A biomimetic camouflaged metal organic framework for enhanced siRNA delivery in the tumor environment.

Gene silencing through RNA interference (RNAi), particularly using small double-stranded RNA (siRNA), has been identified as a potent strategy for targeted cancer treatment. Yet, its application faces challenges such as nuclease degradation, inefficient cellular uptake, endosomal entrapment, off-target effects, and immune responses, which have hindered its effective delivery. In the past few years, these challenges have been addressed significantly by using camouflaged metal-organic framework (MOF) nanocarriers. These nanocarriers protect siRNA from degradation, enhance cellular uptake, and reduce unintended side effects by effectively targeting desired cells while evading immune detection. By combining the properties of biomimetic membranes and MOFs, these nanocarriers offer superior benefits such as extended circulation times, enhanced stability, and reduced immune responses. Moreover, through ligand-receptor interactions, biomimetic membrane-coated MOFs achieve homologous targeting, minimizing off-target adverse effects. The MOFs, acting as the core, efficiently encapsulate and protect siRNA molecules, while the biomimetic membrane-coated surface provides homologous targeting, further increasing the precision of siRNA delivery to cancer cells. In particular, the biomimetic membranes help to shield the MOFs from the immune system, avoiding unwanted immune responses and improving their biocompatibility. The combination of siRNA with innovative nanocarriers, such as camouflaged-MOFs, presents a significant advancement in cancer therapy. The ability to deliver siRNA with precision and effectiveness using these camouflaged nanocarriers holds great promise for achieving more personalized and efficient cancer treatments in the future. This review article discusses the significant progress made in the development of siRNA therapeutics for cancer, focusing on their effective delivery through novel nanocarriers, with a particular emphasis on the role of metal-organic frameworks (MOFs) as camouflaged nanocarriers.

Scale and Safety: Analyzing the Association Between Intraoperative Difficulty and Achieving the Critical View of Safety in Laparoscopic Cholecystectomy.

BACKGROUND:  Laparoscopic cholecystectomy (LC) is the preferred method for gallstone removal, but bile duct injuries remain a concern. Achieving the critical view of safety (CVS) is pivotal in preventing such injuries. The aim of this study was to compare the rates of difficult LC in those with CVS achieved compared to those with CVS not achieved. METHODS: We performed a single-center prospective study on all patients with ultrasound-confirmed symptomatic gallstones. Patients were excluded if they refused to consent or if they underwent LC for indications other than gallstone disease. Patients were stratified into two groups as CVS not achieved and CVS achieved groups and compared for outcomes. Our primary outcome was the rate of intraoperative difficulty on the modified Nassar scale (MNS). Statistical analysis was performed using SPSS version 25.0 (IBM Corp., Armonk, NY). RESULTS: We included 70 patients who underwent LC for gallstones (CVS not achieved = 24 and CVS achieved = 46). The mean (SD) age was 42.2 (12.3) years, and 73.5% were females. The mean (SD) weight in our study cohort was 74.1 (10.9) kg, and there was no difference between the two groups in terms of the baseline demographic characteristics, disease characteristics, and comorbid conditions (p > 0.05). On univariate analyses, achieving CVS was associated with lower rates of higher-grade operative difficulty on the MNS and lower rates of length of stay of more than one day. CONCLUSION: Achieving CVS is associated with easy LC based on significantly lower Nassar scores. These findings highlight the role of the MNS in the successful identification of the operative difficulty of LC and its correlation with achieving CVS.

Tailoring Bi2Se3 Topological Insulator for Visible-NIR Photodetectors with Schottky Contacts Using Liquid Phase Exfoliation.

