Life

For more than 20 years, yeast has been a widely used system for the expression of human membrane transporters. Among them, more than 400 are members of the largest transporter family, the SLC superfamily. SLCs play critical roles in maintaining cellular homeostasis by transporting nutrients, ions, and waste products. Based on their involvement in drug absorption and in several human diseases, they are considered emerging therapeutic targets. Despite their critical role in human health, a large part of SLCs’ is ‘orphans’ for substrate specificity or function. Moreover, very few data are available concerning their 3D structure. On the basis of the human health benefits of filling these knowledge gaps, an understanding of protein expression in systems that allow functional production of these proteins is essential. Among the 500 known yeast species, S. cerevisiae and P. pastoris represent those most employed for this purpose. This review aims to provide a comprehensive state-of-the-art on the attempts of human SLC expression performed by exploiting yeast. The collected data will hopefully be useful for guiding new attempts in SLCs expression with the aim to reveal new fundamental data that could lead to potential effects on human health. Full article

Type 2 diabetes mellitus (T2DM) is one of the world’s leading causes of death and life-threatening conditions. Therefore, we review the complex vicious circle of causes responsible for T2DM and risk factors such as the western diet, obesity, genetic predisposition, environmental factors, and SARS-CoV-2 infection. The prevalence and economic burden of T2DM on societal and healthcare systems are dissected. Recent progress on the diagnosis and clinical management of T2DM, including both non-pharmacological and latest pharmacological treatment regimens, are summarized. The treatment of T2DM is becoming more complex as new medications are approved. This review is focused on the non-insulin treatments of T2DM to reach optimal therapy beyond glycemic management. We review experimental and clinical findings of SARS-CoV-2 risks that are attributable to T2DM patients. Finally, we shed light on the recent single-cell-based technologies and multi-omics approaches that have reached breakthroughs in the understanding of the pathomechanism of T2DM. Full article

Background: Patient access to medical records can improve quality of care. The phellow application (app) was developed to provide patients access to selected content of their medical record. It was tested at a heart transplantation (HTx) outpatient clinic. The aims of this study were (1) to assess usability of phellow, (2) to determine feasibility of implementation in routine care, and (3) to study the effects app use had on patients’ self-management. Methods: Usability was measured quantitatively through the System Usability Scale (SUS). Furthermore, usability, feasibility, and effects on self-management were qualitatively assessed through interviews with users, non-users, and health care providers. Results: The SUS rating (n = 31) was 79.9, indicating good usability. Twenty-three interviews were conducted. Although appreciation and willingness-to-use were high, usability problems such as incompleteness of record, technical issues, and complex registration procedures were reported. Improved technical support infrastructure, clearly defined responsibilities, and app-specific trainings were suggested for further implementation. Patients described positive effects on their self-management. Conclusions: To be feasible for implementation in routine care, usability problems should be addressed. Feedback on the effect of app use was encouraging. Accompanying research is crucial to monitor usability improvements and to further assess effects of app use on patients. Full article

Heart failure (HF) is a common disease that causes significant limitations on the organism’s capacity and, in extreme cases, leads to death. Clinically, iron deficiency (ID) plays an essential role in heart failure by deteriorating the patient’s condition and is a prognostic marker indicating poor clinical outcomes. Therefore, in HF patients, supplementation of iron is recommended. However, iron treatment may cause adverse effects by increasing iron-related apoptosis and the production of oxygen radicals, which may cause additional heart damage. Furthermore, many knowledge gaps exist regarding the complex interplay between iron deficiency and heart failure. Here, we describe the current, comprehensive knowledge about the role of the proteins involved in iron metabolism. We will focus on the molecular and clinical aspects of iron deficiency in HF. We believe that summarizing the new advances in the translational and clinical research regarding iron deficiency in heart failure should broaden clinicians’ awareness of this comorbidity. Full article

