Effectiveness of toric intraocular lens implantation for correcting irregular corneal astigmatism in cataract eyes.

A retrospective cohort study was conducted to observe the correction effect of Toric intraocular lens (IOL) implantation in cataract eyes with specific types of irregular corneal astigmatism. Thirty-four eyes with either the "asymmetric bow-tie" pattern (Type I) or the "angled bow-tie" pattern (Type II) were included. Corneal topography was assessed using Pentacam HR, and changes in preoperative corneal astigmatism, visual acuity, manifest refraction, and objective visual quality were measured and compared. The average uncorrected distance visual acuity improved significantly from 0.86 ± 0.40 logMAR to 0.22 ± 0.15 logMAR (P < 0.001). Preoperative corneal astigmatism of 2.05 ± 0.90 D was corrected to a postoperative residual astigmatism of 0.78 ± 0.57 D (P < 0.001), with 32% of eyes within 0.50 D. The residual astigmatism prediction errors in Type I and Type II cases were (0.97 ± 0.68 D) and (0.66 ± 0.37 D), respectively (P = 0.100). The mean spherical equivalent prediction error in Type II cases (0.07 ± 0.36 D) was significantly smaller than that in Type I cases (- 0.29 ± 0.52 D) (P = 0.030). This study concludes that Toric IOL implantation effectively corrects specific types of irregular corneal astigmatism in cataract surgery. Eyes with the "angled bow-tie" pattern show higher accuracy in refractive predictions compared to eyes with the "asymmetric bow-tie" pattern.

Proximity to the water surface markedly enhances the force production on underwater flapping wings.

The potential application of flapping wings in micro-aerial vehicles is gaining interest due to their ability to generate high lift even in confined spaces. Most studies in the past have investigated hovering wings as well as those flapping near solid surfaces. However, the presence of surface tension at the water-air interface and the ability of the water surface to move might differentiate its response to the proximity of wings, compared to that of solid surfaces. Motivated by underwater, amphibian robots and several underwater experimental studies on flapping wings, our study investigated the effects of the proximity of flapping wings to the water surface at low Reynolds numbers (Re = 3400). Experiments were performed on a rectangular wing in a water tank with prescribed flapping kinematics and the aerodynamic forces were measured. The effects of surface proximity on the wing in its both upright and inverted orientations were studied. Broadly, the mean lift and drag coefficients in both orientations decreased significantly (by up to 60%) as the distance from the water surface was increased. In the case of the upright orientation, the mean lift coefficient was slightly decreased very close to the water surface with its peak being observed at the normalized clearance of [Formula: see text]. Overall, the study revealed an enhancement in the aerodynamic forces closer to the water surface.

Identification of membrane curvature sensing motifs essential for VPS37A phagophore recruitment and autophagosome closure.

VPS37A, an ESCRT-I complex component, is required for recruiting a subset of ESCRT proteins to the phagophore for autophagosome closure. However, the mechanism by which VPS37A is targeted to the phagophore remains obscure. Here, we demonstrate that the VPS37A N-terminal domain exhibits selective interactions with highly curved membranes, mediated by two membrane-interacting motifs within the disordered regions surrounding its Ubiquitin E2 variant-like (UEVL) domain. Site-directed mutations of residues in these motifs disrupt ESCRT-I localization to the phagophore and result in defective phagophore closure and compromised autophagic flux in vivo, highlighting their essential role during autophagy. In conjunction with the UEVL domain, we postulate that these motifs guide a functional assembly of the ESCRT machinery at the highly curved tip of the phagophore for autophagosome closure. These results advance the notion that the distinctive membrane architecture of the cup-shaped phagophore spatially regulates autophagosome biogenesis.

Decolorization and detoxification of Brilliant Crocein GR by a newly enriched thermophilic consortium.

