Optimizing graphene content in scaffolds for evenly distributed crumpled MoS2paper wads as anodes for high-performance Li-ion batteries.

Lithium-ion batteries (LIBs) have revolutionized portable electronics, yet their conventional graphite anodes face capacity limitations. Integrating graphene and 3D molybdenum disulfide (MoS2) offers a promising solution. Ensuring a uniform distribution of 3D MoS2nanostructures within a graphene matrix is crucial for optimizing battery performance and preventing issues like agglomeration and capacity degradation. This study focuses on synthesizing a uniformly distributed paper wad structure by optimizing a composite of reduced graphene oxide RGO@MoS2through structural and morphological analyses. Three composites with varying graphene content were synthesized, revealing that the optimized sample containing 30 mg RGO demonstrates beneficial synergy between MoS2and RGO. The interconnected RGO network enhances reactivity and conductivity, addressing MoS2aggregation. Experimental results exhibit an initially superior capacity of 911 mAh g-1, retained at 851 mAh g-1even after 100 cycles at 0.1 A g-1current density, showcasing improved rate efficiency and long-term stability. This research underscores the pivotal role of graphene content in customizing RGO@MoS2composites for enhanced LIB performance.

Dietary approaches to stop hypertension (DASH) diet improves hepatic fibrosis, steatosis and liver enzymes in patients with non-alcoholic fatty liver disease: a randomized controlled trial.

PURPOSE: Recent evidence suggests that adherence to dietary approaches to stop hypertension (DASH) diet can be effective in managing non-alcoholic fatty liver disease (NAFLD). We investigated the effect of DASH diet on hepatic fibrosis, steatosis and liver enzymes in patients with NAFLD. METHODS: This 12-week randomized controlled trial was conducted among seventy patients with NAFLD who were randomly assigned into two groups including intervention group (DASH diet containing 50-55% carbohydrate, 15-20% protein, and 30% total fat) and the control group (a healthy diet containing 50-55% carbohydrate, 15-20% protein, and 30% total fat). Both diets were calorie-restricted (500-700 kcal lower than the energy requirement). The primary outcomes included hepatic fibrosis, hepatic steatosis, alanine transaminase (ALT), aspartate transaminase (AST) and gamma-glutamyl transpeptidase (GGT). RESULTS: At the baseline, there was no significant difference between two groups in the level of hepatic fibrosis (P = 0.63), hepatic steatosis (P = 0.53), ALT (P = 0.93), AST (P = 0.18) and GGT (P = 0.76). A significant reduction was found in the intervention group compared to the control group in hepatic fibrosis (23 grades reduction vs. 7 grades reduction; P = 0.008) and hepatic steatosis (31 grades reduction vs. 9 grades reduction; P = 0.03) after intervention. In addition, a significant change was observed in the intervention group compared to control group in ALT ( - 8.50 ± 8.98 vs. - 2.09 ± 7.29; P = 0.002), and AST ( - 5.79 ± 6.83 vs. - 0.51 ± 6.62; P = 0.002). CONCLUSIONS: Adherence to DASH diet may be effective in management of NAFLD. TRIAL REGISTRATION: The trial was registered on 06 February 2022 at Iranian Registry of Clinical Trials (IRCT20170117032026N3) with URL: https://www.irct.ir/trial/60887 .

Unraveling nitrogen loss in paddy soils: A study of anaerobic nitrogen transformation in response to various irrigation practice.

