Combinatorial lipidomics and proteomics underscore erythrocyte lipid membrane aberrations in the development of adverse cardio-cerebrovascular complications in maintenance hemodialysis patients.

Age-associated deterioration of physiological functions occur at heterogeneous rates across individual organs. A granular evaluation of systemic metabolic mediators of aging in a healthy human cohort (n = 225) identified prominent increases in circulating uremic toxins that were recapitulated in mice, on which we further characterized the aging phenome across five peripheral organs. Our multi-omics analyses connected systemic aging profiles primarily to kidney metabolism, uncovering a metabolic association between localized glucosylceramide (GluCer) accretion and renal functional decline. Elevated GluCers were also associated with higher risk of deaths in an independent cohort of aged individuals (n = 271). We report GluCer-mTOR signaling commencing at late middle-age that disrupts mitophagy and undermines mitochondrial respiration in kidney. Conserved between human and mice, GluCer-mediated renal dysfunction is female-biased and modulated by intracellular purines. Our work provides molecular basis for the sexually disparate effects of mTOR inhibition on mammalian lifespan, possibly ascribed to the evolutionary cost of female reproduction.

A centrifugal-driven spiral microchannel microfiltration chip for emulsion and deformable particle sorting.

Droplet sorting and enrichment, as a prominent field within microfluidic technology, represent a pivotal stage in the manipulation of droplets and particles. In recent times, droplet sorting methods based on lab-on-disk (LOD) have garnered significant interest among researchers for their inherent merits, including high throughput, ease of operation, seamless device integration, and independence from supplementary driving forces. This study introduces a centrifugal force-driven microfluidic chip comprising spiral microchannels. The chip incorporates microhole arrays along the sidewall of the spiral channels, enabling size-based sorting and enrichment of microdroplets under the influence of multiple forces. Firstly, a comparative analysis was performed to assess the influence of the separation port structure and rotational speed on efficiency, and a mechanical modeling approach was employed to conduct kinetic analyses of droplet behavior during instantaneous separation. Those findings demonstrated a good agreement with the experimental results at ω < 100 rpm. Subsequently, sorting experiments on homogeneous droplets indicated that repetitive sorting could increase the recovery ratios, RT(α), of high-concentration droplets (20.7%) from 35.3% to over 80%. We also conducted a sorting experiment on three-component homogeneous-phase emulsions using a serially connected chip array, and the sorting throughput was 0.58 mL min-1. As a result, the RT(α) for 60 and 160 µm droplets were 99.4% and 88.9%, respectively. Lastly, we conducted elution experiments and dual-sample sorting on a single chip, and the fluorescence results demonstrated that this study provided an efficient and non-cross-contaminating sorting method for non-homogenous phase multi-sample microreactor units.

Knowledge, attitude, and practice of non-ophthalmic medical staff toward myopia-related fundus lesions.

This study assessed the knowledge, attitude, and practice (KAP) of non-ophthalmic medical staff towards myopia-related fundus lesions. This multicenter, cross-sectional study enrolled non-ophthalmic medical staff of Suining City between January and May 2023 using a self-designed questionnaire. A total of 505 (93.19%) valid questionnaires were included. Their mean KAP scores were 8.10 ± 2.32 (range: 0-12), 20.27 ± 2.68 (range: 0-24), and 17.77 ± 5.04 (range: 0-28), respectively. Structural equation modeling indicated that knowledge has a positive effect on attitude (ß = 0.307, P < 0.001), and attitude has a positive effect on practice (ß = 0.604, P < 0.001). Moreover, a higher degree of myopia exhibited a positive effect on knowledge (ß = 0.510, P < 0.001). Nurses and other medical staff showed a negative effect on knowledge (ß = - 0.706, P < 0.001) compared to doctors. Working in secondary and tertiary public hospitals, as well as private hospitals, demonstrated a negative effect on practice (ß = - 1.963, P < 0.001) compared to those working in primary hospitals. Non-ophthalmic medical staff exhibited moderate knowledge, positive attitudes, and moderate practices toward myopia-related fundus lesions. The degree of myopia, doctors vs. other medical staff, and the hospital level influence the KAP of non-ophthalmic medical staff.

Nozzle Wear in Abrasive Water Jet Based on Numerical Simulation.