Layered semiconductors of the V-VI group have attracted considerable attention in optoelectronic applications owing to their atomically thin structures. They offer thickness-dependent optical and electronic properties, promising ultrafast response time, and high sensitivity. Compared to the bulk, 2D bismuth selenide (Bi2Se3) is recently considered a highly promising material. In this study, 2D nanosheets are synthesized by prolonged sonication in two different solvents, such as N-methyl-2-pyrrolidone (NMP) and chitosan-acetic acid solution (CS-HAc), using the liquid-phase exfoliation (LPE) method. X-ray diffraction confirms the amorphous nature of exfoliated 2D nanosheets with maximum peak intensity at the same position (015) crystal plane as that obtained in its bulk counterpart. SEM confirms the thin 2D nanosheet-like morphology. Successful exfoliation of Bi2Se3 nanosheets up to five layers is achieved using CS-HAc solvent. The as-synthesized 2D nanosheets in different solvents are employed to fabricate the photodetector. At minimum selected power density, the photodetector fabricated using exfoliated ultrathin 2D nanosheets exhibits the highest range of responsivity, varying from 15 to 2.5 mA/W, and detectivity ranging from 2.83 × 109 to 6.37 × 107. Ultrathin 2D Bi2Se3 nanosheets have fast rise and fall times, ranging from 0.01 to 0.12 and 0.01 to 0.06 s, respectively, at different wavelengths. Ultrathin Bi2Se3 nanosheets have improved photodetection parameters as compared to multilayered nanosheets due to the high surface to volume ratio, reduced recombination and trapping of charge carrier, improved carrier confinement, and faster carrier transport due to the thin layer.

Hierarchical-Bioinspired MOFs Enhanced Electromagnetic Wave Absorption.

Proteins exhibit complex and diverse multi-dimensional structures, along with a wide range of functional groups capable of binding metal ions. By harnessing the unique characteristics of proteins, it is possible to enhance the synthesis of metal-organic frameworks (MOFs) and modify their morphology. Here, the utilization of biomineralized bovine serum albumin (BSA) protein as a template for synthesizing Mil-100 with superior microwave absorption (MA) properties is investigated. The multi-dimensional structure and abundant functional groups of biomineralized BSA protein make it an ideal candidate for guiding the synthesis of Mil-100 with intricate network structures. The BSA@Mil-100 synthesized using this method exhibits exceptional uniformity and monodispersity of nanocrystals. The findings suggest that the BSA protein template significantly influences the regulation of nanocrystal and microstructure formation of Mil-100, resulting in a highly uniform and monodisperse structure. Notably, the synthesized 2-BSA@Mil-100 demonstrates a high reflection loss value of -58 dB at 8.85 GHz, along with a maximum effective absorption bandwidth value of 6.79 GHz, spanning from 6.01 to 12.8 GHz. Overall, this study highlights the potential of utilizing BSA protein as a template for MOF synthesis, offering an effective strategy for the design and development of high-performance MA materials.

Boosting SARS-CoV-2 Enrichment with Ultrasmall Immunomagnetic Beads Featuring Superior Magnetic Moment.

The isolation and enrichment efficiency of SARS-CoV-2 virus in complex biological environments is often relatively low, presenting challenges in direct detection and an increased risk of false negatives, particularly during the early stages of infection. To address this issue, we have developed a novel approach using ultrasmall magnetosome-like nanoparticles (≤10 nm) synthesized via biomimetic mineralization of the Mms6 protein derived from magnetotactic bacteria. These nanoparticles are surface-functionalized with hydrophilic carboxylated polyethylene glycol (mPEG2000-COOH) to enhance water solubility and monodispersity. Subsequently, they are coupled with antibodies targeting the receptor-binding domain (RBD) of the virus. The resulting magnetosome-like immunomagnetic beads (Mal-IMBs) exhibit high magnetic responsiveness comparable to commercial magnetic beads, with a saturation magnetization of 90.6 emu/g. Moreover, their smaller particle size provides a significant advantage by offering a higher specific surface area, allowing for a greater number of RBD single-chain fragment variable (RBD-scFv) antibodies to be coupled, thereby enhancing immune capture ability and efficiency. To validate the practicality of Mal-IMBs, we evaluated their performance in recognizing the RBD antigens, achieving a maximum capture ability of 83 µg/mg per unit mass. Furthermore, we demonstrated the binding capability of Mal-IMBs to SARS-CoV-2 pseudovirus using fluorescence microscopy. The Mal-IMBs effectively enriched the pseudovirus at a low copy concentration of 70 copies/mL. Overall, the small Mal-IMB exhibited excellent magnetic responsiveness and binding efficiency. By employing a multisite virus binding mechanism, it significantly improves the enrichment and separation of SARS-CoV-2 in complex environments, facilitating rapid detection of COVID-19 and contributing to effective measures against its spread.

