Oocyte quality is enhanced by hypoglycosylated FSH through increased cell-to-cell interaction during mouse follicle development.

Macroheterogeneity in follicle-stimulating hormone (FSH) ß-subunit N-glycosylation results in distinct FSH glycoforms. Hypoglycosylated FSH21 is the abundant and more bioactive form in pituitaries of females under 35 years of age, whereas fully glycosylated FSH24 is less bioactive and increases with age. To investigate whether the shift in FSH glycoform abundance contributes to the age-dependent decline in oocyte quality, the direct effects of FSH glycoforms on folliculogenesis and oocyte quality were determined using an encapsulated in vitro mouse follicle growth system. Long-term culture (10-12 days) with FSH21 (10 ng/ml) enhanced follicle growth, estradiol secretion and oocyte quality compared with FSH24 (10 ng/ml) treatment. FSH21 enhanced establishment of transzonal projections, gap junctions and cell-to-cell communication within 24 h in culture. Transient inhibition of FSH21-mediated bidirectional communication abrogated the positive effects of FSH21 on follicle growth, estradiol secretion and oocyte quality. Our data indicate that FSH21 promotes folliculogenesis and oocyte quality in vitro by increasing cell-to-cell communication early in folliculogenesis, and that the shift in in vivo abundance from FSH21 to FSH24 with reproductive aging may contribute to the age-dependent decline in oocyte quality.

Effects of follicle-stimulating hormone on energy balance and tissue metabolic health after loss of ovarian function.

Loss of ovarian function imparts increased susceptibility to obesity and metabolic disease. These effects are largely attributed to decreased estradiol (E2), but the role of increased follicle-stimulating hormone (FSH) in modulating energy balance has not been fully investigated. Previous work that blocked FSH binding to its receptor in mice suggested this hormone may play a part in modulating body weight and energy expenditure after ovariectomy (OVX). We used an alternate approach to isolate the individual and combined contributions of FSH and E2 in mediating energy imbalance and changes in tissue-level metabolic health. Female Wistar rats were ovariectomized and given the gonadotropin releasing hormone (GnRH) antagonist degarelix to suppress FSH production. E2 and FSH were then added back individually and in combination for a period of 3 wk. Energy balance, body mass composition, and transcriptomic profiles of individual tissues were obtained. In contrast to previous studies, suppression and replacement of FSH in our paradigm had no effect on body weight, body composition, food intake, or energy expenditure. We did, however, observe organ-specific effects of FSH that produced unique transcriptomic signatures of FSH in retroperitoneal white adipose tissue. These included reductions in biological processes related to lipogenesis and carbohydrate transport. In addition, rats administered FSH had reduced liver triglyceride concentration (P < 0.001), which correlated with FSH-induced changes at the transcriptomic level. Although not appearing to modulate energy balance after loss of ovarian function in rats, FSH may still impart tissue-specific effects in the liver and white adipose tissue that might affect the metabolic health of those organs.NEW & NOTEWORTHY We find no effect of follicle-stimulating hormone (FSH) on energy balance using a novel model in which rats are ovariectomized, subjected to gonadotropin-releasing hormone antagonism, and systematically given back FSH by osmotic pump. However, tissue-specific effects of FSH on adipose tissue and liver were observed in this study. These include unique transcriptomic signatures induced by the hormone and a stark reduction in hepatic triglyceride accumulation.

The effects of short-term and long-term phthalate exposures on ovarian follicle growth dynamics and hormone levels in female mice†.

