Epidemiology and phylogeny of Haemonchus contortus through internal transcribed spacer 2 gene in small ruminants.

Introduction: Haemonchus contortus (H. contortus) is a blood-feeding nematode causing infectious disease haemonchosis in small ruminants of tropical and subtropical regions around the world. This study aimed to explore the prevalence and phylogeny of H. contortus in small ruminants using the internal transcribed spacer-2 (ITS-2) gene. In addition, a comprehensive review of the available literature on the status of H. contortus in Pakistan was conducted. Methods: Fecal samples were collected from sheep and goats (n = 180). Microscopically positive samples were subjected to DNA extraction followed by PCR using species-specific primers. Results: The overall prevalence of H. contortus was 25.55% in small ruminants. The prevalence of H. contortus was significantly associated with months and area. The highest occurrence of haemonchosis was documented in July (38.70%), whereas the lowest occurred in December (11.11%), with significant difference. The prevalence was highest in the Ghamkol camp (29.4%) and lowest in the arid zone of the Small Ruminant Research Institute (17.5%) (p = 0.01). The results of the systematic review revealed the highest prevalence of haemonchosis (34.4%) in Khyber Pakhtunkhwa (p = 0.001). Discussion: Phylogenetic analysis revealed a close relationship between H. contortus and isolates from Asia (China, India, Iran, Bangladesh, Malaysia, and Mongolia) and European countries (Italy and the United Kingdom). It has been concluded that H. contortus is prevalent in small ruminants of Kohat district and all over Pakistan, which could be a potential threat to food-producing animals, farmers, dairy, and the meat industry. Phylogenetic analysis indicates that H. contortus isolates share close phylogenetic relationships with species from Asia and Europe.

Dietary nano-Selenium supplementation improves growth performance, nutrient digestibility and hematology in Cirrhinus mrigala fingerlings.

The following investigation was carried out to determine the effects of Selenium nanoparticles (Se NPs) on the growth rates, nutrient digestibility, and hematology of Cirrhinus mrigala fingerlings fed sunflower meal as basal diet. The experiment included seven test diets with varying Se levels (0, 0.5, 1, 1.5, 2, 2.5, and 3 mg/kg) based on Se NPs supplementation. Chromic oxide, an inert maker, was also added. Fingerlings were fed at a rate of 5% of their body weight. The test meal of 1 mg/kg Se NPs resulted in the highest weight gain (12.31 g) and the lowest feed conversion ratio (1.58). Best hematological indices (RBCs 2.84 106 mm-3, WBCs 7.79 103 mm-3, PLT 66, Hb 8.5 g/100 ml, PCV 25% and MCV 190 fl) and maximum nutrient absorption (crude protein 72%, ether extract 73% and gross energy 67%) were also observed in the case of 1 mg/kg supplementation of Se NPs. Hematology studies indicated that when fish were fed 0.5 mg/kg Se NPs, their levels began to rise. Maximum results were achieved with feed containing 1 mg/kg of Se NPs, but when the concentration increased above 1 mg/kg, the values began to decline. Instead, nutrient digestibility began to increase when the concentration of Se NPs increased to 1 mg/kg and abruptly started to decline with a further increase in Se NPs. The results demonstrated that a sunflower meal-based diet supplemented with Se NPs (1 mg/kg) increased the growth performance, nutritional digestibility, and hematology of C. mrigala fingerlings.

Ethnobotanical assessment of antidiabetic medicinal plants in District Karak, Pakistan.

