A novel methodology for stabilization of silver nanoparticles on cotton, nylon and cotton/nylon fabrics using chitosan and triethyl orthoformate for enhanced and elongated antibacterial performance.

In the present study, the commercially available three different fabrics cotton, nylon and cotton/nylon were modified by chitosan and silver nanoparticles using a crosslinker triethyl orthoformate (TEOF). Resulted cotton­silver (Ag-Cs-Cot), nylon­silver (Ag-Cs-Nyl) and cotton-nylon silver (Ag-Cs-Cot-Nyl) fabrics showed significant anti-bacterial activity even after 50 washing cycles. Silver nanoparticles were prepared by reducing silver nitrate through sodium borohydride at 0 °C. In FTIR spectra the peak at near 1650 cm-1 confirmed that TEOF mediated attachment of chitosan with fabrics (due to C=N) and the stretching of secondary amine near the 3375 cm-1 indicated the silver attachment to the amine group of the chitosan. In Scanning Electron Microscope (SEM) images smooth surfaces of fabrics without any damage by modification process were observed. The antibacterial activity was Analyzed by agar diffusion and broth dilution assays against Escherichia coli and Staphylococcus aureus bacterial strains and results showed 90% bacterial inhibition against E. coli and 89% bacterial inhibition against S. aureus. For testing the antibacterial durability, the modified fabrics were washed with non-ionic detergent (10g/l) for 15 minutes under aggressive stirring (100 rpm) at room temperature. The modified fabrics retained antibacterial activity over the 50 washing cycles. Finally, the commercial potential of cotton-silver fabric was evaluated by stitching it with the socks of football players and interestingly results showed that the modified fabric on the socks showed more than 90% bacterial inhibition as compared to the plain fabric after 70 minutes of playing activity.

Multimodal CNN-DDI: using multimodal CNN for drug to drug interaction associated events.

Drug-to-drug interaction (DDIs) occurs when a patient consumes multiple drugs. Therefore, it is possible that any medication can influence other drugs' effectiveness. The drug-to-drug interactions are detected based on the interactions of chemical substructures, targets, pathways, and enzymes; therefore, machine learning (ML) and deep learning (DL) techniques are used to find the associated DDI events. The DL model, i.e., Convolutional Neural Network (CNN), is used to analyze the DDI. DDI is based on the 65 different drug-associated events, which is present in the drug bank database. Our model uses the inputs, which are chemical structures (i.e., smiles of drugs), enzymes, pathways, and the target of the drug. Therefore, for the multi-model CNN, we use several layers, activation functions, and features of drugs to achieve better accuracy as compared to traditional prediction algorithms. We perform different experiments on various hyperparameters. We have also carried out experiments on various iterations of drug features in different sets. Our Multi-Modal Convolutional Neural Network - Drug to Drug Interaction (MCNN-DDI) model achieved an accuracy of 90.00% and an AUPR of 94.78%. The results showed that a combination of the drug's features (i.e., chemical substructure, target, and enzyme) performs better in DDIs-associated events prediction than other features.

Chitosan-sodium percarbonate-based hydrogels with sustained oxygen release potential stimulated angiogenesis and accelerated wound healing.

The prolonged hypoxic conditions hinder chronic wounds from healing and lead to severe conditions such as delayed re-epithelialization and enhanced risk of infection. Multifunctional wound dressings are highly required to address the challenges of chronic wounds. Herein, we report polyurethane-coated sodium per carbonate-loaded chitosan hydrogel (CSPUO2 ) as a multifunctional dressing. The hydrogels (Control, CSPU, and CSPUO2 ) were prepared by freeze gelation method and the developed hydrogels showed high porosity, good absorption capacity, and adequate biodegradability. The release of oxygen from the CSPUO2 hydrogel was confirmed by the increase in pH and a sustained oxygen release was observed over the period of 21 days, due to polyurethane (CSPU) coating. The CSPUO2 hydrogel exhibited around 2-fold increased angiogenic potential in CAM assay when compared with Control and CSPU dressing. CSPUO2 also showed good level of antibacterial efficacy against E. coli and S. aureus. In a full-thickness rat wound model, CSPUO2 hydrogel considerably accelerated wound healing with exceptional re-epithelialization granulation tissue formation less inflammatory cells and improved skin architecture highlighting the tremendous therapeutic potential of this hydrogel when compared with control and CSPU to treat chronic diabetic and burn wounds.

