Miracle-dz/UniFAR-FTUs huggingface dataset:
Social differentiation of the perception and human tissues donation for research purposes

The willingness to donate human biological material for research purposes is shaped by socio-cultural factors; however, there is a lack of studies analysing the social perception of different human tissues, which may affect such willingness. This study aimed to distinguish different sociocultural categories of human tissues and types of potential donors based on their willingness to donate material. Quantitative research was conducted on a sample of 1,100 adult Poles representative in terms of sex, place of residence and education. According to the study, people were most willing to donate urine (73.9%), blood (69.7%), hair and tears (69.6%) and the least willing to donate post-mortem brain fragments (20%), sperm (males; 36.4%) and egg cells (females; 39.6%). A factor analysis revealed four sociocultural categories of donated tissues: irrelevant, redundant, ordinary and sensitive. Based on these sociocultural categories of tissues, four types of donors were identified: reluctant, highly cooperative, average cooperative and selectively cooperative. The willingness to donate human samples for research is shaped by the sociocultural perception of different body parts and tissues. The lower the sense of “personal relationship” with a specific type of tissue, organ or part of the body, the higher the motivation to donate such biological material for research purposes. Additionally, the willingness to donate is mostly shaped by social trust in physicians and scientists, and potential donors’ engagement in charity activities.
Mycobacterium tuberculosis KasA as a drug target: Structure-based inhibitor design

Recent studies have reported the β-ketoacyl-acyl carrier protein KasA as a druggable target for Mycobacterium tuberculosis. This review summarizes the current status of major classes of KasA inhibitors with an emphasis on significant contributions from structure-based design methods leveraging X-ray crystal structures of KasA alone and in complex with inhibitors. The issues addressed within each inhibitor class are discussed while detailing the characterized interactions with KasA and structure-activity relationships. A critical analysis of these findings should lay the foundation for new KasA inhibitors to study the basic biology of M. tuberculosis and to form the basis of new antitubercular molecules of clinical significance with activity against drug-sensitive and drug-resistant infections.
Phylogeny and adaptative evolution to chemosynthetic habitat in barnacle (Cirripedia: Thoracica) revealed by mitogenomes

Thoracican barnacles represent a unique group that has evolved in parallel identical somatotype s (sessile, stalked and asymmetric) in both normal and chemosynthetic environments. Hydrothermal vents and methane seeps are typical extreme deep-sea chemosynthetic habitats for marine macrobenthos. Characterizing the evolutionary history and adaptive strategy of barnacles is fundamentally important for understanding their origin, speciation, and diversification. Herein, we performed a series of phylogenetic analyses focusing on the mitochondrial genomes of the main extant barnacle lineages. Phylogenetic inferences and topology tests contradict the view of the sister relationship between verrucomorphs and balanomorphs, instead revealing that pollicipedids, calanticids and balanomorphs share common ancestor. Selective pressure analyses indicate that the two barnacle lineages of chemosynthetic ecosystems exhibit similar patterns in their evolution of adaptive characters, but have diverse and specific positive substitution sites of mitogenomes. Divergence times suggest that chemosynthetic barnacles originated in the Cenozoic, coinciding with the origins of other metazoan animals in chemosynthetic habitats as well as the Paleogene mass extinction and oceanic anoxic events. It is reasonable to suppose that ecological niche vacancy, sitotaxis, gene specificity in adaptive stress responses, and the subdivision of the ecological niche contributed to the origin and diversification of barnacles in chemosynthetic ecosystems.
In-situ electro-stimulation enhanced branching but not massive scleractinian coral growth

