Divergent Gold Catalysis: Unlocking Molecular Diversity through Catalyst Control.

The catalyst-directed divergent synthesis, commonly termed as "divergent catalysis", has emerged as a promising technique as it allows chartering of structurally distinct products from common substrates simply by modulating the catalyst system. In this regard, gold complexes emerged as powerful catalysts as they offer unique reactivity profiles as compared to various other transition metal catalysts, primarily due to their salient electronic and geometrical features. Owing to the tunable soft π-acidic nature, gold catalysts not only evolved as superior contenders for catalyzing the reactions of alkynes, alkenes, and allenes but also, more intriguingly, have been found to provide divergent reaction pathways over other π-acid catalysts such as Ag, Pt, Pd, Rh, Cu, In, Sc, Hg, Zn, etc. The recent past has witnessed a renaissance in such examples wherein, by choosing gold catalysts over other transition metal catalysts or by fine-tuning the ligands, counteranions or oxidation states of the gold catalyst itself, a complete reactivity switch was observed. However, reviews documenting such examples are sporadic; as a result, most of the reports of this kind remained scattered in the literature, thereby hampering further development of this burgeoning field. By conceptualizing the idea of "Divergent Gold Catalysis (DGC)", this review aims to consolidate all such reports and provide a unified approach necessary to pave the way for further advancement of this exciting area. Based on the factors governing the divergence in product formation, an explicit classification of DGC has been provided. To gain a fundamental understanding of the divergence in observed reactivities and selectivities, the review is accompanied by mechanistic insights at appropriate places.

Designing a Pro-Equity HPV Vaccine Delivery Program for Girls Who Have Dropped Out of School: Community Perspectives From Uttar Pradesh, India.

India experiences a substantial burden of cervical cancer and accounts for nearly one third of cervical cancer deaths worldwide. While human papillomavirus (HPV) vaccines have been introduced subnationally in some states, HPV has not yet been rolled out nationally. Given the target age group, schools are the most common delivery channel for HPV vaccines, but this fails to account for local girls who never attended or no longer attend school. We conducted a qualitative, design-informed, community-based study conducted in Uttar Pradesh, India. We assessed facilitators and barriers among out-of-school girls and proposed program characteristics to inform the design of pro-equity HPV vaccine delivery programs for out-of-school girls. Programs should improve parental knowledge of the risk of cervical cancer, engage vaccinated girls as vaccine champions, utilize varied media options for low-literacy populations, and ensure that HPV vaccine services are accessible and flexible to accommodate out-of-school girls. In areas with poor or irregular school attendance among adolescent girls, HPV vaccine coverage will remain suboptimal until programs can effectively address their needs and reach this priority population. Our findings present a meaningful opportunity for program planners to purposefully design HPV vaccination programs according to these parameters, rather than modifying existing programs to include HPV vaccine. Adolescent girls, their parents, and other community members should be involved in program design to ensure that the program can effectively meet the needs of adolescent girls who are not in school.

Emerging role of trimethylamine-N-oxide (TMAO) in colorectal cancer.

Among gut microbiota-derived metabolites, trimethylamine-N-oxide (TMAO) is receiving increased attention due to its possible role in the carcinogenesis of colorectal cancer (CRC). In spite of numerous reports implicating TMAO with CRC, there is a lack of empirical mechanistic evidences to concretize the involvement of TMAO in the carcinogenesis of CRC. Possible mechanisms such as inflammation, oxidative stress, DNA damage, and protein misfolding by TMAO have been discussed in this review in the light of the latest advancements in the field. This review is an attempt to discuss the probable correlation between TMAO and CRC but this linkage can be concretized only once we get sufficient empirical evidences from the mechanistic studies. We believe, this review will augment the understanding of linking TMAO with CRC and will motivate researchers to move towards mechanistic study for reinforcing the idea of implicating TMAO with CRC causation. KEY POINTS: • TMAO is a gut bacterial metabolite which has been implicated in CRC in recent years. • The valid mechanistic approach of CRC causation by TMAO is unknown. • The article summarizes the possible mechanisms which need to be explored for validation.

