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The current study explored the differential interaction between ethylene (ET) and abscisic acid (ABA) in relation to salt stress in mustard ( Brassica juncea L.) plants. Significant reductions in seed germination, growth, and photosynthesis were observed with 100 mmol NaCl. Among the cultivars tested, the Pusa Vijay cultivar was noted as ET-sensitive. Pusa Vijay responded maximally to an application of 2.0 mmol ethephon (Eth; 2-chloethyl phosphonic acid-ethylene source), and exhibited the greatest growth, photosynthesis, activity of 1-aminocyclopropane carboxylic acid (ACC) synthase (ACS), and ET evolution. Notably, Eth (2.0 mmol) more significantly improved the seed germination percentage, germination and vigor index, amylase activity, and reduced H 2 O 2 content under salt stress, while ABA (25 µmol) had negative effects. Moreover, the individual application of Eth and ABA on Pusa Vijay under both optimal and salt-stressed conditions increased the growth and photosynthetic attributes, nitrogen (N) and sulfur (S) assimilation, and antioxidant defense machinery. The addition of aminoethoxyvinylglycine (0.01 µmol AVG, ET biosynthesis inhibitor) to ABA + NaCl-treated plants further added to the effects of ABA on parameters related to seed germination and resulted in less effectiveness of growth and photosynthesis. In contrast, the effects of Eth were seen with the addition of fluoridone (25 µmol Flu, ABA biosynthesis inhibitor) to Eth + NaCl. Thus, it can be suggested that ET is crucial for alleviating salt-induced inhibition in seed germination, growth, and photosynthesis, while ABA collaborated with ET to offer protection by regulating nutrient assimilation and enhancing antioxidant metabolism. These findings provide insight into the complex regulatory processes involved in ET-ABA interaction, enhancing our understanding of plant growth and development and the mitigation of salt stress in mustard. It opens pathways for developing hormonal-based strategies to improve crop productivity and resilience, ultimately benefiting agricultural practices amidst a challenging environment.

A significant threat to the ongoing rise in temperature caused by global warming. Plants have many stress-resistance mechanisms, which is responsible for maintaining plant homeostasis. Abiotic stresses largely increase gaseous molecules' synthesis in plants. The study of gaseous signaling molecules has gained attention in recent years. The role of gaseous molecules, such as nitric oxide (NO), hydrogen sulfide (H 2 S), carbon dioxide (CO 2 ), carbon monoxide (CO), methane (CH 4 ), and ethylene, in plants under temperature high-temperature stress are discussed in the current review. Recent studies revealed the critical function that gaseous molecules play in controlling plant growth and development and their ability to respond to various abiotic stresses. Here, we provide a thorough overview of current advancements that prevent heat stress-related plant damage via gaseous molecules. We also explored and discussed the interaction of gaseous molecules. In addition, we provided an overview of the role played by gaseous molecules in high-temperature stress responses, along with a discussion of the knowledge gaps and how this may affect the development of high-temperature-resistant plant species.

Background: The Trauma Quality Improvement Program (American College of Surgery (ACS-TQIP)) uses the existing infrastructure of the Committee on Trauma programs and provides feedback to participating hospitals on risk-adjusted outcomes. This study aimed to analyze and compare the performance of the Level I Hamad Trauma Centre (HTC) with other TQIP participating centers by comparing TQIP aggregate database reports. The primary goal was to pinpoint the variations in adult trauma outcomes and quality measures, identify areas that need improvement, and leverage existing resources to facilitate quality improvement., Methods: A retrospective analysis was performed for the TQIP data from April 2019-March 2020 to April 2020-March 2021. We used the TQIP methodology, inclusion and exclusion criteria, and outcomes., Results: There were 915 patients from Fall 2020 and 884 patients from Fall 2021 that qualified for the TQIP database. The HTC patients' demographics differed from the TQIP's aggregate data; they were younger, more predominantly male, and had significantly different mechanisms of injury (MOI) with more traffic-related blunt trauma. Penetrating injuries were more severe in the other centers. During the TQIP Fall 2020 report, the HTC was a low outlier (good performer) in one cohort (all patients) and an average performer in the remaining cohorts. However, during Fall 2021, the HTC showed an improvement and was a low outlier in two cohorts (all patients and severe TBI patients). Overall, the HTC remained an average performer during the report cycles., Conclusions: There was an improvement over time in the risk-adjusted mortality, which reflects the continuous and demanding effort put together by the trauma team. The ACS-TQIP for the external benchmarking of quality improvement could be a contributor to better monitored patient care. Evaluating the TQIP data with emphases on appropriate methodologies, quality measurements, corrective measures, and accurate reporting is warranted.

Despite the availability of human papillomavirus (HPV) vaccines and screening facilities at various health centers in Saudi Arabia, the annual death rate due to cervical cancer is high. Therefore, knowledge and awareness are essential for self-care and educating others, particularly among healthcare students. The present descriptive, cross-sectional study explored female pharmacy students' knowledge, attitudes, and practices related to cervical cancer. A total of 140 students participated in the survey. The survey was conducted for the period between April 2022 to September 2023. We observed a good knowledge score and positive attitudes among 8.5% and 93.5% of participants, respectively. A total of 10% of the study participants reported good practice scores. Most participants had never been screened for cervical cancer (94.3%). Among the non-screened subjects, feeling healthy and lacking information were the participants' significant reasons for not screening for cervical cancer. A positive history of cancer related to smoking significantly impacted the knowledge score ( p = 0.050). The current study reveals that healthcare awareness programs for cervical cancer and HPV vaccination are necessary at the level of educational institutions to improve public health.

Melatonin is a pleiotropic, nontoxic, regulatory biomolecule with various functions in abiotic stress tolerance. It reverses the adverse effect of heat stress on photosynthesis in plants and helps with sulfur (S) assimilation. Our research objective aimed to find the influence of melatonin, along with excess sulfur (2 mM SO 4 2- ), in reversing heat stress's impacts on the photosynthetic ability of the mustard ( Brassica juncea L.) cultivar SS2, a cultivar with low ATP-sulfurylase activity and a low sulfate transport index (STI). Further, we aimed to substantiate that the effect was a result of ethylene modulation. Melatonin in the presence of excess-S (S) increased S-assimilation and the STI by increasing the ATP-sulfurylase (ATP-S) and serine acetyltransferase (SAT) activity of SS2, and it enhanced the content of cysteine (Cys) and methionine (Met). Under heat stress, melatonin increased S-assimilation and diverted Cys towards the synthesis of more reduced glutathione (GSH), utilizing excess-S at the expense of less methionine and ethylene and resulting in plants' reduced sensitivity to stress ethylene. The treatment with melatonin plus excess-S increased antioxidant enzyme activity, photosynthetic-S use efficiency (p-SUE), Rubisco activity, photosynthesis, and growth under heat stress. Further, plants receiving melatonin and excess-S in the presence of norbornadiene (NBD; an ethylene action inhibitor) under heat stress showed an inhibited STI and lower photosynthesis and growth. This suggested that ethylene was involved in the melatonin-mediated heat stress reversal effects on photosynthesis in plants. The interaction mechanism between melatonin and ethylene is still elusive. This study provides avenues to explore the melatonin-ethylene-S interaction for heat stress tolerance in plants.

Background: Cardiovascular diseases (CVDs) have been identified as the leading reason for morbidity and mortality in Saudi Arabia. Pharmacists play a major role in CVD prevention and health promotion. We aimed to assess the knowledge, attitudes, and involvement of pharmacists in CVD prevention and evaluate the influence of continuing medical education in CVD-prevention services in Saudi Arabia., Method: A cross-sectional study was conducted to evaluate the involvement of pharmacists in CVD-related prevention services along with their knowledge and attitudes. A 34-item questionnaire was developed and distributed among the participants., Results: A total of 324 responses were included in the study. More than 60% of pharmacists had provided counseling regarding the importance of healthy lifestyles and self-monitoring CVD risk factors. About half of the participants (49.1%) had never received any CVD-related continuing medical education. Overall, more than 60% of the participants reported positively towards their role in CVD prevention. Lack of time (66%) and lack of educational materials and tools (41%) were the top perceived barriers for providing CVD-prevention and health-promotion activities, followed by lack of skills in using tools (36%) and lack of privacy/space (33%)., Conclusions: The involvement of pharmacists in the prevention of CVD is limited in this study. Further education and capacity building are required to strengthen pharmacists' involvement in CVD-prevention and health-promotion activities.

