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(1) Background: Few studies have been carried out to appraise abamectin toxicity toward Locusta migratoria nymphs. (2) Methods: This study aimed to evaluate the cytotoxic effect of abamectin as an insecticide through examining the changes and damage caused by this drug, in both neurosecretory cells and midgut, using L. migratoria nymphs as a model of the cytotoxic effect. Histopathological change in the brain was examined in both normal and abamectin-treated fifth-instar nymphs. Neurosecretory cells (NSCs) were also examined where there were loosely disintegrated cells or vacuolated cytoplasm. (3) Results: The results showed distinct histological changes in the gastrointestinal tract of L. migratoria nymphs treated with abamectin, with significant cellular damage and disorganization, i.e., characteristic symptoms of cell necrosis, a destroyed epithelium, enlarged cells, and reduced nuclei. The observed biochemical changes included an elevation in all measured oxidative stress parameters compared to untreated controls. The malondialdehyde activities (MDAs) of the treated nymphs had a five- to six-fold increase, with a ten-fold increase in superoxide dismutase (SOD), nine-fold increase in glutathione-S-transferase (GST), and four-fold increase in nitric oxide (NO). (4) Conclusions: To further investigate the theoretical method of action, a molecular docking simulation was performed, examining the possibility that abamectin is an inhibitor of the fatty acid-binding protein Lm-FABP (2FLJ) and that it binds with two successive electrostatic hydrogen bonds.

The release of harmful wastes via different industrial activities is the main cause of heavy metal toxicity. The present study was conducted to assess the effects of heavy metal stress on the plant growth traits, antioxidant enzyme activities, chlorophyll content and proline content of Sesbania sesban with/without the inoculation of heavy-metal-tolerant Bacillus gibsonii and B. xiamenensis. Both PGP strains showed prominent ACC-deaminase, indole acetic acid, exopolysaccharides production and tolerance at different heavy metal concentrations (50–1000 mg/L). Further, in a pot experiment, S. sesban seeds were grown in contaminated and noncontaminated soils. After harvesting, plants were used for the further analysis of growth parameters. The experiment comprised of six different treatments. The effects of heavy metal stress and bacterial inoculation on the plant root length; shoot length; fresh and dry weight; photosynthetic pigments; proline content; antioxidant activity; and absorption of metals were observed at the end of the experiment. The results revealed that industrially contaminated soils distinctly reduced the growth of plants. However, both PGPR strains enhanced the root length up to 105% and 80%. The shoot length was increased by 133% and 75%, and the fresh weight was increased by 121% and 129%. The proline content and antioxidant enzymes posed dual effects on the plants growing in industrially contaminated soil, allowing them to cope with the metal stress, which enhanced the plant growth. The proline content was increased up to 190% and 179% by the inoculation of bacterial strains. Antioxidant enzymes, such as SOD, increased to about 216% and 245%, while POD increased up to 48% and 49%, respectively. The results clearly show that the utilized PGPR strains might be strong candidates to assist S. sesban growth under heavy metal stress conditions. We highly suggest these PGPR strains for further implementation in field experiments.

Purpose Congenital microcephaly (CM) is an important birth defect with long term neurological sequelae. We aimed to perform detailed phenotypic and genomic analysis of patients with Mendelian forms of CM. Methods Clinical phenotyping, targeted or exome sequencing, and autozygome analysis. Results We describe 150 patients (104 families) with 56 Mendelian forms of CM. Our data show little overlap with the genetic causes of postnatal microcephaly. We also show that a broad definition of primary microcephaly —as an autosomal recessive form of nonsyndromic CM with severe postnatal deceleration of occipitofrontal circumference—is highly sensitive but has a limited specificity. In addition, we expand the overlap between primary microcephaly and microcephalic primordial dwarfism both clinically (short stature in >52% of patients with primary microcephaly) and molecularly (e.g., we report the first instance of CEP135 -related microcephalic primordial dwarfism). We expand the allelic and locus heterogeneity of CM by reporting 37 novel likely disease-causing variants in 27 disease genes, confirming the candidacy of ANKLE2, YARS , FRMD4A , and THG1L , and proposing the candidacy of BPTF , MAP1B , CCNH , and PPFIBP1 . Conclusion Our study refines the phenotype of CM, expands its genetics heterogeneity, and informs the workup of children born with this developmental brain defect.