Diabetes is one of the leading causes of kidney disease. Diabetic kidney disease (DKD) is a major cause of end-stage kidney disease (ESKD) worldwide, and it is linked to an increase in cardiovascular (CV) risk. Diabetic nephropathy (DN) increases morbidity and mortality among people living with diabetes. Risk factors for DN are chronic hyperglycemia and high blood pressure; the renin-angiotensin-aldosterone system blockade improves glomerular function and CV risk in these patients. Recently, new antidiabetic drugs, including sodium–glucose transport protein 2 inhibitors and glucagon-like peptide-1 agonists, have demonstrated additional contribution in delaying the progression of kidney disease and enhancing CV outcomes. The therapeutic goal is regression of albuminuria, but an atypical form of non-proteinuric diabetic nephropathy (NP-DN) is also described. In this review, we provide a state-of-the-art evaluation of current treatment strategies and promising emerging treatments. Full article

Pathogen infection seriously affects plant development and crop productivity, sometimes causing total crop failure. In this study, artificial stab inoculation was used to inoculate sugarcane smut. The changes in leaf gas exchange, chlorophyll fluorescence variables, and related defense enzyme activities were measured in sugarcane cultivar ROC22 after pathogen infection. The results showed that the net photosynthetic rate (Pn), stomatal conductance (gs), and transpiration rate (Tr) downregulated in the first three days after smut infection and upregulated on the fourth day; intercellular CO₂ concentration (Ci) increased in the first three days of smut infection and reduced on the fourth day. The chlorophyll fluorescence parameters, i.e., Fo, Fm, Fv/Fm, Fs, and Fv′/Fm′ decreased at the initial stage of pathogen infection but increased rapidly up to 3 days after smut infection. It can be seen that sugarcane seedlings showed a positive response to pathogen infection. The correlation coefficient relationship between Pn, gs, and Tr reached above 0.800, showing a significant correlation; Ci was positively correlated with Fv′/Fm′ and ΦPSII, reaching above 0.800 and showing a significant correlation; Fo positively correlated with Fv/Fm, Fs, and ETR; Fv /Fm was positively correlated with Fv′/Fm′; Fs significantly correlated with Fv′/Fm′; and Fv′/Fm′ positively correlated with ΦPSII. After inoculation with smut, the related defense enzymes, i.e., POD, SOD, PPO, and PAL, were increased and upregulated; photosynthetic parameters can be associated with an increase in enzymatic activities. The results of this study will help to further study of the response mechanism to smut in the sugarcane growing period and provide a theoretical reference for sugarcane resistance to smut breeding. Full article

Peroxidases and laccases are oxidative enzymes involved in physiological processes in plants, covering responses to biotic and abiotic stress as well as biosynthesis of health-promoting specialized metabolites. Although they are thought to be involved in the biosynthesis of (+)-pinoresinol, a comprehensive investigation of this class of enzymes has not yet been conducted in the emerging oil crop sesame and no information is available regarding the potential (+)-pinoresinol synthase genes in this crop. In the present study, we conducted a pan-genome-wide identification of peroxidase and laccase genes coupled with transcriptome profiling of diverse sesame varieties. A total of 83 and 48 genes have been identified as coding for sesame peroxidase and laccase genes, respectively. Based on their protein domain and Arabidopsis thaliana genes used as baits, the genes were classified into nine and seven groups of peroxidase and laccase genes, respectively. The expression of the genes was evaluated using dynamic transcriptome sequencing data from six sesame varieties, including one elite cultivar, white vs black seed varieties, and high vs low oil content varieties. Two peroxidase genes (SiPOD52 and SiPOD63) and two laccase genes (SiLAC1 and SiLAC39), well conserved within the sesame pan-genome and exhibiting consistent expression patterns within sesame varieties matching the kinetic of (+)-pinoresinol accumulation in seeds, were identified as potential (+)-pinoresinol synthase genes. Cis-acting elements of the candidate genes revealed their potential involvement in development, hormonal signaling, and response to light and other abiotic triggers. Transcription factor enrichment analysis of promoter regions showed the predominance of MYB binding sequences. The findings from this study pave the way for lignans-oriented engineering of sesame with wide potential applications in food, health and medicinal domains. Full article