Numerical optimization and performance evaluation of ZnPC:PC70BM based dye-sensitized solar cell.

The increase in global energy consumption and the related ecological problems have generated a constant demand for alternative energy sources superior to traditional ones. This is why unlimited photon-energy harnessing is important. A notable focus to address this concern is on advancing and producing cost-effective low-loss solar cells. For efficient light energy capture and conversion, we fabricated a ZnPC:PC70BM-based dye-sensitized solar cell (DSSC) and estimated its performance using a solar cell capacitance simulator (SCAPS-1D). We evaluated the output parameters of the ZnPC:PC70BM-based DSSC with different photoactive layer thicknesses, series and shunt resistances, and back-metal work function. Our analyses show that moderate thickness, minimum series resistance, high shunt resistance, and high metal-work function are favorable for better device performance due to low recombination losses, electrical losses, and better transport of charge carriers. In addition, in-depth research for clarifying the impact of factors, such as thickness variation, defect density, and doping density of charge transport layers, has been conducted. The best efficiency value found was 10.30% after tweaking the parameters. It also provides a realistic strategy for efficiently utilizing DSSC cells by altering features that are highly dependent on DSSC performance and output.

Rhodium-Catalyzed Regio- and Enantioselective Allylic Sulfonylation from Sulfonyl Hydrazides.

A highly regio- and enantioselective allylic sulfonylation has been developed with rhodium and bisoxazolinephosphine (NPN*) ligands from racemic branched allylic carbonates and readily available sulfonyl hydrazides under neutral conditions. Branch-selective allylic sulfones with a >20:1 branch:linear ratio and >99% ee could be synthesized in ≤96% yield. Both Z and E linear allylic carbonates could also be converted into the same chiral branched allylic sulfones with high regio- and enantioselectivities.

Magnetosome-inspired synthesis of soft ferrimagnetic nanoparticles for magnetic tumor targeting.

Magnetic targeting is one of the most promising approaches for improving the targeting efficiency by which magnetic drug carriers are directed using external magnetic fields to reach their targets. As a natural magnetic nanoparticle (MNP) of biological origin, the magnetosome is a special "organelle" formed by biomineralization in magnetotactic bacteria (MTB) and is essential for MTB magnetic navigation to respond to geomagnetic fields. The magnetic targeting of magnetosomes, however, can be hindered by the aggregation and precipitation of magnetosomes in water and biological fluid environments due to the strong magnetic attraction between particles. In this study, we constructed a magnetosome-like nanoreactor by introducing MTB Mms6 protein into a reverse micelle system. MNPs synthesized by thermal decomposition exhibit the same crystal morphology and magnetism (high saturation magnetization and low coercivity) as natural magnetosomes but have a smaller particle size. The DSPE-mPEG-coated magnetosome-like MNPs exhibit good monodispersion, penetrating the lesion area of a tumor mouse model to achieve magnetic enrichment by an order of magnitude more than in the control groups, demonstrating great prospects for biomedical magnetic targeting applications.

Exploring 2-Tetradecanoylimino-3-aryl-4-methyl-1,3-thiazolines Derivatives as Alkaline Phosphatase Inhibitors: Biochemical Evaluation and Computational Analysis.

The current study focused on the laboratory approach in conjunction with computational methods for the synthesis and bioactivity assessment of unique 2-tetradecanoylimino-3-aryl-4-methyl-1,3-thiazolines (2a-2k). Processes included cyclizing 1-aroyl-3-arylthioureas with propan-2-one in the presence of trimethylamine and bromine. By using spectroscopic techniques and elemental analyses, structures were elucidated. To assess the electronic properties, density functional theory (DFT) calculations were made, while binding interactions of synthesized derivatives were studied by the molecular docking tool. Promising results were found during the evaluation of bioactivity of synthesized compounds against alkaline phosphatase. The drug likeliness score, an indicator used for any chemical entity posing as a drug, was within acceptable limits. The data suggested that most of the derivatives were potent inhibitors of alkaline phosphatase, which in turn may act as lead molecules to synthesize derivatives having desired pharmacological profiles for the treatment of specific diseases associated with abnormal levels of ALPs.

