Composition of mucus- and digesta-associated bacteria in growing pigs with and without diarrhea differed according to the presence of colonic inflammation.

BACKGROUND: In the pig production, diarrhea can occur during different growth stages including the period 4-16 weeks post weaning, during which a diarrheal outbreak also termed as colitis-complex diarrhea (CCD) can occur and it is distinct from post-weaning diarrhea (1-2 weeks post weaning). We hypothesized that CCD in growing pigs is associated with changes in colonic microbiota composition and fermentation patterns, and the aim of the present observational study was to identify changes in digesta-associated bacteria (DAB) and mucus-associated bacteria (MAB) in the colon of growing pigs with and without diarrhea. A total number of 30 pigs (8, 11, and 12 weeks of age) were selected; 20 showed clinical signs of diarrhea and 10 appeared healthy. Based on histopathological examination of colonic tissues, 21 pigs were selected for further studies and classified as follows: without diarrhea, no colon inflammation (NoDiar; n = 5), with diarrhea, without colonic inflammation (DiarNoInfl; n = 4), and with diarrhea, with colonic inflammation (DiarInfl; n = 12). Composition (based on 16S rRNA gene amplicon sequencing) and fermentation pattern (short-chain fatty acids; SCFA profile) of the DAB and MAB communities were characterized. RESULTS: The DAB showed higher alpha diversity compared to MAB in all pigs, and both DAB and MAB showed lowest alpha diversity in the DiarNoInfl group. Beta diversity was significantly different between DAB and MAB as well as between diarrheal groups in both DAB and MAB. Compared to NoDiar, DiarInfl showed increased abundance of various taxa, incl. certain pathogens, in both digesta and mucus, as well as decreased digesta butyrate concentration. However, DiarNoInfl showed reduced abundance of different genera (mainly Firmicutes) compared to NoDiar, but still lower butyrate concentration. CONCLUSION: Diversity and composition of MAB and DAB changed in diarrheal groups depending on presence/absence of colonic inflammation. We also suggest that DiarNoInfl group was at the earlier stage of diarrhea compared with DiarInfl, with a link to dysbiosis of colonic bacterial composition as well as reduced butyrate concentration, which plays a pivotal role in gut health. This could have led to diarrhea with inflammation due to a dysbiosis, associated with an increase in e.g., Escherichia-Shigella (Proteobacteria), Helicobacter (Campylobacterota), and Bifidobacterium (Actinobacteriota), which may tolerate or utilize oxygen and cause epithelial hypoxia and inflammation. The increased consumption of oxygen in epithelial mucosal layer by infiltrated neutrophils may also have added up to this hypoxia. Overall, the results confirmed that changes in DAB and MAB were associated with CCD and reduced butyrate concentration in digesta. Moreover, DAB might suffice for future community-based studies of CCD.

Population genetic study of 17 Y-STR Loci of the Sorani Kurds in the Province of Sulaymaniyah, Iraq.

BACKGROUND: The Kurds as an ethnic group are believed to be a combination of earlier Indo-European tribes who migrated and inhabited a mountainous area thousands of years ago. However, as it is difficult to describe the precise history of their origin, it is necessary to investigate their population relationship with other geographical and ethnic groups. RESULTS: Seventeen Short Tandem Repeat markers on the Y chromosome (Y-STR) included in the AmpFLSTR™ Yfiler™ PCR Amplification Kit (Thermo Fisher Scientific, USA) were used to type DNA samples from the Sorani (Central) Kurdish population in Sulaymaniyah province. One hundred fifty-seven haplotypes were obtained from 162 unrelated male individuals. The highest and lowest gene diversities were DYS385a/b (GD = 0.848) and DYS392 (GD = 0.392), respectively. The haplotypes were used to predict the most likely haplogroups in the Sulaymaniyah population. CONCLUSION: Haplogroup prediction indicated predominance (28%) of subclade J2 (44/157) in the Sorani Kurds, northeast of Iraq. The pairwise genetic distance results showed that the Kurdish group clustered along with Asian populations, whereas the furthest countries were Europeans and Africans.