BACKGROUND: Diabetes is a leading health disorder and is responsible for high mortality rates across the globe. Multiple treatment protocols are being applied to overcome this morbidity and mortality including plant-based traditional medicines. This study was designed to investigate the ethnomedicinal status of plant species used to treat diabetes in District Karak, Pakistan. MATERIALS AND METHODS: A semi-structured survey was created to collect data about traditionally used medicinal plants for diabetes and other ailments. The convenience sampling method was applied for the selection of informants. The collected data was evaluated through quantitative tools like frequency of citation (FC), relative frequency of citation (RFC), informant consensus factor (FIC), fidelity level (FL), and use value (UV). RESULTS: A total of 346 local informants were selected for this research. Out of them, 135 participants were men and 211 participants were women. Overall 38 plant species belonging to 29 plant families were used to treat diabetes. The most dominant plant family was Oleaceae having 11 species. Powder form (19%) was the most recommended mode of preparation for plant-based ethnomedicines. Leaves (68%) were the most frequently used parts followed by fruit (47%). The highest RFC was recorded for Apteranthes tuberculata (0.147). The maximum FL was reported for Apteranthes tuberculata (94.4) and Zygophyllum indicum (94.11) for diabetes, skin, and wounds. Similarly, the highest UV of (1) each was found for Brassica rapa, Melia azedarach, and Calotropis procera. Based on documented data, the reported ailments were grouped into 7 categories. The ICF values range between 0.89 (diabetes) to 0.33 (Cardiovascular disorders). CONCLUSION: The study includes a variety of antidiabetic medicinal plants, which are used by the locals in various herbal preparations. The species Apteranthes tuberculata has been reported to be the most frequently used medicinal plant against diabetes. Therefore, it is recommended that such plants be further investigated in-vitro and in-vivo to determine their anti-diabetic effects.

Hydrazyl hydroxycoumarins as new potential conquerors towards Pseudomonas aeruginosa.

A class of unique hydrazyl hydroxycoumarins (HHs) as novel structural scaffold was developed to combat dreadful bacterial infections. Some HHs could effectively suppress bacterial growth at low concentrations, especially, pyridyl HH 7 exhibited a good inhibition against Pseudomonas aeruginosa 27853 with a low MIC value of 0.5 µg/mL, which was 8-fold more active than norfloxacin. Furthermore, pyridyl HH 7 with low hemolytic activity and low cytotoxicity towards NCM460 cells showed much lower trend to induce the drug-resistant development than norfloxacin. Preliminarily mechanism exploration indicated that pyridyl HH 7 could eradicate the integrity of bacterial membrane, result in the leakage of intracellular proteins, and interact with bacterial DNA gyrase via non-covalent binding, and ADME analysis manifested that compound 7 gave good pharmacokinetic properties. These results suggested that the newly developed hydrazyl hydroxycoumarins as potential multitargeting antibacterial agents should be worthy of further investigation for combating bacterial infection.

Toxicological assessment of dietary exposure of polyethylene microplastics on growth, nutrient digestibility, carcass and gut histology of Nile Tilapia (Oreochromis niloticus) fingerlings.

This study was conducted to ascertain the negative effects of dietary low-density polyethylene microplastics (LDPE-MPs) exposure on growth, nutrient digestibility, body composition and gut histology of Nile tilapia (Oreochromis niloticus). Six sunflower meal-based diets (protein 30.95%; fat 8.04%) were prepared; one was the control (0%) and five were incorporated with LDPE-MPs at levels of 2, 4, 6, 8 and 10% in sunflower meal-based diets. A total of eighteen experimental tanks, each with 15 fingerlings, were used in triplicates. Fish were fed at the rate of 5% biomass twice a day for 60 days. Results revealed that best values of growth, nutrient digestibility, body composition and gut histology were observed by control diet, while 10% exposure to LDPE-MPs significantly (P < 0.05) reduced weight gain (WG%, 85.04%), specific growth rate (SGR%, 0.68%), and increased FCR (3.92%). The findings showed that higher level of LDPE-MPs (10%) exposure in the diet of O. niloticus negatively affects nutrient digestibility. Furthermore, the results revealed that the higher concentration of LDPE-MPs (10%) had a detrimental impact on crude protein (11.92%) and crude fat (8.04%). A high number of histological lesions were seen in gut of fingerlings exposed to LDPE-MPs. Hence, LDPE-MPs potentially harm the aquatic health.

