A genome-wide spectrum of tandem repeat expansions in 338,963 humans.

The Genome Aggregation Database (gnomAD), widely recognized as the gold-standard reference map of human genetic variation, has largely overlooked tandem repeat (TR) expansions, despite the fact that TRs constitute ∼6% of our genome and are linked to over 50 human diseases. Here, we introduce the TR-gnomAD (https://wlcb.oit.uci.edu/TRgnomAD), a biobank-scale reference of 0.86 million TRs derived from 338,963 whole-genome sequencing (WGS) samples of diverse ancestries (39.5% non-European samples). TR-gnomAD offers critical insights into ancestry-specific disease prevalence using disparities in TR unit number frequencies among ancestries. Moreover, TR-gnomAD is able to differentiate between common, presumably benign TR expansions, which are prevalent in TR-gnomAD, from those potentially pathogenic TR expansions, which are found more frequently in disease groups than within TR-gnomAD. Together, TR-gnomAD is an invaluable resource for researchers and physicians to interpret TR expansions in individuals with genetic diseases.

Gasdermin D licenses MHCII induction to maintain food tolerance in small intestine.

The intestinal epithelial cells (IECs) constitute the primary barrier between host cells and numerous foreign antigens; it is unclear how IECs induce the protective immunity against pathogens while maintaining the immune tolerance to food. Here, we found IECs accumulate a less recognized 13-kD N-terminal fragment of GSDMD that is cleaved by caspase-3/7 in response to dietary antigens. Unlike the 30-kD GSDMD cleavage fragment that executes pyroptosis, the IEC-accumulated GSDMD cleavage fragment translocates to the nucleus and induces the transcription of CIITA and MHCII molecules, which in turn induces the Tr1 cells in upper small intestine. Mice treated with a caspase-3/7 inhibitor, mice with GSDMD mutation resistant to caspase-3/7 cleavage, mice with MHCII deficiency in IECs, and mice with Tr1 deficiency all displayed a disrupted food tolerance phenotype. Our study supports that differential cleavage of GSDMD can be understood as a regulatory hub controlling immunity versus tolerance in the small intestine.

Nuclear Receptor Nur77 Facilitates Melanoma Cell Survival under Metabolic Stress by Protecting Fatty Acid Oxidation.

Fatty acid oxidation (FAO) is crucial for cells to overcome metabolic stress by providing ATP and NADPH. However, the mechanism by which FAO is regulated in tumors remains elusive. Here we show that Nur77 is required for the metabolic adaptation of melanoma cells by protecting FAO. Glucose deprivation activates ERK2 to phosphorylate and induce Nur77 translocation to the mitochondria, where Nur77 binds to TPß, a rate-limiting enzyme in FAO. Although TPß activity is normally inhibited by oxidation under glucose deprivation, the Nur77-TPß association results in Nur77 self-sacrifice to protect TPß from oxidation. FAO is therefore able to maintain NADPH and ATP levels and prevent ROS increase and cell death. The Nur77-TPß interaction further promotes melanoma metastasis by facilitating circulating melanoma cell survival. This study demonstrates a novel regulatory function of Nur77 with linkage of the FAO-NADPH-ROS pathway during metabolic stress, suggesting Nur77 as a potential therapeutic target in melanoma.

Giant self-driven exciton-Floquet signatures in time-resolved photoemission spectroscopy of MoS2 from time-dependent GW approach.

Time-resolved, angle-resolved photoemission spectroscopy (TR-ARPES) is a one-particle spectroscopic technique that can probe excitons (two-particle excitations) in momentum space. We present an ab initio, time-domain GW approach to TR-ARPES and apply it to monolayer MoS2. We show that photoexcited excitons may be measured and quantified as satellite bands and lead to the renormalization of the quasiparticle bands. These features are explained in terms of an exciton-Floquet phenomenon induced by an exciton time-dependent bosonic field, which are orders of magnitude stronger than those of laser field-induced Floquet bands in low-dimensional semiconductors. Our findings imply a way to engineer Floquet matter through the coherent oscillation of excitons and open the new door for mechanisms for band structure engineering.