Calcium carbonate (CaCO3) is the main component of the skeleton of scleractinian corals and is a preferable substrate for attachment and growth. An electro-stimulation method based on the electrolysis of seawater, which generates calcium and magnesium minerals as a crystalline coating over artificial metal structures, was used to boost coral growth during the 1970s. Few studies have attempted to compare survival and growth between electro-stimulated corals and non-electro-stimulated corals in situ. In this study, we used 2D image analysis to quantify the growth of branching and massive corals on electro-stimulated structures. Among four metallic structures that were deployed in Sabang, Aceh, Indonesia, three were electro-stimulated (12 V) and one was used as a control. Two branching corals (Acropora gemmifera and Pocillopora verrucosa) and two massive coral species (Porites murrayensis and Porites lobata) were selected. A total of 256 fragments, comprising 128 fragments derived from two branching species and 128 fragments derived from two massive species, were randomly dispatched to each structure. Underwater photographs were taken at three intervals from August 2019 to December 2020. The results showed that the survival rates (excluding lost fragments) of branching corals under electro-stimulation were approximately 19% higher than massive. However, no significant difference was found between the survival rates of the treatment and control groups for both branching and massive corals. Furthermore, we found that under electro-stimulation, branching corals grew faster than controls but not massive. Our study provides pieces of evidence for the potential use of electrochemical processes in stimulating the growth of branching corals.
Iron oxides impact sulfate-driven anaerobic oxidation of methane in diffusion-dominated marine sediments

Microbial iron (Fe) reduction by naturally abundant iron minerals has been observed in many anoxic aquatic sediments in the sulfidic and methanic zones, deeper than it is expected based on its energetic yield. However, the potential consequence of this “deep” iron reduction on microbial elemental cycles is still unclear in sediments where diffusion is the dominant transport process. In this contribution, we experimentally quantify the impact of iron oxides on sulfate-driven anaerobic oxidation of methane (S-AOM) within the sulfate methane transition zone (SMTZ) of marine diffusive controlled sediments. Sediments were collected from the oligotrophic Southeastern (SE) Mediterranean continental shelf and were incubated with 13C-labeled methane. We followed the conversion of 13C-labeled methane as a proxy of S-AOM and monitored the sediment response to hematite addition. Our study shows microbial hematite reduction as a significant process in the SMTZ, which appears to be co-occurring with S-AOM. Based on combined evidence from sulfur and carbon isotopes and functional gene analysis, the reduction of hematite seems to slow down S-AOM. This contrasts with methane seep environments, where iron oxides appear to stimulate S-AOM and hence attenuate the release of the greenhouse gas methane from the sediments. In the deep methanic zone, the addition of iron oxides inhibits the methanogenesis process and hence methane gas production. The inhibition effect deeper in the sediment is not related to Fe-AOM as a competing process on the methane substrate, since Fe-AOM was not observed throughout the methanic sediments with several iron oxides additions.
T cell receptor repertoire analysis in HTLV-1-associated diseases

Human T lymphotropic virus 1 (HTLV-1) is a human retrovirus identified as the causative agent in adult T-cell leukemia/lymphoma (ATL) and chronic-progressive neuroinflammatory disorder HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). HTLV-1 is estimated to infect between 5-20 million people worldwide, although most infected individuals remain asymptomatic. HTLV-1 infected persons carry an estimated lifetime risk of approximately 5% of developing ATL, and between 0.25% and 1.8% of developing HAM/TSP. Most HTLV-1 infection is detected in CD4+ T cells in vivo which causes the aggressive malignancy in ATL. In HAM/TSP, the increase of HTLV-1 provirus induces immune dysregulation to alter inflammatory milieu, such as expansion of HTLV-1-specific CD8+ T cells, in the central nervous system of the infected subjects, which have been suggested to underlie the pathogenesis of HAM/TSP. Factors contributing to the conversion from asymptomatic carrier to disease state remain poorly understood. As such, the identification and tracking of HTLV-1-specific T cell biomarkers that may be used to monitor the progression from primary infection to immune dysfunction and disease are of great interest. T cell receptor (TCR) repertoires have been extensively investigated as a mechanism of monitoring adaptive T cell immune response to viruses and tumors. Breakthrough technologies such as single-cell RNA sequencing have increased the specificity with which T cell clones may be characterized and continue to improve our understanding of TCR signatures in viral infection, cancer, and associated treatments. In HTLV-1-associated disease, sequencing of TCR repertoires has been used to reveal repertoire patterns, diversity, and clonal expansions of HTLV-1-specific T cells capable of immune evasion and dysregulation in ATL as well as in HAM/TSP. Conserved sequence analysis has further been used to identify CDR3 motif sequences and exploit disease- or patient-specificity and commonality in HTLV-1-associated disease. In this article we review current research on TCR repertoires and HTLV-1-specific clonotypes in HTLV-1-associated diseases ATL and HAM/TSP and discuss the implications of TCR clonal expansions on HTLV-1-associated disease course and treatments.
A novel cuproptosis-related prognostic lncRNA signature for predicting immune and drug therapy response in hepatocellular carcinoma

