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Background and Objectives: Detecting thyroid tumors depends on histologic characteristics. However, distinguishing malignant from benign thyroid abnormalities may be challenging and contentious, particularly in tumors with a follicular appearance. Therefore, immunohistochemistry might be useful and essential. Immunohistochemical biomarkers, such as human trophoblast cell surface antigen (TROP) and Hector Battifora Mesothelial-1 (HBME-1), have helped diagnose thyroid cancers. In addition, mesothelial cells have an antigen called HBME-1 on their membranes, but its role is unclear. Thyroid epithelial neoplasms have lately been studied, and TROP-2 is a helpful marker of these tumors. Recently, researchers have explored HBME-1 upregulation in benign and malignant thyroid tumors. This research aimed to show that the immunohistochemical biomarkers TROP-2 and HBME-1 might be employed to distinguish malignant from benign follicular-derived thyroid lesions., Materials and Methods: The research consisted of 50 specimens of various follicular thyroid lesions. From October 2018 to March 2021, blocks of follicular thyroid lesions and clinical information were collected from the Pathology Departments of Al-Azhar University Hospitals. Additionally, the HBME-1 and TROP-2 antigens were stained immunohistochemically., Results: Expression of TROP-2 along with HBME-1 distinguished benign from malignant follicular-derived thyroid lesions with respective sensitivities of 74.2 and 87.1% and specificities of 84.2 and 78.9%. Furthermore, positive HBME-1 expression was significantly less prevalent in benign lesions (15.8%) than in malignant lesions (74.2%) (P-value <0.001). Moreover, positive TROP-2 expression was significantly lower in benign lesions (21.1%) than in malignant lesions (87.1%) (P-value <0.001). The P value of <0.001 indicated an extremely strong positive correlation between HBME-1 and TROP-2 expression across all instances investigated., Conclusion: With high sensitivity and specificity, both HBME-1 and TROP-2 are beneficial in identifying thyroid cancer, particularly papillary carcinoma, and separating malignant follicular-derived thyroid lesions from benign ones.

Background and Purpose: Cannabinoids are a promising therapeutic avenue for chronic pain. However, clinical trials often fail to report analgesic efficacy of cannabinoids. Inhibition of voltage gate calcium (Ca v ) channels is one mechanism through which cannabinoids may produce analgesia. We hypothesized that cannabinoids and cannabinoid receptor agonists target different types of Ca v channels through distinct mechanisms., Experimental Approach: Electrophysiological recordings from tsA-201 cells expressing either Ca v 3.2 or Ca v 2.2 were used to assess inhibition by HU-210 or cannabidiol (CBD) in the absence and presence of the CB 1 receptor. Homology modelling assessed potential interaction sites for CBD in both Ca v 2.2 and Ca v 3.2. Analgesic effects of CBD were assessed in mouse models of inflammatory and neuropathic pain., Key Results: HU-210 (1 μM) inhibited Ca v 2.2 function in the presence of CB 1 receptor but had no effect on Ca v 3.2 regardless of co-expression of CB 1 receptor. By contrast, CBD (3 μM) produced no inhibition of Ca v 2.2 and instead inhibited Ca v 3.2 independently of CB 1 receptors. Homology modelling supported these findings, indicating that CBD binds to and occludes the pore of Ca v 3.2, but not Ca v 2.2. Intrathecal CBD alleviated thermal and mechanical hypersensitivity in both male and female mice, and this effect was absent in Ca v 3.2 null mice., Conclusion and Implications: Our findings reveal differential modulation of Ca v 2.2 and Ca v 3.2 channels by CB 1 receptors and CBD. This advances our understanding of how different cannabinoids produce analgesia through action at different voltage-gated calcium channels and could influence the development of novel cannabinoid-based therapeutics for treatment of chronic pain., (© 2023 The Authors. British Journal of Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.)

Background: Transurethral resection (TUR) followed by adjuvant therapy is still the treatment of choice of Non-Muscle-Invasive Bladder Urothelial Carcinoma (NMIBUC). However, recurrence is one of the most troublesome features of these lesions. Early second resection and adjuvant BCG therapy has been shown to improve the outcome., Objective: To evaluate the prognostic value of C-erbB-2 (HER2/neu) expression status in Non-Muscle-Invasive Bladder Urothelial Carcinoma cases, before and after intravesical Bacillus Calmette Guerin (BCG immunotherapy)., Materials and Methods: HER2/neu expression was studied in 120 (Ta-T1) Non-Muscle-Invasive Urothelial Carcinoma cases. The expression was evaluated and compared to the expression after Bacillus Calmette Guerin (BCG) immunotherapy., Results: HER2/neu expression in low and high grade of the Non- Muscle-Invasive Urothelial Carcinoma was (38%) and (83%) respectively. The difference of the expression rates by tumor grade was statistically significant. In recurring lesions post BCG therapy, C-erbB-2 expression was markedly decreased (31.6%) when compared to its expression before therapy (65%)., Conclusions: The HER2/neu expression increased as the tumor grade rose. The reduction in expression following BCG treatment in Non-Invasive transitional cell carcinoma cases could reflect a reduction of the potential malignancy of the tumor.

Cav3.2 channels play an important role in the afferent nociceptive pathway, which is responsible for both physiological and pathological pain transmission. Cav3.2 channels are upregulated during neuropathic pain or peripheral inflammation in part due to an increased association with the deubiquitinase USP5. In this study, we investigated nine naturally occurring flavonoid derivatives which we tested for their abilities to inhibit transiently expressed Cav3.2 channels and their interactions with USP5. Icariside II (ICA-II), one of the flavonols studied, inhibited the biochemical interactions between USP5 and Cav3.2 and concomitantly and effectively blocked Cav3.2 channels. Molecular docking analysis predicts that ICA-II binds to the cUBP domain and the Cav3.2 interaction region. In addition, ICA-II was predicted to interact with residues in close proximity to the Cav3.2 channel's fenestrations, thus accounting for the observed blocking activity. In mice with inflammatory and neuropathic pain, ICA-II inhibited both phases of the formalin-induced nocifensive responses and abolished thermal hyperalgesia induced by injection of complete Freund's adjuvant (CFA) into the hind paw. Furthermore, ICA-II produced significant and long-lasting thermal anti-hyperalgesia in female mice, whereas Cav3.2 null mice were resistant to the action of ICA-II. Altogether, our data show that ICA-II has analgesic activity via an action on Cav3.2 channels.

Artemisia is one of the largest genera in the plant family Asteraceae and has long been used in traditional medicine for its antitussive, analgesic, antihypertensive, antitoxic, antiviral, antimalarial, and anti-inflammatory properties. However, the anti-diabetic activity of Artemisia montana has not been broadly studied. The goal of this study was to determine whether extracts of the aerial parts of A. montana and its main constituents inhibit protein tyrosine phosphatase 1B (PTP1B) and α-glucosidase activities. We isolated nine compounds from A. montana including ursonic acid (UNA) and ursolic acid (ULA), which significantly inhibited PTP1B with IC 50 values of 11.68 and 8.73 μM, respectively. In addition, UNA showed potent inhibitory activity against α-glucosidase (IC 50  = 61.85 μM). Kinetic analysis of PTP1B and α-glucosidase inhibition revealed that UNA was a non-competitive inhibitor of both enzymes. Docking simulations of UNA demonstrated negative binding energies and close proximity to residues in the binding pockets of PTP1B and α-glucosidase. Molecular docking simulations between UNA and human serum albumin (HSA) revealed that UNA binds tightly to all three domains of HSA. Furthermore, UNA significantly inhibited fluorescent AGE formation (IC 50  = 4.16 μM) in a glucose-fructose-induced HSA glycation model over the course of four weeks. Additionally, we investigated the molecular mechanisms underlying the anti-diabetic effects of UNA in insulin-resistant C2C12 skeletal muscle cells and discovered that UNA significantly increased glucose uptake and decreased PTP1B expression. Further, UNA increased GLUT-4 expression level by activating the IRS-1/PI3K/Akt/GSK-3 signaling pathway. These findings clearly demonstrate that UNA from A. montana shows great potential for treatment of diabetes and its complications., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)

Morus bombycis has a long history of usage as a treatment for metabolic diseases, especially, diabetes mellitus (DM). Thus, we aimed to isolate and evaluate bioactive constituents derived from M. bombycis leaves for the treatment of DM. According to bioassay-guided isolation by column chromatography, eight compounds were obtained from M. bombycis leaves: two phenolic compounds, p -coumaric acid ( 1 ) and chlorogenic acid methyl ester ( 2 ), one stilbene, oxyresveratrol ( 3 ), two stilbene dimers, macrourin B ( 4 ) and austrafuran C ( 6 ), one 2-arylbenzofuran, moracin M ( 5 ), and two Diels-Alder type adducts, mulberrofuran F ( 7 ) and chalcomoracin ( 8 ). Among the eight isolated compounds, the anti-DM activity of 3 - 8 (which possess chemotaxonomic significance in Morus species) was evaluated by inhibition of α-glucosidase, protein tyrosine phosphatase 1B (PTP1B), human recombinant aldose reductase (HRAR), and advanced glycation end-product (AGE) formation as well as by scavenging peroxynitrite (ONOO - ), which are crucial therapeutic targets of DM and its complications. Compounds 4 and 6 - 8 significantly inhibited α-glucosidase, PTP1B, and HRAR enzymes with mixed-type and non-competitive-type inhibition modes. Furthermore, the four compounds had low negative binding energies in both enzymes according to molecular docking simulation, and compounds 3 - 8 exhibited strong antioxidant capacity by inhibiting AGE formation and ONOO - scavenging. Overall results suggested that the most active stilbene-dimer-type compounds ( 4 and 6 ) along with Diels-Alder type adducts ( 7 and 8 ) could be promising therapeutic and preventive resources against DM and have the potential to be used as antioxidants, anti-diabetic agents, and anti-diabetic complication agents.

