A Comprehensive Review on Benzofuran Synthesis Featuring Innovative and Catalytic Strategies.

Benzofurans have intrigued both pharmaceutical researchers and chemists owing to the medicinal usage of their derivatives against copious disease-causing agents (i.e., bacteria, viruses, and tumors). These heterocyclic scaffolds are pervasively encountered in a number of natural products and drugs. The ever-increasing utilization of benzofuran derivatives as pharmaceutical agents persuaded the chemists to devise novel and facile methodological approaches to assemble the biologically potent benzofuran nucleus. This review summarizes the current developments regarding the innovative synthetic routes and catalytic strategies to procure the synthesis of benzofuran heterocycles with their corresponding mechanistic details, reported by several research groups during 2021-2023.

Cloke-Wilson rearrangement: a unique gateway to access five-membered heterocycles.

Cyclopropanes are of great synthetic value in heterocyclic chemistry due to their highly reactive nature. They are widely employed to synthesize various biologically active organic compounds. Generally, vinyl, carbonyl, imine, and alkylidene cyclopropanes are utilized as efficient synthetic precursors in organic synthesis. The Cloke-Wilson rearrangement of these activated cyclopropanes is carried out to achieve the synthesis of diverse heterocyclic scaffolds. Various oxygen, nitrogen, and sulfur-containing heterocyclic compounds have been synthesized employing this rearrangement. With time, Cloke-Wilson rearrangement has evolved into a high yielding enantioselective and diastereoselective approach utilizing integrated novel methods. Our review focuses on the recent approaches for Cloke-Wilson rearrangement to synthesize several five-membered heterocycles and its applicability towards the natural product syntheses reported during 2000-2020.

Psychosocial Aspects of Rheumatic Disease Management: Addressing Mental Health and Well-Being.

Rheumatic disease imposes a substantial emotional burden on individuals, leading to chronic pain, discomfort, anxiety, and depression. Coping with unpredictability and physical limitations can create a detrimental feedback loop, exacerbating mental and physical symptoms. Poor mental health can hinder treatment adherence and worsen disease progression. Addressing the emotional impact of rheumatic disease is crucial for comprehensive management. Healthcare providers play a critical role in recognizing psychosocial concerns through attentive listening and standardized screenings. Open communication and a collaborative approach lead to more effective care. Support systems involving family, friends, and support groups provide emotional help and reduce isolation. Coping strategies and self-management techniques empower patients to navigate their conditions. The stigma associated with mental health is a challenge that requires education, awareness, and patient advocacy. A multidisciplinary approach integrating mental health services is pivotal for addressing the psychosocial aspects of rheumatic disease, offering a holistic perspective. Ongoing research explores the interplay between mental health and physical symptoms, aiming for innovative therapies and improved patient care. Collaborative care models and patient advocacy are essential to reducing barriers and improving patient outcomes. The future of rheumatic disease management lies in a patient-centered, multidisciplinary approach that addresses both physical and mental aspects.

Mukaiyama aldol reaction: an effective asymmetric approach to access chiral natural products and their derivatives/analogues.

The Mukaiyama aldol reaction is generally a Lewis-acid catalyzed cross-aldol reaction between an aldehyde or ketone and silyl enol ether. It was first described by Mukaiyama in 1973, almost 5 decades ago, to achieve the enantioselective synthesis of ß-hydroxy carbonyl compounds in high percentage yields. Mukaiyama aldol adducts play a pivotal role in the synthesis of various naturally occurring and medicinally important organic compounds such as polyketides, alkaloids, macrolides, etc. This review highlights the significance of the Mukaiyama aldol reaction towards the asymmetric synthesis of a wide range of biologically active natural products reported recently (since 2020).

The Corey-Seebach Reagent in the 21st Century: A Review.