Optimisation and characterization of double emulsion derived from rice starch, rice protein isolates and rice bran oil.

This study focused on the development and evaluation of a stable emulsion system using rice starch, protein isolates, and bran oil as food ingredients. This was performed using a one-factor-at-a-time (OFAT) experimental strategy, which was subsequently refined using response surface modeling (RSM), and the emulsion was then characterized. The resulting quadratic polynomial model effectively captured all the responses, with regression coefficients exceeding 0.90. The emulsion activity index, emulsion stability index, and droplet size were 86.29 %, 93.44 %, and 100.59 nm, respectively. Turbidity was significantly influenced by particle size, with the double emulsion (sample B) exhibiting higher turbidity index (43,250.34 ± 0.046) than the reference sample (29,433.303 ± 0.018). The viscosity of the emulsion increased with the addition of the protein isolates. This inferred that a stable emulsion system derived from rice could serve a multifunctional purpose as carriers, fillers, and binders to enhance the physical, functional and sensory properties of foods.

Serum and salivary Cu/Zn ratio as a diagnostic biomarker for oral submucosal fibrosis: an analysis of trace metals and LOX gene variants.

This study aimed to analyze the serum and salivary levels of copper (Cu), zinc (Zn), iron (Fe), chromium (Cr), manganese (Mn) and the Cu/Zn ratio and investigate the association between LOX gene variants (rs18800449 and rs2288393) and oral submucosal fibrosis (OSMF). A total of 250 subjects were included in the study: OSMF patients (n = 50), areca nut chewers without OSMF (n = 100) and controls (n = 100). Trace metals were measured using an atomic absorption spectrophotometer, while LOX gene variants were genotyped using the tetra primer amplification refractory mutation system (tetra ARMS) polymerase chain reaction (PCR) method. The results showed significant variations in serum and salivary Cu, Zn, Fe and Cr levels and serum Mn concentrations among the three groups (p < 0.0001). Serum Cu levels were significantly higher in OSMF patients, while serum Zn levels were significantly lower. Both serum and salivary Cu/Zn ratios demonstrated a statistically significant difference (p < 0.0001) and diagnostic potential to differentiate OSMF from chewers and controls. However, LOX gene variants did not show an association between OSMF and chewers, except for rs1800449 genotypes, which showed a significant and increased risk with the AA genotype in OSMF patients compared to controls (OR = 7.58; 95%CI 2.30-24.97). The study suggests that trace elements and genetic variants may impact the etiology of OSMF. The findings may aid in early diagnosis, suitable treatment, and as a prognostic indicator for disease progression.

Identification of useful biomolecular markers in kidney renal clear cell carcinoma: an in silico and in vitro analysis-based study.