Carbon cloth-based immunosensor for detection of 25-hydroxy vitamin D3.

Vitamin D (VD) deficiency is a global health concern due to its serious health impacts, and at present, the monitoring of VD status is expensive. Here, a novel immunosensor for sensitive and label-free detection of 25-hydroxy vitamin D3 (25VD3) is reported. Nanostructured cerium(IV) oxide (nCeO2) was anchored onto carbon cloth (CC) via electrophoretic deposition to fabricate a nanoplatform (nCeO2/CC). Subsequently, bioactive molecules (anti-25VD3 and BSA) were introduced to fabricate the nanobioplatform BSA/anti-25VD3/nCeO2/CC as an immunosensor. The analytical performance of the developed immunosensor was studied towards 25VD3 detection. The immunosensor provides a broad linear range of 1-200 ng mL-1, high sensitivity of 2.08 µA ng-1 mL cm-2, a detection limit of 4.63 ng mL-1, and a response time of 15 min, which is better than that of previous reports. The biosensor exhibited high selectivity, good reproducibility, and excellent stability for about 45 days. The potential application of the proposed immunosensor was observed for real serum samples towards 25VD3 detection that demonstrated a high correlation with the conventional enzyme-linked immunosorbent assay. Graphical abstract.

Potential amelioration of waterborne iron toxicity in channel catfish (Ictalurus punctatus) through dietary supplementation of vitamin C.

Iron overload in water is a problem in many areas of the world, which could exert toxic effects on fish. To achieve maximum growth and overall fitness, iron induced toxicity must be alleviated. Therefore, this research was undertaken to investigate the potential mitigation of iron toxicity by dietary vitamin C supplementation in channel catfish (Ictalurus punctatus). Two doses of vitamin C (143 and 573 mg/kg diet) were tested against high environmental iron (HEI, 9.5 mg/L representing 25% of 96 h LC50). Fish were randomly divided into six groups with four replicated tanks. The groups were Control (vitamin C deficient feed), LVc (143 mg vitamin C supplemented per kg diet), HVc (573 mg vitamin C supplemented per kg diet), Con + Fe (control exposed to HEI), LVc + Fe (LVc exposed to HEI) and HVc + Fe (HVc exposed to HEI). Following an 8 week trial, there was a significant reduction in weight gain (WG%) in Con + Fe compared to the control, indicating a toxic effect of HEI on fish growth performance. Interestingly, WG% in both LVc + Fe and HVc + Fe groups were significantly higher than Cont + Fe, signifying that HEI inhibited growth, but this was alleviated by vitamin C. Both hemoglobin content and hematocrit were higher in LVc + Fe compared to the control and Con + Fe. In addition, exposure to HEI (Con + Fe) incited hepatic oxidative stress based on an over-accumulation of malondialdehyde (MDA) along with a significant inhibition in superoxide dismutase (SOD) and catalase (CAT) activities; whereas in LVc + Fe and HVc + Fe, the MDA content restored to basal level. A series of histopathological alterations were observed in the liver and gills, with the most severe lesions in Con + Fe, which was also complemented with a remarkable increase in hepatic iron accumulation. Vitamin C supplementations reduced the augmented concentrations of iron accumulation to that of the control. No effect, regardless of the treatments, was noted for fatty acid composition of muscle. Overall, our findings suggest that the vitamin C supplementation can be an effective therapeutic approach for boosting growth as well as alleviating iron toxicity in catfish.

Gold-Catalyzed 1,2-Diarylation of Alkenes.

Herein, we disclose the gold-catalyzed 1,2-diarylation of alkenes through the interplay of ligand-enabled AuI /AuIII catalysis with the idiosyncratic π-activation mode of gold complexes. Unlike the classical migratory-insertion-based approach to 1,2-diarylation, the present approach not only circumvents the formation of direct Ar-Ar' coupling and Heck-type side products but more intriguingly demonstrates reactivity and selectivity complementary to those of previously known metal catalysis (Pd, Ni, or Cu). Detailed investigations to underpin the mechanistic scenario revealed oxidative addition of aryl iodides to an AuI complex to be the rate-limiting step owing to the non-innocent nature of the aryl alkene.

