e.g. neighbouring countries with high levels of resistance) may produce a greater risk during low-transmission periods.

Assessing emergence risk of double-resistant and triple-resistant genotypes of Plasmodium falciparum.

Delaying and slowing antimalarial drug resistance evolution is a priority for malaria-endemic countries. Until novel therapies become available, the mainstay of antimalarial treatment will continue to be artemisinin-based combination therapy (ACT). Deployment of different ACTs can be optimized to minimize evolutionary pressure for drug resistance by deploying them as a set of co-equal multiple first-line therapies (MFT) rather than rotating therapies in and out of use. Here, we consider one potential detriment of MFT policies, namely, that the simultaneous deployment of multiple ACTs could drive the evolution of different resistance alleles concurrently and that these resistance alleles could then be brought together by recombination into double-resistant or triple-resistant parasites. Using an individual-based model, we compare MFT and cycling policies in malaria transmission settings ranging from 0.1% to 50% prevalence. We define a total risk measure for multi-drug resistance (MDR) by summing the area under the genotype-frequency curves (AUC) of double- and triple-resistant genotypes. When prevalence ≥ 1%, total MDR risk ranges from statistically similar to 80% lower under MFT policies than under cycling policies, irrespective of whether resistance is imported or emerges de novo. At 0.1% prevalence, there is little statistical difference in MDR risk between MFT and cycling.