Intratumoral copper levels are closely associated with immune escape from diverse cancers. Cuproptosis-related lncRNAs (CRLs), however, have an unclear relationship with hepatocellular carcinoma (HCC). Gene expression data from 51 normal tissues and 373 liver cancer tissues from the Cancer Genome Atlas (TCGA) database were collected and analyzed. To identify CRLs, we employed differentially expressed protein-coding genes (DE-PCGs)/lncRNAs (DE-lncRNAs) analysis, Kaplan–Meier (K-M) analysis, and univariate regression. By univariate and Lasso Cox regression analyses, we screened 10 prognosis-related lncRNAs. Subsequently, five CRLs were identified by multivariable Cox regression analysis to construct the prognosis model. This feature is an independent prognostic indicator to forecast overall survival. According to Gene Set Variation Analysis (GSVA) and Gene Ontology (GO), both immune-related biological processes (BPS) and pathways have CRL participation. In addition, we found that the characteristics of CRLs were associated with the expression of the tumor microenvironment (TME) and crucial immune checkpoints. CRLs could predict the clinical response to immunotherapy based on the studies of tumor immune dysfunction and rejection (TIDE) analysis. Additionally, it was verified that tumor mutational burden survival and prognosis were greatly different between high-risk and low-risk groups. Finally, we screened potential sensitive drugs for HCC. In conclusion, this study provides insight into the TME status in patients with HCC and lays a basis for immunotherapy and the selection of sensitive drugs.
Integrative metabolome and transcriptome analyses reveal the molecular mechanism underlying variation in floral scent during flower development of Chrysanthemum indicum var. aromaticum

Chrysanthemum indicum var. aromaticum (CIA) is an endemic plant that occurs only in the high mountain areas of the Shennongjia Forest District in China. The whole plant, in particular the flowers of CIA, have intense fragrance, making it a novel resource plant for agricultural, medicinal, and industrial applications. However, the volatile metabolite emissions in relation to CIA flower development and the molecular mechanisms underlying the generation of floral scent remain poorly understood. Here, integrative metabolome and transcriptome analyses were performed to investigate floral scent-related volatile compounds and genes in CIA flowers at three different developmental stages. A total of 370 volatile metabolites, mainly terpenoids and esters, were identified, of which 89 key differential metabolites exhibited variable emitting profiles during flower development. Transcriptome analysis further identified 8,945 differentially expressed genes (DEGs) between these samples derived from different flower developmental stages and KEGG enrichment analyses showed that 45, 93, and 101 candidate DEGs associated with the biosynthesis of phenylpropanoids, esters, and terpenes, respectively. Interestingly, significant DEGs involved into the volatile terpenes are only present in the MEP and its downstream pathways, including those genes encoding ISPE, ISPG, FPPS, GPPS, GERD, ND and TPS14 enzymes. Further analysis showed that 20 transcription factors from MYB, bHLH, AP2/EFR, and WRKY families were potentially key regulators affecting the expressions of floral scent-related genes during the CIA flower development. These findings provide insights into the molecular basis of plant floral scent metabolite biosynthesis and serve as an important data resources for molecular breeding and utilization of CIA plants in the future.
Dysbiosis and Depletion of Fecal Organic Acids Correlate With the Severity of Rejection After Rat Liver Transplantation