Human serum albumin (HSA) is the frontline antioxidant protein in blood with established anti-inflammatory and anticoagulation functions. Here, we report that COVID-19-induced oxidative stress inflicts structural damages to HSA and is linked with mortality outcome in critically ill patients. We recruited 39 patients who were followed up for a median of 12.5 days (1–35 days), among them 23 had died. Analyzing blood samples from patients and healthy individuals (n=11), we provide evidence that neutrophils are major sources of oxidative stress in blood and that hydrogen peroxide is highly accumulated in plasmas of non-survivors. We then analyzed electron paramagnetic resonance spectra of spin-labeled fatty acids (SLFAs) bound with HSA in whole blood of control, survivor, and non-survivor subjects (n=10–11). Non-survivors’ HSA showed dramatically reduced protein packing order parameter, faster SLFA correlational rotational time, and smaller S/W ratio (strong-binding/weak-binding sites within HSA), all reflecting remarkably fluid protein microenvironments. Following loading/unloading of 16-DSA, we show that the transport function of HSA may be impaired in severe patients. Stratified at the means, Kaplan–Meier survival analysis indicated that lower values of S/W ratio and accumulated H 2 O 2 in plasma significantly predicted in-hospital mortality (S/W≤0.15, 81.8% (18/22) vs. S/W>0.15, 18.2% (4/22), p=0.023; plasma [H 2 O 2 ]>8.6 μM, 65.2% (15/23) vs. 34.8% (8/23), p=0.043). When we combined these two parameters as the ratio ((S/W)/[H 2 O 2 ]) to derive a risk score, the resultant risk score lower than the mean (<0.019) predicted mortality with high fidelity (95.5% (21/22) vs. 4.5% (1/22), log-rank χ 2 =12.1, p=4.9×10 −4 ). The derived parameters may provide a surrogate marker to assess new candidates for COVID-19 treatments targeting HSA replacements and/or oxidative stress.

Endophytes are promising bio-control agents and rich sources of secondary metabolites known for their biological activities. Two medicinal plants, Pelargonium graveolens and Melia azedarach , and two weeds, Chenopodium album and Malva parviflora , were selected to isolate endophytic fungi. Spore suspension of Alternaria alternata (MG786545), Alternaria solani (MG786543), Curvularia lunata (MF113056), Nigrospora sphaerica (MF113055), and Stemphylium sp. endophytes was tested for their pathogenicity to the third-instar larvae of the cotton leaf worm, Spodoptera littoralis (Boisd.) (Lepidoptera: Noctuidae). Two techniques were used: dipping in spore suspension and residual film assay. Secondary metabolites were extracted, and ethyl acetate extracts of A. alternata (MG786545), C. lunata (MF113056), and N. sphaerica (MF113055) were tested for their insecticidal activity by both techniques. C. lunata (MF113056) showed the most potent pathogenicity causing 60% mortality after 7 days by dipping bioassay, while A. solani (MG7865453) and A. alternata (MG786545) caused 40 and 33.3% mortality, respectively. All tested endophytes showed no effect against S. littoralis by residual film method. N. sphaerica ethyl acetate extract activated larval feeding on castor leaves causing 25% mortality by residual film at 2000 mg/l.

Tuberculosis (TB) caused by the bacterial pathogen Mycobacterium tuberculosis (Mtb) remains a threat to mankind, with over a billion of deaths in the last two centuries. Recent advancements in science have contributed to an understanding of Mtb pathogenesis and developed effective control tools, including effective drugs to control the global pandemic. However, the emergence of drug resistant Mtb strains has seriously affected the TB eradication program around the world. There is, therefore, an urgent need to develop new drugs for TB treatment, which has grown researchers’ interest in small molecule-based drug designing and development. The small molecules-based treatments hold significant potential to overcome drug resistance and even provide opportunities for multimodal therapy. In this context, various natural and synthetic flavonoids were reported for the effective treatment of TB. In this review, we have summarized the recent advancement in the understanding of Mtb pathogenesis and the importance of both natural and synthetic flavonoids against Mtb infection studied using in vitro and in silico methods. We have also included flavonoids that are able to inhibit the growth of non-tubercular mycobacterial organisms. Hence, understanding the therapeutic properties of flavonoids can be useful for the future treatment of TB.