Preparation of MgO-MnO2 nanocomposite particles for cholesterol sensors.

Various nanoparticles have been developed for bio-applications. However, nanocomposites particles, (NCPs) with effective and ability to sensing cholesterol, are still needed. Herein, we present new cholesterol and pH-responsive NCPs as sensor particles to promote sensitivity. The traditional method of mixing and grinding was used to fabricate the oxides of magnesium and manganese MgO-MnO2 NCPs with different mixing ratios. Structural properties, detection of cholesterol, and pH sensitivity were examined. Results propped the high efficiency of MgO-MnO2 NCPs compared with individual oxides (MgO and MnO2), low response time, while the analytical results confirmed the homogeneous structure of MgO-MnO2 NCPs. Particle size distribution results for NCPs were within 16.4 to 100 nm, which makes it promising in medical and bio-applications.

Can subcentimetre ultrasound detected angiomyolipomas be safely disregarded?

AIM: To optimise follow-up by dismissing lesions on baseline ultrasound (US) if renal lesions conform to US criteria of an angiomyolipoma (AML). METHOD AND MATERIALS: The present study was a 10-year retrospective review of patients who were found to have incidental hyperechoic renal lesions on US to ascertain the outcome from subsequent imaging, clinical encounters, and cancer registrations. Exclusions included renal calculi, tuberous sclerosis, Von-Hippel-Lindau, or a known cancer. RESULTS: After excluding 39 patients, 1,493 patients were identified. One hundred and sixty had more than one lesion with 87 patients having bilateral lesions. Regardless of indication, 889 patients had subsequent imaging within 5 years (59.5%). The average size of all AMLs was 13.2 mm. In the group with lesions that were <10 mm (807), 438 had imaging follow-up with an average follow-up time of 1.5 years. Mean lesion size in this group was 7 mm, with an average increase of <0.5 mm on follow-up. No lesions were found to be malignant on subsequent imaging nor did any of these patients have a subsequent renal cancer diagnosis registered at local multidisciplinary team meetings. CONCLUSION: No incidental subcentimetre hyperechoic renal lesion with imaging characteristics of an AML demonstrated significant growth or developed into a malignancy on follow-up.

Effect of toasting and decortication of oat on rumen biohydrogenation and intestinal digestibility of fatty acids in dairy cows.

This experiment quantified the effect of decorticated and toasted oat (Avena sativa L.) on fatty acid (FA) supply, ruminal biohydrogenation (BH) of FA, and intestinal digestibility of FA in 4 ruminal and intestinal cannulated Danish Holstein cows. Experimental diets containing untreated oat, decorticated oat, toasted oat, and decorticated and toasted oat were fed ad libitum to the cows in a 2 × 2 factorial arrangement in a Latin square design throughout 4 periods. Unless otherwise mentioned, the results of this study indicate the main effect of decortication and toasting. Decortication increased the intake of FA by 40.3 g/d and increased feed-ileum digested FA, whereas toasting decreased the intake of FA by 69.3 g/d. Toasting increased both feed-ileum and total-tract digestibility of FA by 59.8 and 67.4 g/kg of FA intake, respectively. The proportion of C18:2n-6 in FA intake increased, and the C18:3n-3 proportion in FA intake decreased due to decortication. Toasting resulted in a dramatic reduction of the C18:2n-6 proportion in FA intake, and it increased the proportions of C18:0 and C18:3n-3 in FA intake. Toasting reduced ruminal BH of C18:1n-9 and C18:2n-6 by 134 and 11.7 g/kg of FA intake, respectively, and toasting increased the proportion of unsaturated FA to saturated FA in the duodenal FA flow. Decortication decreased the ruminal BH of C18:3n-3 by 38.0 g/kg of FA intake. Decortication increased small intestinal digestibility of C12:0, C15:0, C20:0, and C22:0. Toasting increased the small intestinal digestibility of C15:0, C18:0, trans-C18:1, C20:0, and C24:0. Toasting reduced the small intestinal digestibility of C18:1n-9, C18:2n-6, and C20:1n-9. This study showed that decortication successfully increased the intake of FA and flow of FA at the duodenum and feed-ileum digested FA. However, toasting oat at 121°C caused a remarkable decline in FA concentration in oat, and thereby FA intake; therefore, toasting cannot be recommended.