Measuring patient safety culture in the community pharmacy can help with identifying areas for development. The current study is a descriptive, cross-sectional, electronic survey conducted among pharmacists working in community pharmacies located in the southern region of Saudi Arabia. The community pharmacy version of the "Pharmacy Survey on Patient Safety Culture" (PSOPSC) was used to collect data. The positive response rate (PRR) was calculated as per the guidance provided by the Agency for Healthcare Research and Quality (AHRQ). Based on the PRR, two least-achieved items (<25%) were taken for further analysis to identify the possible predictors. A sum of 195 pharmacists were included in this study and most of them were working in chain pharmacies. The highest PRRs were observed with teamwork (94.99), and patient counseling (94.13), followed by physical space and environment (93.07). The lowest PRRs were observed with staffing, work pressure, and pace (47.70), followed by communication openness (72.60). Specific characteristics, such as experience and the number of working hours, are significantly related to a poor PRR. The current study results indicate that the scope for improving patient safety exists in various areas of community pharmacies. However, it is necessary to prioritize the need based on a positive response rate.

Water monitor lizards (WMLs) reside in unhygienic and challenging ecological surroundings and are routinely exposed to various pathogenic microorganisms. It is possible that their gut microbiota produces substances to counter microbial infections. Here we determine whether selected gut bacteria of water monitor lizards (WMLs) possess anti-amoebic properties using Acanthamoeba castellanii of the T4 genotype. Conditioned media (CM) were prepared from bacteria isolated from WML. The CM were tested using amoebicidal, adhesion, encystation, excystation, cell cytotoxicity and amoeba-mediated host cell cytotoxicity assays in vitro . Amoebicidal assays revealed that CM exhibited anti-amoebic effects. CM inhibited both excystation and encystation in A. castellanii . CM inhibited amoebae binding to and cytotoxicity of host cells. In contrast, CM alone showed limited toxic effects against human cells in vitro . Mass spectrometry revealed several antimicrobials, anticancer, neurotransmitters, anti-depressant and other metabolites with biological functions. Overall, these findings imply that bacteria from unusual places, such as WML gut, produce molecules with anti-acanthamoebic capabilities.

Sorghum ( Sorghum bicolor ) is the fifth most important cereal crop worldwide; however, its utilization in food products can be limited due to reduced nutritional quality related to amino acid composition and protein digestibility in cooked products. Low essential amino acid levels and digestibility are influenced by the composition of the sorghum seed storage proteins, kafirins. In this study, we report a core collection of 206 sorghum mutant lines with altered seed storage proteins. Wet lab chemistry analysis was conducted to evaluate the total protein content and 23 amino acids, including 19 protein-bound and 4 non-protein amino acids. We identified mutant lines with diverse compositions of essential and non-essential amino acids. The highest total protein content in these lines was almost double that of the wild-type (BTx623). The mutants identified in this study can be used as a genetic resource to improve the sorghum grain quality and determine the molecular mechanisms underlying the biosynthesis of storage protein and starch in sorghum seeds.

The emergence of drug-resistant bacterial strains that reduce the effectiveness of antimicrobial agents has become a major ongoing health concern in recent years. It is therefore necessary to find new antibacterials with broad-spectrum activity against both Gram-positive and Gram-negative bacteria, and/or to use nanotechnology to boost the potency of already available medications. In this research, we examined the antibacterial efficacy of sulfamethoxazole and ethacridine lactate loaded two-dimensional glucosamine functionalized graphene-based nanocarriers against a range of bacterial isolates. Graphene oxide was first functionalized with glucosamine, which as a carbohydrate moiety can render hydrophilic and biocompatible characters to the GO surface, and subsequently loaded with ethacridine lactate and sulfamethoxazole. The resulting nanoformulations had distinct, controllable physiochemical properties. By analyzing the formulation using Fourier Transform Infrared Spectroscopy (FTIR), X-ray diffraction (PXRD), a thermogravimetric analysis (TGA), zetasizer, and a morphological analysis using Scanning Electron Microscopy and Atomic Force Microscopy, researchers were able to confirm the synthesis of nanocarriers. Both nanoformulations were tested against Gram-negative bacteria, including Escherichia coli K1, Serratia marcescens , Pseudomonas aeruginosa , Salmonella enterica , as well as Gram-positive bacteria, including Bacillus cereus , Streptococcus pyogenes , and Streptococcus pneumoniae . Importantly, ethacridine lactate and its nanoformulations exhibited significant antibacterial properties against all bacteria tested in this study. When tested for minimum inhibitory concentration (MIC), the results were remarkable and revealed that ethacridine lactate presented MIC 90 at 9.7 µg/mL against S. enteric , and MIC 90 at 6.2 µg/mL against B. cereus . Notably, ethacridine lactate and its nanoformulations showed limited toxicity effects against human cells using lactate dehydrogenase assays. Overall, the results revealed that ethacridine lactate and its nanoformulations possess antibacterial activities against various Gram-negative and Gram-positive bacteria and that nanotechnology can be employed for the targeted delivery of effective drugs without harming the host tissue.

Given the opportunity and access, pathogenic protists ( Balamuthia mandrillaris and Naegleria fowleri ) can produce fatal infections involving the central nervous system. In the absence of effective treatments, there is a need to either develop new antimicrobials or enhance the efficacy of existing compounds. Nanocarriers as drug delivery systems are gaining increasing attention in the treatment of parasitic infections. In this study, novel nanocarriers conjugated with amphotericin B and curcumin were evaluated for anti-amoebic efficacy against B. mandrillaris and N. fowleri . The results showed that nanocarrier conjugated amphotericin B exhibited enhanced cidal properties against both amoebae tested compared with the drug alone. Similarly, nanocarrier conjugated curcumin exhibited up to 75% cidal effects versus approx. 50% cidal effects for curcumin alone. Cytopathogenicity assays revealed that the pre-treatment of both parasites with nanoformulated-drugs reduced parasite-mediated host cellular death compared with the drugs alone. Importantly, the cytotoxic effects of amphotericin B on human cells alone were reduced when conjugated with nanocarriers. These are promising findings and further suggest the need to explore nanocarriers as a means to deliver medicine against parasitic infections.

Acanthamoeba is well known to host a variety of microorganisms such as viruses, bacteria, protozoa, and yeast. Given the recent number of cases of monkeypox infection, we speculate that amoebae may be aiding viral transmission to the susceptible hosts. Although there is no confirmatory evidence to suggest that Acanthamoeba is a host to monkeypox (a double-stranded DNA virus), the recent discovery of mimivirus (another double-stranded DNA virus) from Acanthamoeba , suggests that amoebae may shelter monkeypox virus. Furthermore, given the possible spread of monkeypox virus from animals to humans during an earlier outbreak, which came about after patients came in contact with prairie dogs, it is likely that animals may also act as mixing vessel between ubiquitously distributed Acanthamoeba and monkeypox virus, in addition to the environmental habitat that acts as an interface in complex interactions between diverse microorganisms and the host.

Pathogenic Acanthamoeba produce keratitis and fatal granulomatous amoebic encephalitis. Treatment remains problematic and often ineffective, suggesting the need for the discovery of novel compounds. For the first time, here we evaluated the effects of the anticancer drugs Irosustat and STX140 alone, as well as their nanoformulations, against A. castellanii via amoebicidal, excystment, cytopathogenicity, and cytotoxicity assays. Nanoformulations of the compounds were successfully synthesized with high encapsulation efficiency of 94% and 82% for Irosustat and STX140, respectively. Nanoparticles formed were spherical in shape and had a unimodal narrow particle size distribution, mean of 145 and 244 nm with a polydispersity index of 0.3, and surface charge of -14 and -15 mV, respectively. Irosustat and STX140 exhibited a biphasic release profile with almost 100% drug released after 48 h. Notably, Irosustat significantly inhibited A. castellanii viability and amoebae-mediated cytopathogenicity and inhibited the phenotypic transformation of amoebae cysts into the trophozoite form, however their nanoformulations depicted limited effects against amoebae but exhibited minimal cytotoxicity when tested against human cells using lactate dehydrogenase release assays. Accordingly, both compounds have potential for further studies, with the hope of discovering novel anti- Acanthamoeba compounds, and potentially developing targeted therapy against infections of the central nervous system.