Alzheimer’s disease (AD) is a devastating illness with limited therapeutic interventions. The aim of this study is to investigate the pathophysiological mechanisms underlying AD and explore the potential neuroprotective effects of cocoa, either alone or in combination with other nutraceuticals, in an animal model of aluminum-induced AD. Rats were divided into nine groups: control, aluminum chloride (AlCl3) alone, AlCl3 with cocoa alone, AlCl3 with vinpocetine (VIN), AlCl3 with epigallocatechin-3-gallate (EGCG), AlCl3 with coenzyme Q10 (CoQ10), AlCl3 with wheatgrass (WG), AlCl3 with vitamin (Vit) B complex, and AlCl3 with a combination of Vit C, Vit E, and selenium (Se). The animals were treated for five weeks, and we assessed behavioral, histopathological, and biochemical changes, focusing on oxidative stress, inflammation, Wnt/GSK-3β/β-catenin signaling, ER stress, autophagy, and apoptosis. AlCl3 administration induced oxidative stress, as evidenced by elevated levels of malondialdehyde (MDA) and downregulation of cellular antioxidants (Nrf2, HO-1, SOD, and TAC). AlCl3 also upregulated inflammatory biomarkers (TNF-α and IL-1β) and GSK-3β, leading to increased tau phosphorylation, decreased brain-derived neurotrophic factor (BDNF) expression, and downregulation of the Wnt/β-catenin pathway. Furthermore, AlCl3 intensified C/EBP, p-PERK, GRP-78, and CHOP, indicating sustained ER stress, and decreased Beclin-1 and anti-apoptotic B-cell lymphoma 2 (Bcl-2) expressions. These alterations contributed to the observed behavioral and histological changes in the AlCl3-induced AD model. Administration of cocoa, either alone or in combination with other nutraceuticals, particularly VIN or EGCG, demonstrated remarkable amelioration of all assessed parameters. The combination of cocoa with nutraceuticals attenuated the AD-mediated deterioration by modulating interrelated pathophysiological pathways, including inflammation, antioxidant responses, GSK-3β-Wnt/β-catenin signaling, ER stress, and apoptosis. These findings provide insights into the intricate pathogenesis of AD and highlight the neuroprotective effects of nutraceuticals through multiple signaling pathways.

Pseudomonas aeruginosa is an opportunistic pathogen causing severe infection in animals and humans. This study aimed to determine the ecological distribution and prevalence of multidrug-resistant (MDR) P. aeruginosa isolated from dairy cattle, the environment, and workers’ hand swabs. Samples (n = 440) were collected from farms and households (n = 3, each). Rectal swabs, udder skin swabs, milk, workers’ hand swabs, feed, water, water sources, and beddings were collected. Samples were subjected to the bacterial identification of P. aeruginosa via 16S rRNA. Antimicrobial resistance (AMR) was detected either phenotypically using an antibiotic susceptibility test or genotypically with AMR resistance genes (ARGs) such as drfA, sul1, and ermB. P. aeruginosa was detected on dairy farms and households (10.3–57.5%, respectively), with an average of 23.2%. The resistance of dairy farm strains was observed against sulfamethoxazole, imipenem, cefepime, piperacillin–tazobactam, and gentamycin (100%, 72.7%, 72.7%, 68.8%, and 63.3%, respectively). Meanwhile, the resistance of household strains was observed against sulfamethoxazole, imipenem, amoxicillin, gentamicin, cefepime, and erythromycin by 91.3%, 82.6%, 75.4%, 75.4%, 68.1%, and 63.8%, respectively. The susceptibility of farm strains was detected against norfloxacin, ciprofloxacin, and levofloxacin (90.9%, 84.8%, and 72.7%, respectively). Meanwhile, the susceptibility of household strains was detected against ciprofloxacin, amikacin, and norfloxacin (100%, 84.1%, and 72.5%, respectively). About 81.4% of P. aeruginosa strains were MDR. ARGs (drfA, sul1, and ermB) were detected in farm strains (48.5%, 72.7%, and 24.4%, respectively) and household strains (50.7%, 72.5%, and 47.8%, respectively). Almost all P. aeruginosa had MAR over 0.2, indicating repeated application of antibiotics. P. aeruginosa prevalence was fivefold higher in households than on farms. MDR strains were higher amongst household strains than farm strains.