Soil nitrogen (N) transformation processes, encompassing denitrification, anaerobic ammonium oxidation (anammox), and anaerobic ammonium oxidation coupled with iron reduction (Feammox), constitute the primary mechanisms of soil dinitrogen (N2) loss. Despite the significance of these processes, there is a notable gap in research regarding the assessment of managed fertilization and irrigation impacts on anaerobic N transformations in paddy soil, crucial for achieving sustainable soil fertility management. This study addressed the gap by investigating the contributions of soil denitrification, anammox, and Feammox to N2 loss in paddy soil across varying soil depths, employing different fertilization and irrigation practices by utilizing N stable isotope technique for comprehensive insights. The results showed that anaerobic N transformation processes decreased with increasing soil depth under alternate wetting and drying (AWD) irrigation, but increased with the increasing soil depth under conventional continuous flooding (CF) irrigation. The denitrification and anammox rates varied from 0.41 to 2.12 mg N kg-1 d-1 and 0.062-0.394 mg N kg-1 d-1, respectively, which accounted for 84.3-88.1% and 11.8-15.7% of the total soil N2 loss. Significant correlations were found among denitrification rate and anammox rate (r = 0.986, p < 0.01), Fe (Ⅲ) reduction rate and denitrification rate (r = 0.527, p < 0.05), and Fe(Ⅲ) reduction rate and anammox rate (r = 0.622, p < 0.05). Moreover, nitrogen loss was more pronounced in the surface layer of the paddy soil compared to the deep layer. The study revealed that denitrification predominantly contributed to N loss in the surface soil, while Feammox emerged as a significant N loss pathway at depths ranging from 20 to 40 cm, accounting for up to 26.1% of the N loss. It was concluded that fertilization, irrigation, and soil depth significantly influenced anaerobic N transformation processes. In addition, the CF irrigation practice is best option to reduce N loss under managed fertilization. Furthermore, the role of microbial communities and their response to varying soil depths, fertilization practices, and irrigation methods could enhance our understanding on nitrogen loss pathways should be explored in future study.

The association between lifelines diet score (LLDS) with depression and quality of life in Iranian adolescent girls.

BACKGROUND: It has been proposed that a greater degree of adherence to a healthy dietary pattern is associated with a lower risk of depression and a poor quality of life (QoL). The Lifelines diet score (LLDS) is a new, evidence-base scoring system to define the quality of diet. We designed a cross-sectional study to investigate the association between LLDS with depression and QoL in Iranian adolescent girls. METHODS: A total of 733 female adolescents were recruited from Mashhad and Sabzevar cities, Iran. Depression and QoL were assessed utilizing the Beck Depression Inventory (BDI) and SF-12v2 questionnaires, respectively. The LLDS was defined by dividing intakes of 12 food groups with negative or positive health effects into quintiles ranging 12 to 60 points. To explore the association between LLDS with QoL and depression, logistic regression was used in crude and adjusted models. RESULTS: The prevalence of depression and poor QoL was 24% and 49%, respectively. After adjusting for confounding factors, adolescent girls in the highest quartile of LLDS compared with the participants in the lowest quartile had a 42% lower probability of reporting depressive symptoms (OR: 0.58; 95% CI: 0.35-0.97, P = 0.03). In addition, the participants in the highest quartile of LLDS had lower odds of poor QoL compared with the subjects in the lowest quartile (OR: 0.65; 95% CI: 0.42-0.92, P = 0.04). CONCLUSIONS: There is an inverse relationship between LLDS with risk of depression and poor QoL. Prospective and interventional investigations are needed to reach a clear vision.

Production and Evaluation of Ag85B:HspX:hFcγ1 Immunogenicity as an Fc Fusion Recombinant Multi-Stage Vaccine Candidate Against Mycobacterium tuberculosis.

An urgent need is to introduce an effective vaccine against Mycobacterium tuberculosis (M.tb) infection. In the present study, a multi-stage M.tb immunodominant Fcγ1 fusion protein (Ag85B:HspX:hFcγ1) was designed and produced, and the immunogenicity of purified protein was evaluated. This recombinant fusion protein was produced in the Pichia pastoris expression system. The HiTrap-rPA column affinity chromatography purified and confirmed the fusion protein using ELISA and Western blotting methods. The co-localisation assay was used to confirm its proper folding and function. IFN-γ, IL-12, IL-4, and TGF-ß expression in C57BL/6 mice then evaluated the immunogenicity of the construct in the presence and absence of BCG. After expression optimisation, medium-scale production and the Western blotting test confirmed suitable production of Ag85B:HspX:hFcγ1. The co-localisation results on antigen-presenting cells (APCs) showed that Ag85B:HspX:hFcγ1 properly folded and bound to hFcγRI. This strong co-localisation with its receptor can confirm inducing proper Th1 responses. The in vivo immunisation assay showed no difference in the expression of IL-4 but a substantial increase in the expression of IFN-γ and IL-12 (P ≤ 0.02) and a moderate increase in TGF-ß (P = 0.05). In vivo immunisation assay revealed that Th1-inducing pathways have been stimulated, as IFN-γ and IL-12 strongly, and TGF-ß expression moderately increased in Ag85B:HspX:hFcγ1 group and Ag85B:HspX:hFcγ1+BCG. Furthermore, the production of IFN-γ from splenocytes in the Ag85B:HspX:hFcγ1 group was enormously higher than in other treatments. Therefore, this Fc fusion protein can make a selective multi-stage delivery system for inducing appropriate Th1 responses and is used as a subunit vaccine alone or in combination with others.