BACKGROUND: Kidney renal clear cell carcinoma (KIRC) is the most prevalent type of renal cell carcinoma (RCC), with a high incidence and mortality rate. There is a lack of sensitive biomarkers. Therefore, the discovery of accurate biomarkers for KIRC patients is critical to improve prognosis. METHODS: We determined hub genes and their associated pathways involved in the pathogenesis of KIRC from the GSE66272 dataset consisting of KIRC (n = 26) and corresponding control (n = 26) samples and later validated the expression and methylation level of the identified hub genes on The Cancer Genomic Atlas (TCGA) datasets and Human RCC 786-O and normal HK-2 cell lines through RNA sequencing (RNA-seq), Reverse transcription-quantitative polymerase chain reaction (RT-qPCR), and targeted bisulfite sequencing (bisulfite-seq) analyses. RESULTS: The identified up-regulated four hub genes include TYROBP (Transmembrane Immune Signaling Adaptor TYROBP), PTPRC (Protein tyrosine phosphatase, receptor type, C), LCP2 (Lymphocyte cytosolic protein 2), and ITGB2 (Integrin Subunit Beta 2). Moreover, the higher expression of TYROBP, PTPRC, LCP2, and ITGB2 in KIRC patients insignificantly correlates with a poor prognosis in KIRC patients. In addition, hub genes were involved in the "Fc epsilon RI signaling pathway, asthma, natural cell killer mediated cytotoxicity, T cell receptor signaling pathway, primary immunodeficiency, Fc gamma R-mediated phagocytosis, malaria, leukocyte transendothelial migration, and legionellosis" pathways and associated with the infiltration level of CD8+ T, CD4+ T, and macrophage cells. CONCLUSION: Our integrated in silico and in vitro analysis identified important hub genes (TYROBP, PTPRC, LCP2, and ITGB2) involved in the pathogenesis of KIRC as possible diagnostic biomarkers.

Metallofullerenes as Robust Single-Atom Catalysts for Adsorption and Dissociation of Hydrogen Molecules: A Density Functional Study.

Hydrogen is currently considered as the best alternative for traditional fuels due to its sustainable and ecofriendly nature. Additionally, hydrogen dissociation is a critical step in almost all hydrogenation reactions, which is crucial in industrial chemical production. A cost-effective and efficient catalyst with favorable activity for this step is highly desirable. Herein, transition-metal-doped fullerene (TM@C60) complexes are designed and investigated as single-atom catalysts for the hydrogen splitting process. Interaction energy analysis (Eint) is also carried out to demonstrate the stability of designed TM@C60 metallofullerenes, which reveals that all the designed complexes have higher thermodynamic stability. Furthermore, among all the studied metallofullerenes, the best catalytic efficiency for hydrogen dissociation is seen for the Sc@C60 catalyst Ea = 0.13 eV followed by the V@C60 catalyst Ea = 0.19 eV. The hydrogen activation and dissociation processes over TM@C60 metallofullerenes is further elaborated by analyzing charge transfer via the natural bond orbital and electron density difference analyses. Additionally, quantum theory of atoms in molecule analysis is carried out to investigate the nature of interatomic interactions between hydrogen molecules and TMs@C60 metallofullerenes. Overall, results of the current study declare that the Sc@C60 catalyst can act as a low cost, highly efficient, and noble metal-free single-atom catalyst to efficiently catalyze hydrogen dissociation reaction.

Impact of ACE2 gene variations on COVID-19 pathogenicity in Pakistani patients.

Background: COVID-19, caused by the SARS-CoV-2 virus, swiftly disseminated and was declared a pandemic. Variations in the ACE2 gene can impact the virus's ability to bind to ACE2 receptor, potentially influencing an individual's susceptibility and its association with COVID-19 severity across various populations. Methods: In total, 200 individuals were sequenced for the ACE2 gene and potential impact of the found variants on the ACE2 protein was assessed using in-silico tools. Results: Eight variations in the ACE2 gene were identified in 27 COVID-19 patients, of which four were missense and four were intronic variants. Three variants had a MAF of < 0.01 (c.251C > T, p.Pro86Leu; 15C > G, p.S5S; and c. 91 A > G, p.Lys31Glu). A missense variant, p.Pro86Leu, C > T, TT genotype, was found in 9 out of 200 individuals with an allele frequency of 0.045 and showed a significant association with COVID-19 (P = 0.003). The heterozygous allele of 15C > G, p.S5S, was found with a frequency of 0.02 (8/400) in eight patients, and its CG genotype showed a significant association with COVID-19 (P = 0.0068). The remaining identified variants were not associated with COVID-19 susceptibility. Conclusion: The ACE2 gene sequence in Pakistani individuals exhibited a low frequency of identified variants in COVID-19 patients. Overall, only two variants were associated with susceptibility to the disease, possibly contributing to Pakistan's lower COVID-19 mortality and infection rates. However, individuals carrying the mutant variant experienced more severe symptoms.

