Miracle-dz/UniFAR-FTUs huggingface dataset:
Taxonomic and Functional Fecal Microbiota Signatures Associated With Insulin Resistance in Non-Diabetic Subjects With Overweight/Obesity Within the Frame of the PREDIMED-Plus Study

Objective An altered gut microbiota has been associated with insulin resistance, a metabolic dysfunction consisting of cellular insulin signaling impairment. The aim of the present study is to determine the taxonomic and functional fecal microbiota signatures associated with HOMA-IR index in a population with high cardiovascular risk. Methods A total of 279 non-diabetic individuals (55–75 years aged) with overweight/obesity and metabolic syndrome were stratified according to tertiles of HOMA-IR index. Blood biochemical parameters, anthropometric measurements and fecal samples were collected at baseline. Fecal microbial DNA extraction, 16S amplicon sequencing and bioinformatics analysis were performed. Results Desulfovibrio, Odoribacter and Oscillospiraceae UCG-002 were negatively associated with HOMA-IR index, whereas predicted total functional abundances revealed gut metabolic modules mainly linked to amino acid degradation. Butyricicoccus, Erysipelotrichaceae UCG-003, Faecalibacterium were positively associated with HOMA-IR index, whereas predicted total functional abundances revealed gut metabolic modules mainly linked to saccharide degradation. These bacteria contribute differentially to the gut metabolic modules, being the degree of contribution dependent on insulin resistance. Both taxa and gut metabolic modules negatively associated to HOMA-IR index were linked to mechanisms involving sulfate reducing bacteria, improvement of intestinal gluconeogenesis and production of acetate. Furthermore, both taxa and gut metabolic modules positively associated to HOMA-IR index were linked to production and mechanisms of action of butyrate. Conclusions Specific taxonomic and functional fecal microbiota signatures associated with insulin resistance were identified in a non-diabetic population with overweight/obesity at high cardiovascular risk. These findings suggest that tailoring therapies based on specific fecal microbiota profiles could be a potential strategy to improve insulin sensitivity.
Dyadic Interdependence in Non-spousal Caregiving Dyads’ Wellbeing: A Systematic Review

Caregiving dyads (i.e., an informal caregiver and a care recipient) work as an interdependent emotional system, whereby it is assumed that what happens to one member of the dyad essentially happens to the other. For example, both members of the dyad are involved in care giving and care receiving experiences and therefore major life events, such as a serious illness affect the dyad and not only the individual. Consequently, informal caregiving may be considered an example of dyadic interdependence, which is “the process by which interacting people influence one another’s experience. ” This systematic review aimed to synthesize studies of dyadic interdependence, specifically in non-spousal caregiving dyads (e.g., adult children—parents, siblings, other relatives, or friends). Electronic databases (PsycINFO, Pubmed, and CINAHL) were systematically searched for dyadic studies reporting on interdependence in the emotional and relational wellbeing of non-spousal caregiving dyads. A total of 239 full-text studies were reviewed, of which 14 quantitative and qualitative studies met the inclusion criteria with a majority of dyads consisting of adult daughters caring for their older mothers. A narrative synthesis suggested mutual influences between non-spousal caregiving dyad members based on: (1) associations between intrapersonal (e.g., psychological functioning) and interpersonal (e.g., relationship processes) variables and emotional and relational wellbeing of the dyad; (2) associations between care context variables (e.g., socio-demographics and care tasks) and emotional and relational wellbeing of the dyad; and (3) patterns of covariation between caregivers’ and care recipients’ wellbeing. Evidence supporting dyadic interdependence among non-spousal caregiving dyads shed light on the ways dyad members influence each other’s wellbeing while providing and receiving care (e.g., via the exchange of support). Future studies investigating mutual influences in dyads, should differentiate subsamples of caregivers based on relationship type, and adopt dyadic and longitudinal designs. Systematic Review Registration [https://www.crd. york.ac. uk/prospero/#recordDetails], identifier [CRD42021213147].
Circulating Glycan Monosaccharide Composite-Based Biomarker Diagnoses Colorectal Cancer at Early Stages and Predicts Prognosis