BAP1 regulation of the key adaptor protein NCoR1 is critical for γ-globin gene repression.

Human globin gene production transcriptionally "switches" from fetal to adult synthesis shortly after birth and is controlled by macromolecular complexes that enhance or suppress transcription by cis elements scattered throughout the locus. The DRED (direct repeat erythroid-definitive) repressor is recruited to the ε-globin and γ-globin promoters by the orphan nuclear receptors TR2 (NR2C1) and TR4 (NR2C2) to engender their silencing in adult erythroid cells. Here we found that nuclear receptor corepressor-1 (NCoR1) is a critical component of DRED that acts as a scaffold to unite the DNA-binding and epigenetic enzyme components (e.g., DNA methyltransferase 1 [DNMT1] and lysine-specific demethylase 1 [LSD1]) that elicit DRED function. We also describe a potent new regulator of γ-globin repression: The deubiquitinase BRCA1-associated protein-1 (BAP1) is a component of the repressor complex whose activity maintains NCoR1 at sites in the ß-globin locus, and BAP1 inhibition in erythroid cells massively induces γ-globin synthesis. These data provide new mechanistic insights through the discovery of novel epigenetic enzymes that mediate γ-globin gene repression.

Celastrol-Induced Nur77 Interaction with TRAF2 Alleviates Inflammation by Promoting Mitochondrial Ubiquitination and Autophagy.

Mitochondria play an integral role in cell death, autophagy, immunity, and inflammation. We previously showed that Nur77, an orphan nuclear receptor, induces apoptosis by targeting mitochondria. Here, we report that celastrol, a potent anti-inflammatory pentacyclic triterpene, binds Nur77 to inhibit inflammation and induce autophagy in a Nur77-dependent manner. Celastrol promotes Nur77 translocation from the nucleus to mitochondria, where it interacts with tumor necrosis factor receptor-associated factor 2 (TRAF2), a scaffold protein and E3 ubiquitin ligase important for inflammatory signaling. The interaction is mediated by an LxxLL motif in TRAF2 and results not only in the inhibition of TRAF2 ubiquitination but also in Lys63-linked Nur77 ubiquitination. Under inflammatory conditions, ubiquitinated Nur77 resides at mitochondria, rendering them sensitive to autophagy, an event involving Nur77 interaction with p62/SQSTM1. Together, our results identify Nur77 as a critical intracellular target for celastrol and unravel a mechanism of Nur77-dependent clearance of inflamed mitochondria to alleviate inflammation.

Immunomodulatory and immunoregulatory nanomedicines for autoimmunity.

Autoimmune diseases, caused by cellularly and molecularly complex immune responses against self-antigens, are largely treated with broad-acting, non-disease-specific anti-inflammatory drugs. These compounds can attenuate autoimmune inflammation, but tend to impair normal immunity against infection and cancer, cannot restore normal immune homeostasis and are not curative. Nanoparticle (NP)- and microparticle (MP)-based delivery of immunotherapeutic agents affords a unique opportunity to not only increase the specificity and potency of broad-acting immunomodulators, but also to elicit the formation of organ-specific immunoregulatory cell networks capable of inducing bystander immunoregulation. Here, we review the various NP/MP-based strategies that have so far been tested in models of experimental and/or spontaneous autoimmunity, with a focus on mechanisms of action.

Regulatory B cells: TIM-1, transplant tolerance, and rejection.