The environmental pollution caused by azo dyes at high temperatures has become an urgent problem. However, little attention has been paid to decolorizing azo dyes by thermophilic consortiums. In this study, a thermophilic bacterial consortium (BCGR-T) mainly composed of two genera, namely, Caldibacillus (70.90%) and Aeribacillus (17.63%) was first enriched, which can decolorize Brilliant Crocein GR (BCGR) at high temperatures (50-75 °C), pH values of 6∼8, dye concentrations (100-400 mg/L) and salinities (1-5%, w/v). The enzyme activity results showed that the azoreductase activity was nearly 8.8 times that of the control (p < 0.01), and the intracellular lignin peroxidase was also highly expressed with enzyme activity of 5.64 U (min-1 mg-1 protein) (p < 0.05), indicated that both azoreductase and intracellular lignin peroxidase played an important part in the decolorization process. Furthermore, seven new intermediate metabolic products, including aniline, phthalic acid, 2-carboxy benzaldehyde, phenylacetic acid, benzoic acid, toluene, and 4-methyl-hexanoic acid, were identified. In addition, functional genes related with the azo dye decolorization, such as those encoding the azoreductase, laccase, FMN reductase, NADPH-/NADH-quinone oxidoreductases and NADPH-/NADH dehydrogenases, catechol dioxygenase, homogentisate 1,2-dioxygenase, protocatechuate 3,4-dioxygenase, gentisate 1,2-dioxygenase, azobenzene reductase, naphthalene 1,2-dioxygenase, benzoate/toluate 1,2-dioxygenase, and anthranilate 1,2-dioxygenase and so on were found in the metagenome of the consortium BCGR-T. Finally, a new decolorization pathway of the thermophilic consortium BCGR-T was proposed. In addition, the phototoxicity of BCGR decreased after decolorization. Overall, the thermophilic consortium BCGR-T could be a promising candidate in the treatment of high concentration azo dye wastewater at high temperatures.

Crystal structure and Hirshfeld surface analysis of a salt of antineoplastic kinase inhibitor vandetanib.

A salt of vandetanib, namely, 4-({4-[(4-bromo-2-fluorophenyl)amino]-6-methoxyquinazolin-7-yl}methoxy)-1-methylpiperazin-1-ium 2-(butylamino)-4-phenoxy-6-sulfamoylbenzoate acetonitrile monosolvate, C22H25BrFN4O2+·C17H19N2O5S-·C2H3N, composed of kinase inhibitor vandetanib and sulfamyl diuretic bumetanide in a 1:1 molar ratio, is reported. There is proton transfer between the piperidine ring of vandetanib and the carboxyl group of bumetanide to form the salt. In the vandetanib cation, the arene and pyrimidine rings are not coplanar, their planes subtending a dihedral angle of 60.47 (14)°. The roles of the intermolecular interactions in the crystal packing were clarified using Hirshfeld surface analysis, and two-dimensional fingerprint plots indicate that the most important contributions to the crystal packing are from H...H (40.5%), O...H/H...C (20.7%), C...H/ H...C (18.8%) and N...C/C...N (9.0%) contacts.

smdi: an R package to perform structural missing data investigations on partially observed confounders in real-world evidence studies.

Objectives: Partially observed confounder data pose a major challenge in statistical analyses aimed to inform causal inference using electronic health records (EHRs). While analytic approaches such as imputation are available, assumptions on underlying missingness patterns and mechanisms must be verified. We aimed to develop a toolkit to streamline missing data diagnostics to guide choice of analytic approaches based on meeting necessary assumptions. Materials and methods: We developed the smdi (structural missing data investigations) R package based on results of a previous simulation study which considered structural assumptions of common missing data mechanisms in EHR. Results: smdi enables users to run principled missing data investigations on partially observed confounders and implement functions to visualize, describe, and infer potential missingness patterns and mechanisms based on observed data. Conclusions: The smdi R package is freely available on CRAN and can provide valuable insights into underlying missingness patterns and mechanisms and thereby help improve the robustness of real-world evidence studies.

Study on the vertical Bridgman method of melt-grown CsPbBr3 single crystals for nuclear radiation detection.

