Recent advances in CAR T-cell engineering using synthetic biology: Paving the way for next-generation cancer treatment.

This book chapter highlights a comprehensive exploration of the transformative innovations in the field of cancer immunotherapy. CAR (Chimeric Antigen Receptor) T-cell therapy represents a groundbreaking approach to treat cancer by reprogramming a patient immune cells to recognize and destroy cancer cells. This chapter underscores the critical role of synthetic biology in enhancing the safety and effectiveness of CAR T-cell therapies. It begins by emphasizing the growing importance of personalized medicine in cancer treatment, emphasizing the shift from one-size-fits-all approaches to patient-specific solutions. Synthetic biology, a multidisciplinary field, has been instrumental in customizing CAR T-cell therapies, allowing for fine-tuned precision and minimizing unwanted side effects. The chapter highlights recent advances in gene editing, synthetic gene circuits, and molecular engineering, showcasing how these technologies are optimizing CAR T-cell function. In summary, this book chapter sheds light on the remarkable progress made in the development of CAR T-cell therapies using synthetic biology, providing hope for cancer patients and hinting at a future where highly personalized and effective cancer treatments are the norm.

Investigating the Influence of ANTXR2 Gene Mutations on Protective Antigen Binding for Heightened Anthrax Resistance.

Bacillus anthracis is the bacterium responsible for causing the zoonotic disease called anthrax. The disease presents itself in different forms like gastrointestinal, inhalation, and cutaneous. Bacterial spores are tremendously adaptable, can persist for extended periods and occasionally endanger human health. The Anthrax Toxin Receptor-2 (ANTXR2) gene acts as membrane receptor and facilitates the entry of the anthrax toxin into host cells. Additionally, mutations in the ANTXR2 gene have been linked to various autoimmune diseases, including Hyaline Fibromatosis Syndrome (HFS), Ankylosing Spondylitis (AS), Juvenile Hyaline Fibromatosis (JHF), and Infantile Systemic Hyalinosis (ISH). This study delves into the genetic landscape of ANTXR2, aiming to comprehend its associations with diverse disorders, elucidate the impacts of its mutations, and pinpoint minimal non-pathogenic mutations capable of reducing the binding affinity of the ANTXR2 gene with the protective antigen. Recognizing the pivotal role of single-nucleotide polymorphisms (SNPs) in shaping genetic diversity, we conducted computational analyses to discern highly deleterious and tolerated non-synonymous SNPs (nsSNPs) in the ANTXR2 gene. The Mutpred2 server determined that the Arg465Trp alteration in the ANTXR2 gene leads to altered DNA binding (p = 0.22) with a probability of a deleterious mutation of 0.808; notably, among the identified deleterious SNPs, rs368288611 (Arg465Trp) stands out due to its significant impact on altering the DNA-binding ability of ANTXR2. We propose these SNPs as potential candidates for hypertension linked to the ANTXR2 gene, which is implicated in blood pressure regulation. Noteworthy among the tolerated substitutions is rs200536829 (Ala33Ser), recognized as less pathogenic; this highlights its potential as a valuable biomarker, potentially reducing side effects on the host while also reducing binding with the protective antigen protein. Investigating these SNPs holds the potential to correlate with several autoimmune disorders and mitigate the impact of anthrax disease in humans.

A Case of Congenital Disorder of Glycosylation Type 1b Presenting as Hyperinsulinemic Hypoglycemia and Failure to Thrive.

We describe initial manifestations, approach to diagnosis, and treatment of a patient with congenital disorder of glycosylation type 1b (CDG 1b), previously managed as acetylcarnitine deficiency. A 9-year-old girl initially diagnosed with and treated for acetylcarnitine deficiency at an outside hospital presented with recurrent hypoglycemia, failure to thrive, poor weight gain, and short stature. She had discontinued levocarnitine therapy because of lack of response, and testing with us demonstrated a normal carnitine and acyl carnitine panel and hyperinsulinemic hypoglycemia during a diagnostic fast. Oral diazoxide and hydrochlorothiazide were initiated with resolution of hypoglycemia. She had iron deficiency anemia, but an upper gastrointestinal evaluation was normal. Genetic testing confirmed a diagnosis of CDG 1b caused by deficiency of mannose phosphate isomerase. Oral mannose was started with gradual reduction in and eventual discontinuation of the diazoxide dose. Hypoglycemia in the pediatric age group needs a systematic approach. It is important to raise awareness of CDG 1b, which can present as persistent hyperinsulinemic hypoglycemia. Mannose supplementation can ameliorate clinical symptoms and biochemical abnormalities.

