Trinuclear ruthenium(II) polypyridyl complexes: Evaluation as photosensitizers for enhanced cervical cancer treatment.

Trinuclear ruthenium(II) polypyridyl complexes anchored to benzimidazole-triazine / trisamine scaffolds were investigated as photosensitizers for photodynamic therapy. The trinuclear complexes were noted to produce a significant amount of singlet oxygen in both DMF and aqueous media, are photostable and show appreciable emission quantum yields (ɸem). In our experimental setting, despite the moderate phototoxic activity in the HeLa cervical cancer cell line, the phototoxic indices (PI) of the trinuclear complexes are superior relative to the PIs of a clinically approved photosensitizer, Photofrin®, and the pro-drug 5-aminolevulinic acid (PI: >7 relative to PI: >1 and PI: 4.4 for 5-aminolevulinic acid and Photofrin®, respectively). Furthermore, the ruthenium complexes were noted to show appreciable long-term cytotoxicity upon light irradiation in HeLa cells in a concentration-dependent manner. Consequently, this long-term activity of the ruthenium(II) polypyridyl complexes embodies their ability to reduce the probability of the recurrence of cervical cancer. Taken together, this presents a strong motivation for the development of polymetallic complexes as anticancer agents.

[18F]FDG PET/CT Signal Correlates with Neoangiogenesis Markers in Patients with Fibrotic Interstitial Lung Disease Who Underwent Lung Biopsy: Implication for the Use of PET/CT in Diffuse Lung Diseases.

The use of [18F]FDG PET/CT as a biomarker in diffuse lung diseases is increasingly recognized. We investigated the correlation between [18F]FDG uptake with histologic markers on lung biopsy of patients with fibrotic interstitial lung disease (fILD). Methods: We recruited 18 patients with fILD awaiting lung biopsy for [18F]FDG PET/CT. We derived a target-to-background ratio (TBR) of maximum pulmonary uptake of [18F]FDG (SUVmax) divided by the lung background (SUVmin). Consecutive paraffin-embedded lung biopsy sections were immunostained for alveolar and interstitial macrophages (CD68), microvessel density (MVD) (CD31 and CD105/endoglin), and glucose transporter 1. MVD was expressed as vessel area percentage per high-power field (Va%/hpf). Differences in imaging and angiogenesis markers between histologic usual interstitial pneumonia (UIP) and non-UIP were assessed using a nonparametric Mann-Whitney test. Correlation of imaging with angiogenesis markers was assessed using the nonparametric Spearman rank correlation. Univariate Kaplan-Meier survival analysis assessed the difference in the survival curves for each of the angiogenesis markers (separated by their respective optimal cutoff) using the log-rank test. Statistical analysis was performed using SPSS. Results: In total, 18 patients were followed for an average of 41.36 mo (range, 5.69-132.46 mo; median, 30.07 mo). Only CD105 MVD showed a significantly positive correlation with [18F]FDG TBR (Spearman rank correlation, 0.556; P < 0.05, n = 13). There was no correlation between [18F]FDG uptake and macrophage expression of glucose transporter 1. CD105 and CD31 were higher for UIP than for non-UIP, with CD105 reaching statistical significance (P = 0.011). In all patients, MVD assessed with either CD105 or CD31 quantification on biopsy predicted overall survival. Patients with CD105 MVD of less than 12 Va%/hpf or CD31 MVD of less than 35 Va%/hpf had a significantly better prognosis (no deaths during follow-up in the case of CD105) than did patients with higher scores of CD105 MVD (median survival, 35 mo; P = 0.041, n = 13) or CD31 MVD (median survival, 28 mo; P = 0.014, n = 13). Conclusion: Previous work has used [18F]FDG uptake in PET/CT as a biomarker in fILD. Here, we highlight a correlation between angiogenesis and [18F]FDG TBR. We show that MVD is higher for UIP than for non-UIP and is associated with mortality in patients with fILD. These data set the scene to investigate the potential role of vasculature and angiogenesis in fibrosis.

Path-dependent morphology of CH4 hydrates and their dissociation studied with high-pressure microfluidics.