A novel formulation of triethyl orthoformate mediated durable, smart and antibacterial chitosan cross-linked cellulose fabrics.

Antibacterial, durable and smart cotton fabrics was developed using chitosan-based formulation. The cellulose was covalently cross-linked with chitosan using TEOF. The antibacterial activity of prepared smart fabrics and CS was studied against S. aureus and E. coli strains. The FTIR, SEM and XRD were employed to confirm the linkage of CS molecules with cellulose in cotton fabrics. The CS of 160 KDa extracted from shrimp shell showed the optimum antibacterial activity. The prominent asymmetric, symmetric alkyl CH peaks of CS were shifted to 2930 and 2845 (cm-1), respectively. Moreover, the shifted peaks at 1590 and 1400 (cm-1) indicate the CO stretching and NH2 bending bands of CS, respectively. This confirm the existence of new imine functional group that was generated after cross-linking of NH2 groups of CS. The SEM results showed more uniform morphology of TEOF cross-linked fabrics versus CS coated fabrics, which revealed a promising microbial growth inhibition activity. The TEOF as a cross-linker has been unveiled, showcasing the effectiveness of this innovative crosslinking approach. The fabric treated with cross-linked CS exhibited remarkable antibacterial properties that endured even after undergoing 30 washing cycles. These antibacterial textiles possess substantial commercial potential across a diverse range of industries.

Photophysical and biological aspects of α, ß-unsaturated ketones: Experimental and in silico approach.

In this work, four fluorinated α, ß-unsaturated ketones named as 3-(3-bromophenyl)-1-(3-(trifluoromethyl)phenyl)prop-2-en-1-one (1), 3-(4-methoxyphenyl)-1-(3-(trifluoromethyl)phenyl) prop-2-en-1-one (2), 3-(3-bromo-5-chloro-2-hydroxyphenyl)-1-(3-(trifluoromethyl)phenyl) prop-2-en-1-one (3) and 3-(2-hydroxy-5-methylphenyl)-1-(3-(trifluoromethyl)phenyl)prop-2-en-1-one (4) were synthesized by Claisen-Schmidt reaction. The synthesized molecules were then characterized through ultraviolet-visible spectroscopy (UV-Vis), Fourier transform infrared (FTIR), 1 H-NMR, 13 C-NMR, and mass spectrometry. The antioxidant potential, Urease inhibition, and interaction of compounds 1-4 with Salmon sperm DNA were experimentally explored and supported by molecular docking studies. The synthesized compounds strongly interact with SS-DNA through intercalative mode. It was noticed that compound 1 served as potent Urease inhibitor while compound 4 as better antioxidant among synthesized compounds. Moreover, frontier molecular orbitals, nonlinear optical (NLO) properties, natural bond orbitals, molecular electrostatic potential, natural population analysis, and photophysical properties of synthesized compounds were accomplished through density functional theory and time-dependent density functional theory. The band gap of all the compounds have been worked out using Taucs method. In addition to that, a precise comparative account of UV and IR data obtained from theoretical and experimental findings showed good agreement between theoretical and experimental data. The findings of our studies reflected that compounds 1-4 possess better NLO properties than Urea standard and the band gap data also reflected their prospective use towards optoelectronic materials. The better NLO behavior of compounds was attributed to the noncentrosymmetric structure of synthesized compounds.

An alginate-Based tube gel delivering 2-deoxy-D-ribose for stimulation of wound healing.