Comprehensive examination on codon usage bias pattern of the Bovine Ephemeral fever virus.

Bovine Ephemeral Fever Virus (BEFV) is a non-contagious virus that commonly infects cattle and water buffalo, reduces milk productivity, decreases the quality of beef, and causes an adverse economic impact on the global livestock industry. However, the evolution of BEFV is unclear, and uncertainty exists regarding its global geodynamics. Consequently, this study aims to comprehend the pattern of viral evolution and gene expression in the BEFV genes G, M, N, and P, including synonymous codons. Additionally, we performed recombination analyses, which exclusively detected recombination signals in the G- and P-genes. Subsequently, a phylogenetic tree was constructed to validate and support these findings. The codon usage bias results showed that the BEFV-selected genes were influenced by both natural and mutation pressure. Furthermore, nucleotide A is more abundant in all the selected genes. The eNC values, ranging from 42.99 to 47.10, revealed the presence of moderate codon usage bias, where gene P exhibited the highest and gene G had the lowest codon usage bias. The neutrality and PR-2 plots, specified codon usage patterns of the genes, are also being shaped by strong selectional pressure. This comprehensive analysis of BEFV genes (G, M, N, and P) sheds light on the molecular evolutionary patterns, co-adaptation, and different genes expression in diverse regions, facilitating the development of preventative programs and insights into viral pathogenesis and vaccine design.Communicated by Ramaswamy H. Sarma.

A review of the effects of environmental hazards on humans, their remediation for sustainable development, and risk assessment.

In the race for economic development and prosperity, our earth is becoming more polluted with each passing day. Technological advances in agriculture and rapid industrialization have drastically polluted the two pillars of natural resources, land and water. Toxic chemicals and microbial contaminants/agents created by natural and anthropogenic activities are rapidly becoming environmental hazards (EH) with increased potential to affect the natural environment and human health. This review has attempted to describe the various agents (chemical, biological, and physical) responsible for environmental contamination, remediation methods, and risk assessment techniques (RA). The main focus is on finding ways to mitigate the harmful effects of EHs through the simultaneous application of remediation methods and RA for sustainable development. It is recommended to apply the combination of different remediation methods using RA techniques to promote recycling and reuse of different resources for sustainable development. The report advocates for the development of site-specific, farmer-driven, sequential, and plant-based remediation strategies along with policy support for effective decontamination. This review also focuses on the fact that the lack of knowledge about environmental health is directly related to public health risks and, therefore, focuses on promoting awareness of effective ways to reduce anthropological burden and pollution and on providing valuable data that can be used in environmental monitoring assessments and lead to sustainable development.

Completely o-Phenylene Bridged N4-Cyclophane: A Missing Link in the Phenylene Bridge N4-Cyclophane Family.

Unprecedented types of metal-free complete o-phenylene bridged N4-cyclophanes (M1 and M2) have been synthesized via sequential palladium-catalyzed Buchwald-Hartwig N-arylation reactions. These cyclophanes may be considered as aromatic analogues of aliphatic group-spaced N4-macrocycles. These have been characterized fully using physicochemical characterization techniques and finally by single crystal X-ray structure determination. Their redox and spectral properties have been characterized by cyclic voltammetry, UV-vis spectro-electrochemistry, fluorescence spectral studies, and DFT calculations. These studies have shown rich redox, spectral, and photophysical properties that could make both M1 and M2 potential candidates for various applications.

Alcohol Dehydrogenation-Triggered Selective C3-Alkylation of Indoles by Homogeneous Azo-aromatic Cobalt Catalysts.

