Thymomas and thymic carcinomas are the most common tumor types among anterior mediastinal lesions. However, the relationship between molecular aberrations and thymoma patients are poorly understood, especially abnormal changes in the expression profiles of circRNAs. The purpose of the present study was to investigate the expression profiles of circRNAs in thymoma patients and their possible roles in the pathogenesis of thymoma.

There are concerns that individuals with chronic immune-mediated diseases are at increased risk of COVID-19 and related severe adverse outcome, including intensive care admission or death. We aimed to explore the absolute and relative risk of severe COVID-19 in inflammatory bowel disease (IBD).

Renal clearance of many drugs is mediated by renal organic anion transporters OAT1/3 and inhibition of these transporters may lead to drug-drug interactions (DDIs). Pyridoxic acid (PDA) and homovanillic acid (HVA) were indicated as potential biomarkers of OAT1/3. The objective of this study was to develop a population pharmacokinetic model for PDA and HVA to support biomarker qualification. Simultaneous fitting of biomarker plasma and urine data in the presence and absence of potent OAT1/3 inhibitor (probenecid, 500 mg every 6 h) was performed. The impact of study design (multiple vs. single dose of OAT1/3 inhibitor) and ability to detect interactions in the presence of weak/moderate OAT1/3 inhibitors was investigated, together with corresponding power calculations. The population models developed successfully described biomarker baseline and PDA/HVA OAT1/3-mediated interaction data. No prominent effect of circadian rhythm on PDA and HVA individual baseline levels was evident. Renal elimination contributed greater than 80% to total clearance of both endogenous biomarkers investigated. Estimated probenecid unbound in vivo OAT inhibitory constant was up to 6.4-fold lower than in vitro values obtained with PDA as a probe. The PDA model was successfully verified against independent literature reported datasets. No significant difference in power of DDI detection was found between multiple and single dose study design when using the same total daily dose of 2000 mg probenecid. Model-based simulations and power calculations confirmed sensitivity and robustness of plasma PDA data to identify weak, moderate, and strong OAT1/3 inhibitors in an adequately powered clinical study to support optimal design of prospective clinical OAT1/3 interaction studies.

Prostate cancer-associated fibroblasts (prostate CAFs) are essential components of the tumor microenvironment and can promote tumor progression through their immunosuppressive functions. MPSSS, a novel polysaccharide purified from Lentinus edodes, has been reported to have anti-tumor activity. MPSSS could also inhibit the immunosuppressive function of prostate CAFs, which has been demonstrated through that the secretome of MPSSS-treated prostate CAFs could inhibit the proliferation of T cells. However, how the secretome of MPSSS-treated prostate CAFs influence prostate cancer progression is still unclear. Interestingly, we found that the low molecular weight (3-100kD) secretome of prostate CAFs (lmwCAFS) could promote the growth of PC-3 cells, while that of MPSSS-treated prostate CAFs (MT-lmwCAFS) could inhibit their growth. We carried out comparative secretomic analysis of lmwCAFS and MT-lmwCAFS to identify functional molecules that inhibit the growth of PC-3 cells, and proteomic analysis of lmwCAFS-treated PC-3 cells and MT-lmwCAFS-treated PC-3 cells to investigate the underlying molecular mechanism. These analyses suggest that TGF-β3 from MT-lmwCAFS may inhibit the growth of PC-3 cells. The validated experiments revealed that TGF-β3 from MT-lmwCAFS activated p21 expression in PC-3 cells by regulating the FoxO pathway thereby inducing G0/G1 cell cycle arrest of PC-3 cells. Overall, our data demonstrated that MPSSS reversed the ability of prostate CAFs to suppress the cell viability of PC-3 cells, which might provide a potential therapeutic strategy to prevent prostate cancer progression.

Traumatic brain injury is a global health problem; worldwide, >60 million people experience a traumatic brain injury each year and incidence is rising. Traumatic brain injury has been proposed as an independent risk factor for stroke.

African descent populations in the United States have high rates of type 2 diabetes and are incorrectly represented as a single group. Current glycated hemoglobin A1c (HbA1c) cutoffs (5.7% to <6.5% for prediabetes; ≥6.5% for type 2 diabetes) may perform suboptimally in evaluating glycemic status among African descent groups. We conducted a scoping review of US-based evidence documenting HbA1c performance to assess glycemic status among African American, Afro-Caribbean, and African people.