Regulatory B cells (Bregs) ameliorate autoimmune disease and prevent allograft rejection. Conversely, they hinder effective clearance of pathogens and malignancies. Breg activity is mainly attributed to IL-10 expression, but also utilizes additional regulatory mechanisms such as TGF-ß, FasL, IL-35, and TIGIT. Although Bregs are present in various subsets defined by phenotypic markers (including canonical B cell subsets), our understanding of Bregs has been limited by the lack of a broadly inclusive and specific phenotypic or transcriptional marker. TIM-1, a broad marker for Bregs first identified in transplant models, plays a major role in Breg maintenance and induction. Here, we expand on the role of TIM-1+  Bregs in immune tolerance and propose TIM-1 as a unifying marker for Bregs that utilize various inhibitory mechanisms in addition to IL-10. Further, this review provides an in-depth assessment of our understanding of Bregs in transplantation as elucidated in murine models and clinical studies. These studies highlight the major contribution of Bregs in preventing allograft rejection, and their ability to serve as highly predictive biomarkers for clinical transplant outcomes.

Combined transcriptome and proteome analysis reveals MSN and ARFIP2 as biomarkers for trastuzumab resistance of breast cancer.

PURPOSE: HER2-positive breast cancer (BC) accounts for 20-30% of all BC subtypes and is linked to poor prognosis. Trastuzumab (Tz), a humanized anti-HER2 monoclonal antibody, is a first-line treatment for HER2-positive breast cancer which faces resistance challenges. This study aimed to identify the biomarkers driving trastuzumab resistance. METHODS: Differential expression analysis of genes and proteins between trastuzumab-sensitive (TS) and trastuzumab-resistant (TR) cells was conducted using RNA-seq and iTRAQ. Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) were used to study their functions. The prognostic significance and protein levels of ARFIP2 and MSN were evaluated using online tools and immunohistochemistry. Sensitivity of MSN and ARFIP2 to other therapies was assessed using public pharmacogenomics databases and the R language. RESULTS: Five genes were up-regulated, and nine genes were down-regulated in TR cells at both transcriptional and protein levels. Low ARFIP2 and high MSN expression linked to poor BC prognosis. MSN increased and ARFIP2 decreased in TR patients, correlating with shorter OS. MSN negatively impacted fulvestrant and immunotherapy sensitivity, while ARFIP2 had a positive impact. CONCLUSION: Our findings suggest that MSN and ARFIP2 could serve as promising biomarkers for predicting response to Tz, offering valuable insights for future research in the identification of diagnostic and therapeutic targets for BC patients with Tz resistance.

In vitro Models for Predicting Bioadhesion Fracture Strength to Ex Vivo Animal Buccal Tissue.

Commitment to the 3Rs principle (Replacement, Reduction, and Refinement) led to the development of a cell-based system to measure buccal bioadhesion in vitro and replace the use of porcine buccal and esophageal tissues (PBT and PET, respectively). Additionally, the aim is to bridge the gap in knowledge regarding the bioadhesion properties of PBT and PET. The in vitro models are based on the human buccal epithelial cell line-TR146 without ("Model I") or with ("Model II") 5% (w/v) mucous layer. The in vitro setup also provides a method to evaluate the bioadhesion between two soft materials. Standard bioadhesive hydrogels (alginate, chitosan, and gelatin) are used to test and compare the results from the in vitro models to the ex vivo tissues. The ex vivo and in vitro models show increased bioadhesion as the applied force and contact time increases. Furthermore, Model I exhibits bioadhesion values-of alginate, chitosan, and gelatin-comparable to those obtained with PBT. It is also found that contact time and applied force similarly affect PBT and PET bioadhesion, while PET exhibits greater values. In conclusion, Model I can replace PBT for measuring bioadhesion and be incorporated into the experimental design of bioadhesive DDS, thus minimizing animal tissue usage.

Combination of XEOL, TR-XEOL and HB-T interferometer at the TPS 23A X-ray nanoprobe for exploring quantum materials.