The effects of exogenously-sourced NO (nitric oxide, as 100 µM SNP) and proline (50 mM) in the protection of the photosynthetic performance of wheat ( Triticum aestivum L.) plants against heat stress were investigated. The study focused on the mechanisms of proline accumulation, activity, gene expression of antioxidant enzymes, and NO generation. Plants were exposed to a temperature of 40 °C for 6 h per day over 15 days, then allowed to recover at 28 °C. Heat-stressed plants showed increased oxidative stress, with higher levels of H 2 O 2 and TBARS (thiobarbituric acid reactive substances) and increased proline accumulation, ACS activity, ethylene evolution, and NO generation, which in turn leads to increased accumulation of antioxidant enzymes and reduced photosynthetic attributes. In the tested wheat cultivar, the exogenous application of SNP and proline under heat stress improved the photosynthesis and reduced oxidative stress by enhancing the enzymatic antioxidant defense system. Potentially, the promoter AOX (alternative oxidase) played a role in maintaining redox homeostasis by lowering H 2 O 2 and TBARS levels. The genes for GR antioxidant and photosystem II core protein encoding psbA and psbB were highly up-regulated in nitric oxide and proline treated heat-stressed plants, indicating that ethylene positively impacted photosynthesis under high temperature stress. Moreover, nitric oxide supplementation under high temperature stress optimized ethylene levels to regulate the assimilation and metabolism of proline and the antioxidant system, lowering the adverse effects. The study showed that nitric oxide and proline increased high temperature stress tolerance in wheat by increasing the osmolytes accumulation and the antioxidant system, resulting in enhanced photosynthesis.

Cochliobolus , Bipolaris , and Curvularia genera contain various devastating plant pathogens that cause severe crop losses worldwide. The species belonging to these genera also perform a variety of diverse functions, including the remediation of environmental contaminations, beneficial phytohormone production, and maintaining their lifestyle as epiphytes, endophytes, and saprophytes. Recent research has revealed that despite their pathogenic nature, these fungi also play an intriguing role in agriculture. They act as phosphate solubilizers and produce phytohormones, such as indole acetic acid (IAA) and gibberellic acid (GAs), to accelerate the growth of various plants. Some species have also been reported to play a significant role in plant growth promotion during abiotic stresses, such as salinity stress, drought stress, heat stress, and heavy metal stress, as well as act as a biocontrol agent and a potential mycoherbicide. Similarly, these species have been reported in numerous industrial applications to produce different types of secondary metabolites and biotechnological products and possess a variety of biological properties, such as antibacterial, antileishmanial, cytotoxic, phytotoxic, and antioxidant activities. Additionally, some of the species have been utilized in the production of numerous valuable industrial enzymes and biotransformation, which has an impact on the growth of crops all over the world. However, the current literature is dispersed, and some of the key areas, such as taxonomy, phylogeny, genome sequencing, phytohormonal analysis, and diversity, are still being neglected in terms of the elucidation of its mechanisms, plant growth promotion, stress tolerance, and bioremediation. In this review, we highlighted the potential role, function, and diversity of Cochliobolus , Curvularia , and Bipolaris for improved utilization during environmental biotechnology.

Background: Taste disorders (TDs) have been reported to be very common in patients suffering from coronavirus disease 2019 (COVID-19), which is caused by the SARS-CoV-2 virus. In most of the hitherto conducted studies, a gustatory assessment was performed on the basis of surveys or self-reports by patients. The aim of our study was to undertake an objective assessment of four basic taste qualities by conducting tasting sessions that allowed detection thresholds in COVID-19 Tunisian patients and to study their associations with inflammation., Methods: This analytical cross-sectional study was conducted on 89 patients aged between 21 to 70 years who had been diagnosed with COVID-19. We used Burghart taste strips to assess taste perception of the four taste qualities, i.e., sour, bitter, sweet, and salty. Serum levels of interleukin-1β (IL-1β), interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-α), and C-reactive protein (CRP) were measured., Results: Taste disorders were reported by 40.4% of the patients, while objective assessments revealed that 63.8% of participants were suffering from hypogeusia and/or ageusia. Sour taste was the most altered (70.8%) gustatory quality. Patients with severe COVID-19 had significantly lower sour and bitter taste scores when compared to patients with minor/moderate forms. There was no significant association between serum inflammatory markers and taste disorders. However, the relationship between bitter and sweet taste qualities and IL-1β levels was significant ( p = 0.018 and p = 0.041)., Conclusions: Our results demonstrate the interest in the objective assessment of taste dysfunctions in COVID-19 patients.

Amoebic keratitis and encephalitis are mainly caused by free-living amoebae of the genus Acanthamoeba , which consists of both pathogenic and nonpathogenic species. The global distribution, amphizoic properties and the severity of the disease caused by Acanthamoeba species have inspired the scientific community to put more effort into the isolation of Acanthamoeba , besides exploring the direct and indirect parameters that could signify a pathogenic potential. Therefore, this study was performed to characterize the pathogenic potential of Acanthamoeba isolated from contact lens paraphernalia and water sources in Malaysia. Various methodologies were utilized to analyze the thermotolerance and osmotolerance, the secretion level of proteases and the cytopathic effect of trophozoites on the cell monolayer. In addition, the in vitro cytopathogenicity of these isolates was assessed using the LDH-release assay. A total of 14 Acanthamoeba isolates were classified as thermo- and osmotolerant and had presence of serine proteases with a molecular weight of 45-230 kDa. Four T4 genotypes isolated from contact lens paraphernalia recorded the presence of serine-type proteases of 107 kDa and 133 kDa. In contrast, all T3 genotypes isolated from environmental samples showed the presence of a 56 kDa proteolytic enzyme. Remarkably, eight T4 and a single T3 genotype isolates demonstrated a high adhesion percentage of greater than 90%. Moreover, the use of the HeLa cell monolayer showed that four T4 isolates and one T3 isolate achieved a cytopathic effect in the range of 44.9-59.4%, indicating an intermediate-to-high cytotoxicity level. Apart from that, the LDH-release assay revealed that three T4 isolates (CL5, CL54 and CL149) and one T3 isolate (SKA5-SK35) measured an exceptional toxicity level of higher than 40% compared to other isolates. In short, the presence of Acanthamoeba T3 and T4 genotypes with significant pathogenic potential in this study reiterates the essential need to reassess the functionality of other genotypes that were previously classified as nonpathogenic isolates in past research.

Acanthamoeba castellanii is a ubiquitous free-living amoeba capable of instigating keratitis and granulomatous amoebic encephalitis in humans. Treatment remains limited and inconsistent. Accordingly, there is a pressing need for novel compounds. Nanotechnology has been gaining attention for enhancing drug delivery and reducing toxicity. Previous work has shown that various antibiotic classes displayed antiamoebic activity. Herein, we employed two antibiotics: ampicillin and ceftriaxone, conjugated with the nanocarrier zinc oxide and β-cyclodextrin, and tested them against A. castellanii via amoebicidal, amoebistatic, encystment, excystment, cytopathogenicity, and cytotoxicity assays at a concentration of 100 μg/mL. Notably, zinc oxide β-cyclodextrin ceftriaxone significantly inhibited A. castellanii growth and cytopathogenicity. Additionally, both zinc oxide β-cyclodextrin ceftriaxone and ceftriaxone markedly inhibited A. castellanii encystment. Furthermore, all the tested compounds displayed negligible cytotoxicity. However, minimal anti-excystment or amoebicidal effects were observed for the compounds. Accordingly, this novel nanoconjugation should be employed in further studies in hope of discovering novel anti- Acanthamoeba compounds.

Phytohormones have a role in stress adaptation. The major mechanism underlying the role of exogenously-sourced nitric oxide (NO; as sodium nitroprusside, SNP: 50.0 µM) and salicylic acid (SA; 0.5 mM) in the presence of 2.0 mM SO 4 -2 was assessed in heat stress (HS; 40 °C for 6 h daily for 15 days) tolerance in wheat (Triticum aestivum L. cv. HD-3226). The cultivar HD-3226 possessed high photosynthetic sulfur use efficiency (p-SUE) among the six cultivars screened. Plants grown under HS exhibited an increased content of reactive oxygen species (ROS; including superoxide radical and hydrogen peroxide) and extent of lipid peroxidation with a consequent reduction in photosynthesis and growth. However, both NO and SA were found to be protective against HS via enhanced S assimilation. Their application reduced oxidative stress and increased the activity of antioxidant enzymes. NO or SA supplementation along with S under HS recovered the losses and improved photosynthesis and growth. The use of SA inhibitor (2-aminoindane-2-phosphonic acid; AIP) and NO scavenger (cPTIO) confirmed that the mitigating effects of SA and NO involved induction in S assimilation.