The Corey-Seebach reagent plays an important role in organic synthesis because of its broad synthetic applications. The Corey-Seebach reagent is formed by the reaction of an aldehyde or a ketone with 1,3-propane-dithiol under acidic conditions, followed by deprotonation with n-butyllithium. A large variety of natural products (alkaloids, terpenoids, and polyketides) can be accessed successfully by utilizing this reagent. This review article focuses on the recent contributions (post-2006) of the Corey-Seebach reagent towards the total synthesis of natural products such as alkaloids (lycoplanine A, diterpenoid alkaloids, etc.), terpenoids (bisnorditerpene, totarol, etc.), polyketide (ambruticin J, biakamides, etc.), and heterocycles such as rodocaine and substituted pyridines, as well and their applications towards important organic synthesis.

Sharpless Asymmetric Dihydroxylation: An Impressive Gadget for the Synthesis of Natural Products: A Review.

Sharpless asymmetric dihydroxylation is an important reaction in the enantioselective synthesis of chiral vicinal diols that involves the treatment of alkene with osmium tetroxide along with optically active quinine ligand. Sharpless introduced this methodology after considering the importance of enantioselectivity in the total synthesis of medicinally important compounds. Vicinal diols, produced as a result of this reaction, act as intermediates in the synthesis of different naturally occurring compounds. Hence, Sharpless asymmetric dihydroxylation plays an important role in synthetic organic chemistry due to its undeniable contribution to the synthesis of biologically active organic compounds. This review emphasizes the significance of Sharpless asymmetric dihydroxylation in the total synthesis of various natural products, published since 2020.

Prevalence of Toxoplasmosis in Sheep and Goats in Pakistan: A Systematic Review and Meta-Analysis.

Toxoplasmosis, a parasitic disease caused by Toxoplasma gondii, results in congenital disorders and miscarriages among livestock and humans worldwide. This systematic review and meta-analysis were conducted to determine the prevalence of T. gondii infection in sheep and goats in Pakistan from 2000 to 2020. We searched the PubMed, Scopus, EMBASE, and Google Scholar databases and selected 17 publications that fulfilled our inclusion criteria. Eight studies were conducted in Southern Punjab, six in Khyber Pakhtunkhwa, two in Northern Punjab, and one in Central Punjab. The diagnostic tests used in the included articles to confirm toxoplasmosis were the latex agglutination test in 56% of the studies, the enzyme-linked immunosorbent assay in 38%, and the indirect hemagglutination assay in 6%. The infection rates were substantially higher among sheep > 1 year of age (37%) than among sheep ≤ 1 year old (19%). Statistically significant differences in infection rates were found between male and female sheep and goats. The overall infection rate by age was also significant among sheep and goats. Sex and age variability between sheep investigations were significant, and sex heterogeneity and age homogeneity were significant among goats. Hence, robust infection control protocols should be implemented to prevent infection in animals and humans.

Heat transfer and hybrid ferrofluid flow over a nonlinearly stretchable rotating disk under the influence of an alternating magnetic field.

Under the influence of an alternating magnetic field, flow and heat transfer of a ferrofluid flow over a flexible revolving disc are examined. The flow is hampered by the external magnetic field, which is dependent on the alternating magnetic field's frequency. The current work examines the heat transfer and three-dimensional flow of fluid with high viscosity on a spinning disc that is stretched in a radial direction. The governing equations' symmetries are computed using Lie group theory. In the problem, there is a resemblance that can accomplish with radially stretching velocities divided into two categories, specifically, linear and power-law, by imposing limits from the boundary conditions. The literature has already covered linear stretching, but this is the first discussion of power-law stretching. The governing partial differential is turned into an ordinary differential equations system using additional similarity transformations, which are then numerically handled. The results are presented for hybrid alumina-copper/ethylene glycol ([Formula: see text]) nanofluid. The calculated findings are novel, and it has been seen that they accord quite well with those of the earlier extended literature. It has been found that hybrid nanofluid flow outperforms nanofluid flow in terms of Nusselt number or heat transfer rate. The heat transmission in the fluid is reduced as the Prandtl number is increased. The heat transfer increases as dimensionless magnetic field intensity [Formula: see text] increases. Also, axial velocity and radial velocity decrease as magnetic field intensity increases. As the ferromagnetic interaction parameter is raised, the efficiency of heat transmission decreased. For non-linear stretching with stretching parameter 0 < m < 1, the velocity decreases with the increase in m.