Effects of toasting and decortication of oat on nutrient digestibility in the rumen and small intestine and on amino acid supply in dairy cows.

This study examined the potential for decorticating and toasting of oat (Avena sativa) to supply crude protein (CP) and amino acids (AA) in dairy cows. Four lactating Danish Holstein Friesian cows fitted with ruminal, duodenal, and ileal cannulas were assigned to a 4 × 4 Latin square design. Cows were fed experimental diets ad libitum based on grass-clover silage and toasted fava beans, with oat included in different forms arranged in a 2 × 2 factorial: whole oat, decorticated oat, toasted oat, and decorticated toasted oat. In situ rumen degradability of processed oat was also evaluated. Decortication increased starch intake by 0.38 kg/d and reduced NDF intake by 0.91 kg/d. Toasting reduced ruminal AA digestibility and increased duodenal flow of CP by 0.41 kg/d. In situ degradation rate and effective degradability of CP in the rumen were reduced by 0.46 h-1 and 310 g/kg CP due to toasting. Both decortication and toasting increased microbial synthesis of CP by 0.20 and 0.41 kg/d, respectively. Decortication and toasting did not affect small intestinal AA digestibility, but did increase the total digested amount of AA by 154 and 250 g/d, respectively. Milk production was not affected by treatments. Methane production (L/d) decreased with decortication and toasting. In conclusion, unless an interaction exists between decortication and toasting, the results indicate additive effects of toasting and decorticating oat for increasing the supply of digestible AA to the small intestine of dairy cows.

The role of fat on cardiomyopathy outcome in mouse models of chronic Trypanosoma cruzi infection.

The underlying pathogenic mechanisms of cardiomyopathy in Chagas disease are still unsolved. In order to better clarify the role of fat on the evolution of cardiomyopathy, the present study employed three murine models of chronic Trypanosoma cruzi infection: (1) aP2-RIDα/ß transgenic mice (RID mice; an adipose tissue model which express a gain-of-function potent anti-inflammatory activity), (2) allograft inflammatory factor-1 knockout mice (Aif1-/-), and (3) a Swiss outbred mice. RID mice and non-transgenic mice (wild type, WT) were infected with blood trypomastigotes of Brazil strain. During the acute stage of infection, RID mice had lower parasitemia, lower heart inflammation, and a decrease in the relative distribution of parasite load from cardiac muscle tissue toward epididymal fat. Nevertheless, comparable profiles of myocardial inflammatory infiltrates and relative distribution of parasite load were observed among RID and WT at the chronic stage of infection. Aif1-/- and Aif1+/+ mice were infected with bloodstream trypomastigotes of Tulahuen strain and fed with high-fat diet (HFD) or regular diet (RD). Interestingly, Aif1+/+ HFD infected mice showed the highest mortality. Swiss mice infected with blood trypomastigotes of Berenice-78 strain on a HFD had higher levels of TNFα and more inflammation in their heart tissue than infected mice fed a RD. These various murine models implicate adipocytes in the pathogenesis of chronic Chagas disease and suggest that HFD can lead to a significant increase in the severity of parasite-induced chronic cardiac damage. Furthermore, these data implicate adipocyte TLR4-, TNFα-, and IL-1ß-mediated signaling in pro-inflammatory pathways and Aif-1 gene expression in the development of chronic Chagas disease.

Correction to: The role of fat on cardiomyopathy outcome in mouse models of chronic Trypanosoma cruzi infection.

The authors regret that Philipp E Scherer's name was spelt incorrectly in the author list. The name of the author is now corrected above.

Effect of oat decortication on chemical composition, in vitro digestibility and in situ degradability.