Early elastic and viscoelastic corneal biomechanical changes after photorefractive keratectomy and small incision lenticule extraction.

PURPOSE: To compare early changes in the corneal biomechanical parameters after photorefractive keratectomy (PRK) and small incision lenticule extraction (SMILE) and their correlations with corneal shape parameters. METHODS: One hundred twenty four eyes received myopic PRK and SMILE for similar amounts of myopia. Corneal tomography with Pentacam HR, biomechanical parameters using Corvis ST, and Ocular Response Analyzer (ORA) were evaluated before and 2 weeks after surgery. The change in each parameter was compared between groups, while the difference in central corneal thickness and cornea-compensated intraocular pressure measured before and after surgery were considered as covariates. RESULTS: A significant reduction was seen in the corneal stiffness parameter at first applanation, and an increase in deformation amplitude ratio (DAR), and integrated inverse radius (IIR) in both groups after surgery (p < 0.001) Changes in DAR, and IIR were significantly greater in the SMILE than in the PRK group (p < 0.001) Corneal hysteresis (CH) and corneal resistance factor (CRF) decreased in both SMILE and PRK groups after surgery, (p < 0.001) with no statistically significant difference between groups (p > 0.05) Among new Corvis ST parameters, DAR showed a significant correlation with changes in Ambrosio relational thickness in both groups (p < 0.05). CONCLUSIONS: Both techniques caused significant changes in corneal biomechanics in the early postoperative period, with greater elastic changes in the SMILE group compared to the PRK group, likely due to lower tension in the SMILE cap and thinner residual stromal bed in SMILE. There were no differences in viscoelastic changes between them, so the lower CH may reflect the volume of tissue removed.

The role of serum circulating microbial toxins in severity and cytokine storm of COVID positive patients.

The emergence of Coronavirus disease 2019 (Covid-19) is a global problem nowadays, causing health difficulty with increasing mortality rates, which doesn't have a verified treatment. SARS-CoV-2 infection has various pathological and epidemiological characteristics, one of them is increased amounts of cytokine production, which in order activate an abnormal unrestricted response called "cytokine storm". This event contributes to severe acute respiratory distress syndrome (ARDS), which results in respiratory failure and pneumonia and is the great cause of death associated with Covid-19. Endotoxemia and the release of bacterial lipopolysaccharides (endotoxins) from the lumen into the bloodstream enhance proinflammatory cytokines. SARS-CoV-2 can straightly interplay with endotoxins via its S protein, leading to the extremely elevating release of cytokines and consequently increase the harshness of Covid-19. In this review, we will discuss the possible role of viral-bacterial interaction that occurs through the transfer of bacterial products such as lipopolysaccharide (LPS) from the intestine into the bloodstream, exacerbating the severity of Covid-19 and cytokine storms.

Targeted Silencing of NRF2 by rituximab-conjugated nanoparticles increases the sensitivity of chronic lymphoblastic leukemia cells to Cyclophosphamide.

BACKGROUND: Targeting influential factors in resistance to chemotherapy is one way to increase the effectiveness of chemotherapeutics. The nuclear factor erythroid 2-related factor 2 (Nrf2) pathway overexpresses in chronic lymphocytic leukemia (CLL) cells and appears to have a significant part in their survival and chemotherapy resistance. Here we produced novel nanoparticles (NPs) specific for CD20-expressing CLL cells with simultaneous anti-Nrf2 and cytotoxic properties. METHODS: Chitosan lactate (CL) was used to produce the primary NPs which were then respectively loaded with rituximab (RTX), anti-Nrf2 Small interfering RNA (siRNAs) and Cyclophosphamide (CP) to prepare the final version of the NPs (NP-Nrf2_siRNA-CP). All interventions were done on both peripheral blood mononuclear cells (PBMCs) and bone marrow mononuclear cells (BMNCs). RESULTS: NP-Nrf2_siRNA-CP had satisfying physicochemical properties, showed controlled anti-Nrf2 siRNA/CP release, and were efficiently transfected into CLL primary cells (both PBMCs and BMNCs). NP-Nrf2_siRNA-CP were significantly capable of cell apoptosis induction and proliferation prevention marked by respectively decreased and increased anti-apoptotic and pro-apoptotic factors. Furthermore, use of anti-Nrf2 siRNA was corresponding to elevated sensitivity of CLL cells to CP. CONCLUSION: Our findings imply that the combination therapy of malignant CLL cells with RTX, CP and anti-Nrf2 siRNA is a novel and efficient therapeutic strategy that was capable of destroying malignant cells. Furthermore, the use of NPs as a multiple drug delivery method showed fulfilling properties; however, the need for further future studies is undeniable. Video Abstract.