Urinary tract infections (UTIs) are among the most common infections in the pediatric population. Over the last two decades, antibiotic resistance is increasing significantly as extended spectrum beta lactamase (ESBL) producing organisms are emerging. The aim of this study is to provide a comprehensive view of the epidemiologic characteristics of UTIs in hospitalized children, examine the risk factors of UTIs caused by ESBL-producing organisms, and determine the resistance patterns in the isolated organisms over the last 10 years. Retrospective chart review was conducted at two Lebanese medical centers. Subjects were identified by looking at the following ICD-9 discharge codes: \"Urinary tract infection,\" \"UTI,\" \"Cystitis,\" and/or \"Pyelonephritis.\" Children less than 18 years of age admitted for UTI between January 1st, 2001 and December 31st, 2011 were included. Cases whose urine culture result did not meet our definition for UTI were excluded. Chi-square, Fisher's exact test, and multivariate logistic regression were used to determine risk factors for ESBL. Linear regression analysis was used to determine resistance patterns. The study included 675 cases with a median age of 16 months and female predominance of 77.7% (525 cases). Of the 584 cases caused by Escherichia coli or Klebsiella spp, 91 cases (15.5%) were found to be ESBL-producing organisms. Vesico-ureteral reflux and previous antibiotics use were found to be independent risk factors for ESBL-producing E. coli and Klebsiella spp. (p < 0.05). A significant linear increase in resistance to all generations of Cephalosporins (r (2) = 0.442) and Fluoroquinolones (r (2) = 0.698) was found. The recognition of risk factors for infection with ESBL-producing organisms and the observation of increasing overall resistance to antibiotics warrant further studies that might probably lead to new recommendations to guide management of UTIs and antibiotic use in children and adolescents.

The available pharmacotherapies (immunosuppressant therapies) for systemic sclerosis (SSc) are not curative, especially in cases with non-lethal but challenging manifestations or complications of the disease. Fatigue, anxiety, depression, an over-activated hypothalamic-pituitary- adrenal axis (stress axis), and low sleeping quality are the common SSc-induced non-lethal manifestations that need close management. Diaphragmatic breathing tele-exercise (DBTE), as a standalone deep breathing retraining and tele-interventional technique, has not been utilized in the rehabilitation context of non-lethal complications in women with SSc. This online interventional study aimed to explore the efficacy of DBTE in controlling depression, cardiovascular autonomic functions, stress, sleep, and anxiety in women with SSc. This randomized controlled tele-interventional trial recruited 40 non-obese women with SSc (aged > 18 years old) from an Egyptian teaching hospital. Women were randomly assigned to the DBTE group ( = 20) or non-DBTE group ( = 20). The DBTE group underwent 12-week 20-minute morning and evening DBTE sessions (sessions were supervised daily through the Zoom video conference program). The non-DBTE group served as a waitlist control group. The outcomes of this study were diastolic blood pressure (BPD), serum cortisol, the total score of the Hamilton Anxiety Rating Scale (HARS-TS), systolic blood pressure (BPS), the general score of the Pittsburgh Sleep Quality Index (PSQI-GS), pulse rate (PR), the eight-item Patient Health Questionnaire (EI-PHQ ), respiratory rate (RR), and the Visual Analogue Scale of fatigue (VAS-F). In the DBTE group, there were significantly lowered values of PSQI-GS, HARS-TS, EI-PHQ , serum cortisol, VAS-F, and cardiovascular/respiratory autonomic functions (BPS, BPD, RR, and PR). In the non-DBTE group, no significant changes were observed for any variables. It can be concluded from this tele-interventional trial that the 12-week application of DBTE may reduce cortisol, EI-PHQ , PSQI-GS, HARS-TS, BPS, BPD, RR, PR, and VAS-F in women with SSc.