No abstract available

Obesity is an increasingly serious epidemic worldwide characterized by an increase in the number and size of adipocytes. Adipose tissue maintains the balance between lipid storage and energy utilization. Therefore, adipose metabolism is of great significance for the prevention, treatment and intervention of obesity. Asprosin, a novel adipokine, is a circulating hormone mainly secreted by white adipose tissue. Previous studies have shown that asprosin plays a role in fasting-induced homeostasis, insulin resistance, and glucose tolerance. However, whether it can regulate the metabolism of adipose tissue itself has not been studied. This study intended to examine the roles and potential mechanisms of asprosin in adipose regulation. We first demonstrated that the expression level of asprosin was significantly downregulated in subcutaneous white adipose tissue (scWAT) of high-fat diet (HFD)-fed or cold-stimulated mice. Overexpression of asprosin in scWAT reduced heat production, decreased expression of the browning marker uncoupling protein 1 (UCP1) and other browning-related genes, along with upregulation of adipogenic gene expression. Mechanistically, we found that Nrf2 was activated upon cold exposure, but this activation was suppressed after asprosin overexpression. In primary cultured adipocytes, adenovirusmediated asprosin overexpression inhibited adipose browning and aggravated lipid deposition, while Nrf2 agonist oltipraz could reverse these changes. Our findings suggest that novel adipokine asprosin negatively regulated browning and elevate lipid deposition in adipose tissue via a Nrf2-mediated mechanism. Asprosin may be a promising target for the prevention and treatment of obesity and other metabolic diseases.

Rocky desertification is a bottleneck that reduces ecological and environmental security in karst areas. Paper mulberry, a unique deciduous tree, shows good performance in rocky desertification areas. Its resistance mechanisms are therefore of high interest. In this study, a lysine acetylation proteomics analysis of paper mulberry seedling leaves was conducted in combination with the purification of acetylated protein by high-precision nano LC-MS/MS. We identified a total of 7130 acetylation sites in 3179 proteins. Analysis of the modified sites showed a predominance of nine motifs. Six positively charged residues: lysine (K), arginine (R), and histidine (H), serine (S), threonine (T), and tyrosine (Y) occurred most frequently at the +1 position, phenylalanine (F) was both detected both upstream and downstream of the acetylated lysines; and the sequence logos showed a strong preference for lysine and arginine around acetylated lysines. Functional annotation revealed that the identified enzymes were mainly involved in translation, transcription, ribosomal structure and biological processes, showing that lysine acetylation can regulate various aspects of primary carbon and nitrogen metabolism and secondary metabolism. Acetylated proteins were enriched in the chloroplast, cytoplasm, and nucleus, and many stress response-related proteins were also discovered to be acetylated, including PAL, HSP70, and ERF. HSP70, an important protein involved in plant abiotic and disease stress responses, was identified in paper mulberry, although it is rarely found in woody plants. This may be further examined in research in other plants and could explain the good adaptation of paper mulberry to the karst environment. However, these hypotheses require further verification. Our data can provide a new starting point for the further analysis of the acetylation function in paper mulberry and other plants.

Retinal prostheses can restore the basic visual function of patients with retinal degeneration, which relies on effective electrical stimulation to evoke the physiological activities of retinal ganglion cells (RGCs). Current electrical stimulation strategies have defects such as unstable effects and insufficient stimulation positions, therefore, it is crucial to determine the optimal pulse parameters for precise and safe electrical stimulation. Biphasic voltages (cathode-first) with a pulse width of 25 ms and different amplitudes were used to ex vivo stimulate RGCs of three wild-type (WT) mice using a commercial microelectrode array (MEA) recording system. An algorithm is developed to automatically realize both spike-sorting and electrical response identification for the spike signals recorded. Measured from three WT mouse retinas, the total numbers of RGC units and responsive RGC units were 1193 and 151, respectively. In addition, the optimal pulse amplitude range for electrical stimulation was determined to be 0.43 V-1.3 V. The processing results of the automatic algorithm we proposed shows high consistency with those using traditional manual processing. We anticipate the new algorithm can not only speed up the elaborate electrophysiological data processing, but also optimize pulse parameters for the electrical stimulation strategy of neural prostheses.