Introduction: The genus Trissolcus includes a number of egg parasitoids that are known to contribute to the control of Halyomorpha halys . The number of progenies, particularly females, is important for the efficient mass rearing of species used in augmentative biological control programs. Cold storage is an important technique for extending the shelf life of natural enemies used in such programs. Methods: We assessed how fecundity, sex ratio, lifespan, and the number of hosts parasitized within 24 h were affected by host density for T. japonicus and T. cultratus when offered fresh H. halys eggs and how these parameters were affected if adult parasitoids were first placed in cold storage (11°C in the dark) for 19 weeks before being used for propagation. Results: The fecundity were 110.2 and 84.2 offspring emerged at 25°C, for parasitoids not placed in cold storage; among the offspring that emerged, 82.6% and 85.6% were female for T. japonicus and T. cultratus , respectively. If first placed in cold storage, T. japonicus and T. cultratus produced 35.1 and 24.6 offspring per female, respectively, although cold storage significantly extended the shelf life. The survival rates of parasitoids that were placed in cold storage were 90.3% and 81.3% for females, and 3.2% and 0.9% for males of T. japonicus and T. cultratus , respectively. The number of hosts parasitized within 24 h was not shown to be density dependent, but it was significantly lower after cold storage. Discussion: This information can be used to estimate the likely production for augmented rearing colonies for use in biological control programs., Competing Interests: GA was employed by The New Zealand Institute for Plant and Food Research Limited. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Li, Chen, Avila, Ali, Tian, Luo, Zhang, Shi and Zhang.)

Glutamate is an important neurotransmitter due to its critical role in physiological and pathological processes. While enzymatic electrochemical sensors can selectively detect glutamate, enzymes cause instability of the sensors, thus necessitating the development of enzyme-free glutamate sensors. In this paper, we developed an ultrahigh sensitive nonenzymatic electrochemical glutamate sensor by synthesizing copper oxide (CuO) nanostructures and physically mixing them with multiwall carbon nanotubes (MWCNTs) onto a screen-printed carbon electrode. We comprehensively investigated the sensing mechanism of glutamate; the optimized sensor showed irreversible oxidation of glutamate involving one electron and one proton, and a linear response from 20 μM to 200 μM at pH 7. The limit of detection and sensitivity of the sensor were about 17.5 μM and 8500 μA·mM -1 ·cm -2 , respectively. The enhanced sensing performance is attributed to the synergetic electrochemical activities of CuO nanostructures and MWCNTs. The sensor detected glutamate in whole blood and urine and had minimal interference with common interferents, suggesting its potential for healthcare applications., Competing Interests: There is no conflict to declare.

Aphelinus mali (Haldeman) (Hymenoptera: Aphelinidae) in China is comprised of two clades (termed, the Shandong and Liaoning clades). In order to clarify the genetic relationship between these two clades, we compared and analyzed the morphological characteristics and the mitochondrial genome of each, and performed a hybridization experiment. Morphological results showed that both males and females of the Liaoning clade were larger than Shandong clade, in terms of whole body, abdominal, wing and antennal lengths, however, there were no significant differences between clades for total length of the middle or hind leg of females. The length of the mitochondrial genome of the Shandong clade was 14415 bp and, for the Liaoning clade, it was 14804 bp. Each contained 31 genes, including 13 protein-encoded genes, 16 tRNA genes, and 2 rRNA genes. The highest AT level among the 13 protein-coding genes for the two clades were the same gene (ATP8) (Shandong clade, 91.52%; Liaoning clade, 90.91%). By hybridization and backcrossing, we found that there was no cross incompatibility between these two clades of A. mali. Our results indicate that the historic geographical isolation between these clades has not yet caused reproductive isolation of these populations, and they belong to the same species., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Su et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Median overall survival is very low in patients with glioblastoma (GBM), largely because these tumors become resistant to therapy. Recently, we found that a decrease in the cytosolic labile iron pool underlies the acquisition of radioresistance. Both cytosolic and mitochondrial iron are important for regulating ROS production, which largely facilitates tumor progression and response to therapy. Here, we investigated the role of the mitochondrial iron transporters mitoferrin-1 (MFRN1) and mitoferrin-2 (MFRN2) in GBM progression. Analysis of The Cancer Genome Atlas database revealed upregulation of MFRN1 mRNA and downregulation of MFRN2 mRNA in GBM tumor tissue compared with non-GBM tissue, yet only the tumor expression level of MFRN1 mRNA negatively correlated with overall survival in patients. Overexpression of MFRN1 in glioma cells significantly increased the level of mitochondrial iron, enhanced the proliferation rate and anchorage-independent growth of these cells, and significantly decreased mouse survival in an orthotopic model of glioma. Finally, MFRN1 overexpression stimulated the upregulation of glutathione, which protected glioma cells from 4-hydroxynonenal-induced protein damage. Overall, these results demonstrate a mechanistic link between MFRN1-mediated mitochondrial iron metabolism and GBM progression. Manipulation of MFRN1 may provide a new therapeutic strategy for improving clinical outcomes in patients with GBM.

Objectives: This study was conducted to assess poultry farmers' knowledge and practices regarding antibiotics, antimicrobial usage (AMU), and antimicrobial resistance (AMR), and to identify the sociodemographic factors of inappropriate use of antibiotics in commercial poultry farms in Bangladesh., Methods: A qualitative survey of 140 farmers in Bangladesh was conducted from March to May 2019. A logistic regression model was used to identify factors associated with the inappropriate use of antibiotics., Results: 47.1% of farmers were unable to explain antibiotics, 42.9% used antibiotics for preventive purposes, 4.3% used them as growth promoters, 25.7% used them as suggested by veterinarians, 42.9% used leftover antibiotics, 50% did not maintain antibiotics residual withdrawal period, and 98.6% did not know about AMR. In bivariable regression analysis, sex and primary occupation of poultry farmers, their knowledge about withdrawal periods for antibiotics, and no contact with veterinary surgeons (VS) were found to be significantly associated with the inappropriate use of antibiotics, while only 'no contact with VS' was identified in multivariable regression analysis., Conclusions: The findings suggest an urgent need to improve understanding of antibiotics and AMR. Adequate supervision by veterinarians would ensure adherence to appropriate AMU patterns, and would limit the misuse of antibiotics and associated AMR development in farms., Competing Interests: The authors declare no conflicts of interest., (© 2023 The Author(s).)

Herbivore-induced plant volatiles (HIPVs) are released by plants upon damaged or disturbance by phytophagous insects. Plants emit HIPV signals not merely in reaction to tissue damage, but also in response to herbivore salivary secretions, oviposition, and excrement. Although certain volatile chemicals are retained in plant tissues and released rapidly upon damaged, others are synthesized de novo in response to herbivore feeding and emitted not only from damaged tissue but also from nearby by undamaged leaves. HIPVs can be used by predators and parasitoids to locate herbivores at different spatial scales. The HIPV-emitting spatial pattern is dynamic and heterogeneous in nature and influenced by the concentration, chemical makeup, breakdown of the emitted mixes and environmental elements (e.g., turbulence, wind and vegetation) which affect the foraging of biocontrol agents. In addition, sensory capability to detect volatiles and the physical ability to move towards the source were also different between natural enemy individuals. The impacts of HIPVs on arthropod natural enemies have been partially studied at spatial scales, that is why the functions of HIPVs is still subject under much debate. In this review, we summarized the current knowledge and loopholes regarding the role of HIPVs in tritrophic interactions at multiple scale levels. Therefore, we contend that closing these loopholes will make it much easier to use HIPVs for sustainable pest management in agriculture.