Herein, we report azo-benzimidazole containing cobalt complexes (1-3) for alcohol dehydrogenation-triggered C3-alkylation of indoles. In complexes 1-3, ligands are redox noninnocent and showed facile irreversible L/L• reduction followed by Co(II)/Co(I) reduction in close-lying potentials. Taking advantage of facile redox events in 1-3, the first aerial dehydrogenation of alcohols to their corresponding carbonyl compounds is explored. Subsequently, C3-alkylation of indole was studied using alcohols as the alkylating agents. The developed catalytic protocol was found to be efficient and very selective. It has a broad substrate scope and good functional group tolerance. As far as we are aware, it is the first homogeneous cobalt catalyst for C3-alkylation of indole using alcohol as the alkylating agent. Detailed mechanistic studies, including a deuterium labeling experiment, have suggested a borrowing hydrogen method for the C3-alkylation of indole. The coordinated ligand, cooperatively with the Co(II)/Co(I) redox couple, oxidized the coordinated alkoxide in a radical pathway to result in the carbonyl compound (Scheme 1), which on subsequent condensation with indole generates the alkylideneindolenine intermediate "X". Reduction of "X" by an azo-anion radical Co(I) catalyst intermediate resulted in the C3-alkylated indole.

Ru x Pd y Alloy Nanoparticles Uniformly Anchored on Reduced Graphene Oxide Nanosheets (Ru x Pd y @rGO): A Recyclable Catalyst.

In this work, Ru x Pd y alloy nanoparticles were uniformly decorated on a two-dimensional reduced graphene oxide (rGO) sheet by an in situ chemical co-reduction process. The resulting products were characterized by various physiochemical techniques such as X-ray diffraction, Raman spectroscopy, energy-dispersive X-ray spectroscopy, inductively coupled plasma atomic absorption spectroscopy, X-ray photoelectron spectroscopy, and transmission electron microscopy. Further, the synthesized Ru x Pd y @rGO nanocomposites have been employed as a heterogeneous catalyst for three different catalytic reactions: (1) dehydrogenation of aqueous ammonia borane (AB); (2) hydrogenation of aromatic nitro compounds using ammonia borane as the hydrogen source, and (3) for the synthesis of aromatic azo derivatives. The present work illustrates the sustainable anchoring of metal nanoparticles over the surface of rGO nanosheets, which could be used for multifarious catalytic reactions.

Influence of pH, ß-Cyclodextrin, and Metal Ions on the Solubility and Stability of the Medicinally Competent Isoxazole Derivative of Curcumin: A Photophysical Study.

The ß-diketo-modified isoxazole derivative of curcumin (IOC) is well renowned for its anticancer, antioxidant, antimalarial, antiproliferative, and many other biological activities. With the aim of obtaining fundamental knowledge on the photophysics of IOC, the present work was directed toward delineating those at different pH environments and studying the degradation profiles of IOC at five different pH values. Because one of the primary drawbacks of curcumin is its rapid degradation at physiological conditions, the studies showed that the problem could be resolved, as the IOC molecule was extremely stable even in a highly alkaline medium. Further, in order to encounter the problems associated with the low solubility of IOC in aqueous media, ß-CD (ß-cyclodextrin) was used and calculations of the thermodynamic parameters revealed that the process of development of the host-guest inclusion complex was highly spontaneous in nature. The synthesis of the IOC:ß-CD inclusion complex has also been accomplished in the solid state, and the solid formed has been characterized using various physicochemical techniques. Finally, while variations in the pH as well as addition of foreign metal ions in +1 and +2 oxidation states showed minimal effect on the photophysics of the IOC:ß-CD inclusion complex, antiproliferative studies performed with 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assays revealed their nontoxic nature on fibroblast L929 normal cell lines and extremely toxic activity on human lung cancer A549 cell lines.

Mesenchymal stem cells protect against malaria pathogenesis by reprogramming erythropoiesis in the bone marrow.