Introduction Early diagnosis could lead to a cure of colorectal cancer (CRC). Since CRC is related to aging and lifestyles, we tested if the environmental information-enriched monosaccharide composite (MC) of circulating glycans could serve as an early diagnostic biomarker for CRC. Meanwhile, we evaluated its role in predicting prognosis. Methods HPAEC-PAD was used to quantify glycan monosaccharide compositions from a total of 467 serum samples including CRC patients, colorectal adenoma (CRA) patients and healthy individuals. Two diagnostic model was constructed by logistic regression analysis. The diagnostic performance of the two models was verified in the retrospective validation group and the prospective validation group. The prognostic performance of the model was assessed by survival analysis. Results The concentrations of monosaccharides in serum were significantly higher in CRA and CRC patients than in healthy individuals. Two diagnostic models were constructed: MC1 was used to distinguish between healthy individuals and CRC; MC2 was used to distinguish between healthy individuals and CRA. Area under receptor operating characteristic curve (AUC) of MC2 and MC1 was 0.8025 and 0.9403 respectively. However, the AUC of CEA between healthy individuals and CRC was 0.7384. Moreover, in early stage of CRC (without lymph node metastasis), the positive rates of CEA and MC1 were 28% and 80%, respectively. The follow-up data showed that the increased MC1 value was associated with poor survival in patients with CRC (p=0.0010, HR=5.30). Discussion The MC1 model is superior to CEA in the diagnosis of CRC, especially in the early diagnosis. MC1 can be used for predicting prognosis of CRC patients, and elevated MC1 values indicate poor survival.
Adenosine A2a Receptor Regulates Autophagy Flux and Apoptosis to Alleviate Ischemia-Reperfusion Injury via the cAMP/PKA Signaling Pathway

Exploring effective methods to lessen myocardial ischemia-reperfusion injury still has positive significance. The adenosine A2a receptor (A2aR) has played a crucial part in cardiac ischemia-reperfusion injury. Previous studies revealed that the adenosine A2a receptor regulated autophagy, but the specific mechanism in myocardial ischemia-reperfusion injury was still unclear. We established an ischemia-reperfusion model (30 min of ischemia and 2 h of reperfusion) in vivo and a model with oxygen-glucose deprivation for 6 h and reoxygenation for 18 h (OGDR) in vitro. The ischemia-reperfusion injury resulted in prolonged QTc interval, left ventricular systolic dysfunction, and myocardial infarction. In vitro model, we found that the OGDR-induced autophagosomes and apoptosis caused myocardial cell death, as evidenced by a significant increase in the generation of lactate dehydrogenase and creatine kinase-MB. Furthermore, overactivated autophagy with rapamycin showed an anti-apoptotic effect. The interaction between autophagy and apoptosis in myocardial ischemia-reperfusion injury was complex and variable. We discovered that the activation of adenosine A2a receptor could promote the expression of Bcl-2 to inhibit the levels of Beclin-1 and LC3II. The number of autophagosomes exceeded that of autolysosomes under OGDR, but the result reversed after A2aR activation. Activated A2aR with its agonist CGS21680 before reperfusion saved cellular survival through anti-apoptosis and anti-autophagy effect, thus improving ventricular contraction disorders, and visibly reducing myocardial infarction size. The myocardial protection of adenosine A2a receptor after ischemia may involve the cAMP-PKA signaling pathway and the interaction of Bcl-2-Beclin-1.
Analyzing Relationships Between Economic and Neighborhood-Related Social Determinants of Health and Intensive Care Unit Length of Stay for Critically Ill Children With Medical Complexity Presenting With Severe Sepsis