Cancer immunotherapy shows durable treatment responses and therapeutic benefits compared to other cancer treatment modalities, but many cancer patients display primary and acquired resistance to immunotherapeutics. Immunosuppressive tumor microenvironment (TME) is a major barrier to cancer immunotherapy. Notably, cancer cells depend on high mitochondrial bioenergetics accompanied with the supply of heme for their growth, proliferation, progression, and metastasis. This excessive mitochondrial respiration increases tumor cells oxygen consumption, which triggers hypoxia and irregular blood vessels formation in various regions of TME, resulting in an immunosuppressive TME, evasion of anti-tumor immunity, and resistance to immunotherapeutic agents. In this review, we discuss the role of heme, heme catabolism, and mitochondrial respiration on mediating immunosuppressive TME by promoting hypoxia, angiogenesis, and leaky tumor vasculature. Moreover, we discuss the therapeutic prospects of targeting heme and mitochondrial respiration in alleviating tumor hypoxia, normalizing tumor vasculature, and TME to restore anti-tumor immunity and resensitize cancer cells to immunotherapy., Competing Interests: LZ reports a patent US 11,358,991 B2. LZ has financial interests in HemePro, which has proprietary interests in materials discussed in this manuscript. This conflict of interest is managed with UTD. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be constructed as a potential conflict of interest., (Copyright © 2023 Akter, Salamat, Ali and Zhang.)

Patients with end-stage kidney disease (ESKD) are at increased risk for SARS-CoV-2 infection and its complications compared with the general population. Several studies evaluated the effectiveness of COVID-19 vaccines in the dialysis population but showed mixed results. The aim of this study was to determine the effectiveness of COVID-19 mRNA vaccines against confirmed SARS-CoV-2 infection in hemodialysis (HD) patients in the State of Qatar. We included all adult ESKD patients on chronic HD who had at least one SARS-CoV-2 PCR test done after the introduction of the COVID-19 mRNA vaccines on 24 December 2020. Vaccinated patients who were only tested before receiving any dose of their COVID-19 vaccine or within 14 days after receiving the first vaccine dose were excluded from the study. We used a test-negative case−control design to determine the effectiveness of the COVID-19 vaccination. Sixty-eight patients had positive SARS-CoV-2 PCR tests (cases), while 714 patients had negative tests (controls). Ninety-one percent of patients received the COVID-19 mRNA vaccine. Compared with the controls, the cases were more likely to be older (62 ± 14 vs. 57 ± 15, p = 0.02), on dialysis for more than one year (84% vs. 72%, p = 0.03), unvaccinated (46% vs. 5%, p < 0.0001), and symptomatic (54% vs. 21%, p < 0.0001). The effectiveness of receiving two doses of COVID-19 mRNA vaccines against confirmed SARS-CoV-2 infection was 94.7% (95% CI: 89.9−97.2) in our HD population. The findings of this study support the importance of using the COVID-19 mRNA vaccine in chronic HD patients to prevent SARS-CoV-2 infection in such a high-risk population.

Polymer electrolytes are attractive candidates to boost the application of rechargeable lithium metal batteries. Single-ion conducting polymers may reduce polarization and lithium dendrite growth, though these materials could be mechanically overly rigid, thus requiring ion mobilizers such as organic solvents to foster transport of Li ions. An inhomogeneous mobilizer distribution and occurrence of preferential Li transport pathways eventually yield favored spots for Li plating, thereby imposing additional mechanical stress and even premature cell short circuits. In this work, we explored ceramic-in-polymer hybrid electrolytes consisting of polymer blends of single-ion conducting polymer and PVdF-HFP, including EC/PC as swelling agents and silane-functionalized LATP particles. The hybrid electrolyte features an oxide-rich layer that notably stabilizes the interphase toward Li metal, enabling single-side lithium deposition for over 700 h at a current density of 0.1 mA cm -2 . The incorporated oxide particles significantly reduce the natural solvent uptake from 140 to 38 wt % despite maintaining reasonably high ionic conductivities. Its electrochemical performance was evaluated in LiNi 0.6 Co 0.2 Mn 0.2 O 2 (NMC622)||Li metal cells, exhibiting impressive capacity retention over 300 cycles. Notably, very thin LiNbO 3 coating of the cathode material further boosts the cycling stability, resulting in an overall capacity retention of 78% over more than 600 cycles, clearly highlighting the potential of hybrid electrolyte concepts.

Hypoxia, an oxygen-deprived condition of the tumor, is one of the major reasons for resistance to chemotherapy. Carbonic anhydrases are generally involved in pH homeostasis in normal conditions, but in solid tumors having a strong relation with hypoxia, the carbonic anhydrase IX (CA-IX) enzyme is overexpressed and results in an extracellular acidic environment. For most weakly basic anticancer drugs, including doxorubicin (Dox), the ionization in an acidic environment limits their cellular uptake, and consequently, the tumor exposure to the drug at sub-therapeutic concentration comes out as chemoresistance. Herein, a combined drug delivery system of liposomes and mesoporous silica nanoparticles (MSNPs) was developed for the co-delivery of the CA-IX enzyme inhibitor and Dox in hypoxic condition. The unique structure of MSNPs with higher surface area was utilized for higher drug loading and sustained release of Dox. Additionally, the biocompatible nature of liposomal coating as a second loading site for the CA-IX enzyme inhibitor has provided gatekeeping effects at pore opening to avoid premature drug release. Lipid coated MSNPs as a co-delivery system for Dox and the CA-IX inhibitor have synergistic cytotoxic effects against MDA-MB 231 breast cancer cells in hypoxic conditions. These findings assure the potential of this drug delivery system to overcome hypoxia-related chemoresistance.

Glioblastoma multiforme (GBM) is the most malignant type of brain tumor and has an extremely poor prognosis. Current treatment protocols lack favorable outcomes, and alternative treatments with superior efficacy are needed. In this study, we demonstrate that loading paclitaxel (PTX) in a polymeric, nanoparticulate delivery system is capable of improving its brain accumulation and therapeutic activity. We independently incorporated two different positively charged surface modifiers, poly(amidoamine) (PAMAM) and poly(ethylenimine) (PEI), onto poly(lactic- co -glycolic acid) (PLGA)-polyethylene glycol (PEG), PLGA-PEG, nanoparticles (NPs) using a modified nanoprecipitation technique that assures the formation of nanosized particles while exposing the positively charged polymer on the surface. The prepared NPs underwent comprehensive analyses of their size, charge, in vitro permeability against a BBB cell line, and in vivo biodistribution. Our results demonstrated the successful fabrication of positively charged NPs using PAMAM or PEI. Importantly, significant improvement in brain accumulation (in vivo) was associated with NPs containing PAMAM compared to unmodified NPs or NPs containing PEI. Finally, the efficacy of PAMAM-modified NPs loaded with PTX was evaluated with orthotopic human GBM xenografts in a mouse model, and the data demonstrated improved survival and equivalent safety compared to soluble PTX. Our data substantiate the importance of surface chemistry on the magnitude of NP accumulation in the brain and pave the way for further in vivo evaluation of chemotherapeutic drugs against GBM that have previously been overlooked because of their limited ability to cross the BBB.

Iron is essential for many cellular processes, but cellular iron homeostasis must be maintained to ensure the balance of cellular signaling processes and prevent disease. Iron transport in and out of the cell and cellular organelles is crucial in this regard. The transport of iron into the mitochondria is particularly important, as heme and the majority of iron-sulfur clusters are synthesized in this organelle. Iron is also required for the production of mitochondrial complexes that contain these iron-sulfur clusters and heme. As the principal iron importers in the mitochondria of human cells, the mitoferrins have emerged as critical regulators of cytosolic and mitochondrial iron homeostasis. Here, we review the discovery and structure of the mitoferrins, as well as the significance of these proteins in maintaining cytosolic and mitochondrial iron homeostasis for the prevention of cancer and many other diseases.

Lumpy skin disease (LSD) is an emerging viral disease of cattle that negatively impacts livestock by reducing animals' production and increasing management costs. Like other countries, Bangladesh has also faced the ominous effects of LSD. Because of this pressing concern, the present study was undertaken to determine the attack rate and risk factors along with economic losses of the recent LSD outbreaks from October 2019 to June 2020 in Bangladesh's Mymensingh and Gaibandha districts. A total of 1187 cattle from 150 randomly selected cattle farms were surveyed. The diagnosis was made both clinically and molecularly. The overall attack rate, mortality and case fatality were 34%, 1.10% and 3.23%, respectively, but in calves up to 1 month of age, the attack rate, mortality and case-fatality were 41.6%, 12.5% and 30%, respectively. In risk factor analysis using multiple logistic regression, the following factors were significantly (p < .05) associated with LSD occurrence: no administration of goat pox vaccine, frequency of goat pox vaccination - single dose, introduction of new cattle, land type (low land and medium-high land), use of common syringe and needle, and use of common utensils. The average economic loss per case was 9384.41 BDT (110.40 US $). The higher economic loss per case was accounted in Mymensingh district (10248.91 BDT ≈ 120.58 US $) than Gaibandha district (8211.52 BDT ≈ 96.61 US $). The loss was higher in crossbred cattle (9709.58 BDT ≈ 114.23 US $) compared to indigenous cattle (7595.94 BDT ≈ 89.36 US $). The total estimated annual loss due to LSD in Mymensingh and Gaibandha districts was 7763.25 million BDT (91.33 million US $). In Gaibandha district, the estimated annual loss was 2666.20 million BDT (31.37 million US $) while in Mymensingh district it was 5097.05 million BDT (59.97 million US $). Findings of the study could provide useful epidemiological data with losses incurred due to LSD to the livestock owners, field veterinarians and government-level livestock regulators, which will help to formulate prevention and control strategies and minimize the negative impact of LSD's probable return or spread., (© 2022 Wiley-VCH GmbH.)