Methane hydrates (MHs) have been considered a promising future energy source due to their vast resource volume and high energy density. Understanding the behavior of MH formation and dissociation at the pore-scale and the effect of MH distribution on the gas-liquid two phase flow is of critical importance for designing effective production strategies from natural gas hydrate (NGH) reservoirs. In this study, we devised a novel high-pressure microfluidic chip apparatus that is capable of direct observation of MH formation and dissociation behavior at the pore-scale. MH nucleation and growth behavior at 10.0 MPa and dissociation via thermal stimulation with gas bubble generation and evolution were examined. Our experimental results reveal that two different MH formation mechanisms co-exist in pores: (a) porous-type MH with a rough surface formed from CH4 gas bubbles at the gas-liquid interface and (b) crystal-type MH formed from dissolved CH4 gas. The growth and movement of crystal-type MH can trigger the sudden nucleation of porous-type MH. Spatially, MHs preferentially grow along the gas-liquid interface in pores. MH dissociation under thermal stimulation practically generates gas bubbles with diameters of 20.0-200.0 µm. Based on a custom-designed image analysis technique, three distinct stages of gas bubble evolution were identified during MH dissociation via thermal stimulation: (a) single gas bubble growth with an expanding water layer at an initial slow dissociation rate, (b) rapid generation of clusters of gas bubbles at a fast dissociation rate, and (c) gas bubble coalescence with uniform distribution in the pore space. The novel apparatus designed and the image analysis technique developed in this study allow us to directly capture the dynamic evolution of the gas-liquid interface during MH formation and dissociation at the pore-scale. The results provide direct first-hand visual evidence of the growth of MHs in pores and valuable insights into gas-liquid two-phase flow behavior during fluid production from NGHs.

Taking cues from machine learning, compartmental and time series models for SARS-CoV-2 omicron infection in Indian provinces.

SARS-CoV-2, the virus responsible for COVID-19, posed a significant threat to the world. We analyzed COVID-19 dissemination data in the top ten Indian provinces by infection incidences using the Susceptible-Infectious-Removed (SIR) model, an Autoregressive Integrated Moving Average (ARIMA) time series model, a machine learning model based on the Random Forest, and distribution fitting. Outbreaks are expected to continue if the Basic Reproduction Number (R0) > 1, and infection waves are anticipated to end if the R0 < 1, as determined by the SIR model. Different parametric probability distributions are also fitted. Data collected from December 12, 2021, to March 31, 2022, encompassing data from both before and during the implementation of strict control measures. Based on the estimates of the model parameters, health agencies and government policymakers can develop strategies to combat the spread of the disease in the future, and the most effective technique can be recommended for real-world application for other outbreaks of COVID-19. The best method out of these could be also implemented further on the epidemiological data of other similar infectious agents.

Campesterol and dithymoquinone as a potent inhibitors of SARS cov-2 main proteases-promising drug candidates for targeting its novel variants.

The sudden outbreak of the COVID-19 pandemic has currently taken approximately 2.4 million lives, with no specific medication and fast-tracked tested vaccines for prevention. These vaccines have their own adverse effects, which have severely affected the global healthcare system. The discovery of the main protease structure of coronavirus (Mpro/Clpro) has resulted in the identification of compounds having antiviral potential, especially from the herbal system. In this study, the computer-associated drug design tools were utilised to analyze the reported phytoconstituents of Nigella sativa for their antiviral activity against the main protease. Fifty-eight compounds were subjected to pharmacological parameter analysis to determine their lead likeness in comparison to the standard drugs (chloroquine and nirmatrelvir) used in the treatment of SARS-CoV-2. Nearly 31 compounds were docked against five different SARS-CoV-2 main proteases, and all compounds showed better binding affinity and inhibition constant against the proteases. However, dithymoquinone and campesterol displayed the best binding scores and hence were further subjected to dynamics and MMPBSA study for 100 ns. The stability analysis shows that dithymoquinone and campesterol show less variation in fluctuation in residues compared to standard complexes. Moreover, dithymoquinone exhibited higher binding affinity and favorable interaction followed by campesterol as compared to the standard drug. The in silico computational analysis provides a promising hit for regulating the main proteases activity.Communicated by Ramaswamy H. Sarma.

Aminoquinoline-based Re(I) tricarbonyl complexes: Insights into their antiproliferative activity and mechanisms of action.