We utilised a ground-based microgravity hindlimb unloading (HU) mouse model to elucidate the gut microbiota bacterial changes in mice under a simulated microgravity environment. Four-month-old, male C57/Bl6 mice were randomly divided into ground-based controls and the HU groups and kept under controlled environmental conditions. For the microgravity environment, the mice were suspended in special cages individually for 20 days. At the end of the suspension, the mice were sacrificed; gut dissections were performed, followed by a metagenomic analysis of bacterial species, which was carried out by extracting DNA and 16S rRNA analysis. The results revealed that the gut bacterial communities of mice under gravity and microgravity were different. Notably, our findings revealed differences in the bacterial community structure. Around 449 bacterial OTUs were specific to mice kept under normal gravity versus 443 bacterial OTUs under microgravity conditions. In contrast, 694 bacterial OTUs were common to both groups. When the relative abundance of taxa was analyzed, Bacteroidetes dominated the gut (64.7%) of normal mice. Conversely, mice in the microgravity environment were dominated by Firmicutes (42.7%), and the relative abundance of Bacteroidetes differed significantly between the two groups (p < 0.05). The distribution of Muribaculaceae between normal mice versus microgravity mice was significantly different, at 62% and 36.4%, respectively (p < 0.05). Furthermore, a significant decrease in 11 bacteria was observed in mice under simulated microgravity, including Akkermansia muciniphila, Eubacterium coprostanoligenes, Bacteroides acidifaciens, Clostridium leptum, Methylorubrum extorquens, Comamonas testosterone, Desulfovibrio fairfieldensis, Bacteroides coprocola, Aerococcus urinaeequi, Helicobacter hepaticus, and Burkholderiales. Further studies are needed to elucidate gut bacterial metabolites of these identified bacterial species in microgravity conditions and normal environment. Notably, the influence of these metabolites on obesity, neuroprotection, musculoskeletal and cardiovascular dysfunction, longevity, inflammation, health, and disease in astronauts ought to be investigated and will be important in developing procedures against adverse effects in astronauts following space travel.

Naegleria fowleri (N. fowleri) is a free-living, unicellular, opportunistic protist responsible for the fatal central nervous system infection, primary amoebic meningoencephalitis (PAM). Given the increase in temperatures due to global warming and climate change, it is estimated that the cases of PAM are on the rise. However, there is a current lack of awareness and effective drugs, meaning there is an urgent need to develop new therapeutic drugs. In this study, the target compounds were synthesized and tested for their anti-amoebic properties against N. fowleri. Most compounds exhibited significant amoebicidal effects against N. fowleri ; for example, 1h , 1j , and 1q reduced N. fowleri's viability to 15.14%, 17.45% and 28.78%, respectively. Furthermore, the majority of the compounds showed reductions in amoeba-mediated host death. Of interest are the compounds 1f , 1k , and 1v , as they were capable of reducing the amoeba-mediated host cell death to 52.3%, 51%, and 56.9% from 100%, respectively. Additionally, these compounds exhibit amoebicidal properties as well; they were found to decrease N. fowleri's viability to 26.41%, 27.39%, and 24.13% from 100%, respectively. Moreover, the MIC 50 values for 1e , 1f , and 1h were determined to be 48.45 µM, 60.87 µM, and 50.96 µM, respectively. Additionally, the majority of compounds were found to exhibit limited cytotoxicity, except for 1l , 1o , 1p , 1m , 1c , 1b , 1zb , 1z , 1y , and 1x , which exhibited negligible toxicity. It is anticipated that these compounds may be developed further as effective treatments against these devastating infections due to brain-eating amoebae.

Vitrification is an important tool to store surplus embryos in assisted reproductive technology (ART). However, vitrification increases oxidative damage and results in decreased viability. Studies have reported that L-glutathione (GSH) supplementation improves the preimplantation development of murine embryos. Glutathione constitutes the major non-protein sulphydryl compound in mammalian cells, which confers protection against oxidative damage. However, the effect of GSH supplementation on embryonic vitrification outcomes has yet to be reported. This study aims to determine whether GSH supplementation in culture media improves in vitro culture and vitrification outcomes, as observed through embryo morphology and preimplantation development. Female BALB/c mice aged 6−8 weeks were superovulated through an intraperitoneal injection of 10 IU of pregnant mare serum gonadotrophin (PMSG), followed by 10 IU of human chorionic gonadotrophin (hCG) 48 h later. The mated mice were euthanized by cervical dislocation 48 h after hCG to harvest embryos. Two-cell embryos were randomly assigned to be cultured in either Group 1 (GSH-free medium), Group 2 (GSH-free medium with vitrification), Group 3 (0.01 mM GSH-supplemented medium), or Group 4 (0.01 mM GSH-supplemented medium with vitrification). Non-vitrified (Groups 1 and 3) and vitrified (Groups 2 and 4) embryos were observed for morphological quality and preimplantation development at 24, 48, 72, and 96 h. In the non-vitrified groups, there were significant increases in the number of Grade-1 blastocysts in GSH cultures (p < 0.05). Similarly, in the vitrified groups, GSH supplementation was also seen to significantly increase blastocyst formation. Exogenous GSH supplementation resulted in a significant increase in intracellular GSH, a release of cytochrome c from mitochondria, and a parallel decrease in intracellular reactive oxygen species (ROS) levels in vitrified eight-cell embryos (p < 0.05). GSH supplementation was shown to upregulate Bcl2 expression and downregulate Bax expression in the vitrified preimplantation embryo group. The action of exogenous GSH was concomitant with an increase in the relative abundance of Gpx1 and Sod1. In conclusion, our study demonstrated the novel use and practical applicability of GSH supplementation for improving embryonic cryotolerance via a decrease in ROS levels and the inhibition of apoptotic events by improvement in oxidative status., Competing Interests: The authors declare no conflict of interest.

Rhizoctonia solani is a soil-borne fungus causing sheath blight disease in cereal crops including rice. Genetic resistance to sheath blight disease in cereal crops is not well understood in most of the host(s). Aside from this, a comparative study on the different hosts at the biochemical and proteomic level upon R. solani infection was not reported earlier. Here, we performed proteomic based analysis and studied defense pathways among cultivated rice (cv. Pusa Basmati-1), wild rice accession ( Oryza grandiglumis ), and barley (cv. NDB-1445) after inoculation with R. solani . Increased levels of phenol, peroxidase, and β-1, 3-glucanase were observed in infected tissue as compared to the control in all of the hosts. Wild rice accession O. grandiglumis showed a higher level of biochemical signals than barley cv. NDB 1445 and cultivated rice cv. Pusa Basmati-1. Using two-dimensional polyacrylamide gel electrophoresis (2D-PAGE) and mass spectrometry (MS), differently expressed proteins were also studied in control and after inoculation with R. solani . Wild rice accession O. grandiglumis induced a cysteine protease inhibitor and zinc finger proteins, which have defense functions and resistance against fungal pathogens. On the other hand, barley cv. NDB-1445 and cultivated rice cv. Pusa Basmati-1 mainly induce energy metabolism-related proteins/signals after inoculation with R. solani in comparison to wild rice accession O. grandiglumis . The present comprehensive study of R. solani interaction using three hosts, namely, Pusa Basmati-1 (cultivated rice), O. grandiglumis (wild rice), and NDB-1445 (barley) would interpret wider possibilities in the dissection of the protein(s) induced during the infection process. These proteins may further be correlated to the gene(s) and other related molecular tools that will help for the marker-assisted breeding and/or gene editing for this distressing disease among the major cereal crops.

Pathogenicity-associated genes are highly host-specific and contribute to host-specific virulence. We tailored the traditional Koch's postulates with integrative omics by hypothesizing that the effector genes associated with host-pathogenicity are determinant markers for virulence, and developed Integrative Pathogenicity (IP) postulates for authenticated pathogenicity testing in plants. To set the criteria, we experimented on datepalm ( Phoenix dactylifera ) for the vascular wilt pathogen and confirmed the pathogen based on secreted in xylem genes (effectors genes) using genomic and transcriptomic approaches, and found it a reliable solution when pathogenicity is in question. The genic regions ITS, TEF1-α, and RPBII of Fusarium isolates were examined by phylogenetic analysis to unveil the validated operational taxonomy at the species level. The hierarchical tree generated through phylogenetic analysis declared the fungal pathogen as Fusarium oxysporum. Moreover, the Fusarium isolates were investigated at the subspecies level by probing the IGS, TEF1-α, and Pgx4 genic regions to detect the forma specialis of F. oxysporum that causes wilt in datepalm. The phylogram revealed a new forma specialis in F. oxysporum that causes vascular wilt in datepalm.

Improving plant resilience to changing environmental conditions is the primary focus of today's scientific research globally. It is essential to find various strategies for the better survival of plants with higher resistance potential to climate change. Strigolactones (SLs) are multifunctional β-carotene derivative molecules that determine a range of plant growth and development aspects, such as root architecture, shoot branching, chlorophyll synthesis, and senescence. SLs facilitate strong defense responses against drought, salinity, heavy metal, nutrient starvation, and heat stress. The SLs trigger other hormonal-responsive pathways and determine plant resilience against stressful environments. This review focuses on the mechanisms regulated by SLs and interaction with other plant hormones to regulate plant developmental processes and SLs' influence on the mitigation of plant damage under abiotic stresses. A better understanding of the signaling and perception of SLs may lead to the path for the sustainability of plants in the changing environmental scenario. The SLs may be considered as an opening door toward sustainable agriculture.