Correction: Biogenic synthesis of silver nanoparticles using Rubus fruticosus extract and their antibacterial efficacy against Erwinia caratovora and Ralstonia solanacearum phytopathogens.

[This corrects the article DOI: 10.1039/D3RA06723H.].

Novel aminothiazoximone-corbelled ethoxycarbonylpyrimidones with antibiofilm activity to conquer Gram-negative bacteria through potential multitargeting effects.

The emergence of drug-resistant microorganisms threatens human health, and it is usually exacerbated by the formation of biofilm, which forces the development of new antibacterial agents with antibiofilm activity. In this work, a novel category of aminothiazoximone-corbelled ethoxycarbonylpyrimidones (ACEs) was designed and synthesized, and some of the prepared ACEs showed potent bioactivity against the tested bacteria. In particular, imidazolyl ACE 6c showed better inhibitory activity towards Acinetobacter baumannii and Escherichia coli with MIC values both of 0.0066 mmol/L than norfloxacin. It was also revealed that imidazolyl ACE 6c not only possessed inconspicuous hemolytic rate and cytotoxicity, low drug resistance and no risk of penetrating the blood-brain barrier, but also exhibited obvious biofilm inhibition and eradication activities. The preliminary mechanism research suggested that imidazolyl ACE 6c could induce metabolic dysfunction by deactivating lactate dehydrogenase and promote the accumulation of reactive oxygen species to decrease the reduced glutathione and ultimately cause oxidative damage in bacteria. Furthermore, ACE 6c was also found that could insert into DNA to form the supramolecular complex of 6c-DNA and trigger cell death. The multidimensional effect might promote bacterial cell rupture, leading to the leakage of intracellular content. These findings manifested that novel imidazolyl ACE 6c as a potential multitargeting antibacterial agent with potent antibiofilm activity could provide new possibility for the treatment of refractory biofilm-intensified bacterial infections.

Biogenic synthesis of silver nanoparticles using Rubus fruticosus extract and their antibacterial efficacy against Erwinia caratovora and Ralstonia solanacearum phytopathogens.

In the current research, we produced green, cost-effective, eco-friendly silver nanoparticles using a single-step approach. Plants are considered highly desirable systems for nanoparticle synthesis because they possess a variety of secondary metabolites with significant reduction potential. In the current research, the dried leaf extract of Rubus fruticosus was utilized as a capping and reducing agent for the fabrication of silver nanoparticles, to prepare reliable biogenic silver nanoparticles and subsequently to investigate their potential against some common phytopathogens. The prepared silver nanoparticles were exploited to quantify the total flavonoid content (TFC), total phenolic content (TPC) and DPPH-based antioxidant activity. Different concentrations of aqueous extracts of plant leaves and silver nitrate (AgNO3) were reacted, and the color change of the reactant mixture confirmed the formation of Rubus fruticosus leaf-mediated silver nanoparticles (RFL-AgNPs). A series of characterization techniques such as UV-vis spectroscopy, transmission electron microscopy, energy dispersive X-ray analysis and X-ray diffraction revealed the successful synthesis of silver nanoparticles. The surface plasmon resonance peak appeared at 449 nm. XRD analysis demonstrated the crystalline nature, EDX confirmed the purity, and TEM demonstrated that the nanoparticles are mostly spherical in form. Furthermore, the biosynthesized nanoparticles were screened for in vitro antibacterial activity, antioxidant activity, and total phenolic and flavonoid content. The nanoparticles were used in different concentrations alone and in combination with plant extracts to inhibit Erwinia caratovora and Ralstonia solanacearum. In high-throughput assays used to inhibit these plant pathogens, the nanoparticles were highly toxic against bacterial pathogens. This study can be exploited for planta assays against phytopathogens utilizing the same formulations for nanoparticle synthesis and to develop potent antibacterial agents to combat plant diseases.

Potent bioactive metabolites from Olea ferruginea.