Antioxidant, Antimicrobial, Phytochemical and FTIR Analysis of Peganum harmala (Fruit) Ethanolic Extract From Cholistan Desert, Pakistan.

The aim of this study was to evaluate antioxidant and antimicrobial potential of Peganum harmala fruit. Ethanolic extract was prepared and phytochemical screening showed the presence of a lot of chemical compounds. Fourier transform infrared spectroscopy (FTIR) spectra indicated the presence of organic acids, hydroxyl and phenolic compounds, amino groups, aliphatic compounds, and functional groups such as amide, ketone, aldehyde, aromatics, and halogen compounds. Antioxidant activity of the ethanolic extract of P. harmala by the DPPH method showed 71.4% inhibition, whereas IC50 ± SEM (µg/mL) was .406 ± .11. Antibacterial activity was performed against Escherichia coli, Bacillus subtilis, Bacillus pumilus, Micrococcus luteus, Pseudomonas aeruginosa, Staphylococcus aureus, Staphylococcus epidermidis and Bordetella bronchiseptica. Maximum antibacterial activity was exhibited by Bacillus subtilis (24.33 ± 2 mm) and Bacillus pumilus (23.33 ± 2 mm). Zone of inhibition was 19 ± 2 mm by P. aeruginosa, and it was 18.33 ± 2 mm by Bordetella bronchiseptica. Staphylococcus aureus and Staphylococcus epidermidis had inhibitory effect in the range of 12.33 ± 2 mm and 13.66 ± 3 mm, respectively. 11.66 ± 2 mm and 10 ± 2 mm was zone of inhibition by Micrococcus luteus and E. coli, respectively. Antifungal activity was performed against Aspergillus terreus, Aspergillus fumigatus, Aspergillus flavus and Candida albicans. Ethanolic extract of P. harmala showed antifungal activity against Aspergillus flavus (5 ± 1 mm) and Candida albicans (4 ± 1 mm). Mild antifungal activity was reported by Aspergillus fumigatus (3 ± 1 mm), whereas no activity was exhibited by Aspergillus terreus. Further research is needed in order to evaluate the cytotoxic effects of P. harmala as well.

Rh-Catalyzed Regio- and Enantioselective Allylic Phosphinylation.

Transition-metal-catalyzed branched and enantioselective allylic substitution of monosubstituted precursors with carbon, nitrogen, oxygen, sulfur, and fluoride nucleophiles has been well-established. However, such a selective carbon-phosphorus bond formation has not been realized probably due to the catalyst deactivation by the strong coordinating nature of phosphinylating reagents. Herein, we report a Rh-catalyzed highly regio- and enantioselective synthesis of allylic phosphine oxides in the presence of a chiral bisoxazoline-phosphine ligand. The application of α-hydroxylalkylphosphine oxides to keep the low concentration of the secondary phosphine oxides is essential for the high yields. The addition of diphenyl phosphoric acid was found to not only activate allylic alcohols but also accelerate the carbon-phosphorus bond formation.

Sensitivity analysis and optimal control of COVID-19 dynamics based on SEIQR model.

It is of great curiosity to observe the effects of prevention methods and the magnitudes of the outbreak including epidemic prediction, at the onset of an epidemic. To deal with COVID-19 Pandemic, an SEIQR model has been designed. Analytical study of the model consists of the calculation of the basic reproduction number and the constant level of disease absent and disease present equilibrium. The model also explores number of cases and the predicted outcomes are in line with the cases registered. By parameters calibration, new cases in Pakistan are also predicted. The number of patients at the current level and the permanent level of COVID-19 cases are also calculated analytically and through simulations. The future situation has also been discussed, which could happen if precautionary restrictions are adopted.