Naegleria fowleri and Balamuthia mandrillaris are opportunistic protists, responsible for fatal central nervous system infections such as primary amoebic meningoencephalitis (PAM) and granulomatous amoebic encephalitis (GAE) with mortality rates higher than 90%. Threatening a rise in cases is the increase in temperature due to global warming. No effective treatment is currently available. Herein, nanotechnology was used to conjugate Zinc oxide with Ampicillin, Ceftrixon, Naringin, Amphotericin B, and Quericitin, and the amoebicidal activity and host cell cytotoxicity of these resulting compounds were investigated. The compounds ZnO-CD-AMPi, ZnO-CD-CFT, ZnO-CD-Nar, ZnO-CD-AMB, and ZnO-CD-QT were found to reduce N. fowleri viability to 35.5%, 39.6%, 52.0%, 50.8%, 35.9%, and 69.9%, respectively, and B. mandrillaris viability to 40.9%, 48.2%, 51.6%, 43.8%, and 62.4%, respectively, when compared with their corresponding controls. Furthermore, the compounds reduced N. fowleri -mediated and B. mandrillaris -mediated host cell death significantly. Additionally, the compounds showed limited cytotoxicity against human cells; cell toxicity was 35.5%, 36.4%, 30.9%, 36.6%, and 35.6%, respectively, for the compounds ZnO-CD-AMPi, ZnO-CD-CFT, ZnO-CD-Nar, ZnO-CD-AMB, and ZnO-CD-QT. Furthermore, the minimum inhibitory concentrations to inhibit amoeba growth by 50% were determined for N. fowleri and B. mandrillaris. The MIC 50 for N. fowleri were determined to be 69.52 µg/mL, 82.05 µg/mL, 88.16 µg/mL, 95.61 µg/mL, and 85.69 µg/mL, respectively; the MIC 50 of the compounds for B. mandrillaris were determined to be 113.9 µg/mL, 102.3 µg/mL, 106.9 µg/mL, 146.4 µg/mL, and 129.6 µg/mL, respectively. Translational research to further develop therapies based on these compounds is urgently warranted, given the lack of effective therapies currently available against these devastating infections.

Gut microbial composition codevelops with the host from birth and is influenced by several factors, including drug use, radiation, psychological stress, dietary changes and physical stress. Importantly, gut microbial dysbiosis has been clearly associated with several diseases, including cancer, rheumatoid arthritis and Clostridium difficile -associated diarrhoea, and is known to affect human health and performance. Herein, we discuss that a shift in the gut microbiota with age and reversal of age-related modulation of the gut microbiota could be a major contributor to the incidence of numerous age-related diseases or overall human performance. In addition, it is suggested that the gut microbiome of long-lived animals such as reptiles should be investigated for their unique properties and contribution to the potent defense system of these species could be extrapolated for the benefit of human health. A range of techniques can be used to modulate the gut microbiota to have higher abundance of "beneficial" microbes that have been linked with health and longevity.

We examined the antiamoebic effect of several imidazothiazole derivatives on Acanthamoeba castellanii of the T4 genotype. Trypan blue exclusion assays and haemocytometer counting were used to determine the reduction in A. castellanii trophozoite proliferation, in response to treatment with these compounds. To determine the effects of these compounds on host cells, lactate dehydrogenase assay was performed using HeLa cell lines. Amoebicidal assays revealed that the tested compounds at concentrations of 50 µM significantly inhibited amoebae trophozoites compared to controls. Compounds 1m and 1zb showed the highest amoebicidal effects eradicating 70% and 67% of A. castellanii , respectively. The compounds blocked both the encystation and excystation process in A. castellanii . Compounds 1m and 1zb blocked 61% and 55%, respectively, of amoeba binding to human cells. Moreover, the compounds showed minimal cytotoxic effects against host cells and considerably reduced amoeba-mediated host cell death. Overall, our study revealed that compounds 1m and 1zb have excellent antiamoebic potential, and should be considered in the development of curative antiamoebic medications in future studies. Further work is critical to determine the translational value of these findings.

Ethylene is a gaseous plant growth hormone that regulates various plant developmental processes, ranging from seed germination to senescence. The mechanisms underlying ethylene biosynthesis and signaling involve multistep mechanisms representing different control levels to regulate its production and response. Ethylene is an established phytohormone that displays various signaling processes under environmental stress in plants. Such environmental stresses trigger ethylene biosynthesis/action, which influences the growth and development of plants and opens new windows for future crop improvement. This review summarizes the current understanding of how environmental stress influences plants' ethylene biosynthesis, signaling, and response. The review focuses on (a) ethylene biosynthesis and signaling in plants, (b) the influence of environmental stress on ethylene biosynthesis, (c) regulation of ethylene signaling for stress acclimation, (d) potential mechanisms underlying the ethylene-mediated stress tolerance in plants, and (e) summarizing ethylene formation under stress and its mechanism of action.

The altered gut microbes of astronauts during space travel may contribute to health issues after their return to Earth. Previously, an association between the elevated endoplasmic reticulum (ER) stress and gut microbial dysbiosis has been described. Herein, we induced gut microbial changes in mice under a simulated microgravity environment in an established model of hindlimb unloaded (HU) mice. The intestinal metabolomic profiles under microgravity conditions using the HU model were examined, along with the potential role of 4-phenylbutyric acid (4-PBA), a potent ER stress inhibitor. For a microgravity environment, the mice were suspended in special cages individually for three weeks. Mice were sacrificed, and gut dissections were performed, followed by amplicon sequencing analysis of bacterial species via DNA extraction and 16S rRNA analysis. The results indicate that the gut bacterial communities of mice differed under gravity and microgravity conditions. Principal component analyses revealed differences in the bacterial community structure in all groups. Around 434 operational taxonomic units (OTUs) were specific to mice seen in controls, while 620 OTUs were specific to HU mice. Additionally, 321 bacterial OTUs were specific to HU mice treated with 4-PBA. When the relative abundance of taxa was analyzed, Bacteroidetes dominated the gut of control and HU mice treated with 4-PBA.. In contrast, the untreated HU mice were dominated by Firmicutes. At the genus level, a reduction in beneficial species of Akkermansia and Lactobacillus was observed in HU but not the unloaded-treated and control mice. Furthermore, an increase in the relative abundance of Lachnospiraceae and Enterorhabdus , associated with inflammation, was observed in HUmice but not in controls and unloaded-treated mice. Following treatment with 4-PBA, the ratio of Firmicutes to Bacteroidetes was restored in unloaded-treated mice, comparable to controls. Of note, beneficial microbes such as Akkermansia and Lactobacillus were observed in unloaded-treated mice but not or in lesser relative abundance in HU mice. Nonetheless, microbial diversity was reduced in unloaded-treated mice compared to controls, and future studies are needed to mitigate this finding. These may comprise the addition of pre-/pro- and postbiotic species in the diet to increase microbial diversity. Overall, the findings suggest that 4-PBA, a potent ER stress inhibitor, may have therapeutic value in treating patients on prolonged bed rest or astronauts during spaceflight.

Rising temperatures worldwide due to global climate change are a major scientific issue at present. The present study reports the effects of gaseous signaling molecules, ethylene (200 µL L -1 ; 2-chloroethylphosphonic acid; ethephon, Eth), nitric oxide (NO; 100 µM sodium nitroprusside; SNP), and hydrogen sulfide (H 2 S; 200 µM sodium hydrosulfide, NaHS) in high temperature stress (HS) tolerance, and whether or not H 2 S contributes to ethylene or NO-induced thermo-tolerance and photosynthetic protection in rice ( Oryza sativa L.) cultivars, i.e., Taipei-309, and Rasi. Plants exposed to an HS of 40 °C for six h per day for 15 days caused a reduction in rice biomass, associated with decreased photosynthesis and leaf water status. High temperature stress increased oxidative stress by increasing the content of hydrogen peroxide (H 2 O 2 ) and thiobarbituric acid reactive substance (TBARS) in rice leaves. These signaling molecules increased biomass, leaf water status, osmolytes, antioxidants, and photosynthesis of plants under non-stress and high temperature stress. However, the effect was more conspicuous with ethylene than NO and H 2 S. The application of H 2 S scavenger hypotaurine (HT) reversed the effect of ethylene or NO on photosynthesis under HS. This supports the findings that the ameliorating effects of Eth or SNP involved H 2 S. Thus, the presence of H 2 S with ethylene or NO can enhance thermo-tolerance while also protecting plant photosynthesis.