Seven known (1-7) and one new compound (8) were isolated and identified from the stem of Olea ferruginea. The species has been recognised as a new source for six of the known metabolites (1, 3, 4, 5, 6, and 7). Based on detailed spectroscopic analyses, these compounds were identified as scopoletin (1), 8-ketosetosterol (2), (+)-cycloolivil (3), (+)-africanal (4), isovanilic acid (5), hydroxytyrosol acetate (6), vanillic acid (7), and cycloolivil A (8). The crude extracts and purified compounds were analysed for their Leishmanicidal, anti-glycation, anti-cancer, and anti-inflammatory activities. n-Hexane fraction was found to be the most active (among all the fractions), against Leishmania parasites, exhibiting 97.85% inhibition at 15 µg/mL. However, none of the extracts showed any significant anti-glycation or anti-cancer potential, all the fractions, except the aqueous layer, displayed moderate to low anti-inflammatory activity. Compound 1 was found to have strong anti-inflammatory activity, exhibiting 96.7% stimulation at 25 µg/mL.

Melatonin-Induced Stress Enhanced Biomass and Production of High-Value Secondary Cell Products in Submerged Adventitious Root Cultures of Stevia rebaudiana (Bert.).

Stress is one of the important factors that directly or indirectly affects the plant architecture, biochemical pathways, and growth and development. Melatonin (MEL) is an important stress hormone; however, the exogenous addition of melatonin to culture media stimulates the defense mechanism and releases higher quantities of secondary metabolites. In this study, submerged adventitious root cultures (SARCs) of diabetically important Stevia rebaudiana were exposed to variable concentrations (0.5-5.0 mg/L) of MEL in combination with 0.5 mg/L naphthalene acetic acid (NAA) to investigate the biomass accumulation during growth kinetics with 07 days intervals for a period of 56 days. The effects of exogenous MEL on the biosynthesis of stevioside (Stev.), total phenolics content (TPC), total flavonoids content (TFC), total phenolics production (TPP), total flavonoids production (TFP), total polyphenolics content (TPPC), fresh and dry weight (FW & DW), and antioxidant potential were also studied. Most of the SARCs displayed lag, exponential, stationary, and decline phases with variable biomass accumulation. The maximum fresh (236.54 g/L) and dry biomass (28.64 g/L) was observed in SARCs exposed to 3.0 mg/L MEL and 0.5 mg/L NAA. The same combination of MEL and NAA also enhanced the accumulation of TPC (18.96 mg/g-DW), TFC (6.33 mg/g-DW), TPP (271.51 mg/L), TFP (90.64 mg/L), and TPPC (25.29 mg/g-DW). Similarly, the highest stevioside biosynthesis (91.45 mg/g-DW) and antioxidant potential (86.15%) were observed in SARCs exposed to 3.0 mg/L MEL and NAA. Moreover, a strong correlation was observed between the biomass and the contents of phenolics, flavonoids, antioxidants, and stevioside. These results suggest that MEL is one of multidimensional stress hormones that modulate the biosynthetic pathways to release higher quantities of metabolites of interest for various industrial applications.

Sr-induced Fermi Engineering of ß-FeOOH for Multifunctional Catalysis.