Staphylococcal enterotoxin B as DNA vaccine against breast cancer in a murine model.

Recently, many efforts have been made to treat cancer using recombinant bacterial toxins and this strategy has been used in clinical trials of various cancers. Therapeutic DNA cancer vaccines are now considered as a promising strategy to activate the immune system against cancer. Cancer vaccines could induce specific and long-lasting immune responses against tumors. This study aimed to evaluate the antitumor potency of the SEB DNA vaccine as a new antitumor candidate against breast tumors in vivo. To determine the effect of the SEB construct on inhibiting tumor cell growth in vivo, the synthetic SEB gene, subsequent codon optimization, and embedding the cleavage sites were sub-cloned to an expression vector. Then, SEB construct, SEB, and PBS were injected into the mice. After being vaccinated, 4T1 cancer cells were injected subcutaneously into the right flank of mice. Then, the cytokine levels of IL-4 and IFN-γ were estimated by the ELISA method to evaluate the antitumor activity. The spleen lymphocyte proliferation, tumor size, and survival time were assessed. The concentration of IFN-γ in the SEB-Vac group showed a significant increase compared to other groups. The production of IL-4 in the group that received the DNA vaccine did not change significantly compared to the control group. The lymphocyte proliferation increased significantly in the mice group that received SEB construct than PBS control group (p < 0.001). While there was a meaningful decrease in tumor size (p < 0.001), a significant increase in tumor tissue necrosis (p < 0.01) and also in survival time of the animal model receiving the recombinant construct was observed. The designed SEB gene construct can be a new model vaccine for breast cancer because it effectively induces necrosis and produces specific immune responses. This structure does not hurt normal cells and is a safer treatment than chemotherapy and radiation therapy. Its slow and long-term release gently stimulates the immune system and cellular memory. It could be applied as a new model for inducing apoptosis and antitumor immunity to treat cancer.

Immune response induced by recombinant pres2/S-protein and a pres2-S-protein fused with a core 18-27 antigen fragment of hepatitis B virus compared to conventional HBV vaccine.

Although comprehensive vaccination is the cornerstone of public health programs to control hepatitis B virus (HBV) infections, 5% of people who receive the existing vaccine do not develop proper immunity against HBV. To overcome this challenge, researchers have tried using various protein fragments encoded by the virus genome to achieve better immunization rates. An important antigenic component of HBsAg called the preS2/S or M protein has also received much attention in this area. The gene sequences of preS2/S and Core18-27 peptide were extracted from the GenBank (NCBI). Final gene synthesis was conducted with pET28. Groups of BALB/c mice were immunized with 10 µg/ml of recombinant proteins and 1 µg/ml CPG7909 adjuvant. Serum levels of IF-γ, TNF-α, IL-2, IL-4, and IL-10 were measured by ELISA assay method on spleen cell cultures on day 45, and IgG1, IgG2a, and total IgG titers obtained from mice serum were quantified on days 14 and 45. Statistical analysis did not show any significant difference between the groups regarding IF-γ level. There were, however, significant differences in terms of IL-2 and IL-4 levels between the groups receiving preS2/S-C18-27 with and without adjuvant and the groups receiving both preS2/S and preS2/S-C18-27 (Plus Recomb-Plus Recomb: the group of mice that received both preS2/S and preS2/S-C18-27 simultaneously). The strongest total antibody production was induced by immunization with both recombinant proteins without CPG adjuvant. The groups that received both preS2/S and preS2/S-C18-27, whether with or without adjuvant, were significantly different from those that received the conventional vaccine considering most abundant interleukins. This difference suggested that higher levels of efficacy can be achieved by the use of multiple virus antigen fragments rather than using a single fragment.