Di(2-ethylhexyl) phthalate and diisononyl phthalate are widely used as plasticizers in polyvinyl chloride products. Short-term exposures to phthalates affect hormone levels, ovarian follicle populations, and ovarian gene expression. However, limited data exist regarding the effects of long-term exposure to phthalates on reproductive functions. Thus, this study tested the hypothesis that short-term and long-term exposure to di(2-ethylhexyl) phthalate or diisononyl phthalate disrupts follicle dynamics, ovarian and pituitary gene expression, and hormone levels in female mice. Adult CD-1 female mice were exposed to vehicle, di(2-ethylhexyl) phthalate, or diisononyl phthalate (0.15 ppm, 1.5 ppm, or 1500 ppm) via the chow for 1 or 6 months. Short-term exposure to di(2-ethylhexyl) phthalate (0.15 ppm) and diisononyl phthalate (1.5 ppm) decreased serum follicle-stimulating hormone levels compared to control. Long-term exposure to di(2-ethylhexyl) phthalate and diisononyl phthalate (1500 ppm) increased the percentage of primordial follicles and decreased the percentages of preantral and antral follicles compared to control. Both phthalates increased follicle-stimulating hormone levels (di(2-ethylhexyl) phthalate at 1500 ppm; diisononyl phthalate at 1.5 ppm) and decreased luteinizing hormone levels (di(2-ethylhexyl) phthalate at 0.15 and 1.5 ppm; diisononyl phthalate at 1.5 ppm and 1500 ppm) compared to control. Furthermore, both phthalates altered the expression of pituitary gonadotropin subunit genes (Cga, Fshb, and Lhb) and a transcription factor (Nr5a1) that regulates gonadotropin synthesis. These data indicate that long-term exposure to di(2-ethylhexyl) phthalate and diisononyl phthalate alters follicle growth dynamics in the ovary and the expression of gonadotropin subunit genes in the pituitary and consequently luteinizing hormone and follicle-stimulating hormone synthesis.

Probiotic potential of a novel endophytic Streptomyces griseorubens CIBA-NS1 isolated from Salicornia sp. against Vibrio campbellii infection in shrimp.

A novel endophytic Streptomyces griseorubens CIBA-NS1 was isolated from a salt marsh plant Salicornia sp. The antagonistic effect of S. griseorubens against Vibrio campbellii, was studied both in vitro and in vivo. The strain was validated for its endophytic nature and characterized through scanning electron microscopy, morphological and biochemical studies and 16SrDNA sequencing. The salinity tolerance experiment has shown that highest antibacterial activity was at 40‰ (16 ± 1.4 mm) and lowest was at 10 ‰ salinity (6.94 ± 0.51 mm). In vivo exclusion of Vibrio by S. griseorubens CIBA-NS1 was studied in Penaeus indicus post larvae and evaluated for its ability to improve growth and survival of P. indicus. After 20 days administration of S. griseorubens CIBA-NS1, shrimps were challenged with V. campbellii. The S. griseorubens CIBA-NS1 reduced Vibrio population in test group when compared to control, improved survival (60.5 ± 6.4%) and growth, as indicated by weight gain (1.8 ± 0.05g). In control group survival and growth were 48.4 ± 3.5% and 1.4 ± 0.03 g respectively. On challenge with V. campbellii, the S. griseorubens CIBA-NS1 administered group showed better survival (85.6 ± 10%) than positive control (64.3 ± 10%). The results suggested that S. griseorubens CIBA-NS1 is antagonistic to V. campbellii, reduce Vibrio population in the culture system and improve growth and survival. This is the first report on antagonistic activity of S. griseorubens isolated from salt marsh plant Salicornia sp, as a probiotic candidate to prevent V. campbellii infection in shrimps.

Photoredox Catalysis by 21-Thiaporphyrins: A Green and Efficient Approach for C-N Borylation and C-H Arylation.

Photoredox catalysis provides a green and sustainable alternative for C-H activation of organic molecules that eludes harsh conditions and use of transition metals. The photocatalytic C-N borylation and C-H arylation mostly depend on the ruthenium and iridium complexes or eosin Y and the use of porphyrin catalysts is still in infancy. A series of novel 21-thiaporphyrins (A2B2 and A3B type) were synthesized having carbazole/phenothiazine moieties at their meso-positions and screened as catalysts for C-N borylation and C-H arylation. This paper demonstrates the 21-thiaporphyrin catalyzed C-N borylation and het-arylation of anilines under visible light. The method utilizes only 0.1 mol % of 21-thiaporphyrin catalyst under blue light for the direct C-N borylation and het-arylation reactions. A variety of substituted anilines were used as source for expensive and unstable aryl diazonium salts in the reactions. The heterobiaryls and aryl boronic esters were obtained in decent yields (up to 88 %). Versatility of the 21-thiaporphyrin catalyst was tested by thiolation and selenylation of anilines under similar conditions. Mechanistic insight was obtained from DFT studies, suggesting that 21-thiaporphyrin undergo an oxidative quenching pathway. The photoredox process catalyzed by 21-thiaporphyrins offers a mild, efficient and metal-free alternative for the formation of C-C, C-S, and C-Se bonds in aryl compounds; it can also be extended to borylation reaction.

