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An optical biosensor is a specialized analytical device that utilizes the principles of optics and light in bimolecular processes. Localized surface plasmon resonance (LSPR) is a phenomenon in the realm of nanophotonics that occurs when metallic nanoparticles (NPs) or nanostructures interact with incident light. Conversely, surface-enhanced Raman spectroscopy (SERS) is an influential analytical technique based on Raman scattering, wherein it amplifies the Raman signals of molecules when they are situated near specific and specially designed nanostructures. A detailed exploration of the recent ground-breaking developments in optical biosensors employing LSPR and SERS technologies has been thoroughly discussed along with their underlying principles and the working mechanisms. A biosensor chip has been created, featuring a high-density deposition of gold nanoparticles (AuNPs) under varying ligand concentration and reaction duration on the substrate. An ordinary description, along with a visual illustration, has been thoroughly provided for concepts such as a sensogram, refractive index shift, surface plasmon resonance (SPR), and the evanescent field, Rayleigh scattering, Raman scattering, as well as the electromagnetic enhancement and chemical enhancement. LSPR and SERS both have advantages and disadvantages, but widely used SERS has some advantages over LSPR, like chemical specificity, high sensitivity, multiplexing, and versatility in different fields. This review confirms and elucidates the significance of different disease biomarker identification. LSPR and SERS both play a vital role in the detection of various types of cancer, such as cervical cancer, ovarian cancer, endometrial cancer, prostate cancer, colorectal cancer, and brain tumors. This proposed optical biosensor offers potential applications for early diagnosis and monitoring of viral disease, bacterial infectious diseases, fungal diseases, diabetes, and cardiac disease biosensing. LSPR and SERS provide a new direction for environmental monitoring, food safety, refining impurities from water samples, and lead detection. The understanding of these biosensors is still limited and challenging.

The letter talks about opinions in the scientific literature that discuss drug combinations. Specifically, it mentions that these combinations lack analytical methods and are published on the Internet. The development of analytical methods involves systematically creating and improving procedures for techniques such as UV/HPLC or mass spectrometry (MS). This ensures accurate analysis and measurement of chemical compounds in a sample. Improving these methods can optimize production processes, leading to increased efficiency, cost-effectiveness, and environmentally friendly practices. The manuscript presents summarized information gathered from various sources about potential drug combinations lacking online analytical methods. This data highlights the importance of addressing this gap and emphasizes the need for robust analytical methods in exploring and understanding these drug combinations. The letter addressed the significance of advancing analytical methods for drug products and drug analysis holds substantial potential to make a meaningful impact in the medical and biomedical fields.

Permeability-glycoprotein (P-gp) belongs to the ABS transporter protein family, with a high expression rate in cancerous cells. The substrate/inhibitors of the protein are structurally diverse, with no lucid mechanism of inhibition. There are two schools of thought on the inhibition mechanism: (i) P-gp inhibitors bind to the huge hydrophobic cavity between two Trans-Membrane Domains (TMDs), supported by ample literary proof and (ii) P-gp inhibitors bind to the vicinity of Nucleotide-Binding Sites (NBSs). Structural biologists have presented several experimental and theoretical structures of P-gp with bound nucleotides and inhibitors to explain the same. However, the available experimental P-gp structures are insufficient to address the catalytic transition path of mammalian P-gp in detail, thus the dynamics and mechanism by which drugs are effluxed is still unknown. Targeted Molecular Dynamics (targeted MD) could be used to minutely analyse and explore the catalytic transition inward open (IO) to outward open (OO) and relaxation path (OO to IO). Finally, analysis of targeted MD trajectory may help to explore different conformational states of Pg-p (reaction coordinate of catalytic transition/relaxation), efflux of compounds aided by the dynamics of Nucleotide Binding Domains/NBDs (ATP coupled process) and TMDs (peristalsis-like movement pushes the bound molecule). This review presents an understanding of the catalytic transition and dynamics of protein which provides insights at the efflux of chemotherapeutic drug using in cancer treatment.