The aim of this study was to evaluate how the inclusion of a blend of essential oils in milk replacer (MR) affects different outcomes of dairy heifers. The outcomes evaluated: feed intake, performance, body development, blood cells and metabolites, insulin-like growth factor-1 (IGF-1), rumen fermentation, fecal scores, and respiratory scores. All outcomes were evaluated during pre-weaning (4-60 d of age), and carry-over effects during post-weaning (61-90 d of age) periods. The experimental units utilized were 29 newborn Holstein × Gyr crossbred dairy heifers, with genetic composition of 5/8 or more Holstein and 3/8 or less Gyr and body weight (BW) at birth of 32.2 ± 5.2 kg. Experimental units were assigned to either a control (CON, n = 15) or a blend of essential oil supplementation (BEO, n = 14) treatment, maintaining a balance of genetic composition. The BEO was supplemented in the MR with 1 g/d/calf of a blend of essential oils (Apex Calf, Adisseo, China) composed by plant extracts derived from anise, cinnamon, garlic, rosemary, and thyme. During the pre-weaning phase, all heifers were fed 5 L of MR/d reconstituted to 15% (dry matter basis), divided into two equal meals. Water and starter were provided ad libitum. During the post-weaning, animals received a maximum of 3 kg of starter/d, and ad libitum corn silage, divided into two meals. Feed intake, fecal and respiratory scores were evaluated daily. The BW was measured every three days, while body development was recorded weekly. Blood samples were collected on 0, 30, and 60 d of age for total blood cell count, weekly and on the weaning day to determinate ß-hydroxybutyrate, urea and glucose, and biweekly for IGF-1. Ruminal parameters (pH, volatile fatty acids, ammonia-N, and acetate:propionate proportion-C2:C3) were measured on days 14, 28, 42, 60, 74 and 90. A randomized complete block design with an interaction between treatment and week was the experimental method of choice to test the hypothesis of the BEO's effect on all outcomes. An ANOVA procedure was used for continuous outcomes, and a non-parametric test was used for the ordered categorical outcomes, both adopting a CI = 95%. Results indicated that there was not enough evidence to accept the alternative hypothesis of the effect of BEO in MR on feed intake, performance, body development, and blood metabolites during both pre-weaning and post-weaning periods. However, results indicated that the inclusion of BEO in MR significantly affects the proportion of C2:C3 during pre- and post-weaning (P = 0.05). Similarly, the effect was significant for basophil (P ≤ 0.001), and platelet (P = 0.04) counts pre-weaning. The interaction between week and treatment was also significant for lymphocytes (P ≤ 0.001), revealing a cumulative effect. Lastly, fecal scores were also significant (P = 0.04) during pre-weaning, with lower values for BEO. The BEO contributed to ruminal manipulation in pre-weaning and carry-over effects in post-weaning, immunity improvement, and decreased morbidity of neonatal diarrhea in the pre-weaning phase.

Citizen science (CS) currently refers to the participation of non-scientist volunteers in any discipline of conventional scientific research. Over the last two decades, nature-based CS has flourished due to innovative technology, novel devices, and widespread digital platforms used to collect and classify species occurrence data. For scientists, CS offers a low-cost approach of collecting species occurrence information at large spatial scales that otherwise would be prohibitively expensive. We examined the trends and gaps linked to the use of CS as a source of data for species distribution models (SDMs), in order to propose guidelines and highlight solutions. We conducted a quantitative literature review of 207 peer-reviewed articles to measure how the representation of different taxa, regions, and data types have changed in SDM publications since the 2010s. Our review shows that the number of papers using CS for SDMs has increased at approximately double the rate of the overall number of SDM papers. However, disparities in taxonomic and geographic coverage remain in studies using CS. Western Europe and North America were the regions with the most coverage (73%). Papers on birds (49%) and mammals (19.3%) outnumbered other taxa. Among invertebrates, flying insects including Lepidoptera, Odonata and Hymenoptera received the most attention. Discrepancies between research interest and availability of data were as especially important for amphibians, reptiles and fishes. Compared to studies on animal taxa, papers on plants using CS data remain rare. Although the aims and scope of papers are diverse, species conservation remained the central theme of SDM using CS data. We present examples of the use of CS and highlight recommendations to motivate further research, such as combining multiple data sources and promoting local and traditional knowledge. We hope our findings will strengthen citizen-researchers partnerships to better inform SDMs, especially for less-studied taxa and regions. Researchers stand to benefit from the large quantity of data available from CS sources to improve global predictions of species distributions.