Advances in Higher Order Multiplexing Techniques in Proteomics.

Proteomics by mass spectrometry (MS) allows the large-scale identification and quantitation of the cellular proteins in a given biological context. Systems biology studies from proteomics data are largely limited by the accuracy and coverage of quantitative proteomics along with missing values. Toward this end, statistically robust biological observations are required, comprising multiple replicates, preferably with little technical variations. Multiplexed labeling techniques in proteomics allow quantitative comparisons of several biological samples or conditions. In this focused Review, we discuss an emerging technique called higher order multiplexing or enhanced multiplexing, a unique combination of traditional MS1- and MS2-based quantitative proteomics methods that allows for expanding the multiplexing capability of MS methods to save valuable instrument time, achieve statistical robustness, enhance coverage and quantitation accuracy, and reduce the run-to-run variability. We discuss the various innovative studies and experimental designs that exploit the power of this technique and its variants to provide an overview of a rapidly growing area and also to highlight the advantages and challenges that lie ahead in the widespread adoption of this technique.

Efficient Cellular Entry of (r-x-r)-Type Carbamate-Plasmid DNA Complexes and Its Implication for Noninvasive Topical DNA Delivery to Skin.

Arginine-rich cell penetrating peptides are powerful tools for in vitro as well as in vivo delivery of a wide plethora of biomolecules. However, presence of consecutive arginine residues leads to enhanced amenability for proteolytic degradation as well as steric hindrances for membrane interactions which compromise its bioavailability. In order to overcome these limitations we previously reported a safe and stable octaarginine based oligomer, i.e., (r-x-r)4-carbamate, where the backbone amide linkages were replaced by carbamate linkages and 6-aminohexanoic acid based spacer moieties were incorporated for better flexibility, hydrophobicity, optimal spacing of guanidinium groups, and protection against proteolytic cleavage; resulting in improved transfection efficiency over its amide counterpart. In the present work we have investigated the mechanism behind this enhanced transfection efficiency and, based on our observations, demonstrate how the synergistic effect of rationalized oligomer designing, complex characteristics, and cell type contributes to overall effective intracellular delivery. Our results indicate that the (r-x-r)4-carbamate-plasmid DNA complexes primarily utilize lipid raft dependent pathway of cellular entry more than other pathways, and this possibly facilitates their increased entry in the lipid raft rich milieu of skin cells. We also emphasize the utility of oligomer (r-x-r)4-carbamate as an efficient carrier for topical delivery of nucleic acids in skin tissue. This carrier can be utilized for safe, efficient, and noninvasive delivery of therapeutically relevant macromolecular hydrophilic cargo like nucleic acids to skin.

Second generation, arginine-rich (R-X'-R)(4)-type cell-penetrating α-ω-α-peptides with constrained, chiral ω-amino acids (X') for enhanced cargo delivery into cells.

The syntheses of novel N-aminoalkyl proline-derived spacers (X') in polycationic (R-X'-R)-motif cell-penetrating α-ω-α-peptides are described as improved molecular transporters and their structural features studied by CD. FACS analysis shows enhanced cellular uptake and confocal microscopy indicates predominantly cytoplasmic localization. The oligomers are efficient at transporting pDNA into cells. The chirality together with the hydrophobicity and flexibility derived from the spacer chain are found to have marked influence on the cell-penetrating and cargo delivery properties of the cell-penetrating peptides (CPPs). The peptides containing N-(3-aminopropyl)-D-proline spacers are found to be the best at cell penetration and cargo delivery in the present study.

A mini review on 6PPD quinone: A new threat to aquaculture and fisheries.