As an excellent representative of all-inorganic perovskite materials, CsPbBr3 has been widely used in high-energy rays or high-energy particles detection for its outstanding high carrier mobility and long diffusion length. The great challenges and opportunities in these fields are crystal growth technology, especially the high-quality and large-sized CsPbBr3 single crystals. In this work, the influences of growth parameters (temperature gradient, growth rate, cooling rate) and thermal stress by the vertical Bridgman method on the quality and performance of CsPbBr3 crystals are systematically studied. The final results show that 10°C cm-1 is the optimized temperature gradient and 0.5 mm h-1 is the suitable growth rate for CsPbBr3 crystal growth. The study also shows that a cooling rate of 10°C h-1 for the general temperature interval and 1°C h-1 for the phase transition temperature interval is helpful to balance crystal growth efficiency as well as crystal quality. Crystal cracks caused by thermal stress as well as crystal adhesion on the ampoule can be effectively solved by depositing a uniform carbon film on the ampoule in advance. The optical, electrical and detection performance are also investigated. The optical characterization in the wavelength region ranging from ultraviolet to infrared indicates the crystal has a low density of deep-level defects and good crystal quality. The resistivity over 109 Ω cm and µτ of electrons over 10-2 cm-2 V-1 proves that the electrical performance of the crystal has met the basic requirement for nuclear radiation detection. The metal-semiconductor-metal structure Ti/Ni/CsPbBr3/Ni/Ti detector fabricated from the optimized CsPbBr3 single crystal has an energy resolution of 12.85% (137Cs, 662 keV). The purpose of this work is to provide a useful guide and reference for the future exploration of repeatable and improvable CsPbBr3 crystal growth technology.

Mechanistic insights into the C-type lectin receptor CLEC12A-mediated immune recognition of monosodium urate crystal.

CLEC12A, a member of the C-type lectin receptor family involved in immune homeostasis, recognizes MSU crystals released from dying cells. However, the molecular mechanism underlying the CLEC12A-mediated recognition of MSU crystals remains unclear. Herein, we reported the crystal structure of the human CLEC12A-C-type lectin-like domain (CTLD) and identified a unique "basic patch" site on CLEC12A-CTLD that is necessary for the binding of MSU crystals. Meanwhile, we determined the interaction strength between CLEC12A-CTLD and MSU crystals using single-molecule force spectroscopy. Furthermore, we found that CLEC12A clusters at the cell membrane and seems to serve as an internalizing receptor of MSU crystals. Altogether, these findings provide mechanistic insights for understanding the molecular mechanisms underlying the interplay between CLEC12A and MSU crystals.

Trajectories of Human Milk Gangliosides during the First Four Hundred Days and Maternal-to-Offspring Transfer of Gangliosides: Results from a Chinese Cohort Study.

BACKGROUND: Gangliosides are crucial for early-life cognition and immunity development. However, limited data exist on gangliosides within the Chinese population, and maternal-to-fetal/infant ganglioside transport remains unclear. OBJECTIVES: This study aimed to investigate gangliosides concentrations and trajectories in Chinese human milk during the first 400 d of lactation, and seek to understand gangliosides transmission between mother and offspring. METHODS: This study involved 921 cross-sectional participants providing human milk samples across 0-400 d of lactation and 136 longitudinal participants offering maternal plasma, cord plasma, and human milk samples within the first 45 d postpartum. Ultrahigh-performance liquid chromatography-tandem mass spectrometry was used for the quantification of gangliosides. RESULTS: Human milk GM3 (Neu5Acα2-3Galß1-4GlcßCer) concentration increased from 2.29 ± 1.87 to 13.93 ± 4.82 µg/mL, whereas GD3 (Neu5Acα2-8Neu5Acα2-3Galß1-4GlcßCer) decreased from 17.94 ± 6.41 to 0.30 ± 0.50 µg/mL during the first 400 d postpartum (all P < 0.05). Consistent results were observed in cross-sectional and longitudinal participants. GD3 concentration gradually increased from maternal plasma (1.58 µg/mL) through cord plasma (2.05 µg/mL) to colostrum (21.35 µg/mL). Significant positive correlations were observed between maternal and cord plasma for both GM3 (r = 0.30, P < 0.001) and GD3 (r = 0.35, P < 0.001), and maternal plasma GD3 also correlated positively with colostrum concentrations (r = 0.21, P = 0.015). Additionally, in maternal and cord plasma, gangliosides were mainly linked with 16- and 18-carbon fatty acids. However, human milk GM3 showed a broad spectrum of fatty acid chain lengths, whereas GD3 was primarily tied to very long-chain fatty acids (≥20 carbon). CONCLUSIONS: We identified an increase in GM3 and a decrease in GD3 concentration in human milk, with GD3 notably more concentrated in cord plasma and colostrum. Importantly, ganglioside concentrations in maternal plasma positively correlated with those in cord plasma and colostrum. Our findings contribute to the existing Chinese data on gangliosides and enhance understanding of their transmission patterns from mother to offspring. This trial was registered at chictr.org.cn as ChiCTR1800015387.