The impact of T cell-mediated rejection (TCMR) after liver transplantation (LT) on the alterations in the gut microbiota (GM) and associated intestinal environment represented by fecal organic acids (OAs) require further elucidation. A rat allogeneic LT model was prepared without immunosuppressants or antibiotics, and a syngeneic model was used as a control. Qualitative and quantitative analyses of fecal samples at fixed time points were performed. Correlation analyses were also performed between liver function and GMs and OA levels. In the allogeneic TCMR group, the number of predominant obligate anaerobes decreased as liver function declined. Clostridioides difficile, Enterobacteriaceae, Enterococcus, Streptococcus, and Staphylococcus were significantly increased. Regarding fecal OA concentration, short-chain fatty acid (SCFA) concentrations were depleted as liver function declined. In contrast, in the syngeneic group, GM and OAs exhibited only slight, transient, and reversible disturbances. In addition, alanine aminotransferase and total bilirubin were positively correlated with the number of Enterobacteriaceae and Enterococcus, and negatively correlated with the fecal concentration of SCFAs. The allogeneic TCMR model demonstrated distinct dysbiosis and depletion of fecal OAs as TCMR progressed after LT. The degree of graft injury was closely related to the number of specific bacterial strains and the concentrations of fecal SCFAs. GRAPHICAL ABSTRACT
Glomerular filtration in the aging population

In the last decades, improvements in the average life expectancy in the world population have been associated with a significant increase in the proportion of elderly people, in parallel with a higher prevalence of non-communicable diseases, such as hypertension and diabetes. As the kidney is a common target organ of a variety of diseases, an adequate evaluation of renal function in the approach of this population is of special relevance. It is also known that the kidneys undergo aging-related changes expressed by a decline in the glomerular filtration rate (GFR), reflecting the loss of kidney function, either by a natural senescence process associated with healthy aging or by the length of exposure to diseases with potential kidney damage. Accurate assessment of renal function in the older population is of particular importance to evaluate the degree of kidney function loss, enabling tailored therapeutic interventions. The present review addresses a relevant topic, which is the effects of aging on renal function. In order to do that, we analyze and discuss age-related structural and functional changes. The text also examines the different options for evaluating GFR, from the use of direct methods to the implementation of several estimating equations. Finally, this manuscript supports clinicians in the interpretation of GFR changes associated with age and the management of the older patients with decreased kidney function.
Predicting lymph node metastasis and recurrence in patients with early stage colorectal cancer

Tumor budding (TB), a powerful, independent predictor of colorectal cancer (CRC), is important for making appropriate treatment decisions. Currently, TB is assessed only using the tumor bud count (TBC). In this study, we aimed to develop a novel prediction model, which includes different TB features, for lymph node metastasis (LNM) and local recurrence in patients with pT1 CRC. Enrolled patients (n = 354) were stratified into training and validation cohorts. Independent predictors of LNM and recurrence were identified to generate predictive nomograms that were assessed using the area under the receiver operating characteristic (AUROC) and decision curve analysis (DCA). Seven LNM predictors [gross type, histological grade, lymphovascular invasion (LVI), stroma type, TBC, TB mitosis, and TB CDX2 expression] were identified in the training cohort. LNM, histology grade, LVI, TBC, stroma type, and TB mitosis were independent predictors of recurrence. We constructed an LNM predictive nomogram with a high clinical application value using the DCA. Additionally, a nomogram predicting recurrence-free survival (RFS) was constructed. It presented an AUROC value of 0.944 for the training cohort. These models may assist surgeons in making treatment decisions. In the high-risk group, radical surgery with a postoperative adjuvant chemotherapy was associated with RFS. Postoperative chemotherapy can be better for high-risk patients with pT1 CRC. We showed that TB features besides TBC play important roles in CRC pathogenesis, and our study provides prognostic information to guide the clinical management of patients with early stage CRC.
Migration of nitrite corrosion inhibitor in calcium silicate hydrate nanopore: A molecular dynamics simulation study