Optimization of a rapid and sensitive nucleic acid lateral flow biosensor for hepatitis B virus detection.

BACKGROUND AND OBJECTIVE: The utilization of direct amplification of nucleic acid from lysate has attracted interest in the advancement of straightforward and economical point-of-care assays. Consequently, this study primarily focuses on the development of a rapid, precise, and cost-effective lateral flow biosensor for the convenient detection of HBV nucleic acid at the point-of-care. Furthermore, the study evaluates the effectiveness of the direct amplification method in comparison to purified nucleic acid samples within the context of LAMP-LF biosensing approaches. METHODS: The experiments conducted in this study utilized clinical serum samples that were confirmed as HBV-positive through real-time PCR assays. Sample preparation involved employing spin column nucleic acid purification and serum heat treatment. To amplify a 250 bp fragment of the HBV polymerase gene, three pairs of specific LAMP primers were utilized, which were biotin-labeled and FITC-labeled for detection purposes. Various incubation temperatures (ranging from 64 to 68 °C) and durations (30 min, 45 min, and 1 h) were investigated to determine the optimal conditions for the LAMP assay. The results were subsequently assessed through fluorometric analysis, white turbidity measurements, and lateral flow assay. Milenia HybriDetect1 strips, designed for immediate use, were employed to visualize the LAMP amplicons. Furthermore, the performance of the lateral flow biosensor was evaluated using 10-fold serial dilutions of a secondary standard containing a viral load of 108 IU/ml. RESULTS: The optimization of the LAMP reaction was achieved at a temperature of 67 °C, resulting in significant turbidity after a 30-minute incubation period. When the spin column purification method was employed, varying test bands were observed for templates ranging from 108 IU/ml to 101 IU/ml viral load. However, when serum samples underwent heat treatment and the resulting supernatant was directly used for LAMP, the lateral flow assay was capable of detecting a minimum viral load of 103 IU/ml. CONCLUSION: In resource-limited settings, the LAMP-LF assay presents a promising solution for HBV testing. However, it is important to note that direct amplification without DNA purification may diminish the performance of the approach.

Unveiling the etiological impact of GST-M1, GST-T1, and P53 genotypic variations on brain carcinogenesis.

BACKGROUND: Functional variants of glutathione-S-transferase (GST)-M1, GST-T1, p53 might modulate brain cancer risk by altering the rate of metabolism and clearance of carcinogens from the brain tissue. In this study, the role of GST-M1, GST-T1, p53 polymorphisms on brain tumor was investigated. METHODS AND RESULTS: Brain tumor tissues of 143 patients were obtained from the Gulhane Training and Research Hospital, Department of Neurosurgery between 2019 and 2020. In the xenobiotic mechanism, the null allele frequency in the GST-T1, GST-M1 gene regions of Phase II enzymes by qPCR method were investigated. Single nucleotide polymorphism encoding Arg/Pro conversion in the p53 gene region was analyzed in 120 cases by sequence analysis method. The data were analyzed statistically with patient's demographic and clinical data. GST-M1, GST-T1, p53 genotypes of the patient group were determined. The most frequent genotype was null genotype (0/0) for GST-M1 (χ2 = 39.756, p < 0.001). GST-M1 genotype frequencies were 30.8%, 23.1%, 44.3% for 1/1, 1/0, 0/0, respectively. The most frequent genotype was GST-T1 1/1 following by GST-T1 1/0 (χ2 = 0.335, p = 0.846). GST-T1 genotype frequencies were 64.3%, 30.8%, 4.9% for 1/1, 1/0, 0/0, respectively. GST-M1 null genotype might be associated with the development of brain tumors. Genotype distribution obtained in p53 exon 4 codon 72; Arg/Arg was determined as 31 (25.8%), Arg/Pro 70 (58.3%), and Pro/Pro 19 (15.8%) in the case group, while there were 18 (38.3%), 23 (48.9%), and 6 (12.8%) respectively in the control group. However, the genotype distribution of p53 exon 4 codon 72 among tumorous tissue did not significantly vary from healthy control tissues (χ²=2.536, p = 0.281). CONCLUSION: The null allele frequency encountered in the GST-M1, GST-T1 gene regions is consistent with the rates in the gene pool called Caucasian in the literature. GST-M1 gene polymorphism may play a crucial role in brain carcinogenesis in Turkish patients. This study based on clinical data is thought to help to understand the important epidemiological features of brain tumors.