Acetyl-CoA carboxylase (ACCase: EC 6.4.1.2) is a crucial enzyme for fatty acid synthesis in plants, particularly in the Graminae family, making it an ideal target for herbicides aimed at selective weed control in agriculture. One persistent challenge is the infestation of Phalaris minor in wheat (Triticum aestivum) fields, leading to significant crop yield losses. While herbicides are the primary solution to manage P. minor, their overuse has led to resistant biotypes, driving the need for novel herbicide molecules. Leveraging artificial intelligence (AI) and machine learning (ML) in the agritech revolution, researchers are now applying advanced computational techniques to identify and design effective ACCase inhibitors. Using small molecule databases such as ZINC, CHEMBL, and DrugBank, an initial screening based on structural similarity to known ACCase inhibitors is performed. AI-driven high-throughput virtual screening (HTVS) then filters these candidates followed by physiochemical properties based screening. The selected herbicide-like molecules are further processed through fragment-based design to generate a library of new compounds, refined using binding affinity thresholds (-8.5 kcal/mol) and Quantitative Structure-Activity Relationship (QSAR) models. Finally, molecular dynamics (MD) simulations validated the interaction stability of these potential herbicides over 100 ns, yielding four promising candidates optimized for ACCase inhibition. This study showcases how AI-powered methodologies are transforming agricultural science by facilitating the design of next-generation herbicides that can address resistant weed biotypes, underscoring the role of technology in sustainable crop protection.

Introduction: Anaemia is one of the micronutrient deficiency disorders that have global public health implications. The present study aims to determine the association of minimum dietary diversity (MDD) with anaemia among children aged 6–59 months in rural North India. Methods: In Rohtak (a north Indian city), a cross-sectional survey was conducted in 2018–19 (n = 266). Univariate and bivariate analyses were performed. The Chi-square test was used for assessing the significance level during bivariate analysis. Further, multivariable regression analysis was used for determining the factors for anaemia prevalence among children aged 6–59 months. Results: About 62.4% (n = 166) of the children aged 6–59 months were found to have anaemia in the study area. The prevalence of MDD was 35.3% (n = 94). It was found that children with no MDD have a higher prevalence of moderate (42% vs. 25.5%; P < 0.001) and severe (12.8% vs. 8.5%; P < 0.001) anaemia. It was revealed that the children with no MDD had a significantly higher likelihood of being anaemic than children with MDD in model-1 [aOR: 2.09; CI: 1.23, 3.55] and model-3 [aOR: 1.70; CI: 1.01, 3.01]. Children with mothers who never attended school had significantly higher odds for anaemia in reference to those children whose mothers ever attended school in model-2 [aOR: 3.62; CI: 2.07,6.34] and model-3 [aOR: 3.00; CI: 1.62,5.56]. Conclusion: Measures to alleviate under-five anaemia should include empowering and educating women, expanding access to supplementation, fortification programmes, and promoting and raising awareness about feeding diverse foods, while also considering the socioeconomic status.

Acetyl-CoA carboxylase (ACCase: EC 6.4.1.2) is one of the essential biotins containing enzymes required by plants for fatty acid synthesis and elongation. The unique enzyme is present in its homomeric form in all the Gramineae family, making it a suitable target for developing herbicides selectively against weeds of the Gramineae family. One such example is infestation of Phalaris minor in winter wheat crop fields, where aryloxyphenoxypropionates (FOP); cyclohexanediones (DIM) and phenyl pyrazoline (DEN) group of ACCase inhibiting herbicides are used. However, the increasing number of ACCase herbicide resistant weed populations has compelled agro-scientists to seek varied possibilities for weed control, through Integrated Weed Management (IWM) strategies. Developing new potential herbicides to regain sensitivity in weeds could be an approach to weed control. The current advancement in computational techniques could be of aid in developing new herbicide-like molecules by exploring the genomics, proteomics and structural details of catalytic sites of herbicide action in crops as well as weeds.