Nitrite is an effective corrosion inhibitor that can inhibit the corrosion of steel reinforcement and extend the service life of reinforced concrete. The transport speed of nitrite in the cement micro-porous channels determines the anti-corrosion effect of reinforcing steel. In this paper, the transport behavior of three nitrite corrosion inhibitors, namely LiNO2, Ca(NO2)2, and NaNO2, in cement micro-porous channels is investigated based on molecular dynamics simulations and finds that NO2 − in LiNO2 has the fastest transport speed in the channels. The ions’ local structure and dynamic behavior of ions analysis reveal that ion clusters and pores adsorption determine the speed of ion transport. Compared with the other two nitrites, the Li ions have the weakest ability to capture NO2 − and form the most unstable clusters (NO2 −-Li-water) in the LiNO2 solution. Meanwhile, the coordination numbers results indicate that water in LiNO2 provides the most potent driving force. These phenomena reasonably explain the fastest transport speed of NO2 − through the pores in LiNO2 solution. The transport behavior of corrosion inhibitors in the micro-porous channels is thoroughly decoded at the atomic level, which is instrumental in solving the problem of the optimal corrosion inhibitor selecting for the design of highly durable concrete.
An Italian multicentre distributed data research network to study the use, effectiveness, and safety of immunosuppressive drugs in transplant patients: Framework and perspectives of the CESIT project

The goal of post-transplant immunosuppressive drug therapy is to prevent organ rejection while minimizing drug toxicities. In clinical practice, a multidrug approach is commonly used and involves drugs with different mechanisms of action, including calcineurin inhibitors (CNI) (tacrolimus or cyclosporine), antimetabolite (antimet) (mycophenolate or azathioprine), inhibitors of mechanistic target of rapamycin (mTOR) (sirolimus or everolimus), and/or steroids. Although evidence based on several randomized clinical trials is available, the optimal immunosuppressive therapy has not been established and may vary among organ transplant settings. To improve the knowledge on this topic, a multiregional research network to Compare the Effectiveness and Safety of Immunosuppressive drugs in Transplant patients (CESIT) has been created with the financial support of the Italian Medicines Agency. In this article, we describe the development of this network, the framework that was designed to perform observational studies, and we also give an overview of the preliminary results that we have obtained. A multi-database transplant cohort was enrolled using a common data model based on healthcare claims data of four Italian regions (Lombardy, Veneto, Lazio, and Sardinia). Analytical datasets were created using an open-source tool for distributed analysis. To link the National Transplant Information System to the regional transplant cohorts, a semi-deterministic record linkage procedure was performed. Overall, 6,914 transplant patients from 2009–19 were identified: 4,029 (58.3%) for kidney, 2,219 (32.1%) for liver, 434 (6.3%) for heart, and 215 (3.1%) for lung. As expected, demographic and clinical characteristics showed considerable variability among organ settings. Although the triple therapy in terms of CNI + antimet/mTOR + steroids was widely dispensed for all settings (63.7% for kidney, 33.5% for liver, 53.3% for heart, and 63.7% for lung), differences in the active agents involved were detected. The CESIT network represents a great opportunity to study several aspects related to the use, safety, and effectiveness of post-transplant maintenance immunosuppressive therapy in real practice.
Strontium-doping promotes bone bonding of titanium implants in osteoporotic microenvironment

Osteoporosis is a major challenge to oral implants, and this study focused on improving the osseointegration ability of titanium (Ti) implants in osteoporosis environment via surface modification, including doping of strontium ion and preparation of nanoscale surface feature. Our previous studies have shown that strontium (Sr) ions can enhance osteogenic activity. Therefore, we aimed to comprehensively evaluate the effect of hydrothermal treatment of Sr-doped titanium implant coating on bone-binding properties in the microenvironment of osteoporosis in this study. We fabricated Sr-doped nanocoating (AHT-Sr) onto the surface of titanium implants via hydrothermal reaction. The rough Sr-doping had good biological functions and could apparently promote osteogenic differentiation of osteoporotic bone marrow mesenchymal stem cells (OVX-BMSCs). Most importantly, AHT-Sr significantly promoted bone integration in the osteoporosis environment. This study provides an effective approach to implant surface modification for better osseointegration in an osteoporotic environment.