The effect of decortication on chemical composition and degradability characteristics of four Danish oat varieties was investigated. Effective degradability (ED) and post-ruminal disappearance (PRD) were measured by in situ and mobile bag techniques respectively. Decorticated oat showed higher (p = .01) concentrations of crude protein (CP; 134 vs. 108 g/kg DM) and crude fat (71.6 vs. 53.1 g/kg DM) and a higher (p = .001) organic matter digestibility (OMD; 888 vs. 703 g/kg OM) than oat. The content of total fatty acids (FA) in DM was higher in decorticated oat. The proportion of linoleic acid (C18:2 n6) increased (p < .05) due to decortication, while the linolenic acid (C18:3 n3) proportion of total FA decreased in decorticated oat. Decortication increased (p = .01) the concentration of amino acids (AA), but the proportion of lysine in total AA decreased (p < .002). Effective degradability (ED) of both DM and CP was (p < .001) higher in decorticated oat. Decortication increased the total tract disappearance (TTD) and PRD of CP (p < .001). In conclusion, decortication can be used as a practical approach to increase the nutritional value of oat.

Systemic therapy for relapsed/refractory meningioma: Is there potential for antiangiogenic agents?

Effective therapies for relapsed/refractory meningioma after surgery and radiation therapy represent an unmet need. Most meningiomas are highly vascularized tumors and, therefore, potentially amenable to antiangiogenic therapy. Herein, we review comprehensively the scientific literature on systemic therapy options for relapsed, persistent or metastatic meningioma, not amenable to local therapy. Also, this review offers insights into the function of vascular endothelial growth factor/receptor pathway both in health and disease. Further, we address the current status of the preclinical and clinical studies targeting vascular endothelial growth factor/receptor signaling in meningioma. Most relevant publications were identified through searching the PubMed/Medline database for articles published from inception to 1 February 2018. Vascular endothelial growth factor pathway activation might represent the primary driver of angiogenesis in meningioma. Positive findings of two prospective phase II trials, supported by the results of several retrospective cohorts, suggest a clinical benefit for the vascular endothelial growth factor inhibitor bevacizumab in refractory meningioma. Bevacizumab causes both peritumoral brain edema reduction and true meningioma shrinkage. Patients with WHO grades II-III meningioma appear to benefit more than patients with grade I disease. Similarly, responses have been documented with certain oral targeted anti-vascular endothelial growth factor/receptor agents. Further exploration of the role of vascular endothelial growth factor/receptor inhibitors in refractory meningioma seems warranted.

Alterations in pancreatic ß cell function and Trypanosoma cruzi infection: evidence from human and animal studies.

The parasite Trypanosoma cruzi causes a persistent infection, Chagas disease, affecting millions of persons in endemic areas of Latin America. As a result of immigration, this disease has now been diagnosed in non-endemic areas worldwide. Although, the heart and gastrointestinal tract are the most studied, the insulin-secreting ß cell of the endocrine pancreas is also a target of infection. In this review, we summarize available clinical and laboratory evidence to determine whether T. cruzi-infection-mediated changes of ß cell function is likely to contribute to the development of hyperglycemia and diabetes. Our literature survey indicates that T. cruzi infection of humans and of experimental animals relates to altered secretory behavior of ß cells. The mechanistic basis of these observations appears to be a change in stimulus-secretion pathway function rather than the loss of insulin-producing ß cells. Whether this attenuated insulin release ultimately contributes to the pathogenesis of diabetes in human Chagas disease, however, remains to be determined. Since the etiologies of diabetes are multifactorial including genetic and lifestyle factors, the use of cell- and animal-based investigations, allowing direct manipulation of these factors, are important tools in testing if reduced insulin secretion has a causal influence on diabetes in the setting of Chagas disease. Long-term clinical investigations will be required to investigate this link in humans.

Draft genome sequences of 53 Lactococcus and Leuconostoc strains isolated from two undefined DL-starter cultures.

This study presents the complete genomes of 53 strains of Lactococcus and Leuconostoc isolated from two undefined DL-starter cultures originating from Denmark, Tistrup, and P. The genomes were reconstructed using long-read, nanopore-based DNA sequencing, delivering comprehensive data set for comparative genomics and taxonomic classification, with potential utility in dairy fermentation processes.

Formation of RRR-α-tocopherol in rumen and intestinal digestibility of tocopherols in dairy cows.