Assessment of endocrine disrupting chemicals in breast milk: Association with dietary habits and duration of lactation.

The present study was aimed to assess infant safety associated with the presence of persistent organochlorine pesticides (OCPs) in breast milk, a possible route of transfer of endocrine-disrupting chemicals to newborns in North India. Colostrum and breast milk samples (n = 130) were collected at different stages of lactation. Pesticides analysis was performed using gas chromatography mass spectrometry (GC-MS). We observed that of all the samples analysed, OCPs concentration was higher in breast milk than in colostrum, suggesting pesticides contamination increases over lactation period. As far as OCPs are concerned, dieldrin [1196.64 ± 673.75 ng/g lipid weight (lw)], and ß-HCH [1107.78 ± 1301.72 ng/g lw], were the predominant OCPs, followed by aldrin [977.09 ± 707.69 ng/g lw], α-HCH [948.04 ± 476.65 ng/g lw] and 1,1'-(2,2-Dichloroethene-1,1-diyl)bis(4-chlorobenzene) (p,p'DDE) [790.11 ± 399.35 ng/g lw]. The association between OCPs levels and women dietary habits were also explored, and all the OCPs were grouped and compared to each other by consumption level of fish, meat, sea foods, eggs, and dairy products. We found that women consuming non vegetarian food, like fish and meat, were exposed 3.5 times more to OCPs than women consuming vegetarian food. In addition, we also observed that factors like mother's age was positively (<0.005 - <0.001) correlated while gestational age and infant birth weight were negatively (<0.005) associated with the levels of OCPs in colostrum and breast milk, respectively. Unfortunately, neither any standards nor guidelines are available for the use of pesticides, therefore, it is suggested that careless use of OCPs should be checked and suitable remedial measures be taken to decrease human contamination. Moreover, further studies are warranted to elucidate relationship between pesticide residues in breast milk and the maternal and child health.

Efficient and green synthesis of novel hexahydro-5H-thiazolo[2',3':2,3]pyrimido[4,5-b]quinoline derivatives.

Herein, we report a catalyst-free, one-pot three-component reaction of 5-amino-2,3-dihydro-7H-thiazolo[3,2-a]pyrimidin-7-one, aromatic aldehyde, and dimedone in ethylene glycol as a green solvent at 100 °C for the easy access of hexahydro-5H-thiazolo[2',3':2,3]pyrimido[4,5-b]quinoline. Catalyst-free, green solvent, simple procedure, mild reaction conditions, easy work-up procedure, and good to excellent yields are the significant advantages of this protocol.

Mesoporous epoxidized soybean oil-supported copper-based magnetic nanocatalyst and amberlite-supported azide as a green and efficient catalytic system for 1,2,3-triazole synthesis.

A new green mesoporous magnetically heterogeneous catalyst was prepared by the copper immobilization onto magnetic epoxidized soybean oil as a nano bio-support and was utilized for the synthesis of 1,4-disubstituted-1,2,3-triazole derivatives in the presence of amberlite supported azide. A great range of triazole derivatives were synthesized from benzyl halides or epoxides halides in high yields at the room temperature. The catalyst was characterized by various techniques such as FT-IR, XRD, VSM, FE-SEM, EDX, TEM, BET, TGA, and ICP analysis. This catalytic system can be reused for five times without any significant decrease in the catalytic activity. Fe3O4@SiO-ESBO/CuO nanocatalyst and amberlite supported azide as a green catalytic system has been used for the regioselective synthesis of triazole derivatives in water. A large range of triazole derivatives were synthesized from benzyl halides or epoxides in high yields.

Interaction Between SARS-CoV-2 and Pathogenic Bacteria.