The free-living amoeba Acanthamoeba castellanii is responsible for the central nervous infection granulomatous amoebic encephalitis and sight-threatening infection Acanthamoeba keratitis . Moreover, no effective treatment is currently present, and a combination drug therapy is used. In this study, twelve DNA minor groove binders (MGBs) were synthesized and tested for their antiamoebic activity via amoebicidal, encystation, excystation, and cytopathogenicity assays. It was found that the compounds MGB3, MGB6, MGB22, MGB24, and MGB16 significantly reduce amoeba viability to 76.20%, 59.45%, 66.5%, 39.32%, and 43.21%, respectively, in amoebicidal assays. Moreover, the compounds MGB6, MGB20, MGB22, MGB28, MGB30, MGB32, and MGB16 significantly inhibit Acanthamoeba cysts, leading to the development of only 46.3%, 39%, 30.3%, 29.6%, 27.8%, 41.5%, and 45.6% cysts. Additionally, the compounds MGB3, MGB4, MGB6, MGB22, MGB24, MGB28, MGB32, and MGB16 significantly reduce the re-emergence of cysts to trophozoites, with viable trophozoites being only 64.3%, 47.3%, 41.4%, 52.9%, 55.4%, 40.6%, 62.1%, and 51.7%. Moreover, the compounds MGB3, MGB4, and MGB6 exhibited the greatest reduction in amoeba-mediated host-cell death, with cell death reduced to 41.5%, 49.4%, and 49.5%. With the following determined, future in vivo studies can be carried out to understand the effect of the compounds on animal models such as mice.

This paper investigates the heat transfer of two-phase nanofluid flow between horizontal plates in a rotating system with a magnetic field and external forces. The basic continuity and momentum equations are considered to formulate the governing mathematical model of the problem. Furthermore, certain similarity transformations are used to reduce a governing system of non-linear partial differential equations (PDEs) into a non-linear system of ordinary differential equations. Moreover, an efficient stochastic technique based on feed-forward neural networks (FFNNs) with a back-propagated Levenberg-Marquardt (BLM) algorithm is developed to examine the effect of variations in various parameters on velocity, gravitational acceleration, temperature, and concentration profiles of the nanofluid. To validate the accuracy, efficiency, and computational complexity of the FFNN-BLM algorithm, different performance functions are defined based on mean absolute deviations (MAD), error in Nash-Sutcliffe efficiency (ENSE), and Theil's inequality coefficient (TIC). The approximate solutions achieved by the proposed technique are validated by comparing with the least square method (LSM), machine learning algorithms such as NARX-LM, and numerical solutions by the Runge-Kutta-Fehlberg method (RKFM). The results demonstrate that the mean percentage error in our solutions and values of ENSE, TIC, and MAD is almost zero, showing the design algorithm's robustness and correctness.

Since the discovery of antibiotics, humans have been benefiting from them by decreasing the morbidity and mortality associated with bacterial infections. However, in the past few decades, misuse of antibiotics has led to the emergence of bacterial infections resistant to multiple drugs, a significant health concern. Bacteria exposed to inappropriate levels of antibiotics lead to several genetic changes, enabling them to survive in the host and become more resistant. Despite the understanding and targeting of genetic-based biochemical changes in the bacteria, the increasing levels of antibiotic resistance are not under control. Many reports hint at the role of epigenetic modifications in the bacterial genome and host epigenetic reprogramming due to interaction with resistant pathogens. Epigenetic changes, such as the DNA-methylation-based regulation of bacterial mutation rates or bacteria-induced histone modification in human epithelial cells, facilitate its long-term survival. In this review article, epigenetic changes leading to the development of antibiotic resistance in clinically relevant bacteria are discussed. Additionally, recent lines of evidence focusing on human host epigenetic changes due to the human-pathogen interactions are presented. As genetic mechanisms cannot explain the transient nature of antimicrobial resistance, we believe that epigenetics may provide new frontiers in antimicrobial discovery.

Naegleria &nbsp; fowleri and Balamuthia mandrillaris are pathogenic free-living amoebae that infect the central nervous system with over 95% mortality rates. Although several compounds have shown promise in vitro but associated side effects and/or prolonged approval processes for clinical applications have led to limited success. To overcome this, drug repurposing of marketed compounds with known mechanism of action is considered a viable approach that has potential to expedite discovery and application of anti-amoebic compounds. In fact, many of the drugs currently employed in the treatment of N. fowleri and B. mandrillaris , such as amphotericin B, fluconazole, rifampin and miltefosine, are repurposed drugs. Here, we evaluated a range of clinical and laboratory compounds including metformin, quinclorac, indaziflam, inositol, nateglinide, 2,6-DNBT, trans-cinnamic acid, terbuthylazine, acarbose, glimepiride, vildagliptin, cellulase, thaxtomin A, repaglinide and dimethyl peptidase (IV) inhibitor against N. fowleri and B. mandrillaris . Anti-amoebic assays revealed that indaziflam, nateglinide, 2,6-DNBT, terbuthylazine, acarbose and glimepiride exhibited potent amoebicidal properties against both N. fowleri and B. mandrillaris . Notably, all compounds tested showed minimal human (HaCaT) cell cytotoxicity as determined by lactate dehydrogenase release. Prospective research using animal models is warranted to determine the potential of these repurposed compounds, as well as the need for investigating the intranasal route of delivery to treat these devastating infections.

To combat the public health threat posed by multiple-drug-resistant (MDR) pathogens, new drugs with novel chemistry and modes of action are needed. In this study, several drugs including Hesperidin (HES), curcumin (CUR), and Amphotericin B (AmpB) drug-nanoparticle formulations were tested for antibacterial strength against MDR Gram-positive bacteria, including Bacillus cereus , Streptococcus pyogenes , Methicillin-resistant Staphylococcus aureus (MRSA), and Streptococcus pneumoniae , and Gram-negative bacteria, including Escherichia coli K1, Pseudomonas aeruginosa , Salmonella enterica, and Serratia marcescens . Nanoparticles were synthesized and subjected to Atomic force microscopy, Fourier transform-infrared spectroscopy, and Zetasizer for their detailed characterization. Antibacterial assays were performed to determine their bactericidal efficacy. Lactate dehydrogenase (LDH) assays were carried out to measure drugs' and drug-nanoparticles' cytotoxic effects on human cells. Spherical NPs ranging from 153 to 300 nm were successfully synthesized. Results from antibacterial assays revealed that drugs and drug-nanoparticle formulations exerted bactericidal activity against MDR bacteria. Hesperidin alone failed to exhibit antibacterial effects but, upon conjugation with cinnamic-acid-based magnetic nanoparticle, exerted significant bactericidal activity against both the Gram-positive and Gram-negative isolates. AmpB-LBA-MNPs produced consistent, potent antibacterial efficacy (100% kill) against all Gram-positive bacteria. AmpB-LBA-MNPs showed strong antibacterial activity against Gram-negative bacteria. Intriguingly, all the drugs and their conjugated counterpart except AmpB showed minimal cytotoxicity against human cells. In summary, these innovative nanoparticle formulations have the potential to be utilized as therapeutic agents against infections caused by MDR bacteria and represent a significant advancement in our effort to counter MDR bacterial infections.

Naegleria fowleri and Balamuthia mandrillaris are free-living, opportunistic protists, distributed widely in the environment. They are responsible for primary amoebic meningoencephalitis (PAM) and granulomatous amoebic encephalitis (GAE), the fatal central nervous infections with mortality rates exceeding 90%. With the rise of global warming and water shortages resulting in water storage in tanks (where these amoebae may reside), the risk of infection is increasing. Currently, as a result of a lack of awareness, many cases may be misdiagnosed. Furthermore, the high mortality rate indicates the lack of effective drugs available. In this study, secondary metabolites from the plants Rinorea vaundensis and Salvia triloba were tested for their anti-amoebic properties against N. fowleri and B. mandrillaris. Three of the nine compounds showed potent and significant anti-amoebic activities against both N. fowleri and B. mandrillaris : ursolic acid, betulinic acid, and betulin. Additionally, all compounds depicted limited or minimal toxicity to human cells and were capable of reducing amoeba-mediated host cell death. Moreover, the minimum inhibitory concentration required to inhibit 50% of amoebae growth, the half-maximal effective concentration, and the maximum non-toxic dose against human cells of the compounds were determined. These effective plant-derived compounds should be utilized as potential therapies against infections due to free-living amoebae, but future research is needed to realize these expectations.