Tocopherol sources in diets are often a combination of all-rac-α-tocopheryl acetate (synthetic α-tocopherol) from vitamin supplements and natural tocopherols and 2R-(4'R, 8'R)-5,7,8-trimethyltocotrienol (α-tocotrienols) from the feed sources. Synthetic α-tocopherol consists of 8 different stereoisomers including 2R-(4'R, 8'R)-5,7,8-trimethyltocol (RRR-α-tocopherol), 2R-(4'S, 8'R)-5,7,8-trimethyltocol (RSR-α-tocopherol), 2R-(4'R, 8'S)-5,7,8-trimethyltocol (RRS-α-tocopherol), 2R-(4'S, 8'S)-5,7,8-trimethyltocol (RSS-α-tocopherol), 2S-(4'S, 8'S)-5,7,8-trimethyltocol (SSS-α-tocopherol), 2S-(4'R, 8'S)-5,7,8-trimethyltocol (SRS-α-tocopherol), 2S-(4'S, 8'R)-5,7,8-trimethyltocol (SSR-α-tocopherol), and 2S-(4'R, 8'R)-5,7,8-trimethyltocol (SRR-α-tocopherol). The pre-absorption metabolism of tocopherols and tocotrienols in ruminants differs from monogastric animals due to the extensive microbial fermentation in the anaerobic rumen. The current study investigated the impact of toasting and decortication of oats on metabolism in the digestive tract (synthesis, digestion), and intestinal digestibility of tocopherols in dairy cows by using 4 ruminal and intestinal cannulated Danish Holstein cows in a 4 × 4 Latin square design for 4 periods. Cows were fed a total mixed ration ad libitum containing different forms of oats: whole oat, decorticated oat, toasted oat, and decorticated toasted oat, all rolled before mixed ration. Overall means across 4 treatments were statistically analyzed, testing whether overall means were different from zero. Decortication or toasting did not affect the balance or digestibility of α-tocopherols in rumen. Average across treatments showed the ruminal degradation of synthetic α-tocopherol (279 mg/d, P = 0.02; P-value shows that average across treatments is different from zero), synthetic 2R-α-tocopherol (133 mg/d, P < 0.01; summation of RRS-, RSR- and RSS-α-tocopherol), and 2S-α-tocopherol (190 mg/d; P < 0.01, summation of SSS-, SRS-, SSR, and SRR-α-tocopherol), while RRR-α-tocopherol was formed in the rumen (221 mg/d, P = 0.10). The average across treatments showed that small intestinal digestibility of tocopherols ranked in the following order: α-tocotrienol > natural α-tocopherol > synthetic α-tocopherols > 2R-(4'R, 8'R)-,7,8-dimethyltocol (γ-tocopherol). The average across treatments for small intestinal and feed-ileum digestibility ranked in the following order: RRR-α-tocopherol > synthetic 2R-α-tocopherol > 2S-α-tocopherol. Results showed the first evidence for RRR-α-tocopherol formation under anaerobic conditions in the rumen. In addition, synthetic α-tocopherol stereoisomers, γ-tocopherol and α-tocotrienol were degraded in the rumen. There was a discrimination against absorption of synthetic 2R- and 2S-α-tocopherol in the small intestine.

A westernized diet changed the colonic bacterial composition and metabolite concentration in a dextran sulfate sodium pig model for ulcerative colitis.