Numerous toxic substances are directly and indirectly discharged by humans into water bodies, causing distress to the organisms living on it. 6PPD, an amino antioxidant from tires reacts with ozone to form 6PPD-Q, which has garnered global attention due to its lethal nature to various organisms. This review aims to provide an understanding of the sources, transformation, and fate of 6PPD-Q in water and the current knowledge on its effects on aquatic organisms. Furthermore, we discuss research gaps pertaining to the mechanisms by which 6PPD-Q acts within fish bodies. Previous studies have demonstrated the ubiquitous presence of 6PPD-Q in the environment, including air, water, and soil. Moreover, this compound has shown high lethality to certain fish species while not affecting others. Toxicological studies have revealed its impact on the nervous system, intestinal barrier function, cardiac function, equilibrium loss, and oxidative stress in various fish species. Additionally, exposure to 6PPD-Q has led to organ injury, lipid accumulation, and cytokine production in C. elegans and mice. Despite studies elucidating the lethal dose and effects of 6PPD-Q in fish species, the underlying mechanisms behind these symptoms remain unclear. Future studies should prioritize investigating the mechanisms underlying the lethality of 6PPD-Q in fish species to gain a better understanding of its potential effects on different organisms.

Granular Hemostatic Composite of Alginate, Calcium, and Zinc for Rapid and Effective Management of Post-Traumatic Hemorrhage.

Post-traumatic hemorrhage, which can result from accidents or battlefield injuries, is a significant global concern due to the high prehospital mortality rate. Substantial efforts have been made to develop hemostatic agents that can effectively reduce hemorrhage in the immediate aftermath of a traumatic event. The present study investigated the potential efficacy of Ca2+ and Zn2+ supplemented sodium alginate-based dry hemostatic particles (SA-CZ DHP) to manage excessive blood loss or post-traumatic hemorrhage. SA-CZ DHP were developed, followed by their physical and biochemical characterization, cytocompatibility and hemocompatibility testing, and critical evaluation of the hemostatic potential in vitro and in vivo. The safe SA-CZ DHP showed high absorption and accelerated blood clotting kinetics with reduced coagulation time (≈70%, p < 0.0001) in whole human blood, observed with insignificant hemolysis and uninterrupted RBC morphology. SA-CZ DHP significantly reduced the mean blood loss (≈90% in SD rats tail incision), and bleeding time (≈60% in BALB/c mice tail incision) was at par with commercially available Celox hemostatic granules. In conclusion, the biocompatible SA-CZ DHP exhibited rapid and effective management of excessive blood loss. It is also pertinent to note that the developed formulation could be a cost-effective alternative to its commercial counterparts.

Nano-modified screen-printed electrode-based electrochemical immunosensors for oral cancer biomarker detection in undiluted human serum and saliva samples.

This proposed work reports the development of in-house made conductive ink-based screen-printed electrodes (SPEs) for label-free detection of oral cancer biomarkers. Carbon ink synthesis includes graphite powder, gum arabic, and water. The selectivity test of the fabricated SPE involves immobilizing antibodies specific to biomarkers and challenges with redox-active interference, other serum molecules, and non-target biomarkers. Three different biomarkers, cytokeratin-19 fragment (CYFRA 21-1), interleukin 8 (IL-8), and tumor protein p53 (TP-53), act as target entities for the detection of oral cancer in patients' samples (serum, N = 28, and saliva, N = 16) at an early stage. The standard technique enzyme-linked immunosorbent assay (ELISA) was employed to estimate the concentration of the biomarkers in serum and saliva samples. SPEs contain amine (-NH2) functional groups involved in covalent bonding with the carboxyl (-COOH) groups of antibody molecules. These immunosensors exhibited remarkably lower detection limits of 829.5 pg mL-1, 0.543 pg mL-1, and 1.165 pg mL-1, and excellent sensitivity of 0.935 µA mL pg-1 cm-1, 0.039 µA mL pg-1 cm-1, and 0.008 µA mL pg-1 cm-1 for CYFRA 21-1, IL-8, and TP-53 biomarkers, respectively. This sensing platform does not require any functionalization for biomolecule immobilization. Thus, it is a cost-effective, disposable, flexible, miniaturized, and sensitive strip to detect oral cancer biomarkers.

A Case Report of Occult Weak 'A' Subgroup: An Important Message for Renal Transplant Physicians.