In this study, a combination of X-ray excited optical luminescence (XEOL), time-resolved XEOL (TR-XEOL) and the Hanbury-Brown and Twiss (HB-T) interferometer at the Taiwan Photon Source (TPS) 23A X-ray nanoprobe beamline for exploring quantum materials is demonstrated. On the basis of the excellent spatial resolution rendered using a nano-focused beam, emission distributions of artificial micro-diamonds can be obtained by XEOL maps, and featured emission peaks of a selected local area can be obtained by XEOL spectra. The hybrid bunch mode of the TPS not only provides a sufficiently high peak power density for experiments at each beamline but also permits high-quality temporal domain (∼200 ns) measurements for investigating luminescence dynamics. From TR-XEOL measurements, the decay lifetime of micro-diamonds is determined to be approximately 16 ns. Furthermore, the XEOL spectra of artificial micro-diamonds can be investigated by the HB-T interferometer to identify properties of single-photon sources. The unprecedented strategy of combining XEOL, TR-XEOL and the HB-T interferometer at the X-ray nanoprobe beamline will open new avenues with significant characterization abilities for unraveling the emission mechanisms of single-photon sources for quantum materials.

B 1 + inhomogeneity mitigation for diffusion weighted MRI at 7T using TR-FOCI pulses.

PURPOSE: The purpose of this study is to improve the image quality of diffusion-weighted images obtained with a single RF transmit channel 7 T MRI setup using time-resampled frequency-offset corrected inversion (TR-FOCI) pulses to refocus the spins in a twice-refocused spin-echo readout scheme. METHODS: We replaced the conventional Shinnar-Le Roux-pulses in the twice refocused diffusion sequence with TR-FOCI pulses. The slice profiles were evaluated in simulation and experimentally in phantoms. The image quality was evaluated in vivo comparing the Shinnar-Le Roux and TR-FOCI implementation using a b value of 0 and of 1000 s/mm2. RESULTS: The b0 and diffusion-weighted images acquired using the modified sequence improved the image quality across the whole brain. A region of interest-based analysis showed an SNR increase of 113% and 66% for the nondiffusion-weighted (b0) and the diffusion-weighted (b = 1000 s/mm2) images in the temporal lobes, respectively. Investigation of all slices showed that the adiabatic pulses mitigated B 1 + $$ {B}_1^{+} $$ inhomogeneity globally using a conventional single-channel transmission setup. CONCLUSION: The TR-FOCI pulse can be used in a twice-refocused spin-echo diffusion pulse sequence to mitigate the impact of B 1 + $$ {B}_1^{+} $$ inhomogeneity on the signal intensity across the brain at 7 T. However, further work is needed to address SAR limitations.

PET Imaging of Differentiated Thyroid Cancer with TSHR-Targeted [89Zr]Zr-TR1402.

Thyroid cancer is the most common endocrine cancer, with differentiated thyroid cancers (DTCs) accounting for 95% of diagnoses. While most DTC patients are diagnosed and treated with radioiodine (RAI), up to 20% of DTC patients become RAI refractory (RAI-R). RAI-R patients have significantly reduced survival rates compared to patients who remain RAI-avid. This study explores [89Zr]Zr-TR1402 as a thyroid-stimulating hormone receptor (TSHR)-targeted PET radiopharmaceutical for DTC. [89Zr]Zr-TR1402 was synthesized with a molar activity of 25.9 MBq/nmol by conjugating recombinant human TSH (rhTSH) analogue TR1402 to chelator p-SCN-Bn-deferoxamine (DFO) in a molar ratio of 3:1 (DFO/TR1402) and radiolabeling with 89Zr (t1/2 = 78.4 h, ß+ = 22.7%). As TSHR is absent in commonly available DTC-derived cell lines, TSHR was reintroduced via stable transduction by delivering a lentivirus containing the full-length coding region of the human TSHR gene. Receptor-mediated uptake of [89Zr]Zr-TR1402 was evaluated in vitro in stably transduced TSHR+ and wild-type TSHR- DTC cell lines. In vivo PET imaging was performed on Days 1-3 postinjection in male and female athymic nude mice bearing TSHR+ and TSHR- xenografts, along with ex vivo biodistribution on Day 3 postinjection. In vitro uptake of 1 nM [89Zr]Zr-TR1402 was significantly higher in TSHR+ THJ529T (P < 0.0001) and FTC133 (P < 0.01) cells than in TSHR- THJ529T and FTC133 cells. This uptake was shown to be specific in both TSHR+ THJ529T (P < 0.0001) and TSHR+ FTC133 (P < 0.0001) cells by blocking uptake with 250 nm DFO-TR1402. In vivo PET imaging showed accumulation of [89Zr]Zr-TR1402 in TSHR+ tumors, which was the highest on Day 1. In the male FTC133 xenograft model, ex vivo biodistribution confirmed a significant difference (P < 0.001) in uptake between FTC133+ (1.3 ± 0.1%ID/g) and FTC133- (0.8 ± 0.1%ID/g) tumors. A significant difference (P < 0.05) in uptake was also seen in the male THJ529T xenograft model between THJ529T+ (1.8 ± 0.6%ID/g) and THJ529T- (0.8 ± 0.4%ID/g) tumors. The in vitro and in vivo accumulation of [89Zr]Zr-TR1402 in TSHR-expressing DTC cell lines support the continued preclinical optimization of this approach.