Developing multifunctional wound dressings capable of inducing rapid angiogenesis and with antibacterial activity would be attractive for diabetic and superficial wound healing. Hydrogels delivered from tubes have several desirable features -they are easy to apply, keep the wound moist, reduce the entry of microorganisms and avoid the need for painful dressing removal. Previously we reported that 2 deoxy-D-ribose (2dDR) delivered from a variety of dressings is capable of promoting wound healing by stimulating angiogenesis. Alginate hydrogels are an ideal vehicle to deliver a bioactive agent capable of promoting wound healing. In this study we developed and evaluated a tube hydrogel capable of delivering 2dDR with the aim of achieving a stable, convenient to administer and biologically effective wound treatment. Further, we included the stabilizer 2-phenoxy ethanol which provided antimicrobial activity. We synthesized hydrogels by the Green method, using simple mixing of sodium alginate, propylene glycol, 2-phenoxy ethanol and 2dDR in water. FTIR (Fourier transformation infrared spectroscopy) analysis confirmed an absence of undesirable chemical changes in the gel components, and SEM images of the freeze-dried gels showed porous structures. When 2dDR alginate gel (2dDR-SA hydrogel) was placed in PBS at 37°C, almost 92% of 2dDR was released within 7 days. When tested on cultured cells, 2dDR-SA hydrogels did not inhibit metabolic activity or proliferation, achieving up to 90 and 98% of control respectively over 7 days. 2dDR-SA hydrogel also showed anti-bacterial activity against E. coli, Pseudomonas aeruginosa, Staphylococcus aureus, and MRSA which was attributable to the stabilizer 2-phenoxy ethanol in the hydrogel. Stimulation of angiogenesis in the chorioallantoic membrane assay by 2dDR-SA hydrogel was found to be significant compared to the blank-SA. Wound healing potential was studied in full-thickness wounds in rats where acceleration of wound healing was seen. H&E staining of the wound tissue showed an enhanced number of blood vessels and re-epithelization, and a reduced number of inflammatory cells in 2dDR-SA treated animals compared to blank-hydrogels while Masson's trichrome staining showed increased collagen deposition. In summary we describe a convenient to apply hydrogel which has promise for use in a range of superficial skin wounds including applications in chronic wound care.

Association of MSX1 Gene Variants with Nonsyndromic Cleft Lip and/or Palate in the Pakistani Population.

OBJECTIVES: This study investigated the association of MSX1 gene variants rs3821949 and rs12532 with nonsyndromic cleft lip and/or palate (NSCL/P) in the Pakistani population. DESIGN: Comparative cross-sectional study.Setting: Multicenter of CL/P malformation.Patients/Participants: Unrelated Non-Syndromic cleft Lip/Palate patients and healthy controls were enrolled. METHODS: One hundred (n = 100) subjects with NSCL/P and n = 50 unrelated healthy controls were enrolled in a multicenter comparative cross-sectional study. A tetra amplification refractory mutation system (ARMS) polymerase chain reaction (PCR) was performed to analyze MSXI gene single nucleotide variants (SNVs). RESULTS: Among 100 NSCL/P subjects, the majority were males (56%; male: female = 1.27: 1). Most of the cases (74%) had cleft lip and palate (CLP) compared to isolated clefts. Genotyping of MSX1 gene variant rs3821949 showed an increased risk for NSCL/P in various genetic models (P < 0.0001), and the A allele exhibited a more than 4-fold increased risk among cases (OR = 4.22: 95% CI = 2.16-8.22; P < 0.0001). Our investigation found no significant difference between the rs12532 variation and NSCL/P. CONCLUSION: Our study findings suggest that MSX1 gene variants may increase predisposition to NSCL/P in the Pakistani population. Further studies comprising large samples are required to identify the genetic aetiology of NSCL/P among our people.

Computational insights of excited state intramolecular proton transfer (ESIPT) based fluorescent detection and imaging of γ-glutamytranspeptidase activity.