Background: Anastatus japonicus Ashmead (Hymenoptera: Eupelmidae) is a solitary egg endoparasitoid that has been studied for inundative biological control of Halyomorpha halys Stål (Hemiptera: Pentatomidae) in China. In this study, we assessed the reproductive attributes and functional response of Anastatus japonicus on a factitious host, Antheraea pernyi (Guérin-Méneville) (Lepidoptera: Anthelidae) at 25 ± 1 °C, 70 ± 5% relative humidity and 16 h:8 h light/dark photoperiod., Results: The mean lifetime fecundity of Anastatus japonicus females was 404.3 progeny produced over an average oviposition period of 42.3 days. The sex ratio of adult progeny was slightly male biased (51.2%), whereas more female progeny were produced before day 20 of a female's life. Single 1-day-old mated Anastatus japonicus females exhibited a type II functional response to increasing host densities (1-50 eggs), with an inverse host density-dependent pattern of percent parasitism. The upper limit to the daily attack rate was estimated as 7.6 Antheraea pernyi eggs. Furthermore, mutual interference among Anastatus japonicus females occurred when increasing densities of parasitoids (1, 2, 4, 8, 16) were exposed to 30 host eggs., Conclusion: Laboratory functional response result revealed that individual Anastatus japonicus might be unable to respond effectively to increasing host density in the field, which could be compensated by releasing larger numbers of wasps. Strong mutual interference among foraging Anastatus japonicus females should be considered in any future inundative biological control programs for the sustainable management of Halyomorpha halys or other host insect pests. © 2022 The Authors. Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry., (© 2022 The Authors. Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.)

Over the years, great attention has been paid to coumarin derivatives, a set of versatile molecules that exhibit a wide variety of biological activities and have few toxic side effects. In this study, we investigated the antidiabetic potential of 6-formyl umbelliferone (6-FU), a novel furanocoumarin isolated from Angelica decursiva . Numerous pharmacological activities of 6-FU have been previously reported; however, the mechanism of its antidiabetic activity is unknown. Therefore, we examined the action of 6-FU on a few candidate-signaling molecules that may underlie its antidiabetic activity, including its inhibition of protein tyrosine phosphatase 1B (PTP1B), α-glucosidase, human recombinant aldose reductase (HRAR), and advanced glycation end-product (AGE) formation (IC 50 = 1.13 ± 0.12, 58.36 ± 1.02, 5.11 ± 0.21, and 2.15 ± 0.13 μM, respectively). A kinetic study showed that 6-FU exhibited mixed-type inhibition against α-glucosidase and HRAR and competitive inhibition of PTP1B. Docking simulations of 6-FU demonstrated negative binding energies and close proximity to residues in the binding pockets of those enzymes. We also investigated the molecular mechanisms underlying 6-FU's antidiabetic effects. 6-FU significantly increased glucose uptake and decreased PTP1B expression in insulin-resistant C2C12 skeletal muscle cells. Moreover, 6-FU (0.8-100 μM) remarkably inhibited the formation of fluorescent AGEs in glucose-fructose-induced human serum albumin glycation over the course of 4 weeks. The findings clearly indicate that 6-FU will be useful in the development of multiple target-oriented therapeutic modalities for the treatment of diabetes and diabetes-related complications.

Although often effective at treating newly diagnosed glioblastoma (GBM), increasing evidence suggests that chemo- and radiotherapy-induced alterations in tumor metabolism promote GBM recurrence and aggressiveness, as well as treatment resistance. Recent studies have demonstrated that alterations in glioma cell metabolism, induced by a switch in the isoform expression of cytochrome c oxidase subunit 4 (COX4), a key regulatory subunit of mammalian cytochrome c oxidase, could promote these effects. To understand how the two COX4 isoforms (COX4-1 and COX4-2) differentially affect glioma metabolism, glioma samples harvested from COX4-1- or COX4-2-overexpressing U251 cells were profiled using Gas chromatography-mass spectrometry GC-MS and Liquid Chromatography - Tandem Mass Spectrometry LC-MS/MS metabolomics platforms. The concentration of 362 metabolites differed significantly in the two cell types. The two most significantly upregulated pathways associated with COX4-1 overexpression were purine and glutathione metabolism; the two most significantly downregulated metabolic pathways associated with COX4-1 expression were glycolysis and fatty acid metabolism. Our study provides new insights into how Cytochrome c oxidase (CcO) regulatory subunits affect cellular metabolic networks in GBM and identifies potential targets that may be exploited for therapeutic benefit.

Introduction: The aim of this study was to formulate the WFNS Spine Committee guidelines on indications, outcomes, and complications of vertebral augmentation in osteoporotic spine fractures., Evidence Acquisition: Computerized literature was searched from 2010 to 2021 using keywords "vertebral augmentation," "osteoporotic fracture," "technique," "surgery," "complication," and "outcome." PubMed yielded 92 articles whereas Google scholar resulted in 120 articles. 29 articles were studied in detail. The studies comprised of seventeen RCT's, two prospective non-randomized studies, three retrospective studies, and seven systematic reviews. The statements were produced to reach a consensus in two separate meetings of WFNS Spine Committee. The statements were voted and reached a positive or negative consensus using Delphi method., Evidence Synthesis: Drafted statements on "Vertebral Augmentation in osteoporotic Spine Fractures" were voted upon by expert panelists in Virtual WFNS Spine Committee Consensus Meetings conducted on January 11, 2021, and February 13, 2021. Statements reaching positive consensus provided the basis for the WFNS guidelines regarding vertebral augmentation in osteoporotic spine fractures., Conclusions: WFNS Spine Committee recommendations on vertebral augmentation in osteoporotic spine fractures are summarized in this article. Vertebral augmentation is superior to conservative treatment for vertebral osteoporotic fractures but has conflicting results on comparison with placebo. Both vertebroplasty and kyphoplasty are equally effective. Most of the studies regarding the efficacy of vertebral augmentation procedures to reduce pain have been largely inconclusive. It is suggested that further high quality, better designed randomized controlled studies are required to establish the role of vertebral augmentation in spine osteoporotic compression fractures.

Due to tremendous design flexibility and ease of light control capability, the photonic crystal fiber offers efficient, flexible, and miniaturized plasmonic biosensors with attractive features. In this work, a high index ( G e O 2 doped silica) core flat fiber is proposed and analyzed for RI sensing ranging from 1.53 to 1.60. A rectangular analyte channel is created on top of a flat fiber to better handle the liquid analyte. To introduce the plasmonic effect, T i O 2 and gold are deposited to the analyte channel. The sensing performance is carried out for two operating wavelengths, as two peaks are obtained for each analyte. The second operating wavelength shows better sensing performance than the first one. However, the proposed sensor offers average wavelength sensitivity of 5000 nm/RIU with a sensor resolution of 2×10 -05 RIU. In addition, the proposed sensor shows identical linearity, which is quite rare in prior sensors. Moreover, the proposed flat sensor provides outstanding detection accuracy of 0.01 n m -1 , detection limit of 79.28 nm, signal to noise ratio of -4.1497 d B , and figure of merit of 50 R I U -1 . Owing to outstanding sensing performance and a unique detection range, this sensor can be effectively used in biological and organic analyte sensing applications.

Antimicrobial resistance (AMR) among foodborne bacteria is a well-known public health problem. A sink survey was conducted to determine the AMR pattern of common foodborne bacteria in cloacal swab of broiler chickens and sewage samples from five wholesale chicken markets of Dhaka city in Bangladesh. Bacteria were identified by culture-based and molecular methods, and subjected to antimicrobial susceptibility testing. Resistance genes were identified by multiplex PCR and sequencing. Multidrug resistance (MDR) was observed in 93.2% of E. coli, 100% of Salmonella spp., and 97.2% of S. aureus from cloacal swab samples. For sewage samples, 80% of E. coli, and 100% of Salmonella and S. aureus showed MDR. Noteworthy, 8.3% of S. aureus from cloacal swab samples showed possible extensively drug resistance. Antimicrobial resistance genes (beta-lactamase-blaTEM, blaSHV; quinolone resistance gene-qnrS) were detected in a number of E. coli and Salmonella isolates from cloacal swab and sewage samples. The methicillin resistance gene (mecA) was detected in 47.2% and 25% S. aureus from cloacal swab and sewage samples, respectively. The findings envisage the potential public health risk and environmental health hazard through spillover of common foodborne MDR bacteria., (© 2022. The Author(s).)