Surface-enhanced Raman spectroscopy (SERS) for monitoring colistin-resistant and susceptible E. coli strains.

The emergence of drug-resistant bacteria is a precarious global health concern. In this study, surface-enhanced Raman spectroscopy (SERS) is used to characterize colistin-resistant and susceptible E. coli strains based on their distinguished SERS spectral features for the development of rapid and cost-effective detection and differentiation methods. For this purpose, three colistin-resistant and three colistin susceptible E. coli strains were analyzed by comparing their SERS spectral signatures. Moreover, multivariate data analysis techniques including Principal component analysis (PCA) and Partial Least Squares-Discriminant Analysis (PLS-DA) were used to examine the SERS spectral data of colistin-resistant and susceptible strains. PCA technique was employed for differentiating colistin susceptible and resistant E.coli strains due to alteration in biochemical compositions of the bacterial cell. PLS-DA is employed on SERS spectral data sets for discrimination of these resistant and susceptible E. coli strains with 100% specificity, 100% accuracy, 99.8% sensitivity, and 86% area under receiver operating characteristics (AUROC) curve.

Surface-enhanced Raman spectroscopic analysis of centrifugally filtered HBV serum samples.

BACKGROUND: Raman spectroscopy is an effective tool for detecting and discriminating centrifugally filtered hepatitis B virus serum and centrifugally filtered control serum. OBJECTIVES: The purpose of current study is to separate high molecular weight fractions from low molecular weight fractions present hepatitis B serum to increase the disease diagnostic ability of surface enhanced Raman spectroscopy (SERS). METHODS: Clinically diagnosed centrifugally filtered serum samples of hepatitis B patients are subjected for surface enhanced Raman spectroscopy (SERS) in comparison with centrifugally filtered serum samples of healthy individuals by using silver nanoparticles (Ag-NPs) as SERS substrates. Some SERS spectral features are solely observed in centrifugally filtered serum samples of hepatitis B and some SERS spectral are solely observed in centrifugally filtered serum samples of healthy individuals. The diagnostic ability of SERS is further enhanced with different statistical techniques like principal component analysis (PCA), partial least square discriminant analysis (PLS-DA) and partial least square regression analysis (PLSR) have applied. RESULTS: The disease biomarkers of hepatitis B are more pronounced after their centrifugation as compared with uncentrifuged form. Statistical tools like principal component analysis (PCA) and partial least square discriminant analysis (PLS-DA) clearly differentiated centrifugally filtered serum samples of hepatitis B from centrifugally filtered serum samples of healthy individuals. Furthermore, partial least square regression analysis (PLSR) has been applied for predicting unknown viral load of centrifugally filtered serum sample of hepatitis B. CONCLUSION: SERS technique along with chemometric tools have successfully differentiated centrifugally filtered serum samples of hepatitis B from centrifugally filtered serum samples of healthy individuals. The centrifugal filtration process has increased the differentiation accuracy of PLS-DA in terms of percentage 98% and regression accuracy of PLSR regression analysis in terms of RMSEP (0.30 IU/mL) of this diagnostic method as compared with that of uncentrifuged method.

Anti-arthritic activity of Ricinus communis L. and Withania somnifera L. extracts in adjuvant-induced arthritic rats via modulating inflammatory mediators and subsiding oxidative stress.