γ-Glutamytranspeptidase (GGT) is an important tumor biomarker that widely appears in the tumor cells. Therefore, accurate imaging and detection of GGT activity in live cells, serum and pathological cells grasp great importance for the diagnosis, management, and treatment of cancer. Herein, 2-(2-hydroxyl-phenyl)-6-chloro-4-(3H)-quinazolinone (HPQ) is considered as the fluorophore probe for the detection of GGT activity, which is known for the typical mechanism of excited-state intramolecular proton transfer (ESIPT). All the simulations adopted to evaluate the sensing mechanism were carried out via DFT and TDDFT calculations at CAM-B3LYP/TZVP level of theory. The emission properties of HPQ and HPQ-TD are thoroughly studied to understand the photoinduced electron transfer (PET) and excited state intramolecular proton transfer (ESIPT) process. The results reveal that the fluorescence quenching of HPQ (enol form) is assigned to the PET process, whereas the large Stokes shift in fluorescence emission of HPQ (keto form) is related with ESIPT mechanism. The obtained results are further cross validated by frontier molecular orbital (FMO) analysis, geometric analysis, and potential energy curve (PEC) scanning. Our calculations provide powerful evidence for the ESIPT based sensing mechanism of HPQ (keto-enol form) for GGT activity.

Transition Metal-Doped C20 Fullerene-Based Single-Atom Catalysts with High Catalytic Activity for Hydrogen Dissociation Reaction.

Hydrogen dissociation is a key step in almost all hydrogenation reactions; therefore, an efficient and cost-effective catalyst with a favorable band structure for this step is highly desirable. In the current work, transition metal-based C20 (M@C20) complexes are designed and evaluated as single-atom catalysts (SACs) for hydrogen dissociation reaction (HDR). Interaction energy (E int) analysis reveals that all the M@C20 complexes are thermodynamically stable, whereas the highest stability is observed for the Ni@C20 complex (E int = -6.14 eV). Moreover, the best catalytic performance for H2 dissociation reaction is computed for the Zn@C20 catalyst (E ads = 0.53 eV) followed by Ti@C20 (E ads = 0.65 eV) and Sc@C20 (E ads = 0.76 eV) among all considered catalysts. QTAIM analyses reveal covalent or shared shell interactions in H2* + M@C20 systems, which promote the process of H2 dissociation over M@C20 complexes. NBO and EDD analyses declare that transfer of charge from the metal atom to the antibonding orbital of H2 causes dissociation of the H-H bond. Overall outcomes of this study reveal that the Zn@C20 catalyst can act as a highly efficient, low-cost, abundant, and precious metal-free SAC to effectively catalyze HDR.

Covalent Triazine Framework C6N6 as an Electrochemical Sensor for Hydrogen-Containing Industrial Pollutants. A DFT Study.

Industrial pollutants pose a serious threat to ecosystems. Hence, there is a need to search for new efficient sensor materials for the detection of pollutants. In the current study, we explored the electrochemical sensing potential of a C6N6 sheet for H-containing industrial pollutants (HCN, H2S, NH3 and PH3) through DFT simulations. The adsorption of industrial pollutants over C6N6 occurs through physisorption, with adsorption energies ranging from -9.36 kcal/mol to -16.46 kcal/mol. The non-covalent interactions of analyte@C6N6 complexes are quantified by symmetry adapted perturbation theory (SAPT0), quantum theory of atoms in molecules (QTAIM) and non-covalent interaction (NCI) analyses. SAPT0 analyses show that electrostatic and dispersion forces play a dominant role in the stabilization of analytes over C6N6 sheets. Similarly, NCI and QTAIM analyses also verified the results of SAPT0 and interaction energy analyses. The electronic properties of analyte@C6N6 complexes are investigated by electron density difference (EDD), natural bond orbital analyses (NBO) and frontier molecular orbital analyses (FMO). Charge is transferred from the C6N6 sheet to HCN, H2S, NH3 and PH3. The highest exchange of charge is noted for H2S (-0.026 e-). The results of FMO analyses show that the interaction of all analytes results in changes in the EH-L gap of the C6N6 sheet. However, the highest decrease in the EH-L gap (2.58 eV) is observed for the NH3@C6N6 complex among all studied analyte@C6N6 complexes. The orbital density pattern shows that the HOMO density is completely concentrated on NH3, while the LUMO density is centred on the C6N6 surface. Such a type of electronic transition results in a significant change in the EH-L gap. Thus, it is concluded that C6N6 is highly selective towards NH3 compared to the other studied analytes.