Lithium-grafted Si-doped γ-graphyne as a reversible hydrogen storage host material.

In recent years, hydrogen (H2) has become the most sought-after sustainable energy carrier by virtue of its high energy content and carbon-free emission. The practical implementation of hydrogen as an alternative fuel calls for an efficient and secure storage medium. Within this framework, we have investigated Li-grafted Si-doped γ-graphyne for H2 storage applications by implementing the cutting-edge density functional theory (DFT). A dynamically and thermally stable Si-doped γ-graphyne (SiG) monolayer is functionalized with Li metal atoms that augmented the hydrogen binding strength of the nanolayer by almost three times, owing to the polarization effect of the Li atoms. The Li metal atoms get adsorbed over the monolayer, allowing a binding energy of -2.73 eV that is greater than the Li cohesive energy (-1.63 eV), which eliminates the metal-metal clustering probability. The reliability of the Li-functionalized SiG monolayer (Li8SiG) at elevated temperature has been further substantiated by performing and analyzing ab initio molecular dynamics (AIMD) simulations at 400 K. It is noteworthy that a total of four H2 molecules are held up by each Li atom with an average adsorption energy of -0.32 eV and a maximum gravimetric capacity of 8.48 wt%, which remarkably follows the US-DOE parameters. Partial density of states and Hirshfeld charge analysis are utilized to recognize the interaction channel which reveals the Kubas and Niu-Rao-Jena-like bonding among the metal atoms and loaded hydrogen molecules. The hydrogen occupancy calculated at different temperatures and pressures indicates that hydrogen molecules can be reversibly stored over the Li8SiG system, and it is noted that adsorbed H2 begins to desorb at 280 K, with complete desorption at 400 K and 20 atm (or lower). AIMD simulations are further performed to authenticate the H2 desorption at various temperatures, which agrees well with the occupation number analysis. All the outcomes advocate for efficient reversible hydrogen storage over the proposed host material.

Quantum rotational dynamics of l-C4(3Σ-g) by H2 at low temperatures employing a machine learning augmented potential energy surface.

A new four dimensional (4D) ab initio potential energy surface (PES) is generated for the collision of C4(3Σg-) with H2(1Σg), considering both molecules as rigid rotors. A supervised neural network model is created to augment the ab initio PES and to get the missing data points. Furthermore, space fixed expansion of the augmented PES is carried out using a least squares fit over two spherical harmonics terms, resulting in radial coefficients (λ1, λ2, and λ). The centre of symmetry in both C4 and H2 forces λ1 and λ2 to have even values, respectively. Moreover, the rotational states of C4 are only populated by odd levels due to its ground state triplet symmetry and the nuclear spin (I = 0) of 12C. The cross-sections and rate coefficients with para and ortho H2 partners are studied for various odd state transitions, where the rate coefficients of the ortho are 10-20% higher than those of the latter. The de-excitation rates obtained by the para H2 collisions are also compared to those of He and are found to be ∼1.7-2.8 times the He rates, across various order transitions. The simple scaling of He rates using a factor of 1.38 proves insufficient to describe para H2 rates. Therefore, these results show the importance of explicitly studying H2 as an important colliding partner, governing the kinetics of various rotational processes in the interstellar space.

Community pharmacists as antimicrobial resistance stewards: a narrative review on their contributions and challenges in low- and middle-income countries.

Antimicrobial resistance (AMR) is a global public health crisis that impedes the therapeutic effectiveness of available antimicrobial agents. Due to the high burden of infectious diseases and limited resources, especially trained healthcare professionals, low- and middle-income countries (LMICs) are particularly susceptible to the detrimental effects of AMR. Sometimes, as the first and last point of contact for patients seeking treatment for infections, community pharmacists can play a pivotal role in the stewardship required for AMR. This review aims to highlight the contributions made by community pharmacists in LMICs as AMR stewards. The review considers the challenges from the perspectives of limited resources, inadequate training, a lack of policies and regulations, and issues related to patient behavior. Community pharmacists in LMICs could optimize their advocacy contributions by focusing on One Health AMR stewardship. Transformational and actionable patient and population-centric antimicrobial stewardship (AMS) is feasible with the synergy of policymakers and other healthcare providers in the implementation of AMS policies and programs that support community pharmacists in their efforts to promote rational antimicrobial use.