Report of three azole-resistant Aspergillus fumigatus cases with TR34/L98H mutation in hematological patients in Barcelona, Spain.

OBJECTIVES: We aimed to report the emergence of azole-resistant invasive aspergillosis in hematologic patients admitted to a tertiary hospital in Spain during the last 4 months. METHODS: Prospective, descriptive study was performed to describe and follow all consecutive proven and probable invasive aspergillosis resistant to azoles from hematological cohort during the last 4 months. All patients had fungal cultures and antifungal susceptibility or real-time PCR detection for Aspergillus species and real-time PCR detection for azole-resistant mutation. RESULTS: Four cases of invasive aspergillosis were diagnosed in 4 months. Three of them had azole-resistant aspergillosis. Microbiological diagnosis was achieved in three cases by means of fungal culture isolation and subsequent antifungal susceptibility whereas one case was diagnosed by PCR-based aspergillus and azole resistance detection. All the azole-resistant aspergillosis presented TR34/L98H mutation. Patients with azole-resistant aspergillosis had different hematologic diseases: multiple myeloma, lymphoblastic acute leukemia, and angioimmunoblastic T lymphoma. Regarding risk factors, one had prolonged neutropenia, two had corticosteroids, and two had viral co-infection. Two of the patients developed aspergillosis under treatment with azoles. CONCLUSION: We have observed a heightened risk of azole-resistant aspergillosis caused by A. fumigatus harboring the TR34/L98H mutation in patients with hematologic malignancies. The emergence of azole-resistant aspergillosis raises concerns for the community, highlighting the urgent need for increased surveillance and the importance of susceptibility testing and new drugs development.

The pros and cons of nucleic acid-amplified immunoassays-a comparative study on the quantitation of prostate-specific antigen with and without rolling circle amplification.

Integrating isothermal nucleic acid amplification strategies into immunoassays can significantly decrease analytical limits of detection (LODs). On the other hand, an amplification step adds time, complication, reagents, and costs to the assay format. To evaluate the pros and cons in the context of heterogeneous multistep immunoassays, we quantified prostate-specific antigen (PSA) with and without rolling circle amplification (RCA). In addition, we compared time-gated (TG) with continuous-wave (CW) photoluminescence (PL) detection using a terbium complex and a fluorescein dye, respectively. For both direct (non-amplified) and amplified assays, TG PL detection provided circa four- to eightfold lower LODs, illustrating the importance of autofluorescence background suppression even for multi-wash assay formats. Amplified assays required an approximately 2.4 h longer assay time but led to almost 100-fold lower LODs down to 1.3 pg/mL of PSA. Implementation of TG-FRET (using a Tb-Cy5.5 donor-acceptor pair) into the RCA immunoassay resulted in a slightly higher LOD (3.0 pg/mL), but the ratiometric detection format provided important benefits, such as higher reproducibility, lower standard deviations, and multiplexing capability. Overall, our direct comparison demonstrated the importance of biological background suppression even in heterogeneous assays and the potential of using isothermal RCA for strongly decreasing analytical LODs, making such assays viable alternatives to conventional enzyme-linked immunosorbent assays (ELISAs).