Abstract Background Bacterial bioagents, Pseudomonas fluorescens, P. putida, Bacillus amyloliquifaciens, and B. megaterium, have management potential against root-knot nematode (RKN), Meloidogyne incognita, in bottle gourd. Results Field and laboratory experiments were conducted to evaluate the effect of bacterial bioagents Bacillus megaterium 1% WP (2 × 106 CFU/g), B. amyloliquifaciens 1% WP (2 × 108 CFU/g), Pseudomonas putida 1% WP (2 × 108 CFU/g), P. fluorescens 1% WP (2 × 109 CFU/g) on egg hatching and juvenile mortality of root-knot nematode, M. incognita. All the bacterial species inhibited the egg hatching in M. incognita and caused juvenile mortality. The lowest mean egg hatching in 120 h. after treatment was observed in P. putida (20.9% mean egg hatching), followed by P. fluorescens (21.1%), B. amyloliquifaciens (23.7%), and B. megaterium (24.7%) at 4% concentration of the formulated product against (47%) egg hatching in control. The juvenile mortality was found highest (57.1% mean mortality) in P. fluorescens in 120 h. of exposure, followed by P. putida (56.13%), B. megaterium (54.46%), and B. amyloliquifaciens (53.13%) at 4% concentration against 0.46 mean juvenile mortality in control, where distilled water was used. Under field conditions, the bottle gourd seeds that were treated either with B. amyloliquefaciens, B. megaterium, P. fluorescens, or P. putida at 10 g/kg seed along with the application of neem cake (1t/ha) significantly resulted in reduced root gall index and the number of nematode juveniles in soil and roots than the non-treated control. Conclusion This study revealed that the tested bacterial bioagents, namely B. amyloquefaciens, B. megaterium, P. fluorescens, and P. putida, showed the potential for controlling of root knot nematode (RKN) in the laboratory as well as in field conditions in bottle gourd.

Foodborne pathogens are a major public health concern and have a significant economic impact globally. From harvesting to consumption stages, food is generally contaminated by viruses, parasites, and bacteria, which causes foodborne diseases such as hemorrhagic colitis, hemolytic uremic syndrome (HUS), typhoid, acute, gastroenteritis, diarrhea, and thrombotic thrombocytopenic purpura (TTP). Hence, early detection of foodborne pathogenic microbes is essential to ensure a safe food supply and to prevent foodborne diseases. The identification of foodborne pathogens is associated with conventional (e.g., culture-based, biochemical test-based, immunological-based, and nucleic acid-based methods) and advances (e.g., hybridization-based, array-based, spectroscopy-based, and biosensor-based process) techniques. For industrial food applications, detection methods could meet parameters such as accuracy level, efficiency, quickness, specificity, sensitivity, and non-labor intensive. This review provides an overview of conventional and advanced techniques used to detect foodborne pathogens over the years. Therefore, the scientific community, policymakers, and food and agriculture industries can choose an appropriate method for better results.

Uncontrolled growth of Phalaris minor in the wheat (Triticum aestivum) crop has remained a problem, leading to a massive reduction in wheat grain production. Herbicides have been used to control the weed, which leads to the development of frequent resistance in P. minor and mutant biotypes were also reported (Trp2027Cys and Ile2041Asn). Development of resistance enforced agro researchers to analyses the action of herbicide on P. minor. In this study, the sequence and structure of P. minor and T. aestivum Acetyl CoA Carboxylase (ACCase) have been analysed to locate the differences in their sequence and structure and to formulate a plausible explanation of the selectivity of herbicides which may help in the rationale discovery of noble herbicides. The sequence and 3D structure analysis of weed and wheat ACCase indicate minute differences in the distantly located amino acid residues. However, proteins are conserved at the binding site of herbicides with no mutation at the catalytic site. Analysis indicates that herbicides selectively target P. minor ACCase might be due to unknown other reasons, but not due to differences in their protein sequence and structure.