Nickel-ion substituted hydroxyapatite matrices for metal-affinity chromatographic purification of recombinant proteins.

Hydroxyapatite (HAp) is a calcium phosphate ceramic, widely used as a matrix for protein chromatography. The crystal structure of HAp is amenable to a wide range of substitutions, thus allowing for the alteration of its properties. In this study, nickel-ion substituted HAp (NiSHAp) was synthesized using a wet-precipitation method, followed by spray drying. This resulted in the structural incorporation of nickel ions within well-defined microspheres, which were suitable for chromatographic applications. The chromatographic experiments were conducted with NiSHAp and compared with spray-dried hydroxyapatite (SHAp) matrices. Protein purification experiments were conducted using refolded recombinant L-asparaginase (L-Asp), which was produced as inclusion bodies in Escherichia coli. The results showed that NiSHAp effectively adsorbed L-Asp, which was selectively eluted using a phosphate buffer, surpassing the efficiency of imidazole-based elution. In contrast, SHAp showed weaker binding and lower selectivity. The significance of this study lies in developing a scalable NiSHAp matrix for protein purification, especially for large-scale applications. The NiSHAp matrix offers a cost-effective alternative to commercial immobilized metal affinity chromatography (IMAC) adsorbents, especially for purifying His-tagged proteins. This innovative approach exhibits the advantages of mixed-mode chromatography by combining the properties of hydroxyapatite and IMAC in a single matrix, with the potential of improved industrial-scale protein purification.

Design and Evaluation of Peer Supervision for Community Mental Health Workers: A Task-Shifting Strategy in Low-Resource Settings.

The use of Lay Mental Health Workers (LMHWs) to tackle the treatment gap in low-resource settings is well established, and although they often receive training, the potential of proper supervision to improve outcomes remains untapped. Indeed, given the strain on expert resources, peer-supervision models based on supervisors' seniority of work experience have significant potential especially in relation to community knowledge and embedding of LMHWs. This study summarizes the evaluation of a pilot program for peer supervision on the basis of Social Cognitive Theories of Self-Efficacy for LMHWs in Kerala, India. Two experienced LMHWs worked as supervisors for a total of 12 LMHWs over the course of a year. These participants were subsequently interviewed to analyze their experiences in order to evaluate the potential of peer supervision and distil relevant information to improve future training of LMHWs. The findings include improved performance and emotional support for the participants.

An integrated buoy-satellite based coastal water quality nowcasting system: India's pioneering efforts towards addressing UN ocean decade challenges.

The Indian coastal waters are stressed due to a multitude of factors, such as the discharge of industrial effluents, urbanization (municipal sewage), agricultural runoff, and river discharge. The coastal waters along the eastern and western seaboard of India exhibit contrasting characteristics in terms of seasonality, the magnitude of river influx, circulation pattern, and degree of anthropogenic activity. Therefore, understanding these processes and forecasting their occurrence is highly necessary to secure the health of coastal waters, habitats, marine resources, and the safety of tourists. This article introduces an integrated buoy-satellite based Water Quality Nowcasting System (WQNS) to address the unique challenges of water quality monitoring in Indian coastal waters and to boost the regional blue economy. The Indian National Centre for Ocean Information Services (INCOIS) has launched a first-of-its-kind WQNS, and positioned the buoys at two important locations along the east (Visakhapatnam) and west (Kochi) coast of India, covering a range of environmental conditions and tourist-intensive zones. These buoys are equipped with different physical-biogeochemical sensors, data telemetry systems, and integration with satellite-based observations for real-time data transmission to land. The sensors onboard these buoys continuously measure 22 water quality parameters, including surface current (speed and direction), salinity, temperature, pH, dissolved oxygen, phycocyanin, phycoerythrin, Coloured Dissolved Organic Matter, chlorophyll-a, turbidity, dissolved methane, hydrocarbon (crude and refined), scattering, pCO2 (water and air), and inorganic macronutrients (nitrite, nitrate, ammonium, phosphate, silicate). This real-time data is transmitted to a central processing facility at INCOIS, and after necessary quality control, the data is disseminated through the INCOIS website. Preliminary results from the WQNS show promising outcomes, including the short-term changes in the water column oxic and hypoxic regimes within a day in coastal waters off Kochi during the monsoon period, whereas effluxing of high levels of CO2 into the atmosphere associated with the mixing of water, driven by local depression in the coastal waters off Visakhapatnam. The system has demonstrated its ability to detect changes in the water column properties due to episodic events and mesoscale processes. Additionally, it offers valuable data for research, management, and policy development related to coastal water quality.