Designing a multifunctional electrocatalyst to produce H2 from water, urea, urine, and wastewater, is highly desirable yet challenging because it demands precise Fermi-engineering to realize stronger π-donation from O 2p to electron(e- )-deficient metal (t2g ) d-orbitals. Here a Sr-induced phase transformed ß-FeOOH/α-Ni(OH)2 catalyst anchored on Ni-foam (designated as pt-NFS) is introduced, where Sr produces plenteous Fe4+ (Fe3+ → Fe4+ ) to modulate Fermi level and e- -transfer from e- -rich Ni3+ (t2g )-orbitals to e- -deficient Fe4+ (t2g )-orbitals, via strong π-donation from the π-symmetry lone-pair of O bridge. pt-NFS utilizes Fe-sites near the Sr-atom to break the H─O─H bonds and weakens the adsorption of *O while strengthening that of *OOH, toward hydrogen evolution reaction (HER) and oxygen evolution reaction (OER), respectively. Invaluably, Fe-sites of pt-NFS activate H2 -production from urea oxidation reaction (UOR) through a one-stage pathway which, unlike conventional two-stage pathways with two NH3 -molecules, involves only one NH3 -molecule. Owing to more suitable kinetic energetics, pt-NFS requires 133 mV (negative potential shift), 193 mV, ≈1.352 V, and ≈1.375 V versus RHE for HER, OER, UOR, and human urine oxidation, respectively, to reach the benchmark 10 mA cm-2 and also demonstrates remarkable durability of over 25 h. This work opens a new corridor to design multifunctional electrocatalysts with precise Fermi engineering through d-band modulation.

Effect of once-a-day milk feeding on behavior and growth performance of pre-weaning calves.

OBJECTIVE: The objectives of the present study were to evaluate the effects of once-a-day milk feeding on growth performance and routine behavior of preweaning dairy calves. METHODS: At 22nd day of age, twenty-four Holstein calves were randomly assigned to one of two treatment groups (n = 12/treatment) based on milk feeding frequency (MF): i) 3 L of milk feeding two times a day; ii) 6 L of milk feeding once a day. The milk feeding amount was reduced to half for all calves between 56 and 60 days of age and weaning was done at 60 days of age. To determine the increase in weight and structural measurements, each calf was weighed and measured at 3 weeks of age and then at weaning. The daily behavioral activity of each calf was assessed from the 22nd day of age till weaning (60th day of age) through Nederlandsche Apparatenfabriek (NEDAP) software providing real-time data through a logger fitted on the calf's foot. RESULTS: There was no interaction (p≥0.17) between MF and sex of the calves for routine behavioral parameters, body weight and structural measurements. Similarly, there was no effect of MF on routine behavioral parameters, body weight and structural measurements. However, the sex of the calves affected body weight gain in calves. Male calves had 27% greater total body weight and average daily gain than female calves. There was no effect of the sex of the calves on behavioral measurements. Collectively, in the current study, no negative effects of a once-a-day milk feeding regimen were found on routine behavioral and growth parameters of preweaning calves in group housing. CONCLUSION: Once-a-day milk feeding can be safely adopted in preweaning calves from 22nd day of age.

Electron-Sponge Nature of Polyoxometalates for Next-Generation Electrocatalytic Water Splitting and Nonvolatile Neuromorphic Devices.

Designing next-generation molecular devices typically necessitates plentiful oxygen-bearing sites to facilitate multiple-electron transfers. However, the theoretical limits of existing materials for energy conversion and information storage devices make it inevitable to hunt for new competitors. Polyoxometalates (POMs), a unique class of metal-oxide clusters, have been investigated exponentially due to their structural diversity and tunable redox properties. POMs behave as electron-sponges owing to their intrinsic ability of reversible uptake-release of multiple electrons. In this review, numerous POM-frameworks together with desired features of a contender material and inherited properties of POMs are systematically discussed to demonstrate how and why the electron-sponge-like nature of POMs is beneficial to design next-generation water oxidation/reduction electrocatalysts, and neuromorphic nonvolatile resistance-switching random-access memory devices. The aim is to converge the attention of scientists who are working separately on electrocatalysts and memory devices, on a point that, although the application types are different, they all hunt for a material that could exhibit electron-sponge-like feature to realize boosted performances and thus, encouraging the scientists of two completely different fields to explore POMs as imperious contenders to design next-generation nanodevices. Finally, challenges and promising prospects in this research field are also highlighted.

Evolution of the Management of Brain Metastases: A Bibliometric Analysis.