Radiotherapy is an important treatment modality for glioblastoma (GBM), yet the initial effectiveness of radiotherapy is eventually lost due to the development of adaptive radioresistance during fractionated radiation therapy. Defining the molecular mechanism(s) responsible for the adaptive radioresistance in GBM is necessary for the development of effective treatment options. The cellular labile iron pool (LIP) is very important for determining the cellular response to radiation, as it contributes to radiation-induced production of reactive oxygen species (ROS) such as lipid radicals through Fenton reactions. Recently, cytochrome c oxidase (CcO), a mitochondrial heme-containing enzyme also involved in regulating ROS production, was found to be involved in GBM chemoresistance. However, the role of LIP and CcO in GBM radioresistance is not known. Herein, we tested the hypothesis that CcO-mediated alterations in the level of labile iron contribute to adaptive radioresistance. Using an in vitro model of GBM adaptive radioresistance, we found an increase in CcO activity in radioresistant cells that associated with a decrease in the cellular LIP, decrease in lipid peroxidation, and a switch in the CcO subunit 4 (COX4) isoform expressed, from COX4-2 to COX4-1. Furthermore, knockdown of COX4-1 in radioresistant GBM cells decreased CcO activity and restored radiosensitivity, whereas overexpression of COX4-1 in radiosensitive cells increased CcO activity and rendered the cells radioresistant. Overexpression of COX4-1 in radiosensitive cells also significantly reduced the cellular LIP and lipid peroxidation. Pharmacological manipulation of the cellular labile iron level using iron chelators altered CcO activity and the radiation response. Overall, these results demonstrate a mechanistic link between CcO activity and LIP in GBM radioresistance and identify the CcO subunit isoform switch from COX4-2 to COX4-1 as a novel biochemical node for adaptive radioresistance of GBM. Manipulation of CcO and the LIP may restore the sensitivity to radiation in radioresistant GBM cells and thereby provide a strategy to improve therapeutic outcome in patients with GBM., (Copyright © 2022. Published by Elsevier Inc.)

Plants have evolved a number of different chemical defenses, covering nearly all classes of (secondary) metabolites, that represent a major barrier to herbivory: some are constitutive; others are induced after attacks from herbivores (HIPVs) and may elicit the attraction of predators and parasitoids. Here, we studied how the female solitary endoparasitoid Aphelinus varipes responds to plant and host aphid volatiles in a series of experiments on five commercially important vegetables that were either healthy or infested with the aphid Myzus persicae : chili pepper, eggplant, crown daisy, Chinese cabbage and cabbage. The results for the olfactory responses of A. varipes showed that the presence of M. persicae increased the attraction of the endoparasitoid to the infested plants. In a second experiment, volatiles from highly attractive and repellent plants were obtained via headspace collection to investigate volatiles from healthy and aphid-damaged plants. The results for the differences in volatile profiles in response to aphid infestation in chili pepper cultivar were dominated by the volatile blends, including α-pinene, decanal and phthalic acid, while in cabbage they were dominated by isophorone. Moreover, when HIPVs with different concentrations were compared, α-pinene at a dose rate of 100 ng/μL attracted more parasitoids, and the comparison was useful to understand the mechanisms of plant secondary volatiles during aphid infestation and to provide new resources to control this insect pest. Overall our study shows how HIPVs can bolster tritrophic interactions by enhancing the attractiveness of parasitoids.

Background: There is a lack of robust epidemiological information on portal vein thrombosis (PVT) in Qatar. This study aimed to describe the risk factors, clinical presentation, diagnosis, and treatment outcomes of PVT in patients with and without liver cirrhosis admitted to Hamad General Hospital., Methods: This retrospective observational study was conducted at Hamad General Hospital, Doha, Qatar. Consecutive patients with PVT between January 1, 2015 and December 31, 2019 were included in this study., Results: We included 363 cases representing 0.05% of all inpatients admitted to our hospital during the study period. Their mean age was 47.79 ± 14.48 years. There were 258 (71.1%) males and 105 (28.9%) females. Abdominal pain was the most common presenting symptom (160 (44.1%)), while splenomegaly was the most common presenting sign (158 (43.5%)). Liver cirrhosis was the most frequent risk factor for PVT (147 (40.5%)), while no risk factors were identified in 49 (13.5%) patients. Anticoagulant therapy was given to 171/207 (82.6%) patients with acute PVT and 19/156 (12.2%) patients with chronic PVT. The options used for anticoagulation treatment were: low molecular weight heparin (LMWH) or unfractionated heparin alone, LMWH/unfractionated heparin followed by warfarin, and direct-acting oral anticoagulants (rivaroxaban). Out of the 262 patients in whom PVT recanalization was assessed, 43.8% of the cases had recanalization after anticoagulation treatment, while 12.6% of them had spontaneous recanalization without such therapy. A comparison between different anticoagulants used in this study showed no significant difference in the effectiveness of the three regimens used. The 30-day mortality was recorded for 71 patients (19.5%). The major risk factors for 30-day mortality were: age over 45 years, male sex, hepatic failure, malignancies, and bilirubin > 34 µmol/L., Conclusion: PVT is a rare clinical entity in Qatar with liver cirrhosis being the most common risk factor. Early administration of anticoagulation therapy is associated with a significant recanalization, while age > 45 years, male sex, hepatic failure, malignancies, and bilirubin > 34 µmol/L are independent risk factors for 30-day mortality., Competing Interests: None to declare., (Copyright 2022, Khan et al.)

This present work is designed to evaluate the anti-diabetic potential of 22 ginsenosides via the inhibition against rat lens aldose reductase (RLAR), and human recombinant aldose reductase (HRAR), using DL -glyceraldehyde as a substrate. Among the ginsenosides tested, ginsenoside Rh2, (20 S ) ginsenoside Rg3, (20 R ) ginsenoside Rg3, and ginsenoside Rh1 inhibited RLAR significantly, with IC 50 values of 0.67, 1.25, 4.28, and 7.28 µM, respectively. Moreover, protopanaxadiol, protopanaxatriol, compound K, and ginsenoside Rh1 were potent inhibitors of HRAR, with IC 50 values of 0.36, 1.43, 2.23, and 4.66 µM, respectively. The relationship of structure-activity exposed that the existence of hydroxyl groups, linkages, and their stereo-structure, as well as the sugar moieties of the ginsenoside skeleton, represented a significant role in the inhibition of HRAR and RLAR. Additional, various modes of ginsenoside inhibition and molecular docking simulation indicated negative binding energies. It was also indicated that it has a strong capacity and high affinity to bind the active sites of enzymes. Further, active ginsenosides suppressed sorbitol accumulation in rat lenses under high-glucose conditions, demonstrating their potential to prevent sorbitol accumulation ex vivo. The findings of the present study suggest the potential of ginsenoside derivatives for use in the development of therapeutic or preventive agents for diabetic complications.

Insect short neuropeptide F (sNPF), an ortholog of prolactin-releasing peptide of invertebrates, regulates diverse biological processes, including feeding, olfaction, locomotion, and sleep homeostasis in insects. However, its function is still unclear in an important model insect and agricultural pest, the pea aphid ( Acyrthosiphon pisum ). Here, we investigated short neuropeptide F ( ApsNPF ) and its receptor ( ApsNPFR ) in A. pisum . The sNPF gene contains three exons and two long introns. In addition, the genome contains a single sNPF receptor with seven transmembrane domains. Stage- and tissue-specific transcript profiling by qRT-PCR revealed that ApsNPF and ApsNPFR were mainly expressed in the central nervous system. The receptor was also detected in antennae, midgut, and integument. The highest expression levels were found in first instar nymphs compared to other developmental stages. Besides, the starvation-induced pattern indicated that the sNPF network depends on the nutritional state of the insect. An electrical penetration graph showed that probing time and phloem duration of A. pisum on broad bean plants decreased in response to dssNPF and dssNPFR in RNAi assays. sNPF silencing reduced the number of nymphs per female but not aphid survival. We believe that our results advance in-depth knowledge of the sNPF/sNPFR signaling cascade and its place in regulating feeding behavior in insects. In turn, it may contribute to the potential design of new strategies to control aphids, with a focus on the sNPF system.

Glioblastoma (GBM) is a fatal disease with recurrences often associated with radioresistance. Although often effective at treating newly diagnosed GBM, increasing evidence suggests that radiotherapy-induced alterations in tumor metabolism promote GBM recurrence and aggressiveness. Using isogenic radiosensitive and radioresistant GBM cell lines and patient-derived xenolines, we found that acquired radioresistance is associated with a shift from a glycolytic metabolism to a more oxidative metabolism marked by a substantial increase in the activity of the mitochondrial respiratory chain complex cytochrome c oxidase (CcO). This elevated CcO activity was associated with a switch in the isoform expression of the CcO regulatory subunit COX4, from COX4-2 to COX4-1, assembly of CcO-containing mitochondrial supercomplexes (SCs), and reduced superoxide (O 2 •- ) production. Overexpression of COX4-1 in the radiosensitive cells was sufficient to promote the switch from glycolytic to oxidative metabolism and the incorporation of CcO into SCs, with a concomitant reduction in O 2 •- production. Conversely, silencing of COX4-1 expression in normally radioresistant cells reduced CcO activity, promoted the disassembly of mitochondrial SCs, and increased O 2 •- production. Additionally, gain or loss of COX4-1 expression was sufficient to induce the radioresistant or radiosensitive phenotype, respectively. Our results demonstrate that COX4-1 promotes SC assembly in GBM cells, and SC assembly may in turn regulate the production of reactive oxygen species and thus the acquisition of radioresistance in GBM., Competing Interests: Conflict of Interest: The authors declare that no competing interests exist., (Copyright: © 2022 Oliva et al.)