Particle diameters and jet pressure in abrasive water jet (AWJ) are significant jet properties which deserve a better understanding for improving AWJ machining performance. Some influence factors have been verified regarding nozzle wear in abrasive water jet polishing application. A three-dimensional model of a nozzle is established to analyze the influence of internal multi-phase flow field distribution, which is based on Euler-Lagrange methodology. With the increase of jet pressure, the erosion rate decreases; with the increase of the diameter and mass flow rate of the erosion particles, the erosion speed increases as well. When the diameter of the outlet is worn to 1.6 mm, the pressure on the work piece caused by the abrasive water jet increases by more than double compared to the non-worn nozzle; when the diameter of the nozzle outlet is worn to 1.6 mm, the shear force is 2.5 times higher than the shear force when the diameter is 1.0, which means that the jet force is divergent when the diameter is 1.6 mm, and the damage of the work piece is very serious. The obtained results could improve polishing efficiency on the work piece, extend nozzle lifetimes, and guide the future design of AWJ nozzles.

Biomolecule-grafted GO enhanced the mechanical and biological properties of 3D printed PLA scaffolds with TPMS porous structure.

Graphene oxide (GO) exhibits excellent mechanical strength and modulus. However, its effectiveness in mechanically reinforcing polymer materials is limited due to issues with interfacial bonding and dispersion arising from differences in the physicochemical properties between GO and polymers. Surface modification using coupling agents is an effective method to improve the bonding problem between polymer and GO, but there may be biocompatibility issues when used in the biomedical field. In this study, the biomolecule L-lysine, was applied to improve the interfacial bonding and dispersion of GO in polylactic acid (PLA) without compromising biocompatibility. The PLA/L-lysine-modified GO (PLA/L-GO) bone scaffold with triply periodic minimal surface (TPMS) structure was prepared using fused deposition modeling (FDM). The FTIR results revealed successful grafting of L-lysine onto GO through the reaction between their -COOH and -NH2 groups. The macroscopic and microscopic morphology characterization indicated that the PLA/L-GO scaffolds exhibited an characteristics of dynamic diameter changes, with good interlayer bonding. It was noteworthy that the L-lysine modification promoted the dispersion of GO and the interfacial bonding with the PLA matrix, as characterized by SEM. As a result, the PLA/0.1L-GO scaffold exhibited higher compressive strength (13.2 MPa) and elastic modulus (226.8 MPa) than PLA/0.1GO. Moreover, PLA/L-GO composite scaffold exhibited superior biomineralization capacity and cell response compared to PLA/GO. In summary, L-lysine not only improved the dispersion and interfacial bonding of GO with PLA, enhancing the mechanical properties, but also improved the biological properties. This study suggests that biomolecules like L-lysine may replace traditional modifiers as an innovative bio-modifier to improve the performance of polymer/inorganic composite biomaterials.

PGD: Shared gene linking polycystic ovary syndrome and endometrial cancer, influencing proliferation and migration through glycometabolism.

The relationship among polycystic ovary syndrome (PCOS), endometrial cancer (EC), and glycometabolism remains unclear. We explored shared genes between PCOS and EC, using bioinformatics to unveil their pathogenic connection and influence on EC prognosis. Gene Expression Omnibus datasets GSE226146 (PCOS) and GSE196033 (EC) were used. A protein-protein interaction (PPI) network was constructed to identify the central genes. Candidate markers were screened using dataset GSE54250. Differences in marker expression were confirmed in mouse PCOS and human EC tissues using RT-PCR and immunohistochemistry. The effect of PGD on EC proliferation and migration was explored using Ki-67 and Transwell assays. PGD's impact on the glycometabolic pathway within carbon metabolism was assessed by quantifying glucose content and lactic acid production. R software identified 31 common genes in GSE226146 and GSE196033. Gene Ontology functional classification revealed enrichment in the "purine nucleoside triphosphate metabolism process," with key Kyoto Encyclopedia of Genes and Genomes pathways related to "carbon metabolism." The PPI network identified 15 hub genes. HK2, NDUFS8, PHGDH, PGD, and SMAD3 were confirmed as candidate markers. The RT-PCR analysis validated distinct HK2 and PGD expression patterns in mouse PCOS ovarian tissue and human EC tissue, as well as in normal and EC cells. Transfection experiments with Ishikawa cells further confirmed PGD's influence on cell proliferation and migration. Suppression of PGD expression impeded glycometabolism within the carbon metabolism of EC cells, suggesting PGD as a significant PCOS risk factor impacting EC proliferation and migration through modulation of single carbon metabolism. These findings highlight PGD's pivotal role in EC onset and prognosis.

Integrative analysis of transcriptome and metabolome reveal the differential tolerance mechanisms to low and high salinity in the roots of facultative halophyte Avicennia marina.