A simple nomogram for predicting aspiration associated with dysphagia in hospitalized patients after stroke.

BACKGROUND: Aspiration is a common complication of poststroke dysphagia (PSD) and is associated with poor prognosis and mortality. There is no uniform criterion for determining aspiration associated with dysphagia. The aim of this study was to identify early predictors of aspiration, leading to the development of a simple nomogram for identifying aspiration risk associated with dysphagia in hospitalized patients after stroke. METHODS: Demographic information and clinical characteristics of 330 patients with PSD in the training cohort were utilized to develop a nomogram. The LASSO regression method was used to screen variables, and logistic regression was used to construct the nomogram. Internal validation was performed with bootstrap in the training cohort, and external validation was performed in the validation cohort of another 82 patients. The area under the curve (AUC), calibration curves, and decision curve analysis (DCA) were used to evaluate the performance of the nomogram. RESULTS: Seven variables were selected based on LASSO and multivariate logistic regression. The AUC of the nomogram was 0.834 (95% CI, 0.790-0.878) in the training cohort, 0.806 (95% CI, 0.791-0.880) in the internal validation cohort, and 0.882 (95% CI, 0.810-0.954) in the external validation cohort, which indicated that the model had good discrimination. The calibration and DCA curves showed that the nomogram had good accuracy and clinical utility. CONCLUSIONS: In this study, we established a nomogram that can be used to identify the risk of aspiration associated with dysphagia after stroke, and patients may benefit from early screening and preventive care.

Navigating the B vitamins: Dietary diversity, microbial synthesis, and human health.

B vitamins are intricately involved in various physiological processes vital for health. Their significance is complicated by the heterogeneous landscape of B vitamin distribution in diets and the contributions of the gut microbiota. Here, we delve into the impact of these factors on B vitamins and introduce strategies, with a focus on microbiota-based therapeutic options, to enhance their availability for improved well-being. Additionally, we provide an ecological and evolutionary perspective on the importance of B vitamins to human-microbiota interactions. In the dynamic realms of nutrition and microbiome science, these essential micronutrients continue to play a fundamental role in our understanding of disease development.

The predictive accuracy of Barrett toric calculator using measured posterior corneal astigmatism derived from swept source-OCT and Scheimpflug camera.

PURPOSE: To compare the performance of Barrett toric calculator incorporated with measured posterior corneal astigmatism (PCA) derived from IOL Master 700 and Pentacam HR versus predicted PCA. METHODS: The predicted residual astigmatism using Barrett toric IOL calculator with predicted PCA, measured PCA from IOL Master 700 and measured PCA from Pentacam were calculated with the preoperative keratometry and intended IOL axis with modification. The vector analysis was performed to calculate the mean absolute prediction error (MAE), the centroid of the prediction error and the percentage of eyes with a prediction error within ±0.50 D, ±0.75 D, and ±1.00 D. RESULTS: In 57 eyes of 57 patients with mean age of 70.42 ± 10.75 years, the MAE among the three calculation methods were 0.59 ± 0.38 D (Predicted PCA), 0.60 ± 0.38 D (Measured PCA from IOL Master 700) and 0.60 ± 0.36 D (Measured PCA from Pentacam) with no significant difference, either in the whole sample, the WTR eyes and the ATR eyes (F = 0.078, 0.306 and 0.083, p = 0.925, 0.739 and 0.920, respectively). Measured PCA obtained from IOL Master 700 resulted in one level reduction (from Tn to Tn-1) in 49.12% eyes in cylindrical model selection, while measured PCA obtained from Pentacam resulted in one level reduction of toric model selection in 18.18% eyes. CONCLUSION: The present study suggested that the incorporation of measured PCA values derived from IOL Master 700 and Pentacam produce comparable clinical outcome with the predicted PCA mode in Barrett toric calculator.

The State of Use and Utility of Negative Controls in Pharmacoepidemiologic Studies.