Nup358, a protein of the nuclear pore complex, facilitates a nuclear positioning pathway that is essential for many biological processes, including neuromuscular and brain development. Nup358 interacts with the dynein adaptor Bicaudal D2 (BicD2), which in turn recruits the dynein machinery to position the nucleus. However, the molecular mechanisms of the Nup358/BicD2 interaction and the activation of transport remain poorly understood. Here for the first time, we show that a minimal Nup358 domain activates dynein/dynactin/BicD2 for processive motility on microtubules. Using nuclear magnetic resonance titration and chemical exchange saturation transfer, mutagenesis, and circular dichroism spectroscopy, a Nup358 α-helix encompassing residues 2162-2184 was identified, which transitioned from a random coil to an α-helical conformation upon BicD2 binding and formed the core of the Nup358-BicD2 interface. Mutations in this region of Nup358 decreased the Nup358/BicD2 interaction, resulting in decreased dynein recruitment and impaired motility. BicD2 thus recognizes Nup358 through a 'cargo recognition α-helix,' a structural feature that may stabilize BicD2 in its activated state and promote processive dynein motility., Competing Interests: JG, HC, MA, XZ, ED, JZ, KT, SS, CW No competing interests declared, (© 2022, Gibson et al.)

The purpose of the study was to develop an SNEDDS to improve the solubility and bioavailability of pitavastatin. The solubility of pitavastatin in different oils, surfactants, and co-surfactants was determined and a pseudo-ternary phase diagram was constructed. The SNEDDS was characterized by zeta-sizer, zeta-potential, FTIR, DSC, and TGA. Release and permeation of pitavastatin from the SNEDDS was studied for 12 and 24 h, respectively. The lipolysis test, RBC lysis, effect on lipid profile, and pharmacokinetics were studied. The SPC3 formulation showed a 104 ± 1.50 nm particle size, a 0.198 polydispersity index (PDI), and a -29 zeta potential. FTIR, DSC, and TGA showed the chemical compatibility and thermal stability. The release and permeation of pitavastatin from SPC3 was 88.5 ± 2.5% and 96%, respectively. In the lipolysis test, the digestion of SPC3 yielded a high amount of pitavastatin and showed little RBC lysis. The lipid profile suggested that after 35 days of administration of the SNEDDS, there was a marked decrease in TC, LDL, and triglyceride levels. The SNEDDS of SPC3 showed an 86% viability of Caco-2 cells. Pharmacokinetics of SPC3 showed improved values of C max , T max , half-life, MRT, AUC, and AUMC compared to the reference formulation. Our study demonstrated that the SNEDDS effectively enhanced the solubility and bioavailability of a BCS class II drug.

Cav3.2 calcium channels are important mediators of nociceptive signaling in the primary afferent pain pathway, and their expression is increased in various rodent models of chronic pain. Previous work from our laboratory has shown that this is in part mediated by an aberrant expression of deubiquitinase USP5, which associates with these channels and increases their stability. Here, we report on a novel bioactive rhodanine compound (II-1), which was identified in compound library screens. II-1 inhibits biochemical interactions between USP5 and the Cav3.2 domain III-IV linker in a dose-dependent manner, without affecting the enzymatic activity of USP5. Molecular docking analysis reveals two potential binding pockets at the USP5-Cav3.2 interface that are distinct from the binding site of the deubiquitinase inhibitor WP1130 (a.k.a. degrasyn). With an understanding of the ability of some rhodanines to produce false positives in high-throughput screening, we have conducted several orthogonal assays to confirm the validity of this hit, including in vivo experiments. Intrathecal delivery of II-1 inhibited both phases of formalin-induced nocifensive behaviors in mice, as well as abolished thermal hyperalgesia induced by the delivery of complete Freund's adjuvant (CFA) to the hind paw. The latter effects were abolished in Cav3.2 null mice, thus confirming that Cav3.2 is required for the action of II-1. II-1 also mediated a robust inhibition of mechanical allodynia induced by injury to the sciatic nerve. Altogether, our data uncover a novel class of analgesics─well suited to rapid structure-activity relationship studies─that target the Cav3.2/USP5 interface.

Background: Antimicrobial resistance (AMR) has become an emerging threat worldwide, and developing countries such as Bangladesh are considered to be at greater risk of disseminating the resistant bacteria between human-animal interfaces., Objectives: The present study was carried out to determine the prevalence and AMR profile of Escherichia coli isolated from broiler chickens, the environment, and farmworkers. This study also aimed to identify the risk factors associated with multidrug-resistant (MDR) E. coli infection in broiler chickens. In addition, the presence of carbapenem resistance gene (NDM-1) was assessed., Methods: A total of 114 E. coli isolates, recovered from 150 samples (cloacal swabs = 50, farm sewage = 50, and hand washed water of farmworkers = 50) collected from 50 broiler farms, were identified by biochemical examination and polymerase chain reaction (PCR) assay. Antimicrobial susceptibility test was performed for 10 antibiotics by disk diffusion test. Carbapenem resistance gene (NDM-1) was detected by PCR. Risk factors were identified through multivariable logistic regression., Results: The highest prevalence of E. coli was recorded in broiler chickens (86%) and the lowest in farmworkers (66%). For MDR E. coli infection, 'winter season', 'absence of specific shoes for staff', and 'use of antibiotics without veterinarian's prescription' were the significant risk factors. High resistance of the E. coli isolates was observed against levofloxacin (81.6%), doxycycline (78.1%), cefotaxime (78.1%), and ciprofloxacin (70.2%). About 76% of the isolates demonstrated MDR. None of the isolates were positive for the NDM-1 gene., Conclusions: The high level and similar pattern of antibiotic resistance in E. coli isolates from broiler chickens, farmworkers, and sewage in poultry farms indicates a good possibility of spreading the antibiotic-resistant E. coli in such settings., (© 2021 The Authors. Veterinary Medicine and Science published by John Wiley & Sons Ltd.)

High-resolution experiments revealed that a single myosin-Va motor can transport micron-sized cargo on actin filaments in a stepwise manner. However, intracellular cargo transport is mediated through the dense actin meshwork by a team of myosin Va motors. The mechanism of how motors interact mechanically to bring about efficient cargo transport is still poorly understood. This study describes a stochastic model where a quantitative understanding of the collective behaviors of myosin Va motors is developed based on cargo stiffness. To understand how cargo properties affect the overall cargo transport, we have designed a model in which two myosin Va motors were coupled by wormlike chain tethers with persistence length ranging from 10 to 80 nm and contour length from 100 to 200 nm, and predicted distributions of velocity, run length, and tether force. Our analysis showed that these parameters are sensitive to both the contour and persistence length of cargo. While the velocity of two couple motors is decreased compared to a single motor (from 531 ± 251 nm/s to as low as 318 ± 287 nm/s), the run length (716 ± 563 nm for a single motor) decreased for short, rigid tethers (to as low as 377 ± 187 μm) and increased for long, flexible tethers (to as high as 1.74 ± 1.50 μm). The sensitivity of processive properties to tether rigidity (persistence length) was greatest for short tethers, which caused the motors to exhibit close, yet anti-cooperative coordination. Motors coupled by longer tethers stepped more independently regardless of tether rigidity. Therefore, the properties of the cargo or linkage must play an essential role in motor-motor communication and cargo transport., Competing Interests: The authors declare that they have no conflicting interests., (© 2021 The Authors.)

Glioblastoma remains the deadliest form of brain cancer, largely because these tumors become resistant to standard of care treatment with radiation and chemotherapy. Intracellular production of reactive oxygen species (ROS) is necessary for chemo- and radiotherapy-induced cytotoxicity. Here, we assessed whether antioxidant catalase (CAT) affects glioma cell sensitivity to temozolomide and radiation. Using The Cancer Genome Atlas database, we found that CAT mRNA expression is upregulated in glioma tumor tissue compared with non-tumor tissue, and the level of expression negatively correlates with the overall survival of patients with high-grade glioma. In U251 glioma cells, CAT overexpression substantially decreased the basal level of hydrogen peroxide, enhanced anchorage-independent cell growth, and facilitated resistance to the chemotherapeutic drug temozolomide and ionizing radiation. Importantly, pharmacological inhibition of CAT activity reduced the proliferation of glioma cells isolated from patient biopsy samples. Moreover, U251 cells overexpressing CAT formed neurospheres in neurobasal medium, whereas control cells did not, suggesting that the radio- and chemoresistance conferred by CAT may be due in part to the enrichment of glioma stem cell populations. Finally, CAT overexpression significantly decreased survival in an orthotopic mouse model of glioma. These results demonstrate that CAT regulates chemo- and radioresistance in human glioma.