Mangroves perform a crucial ecological role along the tropical and subtropical coastal intertidal zone where salinity fluctuation occurs frequently. However, the differential responses of mangrove plant at the combined transcriptome and metabolome level to variable salinity are not well documented. In this study, we used Avicennia marina (Forssk.) Vierh., a pioneer species of mangrove wetlands and one of the most salt-tolerant mangroves, to investigate the differential salt tolerance mechanisms under low and high salinity using inductively coupled plasma-mass spectrometry, transcriptomic and metabolomic analysis. The results showed that HAK8 was up-regulated and transported K+ into the roots under low salinity. However, under high salinity, AKT1 and NHX2 were strongly induced, which indicated the transport of K+ and Na+ compartmentalization to maintain ion homeostasis. In addition, A. marina tolerates low salinity by up-regulating ABA signaling pathway and accumulating more mannitol, unsaturated fatty acids, amino acids' and L-ascorbic acid in the roots. Under high salinity, A. marina undergoes a more drastic metabolic network rearrangement in the roots, such as more L-ascorbic acid and oxiglutatione were up-regulated, while carbohydrates, lipids and amino acids were down-regulated in the roots, and, finally, glycolysis and TCA cycle were promoted to provide more energy to improve salt tolerance. Our findings suggest that the major salt tolerance traits in A. marina can be attributed to complex regulatory and signaling mechanisms, and show significant differences between low and high salinity.

Cepharanthine triggers ferroptosis through inhibition of NRF2 for robust ER stress against lung cancer.

BACKGROUND: Severe endoplasmic reticulum (ER) stress elicits apoptosis to suppress lung cancer. Our previous research identified that Cepharanthine (CEP), a kind of phytomedicine, possessed powerful anti-cancer efficacy, for which the underlying mechanism was still uncovered. Herein, we investigated how CEP induced ER stress and worked against lung cancer. METHODS: The differential expression genes (DEGs) and enrichment were detected by RNA-sequence. The affinity of CEP and NRF2 was analyzed by cellular thermal shift assay (CETSA) and molecular docking. The function assay of lung cancer cells was measured by western blots, flow cytometry, immunofluorescence staining, and ferroptosis inhibitors. RESULTS: CEP treatment enriched DEGs in ferroptosis and ER stress. Further analysis demonstrated the target was NRF2. In vitro and in vivo experiments showed that CEP induced obvious ferroptosis, as characterized by the elevated iron ions, ROS, COX-2 expression, down-regulation of GPX4, and atrophic mitochondria. Moreover, enhanced Grp78, CHOP expression, ß-amyloid mass, and disappearing parallel stacked structures of ER were observed in CEP group, suggesting ER stress was aroused. CEP exhibited excellent anti-lung cancer efficacy, as evidenced by the increased apoptosis, reduced proliferation, diminished cell stemness, and prominent inhibition of tumor grafts in animal models. Furthermore, the addition of ferroptosis inhibitors weakened CEP-induced ER stress and apoptosis. CONCLUSION: In summary, our findings proved CEP drives ferroptosis through inhibition of NRF2 for induction of robust ER stress, thereby leading to apoptosis and attenuated stemness of lung cancer cells. The current work presents a novel mechanism for the anti-tumor efficacy of the natural compound CEP.

The molecular signature and prognosis of glioma with preoperative intratumoral hemorrhage: a retrospective cohort analysis.

BACKGROUND: Intratumoral hemorrhage, though less common, could be the first clinical manifestation of glioma and is detectable via MRI; however, its exact impacts on patient outcomes remain unclear and controversial. The 2021 WHO CNS 5 classification emphasised genetic and molecular features, initiating the necessity to establish the correlation between hemorrhage and molecular alterations. This study aims to determine the prevalence of intratumoral hemorrhage in glioma subtypes and identify associated molecular and clinical characteristics to improve patient management. METHODS: Integrated clinical data and imaging studies of patients who underwent surgery at the Department of Neurosurgery at Peking Union Medical College Hospital from January 2011 to January 2022 with pathological confirmation of glioma were retrospectively reviewed. Patients were divided into hemorrhage and non-hemorrhage groups based on preoperative magnetic resonance imaging. A comparison and survival analysis were conducted with the two groups. In terms of subgroup analysis, we classified patients into astrocytoma, IDH-mutant; oligodendroglioma, IDH-mutant, 1p/19q-codeleted; glioblastoma, IDH-wildtype; pediatric-type gliomas; or circumscribed glioma using integrated histological and molecular characteristics, according to WHO CNS 5 classifications. RESULTS: 457 patients were enrolled in the analysis, including 67 (14.7%) patients with intratumoral hemorrhage. The hemorrhage group was significantly older and had worse preoperative Karnofsky performance scores. The hemorrhage group had a higher occurrence of neurological impairment and a higher Ki-67 index. Molecular analysis indicated that CDKN2B, KMT5B, and PIK3CA alteration occurred more in the hemorrhage group (CDKN2B, 84.4% vs. 62.2%, p = 0.029; KMT5B, 25.0% vs. 8.9%, p = 0.029; and PIK3CA, 81.3% vs. 58.5%, p = 0.029). Survival analysis showed significantly worse prognoses for the hemorrhage group (hemorrhage 18.4 months vs. non-hemorrhage 39.1 months, p = 0.01). In subgroup analysis, the multivariate analysis showed that intra-tumoral hemorrhage is an independent risk factor only in glioblastoma, IDH-wildtype (162 cases of 457 overall, HR = 1.72, p = 0.026), but not in other types of gliomas. The molecular alteration of CDK6 (hemorrhage group p = 0.004, non-hemorrhage group p < 0.001), EGFR (hemorrhage group p = 0.003, non-hemorrhage group p = 0.001), and FGFR2 (hemorrhage group p = 0.007, non-hemorrhage group p = 0.001) was associated with shorter overall survival time in both hemorrhage and non-hemorrhage groups. CONCLUSIONS: Glioma patients with preoperative intratumoral hemorrhage had unfavorable prognoses compared to their nonhemorrhage counterparts. CDKN2B, KMT5B, and PIK3CA alterations were associated with an increased occurrence of intratumoral hemorrhage, which might be future targets for further investigation of intratumoral hemorrhage.