In an effort to develop new potent anticancer agents, two Schiff base rhenium(I) tricarbonyl complexes, containing the ubiquitous aminoquinoline scaffold, were synthesized. Both aminoquinoline ligands and Re(I) complexes showed adequate stability over a 48-h incubation period. Furthermore, the cytotoxic activity of the precursor ligands and rhenium(I) complexes were evaluated against the hormone-dependent MCF-7 and hormone-independent triple negative MDA-MB-231 breast cancer cell lines. Inclusion of the [Re(CO)3Cl]+ entity significantly enhanced the cytotoxicity of the aminoquinoline Schiff base ligands against the tested cancer cell lines. Remarkably, the incorporation of the Schiff-base iminoquinolyl entity notably enhanced the cytotoxic activity of the Re(I) complexes, in comparison with the iminopyridyl entity. Notably, the quinolyl-substituted complex showed up to three-fold higher activity than cisplatin against breast cancer cell lines, underpinning the significance of the quinoline pharmacophore in rational drug design. In addition, the most active Re(I) complex showed better selectivity towards the breast cancer cells over non-tumorigenic FG-0 cells. Western blotting revealed that the complexes increased levels of γH2AX, a key DNA damage response protein. Moreover, apoptosis was confirmed in both cell lines due to the detection of cleaved PARP. The complexes show favourable binding affinities towards both calf thymus DNA (CT-DNA), and bovine serum albumin (BSA), and the order of their interactions align with their cytotoxic effects. The in silico molecular simulations of the complexes were also performed with CT-DNA and BSA targets.

In silico analysis to identify potential antitubercular molecules in Morus alba through virtual screening and molecular dynamics simulations.

A major obstacle in the treatment of tuberculosis (TB) is to combat the emerging resistant strains of its causing agent i.e. Mycobacterium tuberculosis (MTb). The emergence of multidrug-resistant and extensively drug-resistant -TB strains raise a requirement of new potential anti-tubercular compounds. In this direction, different plant parts of Morus alba were tested against MTb and found to be active with a minimum inhibitory concentration ranging between 125 µg/ml to 31.5 µg/ml. Further to identify the phytochompounds having anti-mycobacterium activity, phytocompounds of the plant were docked against the five MTb proteins (PDB ID: 3HEM, 4OTK, 2QO0, 2AQ1 and 6MNA). Among twenty-two tested phytocompounds, four phytocompounds with effective binding energy (kcal/mol): Petunidin-3-rutinoside (3HEM: -8.2, 4OTK: -6.9, 2QO0: -9.0, 2AQ1: -8.3 and 6MNA:-7.8), Quercetin-3'-glucoside (3HEM:-6.7, 4OTK:-7.6, 2QO0:-7.6, 2AQ1:7.6 and 6MNA:-6.4), Rutin (3HEM:-7.8, 4OTK:-7.5, 2QO0:-9.1, 2AQ1:9.3 and 6MNA:-6.9) and Isoquercitrin (3HEM:-7.3, 4OTK:-6.6, 2QO0:-7.7, 2AQ1:8.3 and 6MNA:-6.6) shows promising activity against all the five target proteins. Further molecular dynamics studies of Petunidin-3-rutinoside with three target proteins 3HEM, 2AQ1 and 2QO0 resulted with low values of average RMSD (3.723 Å, 3.261 Å, and 2.497 Å, respectively) show that the complexes have better conformational stability. The wet lab validation of the current study will pave the new dimensions for the cure of TB patients.Communicated by Ramaswamy H. Sarma.

Generation of autoantibodies against glycated fibrinogen: Role in diabetic nephropathy and retinopathy.

The process of glycation, characterized by the non-enzymatic reaction between sugars and free amino groups on biomolecules, is a key contributor to the development and progression of both microvascular and macrovascular complications associated with diabetes, particularly due to persistent hyperglycemia. This glycation process gives rise to advanced glycation end products (AGEs), which play a central role in the pathophysiology of diabetes complications, including nephropathy. The d-ribose-mediated glycation of fibrinogen plays a central role in the pathogenesis of diabetes nephropathy (DN) and retinopathy (DR) by the generation and accumulation of advanced glycation end products (AGEs). Glycated fibrinogen with d-ribose (Rb-gly-Fb) induces structural changes that trigger an autoimmune response by generating and exposing neoepitopes on fibrinogen molecules. The present research is designed to investigate the prevalence of autoantibodies against Rb-gly-Fb in individuals with type 2 diabetes mellitus (T2DM), DN & DR. Direct binding ELISA was used to test the binding affinity of autoantibodies from patients' sera against Rb-gly-Fb and competitive ELISA was used to confirm the direct binding findings by checking the bindings of isolated IgG against Rb-gly-Fb and its native conformer. In comparison to healthy subjects, 32% of T2DM, 67% of DN and 57.85% of DR patients' samples demonstrated a strong binding affinity towards Rb-gly-Fb. Both native and Rb-gly-Fb binding by healthy subjects (HS) sera were non-significant (p > 0.05). Furthermore, the early, intermediate, and end products of glycation have been assessed through biochemical and physicochemical analysis. The biochemical markers in the patient groups were also significant (p < 0.05) in comparison to the HS group. This study not only establishes the prevalence of autoantibodies against d-ribose glycated fibrinogen in DN but also highlights the potential of glycated fibrinogen as a biomarker for the detection of DN and/or DR. These insights may open new avenues for research into novel therapeutic strategies and the prevention of diabetes-related nephropathy and retinopathy.