Malaria remains a major public health problem worldwide. The immune mechanisms that mediate protection against malaria are still unclear. Previously, we reported that mesenchymal stem cells (MSCs) play a critical role in host protection against malaria by altering the dynamic balance of T regulatory cells and effector T cells producing inflammatory cytokines. Here, we report that MSCs reprogram haematopoiesis in primary (bone marrow) and secondary (spleen) lymphoid organs to provide host protection against malaria. Adoptive transfer of MSCs from malaria-infected mice to naïve recipient mice that were subsequently infected with malaria parasites dramatically accelerated the formation of colony-forming units-erythroid cells in the bone marrow. Adoptively transferred MSCs also induced expression of the key erythroid cell differentiation factor GATA-1 in the spleen of recipient animals. Interestingly, we further observed a subtle increase in the CD34+ hematopoietic stem and progenitor cells in lymphoid organs, including spleen and lymph nodes. Infusion of MSCs also enhanced T cell proliferation, resulting in increased numbers of both CD4+ and CD8+ T cells in the spleen. MSCs also inhibited the induction of the negative co-stimulatory receptor programmed death-1 by T cells in recipient animals upon infection with malaria parasites. Taken together, our findings suggest that MSCs play a critical role in host protection against malaria infection by modulating erythropoiesis and lymphopoiesis.

The Role of Imidazolium-Based Surface-Active Ionic Liquid to Restrain the Excited-State Intramolecular H-Atom Transfer Dynamics of Medicinal Pigment Curcumin: A Theoretical and Experimental Approach.

The naturally occurring polyphenolic compound curcumin has shown various medicinal and therapeutic effects. However, there are various challenges associated with curcumin, which limits its biomedical applications, such as its high degradation rate and low aqueous solubility at neutral and alkaline pH. In the present study, efforts have been directed towards trying to resolve such issues by encapsulating curcumin inside the micelles formed by imidazolium-based surface-active ionic liquid (SAIL). The shape and size of the micelles formed by the SAIL have been characterized by using DLS analysis as well as TEM measurements. The photo-physics of curcumin in the presence of ionic liquid (IL) and also with the addition of salt (NaCl) has been explored by using different optical spectroscopic tools. The time-dependent absorption studies have shown that there is relatively higher suppression in the degradation rate of curcumin after encapsulation by the imidazolium-based SAIL in an aqueous medium. The TCSPC studies have revealed that there is deactivation in the nonradiative intramolecular hydrogen transfer process of curcumin in the presence of IL micelles as well as with the addition of salt. Furthermore, the time-dependent fluorescence anisotropy measurement has been carried out to figure out the location of curcumin inside the micellar system. In order to correlate all experimental findings, density functional theory (DFT) and classical molecular dynamics (MD) simulations at neutral pH media have been performed. It has been found that the van der Waals force of interactions plays a major role in the stabilization of curcumin in the micelles rather than the coulombic forces. It also has been observed that the van der Waals interactions remain unaffected in the presence of salt. However, as revealed by the MD simulation results, the micelles are found to be more compact in size after the addition of salt. The RMSD results show that the micelles formed by the SAIL achieve greater stability after a particular time constraint. Our results have divulged that the SAIL could act as a promising drug delivery system.

Nitrogen-Rich and Porous Graphitic Carbon Nitride Nanosheet-Immobilized Palladium Nanoparticles as Highly Active and Recyclable Catalysts for the Reduction of Nitro Compounds and Degradation of Organic Dyes.

In the present study, we have successfully synthesized nitrogen-rich graphitic carbon nitride (g-C3N4) nanosheets by a simple direct thermal polymerization approach. The synthesized g-C3N4 nanosheets were exfoliated using HCl to make their surface a few nanometers thick. The ultrathin surface was achieved by simply mixing g-C3N4 in 3 M HCl. After that, palladium nanoparticles were uniformly immobilized on the surface of g-C3N4. The synthesized materials were characterized by various physiochemical techniques such as X-ray diffraction, energy-dispersive X-ray spectroscopy, and Fourier transform infrared spectroscopy. Information about morphology and size was obtained through transmission electron microscopy and scanning electron microscopy. The Brunauer-Emmett-Teller surface area, pore volume, and pore diameter were determined using nitrogen adsorption-desorption measurements. The prepared material (Pd/g-C3N4) was utilized as an efficient catalyst for the reduction of hazardous nitroarenes and degradation of organic dyes. The catalyst could be easily recovered through centrifugation and then could be reused multiple times for the further catalytic cycles with a little loss in its catalytic activity. The work presented here illustrates the sustainable anchoring of metal nanoparticles over the surface of nitrogen-rich g-C3N4 nanosheets and could be utilized for different types of catalytic reactions.