Background. Polyherbal formulations (PLFs) have been widely used for liver protection, treatment for hepatic dysfunction, and regeneration. They can also enhance appetite and protect the gastrointestinal tract from injury. In spite of the prevalent use, there is a need of scientific evidence on their effectiveness and safety. The objective of the present study was to assess the hepatoprotective effect of polyherbal formulations (commercially available in Bangladesh namely Heptaliv, Holyliv, Icturn, and J-deenar) in CCl4-induced hepatotoxicity in mice. Methods. In this study, Swiss albino mice were treated for 7 days with distilled water or PLFs (2.6 and 5.2 ml/kg body weight/day, per os.) followed by single subcutaneous injection of CCl4 (1 ml/kg body weight, diluted with olive oil in 1 : 1 ratio) on day 8. Twenty-four hours after CCl4 administration, the mice were monitored for the effects of PLFs on liver morphology, biochemical parameters including serum aspartate transaminase (AST), serum alanine transaminase (ALT), alkaline phosphatase (ALP), and total bilirubin. Phenobarbitone-induced sleeping time and histopathology changes in liver tissues were also monitored. Results. CCl4 administration caused significant hepatotoxicity as evidenced by marked elevation in AST, ALT, ALP, and total bilirubin. Phenobarbitone-induced sleeping time and infiltration of inflammatory cells and centrizonal necrosis on histological examination of liver demonstrated hepatic injury after CCl4 administration. However, the administration of Icturn and J-deenar polyherbal formulations at the higher dose significantly decreased the levels of AST, ALT, ALP, and total bilirubin. Moreover, pentobarbitone-induced sleeping time and histopathological analysis also revealed significant improvement as result of treatment with formulations Icturn and J-deenar. Conclusion. Our results confirmed that polyherbal formulations (Icturn and J-deenar) can significantly prevent CCl4-induced hepatotoxicity in mice, demonstrating their protective effect for liver.

The proximate, minerals, amino acid and fatty acid composition of wild, pond-, gher- and cage-cultured tilapia in Bangladesh were evaluated and varied significantly (p < 0.05). The major component of the tilapia was moisture (79.12%–81.36%), followed by protein (14.93%–16.03%), lipid (0.59%–2.35%), carbohydrate (1.23%–1.51%), fibre (0.47%–0.88%), ash (0.31%–0.53%); the energy value was between 97.62 and 126.73 kcal/100 g. Macro-nutrients and micro-nutrients were detected in following order: K > Na > Mg > Ca and Fe > Mn, respectively in all the tilapia and the ratio of Na/K was

Assessment of benthic diversity and estuarine ecological quality is becoming increasingly important. Estuaries are not only highly productive and variable environments, but they are also areas of high anthropogenic perturbations. In this study, benthic macrofauna were sorted, identified and analyzed from a freshwater-dominated tropical estuary along the Bay of Bengal to assess their community structure, distribution and functional guilds, and to uncover the environmental drivers influencing their distributional patterns. Results revealed that the studied physio-chemical variables (DO, pH, alkalinity and temperature) were significantly varied (p < 0.05) among the sites. Capitella sp. was dominant (18%) of the forty morphospecies recorded, indicating organic richness of the area. The ANOVA results revealed that macrobenthic density differed significantly (p < 0.01) between the study locations, and diversity indices (Shannon diversity index, H′) also differed significantly (F4,12 = 5.89; p = 0.02). The benthic density decreased from the head to the mouth, which could be related to salinity fluctuations and large freshwater discharges. Upstream sites were completely segregated from downstream and mid-estuarine sites, according to cluster analysis (CA). The SIMPER results clarified the site grouping pattern, showing that Mysis-1 spp., Capitella spp. and Nephtys-1 were the most significant contributors. From the communities, five functional trophic groups were identified where deposit feeders were the most dominant (66.44%). Most of the macrobenthos had strong positive correlations with DO (r = 0.92) and water temperature (r = 0.86) and a negative correlation with soil pH (r = −0.28), per correlation and CCA analyses. Individually, soil pH (r = 0.88) and alkalinity (r = 0.898) showed strong positive correlation with Capitella sp. and Chironomus sp.2. The above results indicate that macrobenthos of this estuary do not follow the usual pattern of spatial distribution, and they are structured by DO, alkalinity and soil pH. In addition, dominance of some pollution indicator species (Capitella sp. and Chironomus sp.) and deposit feeders indicates a poor ecological condition of the estuary.