Uses of real-world data in drug safety and effectiveness studies are often challenged by various sources of bias. We undertook a systematic search of the published literature through September 2020 to evaluate the state of use and utility of negative controls to address bias in pharmacoepidemiologic studies. Two reviewers independently evaluated study eligibility and abstracted data. Our search identified 184 eligible studies for inclusion. Cohort studies (115, 63%) and administrative data (114, 62%) were, respectively, the most common study design and data type used. Most studies used negative control outcomes (91, 50%), and for most studies the target source of bias was unmeasured confounding (93, 51%). We identified 4 utility domains of negative controls: 1) bias detection (149, 81%), 2) bias correction (16, 9%), 3) P-value calibration (8, 4%), and 4) performance assessment of different methods used in drug safety studies (31, 17%). The most popular methodologies used were the 95% confidence interval and P-value calibration. In addition, we identified 2 reference sets with structured steps to check the causality assumption of the negative control. While negative controls are powerful tools in bias detection, we found many studies lacked checking the underlying assumptions. This article is part of a Special Collection on Pharmacoepidemiology.

Comparison of two swept-source optical coherence tomography devices, a Scheimpflug camera system and a ray-tracing aberrometer in the measurement of corneal power in patients with cataract.

PURPOSE: To assess the differences and similarities in the corneal curvature obtained by two swept-source optical coherence tomography (SS-OCT) devices, Scheimpflug imaging system and one ray tracing aberrometer in patients with cataracts. Moreover, this study aimed to compare the differences in posterior corneal (PK), total corneal (TK) and true net power (TNP) measurements among the IOLMaster 700, CASIA2, and Pentacam. METHODS: A total of 200 eyes of 200 patients (116 female, 58%) were enrolled in this study, with a mean age of 65.9 ± 9.5 years. The flattest (Kf), steepest (Ks), and mean cornal powers (Km), J0, and J45 were obtained using two SS-OCT-based biometric devices, one rotating camera system and one ray-tracing aberrometer. The PK, TK and TNP values were also measured using these devices. To evaluate the differences and similarities between the devicves, the Friedman test, Pearson correlation coefficient (r), intraclass coefficient correlation (ICC) and Bland‒Altman plots with 95% limits of agreement (LoA) were used, and boxplots and stacked histograms were generated to describe the distributions of the data. RESULTS: There were no significant differences between the IOLMaster 700 and Pentacam for any of the keratometry values. Additionally, there were no significant differences between the IOLMaster 700 and iTrace in evaluating J0 and J45. Bland‒Altman plots revealed relatively wide LoA widths, almost larger than 1 diopter for the keratometry values and almost larger than 0.5 diopter for J0 and J45 values among the four devices. In terms of PK and TK values, significant differences and low ICCs were found among the three devices. CONCLUSIONS: Although strong correlations and good agreement were found among the IOLMaster700, CASIA2, Pentacam and iTrace for Kf, Ks, Km and J0, J45, it seems that the measurements should not be used interchangeably because of the wide LoA widths and the presence of significant differences among the devices. Similarly, due to significant differences and low ICCs, the PK, TK and TNP values obtained by IOLMaster 700, CASIA2, and Pentacam should not be used interchangeably.

Multidrug resistance protein 5 affects cell proliferation, migration and gemcitabine sensitivity in pancreatic cancer MIA Paca­2 and PANC­1 cells.

Gemcitabine­based chemotherapy has been widely adopted as the standard and preferred chemotherapy regimen for treating advanced pancreatic cancer. However, the contribution of multidrug resistance protein 5 (MRP5) to gemcitabine resistance and pancreatic cancer progression remains controversial. In the present study, the effect of silencing MRP5 on gemcitabine resistance and cell proliferation and migration of human pancreatic cancer MIA Paca­2 and PANC­1 cells was investigated by using short­hairpin RNA delivered by lentiviral vector transduction. The knockdown of MRP5 was confirmed on both mRNA and protein levels using qPCR and surface staining assays, respectively. MRP5­regulated gemcitabine sensitivity was assessed by MTT, PrestoBlue and apoptosis assays. The effect of MRP5 on pancreatic cancer cell proliferation and migration was determined using colony­formation, wound­healing and Transwell migration assays. The interaction of gemcitabine and cyclic guanosine monophosphate (cGMP) with MRP5 protein was explored using molecular docking. The results indicated that the MRP5 mRNA and protein levels were significantly reduced in all the MIA Paca­2 and PANC­1 clones. MRP5 affected gemcitabine cytotoxicity and the rate of gemcitabine­induced apoptosis. Silencing MRP5 decreased cell proliferation and migration in both MIA Paca­2 and PANC­1 cells. Docking studies showed high binding affinity of cGMP towards MRP5, indicating the potential of MRP5­mediated cGMP accumulation in the microenvironment. In conclusion, MRP5 has an important role in cancer proliferation and migration in addition to its drug efflux functions in two widely available pancreatic tumour cell lines (MIA Paca­2 and PANC­1).