Zinc oxide loaded chitosan-elastin-sodium alginate nanocomposite gel using freeze gelation for enhanced adipose stem cell proliferation and antibacterial properties.

Hydrogels have been the material of choice for regenerative medicine applications due to their biocompatibility that can facilitate cellular attachment and proliferation. The present study aimed at constructing a porous hydrogel composite scaffold (chitosan, sodium alginate and elastin) for the repair of chronic skin wounds. Chitosan-based hydrogel incorporating varying concentrations of zinc oxide nanoparticles i.e. ZnO-NPs (0, 0.001, 0.01, 0.1 and 1 % w/w) as the antimicrobial agent tested against Escherichia coli (E.coli) and Staphylococcus aureus (S. aureus) exhibited good antibacterial activities. ZnO-NPs were characterized by UV visible spectroscopy, Scanning electron microscopy (SEM) analysis, Fourier transform infrared spectroscopy (FTIR) and X-ray diffraction (XRD) analysis. Fabricated gels were characterized by SEM analysis, FTIR, XRD, swelling ratio, degradation behavior and controlled release kinetics of ZnO-NPs. In vitro cytocompatibility of the composite was investigated using human adipose stem cells (ADSCs) by MTT and lactate dehydrogenase (LDH) assay, further assessed by SEM analysis and PKH26 staining. The SEM and XRD analysis confirmed the successful loading of ZnO-NPs into these scaffolds. Fluorescence PKH26 stained images and SEM analysis of ADSCs seeded scaffolds revealed biocompatible nature. The findings suggested that the developed composite gels have potential clinically for tissue engineering and chronic wound treatment.

Delineating the Spectrum of Genetic Variants Associated with Bardet-Biedl Syndrome in Consanguineous Pakistani Pedigrees.

This study aimed to find the molecular basis of Bardet-Biedl syndrome (BBS) in Pakistani consanguineous families. A total of 12 affected families were enrolled. Clinical investigations were performed to access the BBS-associated phenotypes. Whole exome sequencing was conducted on one affected individual from each family. The computational functional analysis predicted the variants' pathogenic effects and modeled the mutated proteins. Whole-exome sequencing revealed 9 pathogenic variants in six genes associated with BBS in 12 families. The BBS6/MKS was the most common BBS causative gene identified in five families (5/12, 41.6%), with one novel (c.1226G>A, p.Gly409Glu) and two reported variants. c.774G>A, Thr259LeuTer21 was the most frequent BBS6/MMKS allele in three families 3/5 (60%). Two variants, c.223C>T, p.Arg75Ter and a novel, c. 252delA, p.Lys85STer39 were detected in the BBS9 gene. A novel 8bp deletion c.387_394delAAATAAAA, p. Asn130GlyfsTer3 was found in BBS3 gene. Three known variants were detected in the BBS1, BBS2, and BBS7 genes. Identification of novel likely pathogenic variants in three genes reaffirms the allelic and genetic heterogeneity of BBS in Pakistani patients. The clinical differences among patients carrying the same pathogenic variant may be due to other factors influencing the phenotype, including variants in other modifier genes.

Efficient Detection of Nerve Agents through Carbon Nitride Quantum Dots: A DFT Approach.

V-series nerve agents are very lethal to health and cause the inactivation of acetylcholinesterase which leads to neuromuscular paralysis and, finally, death. Therefore, rapid detection and elimination of V-series nerve agents are very important. Herein, we have carried out a theoretical investigation of carbon nitride quantum dots (C2N) as an electrochemical sensor for the detection of V-series nerve agents, including VX, VS, VE, VG, and VM. Adsorption of V-series nerve agents on C2N quantum dots is explored at M05-2X/6-31++G(d,p) level of theory. The level of theory chosen is quite adequate in systems describing non-bonding interactions. The adsorption behavior of nerve agents is characterized by interaction energy, non-covalent interaction (NCI), Bader's quantum theory of atoms in molecules (QTAIM), frontier molecular orbital (FMO), electron density difference (EDD), and charge transfer analysis. The computed adsorption energies of the studied complexes are in the range of -12.93 to -17.81 kcal/mol, which indicates the nerve agents are physiosorbed onto C2N surface through non-covalent interactions. The non-covalent interactions between V-series and C2N are confirmed through NCI and QTAIM analysis. EDD analysis is carried out to understand electron density shifting, which is further validated by natural bond orbital (NBO) analysis. FMO analysis is used to estimate the changes in energy gap of C2N on complexation through HOMO-LUMO energies. These findings suggest that C2N surface is highly selective toward VX, and it might be a promising candidate for the detection of V-series nerve agents.