Whole-genome sequence of Proteus faecis CR112, isolated from the gut of a healthy Labeo rohita.

Bacteria of the genus Proteus are gram-negative bacilli. Proteus faecis CR112 was isolated from fish gut based on its antibacterial activity against fish pathogens. The genome sequence of CR112 provided valuable information about its secondary metabolite gene clusters.

Non-prescription antibiotics dispensing by community pharmacies: implications for antimicrobial resistance.

Introduction: The non-prescription antibiotics dispensing (NPAD) from pharmacies is on the rise in low- and middle-income countries, which contributes to the emergence of antimicrobial resistance (AMR). This study was conducted with the objective to determine the community pharmacy personnel's perspectives on NPAD and its implications for AMR. Methods: A questionnaire-based cross-sectional survey was conducted in Pakistan among 336 pharmacies. The data were analyzed using SPSS v21 and MedCalc for Windows v12.3.0. Modified Bloom's cut-off point was utilized to categorize the participants' overall knowledge, attitude, and practice. For univariable logistic regression analyses, odds ratio (OR) was calculated at 95% confidence interval (CI). For multivariable logistic regression analyses, adjusted OR was calculated at 95% CI. Spearman's rank correlation coefficient test was used to assess the relationships among knowledge, attitude, and/or practice scores. Results: The majority of the respondents were staff pharmacists (45.5%). About four-fifths (78.9%) and half (50.9%) of the participants demonstrated moderate to good knowledge and practice, respectively. However, about only one-third (33.1%) had a moderate to good attitude. Staff pharmacists had higher odds of moderate to good knowledge (OR: 2.4, 95% CI: 1.2-4.7) and practice (OR: 2.3, 95% CI: 1.4-3.8). Total knowledge and practice (Spearman's ρ: 0.280; P <0.001) and total attitude and practice (Spearman's ρ: 0.299; P <0.001) scores were significantly correlated. Conclusion: The qualified pharmacists had satisfactory knowledge, attitude, and practices toward antibiotics. However, non-pharmacist staff lacked knowledge and had probable NPAD practice, which has a negative impact on public health. Regular refresher training, seminars, and strict enforcement of rules and regulations are essential.

Comparative Assessment of Periodontal Status in Subjects with and without Polycystic Ovary Syndrome and its Correlation with Body Mass Index: A Cross-Sectional Study.

New avenues for research have opened, which assess the influence of systemic disease on periodontium and vice versa. To find the correlation between polycystic ovary syndrome (PCOS) and periodontium by assessing clinical parameters [plaque index (PI), probing depth, periodontal disease index (PDI)] and the anthropological parameter [body mass index (BMI)] and to find the correlation between body mass index and periodontal disease index in subjects with and without PCOS. Sixty females comprising 30 with PCOS and 30 without PCOS were selected. Clinical, anthropological, and radiological assessment was done. Double blinding was incorporated. There was a statistically highly significant difference in mean age, mean PI, and mean PDI (P < 0.001) in PCOS group when compared to those without PCOS group by unpaired t-test for inter-group analysis. A statistically significant difference was found in mean probing depth and mean BMI (P < 0.05) in PCOS group when compared to those without PCOS group by unpaired t-test for inter-group analysis. No statistically significant correlation was found between mean PDI and mean BMI in PCOS and non-PCOS group subjects using Spearman's rank correlation. Women suffering from PCOS may be at a heightened risk for developing periodontal disease as our study re-establishes this association with respect to some periodontal parameters. With such a result, general practitioners/gynecologists can be encouraged to refer cases of PCOS to periodontists for early detection, prevention of periodontal disease, and maintenance of periodontal health.