Dihydroartemisinin inhibits the development of colorectal cancer by GSK-3ß/TCF7/MMP9 pathway and synergies with capecitabine.

Patients with colorectal cancer (CRC) suffer from poor prognosis and lack effective drugs. Dihydroartemisinin (DHA) has anti-cancer potential but the mechanism remains unclear. We elucidated the effects and mechanism of DHA on CRC development with the aim of providing an effective, low-toxicity drug and a novel strategy for CRC. Herein, proliferation assay, transwell assay, tube formation assay, metastasis models, PDX model and AOM/DSS model were used to reveal the effects of DHA on CRC. The key pathway and target were identified by RNA-seq, ChIP, molecular docking, pull down and dual-luciferase reporter assays. As a result, DHA showed a strong inhibitory effect on the growth, metastasis and angiogenesis of CRC with no obvious toxicity, and the inhibitory effect was similar to that of the clinical drug Capecitabine (Cap). Indeed, DHA directly targeted GSK-3ß to inhibit CRC development through the GSK-3ß/TCF7/MMP9 pathway. Meaningfully, DHA in combination with Cap enhanced the anti-cancer effect, and alleviated Cap-induced diarrhoea, immunosuppression and inflammation. In conclusion, DHA has the potential to be an effective and low-toxicity drug for the treatment of CRC. Furthermore, DHA in combination with Cap could be a novel therapeutic strategy for CRC with improved efficacy and reduced side effects.

miR2118 Negatively Regulates Bacterial Blight Resistance through Targeting Several Disease Resistance Genes in Rice.

Plant miRNAs are a class of noncoding RNA with a length of 21-24 nt that play an important role in plant responses to biotic and abiotic stresses. Bacterial blight (BB) caused by Xanthomonas oryzae pv. oryzae (Xoo) is one of the most serious bacterial diseases in rice. Our previous work showed that osa-miR2118b/n was induced by Xoo infection. However, the biological function of miR2118 has not yet been characterized in experiments. Herein, we constructed MIR2118b OE, as well as single and double mutants of MIR2118b/n using CRISPR/Cas9. Further results showed that osa-MIR2118b OE plants exhibited longer lesion lengths than the wild type after Xoo inoculation, while MIR2118 CRISPR plants exhibited shorter lesion lengths than the wild type after Xoo inoculation. Co-transformation experiments in rice protoplasts indicated that osa-miR2118 negatively regulated the transcripts of three nucleotide-binding sites and leucine-rich repeat (NLR) genes (LOC_Os08g42700.1, LOC_Os01g05600.1, and LOC_Os12g37290.1) which are predicted target genes of miR2118, but not the mutated NLR genes with a 3 bp insertion at the center of the binding sites. The transcriptional level of the three NLR genes was reversed relative to osa-miR2118 in the MIR2118b OE and MIR2118b CRISPR plants. The above results demonstrate that osa-miR2118b/n negatively regulates the resistance to bacterial blight through negatively regulating several NLR genes.

Standardized In Vitro Models of Human Adipose Tissue Reveal Metabolic Flexibility in Brown Adipocyte Thermogenesis.