Introduction: Ulcerative colitis (UC) is characterized by chronic inflammation in the colonic epithelium and has a blurred etiology. A western diet and microbial dysbiosis in the colon were reported to play a role in UC development. In this study, we investigated the effect of a westernized diet, i.e., increasing fat and protein content by including ground beef, on the colonic bacterial composition in a dextran sulfate sodium (DexSS) challenged pig study. Methods: The experiment was carried out in three complete blocks following a 2×2 factorial design including 24 six-week old pigs, fed either a standard diet (CT) or the standard diet substituted with 15% ground beef to simulate a typical westernized diet (WD). Colitis was induced in half of the pigs on each dietary treatment by oral administration of DexSS (DSS and WD+DSS, respectively). Samples from proximal and distal colon and feces were collected. Results and discussion: Bacterial alpha diversity was unaffected by experimental block, and sample type. In proximal colon, WD group had similar alpha diversity to CT group and the WD+DSS group showed the lowest alpha diversity compared to the other treatment groups. There was a significant interaction between western diet and DexSS for beta diversity, based on Bray-Curtis dissimilarly. The westernized diet and DexSS resulted in three and seven differentially abundant phyla, 21 and 65 species, respectively, mainly associated with the Firmicutes and Bacteroidota phyla followed by Spirochaetota, Desulfobacterota, and Proteobacteria. The concentration of short-chain fatty acids (SCFA) was lowest in the distal colon. Treatment had a slight effect on the estimates for microbial metabolites that might have valuable biological relevance for future studies. The concentration of putrescine in the colon and feces and that of total biogenic amines was highest in the WD+DSS group. We conclude that a westernized diet could be a potential risk factor and an exacerbating agent for UC by reducing the abundance of SCFA-producing bacteria, increasing the abundance of pathogens such as Helicobacter trogontum, and by increasing the concentration of microbial proteolytic-derived metabolites in the colon.

Corrigendum: A westernized diet changed the colonic bacterial composition and metabolite concentration in a dextran sulfate sodium pig model for ulcerative colitis.

[This corrects the article DOI: 10.3389/fmicb.2023.1018242.].

Prehospital trauma system reduces mortality in severe trauma: a controlled study of road traffic casualties in Iraq.

INTRODUCTION: In low-resource communities with long prehospital transport times, most trauma deaths occur outside the hospital. Previous studies from Iraq demonstrate that a two-tier network of rural paramedics with village-based first helpers reduces mortality in land mine and war-injured from 40% to 10%. However, these studies of prehospital trauma care in low-income countries have been conducted with historical controls, thus the results may be unreliable due to differences in study contexts. The aim of this study was to use a controlled study design to examine the effect of a two-tier prehospital rural trauma system on road traffic accident trauma mortality. METHODS: A single referral surgical hospital was the endpoint in a single-blinded, non-randomized cohort study. The catchment areas consisted of some districts with no formal Emergency Medical Services (EMS) system, and other districts where 95 health center paramedics had been trained and equipped to provide advanced life support, and 5,000 laypersons had been trained to give on-site first aid. The hospital staff registered trauma mortality and on-admission physiological severity blindly. Assuming that prehospital care would have no significant impact on mortality in moderate injuries, only road traffic accident (RTA) casualties with an Injury Severity Score (ISS)≥9 were selected for study. RESULTS: During a three-month study period, 205 patients were selected for study (128 in the treatment group and 77 in the control group). The mean prehospital transit time was approximately two hours. The two groups were comparable with regards to demographic characteristics, distribution of wounds and injuries, and mean anatomical severity. The mortality rate was eight percent in the treatment group, compared to 44% in the control group (95% CI, 25%-48%). Adjusted for severity differences between the treatment and control groups, prehospital care was a significant contributor to survival. CONCLUSION: Where prehospital transport time is long, a two-tier prehospital system of trained paramedics and layperson first responders reduces trauma mortality in severe RTA injuries. The findings may be valid for civilian Emergency Medical Services interventions in other low-resource countries.

Etiology of Colitis-Complex Diarrhea in Growing Pigs: A Review.

Colitis-complex diarrhea (CCD) in pigs can be defined as a type of diarrhea, which is associated with colonic inflammation and disrupted colonic gut barrier functionality in growing pigs (4-16 weeks post-weaning). It is a challenge for the pig industry as it is associated with the high use of antibiotics, reduced animal welfare, and depressed growth rate. The exact etiology of CCD is still unclear; however, pathogens including Brachyspira (B.) hyodysenteriae, B. pilosicoli, and swine whipworms such as Trichuris (T.) suis have been involved in specific colitis (SC). In the absence of specific pathogens, dietary factors, such as high levels of protein, pelleted feedstuffs, and lack of sufficient antioxidants, can result in non-specific colitis (NSC). On the other hand, supplement of polyunsaturated fatty acids (PUFA) and polyphenols, sufficient supply of essential amino acids (e.g., threonine, cysteine, and proline), short-chain fatty acids (SCFA; especially butyrate), and resistant starch have shown to confer preventing/ameliorating effects on CCD. Different putative biomarkers associated with CCD have been presented. It is anticipated that a comprehensive picture of the possible causes of CCD and potential dietary interventions could cast light on the direction of future studies aimed at developing preventive and curative strategies against CCD in growing pigs.