Compartmental models in epidemiology characterize the spread of an infectious disease by formulating ordinary differential equations to quantify the rate of disease progression through subpopulations defined by the Susceptible-Infectious-Removed (SIR) scheme. The classic rate law central to the SIR compartmental models assumes that the rate of transmission is first order regarding the infectious agent. The current study demonstrates that this assumption does not always hold and provides a theoretical rationale for a more general rate law, inspired by mixed-order chemical reaction kinetics, leading to a modified mathematical model for non-first-order kinetics. Using observed data from 127 countries during the initial phase of the COVID-19 pandemic, we demonstrated that the modified epidemic model is more realistic than the classic, first-order-kinetics based model. We discuss two coefficients associated with the modified epidemic model: transmission rate constant k and transmission reaction order n. While k finds utility in evaluating the effectiveness of control measures due to its responsiveness to external factors, n is more closely related to the intrinsic properties of the epidemic agent, including reproductive ability. The rate law for the modified compartmental SIR model is generally applicable to mixed-kinetics disease transmission with heterogeneous transmission mechanisms. By analyzing early-stage epidemic data, this modified epidemic model may be instrumental in providing timely insight into a new epidemic and developing control measures at the beginning of an outbreak.

This study was conducted to retrospectively assess the relationships between: rhabdomyolysis (quantified by creatine kinase (CK) activity) and kidney injury (quantified by serum creatinine concentration), sex, age, body temperature on admission, presence of seizures, and agitation or aggression in patients presenting to the Emergency Department with acute recreational drug toxicity. We also investigated the association with the substances ingested.

The coronavirus infectious disease 19 (COVID-19) pandemic has resulted in significant morbidities, severe acute respiratory failures and subsequently emergency departments' (EDs) overcrowding in a context of insufficient laboratory testing capacities. The development of decision support tools for real-time clinical diagnosis of COVID-19 is of prime importance to assist patients' triage and allocate resources for patients at risk.

In canine leishmaniosis caused by the protozoan Leishmania infantum, little is known about how co-infections with or co-seropositivities for other pathogens can influence aggravation of this disease. Therefore, the objectives of this study were to evaluate the frequency of co-infections with or co-seropositivities for certain pathogens in dogs seropositive for L. infantum and their relationship with clinical signs, histological changes and L. infantum load. Sixty-six L. infantum-seropositive dogs were submitted to clinical examination, collection of blood and bone marrow, culling, and necropsy. Antibodies against Anaplasma spp., Borrelia burgdorferi sensu lato, Ehrlichia spp. and Toxoplasma gondii and Dirofilaria immitis antigens were investigated in serum. Samples from different tissues were submitted to histopathology and immunohistochemistry for the detection of Leishmania spp. and T. gondii. Quantitative real-time PCR was used to assess the L. infantum load in spleen samples. For detection of Coxiella burnetii, conventional PCR and nested PCR were performed using bone marrow samples. All 66 dogs tested positive for L. infantum by qPCR and/or culture. Fifty dogs (76%) were co-seropositive for at least one pathogen: T. gondii (59%), Ehrlichia spp., (41%), and Anaplasma spp. (18%). Clinical signs were observed in 15 (94%) dogs monoinfected with L. infantum and in 45 (90%) dogs co-seropositive for certain pathogens. The L. infantum load in spleen and skin did not differ significantly between monoinfected and co-seropositive dogs. The number of inflammatory cells was higher in the spleen, lung and mammary gland of co-seropositive dogs and in the mitral valve of monoinfected dogs. These results suggest that dogs infected with L. infantum and co-seropositive for certain pathogens are common in the region studied. However, co-seropositivities for certain pathogens did not aggravate clinical signs or L. infantum load, although they were associated with a more intense inflammatory reaction in some organs.

The first case of the novel coronavirus in Brazil was notified on February 26, 2020. After 21 days, the first case was reported in the second largest State of the Brazilian Amazon. The State of Pará presented difficulties in combating the pandemic, ranging from underreporting and a low number of tests to a large territorial distance between cities with installed hospital capacity. Due to these factors, mathematical data-driven short-term forecasting models can be a promising initiative to assist government officials in more agile and reliable actions. This study presents an approach based on artificial neural networks for the daily and cumulative forecasts of cases and deaths caused by COVID-19, and the forecast of demand for hospital beds. Six scenarios with different periods were used to identify the quality of the generated forecasting and the period in which they start to deteriorate. Results indicated that the computational model adapted capably to the training period and was able to make consistent short-term forecasts, especially for the cumulative variables and for demand hospital beds.