Nitazoxanide and quercetin co-loaded nanotransfersomal gel for topical treatment of cutaneous leishmaniasis with macrophage targeting and enhanced anti-leishmanial effect.

Purpose: Anti-leishmanial medications administered by oral and parenteral routes are less effective for treatment of cutaneous leishmaniasis (CL) and cause toxicity, hence targeted drug delivery is an efficient way to improve drug availability for CL with reduced toxicity. This study aimed to develop, characterize and evaluate nitazoxanide and quercetin co-loaded nanotransfersomal gel (NTZ-QUR-NTG) for the treatment of CL. Methods: NTZ-QUR-NT were prepared by thin film hydration method and were statistically optimized using Box-Behnken design. To ease the topical delivery and enhance the retention time, the NTZ-QUR-NT were dispersed in 2 % chitosan gel. Moreover, in-vitro drug release, ex-vivo permeation, macrophage uptake, cytotoxicity and anti-leishmanial assays were performed. Results: The optimized formulation indicated mean particle size 210 nm, poly dispersity index (PDI) 0.16, zeta potential (ZP) -15.1 mV and entrapment efficiency (EE) of NTZ and QUR was 88 % and 85 %, respectively. NTZ-QUR-NT and NTZ-QUR-NTG showed sustained release of the incorporated drugs as compared to the drug dispersions. Skin permeation of NTZ and QUR in NTZ-QUR-NTG was 4 times higher in comparison to the plain gels. The NTZ-QUR-NT cell internalization was almost 10-folds higher than NTZ-QUR dispersion. The cytotoxicity potential (CC50) of NTZ-QUR-NT (71.95 ± 3.32 µg/mL) was reduced as compared to NTZ-QUR dispersion (49.77 ± 2.15 µg/mL. A synergistic interaction was found between NTZ and QUR. Moreover, in-vitro anti-leishmanial assay presented a lower IC50 value of NTZ-QUR-NT as compared to NTZ-QUR dispersion. Additionally, a significantly reduced lesion size was observed in NTZ-QUR-NTG treated BALB/c mice, indicating its antileishmanial potential. Conclusion: It can be concluded that nanotransfersomal gel has the capability to retain and permeate the incorporated drugs through stratum corneum and induce synergetic anti-leishmanial effect of NTZ and QUR against cutaneous leishmaniasis.

Modeling Global Monkeypox Infection Spread Data: A Comparative Study of Time Series Regression and Machine Learning Models.

The global impact of COVID-19 has heightened concerns about emerging viral infections, among which monkeypox (MPOX) has become a significant public health threat. To address this, our study employs a comprehensive approach using three statistical techniques: Distribution fitting, ARIMA modeling, and Random Forest machine learning to analyze and predict the spread of MPOX in the top ten countries with high infection rates. We aim to provide a detailed understanding of the disease dynamics and model theoretical distributions using country-specific datasets to accurately assess and forecast the disease's transmission. The data from the considered countries are fitted into ARIMA models to determine the best time series regression model. Additionally, we employ the random forest machine learning approach to predict the future behavior of the disease. Evaluating the Root Mean Square Errors (RMSE) for both models, we find that the random forest outperforms ARIMA in six countries, while ARIMA performs better in the remaining four countries. Based on these findings, robust policy-making should consider the best fitted model for each country to effectively manage and respond to the ongoing public health threat posed by monkeypox. The integration of multiple modeling techniques enhances our understanding of the disease dynamics and aids in devising more informed strategies for containment and control.

Identification of Glycoxidative Lesion in Isolated Low-Density Lipoproteins from Diabetes Mellitus Subjects.