Accurate ABO grouping is the cornerstone of a successful ABO-compatible organ transplant. While conventional methods identify blood groups accurately in most cases, rare and weak blood groups could occasionally be misread/missed. Weak A subgroups such as A3, Ax, Aend, Am, Ay, and Ael are often mistyped as group O. We present one interesting case of 'weak A' subgroup in a renal transplant donor, who was wrongly typed as 'O' Rh D positive by conventional grouping techniques. It was a near miss as the donor was almost selected for transplant for the patient with blood group B positive.

Enhanced Electrochemical Biosensing of the Sp17 Cancer Biomarker in Serum Samples via Engineered Two-Dimensional MoS2 Nanosheets on the Reduced Graphene Oxide Interface.

In the present investigation, we reported a label-free and highly effective immunosensor for the first time employing a nanostructured molybdenum disulfide nanosheets@reduced graphene oxide (nMoS2 NS@rGO) nanohybrid interface for the determination of sperm protein 17 (Sp17), an emerging cancer biomarker. We synthesized the nMoS2 NS@rGO nanohybrid using a one-step hydrothermal technique and then functionalized it with 3-aminopropyltriethoxysilane (APTES). Furthermore, the anti-Sp17 monoclonal antibodies were covalently attached to the APTES/nMoS2 NS@rGO/indium tin oxide (ITO) electrode utilizing 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide-N-hydroxy succinimide (EDC-NHS) coupling chemistry. Bovine serum albumin (BSA) was then used to block nonspecific binding regions on the anti-Sp17/APTES/nMoS2 NS@rGO/ITO bioelectrode. The morphological and structural features of the synthesized nanohybrid and the modified electrodes were studied using transmission electron microscopy, scanning electron microscopy with energy dispersive X-ray (EDX) composition studies, atomic force microscopy, Fourier transform infrared spectroscopy, and Raman spectroscopy. The immunoreaction between the Sp17 antigen and anti-Sp17 antibodies on the surface of the BSA/anti-Sp17/APTES/nMoS2 NS@rGO/ITO sensing bioelectrode was applied as the basis for the detection technique, which measured the electrocatalytic current and impedimetric response change. The designed BSA/anti-Sp17/APTES/nMoS2 NS@rGO/ITO bioelectrode showed improved amperometric and impedimetric biosensing performance in the response studies, including remarkable sensitivity (23.2 µA ng-1mL cm-2 and 0.48 kΩ mL ng-1 cm-2), wider linearity (0.05-8 and 1-8 ng mL-1), an excellent lower detection limit (0.13 and 0.23 ng mL-1), and a rapid response time of 20 min. The biosensor exhibited impressive storage durability lasting 7 weeks and showed remarkable precision in identifying Sp17 in serum samples from cancer patients, as confirmed using the enzyme-linked immunosorbent assay method.

FRET Based Biosensor: Principle Applications Recent Advances and Challenges.

Förster resonance energy transfer (FRET)-based biosensors are being fabricated for specific detection of biomolecules or changes in the microenvironment. FRET is a non-radiative transfer of energy from an excited donor fluorophore molecule to a nearby acceptor fluorophore molecule. In a FRET-based biosensor, the donor and acceptor molecules are typically fluorescent proteins or fluorescent nanomaterials such as quantum dots (QDs) or small molecules that are engineered to be in close proximity to each other. When the biomolecule of interest is present, it can cause a change in the distance between the donor and acceptor, leading to a change in the efficiency of FRET and a corresponding change in the fluorescence intensity of the acceptor. This change in fluorescence can be used to detect and quantify the biomolecule of interest. FRET-based biosensors have a wide range of applications, including in the fields of biochemistry, cell biology, and drug discovery. This review article provides a substantial approach on the FRET-based biosensor, principle, applications such as point-of-need diagnosis, wearable, single molecular FRET (smFRET), hard water, ions, pH, tissue-based sensors, immunosensors, and aptasensor. Recent advances such as artificial intelligence (AI) and Internet of Things (IoT) are used for this type of sensor and challenges.