Synthesis of dendritic fibrous nanosilica over a cubic core (cSiO2@DFNS) with catalytically efficient silver nanoparticles for reduction of nitroarenes and degradation of organic dyes.

In this study, dendritic fibrous core-shell silica particles having cubic morphology with uniform and vertical nanochannels have been successfully synthesised. The synthesized dendritic fibrous nanosilica over a cubic core (cSiO2@DFNS) have been characterized by using various techniques, such as powder X-ray diffraction, TEM, FE-SEM, TGA EDS, FT-IR and N2 adsorption-desorption experiments. The prepared DFNS particles demonstrated a very high surface area and pore diameter. Amine groups were functionalized on the fibres of cSiO2@DFNS and after that silver nanoparticles could be successfully immobilized on amine functionalized cubic silica particles. Due to the presence of a high surface area and a uniform pore diameter, the silver nanoparticle loaded cSiO2@DFNS could be successfully employed as an efficient and recoverable catalyst for reduction of toxic aromatic nitro compounds and degradation of organic dyes. Higher catalytic activity of the prepared material could be attributed to its fibrous morphology which could facilitate proper interactions of the reactants molecules with the silver nanoparticles.

An ultrasensitive amperometric determination of lactate by lactate dehydrogenase nanoparticles immobilized onto Au electrode.

The nanoparticles (NPs) of commercial lactate dehydrogenase (LDH) from rabbit muscle were prepared, characterized and immobilized covalently onto Au electrode to construct an improved amperometric lactate biosensor. The biosensor showed optimum response within 2.5 s at an applied potential of 0.10 V, pH 7.0 and 35 °C. The biosensor had a wider working range linear (0.01 µM to 55 mM) with a higher sensitivity (3.45 ±â€¯0.02 µA cm-2 mM-1) and a lower detection limit (0.01 µM) compared to earlier biosensors. The analytical recovery of added lactate in sera was 98.61% and within and between batches coefficients of variations (CVs) were 1.38% and 1.03%, respectively. A good correlation coefficient (R2 = 0.99) was observed between sera lactate values as measured by the standard enzymatic colorimetric method and the present biosensor. The biosensor measured lactic acid in the sera of apparently healthy subjects and persons suffering from cardiogenic shocks. There was a 10% loss in the initial activity of LDHNPs/Au electrode after its regular use over a period of 210 days, while being stored dry at 4 °C.

Malaria diagnosis by PCR revealed differential distribution of mono and mixed species infections by Plasmodium falciparum and P. vivax in India.

Malaria is a vector-borne infectious disease, caused by five different species of the genus Plasmodium, and is endemic to many tropical and sub-tropical countries of the globe. At present, malaria diagnosis at the primary health care level in India is conducted by either microscopy or rapid diagnostic test (RDT). In recent years, molecular diagnosis (by PCR assay), has emerged as the most sensitive method for malaria diagnosis. India is highly endemic to malaria and shoulders the burden of two major malaria parasites, Plasmodium falciparum and P. vivax. Previous studies using PCR diagnostic assay had unraveled several interesting facts on distribution of malaria parasites in India. However, these studies had several limitations from small sample size to limited geographical areas of sampling. In order to mitigate these limitations, we have collected finger-prick blood samples from 2,333 malaria symptomatic individuals in nine states from 11 geographic locations, covering almost the entire malaria endemic regions of India and performed all the three diagnostic tests (microscopy, RDT and PCR assay) and also have conducted comparative assessment on the performance of the three diagnostic tests. Since PCR assay turned out to be highly sensitive (827 malaria positive cases) among the three types of tests, we have utilized data from PCR diagnostic assay for analyses and inferences. The results indicate varied distributional prevalence of P. vivax and P. falciparum according to locations in India, and also the mixed species infection due to these two species. The proportion of P. falciparum to P. vivax was found to be 49:51, and percentage of mixed species infections due to these two parasites was found to be 13% of total infections. Considering India is set for malaria elimination by 2030, the present malaria epidemiological information is of high importance.