Methylglyoxal (MG) is a precursor for advanced glycation end-products (AGEs), which have a significant role in diabetes. The present study is designed to probe the immunological response of native and glycated low-density lipoprotein (LDL) in experimental animals. The second part of this study is to probe glycoxidative lesion detection in low-density lipoproteins (LDL) in diabetes subjects with varying disease duration. The neo-epitopes attributed to glycation-induced glycoxidative lesion of LDL in DM patients' plasma were, analyzed by binding of native and MG-modified LDL immunized animal sera antibodies using an immunochemical assay. The plasma purified human LDL glycation with MG, which instigated modification in LDL. Further, the NewZealand-White rabbits were infused with unmodified natural LDL (N-LDL) and MG-glycatedLDL to probe its immunogenicity. The glycoxidative lesion detection in LDL of DM with disease duration (D.D.) of 5-15 years and D.D. > 15 years was found to be significantly higher as compared to normal healthy subjects (NHS) LDL. The findings support the notion that prolonged duration of diabetes can cause structural alteration in LDL protein molecules, rendering them highly immunogenic in nature. The presence of LDL lesions specific to MG-associated glycoxidation would further help in assessing the progression of diabetes mellitus.

Investigation of the treatment potential of Raloxifene-loaded polymeric nanoparticles in osteoporosis: In-vitro and in-vivo analyses.

Osteoporosis (OP), is a systemic bone disorder associated with low bone mass and bone tissue corrosion. Worsening of the disease condition leads to bone delicacy and fracture. Various drugs are available for the treatment of OP, however they have limitations including poor solubility, bioavailability and toxicity. Herein, Raloxifene-loaded polymeric nanoparticles (RLX-PNPs) were developed and investigated for the treatment of OP with possible solutions to the above mentioned problems. RLX-PNPs were prepared by modified ionic gelation method followed by determining their particle properties. FTIR, DSC and PXRD analysis of the RLX-PNPs were performed to check chemical interaction, thermal behavior and crystallinity, respectively. In-vitro release profile of RLX-PNPs was checked in lab setting, whereas its pharmacokinetics was investigated in Sprague-Dawley rats, in-vivo. Finally, the treatment potential of RLX-PNPs was analyzed in OP induced animal model. The optimized PNPs formulation indicated 134.5 nm particle size, +24.4 mV charge and 91.73% % EE. TEM analysis showed spherical and uniform sized particles with no interactions observed in FTIR analysis. In-vitro release of RLX from RLX-PNPs showed more sustained release behavior as compared to RLX-suspension. Moreover, pharmacokinetic investigations showed a significantly enhanced bioavailability of the RLX-PNPs as well as reduced serum levels of alkaline phosphatase and calcium in OP induced rats when compared with RLX-Suspension after oral administration. Findings of this study suggested that the developed RLX-PNPs have the potential to treat OP due to sustained release and improved bioavailability of the incorporated drug.

Metformin HCl-loaded transethosomal gel; development, characterization, and antidiabetic potential evaluation in the diabetes-induced rat model.

Herein we designed, optimized, and characterized the Metformin Hydrochloride Transethosomes (MTF-TES) and incorporate them into Chitosan gel to develop Metformin Hydrochloride loaded Transethosomal gel (MTF-TES gel) that provides a sustained release, improved transdermal flux and improved antidiabetic response of MTF. Design Expert® software (Ver. 12, Stat-Ease, USA) was applied for the statistical optimization of MTF-TES. The formulation with Mean Particle Size Distribution (MPSD) of 165.4 ± 2.3 nm, Zeta Potential (ZP) of -21.2 ± 1.9 mV, Polydispersity Index (PDI) of 0.169 ± 0.033, and MTF percent Entrapment Efficiency (%EE) of 89.76 ± 4.12 was considered to be optimized. To check the chemical incompatibility among the MTF and other formulation components, Fourier Transform Infrared (FTIR) spectroscopy was performed and demonstrated with no chemical interaction. Surface morphology, uniformity, and segregation were evaluated through Transmission Electron Microscopy (TEM). It was revealed that the nanoparticles were spherical and round in form with intact borders. The fabricated MTF-TES has shown sustained release followed by a more pronounced effect in MTF-TES gel as compared to the plain MTF solution (MTFS) at a pH of 7.4. The MTF-TES has shown enhanced permeation followed by MTF-TES gel as compared to the MTFS at a pH of 7.4. In vivo antidiabetic assay was performed and results have shown improved antidiabetic potential of the MTF-TES gel, in contrast to MTF-gel. Conclusively, MTF-TES is a promising anti-diabetic candidate for transdermal drug delivery that can provide sustained MTF release and enhanced antidiabetic effect.

The Effectiveness and Safety of Direct Oral Anticoagulants in Obese Patients With Atrial Fibrillation: A Network Meta-Analysis.