Effects of microplastics and nanoplastics in shrimp: Mechanisms of plastic particle and contaminant distribution and subsequent effects after uptake.

To date, previous studies have reported the adverse effects of microplastics (MPs) and nanoplastics (NPs) on both freshwater and marine organisms. However, the information on MPs' and NPs' effects on shrimp species is scarce. In addition, the factors influencing the distribution of these particles in aquatic systems have been explained, yet the mechanisms behind MPs and NPs distribution and consumption, specifically to crustaceans and shrimp, have not been elucidated in detail. The effects of MPs and NPs as well as plastic-carried contaminants and pathogens on shrimp are critical to shrimp production and subsequent human consumption. Recent findings are required to review and discuss to open up new avenues for emerging Shrimp and crustacean research for sustainability. This review summarizes the distribution and fate of MPs and NPs along with contaminants and pathogens and identifies potential risks to shrimp health. The transport of MPs and NPs is influenced by their plastic properties, hydrodynamics, and water properties. Additionally, the fate of these particles on a plastic surface (plastisphere) is regulated by contaminant properties. Pathogens thriving on plastic surfaces and contaminants adsorbed can reach aquatic organisms directly with plastic particles or indirectly after release to an aquatic environment. MPs and NPs can be absorbed by shrimp through their gills and mouth and accumulate in their internal organs. Innate immunity influenced the degree of survival rate, tissue damage, alteration of gut microbiota, and increased oxidative stress caused by MPs and NPs accumulation. The studies on the effects of MPs and NPs are still not sufficient to understand how these particles are absorbed from various parts of the shrimp body and the fate of these plastics inside the body.

Biocompatible epoxysilane substituted polymer-based nano biosensing platform for label-free detection of cancer biomarker SP17 in patient serum samples.

Herein, we report the results of the studies relating to developing a simple, sensitive, cost-effective, and disposable electrochemical-based label-free immunosensor for real-time detection of a new cancer biomarker, sperm protein-17 (SP17), in complex serum samples. An indium tin oxide (ITO) coated glass substrate modified with self-assembled monolayers (SAMs) of 3-glycidoxypropyltrimethoxysilane (GPTMS) was functionalized via covalent immobilization of monoclonal anti-SP17 antibodies using EDC(1-(3-(dimethylamine)-propyl)-3-ethylcarbodiimide hydrochloride) - NHS (N-hydroxy succinimide) chemistry. The developed immunosensor platform (BSA/anti-SP17/GPTMS@SAMs/ITO) was characterized via scanning electron microscopy (SEM), atomic force microscopy (AFM), contact angle (CA), Fourier transform infrared (FT-IR) spectroscopic, and electrochemical techniques such as cyclic voltammetry (CV), differential pulse voltammetry (DPV), and electrochemical impedance spectroscopy (EIS) techniques. The fabricated BSA/anti-SP17/GPTMS@SAMs/ITO immunoelectrode platform was used to measure changes in the magnitude of the current of the electrodes through an electrochemical CV and DPV technique. A calibration curve between current and SP17 concentrations exhibited a broad linear detection range of (100-6000 & 50-5500 pg mL-1), with enhanced sensitivity (0.047 & 0.024 µA pg mL-1 cm-2), limit of detection (LOD) and limit of quantification (LOQ) of 47.57 & 142.9 pg mL-1 and 158.58 & 476.3 pg mL-1, by CV and DPV technique, respectively with a rapid response time of 15 min. It possessed exceptional repeatability, outstanding reproducibility, five-time reusability, and high stability. The biosensor's performance was evaluated in human serum samples, giving satisfactory findings obtained via the commercially available enzyme-linked immunosorbent assay (ELISA) technique, proving the clinical applicability for early diagnosis of cancer patients. Moreover, various in vitro studies in murine fibroblast cell line L929 have been performed to assess the cytotoxicity of GPTMS. The results demonstrated that GPTMS has excellent biocompatibility and can be used for biosensor fabrication.

Fabrication of alkoxysilane substituted polymer-modified disposable biosensing platform: Towards sperm protein 17 sensing as a new cancer biomarker.