Co-expression of galectin-3 and vimentin in triple negative breast cancer cells promotes tumor progression, metastasis and survival.

BACKGROUND: Lack of druggable targets and complex expression heterogeneity of known targets is common among TNBC subtypes. An enhanced expression of galectin-3 in TNBCs has already been documented. We have observed a tumor progression-dependent galectin-3 expression in TNBCs compared to adjacent epithelium and non TNBCs. OBJECTIVE: To unravel the association of galectin- 3 in tumor progression, aggressiveness and drug resistance in TNBC patients. METHODS: Galectin-3 expression in 489 breast cancer tissues was correlated with clinicopathological features and the results were validated in cell lines and mouse model by silencing galectin-3 using shRNA and the proteins were profiled by western blot and qRT-PCR. Protein interaction was analyzed by GFP Trap and Mass spectrometry. RESULTS: Galectin-3 expression correlated with tumor stage in TNBC and a lower galectin-3 expression was associated with poor patient survival. The positive correlation between galectin-3, vimentin and CD44 expression, pinpoints galectin-3 contribution to epithelial to mesenchymal transition, drug resistance and stemness. Vimentin was found as an interacting partner of galectin-3. Duplexing of galecin-3 and vimentin in patient samples revealed the presence of tumor cells co-expressing both galectin-3 and vimentin. In vitro studies also showed its role in tumor cell survival and metastatic potential, elementary for tumor progression. In vivo studies further confirmed its metastatic potential. CONCLUSIONS: Tumor progression dependent expression pattern of galectin 3 was found to indicate prognosis. Co-expression of galectin-3 and vimentin in tumor cells promotes tumor dissemination, survival and its metastatic capability in TNBCs.

Sulfonyl Diazaborine 'Click' Chemistry Enables Rapid and Efficient Bioorthogonal Labeling.

Finding an ideal bioorthogonal reaction that responds to a wide range of biological queries and applications is of great interest in biomedical applications. Rapid diazaborine (DAB) formation in water by the reactions of ortho-carbonyl phenylboronic acid with α-nucleophiles is an attractive conjugation module. Nevertheless, these conjugation reactions demand to satisfy stringent criteria for bioorthogonal applications. Here we show that widely used sulfonyl hydrazide (SHz) offers a stable DAB conjugate by combining with ortho-carbonyl phenylboronic acid at physiological pH, competent for an optimal biorthogonal reaction. Remarkably, the reaction conversion is quantitative and rapid (k2 >103  M-1 s-1 ) at low micromolar concentrations, and it preserves comparable efficacy in a complex biological milieu. DFT calculations support that SHz facilitates DAB formation via the most stable hydrazone intermediate and the lowest energy transition state compared to other biocompatible α-nucleophiles. This conjugation is extremely efficient on living cell surfaces, enabling compelling pretargeted imaging and peptide delivery. We anticipate this work will permit addressing a wide range of cell biology queries and drug discovery platforms exploiting commercially available sulfonyl hydrazide fluorophores and derivatives.

New potential energy surface and rotational deexcitation cross-sections of CNNC by para-H2 (jp = 0).