Association of Hippo Signalling Pathway with Epigenetic Changes in Cancer Cells and Therapeutic Approaches: A Review.

Hippo signalling pathway that is evolutionarily conserved affects diver's pathology and physiology processes, including tissue repair, wound healing, tissue size and tissue regeneration. Epigenetic changes are post-translational modifications in DNA proteins and histones. Epigenetic changes including histone acetylation and deacetylation, miRNAs dysregulation, and aberrant DNA methylation, inflammatory genes actives abnormal in Hippo signaling pathway. Using some treatments, including Histone Deacetylases (HDACs), herbal composition, siRNAs and long non-coding RNA (lncRNA) for suppressing cancer cells by targeting Hippo pathways, may open new views in cancer target therapy fields. The aim of this review study is firstly to demonstrate the importance of Hippo signalling and its association with epigenetic changes in cancer and then to demonstrate progress in targeting Hippo signalling in cancer therapy.

Multistage porogen-induced heteroporous Co, N-doped carbon catalyst toward efficient oxygen reduction.

Co, N co-doped carbon (CoN@C) with properly engineered heteropores was facilely synthesized using metal carbonate hydroxides as metal precursor and multistage porogen. CoN@C therefore exhibits superior ORR catalytic activity with a half-wave potential of 0.876 V vs. RHE, and the CoN@C-based zinc-air battery can be stably cycled for 100 h.

COVID-19: Our Current Knowledge of Epidemiology, Pathology, Therapeutic Approaches, and Diagnostic Methods.

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) firstly emerged in Wuhan, China at the end of 2019. After going through the experimental process, the virus was named the novel coronavirus (2019-nCoV) by the World Health Organization (WHO) in February 2020 which has created a global pandemic. The coronavirus disease 2019 (COVID-19) infection is challenging the people who are especially suffering from chronic health problems such as asthma, diabetes, and heart disease or immune system deteriorating disorders, including cancers, Alzheimer's, etc. Other predisposing/risk factors consist of smoking and age (elderly people are at higher risk). The 2019-nCoV attacks epithelial cells in all organs, particularly epithelial cells in the lungs, resulting in viral pneumonia. The 2019-nCoV starts its invasion with the attachment and entry into the respiratory tract epithelial cells via Angiotensin-Converting Enzyme 2 (ACE2) receptors on the epithelial cells. The critical problem with 2019-nCoV is its ability in human to human asymptomatic transmission which causes the rapid and hidden spread of the virus among the population. Also, there are several reports of highly variable and tightly case-dependent clinical manifestations caused by SARS-CoV2, which made the virus more enigmatic. The clinical symptoms are varied from common manifestations which occurred in flu and cold, such as cough, fever, body-ache, trembling, and runny nose to severe conditions, like the Acute Respiratory Distress Syndrome (ARDS) or even uncommon/unusual symptoms such as anosmia, skin color change, and stroke. In fact, besides serious injuries in the respiratory system, COVID-19 invades and damages various organs, including the kidney, liver, gastrointestinal, and nervous system. Accordingly, to cut the transmission chain of disease and control the infection spread. One of the major solutions seems to be early detection of the carriers, particularly the asymptomatic people, with sensitive and accurate diagnostic techniques. Moreover, developing novel and appropriate therapeutic approaches will contribute to the suitable management of the pandemic. Therefore, there is an urgent necessity to make comprehensive investigations and study reviews about COVID-19, offering the latest findings of novel therapies, drugs, epidemiology, and routes of virus transmission and pathogenesis. In this review, we discuss new therapeutic outcomes and cover and the most significant aspects of COVID-19, including the epidemiology, biological features, organs failure, and diagnostic techniques.