Differences in Subjective Transition Outcomes Between Transgender and Gender-Diverse Individuals Who Completed Mandatory Psychiatric Assessment and Those Who Received Gender-Affirmative Medical Treatment in Croatia: A Cross-Sectional Online Survey.

The aim of this study was to evaluate different aspects of transition outcomes in groups of transgender and gender diverse (TGD) people based on their transition status. We divided the 70 TGD participants (19 individuals assigned male at birth and 51 assigned female at birth) into two groups: those who had completed their psychiatric and psychological evaluation (PPE), which is mandatory in Croatia, and those who had undergone gender-affirming medical treatment (GAMT) (both gender-affirming hormone treatment and gender-affirming surgery). The online survey included sociodemographic questions and a custom-designed nine-item scale. The items were specifically designed based on the DSM-5-TR criteria for gender dysphoria to assess subjectively perceived transition outcomes. We conducted a factor analysis of the scale followed by structural equation modeling for confirmation. Chi-squared and Mann-Whitney U tests were used to compare group differences. The following three-factor structure was confirmed: better functioning, reduced body dysphoria, and satisfaction with decision. A positive influence of better functioning on satisfaction with the decision was found. In addition, our results showed that TGD individuals who had undergone GAMT scored higher on better functioning than those who had just completed PPE. Both groups consistently scored high on satisfaction with the decision, with no statistically significant differences between them. Our findings suggest that TGD individuals view gender-affirming medical care as beneficial to their overall functioning.

Quantitative analysis of Tr1 lymphocytes in patients with type 2 diabetes mellitus.

BACKGROUND: Type 2 diabetes mellitus (T2DM) is usually accompanied by a low-grade inflammatory phenomenon, which participates in the pathogenesis of different complications of this condition. The inflammatory response is under the regulation of different mechanisms, including T regulatory (Treg) lymphocytes. However, the possible role of type 1 T regulatory (Tr1) cells in T2DM has not been explored so far. AIM: To carry out a quantitative analysis of Tr1 lymphocytes and other immune cell subsets in patients with T2DM and correlate these results with clinical findings and treatments. MATERIALS AND METHODS: Sixty patients with T2DM and twenty-three healthy controls were included in the study. Biochemical and anthropometric variables were evaluated, and Tr1 lymphocytes (CD4+CD49+LAG-3+IL-10+) and other cell subsets (Th17, Th22 and Foxp3 + Treg cells) were analyzed in peripheral blood samples by multiparametric flow cytometry. RESULTS: Significant increased levels of Tr1 cells were detected in patients with severe and mild disease, compared to healthy controls. In addition, CD4+IL-10+ lymphocytes were also increased in patients with T2DM. In contrast, similar levels of Foxp3+ Treg cells, Th17 and Th22 lymphocytes were observed in patients and controls. Likewise, no significant associations were detected between Tr1 cell levels and different clinical and laboratory parameters. However, those patients receiving glucagon-like peptide-1 receptor agonists (GLP-1-RA) showed similar levels of Tr1 cells than healthy controls, and significant lower numbers than untreated patients. CONCLUSION: We observed an increase in Tr1 and CD4+IL10+ lymphocyte levels in T2DM. Moreover, GLP1-RA treatment was significantly associated with normalization of the Tr1 levels. This highlights another potential immune dysfunction in patients with T2DM, which could participate in the pathogenesis of this condition.

First detection of triazole-resistant aspergillus fumigatus harbouring the TR34/L98H Cyp51A mutation in Burkina Faso.