Objectives Of the Social Determinants of Health (SDoH), we evaluated socioeconomic and neighborhood-related factors which may affect children with medical complexity (CMC) admitted to a Pediatric Intensive Care Unit (PICU) in Shelby County, Tennessee with severe sepsis and their association with PICU length of stay (LOS). We hypothesized that census tract-level socioeconomic and neighborhood factors were associated with prolonged PICU LOS in CMC admitted with severe sepsis in the underserved community. Methods This single-center retrospective observational study included CMC living in Shelby County, Tennessee admitted to the ICU with severe sepsis over an 18-month period. Severe sepsis CMC patients were identified using an existing algorithm incorporated into the electronic medical record at a freestanding children's hospital. SDoH information was collected and analyzed using patient records and publicly available census-tract level data, with ICU length of stay as the primary outcome. Results 83 encounters representing 73 patients were included in the analysis. The median PICU LOS was 9.04 days (IQR 3.99–20.35). The population was 53% male with a median age of 4.1 years (IQR 1.96–12.02). There were 57 Black/African American patients (68.7%) and 85.5% had public insurance. Based on census tract-level data, about half (49.4%) of the CMC severe sepsis population lived in census tracts classified as suffering from high social vulnerability. There were no statistically significant relationships between any socioeconomic and neighborhood level factors and PICU LOS. Conclusion Pediatric CMC severe sepsis patients admitted to the PICU do not have prolonged lengths of ICU stay related to socioeconomic and neighborhood-level SDoH at our center. A larger sample with the use of individual-level screening would need to be evaluated for associations between social determinants of health and PICU outcomes of these patients.
In Vitro Synergy of Isavuconazole Combined With Colistin Against Common Candida Species

Interactions of isavuconazole and colistin were evaluated against 57 common Candida strains belonging to the species Candida albicans (n = 10), Candida glabrata (n = 10), Candida kefyr (n = 8), Candida krusei (n = 10), Candida parapsilosis (n = 9), and Candida tropicalis (n = 10) by a broth microdilution checkerboard technique based on the European Committee on Antimicrobial Susceptibility Testing (EUCAST) reference methodology for antifungal susceptibility testing. Results were analyzed with the fractional inhibitory concentration index and by the response surface analysis. Interpretation by the fractional inhibitory concentration index showed synergy for 50%, 80%, 90%, and 90% of the C. kefyr, C. krusei, C. glabrata, and C. tropicalis strains, respectively. Combination of isavuconazole with colistin against C. albicans and C. parapsilosis exhibited only indifference for 100% and 90% of the strains, respectively. The results were confirmed by response surface analysis for all species except for C. glabrata, for which an indifferent interaction was found for the majority of strains. Antagonistic interaction was never seen regardless of the interpretation model was used.
It’s the Little Things: The Role of Microscopic Life Stages in Maintaining Kelp Populations

Kelp forests are experiencing broad scale declines in abundance and shifts in latitudinal ranges in many areas of the world due to numerous environmental stressors, especially those associated with climate change. While the majority of studies on kelp ecology have focused exclusively on the macroscopic sporophyte life stage, a growing number of studies is showing quite convincingly that the microscopic zoospore and gametophyte life stages can be important to establishing spatial patterns in these marine forests, and in facilitating their recovery following deforestation. Unfortunately, their microscopic sizes have made them difficult to study in the field, leading to a ‘black box’ surrounding what we know about their ecologies. However, advances in experimental methodologies and a growing number of laboratories studying kelp microscopic life stages are revealing how they are affected by variability in environmental conditions, and are providing a clearer picture of how kelp forests might respond to a changing ocean climate. These studies have largely revealed that kelps can disperse over a wide range of distances, enhanced by the synchronous release and vertical transport of zoospores into shallower water, and by floating rafts of reproductive thalli. Settlement on the benthos is facilitated by both positive and negative chemotaxis, and by active selection of microhabitats that favor their growth and survival. Following settlement and subsequent germination, the haploid gametophytes can delay their development and form a bank of microscopic forms that persist during periods that are unfavorable for the large sporophyte populations, or they can develop and undergo sexual reproduction during which they respond to variability in environmental conditions. In particular, they are strongly affected by increases in irradiance (PAR, UVA + UVB) and temperature, decreases in nutrients and salinity, and by sedimentation and grazing. However, the manner in which they respond to these stressors varies among species and with their geographic distributions, which is integral to establishing biogeographic patterns in the large sporophyte populations. Given these factors are expected to change as the ocean climate changes, these species-specific responses have significant implications for future patterns of distribution and abundance of these iconic marine forests.
Effects of Crowding and Water Flow on Golden Shiners Notemigonus crysoleucas, Held in a Flow Tank