In last decades, a large body of evidence clarified nitrogen isotope composition (δ15N) patterns in plant leaves, roots and metabolites, showing isotopic fractionation along N uptake and assimilation pathways, in relation to N source and use efficiency, also suggesting 15N depletion in plant DNA. Here we present a manipulative experiment on Brassica napus var. oleracea, where we monitored δ 15N of purified, lyophilized DNA and source leaf and root materials, over a 60-days growth period starting at d 60 after germination, in plants initially supplied with a heavy labelled (δ 15NAir-N2 = 2100 mUr) ammonium nitrate solution covering nutrient requirements for the whole observation period (470 mg N per plant) and controlling for the labelled N species (ṄH4, ṄO3 and both). Dynamics of Isotopic Ratio Mass Spectrometry (IRMS) data for the three treatments showed that: (1) leaf and root δ 15N dynamics strictly depend on the labelled chemical species, with ṄH4, ṄO3 and ṄH4ṄO3 plants initially showing higher, lower and intermediate values, respectively, then converging due to the progressive NH4+ depletion from the nutrient solution; (2) in ṄH4ṄO3, where δ15N was not affected by the labelled chemical species, we did not observe isotopic fractionation associated to inorganic N uptake; (3) δ15N values in roots compared to leaves did not fully support patterns predicted by differences in assimilation rates of NH4+ and NO3-; (4) DNA is depleted in 15N compared to the total N pools of roots and leaves, likely due to enzymatic discrimination during purine biosynthesis. In conclusion, while our experimental setup did not allow to assess the fractionation coefficient (ε) associated to DNA bases biosynthesis, this is the first study specifically reporting on dynamics of specific plant molecular pools such as nucleic acids over a long observation period with a heavy labelling technique.

Cancer-associated fibroblasts (CAFs) play a crucial role in cancer progression, drug resistance and tumor recurrence. We have recently shown that the Notch pathway determines the tumor-regulatory role of experimentally created 'CAFs'. Here, we examined the status of Notch signaling in human melanoma-associated fibroblasts (MAFs) versus their normal counterparts and tested whether manipulation of the Notch pathway activity in MAFs alters their tumor-regulatory function. Using tissue microarrays, we found that MAFs exhibit decreased Notch pathway activity compared with normal fibroblasts in adjacent and non-adjacent skin. Consistently, MAFs isolated from human metastatic melanoma exhibited lower Notch activity than did normal human fibroblasts, demonstrating that Notch pathway activity is low in MAFs. We then investigated the effect of increasing Notch pathway activity in MAF on melanoma growth in co-cultures and in a mouse co-graft model. We found that activation of the Notch pathway in MAFs significantly restricted melanoma cell growth in vitro and suppressed melanoma skin growth and tumor angiogenesis in vivo. Our study demonstrates that the Notch signaling is inhibited in MAFs. Increase of Notch pathway activity can confer tumor-suppressive function on MAFs. Thus, targeting melanoma by activating Notch signaling in MAF may represent a novel therapeutic approach.

Previous research suggests that childhood maltreatment is associated with epigenetic modification of genes involved in hypothalamic-pituitary-adrenal (HPA) functioning, which could cause dysregulation of the stress response system. If pervasive, this may be associated with the development of stress-related disorder in adults, including affective disorders, anxiety disorders, post-traumatic stress disorder (PTSD) or borderline-personality disorder (BPD). The majority of studies have focused on DNA methylation of the glucocorticoid receptor gene (NR3C1) and the FKBP5 encoding gene, which regulates the sensitivity of the glucocorticoid receptor (GR). How methylation of NR3C1 and FKBP5 interferes with childhood adversity and psychopathology as well as empathy is an under-researched issue. Here, we sought to investigate the association of childhood maltreatment in a sample of 89 individuals (44 healthy participants and 45 patients diagnosed with BPD) with the methylation of the 1F promoter region of NR3C1 and the intron 7 of FKBP5 as well as with different measures of psychopathology and empathy. Methylation of FKBP5 (bin 2) correlated with anxiety (SCL-90-R) and the global psychopathological symptom load index (GSI), as well as with lower empathic perspective-taking abilities. Psychopathology and empathy impairments correlated with the level of childhood maltreatment. No difference in FKBP5 methylation was observed between the clinical and the non-clinical group. Methylation of NR3C1 was lower in BPD patients compared to controls, yet with small differences. The results are discussed regarding their biological relevance, including possible evolutionary explanations. In short, the regulation of the GR sensitivity by methylation of FKBP5 correlated with psychopathology and empathy scores, while no correlation emerged with the severity of childhood adversity.