Tailoring the solar cell efficiency of Y-series based non-fullerene acceptors through end cap modification.

Y-series-based non-fullerene acceptors (NFAs) have achieved significant deliberation by chemists and physicists because the promising optical and photochemical properties associated with high-performance OSCs can be further tuned through end-capped modification. In this work, such modifications of Y-series benzothiadiazole-based NFAs were accomplished theoretically to propose new acceptors for photovoltaic cells (PVCs). The recently synthesized Y-series non-fullerene acceptor m-BTP-PhC6 was taken as a reference acceptor. We designed five new acceptors (BTP1-BTP5) through the structural modification at both ends of acceptor groups and evaluated their performance by applying DFT and TD-DFT. The newly engineered molecules exhibited a narrower bandgap (Eg) than the reference (R) resulting in better intramolecular charge transfer (ICT). Further, the designed acceptors expressed the maximum absorption in the region of 600-800 nm revealing a redshift in their absorption spectrum. Low excitation energy and low exciton binding energy were noted for designed acceptors confirming them as better candidates for high PCE of solar cells. Low reorganizational energy for the mobility of holes and electrons was also observed for the designed molecules, indicating improved charge transfer properties. The newly tailored acceptor BTP4 was found to be the promising candidate among all acceptors because of lower bandgap, lower exciton binding energy, reorganizational energy, and redshift of the absorption spectrum. The complex analysis of BTP4 with donor polymer PTB7-Th and PM6 was executed at the same DFT level. Furthermore, FMOs studies showed relatively rich electron density in the acceptor groups of LUMO as compared to the reference molecule. The overall theoretical results of this study showed that the designed acceptors played a productive and effective role in uplifting the efficiency of fullerene-free energy devices.

Aloe vera and ofloxacin incorporated chitosan hydrogels show antibacterial activity, stimulate angiogenesis and accelerate wound healing in full thickness rat model.

Burns are potentially fatal and physically debilitating injuries, causing psychological and physical scars and result in chronic disabilities. A well vascularized wound bed is required to achieve complete and scar free wound closure. For many centuries, a variety of herbal plants have been used for wound healing, among these aloe vera (AV) has been found to be very effective in wound healing. Secondly, the main reason for delayed wound healing is bacterial infections. Ofloxacin (OX) has been reported as an active antibacterial drug for topical infections and it is effective against both positive and negative bacterial strains. In current research three different concentrations of OX (0.5, 2.5, and 5 mg) were loaded into chitosan (CS)/AV based hydrogels prepared by freeze gelation. The surface morphology of prepared CS/AV based OX loaded hydrogels were evaluated by scanning electron microscopy (SEM). In drug release analysis, 0.5 mg OX loaded hydrogel showed a sustained drug release behavior over 3 days period. An effective dose dependent antibacterial activity was exhibited by OX loaded hydrogels. Alamar Blue cells viability assay revealed that 0.5 mg OX hydrogel (CA 0.5 OX) showed comparatively better 3 T3 fibroblast cells proliferation as compared to CA 2.5 OX (2.5 mg OX) and CA 5 OX hydrogel (5 mg OX). Moreover, all OX loaded hydrogels showed good angiogenic activity in CAM bioassay while higher angiogenic potential was observed from CA 0.5 OX containing comparatively lower concentration of OX. These OX incorporated CS/AV based hydrogels are promising wound dressings for future clinical use.