BACKGROUND: Triazole-resistant Aspergillus fumigatus (TRAF) isolates are a growing public health problem with worldwide distribution. Epidemiological data on TRAF is limited in Africa, particularly in West Africa. OBJECTIVES: This study aimed to screen for the environmental presence of TRAF isolates in the indoor air of two hospitals in Burkina Faso. MATERIALS AND METHODS: Air samples were collected in wards housing patients at risk for invasive aspergillosis, namely infectious diseases ward, internal medicine ward, nephrology ward, pulmonology ward, medical emergency ward and paediatric ward. Sabouraud Dextrose Agar supplemented with triazoles was used to screen the suspected TRAF isolates and EUCAST method to confirm the resistance of suspected isolates. Sequencing of cyp51A gene was used to identify the resistance mechanism of confirmed TRAF isolates. RESULTS: Of the 198 samples collected and analysed, 67 showed growth of A. fumigatus isolates. The prevalence of TRAF isolates was 3.23% (4/124). One TRAF isolate exhibited a pan-triazole resistance. Sequencing of cyp51A gene identified the TR34/L98H mutation for this pan-triazole resistant isolate. This study showed for the first time the circulation of the pan-azole resistant isolate harbouring the TR34/L98H mutation in Burkina Faso. CONCLUSIONS: These findings emphasise the need to map these TRAF isolates in all parts of Burkina Faso and to establish local and national continuous surveillance of environmental and clinical TRAF isolates in this country.

Passive coupling of membrane tension and cell volume during active response of cells to osmosis.

During osmotic changes of their environment, cells actively regulate their volume and plasma membrane tension that can passively change through osmosis. How tension and volume are coupled during osmotic adaptation remains unknown, as their quantitative characterization is lacking. Here, we performed dynamic membrane tension and cell volume measurements during osmotic shocks. During the first few seconds following the shock, cell volume varied to equilibrate osmotic pressures inside and outside the cell, and membrane tension dynamically followed these changes. A theoretical model based on the passive, reversible unfolding of the membrane as it detaches from the actin cortex during volume increase quantitatively describes our data. After the initial response, tension and volume recovered from hypoosmotic shocks but not from hyperosmotic shocks. Using a fluorescent membrane tension probe (fluorescent lipid tension reporter [Flipper-TR]), we investigated the coupling between tension and volume during these asymmetric recoveries. Caveolae depletion and pharmacological inhibition of ion transporters and channels, mTORCs, and the cytoskeleton all affected tension and volume responses. Treatments targeting mTORC2 and specific downstream effectors caused identical changes to both tension and volume responses, their coupling remaining the same. This supports that the coupling of tension and volume responses to osmotic shocks is primarily regulated by mTORC2.

Determination of the relationship between parents' health literacy and fever management of their children: A cross-sectional study.

AIMS: The research was conducted to determine the practices of parents regarding the fever management of their children and reveal the relationship between their health literacy (HL) and fever management of their children. DESIGN: Cross-sectional study was used. METHODS: This study was carried out with 242 parents. The data were collected using the Parent Descriptive Information Form, Turkish HL Scale-32 and Parents' Fever Management Scale between September 2021 and September 2022. The data were evaluated with the SPSS program, using percentages, averages, Pearson's correlation and regression analysis. RESULTS: The mean age of the parents was 31.87 ± 6.59. The parents' mean Parents' Fever Management Scale score was 36.22. It means that parents had high fever management practice. Their mean Turkish HL Scale-32 total score was 34.43. 51.6% of the parents had a problematic or insufficient HL level. In the cases of fever, 61.2% of the parents stated that they took off the child's clothes, 69.0% measured temperature from the armpit, and 55.4% gave antipyretics according to the doctor's prescription. There is a statistically significant positive correlation between the Parents' Fever Management Scale and Turkish HL Scale-32. It is observed that 8.2% of the change in parents' fever management is explained by HL. CONCLUSION: The study found that with an increase in parents' HL, fever management of their children also increased. IMPLICATIONS FOR THE PROFESSION AND/OR PATIENT CARE: Emerging evidence showed that developing parents' HL knowledge and skills could be an option/approach in fever management. It should be a basic nursing skill that to provide HL support to parents. REPORTING METHOD: This study adhered to the relevant cross-sectional STROBE (the Strengthening the Reporting of Observational Studies in Epidemiology) guidelines. PATIENT OR PUBLIC CONTRIBUTION: No patient or public contribution.