A systematic review of the published literature was conducted to analyze the management evolution of brain metastases from different cancers. Using the keywords "brain metastasis", "brain metastases", "CNS metastasis", "CNS metastases", "phase III" AND/OR "Randomized Controlled Trial" (RCT), relevant articles were searched for on the SCOPUS database. A total of 1986 articles were retrieved, published over a 45-year period (1977-2022). Relevant articles were defined as clinical studies describing the treatment or prevention of brain metastases from any cancer. Articles on imaging, quality of life, cognitive impairment after treatment, or primary brain tumors were excluded. After a secondary analysis, reviewing the abstracts and/or full texts, 724 articles were found to be relevant. Publications significantly increased in the last 10 years. A total of 252 articles (34.8%) were published in 12 core journals, receiving 50% of the citations. The number of publications in Frontiers in Oncology, BMC Cancer, and Radiotherapy and Oncology have increased considerably over the last few years. There were 111 randomized controlled trials, 128 review articles, and 63 meta-analyses. Most randomized trials reported on brain metastases management from unselected tumors (49), lung cancer (47), or breast cancer (11). In the last 5 years (2017 to 2022), management of brain metastasis has moved on from WBRT, the use of chemotherapy, and radio-sensitization to three directions. First, Radiosurgery or Radiotherapy (SRS/SRT), or hippocampal-sparing WBRT is employed to reduce radiation toxicity. Second, it has moved to the use of novel agents, such as tyrosine kinase inhibitors (TKI) and immune checkpoint inhibitors (ICI) and third, to the use of molecularly directed therapy such as TKIs, in asymptomatic low volume metastasis, obviating the need for WBRT.

Heat Stress Mitigation: Impact of Increased Cooling Sessions on Milk Yield and Welfare of Dairy Buffaloes in a Semiarid Summer.

The current study aimed to evaluate the impact of increasing cooling sessions from three to five times a day on milk yield and the welfare of dairy buffaloes during a semiarid summer in Pakistan. Eighteen Nili Ravi buffaloes were randomly assigned to three cooling strategies: (1) CTL, where buffaloes were cooled with a handheld hosepipe twice daily for 5 min each; (2) 3CS, where buffaloes were cooled using sprinklers three times daily; and (3) 5CS, where buffaloes were cooled using sprinklers five times daily. Each sprinkler cooling session lasted 1 h, with a 6 min cycle of 3 min of water on and 3 min off. Results showed that the 5CS group produced 1.6 and 3.2 kg more milk per day compared to the 3CS and CTL groups, respectively (p < 0.001). Both the 5CS and 3CS groups had consistently lower core body temperatures and respiration rates than the CTL group. Buffaloes in the 5CS group spent significantly more time eating (p < 0.001). Additionally, the 5CS group exhibited lower cortisol and blood urea nitrogen levels (p = 0.001) and higher glucose levels than the CTL group (p = 0.006). In conclusion, increasing cooling sessions to five times daily improved milk yield and welfare compared to the traditional cooling strategy (CTL) in dairy buffaloes during semiarid summers, highlighting the benefits of optimized cooling practices.

Genome wide identification, structural characterization and phylogenetic analysis of High-Affinity potassium (HAK) ion transporters in common bean (Phaseolus vulgaris L.).

BACKGROUND: High-Affinity Potassium ions represent one of the most important and large group of potassium transporters. Although HAK genes have been studied in a variety of plant species, yet, remain unexplored in common bean. RESULTS: In the current study, 20 HAK genes were identified in common bean genome. Super-family "K_trans" domain was found in all PvHAK genes. Signals for localization of PvHAK proteins were detected in cell membrane. Fifty three HAKs genes, across diverse plant species, were divided into 5 groups based on sequential homology. Twelve pairs of orthologs genes were found in various plant species. PvHAKs genes were distributed unequally on 7 chromosomes with maximum number (7) mapped on chromosome 2 while only 1 PvHAK found on each chromosome 1, 4, and 6. Tandem gene duplication was witnessed in 2 paralog pairs while 1 pair exhibited segmental gene duplication. Five groups were made in PvHAK gene family based on Phylogeny. Maximum PvHAKs (10) were detected in Group-V while group-II composed of only 1 PvHAK gene. Variation was witnessed in number and size of motifs, and structure of PvHAKs associated with different groups. Light and hormone responsive elements contributed 57 and 24% share, respectively, to cis regulatory elements. qRT-PCR based results revealed significant increase in expression of all 4 PvHAK genes under low-potassium stress. CONCLUSION: The current study provides valuable information for further functional characterization and uncovering the molecular mechanism associated with Potassium transportation in plants.