The objective of this study is to enhance our understanding of the existence of molecules in interstellar space by determining the collisional rate coefficients with the most prevalent species. The study examines the impact of para-H2 collisions, specifically when it is in its ground vibrational state with a nuclear spin of para-H2, i.e., jp = 0, on causing the rotational deexcitation of the diisocyanogen (CNNC) molecule. These scattering data are obtained as a result of spherically averaging a four-dimensional potential energy surface (4DPES) over the H2 orientations. Using the CCSD(T)-F12a approach and aug-cc-pVTZ basis sets, the ab initio 4DPES for the CNNC-H2 van der Waals system is calculated. The CNNC-para-H2 4DPES attains a global minimum of 221.38 cm-1 at the CNNC and H2 center of mass distance (R) of 3.1 Å. The method of close coupling calculations is employed for the purpose of calculating the cross-sectional data of CNNC with para-H2 (jp = 0), for total energies up to 1000 cm-1. Rate coefficients are computed over the temperature range of 1 K to 100 K. Propensity suggests that even Δj transitions are strongly preferred. The rate coefficients for CNNC-H2 are determined to be 0.90-2.95 times those of CNNC-He, which implies it is not reliable to estimate the H2 rate coefficients by multiplying the rate coefficients for CNNC-He collision with a scaling factor of 1.38.

Boron-pnictogen monolayers with a negative Poisson's ratio and excellent band edge positions for photocatalytic water splitting.

Boron-pnictogen (BX; X = N, P, As, Sb) materials, in most cases, share structural characteristics with the aesthetically pleasing architectures of carbon allotropes. Recently, a two-dimensional (2D) metallic carbon allotrope (biphenylene) has been synthesized using experimental methods. In the present study, we have examined the structural stabilities, mechanical properties, and electronic fingerprints of biphenylene analogs of boron-pnictogen (bp-BX) monolayers using state-of-the-art electronic structure theory. We have validated the dynamical stability using phonon band dispersion analysis and thermal stabilities using ab initio molecular dynamics studies. The bp-BX monolayers exhibit a positive (bp-BN) and negative (bp-BP, bp-BAs, bp-BSb) Poisson's ratio with anisotropic mechanical properties in the 2D plane. Electronic structure studies unveil that the bp-BX monolayers show semiconducting properties with an energy gap of 4.50, 1.30, 2.28 and 1.24 eV for X = N, P, As and Sb, respectively. Computed band edge positions, lighter charge carriers and optimally separated hole and electron regions indicate that the bp-BX monolayers can serve as potential candidates for the metal-free water dissociation reaction using photocatalysis.

Blocking FSH induces thermogenic adipose tissue and reduces body fat.

Menopause is associated with bone loss and enhanced visceral adiposity. A polyclonal antibody that targets the ß-subunit of the pituitary hormone follicle-stimulating hormone (Fsh) increases bone mass in mice. Here, we report that this antibody sharply reduces adipose tissue in wild-type mice, phenocopying genetic haploinsufficiency for the Fsh receptor gene Fshr. The antibody also causes profound beiging, increases cellular mitochondrial density, activates brown adipose tissue and enhances thermogenesis. These actions result from the specific binding of the antibody to the ß-subunit of Fsh to block its action. Our studies uncover opportunities for simultaneously treating obesity and osteoporosis.

Bio-waste mediated synthesis of zirconium nanoparticle fuel: Energy management strategy for performance evaluation in a diesel engine.

The impact of biosynthesized zirconium nanoparticles originated from biological waste, blended in diesel fuel processed through bio-refining strategy and its combustion, emissions, and overall diesel engine performance towards safety has been examined. Different weight fractions of zirconia nanoparticles were combined with crude diesel at 10, 20, and 30 mg/L values. According to the engine tests, Zirconia (20 nm) added to pure diesel at a concentration of 30 parts per million incremented thermal efficiencies by 4.9% compared to regular diesel fuel. The average reduction in specific fuel consumption for clean diesel fuel when the engine was operating at full power was 2.9%, 3.9%, and 4.9%. Diesel smoke, hydrocarbon, CO, and NOx emissions were reduced by 13%, 20%, 25%, and 29%, respectively, when nano additives were used at a concentration of 30 ppm.Nanoparticles enhance fuel stability, overcome detonation difficulties, and avoid fouling spark plugs. The pressure within cylinder, the temperature, and the rate at which heat is released was improved when alumina nanoparticles were appended to diesel fuel. However, both the length of the combustion and further delay in ignition were cut down. The ideal concentration of zirconia nanoparticles for improving combustion, efficiency, and emissions along with safety attainment in an internal combustion engine is recorded at 30 ppm.

Cobalt ferrite/semiconducting single-walled carbon nanotubes based field-effect transistor for determination of carbamate pesticides.