Functional human brown and white adipose tissue (BAT and WAT) are vital for thermoregulation and nutritional homeostasis, while obesity and other stressors lead, respectively, to cold intolerance and metabolic disease. Understanding BAT and WAT physiology and dysfunction necessitates clinical trials complemented by mechanistic experiments at the cellular level. These require standardized in vitro models, currently lacking, that establish references for gene expression and function. We generated and characterized a pair of immortalized, clonal human brown (hBA) and white (hWA) preadipocytes derived from the perirenal and subcutaneous depots, respectively, of a 40-year-old male individual. Cells were immortalized with hTERT and confirmed to be of a mesenchymal, nonhematopoietic lineage based on fluorescence-activated cell sorting and DNA barcoding. Functional assessments showed that the hWA and hBA phenocopied primary adipocytes in terms of adrenergic signaling, lipolysis, and thermogenesis. Compared to hWA, hBA were metabolically distinct, with higher rates of glucose uptake and lactate metabolism, and greater basal, maximal, and nonmitochondrial respiration, providing a mechanistic explanation for the association between obesity and BAT dysfunction. The hBA also responded to the stress of maximal respiration by using both endogenous and exogenous fatty acids. In contrast to certain mouse models, hBA adrenergic thermogenesis was mediated by several mechanisms, not principally via uncoupling protein 1 (UCP1). Transcriptomics via RNA-seq were consistent with the functional studies and established a molecular signature for each cell type before and after differentiation. These standardized cells are anticipated to become a common resource for future physiological, pharmacological, and genetic studies of human adipocytes.

Nanobead-based single-molecule pulldown for single cells.

Investigation of cell-to-cell variability holds critical physiological and clinical implications. Thus, numerous new techniques have been developed for studying cell-to-cell variability, and these single-cell techniques can also be used to investigate rare cells. Moreover, for studying protein-protein interactions (PPIs) in single cells, several techniques have been developed based on the principle of the single-molecule pulldown (SiMPull) assay. However, the applicability of these single-cell SiMPull (sc-SiMPull) techniques is limited because of their high technical barrier and special requirements for target cells and molecules. Here, we report a highly innovative nanobead-based approach for sc-SiMPull that is based on our recently developed microbead-based, improved version of SiMPull for cell populations. In our sc-SiMPull method, single cells are captured in microwells and lysed in situ, after which commercially available, pre-surface-functionalized magnetic nanobeads are placed in the microwells to specifically capture proteins of interest together with their binding partners from cell extracts; subsequently, the PPIs are examined under a microscope at the single-molecule level. Relative to previously published methods, nanobead-based sc-SiMPull is considerably faster, easier to use, more reproducible, and more versatile for distinct cell types and protein molecules, and yet provides similar sensitivity and signal-to-background ratio. These crucial features should enable universal application of our method to the study of PPIs in single cells.

Nursing Management of a Patient With Fulminant Myocarditis and Electrical Storm Receiving ECMO: A Case Report.

INTRODUCTION: Fulminant myocarditis is a devastating disease with significant mortality and complications. The care of patients with fulminant myocarditis is rarely reported. CLINICAL FINDINGS: A 17-year-old female patient was admitted to the emergency department with dizziness, amaurosis fugax, and chest tightness. Initial assessment revealed elevated levels of troponin T (4.753 ng/mL), troponin I (49.540 ng/mL), creatine kinase (1306 U/L), creatine kinase-MB isoenzymes (75.71 ng/mL), lactate dehydrogenase (509 U/L), and N-terminal pro-B-type natriuretic peptide (6345 pg/mL). The patient had recurrent ventricular tachycardia and failed to maintain a sinus rhythm after multiple electrical cardioversions. DIAGNOSIS: Echocardiography revealed a left ventricular ejection fraction of 34%. Magnetic resonance imaging results confirmed the diagnosis of myocarditis. INTERVENTIONS: The patient received extracorporeal membrane oxygenation for 6 days, intra-aortic balloon pump support for 7 days, and mechanical ventilation for 5 days. Norepinephrine and dopamine were used to keep circulation stable, lidocaine and amiodarone were used to control heart rate, and glucocorticoids and immunoglobulins were used to modulate immunity. OUTCOMES: The patient was discharged after 23 days. A month after discharge, echocardiography showed that the ejection fraction was 60%. The patient reported complete resolution of signs and symptoms of fulminant myocarditis at follow-up assessment. CONCLUSION: This case report presents the activities of bedside nurses in caring for a patient with fulminant myocarditis and broadens the literature describing nursing interventions for patients with fulminant myocarditis.