Vascular malformations are frequent in the head and neck region, affecting the nervous system. The wide range of therapeutic approaches demand the correct anatomical, morphological, and functional characterization of these lesions supported by imaging. Using a systematic search protocol in PubMed, Google Scholar, Ebsco, Redalyc, and SciELO, the authors extracted clinical studies, review articles, book chapters, and case reports that provided information about vascular cerebral malformations, in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A total of 385,614 articles were grouped; using the inclusion and exclusion criteria, three of the authors independently selected 51 articles about five vascular cerebral malformations: venous malformation, brain capillary telangiectasia, brain cavernous angiomas, arteriovenous malformation, and leptomeningeal angiomatosis as part of Sturge–Weber syndrome. We described the next topics—“definition”, “etiology”, “pathophysiology”, and “treatment”—with a focus on the relationship with the imaging approach. We concluded that the correct anatomical, morphological, and functional characterization of cerebral vascular malformations by means of various imaging studies is highly relevant in determining the therapeutic approach, and that new lines of therapeutic approaches continue to depend on the imaging evaluation of these lesions. Full article

Thromboembolic events (TEE) are high-risk complications in patients undergoing neoadjuvant chemotherapy (NAC) and radical cystectomy (RC) for urothelial muscle-invasive bladder cancer (MIBC). The purpose of the study was to investigate any differences in TEE-incidence, comparing peripherally inserted central catheter (PICC) versus a totally implanted port (PORT) as CVA (central venous access) during NAC. We identified 947 cystectomized MIBC-patients from four Swedish medical centers in 2009–2021. Inclusion criteria were cT2-T4aN0M0 and 375 patients were finally eligible and evaluated, divided into: NAC-administered (n = 283) resp. NAC-naïve-NAC-eligible (n = 92), the latter as tentative control group. Data on TEEs and types of CVA were retrospectively collected and individually validated, from final transurethral resection of the bladder tumor (TUR-B) to 30 days post-RC. Adjusted logistic regression and log rank test were used for statistical analyses. Amongst NAC-administered, 83% (n = 235) received PICCs and 15% (n = 42) PORTs. Preoperative TEEs occurred in 38 PICC-patients (16.2%) and in one PORT-patient (2.4%), with 47 individual events registered. We found a significantly increased odds ratio of TEE in NAC-administered PICC-patients compared to in PORT-patients (OR: 8.140, p-value: 0.042, 95% CI 1.078–61.455). Our findings indicate a greater risk for pre-RC TEEs with PICCs than with PORTs, suggesting favoring the usage of PORTs for MIBC-NAC-patients. Full article

Non-communicable diseases are those conditions to which causative infectious agents cannot readily be assigned. It is increasingly likely that at least some of these conditions are due to the breakdown of the previously mutualistic intestinal microbiota under the influence of a polluted, biocide-rich, environment. Following the mid-20th century African studies of Denis Burkitt, the environmental cause of conditions such as obesity has been ascribed to the absence of sufficient fibre in the modern diet, however in itself that is insufficient to explain the parallel rise of problems with both the immune system and of mental health. Conversely, Burkitt himself noted that the Maasai, a cattle herding people, remained healthy even with their relatively low intake of dietary fibre. Interestingly, however, Burkitt also emphasised that levels of non-communicable disease within a population rose as faecal weight decreased significantly, to about one third of the levels found in healthy populations. Accordingly, a more cogent explanation for all the available facts is that the fully functioning, adequately diverse microbiome, communicating through what has been termed the microbiota–gut–brain axis, helps to control the passage of food through the digestive tract to provide itself with the nutrition it needs. The method of communication is via the production of semiochemicals, interkingdom signalling molecules, potentially including dopamine. In turn, the microbiome aids the immune system of both adult and, most importantly, the neonate. In this article we consider the role of probiotics and prebiotics, including fermented foods and dietary fibre, in the stimulation of the immune system and of semiochemical production in the gut lumen. Finally, we reprise our suggestion of an ingestible sensor, calibrated to the detection of such semiochemicals, to assess both the effectiveness of individual microbiomes and methods of amelioration of the associated non-communicable diseases. Full article