Artificial intelligence (AI) has been described as one of the extremely effective and promising scientific tools available to mankind. AI and its associated innovations are becoming more popular in industry and culture, and they are starting to show up in healthcare. Numerous facets of healthcare, as well as regulatory procedures within providers, payers, and pharmaceutical companies, may be transformed by these innovations. As a result, the purpose of this review is to identify the potential machine learning applications in the field of infectious diseases and the general healthcare system. The literature on this topic was extracted from various databases, such as Google, Google Scholar, Pubmed, Scopus, and Web of Science. The articles having important information were selected for this review. The most challenging task for AI in such healthcare sectors is to sustain its adoption in daily clinical practice, regardless of whether the programs are scalable enough to be useful. Based on the summarized data, it has been concluded that AI can assist healthcare staff in expanding their knowledge, allowing them to spend more time providing direct patient care and reducing weariness. Overall, we might conclude that the future of "conventional medicine" is closer than we realize, with patients seeing a computer first and subsequently a doctor.

Due to global warming, coupled with global water shortages and the reliance of the public on household water tanks, especially in developing countries, it is anticipated that infections caused by free-living amoebae such as Acanthamoeba will rise. Thus, the development of novel disinfectant(s) which can target pathogenic free-living amoebae effectively is warranted. Herein, we extracted and isolated several plant-based secondary metabolites as novel disinfectants for use against pathogenic Acanthamoeb a . The identity of the compounds was confirmed by nuclear magnetic resonance and tested for antiamoebic activities against clinical isolate of A. castellanii , belonging to the T4 genotype. Amoebicidal assays revealed that the compounds tested showed antiamoebic properties. Betulinic acid and betulin exhibited parasite killing of more than 65%. When tested against the cyst stage, betulinic acid, betulin, and vanillic acid inhibited both encystation and excystation processes. Furthermore, the plant-based metabolites significantly inhibited the binding capability of A. castellanii to host cells. Finally, most of the tested compounds displayed minimal cytotoxic activities against human cells and noticeably perturbed amoeba-mediated host cell cytotoxicity. Notably, both alkaloid and betulinic acid showed 20% cytotoxic effects, whereas betulin and lupeol had cytotoxic effects of 24% and 30%, respectively. Overall, our findings indicate that plant-based natural compounds demonstrate anti-Acanthamoebic properties, and they have potential candidates for water disinfectants or contact lens disinfecting solutions, as well as possible therapeutic drugs against Acanthamoeba infections.

This study investigated the steady two-phase flow of a nanofluid in a permeable duct with thermal radiation, a magnetic field, and external forces. The basic continuity and momentum equations were considered along with the Buongiorno model to formulate the governing mathematical model of the problem. Furthermore, the intelligent computational strength of artificial neural networks (ANNs) was utilized to construct the approximate solution for the problem. The unsupervised objective functions of the governing equations in terms of mean square error were optimized by hybridizing the global search ability of an arithmetic optimization algorithm (AOA) with the local search capability of an interior point algorithm (IPA). The proposed ANN-AOA-IPA technique was implemented to study the effect of variations in the thermophoretic parameter (Nt), Hartmann number (Ha), Brownian (Nb) and radiation (Rd) motion parameters, Eckert number (Ec), Reynolds number (Re) and Schmidt number (Sc) on the velocity profile, thermal profile, Nusselt number and skin friction coefficient of the nanofluid. The results obtained by the designed metaheuristic algorithm were compared with the numerical solutions obtained by the Runge-Kutta method of order 4 (RK-4) and machine learning algorithms based on a nonlinear autoregressive network with exogenous inputs (NARX) and backpropagated Levenberg-Marquardt algorithm. The mean percentage errors in approximate solutions obtained by ANN-AOA-IPA are around 10-6 to 10-7. The graphical analysis illustrates that the velocity, temperature, and concentration profiles of the nanofluid increase with an increase in the suction parameter, Eckert number and Schmidt number, respectively. Solutions and the results of performance indicators such as mean absolute deviation, Theil's inequality coefficient and error in Nash-Sutcliffe efficiency further validate the proposed algorithm's utility and efficiency.

Nitric oxide (NO) and abscisic acid (ABA) play a significant role to combat abiotic stress. Application of 100 µM sodium nitroprusside (SNP, NO donor) or ABA alleviated heat stress effects on photosynthesis and growth of wheat ( Triticum aestivum L.) plants exposed to 40 °C for 6 h every day for 15 days. We have shown that ABA and NO synergistically interact to reduce the heat stress effects on photosynthesis and growth via reducing the content of H 2 O 2 and thiobarbituric acid reactive substances (TBARS), as well as maximizing osmolytes production and the activity and expression of antioxidant enzymes. The inhibition of NO and ABA using c-PTIO (2-4 carboxyphenyl-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide) and fluridone (Flu), respectively, reduced the osmolyte and antioxidant metabolism and heat stress tolerance. The inhibition of NO significantly reduced the ABA-induced osmolytes and antioxidant metabolism, exhibiting that the function of ABA in the alleviation of heat stress was NO dependent and can be enhanced with NO supplementation.Thus, regulating the activity and expression of antioxidant enzymes together with osmolytes production could act as a possible strategy for heat tolerance.

A targeted and timely treatment can be a beneficial tool for patients with hematological emergencies (particularly acute leukemias). The key challenges in the early diagnosis of leukemias and related hematological disorders are their symptom-sharing nature and prolonged turnaround time as well as the expertise needed in reporting confirmatory tests. The present study made use of the potential morphological and immature fraction-related parameters (research items or cell population data) generated during complete blood cell count (CBC), through artificial intelligence (AI)/machine learning (ML) predictive modeling for early (at the pre-microscopic level) differentiation of various types of leukemias: acute from chronic as well as myeloid from lymphoid. The routine CBC parameters along with research CBC items from a hematology analyzer in the diagnosis of 1577 study subjects with hematological neoplasms were collected. The statistical and data visualization tools, including heat-map and principal component analysis (PCA,) helped in the evaluation of the predictive capacity of research CBC items. Next, research CBC parameter-driven artificial neural network (ANN) predictive modeling was developed to use the hidden trend (disease's signature) by increasing the auguring accuracy of these potential morphometric parameters in differentiation of leukemias. The classical statistics for routine and research CBC parameters showed that as a whole, all study items are significantly deviated among various types of leukemias (study groups). The CPD parameter-driven heat-map gave clustering (separation) of myeloid from lymphoid leukemias, followed by the segregation (nodding) of the acute from the chronic class of that particular lineage. Furthermore, acute promyelocytic leukemia (APML) was also well individuated from other types of acute myeloid leukemia (AML). The PCA plot guided by research CBC items at notable variance vindicated the aforementioned findings of the CPD-driven heat-map. Through training of ANN predictive modeling, the CPD parameters successfully differentiate the chronic myeloid leukemia (CML), AML, APML, acute lymphoid leukemia (ALL), chronic lymphoid leukemia (CLL), and other related hematological neoplasms with AUC values of 0.937, 0.905, 0.805, 0.829, 0.870, and 0.789, respectively, at an agreeably significant (10.6%) false prediction rate. Overall practical results of using our ANN model were found quite satisfactory with values of 83.1% and 89.4.7% for training and testing datasets, respectively. We proposed that research CBC parameters could potentially be used for early differentiation of leukemias in the hematology-oncology unit. The CPD-driven ANN modeling is a novel practice that substantially strengthens the predictive potential of CPD items, allowing the clinicians to be confident about the typical trend of the "disease fingerprint" shown by these automated potential morphometric items.

Microgravity environments are known to cause a plethora of stressors to astronauts. Recently, it has become apparent that gut microbiome composition of astronauts is altered following space travel, and this is of significance given the important role of the gut microbiome in human health. Other changes observed in astronauts comprise reduced muscle strength and bone fragility, visual impairment, endothelial dysfunction, metabolic changes, behavior changes due to fatigue or stress and effects on mental well-being. However, the effects of microgravity on angiogenesis, as well as the connection with the gut microbiome are incompletely understood. Here, the potential association of angiogenesis with visual impairment, skeletal muscle and gut microbiome is proposed and explored. Furthermore, metabolites that are effectors of angiogenesis are deliberated upon along with their connection with gut bacterial metabolites. Targeting and modulating the gut microbiome may potentially have a profound influence on astronaut health, given its impact on overall human health, which is thus warranted given the likelihood of increased human activity in the solar system, and the determination to travel to Mars in future missions.