The novel human coronavirus, Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), which results in the coronavirus disease 2019 (COVID-19), has caused a serious threat to global public health. Therefore, many studies are performed on the causes and prevalence of this disease and the possible co-occurrence of the infection with other viral and bacterial pathogens is investigated. Respiratory infections predispose patients to co-infections and these lead to increased disease severity and mortality. Numerous types of antibiotics have been employed for the prevention and treatment of bacterial co-infection and secondary bacterial infections in patients with a SARS-CoV-2 infection. Although antibiotics do not directly affect SARS-CoV-2, viral respiratory infections often result in bacterial pneumonia. It is possible that some patients die from bacterial co-infection rather than virus itself. Therefore, bacterial co-infection and secondary bacterial infection are considered critical risk factors for the severity and mortality rates of COVID-19. In this review, we will summarize the bacterial co-infection and secondary bacterial infection in some featured respiratory viral infections, especially COVID-19.

Binding of DNA origami to lipids: maximizing yield and switching via strand displacement.

Liposomes are widely used as synthetic analogues of cell membranes and for drug delivery. Lipid-binding DNA nanostructures can modify the shape, porosity and reactivity of liposomes, mediated by cholesterol modifications. DNA nanostructures can also be designed to switch conformations by DNA strand displacement. However, the optimal conditions to facilitate stable, high-yield DNA-lipid binding while allowing controlled switching by strand displacement are not known. Here, we characterized the effect of cholesterol arrangement, DNA structure, buffer and lipid composition on DNA-lipid binding and strand displacement. We observed that binding was inhibited below pH 4, and above 200 mM NaCl or 40 mM MgCl2, was independent of lipid type, and increased with membrane cholesterol content. For simple motifs, binding yield was slightly higher for double-stranded DNA than single-stranded DNA. For larger DNA origami tiles, four to eight cholesterol modifications were optimal, while edge positions and longer spacers increased yield of lipid binding. Strand displacement achieved controlled removal of DNA tiles from membranes, but was inhibited by overhang domains, which are used to prevent cholesterol aggregation. These findings provide design guidelines for integrating strand displacement switching with lipid-binding DNA nanostructures. This paves the way for achieving dynamic control of membrane morphology, enabling broader applications in nanomedicine and biophysics.

Saffron and crocin ameliorate prenatal valproic acid-induced autistic-like behaviors and brain oxidative stress in the male offspring rats.

Autism is a neurobehavioral disease that induces cognitive and behavioral alterations, usually accompanied by oxidative stress in the brain. Crocus sativus (saffron) and its active ingredient, crocin, have potent antioxidative effects that may benefit autistic behaviors. This study aimed to determine the effects of saffron extract and crocin against brain oxidative stress and behavioral, motor, and cognitive deficits in an animal model of autism in male offspring rats. 14 female rats were randomly divided into the saline and valproic acid (VPA) groups. Then, they were placed with mature male rats to mate and produce offspring. VPA (500 mg/kg, i.p.) was injected on day 12.5 of pregnancy (gestational day, GD 12.5) to induce an experimental model of autism. 48 male pups were left undisturbed for 29 days. First-round behavioral tests (before treatments) were performed on 30-33 post-natal days (PND), followed by 28 days of treatment (PND 34-61) with saffron (30 mg/kg, IP), crocin (15 or 30 mg/kg, i.p.), or saline (2 ml/kg, i.p.). The second round of behavioral tests (after treatments) was performed on PND 62-65 to assess the effects of the treatments on behavioral and cognitive features. In the end, animals were sacrificed under deep anesthesia, and their brains were dissected to evaluate the brain oxidative stress parameters, including malondialdehyde (MDA), glutathione (GSH), and catalase (CAT). VPA injection into female rats increased anxiety-like behaviors, enhanced pain threshold, impaired motor functions, disturbed balance power, increased MDA, and decreased GSH and CAT in their male offspring. 28 days of treatment with saffron or crocin significantly ameliorated behavioral abnormalities, reduced MDA, and increased GSH and CAT levels. Brain oxidative stress has been implicated in the pathophysiology of autistic-like behaviors. Saffron and crocin ameliorate anxiety-like behaviors, pain responses, motor functions, and brain oxidative stress parameters in an experimental model of autism. Saffron and crocin may hold promise as herbal-based pharmacological treatments for individuals with autism. However, further histological evidence is needed to confirm their efficacy.

Non-occupational physical activity and risk of cardiovascular disease, cancer and mortality outcomes: a dose-response meta-analysis of large prospective studies.