Antimicrobial efficacy of Mentha piperata-derived biogenic zinc oxide nanoparticles against UTI-resistant pathogens.

Misuse of antibiotics leads to the worldwide spread of antibiotic resistance, which motivates scientists to create new antibiotics. The recurring UTI due to antibiotics-resistant microorganism's challenges scientists globally. The biogenic nanoparticles have the potential to meet the escalating requirements of novel antimicrobial agents. The green synthesis of nanoparticles (NPs) gained more attention due to their reliable applications against resistant microbes. The current study evaluates the biogenic ZnO NPs of Mentha piperata extract against resistant pathogens of urinary tract infections by agar well diffusion assay. The biogenic ZnO NPs revealed comparatively maximum inhibition in comparison to synthetic antibiotics against two bacterial strains (Proteus mirabilis, Pseudomonas aeruginosa) and a fungal strain (Candida albicans).The synthesized biogenic ZnO NPs alone revealed maximum activities than the combination of plant extract (PE) and ZnO NPs, and PE alone. The physiochemical features of ZnO NPs characterized through UV-Vis spectroscopy, FTIR, XRD, SEM, and EDX. The UV-Vis spectroscopy revealed 281.85 nm wavelengths; the XRD pattern revealed the crystalline structure of ZnO NPs. The FTIR analysis revealed the presence of carboxylic and nitro groups, which could be attributed to plant extract. SEM analysis revealed spherical hollow symmetry due to electrostatic forces. The analysis via EDX confirmed the presence of Zn and oxygen in the sample. The physiochemical features of synthesized ZnO NPs provide pivotal information such as quality and effectiveness. The current study revealed excellent dose-dependent antimicrobial activity against the pathogenic isolates from UTI-resistant patients. The higher concentration of ZnONPs interacts with the cell membrane which triggers oxidative burst. They may bind with the enzymes and proteins and brings epigenetic alteration which leads to membrane disruption or cell death.

Effects of Saccharomyces cerevisiae live cells and culture on growth and productive performance in lactating Nili-Ravi buffaloes.

An experimental work was conducted to evaluate the effects of Saccharomyces cerevisiae live cells and its culture on dry matter intake (DMI), milk yield, milk composition, body condition score, selected blood metabolites, feed conversion efficiency (FCE), nutrient digestibility, body weight gain, and economics of milk production in lactating multiparous Nili-Ravi buffaloes. In total, 20 buffaloes of age 5 years ± 6 months and weighing 550 ± 20 kg were selected and assigned to four dietary treatments (n=5 buffalo/treatment) under completely randomized design. The dietary treatments include treatment 1 (T1) control, treatment 2 (T2) 5g/head live yeast, treatment 3 (T3) 5g/head yeast culture, and treatment 4 (T4) 10 g/head yeast culture per day for 60 days excluding 14 days as an adjustment period. The results indicated that T4 showed significant (p<0.05) improvement in DMI, milk yield and components, blood glucose level, digestibility of nutrients, and body weight gain while significant decrease in blood urea nitrogen as compared to other treatment groups. Body condition score was not affected among treatments. In conclusion, yeast culture supplementation significantly improved (p <0.05) milk yield, milk composition, DMI, body weight gain, blood glucose level, and digestibility while significantly decreased blood urea level as compare to control. Economic return was also improved. BCS was not improved. Comparatively, yeast culture showed significant improvement in growth and productive performance as compare to live yeast. Meanwhile, 10-g yeast culture showed better results as compare to 5-g yeast culture.