OBJECTIVES: This study aimed to evaluate the anti-arthritic activity of Ricinus communis leaves' and Withania somnifera roots' hydroalcoholic extracts in Complete Freund's adjuvant-induced arthritis in Wistar rats. MATERIALS AND METHODS: HPLC and FT-IR analysis detected pharmacologically important phytocompounds in both plant extracts. Oral treatments including methotrexate (MTX; 3 mg/kg twice a week) and extracts at 250 and 500 mg/kg/day were initiated after arthritis induction. Changes in paw swelling, arthritic score, body weight, organ indices (thymus and spleen), hematological and biochemical parameters, and pro-/anti-inflammatory cytokine expression using qRT-PCR were assessed. Oxidative stress markers in hepatic tissue were determined. Histopathological and radiological examinations were also performed. RESULTS: RCE (R. communis extract) and WSE (W. somnifera extract) demonstrated a reduction in paw swelling, arthritic score, and restoration of body weight and organ indices. Hematological parameters, serum inflammatory markers such as CRP and RF, and liver function markers of arthritic rats were significantly (P<0.01) ameliorated with RCE and WSE treatment. Both plants persuasively down-regulated IL-1ß, IL-6, IL-17a, TNF-α, and RANKL and up-regulated IL-4, INF-γ, and OPG relative expression as well as alleviating hepatic oxidative stress parameters. Histopathological and radiological findings revealed a marked reduction in tissue inflammation and bone erosion in extracts treated groups. CONCLUSION: The study findings suggest that R. communis leaves and W. somnifera roots have markedly subsided inflammation and improved health through modulating pro-/anti-inflammatory cytokine expression and reducing oxidative stress.

Tick-borne Diseases in Sheep and Goats in Pakistan: A Systematic Review and Meta-analysis.

BACKGROUND: Ticks are blood-sucking ectoparasites and transmit various types of protozoal, bacterial, and viral diseases in a wild as well as domestic animals and humans globally. Only a few  published reports are avaliable on the prevalence of tick-borne diseases in sheep and goats in Pakistan. AIM AND OBJECTIVE: The aim of this systematic review and meta-analysis was to evaluate the prevalence (2000-2020) of tick-borne disease (theileriosis, babesiosis, Crimean-Congo hemorrhagic fever infection, and anaplasmosis) in sheep and goats in Pakistan. METHODS: A systematic review of articles published in English language (since 2000-2020) was conducted using PubMed and Google Scholar. Diagnostic methods used in the original reference articles were PCR, PCR-RLB, microscopy, and ELISA. RESULTS: The overall prevalence of theileriosis, babesiosis, anaplasmosis, and Crimean-Congo hemorrhagic fever (CCHF) infections was 15.40%, 21.18%, 26.78%, and 11.62%, respectively. The prevalence of anaplasmosis was 22.06% (90/408) in sheep, 21.11% (76/360) in goats, and 40% (120/300) in both sheep and goats with substantial differences (P < 0.001). The prevalence of babesiosis among sheep was 29.88% (104/348) with highly significant differences (P < 0.001), in goats was 29.88% (25/60) with slightly significant differences (P < 0.031%), and in both sheep and goats were 7% (21/300) with highly significant differences (P < 0.001) according to subgroup analysis. The percentage of prevalence of theileriosis was 17.70% (207/1169) in sheep with highly substantial differences (P < 0.001), 4.51% (31/687) in goats with significant differences (P < 0.133), and 25% (125/500) in both sheep and goats with a significant difference among them (P < 0.001). The prevalence of CCHF among sheep was 18.63% (149/800) and 4.63% (37/800) in goats, respectively. The widely used detection method was microscopy (45.56%) followed by ELISA (38.38%), PCR (12.56%), and PCR-RLB (3.48%) test, respectively. This is a comprehensive report on the status of tick-borne disease in sheep and goats in Pakistan. CONCLUSION: Based on our results, among tick-borne diseases anaplasmosis had the highest prevalence rate in sheep and goats. Due to its high prevalence, control measures should be taken to diagnose and prevent it.

Heterologous expression of azoreductase-encoding gene azrS of Bacillus sp. MR-1/2 for enhanced azo dye decolorization and wastewater treatment.