Atrial fibrillation (AF) is a cardiac condition characterized by an irregular heart rhythm, which is increasingly prevalent in the modern era. All international guidelines strongly advise the administration of anticoagulants to individuals with AF who are at high risk of stroke. These guidelines recommend the use of direct oral anticoagulants (DOACs) over warfarin because warfarin is significantly associated with increased rates of major bleeding, numerous interactions with food and drugs, and the necessity for frequent monitoring. The aim of this study is to compare the effectiveness and safety of direct oral anticoagulants (DOACs) in obese patients with atrial fibrillation. Two authors independently conducted a comprehensive literature search using electronic databases including PubMed, CINAHL, and EMBASE from inception to June 1, 2023. The efficacy outcome assessed in this meta-analysis included the composite of stroke and systemic embolism. For safety analysis, major bleeding events were compared among the study groups. Eleven studies fulfilled all the inclusion criteria and were included in the present meta-analysis enrolling 144,502 patients. In this study, DOACs demonstrate superior efficacy in preventing stroke/systemic embolism compared to warfarin. Among the DOACs, apixaban emerged as the most effective, followed by rivaroxaban, warfarin, and dabigatran. In terms of safety, apixaban was also found to be the most favorable treatment option, followed by rivaroxaban, dabigatran, and warfarin. In summary, our study concludes that apixaban exhibited greater effectiveness and safety when compared to other DOACs and warfarin in obese patients with AF.

Transfer Learning of Full Molecular Weight Distributions via High-Throughput Computer-Controlled Polymerization.

The skew and shape of the molecular weight distribution (MWD) of polymers have a significant impact on polymer physical properties. Standard summary metrics statistically derived from the MWD only provide an incomplete picture of the polymer MWD. Machine learning (ML) methods coupled with high-throughput experimentation (HTE) could potentially allow for the prediction of the entire polymer MWD without information loss. In our work, we demonstrate a computer-controlled HTE platform that is able to run up to 8 unique variable conditions in parallel for the free radical polymerization of styrene. The segmented-flow HTE system was equipped with an inline Raman spectrometer and offline size exclusion chromatography (SEC) to obtain time-dependent conversion and MWD, respectively. Using ML forward models, we first predict monomer conversion, intrinsically learning varying polymerization kinetics that change for each experimental condition. In addition, we predict entire MWDs including the skew and shape as well as SHAP analysis to interpret the dependence on reagent concentrations and reaction time. We then used a transfer learning approach to use the data from our high-throughput flow reactor to predict batch polymerization MWDs with only three additional data points. Overall, we demonstrate that the combination of HTE and ML provides a high level of predictive accuracy in determining polymerization outcomes. Transfer learning can allow exploration outside existing parameter spaces efficiently, providing polymer chemists with the ability to target the synthesis of polymers with desired properties.

Chitosan-based hydrogel system for efficient removal of Cu[II] and sustainable utilization of spent adsorbent as a catalyst for environmental applications.

The growing requirement for clean potable water requires sustainable methods of eliminating heavy metal ions and other organic contaminants. Herein, we synthesized a novel dual-purpose magnetically separable chitosan-based hydrogel system (CSGO-R@IO) that can efficiently remove toxic Cu2+ pollutants from water. FT-IR, XRD, SEM-EDX, VSM, XPS analyses were used to characterize the synthesized hydrogel. The CSGO-R@IO hydrogel showed high swelling capacity (1036.06 %), prominent adsorption capacity for Cu2+ ions (119.5 mg/g), and good recyclability up to four cycles. The adsorption data of Cu+2 ions on hydrogel fitted better to the Langmuir isotherm model (R2 = 0.9942), indicating spontaneous monolayer adsorption of Cu2+ ions on a homogenous surface. The adsorption kinetic studies fitted better with the pseudo-second-order model (R2 = 0.9992), suggesting that the adsorption process was controlled by chemisorption. We also showed a sustainable way to convert harmful Cu2+ pollutants into valuable Cu nanoparticles for catalysis, and Cu nanoparticles loaded hydrogel (CSGO-R@IO/Cu) had high catalytic activity. Hence, building attractive multipurpose hydrogel systems will give us new ideas about how to design and use new adsorbents to clean water in real life. They will also help in recycle metals (copper and maybe others) to conserve resources.

Decoding the mechanisms of allostery.

A complex interplay between structure, conformational dynamics and pharmacology defines distant regulation of G protein-coupled receptors.