BackgroundAnthropogenic air pollution has been implicated in aberrant changes of DNA methylation and homocysteine increase (>15μM/L). Folate (MethodsWe examined cross-sectionally, homocysteine, folate, vitamin B12 (chemiluminescence) and global DNA methylation (colorimetric ELISA Assay) among 274 and 270 individuals from low- and high- polluted areas, respectively, from a single Mendelian population. Global DNA methylation results were obtained on 254 and 258 samples from low- and high- polluted areas, respectively.ResultsSignificant decline in median global DNA methylation was seen as a result of air pollution [high-0.84 (0.37-1.97) vs. low-0.96 (0.45-2.75), p = 0.01]. High homocysteine in combination with air pollution significantly reduced global DNA methylation [high-0.71 (0.34-1.90) vs. low-0.93 (0.45-3.00), p = 0.003]. Folate deficient individuals in high polluted areas [high-0.70 (0.37-1.29) vs. low-1.21 (0.45-3.65)] showed significantly reduced global methylation levels (p = 0.007). In low polluted areas, despite folate deficiency, if normal vitamin B12 levels were maintained, global DNA methylation levels improved significantly [2.03 (0.60-5.24), p = 0.007]. Conversely, in high polluted areas despite vitamin B12 deficiency, if normal folate status was maintained, global DNA methylation status improved significantly [0.91 (0.36-1.63)] compared to vitamin B12 normal individuals [0.54 (0.26-1.13), p = 0.04].ConclusionsHigh homocysteine may aggravate the effects of air pollution on DNA methylation. Vitamin B12 in low-polluted and folate in high-polluted areas may be strong determinants for changes in DNA methylation levels. The effect of air pollution on methylation levels may be reduced through inclusion of dietary or supplemented B-vitamins. This may serve as public level approach in natural settings to prevent metabolic adversities at community level.

Background and Objectives: Tumor necrosis factor-alpha (TNF-α)-238G/A and -308G/A single-nucleotide polymorphisms (SNPs) in the promoter region of the gene have been implicated in numerous diseases. The present study aims to investigate the frequency of two TNF-α polymorphisms among Mendelian population of India and to assess their association with various cardiovascular risk variables and outcomes (hypertension [HTN], metabolic syndrome [MetS], and type 2 diabetes mellitus). Materials and Methods: A total of 1142 unrelated individuals aged 35–75 years belonging to Meitei community of Manipur were included in the study. Height, weight, waist and hip circumferences, blood pressures (systolic and diastolic), and lipid profile were measured. Polymerase chain reaction was done using standard protocols. Further, HTN, MetS, diabetic, and healthy individuals were identified, and a nested case–control study design was formulated. Results: The mutant allele frequency was found to be similar (4%) for both the polymorphisms among the Meiteis of Manipur. No mutant homozygote of TNF-α-308G/A polymorphism was observed. No significant risk of the two polymorphisms was found with any of the disease groups in nested case–control analysis. However, TNF-α-308G/A polymorphism, but not TNF-α-238G/A polymorphism, was found to be associated with total cholesterol (TC), triglyceride (TG), and very-low-density lipoprotein (VLDL) in overall population only with TG and VLDL among the HTN cases. Conclusion: The association of TNF-α-308A allele with metabolic risk factors such as TC, TG, and VLDL suggests that though it may not increase the development of any of the diseases considered in the present study, it could possibly enhance the risk of human metabolic disorder. The absence of mutant homozygote among cases is suggestive of lethality of TNF-α-308A allele in double dose coupled with other environmental factors or in the presence of haplotype pairing with TNF-α-238A allele.