The main aim of this study is to compare the incidence rate and severity of deep neck infection (DNI) in patients post-UPPP+ T (uvulopalatopharyngoplasty plus tonsillectomy) and without UPPP+ T. We utilized the data derived from the Longitudinal Health Insurance Database (LHID) of the National Health Insurance Research Database (NHIRD) in Taiwan from 1 January 2000 to 31 December 2012. Patients who had undergone combined UPPP and tonsillectomy were selected using National Health Insurance (NHI) surgical order. Patients with DNI were selected using International Classification of Diseases (ICD-9-CM) code. A logistic regression model was applied for risk analysis. There were 1574 patients in the UPPP+ T cohort, and 6,296 patients who did not undergo combined UPPP and tonsillectomy for the control group. Our analysis showed that patients with an obstructive sleep apnea syndrome (OSAS) history constitute 76.1% (n = 1198) of the UPPP+ T cohort. Compared to the control group, there was no significantly increased incidence rate of DNI after UPPP+ T within 1–60 months. Patients undergoing combined UPPP and tonsillectomy had a lower intubation rate for DNI, with an adjusted odds ratio of 0.47 (95% CI = 0.32–0.69). The combined UPPP and tonsillectomy does not increase the risk of DNI within 1–60 months. Furthermore, combined UPPP and tonsillectomy can reduce the severity for DNI by decreasing the intubation rate and length of hospitalization. Full article

Background: The benefit of the combined use of an intra-aortic balloon pump (IABP) and venoarterial extracorporeal membrane oxygenation (VA-ECMO) for postcardiotomy shock remains unclear. We aimed to analyse the potential benefits and safety of combining these two devices. Methods: We enrolled 200 patients treated with either VA-ECMO only or in combination with IABP (ECMO-I group) between January 2012 and January 2021. To adjust the patients’ backgrounds, we used propensity score matching for additional analyses, resulting in 57 pairs. The primary endpoint was 30-day survival. Secondary endpoints included successful weaning and complication rates. We also analysed hemodynamic parameters in both groups. Results: After propensity score matching, 30-day survival was better in the ECMO-I group (log-rank p = 0.004). The ECMO-I and ECMO-only groups differed regarding the secondary endpoints, including successful weaning (50.9% and 26.3%, respectively; p = 0.012) and the need for continuous renal replacement therapy (28.1% and 50.9%, p = 0.021). Complication rates were not statistically different between the two groups. Conclusion: Compared to VA-ECMO alone, the combined use of VA-ECMO and IABP is beneficial regarding 30-day survival in selected patients with postcardiotomy shock; successful ECMO weaning and freedom from renal replacement therapy is more common in patients supported with VA-ECMO plus IABP. Full article

Protein arginine methyltransferases 7 (Prmt7) is expressed in male germ cells, including primordial germ cells, gonocytes, and spermatogonia. Our previous study demonstrated that Prmt7 downregulation reduced the proliferation of GC-1 cells (a cell line of mouse immortalized spermatogonia). However, how Prmt7 regulates spermatogonial proliferation through miRNA and the target gene remains elusive. Here, we experimentally reduced the Prmt7 expression in the GC-1 cells and subjected them to miRNA sequencing to explore the miRNA profile and its Prmt7-responsive members. In total, 48 differentially expressed miRNAs (DEmiRNAs), including 36 upregulated and 12 downregulated miRNAs, were identified. After verifying the validity of sequencing results through qRT-PCR assays in randomly selected DEmiRNAs, we predicted the target genes of these DEmiRNAs. Next, we combined DEmiRNA target genes and previously identified differentially expressed genes between Prmt7 knockdown and control groups of GC-1 cells, which resulted in seven miRNA/target gene pairs. Among these miRNA/target gene pairs, we further detected the expression of Col6a3 (collagen type VI alpha 3) as the target gene of mmu-miR-877-3p. The results suggested that Prmt7 downregulation in mouse spermatogonia might function through miR-877-3p/Col6a3. Overall, these findings provide new insights into the role of Prmt7 in male germ cell development through miRNA and target genes. Full article

Orthotopic neobladder (ONB) reconstruction is a continent urinary diversion procedure increasingly used in patients with muscle-invasive bladder cancer following radical cystectomy (RC). It represents a valid alternative to the ileal duct in suitable patients who do not prefer a stoma and are motivated to undergo adequate training of the neobladder. Careful patient selection, taking into account the absolute and relative contraindications for ONB as well as an adequate recovery protocol after surgery are integral to the success of this procedure and the oncological and functional outcomes. The objective of this review is to summarize the current data on RC with ONB in terms of patient selection, preoperative preparation, surgical techniques and functional (continence and sexual activity) and oncological outcomes, with particular attention to the management of complications and the impact on quality of life (QoL). Full article