In Pakistan, 55% of textile exports are contributed by textile-units of Faisalabad. The effluents of these textile units, being discharged without any treatment, contain the contamination of a huge amount of synthetic azo dyes. The objective of the current research was to evaluate the contribution of an azoreductase-encoding gene (azrS) from a pre-characterized azo dye decolorizing bacterial strain Bacillus sp. MR-1/2 in a high copy number host system (pUC19-T7-Top-T) of Escherichia coli strain DH5α followed by in-silico prediction of azoreductase enzyme (AzrS) function. The recombinant cells that contained azrS had a significantly higher rate of color removal in congo red and reactive black-5 dyes when compared to wild-type MR-1/2 and E. coli DH5α after 72 h of incubation. Moreover, we were able to show that the recombinant strain significantly reduced the values of all tested parameters (pH, EC, turbidity, TSS, and COD) in actual wastewater. In support of our results, it was also predicted through bioinformatics analysis that the deduced azoreductase protein of strain MR-1/2 is linked with the dye decolorization ability of the strain through NAD(P)H-ubiquinone: oxidoreductase activity. Furthermore, we also found that the deduced protein resembled closely related proteins of protein databank in many features, yet some unique features were predicted in the enzyme activity of strain MR-1/2. It was concluded that the recombinant strain could be examined in pilot-scale experiments for textile wastewater treatment.

Enzymatic detoxification of azo dyes by a multifarious Bacillus sp. strain MR-1/2-bearing plant growth-promoting characteristics.

This study was conducted to elucidate the inherent potential of Bacillus sp. MR-1/2, which was isolated from root zone of maize crop grown on a textile wastewater-irrigated soil. The isolated strain was identified through its ribosomal RNA sequence. Under in vitro conditions, the strain demonstrated its tolerance for high concentrations of various heavy metal ions as determined by minimum inhibitory concentration. Moreover, the strain MR-1/2 exhibited many important phytobeneficial traits such as inorganic P solubilization and 1-aminocyclopropane-1-carboxylate (ACC) deaminase ability even under high metal and salt stress. Results showed that the strain proficiently decolorizes various azo dye compounds, e.g., reactive black-5, reactive red-120, and direct blue-1 and congo red, in broth culture. The bioremediation potential of the strain MR-1/2 was further confirmed by analyzing the retrieved azoreductase gene sequence through bioinformatics tools, whereby a subsequent prediction revealed that the azoreductase enzyme activity was involved in decolorization process. When mung bean seeds were grown in pots under various concentrations of decolorized and non-decolorized azo dye, the Bacillus sp. MR-1/2 not only alleviated the azo dye toxicity, but also increased the plant growth parameters. In conclusion, the strain MR-1/2 efficiently decolorized the azo dyes and helped in mung bean plant growth by alleviating azo dye toxicity.

Role of Wheat Based Diet on the Pathology of Necrotic Enteritis in Turkeys.

The study was conducted to investigate the effects of wheat based diet on the pathology of necrotic enteritis in turkeys. Turkeys were divided into four groups. Groups A and B were kept as noninoculated and fed normal commercial diet while groups C and D were challenged orally with C. perfringens and fed wheat based diet to promote the development of experimental disease. Infected turkeys showed clinical signs of depression, ruffled feathers, and dark yellowish faeces showing the most prominent disease signs in turkeys of group D with 30% mortality. Similarly, turkeys of group D showed more striking gross and histopathologic lesions as compared to turkeys of group C. The most severe gross lesions comprised intestinal distension, small necrotic spots and haemorrhages on intestine, fragile intestinal wall, and gas bubble formation in the small intestine. Histologically, inoculated turkeys showed patchy necrosis, desquamation of intestinal epithelium, and intense leukocyte infiltration in the intestine. Microscopic examination showed significant decrease in the height of intestinal villi of inoculated birds. Haematological studies showed significant influence of necrotic enteritis on the blood profile of turkeys in group D. The findings revealed that simultaneous feeding of wheat enhanced the pathology of necrotic enteritis in turkeys.