In the present study, we investigated the structure-activity relationship of naturally occurring hesperetin derivatives, as well as the effects of their glycosylation on the inhibition of diabetes-related enzyme systems, protein tyrosine phosphatase 1B (PTP1B) and α-glycosidase. Among the tested hesperetin derivatives, hesperetin 5- O -glucoside, a single-glucose-containing flavanone glycoside, significantly inhibited PTP1B with an IC 50 value of 37.14 ± 0.07 µM. Hesperetin, which lacks a sugar molecule, was the weakest inhibitor compared to the reference compound, ursolic acid (IC 50 = 9.65 ± 0.01 µM). The most active flavanone hesperetin 5- O -glucoside suggested that the position of a sugar moiety at the C-5-position influences the PTP1B inhibition. It was observed that the ability to inhibit PTP1B is dependent on the nature, position, and number of sugar moieties in the flavonoid structure, as well as conjugation. In the kinetic study of PTP1B enzyme inhibition, hesperetin 5- O -glucoside led to mixed-type inhibition. Molecular docking studies revealed that hesperetin 5- O -glucoside had a higher binding affinity with key amino residues, suggesting that this molecule best fits the PTP1B allosteric site cavity. The data reported here support hesperetin 5- O -glucoside as a hit for the design of more potent and selective inhibitors against PTP1B in the search for a new anti-diabetic treatment.

Background: Pink bollworm, Pectinophora gossypiella (Lepidoptera: Gelechiidae) is a native pest of Asia and preferably invasion on cotton (Gossypium hirsutum L.) crop as a commendatory host plant. Commercially, G. hirsutum is known as white gold and is an important cash crop all over the globe. Limited studies were published to focus on certain dietary compositions against different cotton pests. Therefore, the present study was undertaken in the laboratory under controlled conditions (temperature: 27 ± 2°C and relative humidity: 60 ± 10%) to determine the impact of three different treatment diets (wheat germ meal, okra, and chickpea) on the biological aspects (lifetime, developmental period) of P. gossypiella., Results: Results revealed that the shortest larval time of P. gossypiella was observed on the okra feed diet while the longest period was recorded on the wheat germ diet. Meanwhile, the pupation delay was noted on the wheat germ diet. The dietary influence was also observed on adult stages of female and male P. gossypiella (43.00 and 37.50 days respectively) and compared with a standard diet (56.50 and 52.50 days respectively). Furthermore, larval weighed more on the okra and chickpea diet followed by the wheat germ diet, whereas highest pupal weight was observed on the standard diet followed by the chickpea diet and okra diet., Conclusion: Developmental parameters were significantly variant across all treatment diets, whereas the higher significant difference was reported on the okra diet. Therefore, the existing data of this study offers fruitful interventions for the future as a modified diet for large-scale and rapid mass production of P. gossypiella larvae., Competing Interests: The authors have declared that no competing interests exist.

Praying mantises are distributed all over the world. Though some Mantodea mitogenomes have been reported, an evolutionary genomic and phylogenetic analysis study lacks the latest taxonomic system. In the present study, four new mitogenomes were sequenced and annotated. Deroplatys truncate, D. lobate, Amorphoscelis chinensis and Macromantis sp. belong to Deroplatyidae, Amorphoscelidae and Photinaidae family, respectively. Our results indicated that the ATP8 gene may be lost in D. truncate and D. lobata mt genome, and four tRNA genes have not been found in D. truncate, D. lobata and Macromantis sp. A dN/dS pair analysis was conducted and it was found that all genes have evolved under purifying selection. Furthermore, we tested the phylogenetic relationships between the eight families of the Mantodea, including 35 species of praying Mantis. Based on the complete mitochondrial genome data, it was also suggested as sister to Deroplatyidae + Mantidae, Metallyticus sp., the only representative of Metallyticidae, is sister to the remaining mantises. Our results support the taxonomic system of Schwarz and Roy and are consistent with previous studies., Competing Interests: Co-Author Guy Smagghe is editor for the PLoS one journal and this does not alter the authors’ adherence to all PLoS one Policies on sharing data and materials.

Cassia obtusifolia L., of the Leguminosae family, is used as a diuretic, laxative, tonic, purgative, and natural remedy for treating headache, dizziness, constipation, tophobia, and lacrimation and for improving eyesight. It is commonly used in tea in Korea. Various anthraquinone derivatives make up its main chemical constituents: emodin, chrysophanol, physcion, obtusifolin, obtusin, au rantio-obtusin, chryso-obtusin, alaternin, questin, aloe-emodin, gluco-aurantio-obtusin, gluco-obtusifolin, naphthopyrone glycosides, toralactone-9-β-gentiobioside, toralactone gentiobioside, and cassiaside. C . obtusifolia &nbsp; L . possesses a wide range of pharmacological properties (e.g., antidiabetic, antimicrobial, anti-inflammatory, hepatoprotective, and neuroprotective properties) and may be used to treat Alzheimer's disease, Parkinson's disease, and cancer. In addition, C . obtusifolia L. contributes to histamine release and antiplatelet aggregation. This review summarizes the botanical, phytochemical, and pharmacological features of C . obtusifolia and its therapeutic uses.

Direct-acting antivirals (DAAs) are used for hepatitis C virus (HCV) treatment. However, treatment failure and hepatocellular carcinoma (HCC) development following treatment was reported. In this study, we assessed the role of serum vitamin D, interleukin 13 (IL-13), and microRNA-135a in the prediction of treatment failure with DAA and HCC development among Egyptian HCV-infected patients. A total of 950 patients with HCV-related chronic liver disease underwent DAA treatment. Before DAAs, serum vitamin D and IL-13 were determined by ELISA, and gene expression of miRNA-135a was assessed in serum by real-time PCR. The predictive abilities of these markers were determined using the receiver operating characteristic (ROC) curve. Sustained virological response (SVR) was achieved in 92.6% of HCV-infected patients (responders). High viral load, IL-13, miRNA-135a, and low vitamin D levels were associated with treatment failure and HCC development. HCC development was recorded in non-responders, but not in the responders (35.7% vs. 0% p < 0.001). In conclusion: serum IL-13, Vitamin D, and miRNA-135a could be potential biomarkers in monitoring DAA treatment and HCC prediction. DAAs-induced SVR may decrease the incidence of HCC.

Nitrogen (N) is the prime nutrient for crop production and carbon-based functions associated with soil quality. The objective of our study (2012 to 2019) was to evaluate the impact of variable rates of N fertilization on soil organic carbon (C) pools and their stocks, stratification, and lability in subtropical wheat (Triticum aestivum)-mungbean (Vigna radiata)-rice (Oryza sativa L) agroecosystems. The field experiment was conducted in a randomized complete block design (RCB) with N fertilization at 60, 80, 100, 120, and 140% of the recommended rates of wheat (100 kg/ha), mungbean (20 kg/ha), and rice (80 kg/ha), respectively. Composite soils were collected at 0-15 and 15-30 cm depths from each replicated plot and analyzed for microbial biomass (MBC), basal respiration (BR), total organic C (TOC), particulate organic C (POC), permanganate oxidizable C (POXC), carbon lability indices, and stratification. N fertilization (120 and 140%) significantly increased the POC at both depths; however, the effect was more pronounced in the surface layer. Moreover, N fertilization (at 120% and 140%) significantly increased the TOC and labile C pools when compared to the control (100%) and the lower rates (60 and 80%). N fertilization significantly increased MBC, C pool (CPI), lability (CLI), and management indices (CMI), indicating improved and efficient soil biological activities in such systems. The MBC and POC stocks were significantly higher with higher rates of N fertilization (120% and 140%) than the control. Likewise, higher rates of N fertilization significantly increased the stocks of labile C pools. Equally, the stratification values for POC, MBC, and POXC show evidence of improved soil quality because of optimum N fertilization (120-140%) to maintain and/or improve soil quality under rice-based systems in subtropical climates., Competing Interests: No.