In recent years, new interest is growing in the left atrium (LA). LA functional analysis and measurement have an essential role in cardiac function evaluation. Left atrial size and function are key elements during the noninvasive analysis of diastolic function in several heart diseases. The LA represents a “neuroendocrine organ” with high sensitivity to the nervous, endocrine, and immune systems. New insights highlight the importance of left atrial structural, contractile, and/or electrophysiological changes, introducing the concept of “atrial cardiomyopathy”, which is closely linked to underlying heart disease, arrhythmias, and conditions such as aging. The diagnostic algorithm for atrial cardiomyopathy should follow a stepwise approach, combining risk factors, clinical characteristics, and imaging. Constant advances in imaging techniques offer superb opportunities for a comprehensive evaluation of LA function, underlying specific mechanisms, and patterns of progression. In this literature review, we aim to suggest a practical, stepwise algorithm with integrative multimodality imaging and a clinical approach for LA geometry and functional analysis. This integrates diastolic flow analysis with LA remodelling by the application of traditional and new diagnostic imaging techniques in several clinical settings such as heart failure (HF), atrial fibrillation (AF), coronary artery disease (CAD), and mitral regurgitation (MR). Full article

Bat genomes are characterized by a diverse transposable element (TE) repertoire. In particular, the genomes of members of the family Vespertilionidae contain both active retrotransposons and active DNA transposons. Each TE type is characterized by a distinct pattern of accumulation over the past ~40 million years. Each also exhibits its own target site preferences (sometimes shared with other TEs) that impact where they are likely to insert when mobilizing. Therefore, bats provide a great resource for understanding the diversity of TE insertion patterns. To gain insight into how these diverse TEs impact genome structure, we performed comparative spatial analyses between different TE classes and genomic features, including genic regions and CpG islands. Our results showed a depletion of all TEs in the coding sequence and revealed patterns of species- and element-specific attraction in the transcript. Trends of attraction in the distance tests also suggested significant TE activity in regions adjacent to genes. In particular, the enrichment of small, non-autonomous TE insertions in introns and near coding regions supports the hypothesis that the genomic distribution of TEs is the product of a balance of the TE insertion preference in open chromatin regions and the purifying selection against TEs within genes. Full article

Non-alcoholic fatty liver disease (NAFLD) represents the hepatic expression of the metabolic syndrome and is the most prevalent liver disease. NAFLD is associated with liver-related and extrahepatic morbi-mortality. Among extrahepatic complications, cardiovascular disease (CVD) is the primary cause of mortality in patients with NAFLD. The most frequent clinical expression of CVD is the coronary artery disease (CAD). Epidemiological data support a link between CAD and NAFLD, underlain by pathogenic factors, such as the exacerbation of insulin resistance, genetic phenotype, oxidative stress, atherogenic dyslipidemia, pro-inflammatory mediators, and gut microbiota. A thorough assessment of cardiovascular risk and identification of all forms of CVD, especially CAD, are needed in all patients with NAFLD regardless of their metabolic status. Therefore, this narrative review aims to examine the available data on CAD seen in patients with NAFLD, to outline the main directions undertaken by the CVD risk assessment and the multiple putative underlying mechanisms implicated in the relationship between CAD and NAFLD, and to raise awareness about this underestimated association between two major, frequent and severe diseases. Full article

We apply the non-Markov-type analysis of state-to-state transitions to nearly microsecond molecular dynamics (MD) simulation data at a folding temperature of a small artificial protein, chignolin, and we found that the time scales obtained are consistent with our previous result using the weighted ensemble simulations, which is a general path-sampling method to extract the kinetic properties of molecules. Previously, we also applied diffusion map (DM) analysis, which is one of a manifold of learning techniques, to the same trajectory of chignolin in order to cluster the conformational states and found that DM and relaxation mode analysis give similar results for the eigenvectors. In this paper, we divide the same trajectory into shorter pieces and further apply DM to such short-length trajectories to investigate how the obtained eigenvectors are useful to characterize the conformational change of chignolin. Full article