SP17 is a mammalian protein found in the testis and spermatozoa that have been identified as a tumor-associated antigen in a range of human cancers. A unique method for fabricating the first ultrasensitive, selective, and label-free immunosensor for the detection of SP17, a new cancer biomarker in complicated serum samples, is presented in this paper. This immunosensor was also the first biosensor built using a disposable ITO sheet modified with an aminosilane known as APTMS as an immobilization platform for fabricating the SP17 biosensor. The immobilization of chemical and biological species onto the electrode surface was cross-verified by various analytical and morphological techniques. Stepwise modifications done on the immunoelectrodes were also studied using electrochemical techniques. Selective interaction between anti-SP17 and SP17 with varying concentrations (100-5000 pg mL-1) was measured with the DPV technique. The immunosensor exhibited low LOD and LOQ of 70.07 and 233.57 pg mL-1, respectively, with a sensitivity of 0.013 µA mL pg-1 cm-2. The fabricated immunosensor performance was analyzed by quantifying the SP17 concentrations in patient serum samples. The data obtained from the developed immunosensor demonstrated excellent reproducibility, repeatability, and selectivity among various interferants, including cancer biomarkers. Further, the observed results have been validated via ELISA, which showed good agreement with the electrochemical results. This could establish a new platform for detecting other cancer biomarkers and can be employed for clinical diagnostics applications.

Nanomaterial-Based Electrochemical Nanodiagnostics for Human and Gut Metabolites Diagnostics: Recent Advances and Challenges.

Metabolites are the intermediatory products of metabolic processes catalyzed by numerous enzymes found inside the cells. Detecting clinically relevant metabolites is important to understand their physiological and biological functions along with the evolving medical diagnostics. Rapid advances in detecting the tiny metabolites such as biomarkers that signify disease hallmarks have an immense need for high-performance identifying techniques. Low concentrations are found in biological fluids because the metabolites are difficult to dissolve in an aqueous medium. Therefore, the selective and sensitive study of metabolites as biomarkers in biological fluids is problematic. The different non-electrochemical and conventional methods need a long time of analysis, long sampling, high maintenance costs, and costly instrumentation. Hence, employing electrochemical techniques in clinical examination could efficiently meet the requirements of fully automated, inexpensive, specific, and quick means of biomarker detection. The electrochemical methods are broadly utilized in several emerging and established technologies, and electrochemical biosensors are employed to detect different metabolites. This review describes the advancement in electrochemical sensors developed for clinically associated human metabolites, including glucose, lactose, uric acid, urea, cholesterol, etc., and gut metabolites such as TMAO, TMA, and indole derivatives. Different sensing techniques are evaluated for their potential to achieve relevant degrees of multiplexing, specificity, and sensitivity limits. Moreover, we have also focused on the opportunities and remaining challenges for integrating the electrochemical sensor into the point-of-care (POC) devices.

2D Materials-Based Aptamer Biosensors: Present Status and Way Forward.

Current advances in constructing functional nanomaterials and elegantly designed nanostructures have opened up new possibilities for the fabrication of viable field biosensors. Two-dimensional materials (2DMs) have fascinated much attention due to their chemical, optical, physicochemical, and electronic properties. They are ultrathin nanomaterials with unique properties such as high surface-to-volume ratio, surface charge, shape, high anisotropy, and adjustable chemical functionality. 2DMs such as graphene-based 2D materials, Silicate clays, layered double hydroxides (LDHs), MXenes, transition metal dichalcogenides (TMDs), and transition metal oxides (TMOs) offer intensified physicochemical and biological functionality and have proven to be very promising candidates for biological applications and technologies. 2DMs have a multivalent structure that can easily bind to single-stranded DNA/RNA (aptamers) through covalent, non-covalent, hydrogen bond, and π-stacking interactions, whereas aptamers have a small size, excellent chemical stability, and low immunogenicity with high affinity and specificity. This review discussed the potential of various 2D material-based aptasensor for diagnostic applications, e.g., protein detection, environmental monitoring, pathogens detection, etc.