Background: Early life nutrition plays a critical role in the development of better health and nutrition in adulthood. However, assessing the nutritional status of Bangladeshi children and adolescents through measurement of body composition using skinfold thickness is barely studied. The current study aims to determine children's body composition and nutritional status, and contributing factors among children aged 2 to 15 years in the northern part of Bangladesh., Methods: This is a descriptive cross-sectional study done in Bangladesh. Anthropometric methods, including multiple skinfold thickness and basic anthropometric and socio-demographic characteristics, were used. Body composition was calculated from multiple skinfold thicknesses using the standard regression equation. Nutritional status was measured using Z score according to WHO 2007 reference standard. A total of 330 children from Naogaon, Bogra and Kurigram districts in Bangladesh were examined from April 2019 to September 2019., Results: The Nutritional status of 2-15 years old child is exceedingly poor in the northern part of Bangladesh. Fat mass and fat-free mass were higher among children from Kurigram district than from Bogra and Naogaon district. Body fat percentages and arm fat area were greater among female children than males. The overall prevalence of stunting, underweight and wasting was around 25%, 32% and 29%, respectively, and the rate was higher among girls and children aged 2-5 years. The average SD score for weight-for-age, height-for-age, and BMI-for-age was -1.295, -0.937 and -1.009. The median weight-for-age and height-for-age Z scores of boys and girls were below the WHO reference percentile rank. Girls were twice (OR:1.951, CI:1.150-3.331) as likely to suffer from being underweight than boys. Children who don't practice handwashing are three times (OR:3.531, CI:1.657-7.525) more likely to be underweight. Children become underweight and stunted when their family income is not sufficient to maintain their nutritional requirements., Conclusions: The children of the three northern districts had a poor nutritional status, and family income was the potential contributing factor. Therefore, interventions like the promotion of income-generating activities and integrated approaches to ensuring food diversification could be an option to address the nutritional problem of children of the three northern districts of Bangladesh., Competing Interests: The authors have declared that no competing interests exist.

This paper reports the comparative growth, nutritional performance, and morphometric variation between wild and hatchery-reared juvenile mud crabs ( Scylla olivacea) in earthen ponds. The crabs were fed daily with boiled tilapia paste at a feeding rate of 5-8% body weight for the first two weeks, followed by feeding with chopped eviscerated tilapia until termination of the experiment. Selected phenotypic trains, including carapace width (CW), carapace length (CL) and abdominal width (AW), were measured weekly. The protein content of the muscle (21.13%), gill (13.51%) and egg (43.28%) were significantly higher in the hatchery-sourced compared to wild female crabs (muscle = 19.15%; gill = 10.09%; egg = 38.15%). Likewise, the hatchery sourced crabs exhibited higher lipid content in the muscle (2.45-2.51%) and eggs (7.51%) compared to the wild counterparts (muscle = 1.45-1.47%; egg = 6.15%). These findings suggested a superior nutritional quality of the hatchery-reared compared to the wild-sourced crabs. Although some selected phenotypic traits did not vary among the wild and hatchery-reared crabs (p < 0.05), their survival rates varied significantly depending on the stocking density (p < 0.05). Overall, the findings suggest that the growth characteristics of the hatchery produced and wild-sourced crab were similar, which will help to remove the misconception among the crab farmers about the hatchery seeds and promote diversification of the crab production system for long-term sustainability., Competing Interests: The authors declare no conflict of interest., (© 2021 Published by Elsevier Ltd.)

The immediate release of chemotherapeutics at the target site, along with no premature release in circulation is always challenging. The purpose of this study was to develop a stimuli responsive drug delivery system, composed of lipid supported mesoporous silica nanoparticles (MSNPs) for triggered drug release at the target site and simultaneously avoiding the premature release. MSNPs with a higher drug loading capacity and very slow release were designed so as to enhance release by FDA approved US-irradiation. Doxorubicin, as a model drug, and perfluoropentane (PFP) as a US responsive material, were entrapped in the porous structure of MSNPs. Lipid coating enhanced the cellular uptake and in addition provided a gatekeeping effect at the pore opening to reduce premature release. The mechanical and thermal effects of US induced the conversion of liquid PFP to a gaseous form that was able to rupture the lipid layer, resulting in triggered drug release. The prolonged stability profile and non-toxic behavior made them suitable candidate for the delivery of anticancer drugs. This smart system, with the abilities of better cellular uptake and higher cytotoxic effects on US-irradiation, would be a good addition to the applied side of chemotherapeutic advanced drug delivery systems.

Neuropeptide CCHamide-2 is a recently discovered peptide presents in many arthropods and it is the ligand of the CCHamide-2 receptor (CCHa2-R), which is playing a regulatory role in diverse physiological processes, such as feeding, insulin production, lipid metabolism, growth and reproduction, however, the function of this gene in aphids is still unknown. Here, we characterized and determined the presumed role of CCHa2-R signaling in the wingless pea aphid, Acyrthosiphon pisum. Quantitative real-time reverse transcription-PCR (qRT-PCR) revealed the expression levels of CCHa2-R transcripts in different development stages and different tissues, which indicates that the CCHa2-R expression was high in the first instar as compared to the upcoming nymphal instars and adult and was predominantly high in the brain. The CCHa2-R transcript levels were significantly up-regulated in starved aphids as compared to fed aphids. Moreover, RNAi knockdown by the injection of dsRNA-CCHa2-R significantly reduced the expression and also reduced their food intake in adult aphids, as revealed by electrical penetration graphs (EPGs) results. CCHa2-R-silencing was also shown to reduce reproduction but not survival in A. pisum. These observations suggest a role for the CCHa2-R pathway in the response of wingless parthenogenetic aphids to their nutritional status, and this role involves the regulation of the expression of CCHa2-R. Overall, the results of these experiments indicate that CCHa2-R plays a dominant role in the regulation of feeding in A. pisum., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Introduction: A cross-sectional study was conducted to determine the prevalence and AMR pattern of Salmonella isolated from broiler chickens, farm sewage, and farm workers. This study also aimed at identifying the risk factors for Salmonella infection in chickens., Methodology: Cloacal swabs (n = 50) from broiler chickens, farm sewage (n = 50), and hand washed water of farm workers (n = 50) were collected along with data on farm management and antimicrobial usage from 50 broiler farms of Mymensingh and Gazipur districts. All samples were analysed for the presence of Salmonella using selective media and PCR assay. Antimicrobial susceptibility test was done for ten antimicrobials by disk diffusion test. Risk factor analyses were carried out by multivariable logistic regression using SPSS., Results: The overall Salmonella prevalence was 66% (99/150). Salmonella prevalence were 82% and 72% in cloacal swabs and farm sewage samples, respectively. From hand washed water, 44% of the samples were positive for Salmonella. Salmonella infection in broiler chickens was significantly associated with farming experience (≤ 5 years) and age of birds (≥ 11 days). Similar pattern of antimicrobial resistance was observed in Salmonella isolated from three types of samples, and high resistances were observed to colistin, doxycycline, ciprofloxacin and ceftazidime. Moreover, isolates from all the three sources showed high percentage of multidrug-resistance (80.6% to 97.6%)., Conclusions: The findings of this study reveal that antimicrobial-resistant Salmonella are prevailing at animal-human-environment interface, which needs an integrated approach to limit further spread of AMR., Competing Interests: No Conflict of Interest is declared, (Copyright (c) 2021 Sudipta Talukder, Md. Mehedi Hasan, Amit Kumar Mandal, Syeda Tanjina Tasmim, Mst. Sonia Parvin, Md. Yamin Ali, Azimun Nahar, Md. Zahorul Islam, Md. Taohidul Islam.)

The Bt-cotton RH-647 was developed by Cotton Research Institute CRI, Khanpur has been acknowledged for its possesses superior plant characteristics and potential to yield out under harsh agro-climatic conditions of cotton productive district of Rahimyar Khan in Bahawalpur Division and southern Punjab in 2016. RH- 647 for its novel plant structure and improved fiber quality heat and drought tolerant to withstand successfully sustain yield out in harsh, highly variable hot and dry climatic conditions of and harsh seasoned. RH-647 was developed through one-way hybridization of elite parental genotypes accompanied by pedigree selection method through gene pyramiding technique for incorporation of excellent combinations of fiber traits and CLCuV disease tolerance with higher yield potential right from F1 population. The superior plant combinations were selected in F2-F6 generations were entirely based on phenotypic plant traits and progeny yield potential in field, plant shape, number of bolls per plant, average boll weight (g) and fiber quality traits over standard varieties. The single plant progenies were selected 56 sister lines were tested for Bt-gene (Cry1 Ac) were evaluated for high yielding performance for this superior cross and finally RH-647 as superior breeding line was bulked in year 2010. The strain was evaluated in Randomized Complete Block Design in preliminary yield trials (PYT) and two years in Advance Yield Trials (AYT) trials and Zonal Varietal trials for two years. The superior line 647/10 was ensued for performance in variety attestation tests as RH-647. RH-647 performed best in two years varietal trials (NCVT and PCCT and DUS) conducted for two successive growing seasons (2014-2015 and 2015-2016). RH-647 yielded out significantly compared with standard varieties MNH-886, FH-142 and CIM 602. After completion of mandatory trials in year 2016, RH-647 was approved as new Bt. cotton variety "RH-647". RH-647 is early in maturity with high yield potential and best suited for wheat-cotton cropping pattern. It has fluffy opening and is easy to pick, strongly tolerant to CLCuV disease, high Ginning out turn GOT% (40.2%) with improved fiber traits; staple length (28.3 mm), fiber strength (4.2ug/inch) is duly capable to fulfill all industrial requisitions., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2021 The Author(s).)