Split-pond systems (SPS) such as those used for catfish are being considered for raising baitfish. When using these systems for baitfish such as golden shiners Notemigonus crysoleucas, an important factor to be considered is how well the species can tolerate crowding, as the design mandates fish be confined to a smaller portion of the pond. Another aspect of the SPS design is the water flow between the two units for at least 10–14 h each day. SPS can be successfully implemented for other species if factors such as crowding, and water flow do not affect growth. Two laboratory studies were conducted each using 12, 40-L tank flow-through system to observe the growth and physiological performance of golden shiners held for 28 days at three crowding densities: 600; 1,200, and 2,400 fish/m3, keeping water flow at 1 cm/s (Experiment 1) and using three flow rates: 1, 2, and 4 cm/s at similar densities (600 fish/m3) (Experiment 2). At the end of the experiments, fish were subject to acute 1-min confinement stress and whole-body cortisol was measured at 30 min intervals for up to 2 h to monitor the secretion pattern and recovery. Results from experiments showed no difference in the final weight, length, feed conversion, and survival among treatment groups; survival rates were lower in the flow study because of columnaris Flavobacterium covae infections. Baseline cortisol was also not different among the treatments. Cortisol increased 30 min after the acute stress and returned to near baseline in 2 h in the crowding study suggesting acclimation to the chronic stressor. However, in the flow study, cortisol remained elevated even after 2 h, and hence a compromised pathophysiological response. Crowding and water flow do not impair feed intake, growth, or survival in golden shiners, and in these aspects may be a suitable species for SPS.
The Effects of Mechanical Stretch on Integrins and Filopodial-Associated Proteins in Normal and Glaucomatous Trabecular Meshwork Cells

The trabecular meshwork (TM) is the tissue responsible for regulating aqueous humor fluid egress from the anterior eye. If drainage is impaired, intraocular pressure (IOP) becomes elevated, which is a primary risk factor for primary open angle glaucoma. TM cells sense elevated IOP via changes in their biomechanical environment. Filopodia cellular protrusions and integrin transmembrane proteins may play roles in detecting IOP elevation, yet this has not been studied in detail in the TM. Here, we investigate integrins and filopodial proteins, such as myosin-X (Myo10), in response to mechanical stretch, an in vitro technique that produces mechanical alterations mimicking elevated IOP. Pull-down assays showed Myo10 binding to α5 but not the β1 subunit, αvβ3, and αvβ5 integrins. Several of these integrins colocalized in nascent adhesions in the filopodial tip and shaft. Using conformation-specific antibodies, we found that β1 integrin, but not α5 or αvβ3 integrins, were activated following 1-h mechanical stretch. Cadherin -11 (CDH11), a cell adhesion molecule, did not bind to Myo10, but was associated with filopodia. Interestingly, CDH11 was downregulated on the TM cell surface following 1-h mechanical stretch. In glaucoma cells, CDH11 protein levels were increased. Finally, mechanical stretch caused a small, yet significant increase in Myo10 protein levels in glaucoma cells, but did not affect cellular communication of fluorescent vesicles via filopodia-like tunneling nanotubes. Together, these data suggest that TM cell adhesion proteins, β1 integrin and CDH11, have relatively rapid responses to mechanical stretch, which suggests a central role in sensing changes in IOP elevation in situ.
Sex/Gender as a Factor That Influences Transcranial Magnetic Stimulation Treatment Outcome: Three Potential Biological Explanations

Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive brain stimulation technique which is now being used in psychiatry clinics across the world as a therapeutic tool for a variety of neural-circuit based disorders (e.g., major depression, obsessive compulsive disorder, substance use disorders, post-traumatic stress disorder, headache, pain). The higher volume of use and publication of multiple large-scale clinical trials has provided researchers with a unique opportunity to retrospectively evaluate factors influencing TMS treatment responses in large samples of patients. While many studies have focused on TMS protocol parameters as moderators of treatment efficacy, sex/gender is another critical, often overlooked factor influencing TMS treatment outcome. Women, especially during periods of high estradiol, appear to be particularly sensitive to the therapeutic effects of rTMS. This manuscript makes a case for three potential biological explanations for these findings. Drawing on literature from cranio-facial anatomy, neuroimaging, and neuroendocrine fields, we posit that observed increases in response rates of women in clinical rTMS trials may be related to: (1) Closer proximity of the brain to the scalp at the prefrontal cortex, leading to larger TMS induced electric fields especially at the medial prefrontal cortex, (2) Greater gray matter density and gyrification in the prefrontal cortex, and (3) High levels of estradiol which facilitate cortical excitability. These biological explanations are empirical ideas which have been evaluated in laboratory studies and lend themselves to prospective evaluation in multisite clinical rTMS trials. The existing literature on this topic and these three potential biological explanations all indicate that the TMS field should routinely evaluate sex/gender (and associated biological metrics like scalp-to-cortex distance, gray matter density, estradiol/progesterone levels) as a factor that may influence treatment outcome.
Sesquiterpene Lactams and Lactones With Antioxidant Potentials From Atractylodes macrocephala Discovered by Molecular Networking Strategy

Atractylodes macrocephala rhizome (called Bái-zhú in China) has a long history as a functional food and herbal medicine in East Asia, especially China. Sesquiterpenoids are one of the main active compounds of Atractylodes macrocephala rhizome. This study aimed to explore the unknown sesquiterpenoids of A. macrocephala rhizome using a molecular networking strategy. Two new nitrogen-containing sesquiterpenoids, atractylenolactam A (1) and atractylenolactam B (2), and 2 new sesquiterpene lactones, 8-methoxy-atractylenolide V (6) and 15-acetoxyl atractylenolide III (7), along with 12 known analogs (3-5 and 8-16) were discovered and isolated. All the structures were assigned based on detailed spectroscopic analyses. The absolute configurations of 1, 2, 6, and 7 were established by time-dependent density functional theory ECD (TDDFT-ECD) calculations. All these compounds had different degrees of concentration-dependent activating effects on nuclear-factor-E2-related factor-2 (Nrf2).
Azole Fungicides and Their Endocrine Disrupting Properties: Perspectives on Sex Hormone-Dependent Reproductive Development

Azoles are antifungal agents used in both agriculture and medicine. They typically target the CYP51 enzyme in fungi and, by so doing, disrupt cell membrane integrity. However, azoles can also target various CYP enzymes in mammals, including humans, which can disrupt hormone synthesis and signaling. For instance, several azoles can inhibit enzymes of the steroidogenic pathway and disrupt steroid hormone biosynthesis. This is of particular concern during pregnancy, since sex hormones are integral to reproductive development. In other words, exposure to azole fungicides during fetal life can potentially lead to reproductive disease in the offspring. In addition, some azoles can act as androgen receptor antagonists, which can further add to the disrupting potential following exposure. When used as pharmaceuticals, systemic concentrations of the azole compounds can become significant as combatting fungal infections can be very challenging and require prolonged exposure to high doses. Although most medicinal azoles are tightly regulated and used as prescription drugs after consultations with medical professionals, some are sold as over-the-counter drugs. In this review, we discuss various azole fungicides known to disrupt steroid sex hormone biosynthesis or action with a focus on what potential consequences exposure during pregnancy can have on the life-long reproductive health of the offspring.
The Yin and Yang of Targeting KLRG1+ Tregs and Effector Cells

The literature surrounding KLRG1 has primarily focused on NK and CD8+ T cells. However, there is evidence that the most suppressive Tregs express KLRG1. Until now, the role of KLRG1 on Tregs has been mostly overlooked and remains to be elucidated. Here we review the current literature on KLRG1 with an emphasis on the KLRG1+ Treg subset role during cancer development and autoimmunity. KLRG1 has been recently proposed as a new checkpoint inhibitor target, but these studies focused on the effects of KLRG1 blockade on effector cells. We propose that when designing anti-tumor therapies targeting KLRG1, the effects on both effector cells and Tregs will have to be considered.