OBJECTIVE: To estimate the dose-response associations between non-occupational physical activity and several chronic disease and mortality outcomes in the general adult population. DESIGN: Systematic review and cohort-level dose-response meta-analysis. DATA SOURCES: PubMed, Scopus, Web of Science and reference lists of published studies. ELIGIBILITY CRITERIA: Prospective cohort studies with (1) general population samples >10 000 adults, (2) ≥3 physical activity categories, and (3) risk measures and CIs for all-cause mortality or incident total cardiovascular disease, coronary heart disease, stroke, heart failure, total cancer and site-specific cancers (head and neck, myeloid leukaemia, myeloma, gastric cardia, lung, liver, endometrium, colon, breast, bladder, rectum, oesophagus, prostate, kidney). RESULTS: 196 articles were included, covering 94 cohorts with >30 million participants. The evidence base was largest for all-cause mortality (50 separate results; 163 415 543 person-years, 811 616 events), and incidence of cardiovascular disease (37 results; 28 884 209 person-years, 74 757 events) and cancer (31 results; 35 500 867 person-years, 185 870 events). In general, higher activity levels were associated with lower risk of all outcomes. Differences in risk were greater between 0 and 8.75 marginal metabolic equivalent of task-hours per week (mMET-hours/week) (equivalent to the recommended 150 min/week of moderate-to-vigorous aerobic physical activity), with smaller marginal differences in risk above this level to 17.5 mMET-hours/week, beyond which additional differences were small and uncertain. Associations were stronger for all-cause (relative risk (RR) at 8.75 mMET-hours/week: 0.69, 95% CI 0.65 to 0.73) and cardiovascular disease (RR at 8.75 mMET-hours/week: 0.71, 95% CI 0.66 to 0.77) mortality than for cancer mortality (RR at 8.75 mMET-hours/week: 0.85, 95% CI 0.81 to 0.89). If all insufficiently active individuals had achieved 8.75 mMET-hours/week, 15.7% (95% CI 13.1 to 18.2) of all premature deaths would have been averted. CONCLUSIONS: Inverse non-linear dose-response associations suggest substantial protection against a range of chronic disease outcomes from small increases in non-occupational physical activity in inactive adults. PROSPERO registration number CRD42018095481.

Evaluation of Adrenal Reserve in Patients with Differentiated Thyroid Cancer Receiving Thyroid Hormone Suppression Therapy- case-control Comparative Study.

BACKGROUND: Patients with differentiated thyroid cancer (DTC) are exposed to subclinical exogenous hyperthyroidism for the suppression of thyroid-stimulating hormone (TSH). In this study, we aimed to evaluate the adrenal reserve in DTC patients receiving suppression therapy. MATERIALS AND METHODS: The study included 55 DTC patients on suppression therapy and 32 healthy volunteers. Basal serum cortisol of all participants and adrenocorticotropic hormone (ACTH) of the patient group were measured. A standard-dose ACTH test (0.25 mg) was performed in patients with a basal cortisol <14.5 mcg/dL. RESULTS: In the patient group, TSH was lower, free thyroxine (fT4) was higher, and free triiodothyronine (fT3) was similar to those of the control group (p < .01, p < .01, p = .140, respectively). The serum cortisol of the patient group was significantly lower than the control group (12.14 ± 5.12 mcg/dL vs 18.00 ± 5.56 mcg/dL, p < .001). A total of 34 (61.8%) patients with DTC had a basal cortisol <14.5 mcg/dL. Prolonged TSH suppression (≥5 years vs <5 years) was associated with lower basal cortisol (7.46 ± 2.63 mcg/dL vs 9.48 ± 2.65 mcg/dL, p = .022). The ACTH stimulation test showed that 2 (5.8%) patients had a cortisol response <18 mcg/dL. The rate of adrenal insufficiency was 3.6% in DTC patients. A moderate negative correlation was found between ACTH and fT3 of patients with low basal cortisol (r = -0.358, p = .038). CONCLUSION: Patients with DTC receiving TSH suppression therapy are at risk for adrenal insufficiency. The duration and severity of suppression might increase this possibility. Dynamic testing with synthetic ACTH can be used to reveal insufficient cortisol response in case of clinical suspicion.