Abstract Background Dyslipidemia and hyper-homocysteinemia are the major independent risk factors of cardio vascular disease. Deficiency of folate and vitamin B-12 are associated with both hyper-homocysteinemia and dyslipidemia. The aim of the study is to evaluate the relationship of homocysteine and its associated dietary determinant levels (Folate and Vitamin B-12) with lipids and obesity parameters (WC, BMI, WHR) in North Indian population. Methods The participants were recruited under a major government funded project through household survey covering 15 villages of Haryana, India. Participants were both males and females, between age group 30–65 years, from a north Indian community. Initially 1634 individuals were recruited, of which 1374 were considered for analysis as they were not found to be on any kind of medication for high blood pressure, CAD, diabetes or any other disorder, and had no missing data. 5 mL of intravenous blood sample was collected after obtaining written informed consent from the participants. Homocysteine, folate and vitamin B12 levels were estimated through Immulite 1000 by chemi-luminescence technique. Triglyceride, total cholesterol and HDL-C were estimated by spectrophotometry technique using commercial kits. The values for LDL and VLDL were calculated using Friedwald’s equation. Height, weight, waist circumference (WC), hip circumference (HC) was measured over light clothing. Statistical analysis for data was performed using SPSS 16.0 version. Results All the lipid indices, except HDL, showed a trend of negative correlation with homocysteine after controlling for confounders, though not significant. No association was found between obesity (WC, BMI, WHR) and homocysteine in the present study. Vitamin B-12 deficiency was significantly associated with both hyper-homocysteinemia and low HDL. Folate was found to have significantly reduced risk for high TC & LDL. Conclusions The “hcy-lipid” hypothesis does not seem to be complementing in the present studied population. The population is vulnerable to severe under-nutrition due to the association of vitamin B-12 with HDL, leading to metabolic disturbance in both the pathways; lipid and one carbon metabolic pathway. Co-factors such as ethnicity, cultural practices, and lifestyle & dietary habits must be considered while making public health policies to control diseases.

Valproic acid (VPA) is a well-established anticonvulsant drug discovered serendipitously and marketed for the treatment of epilepsy, migraine, bipolar disorder and neuropathic pain. Apart from this, VPA has potential therapeutic applications in other central nervous system (CNS) disorders and in various cancer types. Since the discovery of its anticonvulsant activity, substantial efforts have been made to develop structural analogues and derivatives in an attempt to increase potency and decrease adverse side effects, the most significant being teratogenicity and hepatotoxicity. Most of these compounds have shown reduced toxicity with improved potency. The simple structure of VPA offers a great advantage to its modification. This review briefly discusses the pharmacology and molecular targets of VPA. The article then elaborates on the structural modifications in VPA including amide-derivatives, acid and cyclic analogues, urea derivatives and pro-drugs, and compares their pharmacological profile with that of the parent molecule. The current challenges for the clinical use of these derivatives are also discussed. The review is expected to provide necessary knowledgebase for the further development of VPA-derived compounds.

We present here the detection of a possible quasi-periodic oscillation (QPO) signal in the X-ray light curve of the active galactic nucleus 3C 120, a broad line radio galaxy at z = 0.033. The hint of a QPO at the 3σ level at 7.1 × 10−6 Hz (∼1.65 days) was detected based on the analysis of X-ray data acquired in the 3–79 keV band by the Nuclear Spectroscopic Telescope Array (NuSTAR). The data, when processed separately in the soft (3–10 keV), hard (10–79 keV) and the total (3–79 keV) bands using four different techniques, namely discrete correlation function, Lomb Scargle periodogram, structure–function, and power spectral density indicated the presence of a QPO. 3C 120 very well fits in the negative correlation in the frequency of the QPO versus the black hole mass (FQPO versus MBH) diagram known for stellar-mass and supermassive black hole sources. Considering the observed signs of QPO to represent the innermost stable orbit of the accretion disk, we found a black hole mass of 1.9×109 M⊙ for a Kerr black hole and 3.04×108 M⊙ for a Schwarzschild black hole. This deduced black hole mass from QPO measurement is a few times larger than the black hole mass obtained from reverberation mapping observations.