Involvement of the Opioidergic Mechanism in the Analgesic Potential of a Novel Indazolone Derivative: Efficacy in the Management of Pain, Neuropathy, and Inflammation Using In Vivo and In Silico Approaches.

Indazolones possess interesting pharmacological activities. The search for indazole and indazolone-containing nuclei as drugs is an important research area of medicinal chemistry. The current work aims to evaluate a novel indazolone derivative against in vivo and in silico targets of pain, neuropathy, and inflammation. An indazolone derivative (ID) was synthesized and characterized using advanced spectroscopic techniques. Well-established animal models of abdominal constriction, hot plate, tail immersion, carrageenan paw edema, and Brewer's yeast-induced pyrexia were employed for evaluating the potential of the ID at different doses (20-60 mg kg-1). Nonselective GABA antagonists, opioid antagonist naloxone (NLX) and pentylenetetrazole (PTZ), were employed to assess the potential role of GABAergic and opioidergic processes. The antineuropathic potential of the drug was evaluated using a vincristine-induced neuropathic pain model. In silico studies were performed to assess any possible interactions of the ID with pain target sites like cyclooxygenases (COX-I/II), GABAA, and opioid receptors. This study revealed that the selected ID (doses of 20-60 mg kg-1) efficiently hampered chemically and thermally induced nociceptive responses, producing significant anti-inflammatory and antipyretic effects. These effects produced by the ID were dose-dependent (i.e., 20-60 mg kg-1 and p range of 0.001-0.01) and significant in comparison to standards (p < 0.001). Antagonistic studies with NLX (1.0 mg kg-1) and PTZ (15.0 mg kg-1) revealed the involvement of the opioidergic mechanism rather than the GABAergic mechanism. The ID showed promising anti-static allodynia effects as well. In silico studies revealed preferential binding interactions of the ID with cyclooxygenases (COX-I/II), GABAA, and opioid receptors. According to the results of the current investigation, the ID may serve in the future as a therapeutic agent for the treatment of pyrexia, chemotherapy-induced neuropathic pain, and nociceptive inflammatory pain.

Resveratrol Enhances Temozolomide Efficacy in Glioblastoma Cells through Downregulated MGMT and Negative Regulators-Related STAT3 Inactivation.

Chemoresistance blunts the efficacy of temozolomide (TMZ) in the treatment of glioblastoma (GBM). Elevated levels of O6-methylguanine-DNA methyltransferase (MGMT) and activation of signal transducer and of transcription 3 (STAT3) have been reported to correlate with GBM resistance to alkylator chemotherapy. Resveratrol (Res) inhibits tumor growth and improves drug chemosensitivity by targeting STAT3 signaling. Whether the combined therapy of TMZ and Res could enhance chemosensitivity against GBM cells and the underlying molecular mechanism remains to be determined. In this study, Res was found to effectively improve chemosensitivities of different GBM cells to TMZ, which was evaluated by CCK-8, flow cytometry, and cell migration assay. The combined use of Res and TMZ downregulated STAT3 activity and STAT3-regulated gene products, thus inhibited cell proliferation and migration, as well as induced apoptosis, accompanied by increased levels of its negative regulators: PIAS3, SHP1, SHP2, and SOCS3. More importantly, a combination therapy of Res and TMZ reversed TMZ resistance of LN428 cells, which could be related to decreased MGMT and STAT3 levels. Furthermore, the JAK2-specific inhibitor AG490 was used to demonstrate that a reduced MGMT level was mediated by STAT3 inactivation. Taken together, Res inhibited STAT3 signaling through modulation of PIAS3, SHP1, SHP2, and SOCS3, thereby attenuating tumor growth and increasing sensitivity to TMZ. Therefore, Res is an ideal candidate to be used in TMZ combined chemotherapy for GBM.