Photosynthesis is a pivotal process that determines the synthesis of carbohydrates required for sustaining growth under normal or stress situation. Stress exposure reduces the photosynthetic potential owing to the excess synthesis of reactive oxygen species that disturb the proper functioning of photosynthetic apparatus. This decreased photosynthesis is associated with disturbances in carbohydrate metabolism resulting in reduced growth under stress. We evaluated the importance of melatonin in reducing heat stress-induced severity in wheat ( Triticum aestivum L.) plants. The plants were subjected to 25 °C (optimum temperature) or 40 °C (heat stress) for 15 days at 6 h time duration and then developed the plants for 30 days. Heat stress led to oxidative stress with increased production of thiobarbituric acid reactive substances (TBARS) and hydrogen peroxide (H 2 O 2 ) content and reduced accrual of total soluble sugars, starch and carbohydrate metabolism enzymes which were reflected in reduced photosynthesis. Application of melatonin not only reduced oxidative stress through lowering TBARS and H 2 O 2 content, augmenting the activity of antioxidative enzymes but also increased the photosynthesis in plant and carbohydrate metabolism that was needed to provide energy and carbon skeleton to the developing plant under stress. However, the increase in these parameters with melatonin was mediated via hydrogen sulfide (H 2 S), as the inhibition of H 2 S by hypotaurine (HT; H 2 S scavenger) reversed the ameliorative effect of melatonin. This suggests a crosstalk of melatonin and H 2 S in protecting heat stress-induced photosynthetic inhibition via regulation of carbohydrate metabolism.

Antibiotic resistance is a major concern given the rapid emergence of multiple-drug-resistant bacteria compared to the discovery of novel antibacterials. An alternative strategy is enhancing the existing available drugs. Nanomedicine has emerged as an exciting area of research, showing promise in the enhanced development of existing antimicrobials. Herein, we synthesized nanocarriers and loaded these with available clinically approved drugs, namely Moxifloxacin and Sulfamethoxazole. Bactericidal activity against Gram-negative ( Serratia marcescens , Pseudomonas aeruginosa , Klebsiella pneumoniae , and Salmonella enterica ) and Gram-positive (methicillin-resistant Staphylococcus aureus , Streptococcus pneumoniae , and Bacillus cereus ) bacteria was investigated. To characterize the nanocarriers and their drug-loaded forms, Fourier-transform infrared spectroscopy, dynamic light scattering, and atomic force microscopy were utilized. Antibacterial assays and hemolysis assays were carried out. Moreover, lactate dehydrogenase assays were performed to determine cytotoxicity against human cells. The results depicted the successful formation of drug-nanocarrier complexes. The potent antibacterial activities of the drug-loaded nanocarriers were observed and were significantly enhanced in comparison to the drugs alone. Hemolysis and cytotoxicity assays revealed minimal or negligible cytotoxic effects against human red blood cells and human cells. Overall, metronidazole-based nanocarriers loaded with Moxifloxacin and Sulfamethoxazole showed enhanced bactericidal effects against multiple-drug-resistant bacteria compared with drugs alone, without affecting human cells. Our findings show that drug-loaded nanocarriers hold promise as potent chemotherapeutic drugs against multiple-drug-resistant bacteria.

The application of 10 µM methyl jasmonate (MeJA) for the protection of wheat ( Triticum aestivum L.) photosystem II (PS II) against heat stress (HS) was studied. Heat stress was induced at 42 °C to established plants, which were then recovered at 25 °C and monitored during their growth for the study duration. Application of MeJA resulted in increased enzymatic antioxidant activity that reduced the content of hydrogen peroxide (H 2 O 2 ) and thiobarbituric acid reactive substances (TBARS) and enhanced the photosynthetic efficiency. Exogenous MeJA had a beneficial effect on chlorophyll fluorescence under HS and enhanced the pigment system (PS) II system, as observed in a JIP-test, a new tool for chlorophyll fluorescence induction curve. Exogenous MeJA improved the quantum yield of electron transport (ET o /CS) as well as electron transport flux for each reaction center (ET 0 /RC). However, the specific energy fluxes per reaction center (RC), i.e., TR 0 /RC (trapping) and DI 0 /RC (dissipation), were reduced by MeJA. These results indicate that MeJA affects the efficiency of PS II by stabilizing the D1 protein, increasing its abundance, and enhancing the expression of the psb A and psb B genes under HS, which encode proteins of the PS II core RC complex. Thus, MeJA is a potential tool to protect PS II and D1 protein in wheat plants under HS and to accelerate the recovery of the photosynthetic capacity.

In the present study, the potential of ethylene as ethephon (an ethylene source) was investigated individually and in combination with split doses of nitrogen (N) and sulfur (S) soil treatments for removal of the damaging effects of salt stress (100 mM NaCl) in mustard ( Brassica juncea L.). Plants were grown with 50 mg N plus 50 mg S kg -1 soil at sowing time and an equivalent dose at 20 days after sowing [N50 + S50] 0d and 20d . Ethephon at 200 μL L ‒1 was applied to combined split doses of N and S with or without NaCl. Plants subjected to NaCl showed a decrease in growth and photosynthetic characteristics as well as N and S assimilation, whereas proline metabolism and antioxidants increased. The application of ethephon to plants grown with split N and S doses significantly enhanced photosynthetic efficiency by increasing the assimilation of N and S, improving the concentration of proline and induction of the antioxidant system with or without NaCl. The regulation of ethylene and/or split forms of N and S application may be potential tools for not just overcoming salt stress effects in this species and in related Brassicaceae but also enhancing their photosynthesis and growth potential through increased nutrient assimilation.

Leucocytes, especially neutrophils featuring pro- and anti-cancerous characteristics, are involved in nearly every stage of tumorigenesis. Phenotypic and functional differences among mature and immature neutrophil fractions are well reported, and their correlation with tumor progression and therapy has emerging implications in modern oncology practices. Technological advancements enabled modern hematology analyzers to generate extended information (research parameters) during complete blood cell count (CBC) analysis. We hypothesized that neutrophil and lymphocyte fractions-related extended differential leucocytes count (DLC) parameters hold superior diagnostic utility over routine modalities. The present study was carried out over a four-and-a-half-year period wherein extended neutrophil (immature granulocyte [IG] and mature neutrophil [NEUT#&]), and lymphocyte (activated/high fluorescence lymphocyte count [HFLC] and resting lymphocyte [LYMP#&]) parameters were challenged over routine neutrophil [NEUT#] and lymphocyte [LYMP#] items in a study population of 1067 hematological neoplasm patients. Extending the classical statistical approaches, machine-learning-backed data visualization was used to explore trends in the study parameters. As a whole, extended neutrophil and lymphocyte count outperformed and was diagnostically more relevant than routine neutrophil and lymphocyte parameters by showing the least difference from their respective (gold-standard) manual DLC counts. The mature neutrophil count was compared to IG, and resting lymphocyte count was compared to HFLC by calling the function 'correlation' as a 'clustering function' for heatmap based visualization. The aforementioned study parameters displayed close clustering (rearrangement) for their respective study items by presenting distinct trends of equally valuable weights (deviated values), advocating fractions-based extended DLC reporting. Importantly, using a Bland and Altman analysis analogously to a manual neutrophil count, the mature neutrophil count [NEUT#&] remained unbiased since a routine neutrophil count [NEUT#] was found to be a negatively biased. The extended DLC-parameter-driven fractions-based reporting has superior diagnostic utility over classical routine approaches; this finding can largely minimize labor-intensive manual DLC practices, especially in hematology-oncology departments.

This study investigated the relationship between six-minute walking test (6MWT) distance walked and preschool-aged children's academic abilities, and behavioral and event-related potentials (ERP) indices of cognitive control. There were 59 children (25 females; age: 5.0 ± 0.6 years) who completed a 6MWT (mean distance: 449.6 ± 82.0 m) to estimate cardiorespiratory fitness. The Woodcock Johnson Early Cognitive and Academic Development Test evaluated academic abilities. A modified Eriksen flanker, hearts and flowers task, and auditory oddball task eliciting ERPs (N2, P3) assessed cognitive control. After adjusting for adiposity, diet, and demographics, linear regressions resulted in positive relationships between 6MWT distance and General Intellectual Ability (β = 0.25, Adj R 2 = 0.04, p = 0.04) and Expressive Language (β = 0.30, Adj R 2 = 0.13, p = 0.02). 6MWT distance was positively correlated with congruent accuracy (β = 0.29, Adj R 2 = 0.18, p < 0.01) and negatively with incongruent reaction time (β = -0.26, Adj R 2 = 0.05, p = 0.04) during the flanker task, and positively with homogeneous (β = 0.23, Adj R 2 = 0.21, p = 0.04) and heterogeneous (β = 0.26, Adj R 2 = 0.40, p = 0.02) accuracy on the hearts and flowers task. Higher fit children showed faster N2 latencies and greater P3 amplitudes to target stimuli; however, these were at the trend level following the adjustment of covariates. These findings indicate that the positive influence of cardiorespiratory fitness on cognitive function is evident in 4-6-year-olds.