Carbaryl and carbofuran are the carbamate pesticides which have been widely used worldwide to control insects in crops and house. If the pesticides entered in to the food products and drinking water, they could cause serious health effects in humans. Therefore, the development of a rapid, simple, sensitive and selective analytical device for on-site detection of carbamates is crucial to evaluate food and environmental samples. Recently, semiconducting single-walled carbon nanotube-based field effect transistors (s-SWCNT/FETs) have shown several advantages such as high carrier mobility, good on/off ratio, quasi ballistic electron transport, label-free detection and real-time response. Herein, cobalt ferrite (CFO) nanoparticles decorated s-SWCNTs have been prepared and used to bridge the source and drain electrodes. As-prepared CFO/s-SWCNT/FET had been used for the non-enzymatic detection of carbaryl and carbofuran. When used as a sensing platform, the CFO/s-SWCNT hybrid film exhibited high sensitivity, and selectivity with a wide linear range of detection from 10 to 100 fMand the lowest limit of detections for carbaryl (0.11 fM) and carbofuran (0.07 fM) were estimated. This sensor was also used to detect carbaryl in tomato and cabbage samples, which confirmed its practical acceptance. Such performance may be attributed to the oxidation of carbamates by potent catalytic activity of CFO, which led to the changes in the charge transfer reaction on the s-SWCNTs/FET conduction channel. This work presents a novel CFO/s-SWCNT based sensing system which could be used to quantify pesticide residues in food samples.

Peptide-based direct electrochemical detection of receptor binding domains of SARS-CoV-2 spike protein in pristine samples.

RNA isolation and amplification-free user-friendly detection of SARS-CoV-2 is the need of hour especially at resource limited settings. Herein, we devised the peptides of human angiotensin converting enzyme-2 (hACE-2) as bioreceptor at electrode interface for selective targeting of receptor binding domains (RBD) of SARS-CoV-2 spike protein (SP). Disposable carbon-screen printed electrode modified with methylene blue (MB) electroadsorbed graphene oxide (GO) has been constructed as cost-efficient and scalable platform for hACE-2 peptide-based SARS-CoV-2 detection. In silico molecular docking of customized 25 mer peptides with RBD of SARS-CoV-2 SP were validated by AutoDock CrankPep. N-terminal region of ACE-2 showed higher binding affinity of - 20.6 kcal/mol with 15 H-bond, 9 of which were < 3 Å. Electrochemical biosensing of different concentrations of SPs were determined by cyclic voltammetry (CV) and chronoamperometry (CA), enabling a limit of detection (LOD) of 0.58 pg/mL and 0.71 pg/mL, respectively. MB-GO devised hACE-2 peptide platform exert an enhanced current sensitivity of 0.0105 mA/pg mL-1 cm-2 (R2 = 0.9792) (CV) and 0.45 nA/pg mL-1 (R2 = 0.9570) (CA) against SP in the range of 1 pg/mL to 1 µg/mL. For clinical feasibility, nasopharyngeal and oropharyngeal swab specimens in viral transport medium were directly tested with the prepared peptide biosensor and validated with RT-PCR, promising for point-of-need analysis.

Molecular docking and simulation studies of some pyrazolone-based bioactive ligands targeting the NF-κB signaling pathways.

NF-κB has become a predominant regulator responsible for multiple physiological and pathological processes. NF-κB signaling pathway has canonical and non-canonical components which strategize the cancer-related metabolic processes. Non-canonical NF-κB pathways are known to contribute towards the chemoresistance of cancer cells. Consequently, NF-κB can be utilized as a potential therapeutic target for modifying the behaviour of tumor cells. In view of this, we herein report a series of pyrazolone-based bioactive ligands that potentially target NF- κB and, thereby, unveil their anticancer properties. The pharmacological screening of the synthesized compounds were carried out using various virtual screening techniques. The anticancer studies of synthesized pyrazolones showed that APAU exhibited the most potent effect against the MCF-7 cells with an IC50 value of 30 µg/ml. Molecular docking studies revealed that the pyrazolones inhibited cell proliferation by targeting the NFκB signaling pathway. The molecular dynamics simulation studies predicted the stability and flexibility of pyrazolone-based bioactive ligands.