Polyvinyl alcohol (PVA)/polyethylene glycol (PEG) blend nanocomposite films reinforced with various loadings of carbon black nanoparticles (CBNPs) were synthesized via a solution casting approach. The structural properties of PVA/PEG/CBNPs nanocomposites were investigated using Fourier-transform infrared (FTIR) spectroscopy, indicating the strong interaction of CBNPs with the polymer blend. The thermogravimetric analysis (TGA) and differential scanning calorimetry (DSC) results respectively confirmed the enhanced thermal stability and the variation in the melting temperature with the addition of CBNPs in polymer blend . The dielectric measurements of nanocomposite films were carried out over a frequency range from 50 Hz–20 MHz at a varied temperature range from 40 °C–150 °C using impedance analyzer . The maximum dielectric constant for neat PVA was observed to be about 21.4 at 50 Hz and 150 °C. For PVA/PEG/CBNPs nanocomposites having higher loading of CBNPs (25 wt%) the maximum value of dielectric constant was found to be ε = 375.1 at 50 Hz, 150 °C. The dielectric properties increased with the addition of CBNPs which validates a significant control on percolation threshold attributing to the well-dispersed CBNPs in the polymer blend. The electromagnetic interference (EMI) shielding effectiveness (SE) was improved from 0.1 dB to 10.6 dB with the addition of CBNPs in the PVA/PEG blend. The improved EMI SE and dielectric performance of these nanocomposites suggest CBNPs as excellent nanofillers for the development of flexible, lightweight and low-cost material for electronic applications.

This study investigated the potential of MET kinase inhibitors, cabozantinib, crizotinib, and PHA665752, in reversing multidrug resistance (MDR) mediated by ABCB1 in cancer cells. The accumulation of the fluorescent probe, Rhodamine 123, was assessed using flow cytometry and fluorescence microscopy in MDR MES-SA/DX5 and parental cells. The growth inhibitory activity of MET inhibitors as monotherapies and in combination with chemotherapeutic drugs was evaluated by MTT assay. CalcuSyn software was used to analyze the combination index (CI) as an index of drug-drug interaction in combination treatments. Results showed that at concentrations of 5, and 25 μM, c-MET inhibitors significantly increased Rhodamine 123 accumulation in MDR cells, with ratios up to 17.8 compared to control cells, while exhibiting no effect in parental cells. Additionally, the combination of c-MET inhibitors with the chemotherapeutic agent doxorubicin synergistically enhanced cytotoxicity in MDR cells, as evidenced by combination index (CI) values of 0.54 ± 0.08, 0.69 ± 0.1, and 0.85 ± 0.07 for cabozantinib, crizotinib, and PHA665752, respectively. While all three c-MET inhibitors stimulated ABCB1 ATPase activity in different manners at certain concentrations, PHA-665752 suppressed it at high concentration. In silico analysis also suggested that the transmembrane domains (TMD) of ABCB1 transporters could be considered potential target for these agents. Our results suggest that c-MET inhibitors can serve as promising MDR reversal agents in ABCB1-medicated drug-resistant cancer cells. [ABSTRACT FROM AUTHOR]

The study examined Xenentodon cancila (Hamilton) breeding biology, reproduction, and larval rearing. In this study, gonadosomatic index (GSI) and fecundity were measured for breeding biology every 15 days. Nine doses of common carp pituitary gland (CPG), human chorionic gonadotropin (HCG), and Ovaprim for breeding were administered, except in the control treatment that was without hormones. Mustard oil cake (D1), powdered feed (D2), and one-day-old live tilapia (Oreochromis sp.) larvae (D3) were used to determine larval survival after 28 days. From the end of May to mid-July, the mean GSI value exceeded 15 ± 0.72%, peaking at 16.02 ± 1.28% in June. Mean fecundity ranged from 110 ± 13.34 to 2961 ± 318.57, peaking at the end of June 2019, which indicated that this was the peak breeding season for X. cancila. The best spawning was with CPG at 20 mg kg−1 fish body weight (BW) and Ovaprim at 1.0 ml kg−1 BW, but the control group (B) and the group administered 500 IU kg-1 HCG (H1) did not spawn. Latency and hatching periods were 19-21 and 260-288 h, respectively. The highest fertilization, hatching, and survival rates were 92 ± 4.63%, 69 ± 5.52%, and 66 ± 4.11% with 20 mg kg−1 CPG (C2), while the next closest value was recorded with 1.0 ml kg−1 Ovaprim (O2). After 28 days, D3 had the highest survival rate (47.5 ± 4.62%), followed by D2 (31 ± 2.42%), and D1 (18 ± 1.54%). The findings will be useful for hatcheries, fish farmers, the ornamental fish sector, and biodiversity protection. [ABSTRACT FROM AUTHOR]