Tris stabilized AuNPs based lateral flow immunochromatography for the simultaneous detection of porcine epidemic diarrhea virus and rotavirus on-site.

Porcine epidemic diarrhea virus (PEDV) and rotavirus has posed a significant threat to the pig industry annually across different nations, resulting in huge economic losses. The frequent co-infection of these two viruses in clinical settings complicates the process of differential diagnoses. Rapid and accurate detection of PEDV and rotavirus is in great demand for timely diarrhea disease prevention and control. In this study, tris stabilized AuNPs were prepared and a sensitive lateral flow immunoassay (LFIA) sensor was developed for the simultaneous and rapid detection of PEDV and rotavirus on site. After the system optimization, the established LFIA can simultaneously identify PEDV and rotavirus with limits of detection (LOD) of 1.25 × 103 TCID50 mL-1 and 3.13 × 102 pg mL-1, respectively. When applying for clinical samples, the LFIA show a concordance of 95 % and 100 % to reverse transcript polymerase chain reaction (RT-PCR) for PEDV and rotavirus respectively. Therefore, this LFIA can qualitatively detect PEDV and rotavirus in 18 min with high sensitivity and accuracy without any sophisticated equipment and operation, making it a promising candidate for the early diagnosis of PEDV or/and rotavirus diarrhea on site.

A Cysteinyl-tRNA Synthetase Mutation Causes Novel Autosomal-Dominant Inheritance of a Parkinsonism/Spinocerebellar-Ataxia Complex.

This study aimed to identify possible pathogenic genes in a 90-member family with a rare combination of multiple neurodegenerative disease phenotypes, which has not been depicted by the known neurodegenerative disease. We performed physical and neurological examinations with International Rating Scales to assess signs of ataxia, Parkinsonism, and cognitive function, as well as brain magnetic resonance imaging scans with seven sequences. We searched for co-segregations of abnormal repeat-expansion loci, pathogenic variants in known spinocerebellar ataxia-related genes, and novel rare mutations via whole-genome sequencing and linkage analysis. A rare co-segregating missense mutation in the CARS gene was validated by Sanger sequencing and the aminoacylation activity of mutant CARS was measured by spectrophotometric assay. This pedigree presented novel late-onset core characteristics including cerebellar ataxia, Parkinsonism, and pyramidal signs in all nine affected members. Brain magnetic resonance imaging showed cerebellar/pons atrophy, pontine-midline linear hyperintensity, decreased rCBF in the bilateral basal ganglia and cerebellar dentate nucleus, and hypo-intensities of the cerebellar dentate nuclei, basal ganglia, mesencephalic red nuclei, and substantia nigra, all of which suggested neurodegeneration. Whole-genome sequencing identified a novel pathogenic heterozygous mutation (E795V) in the CARS gene, meanwhile, exhibited none of the known repeat-expansions or point mutations in pathogenic genes. Remarkably, this CARS mutation causes a 20% decrease in aminoacylation activity to charge tRNACys with L-cysteine in protein synthesis compared with that of the wild type. All family members carrying a heterozygous mutation CARS (E795V) had the same clinical manifestations and neuropathological changes of Parkinsonism and spinocerebellar-ataxia. These findings identify novel pathogenesis of Parkinsonism-spinocerebellar ataxia and provide insights into its genetic architecture.

Capillary Force-Driven Quantitative Plasma Separation Method for Application of Whole Blood Detection Microfluidic Chip.

Separating plasma or serum from blood is essential for precise testing. However, extracting precise plasma quantities outside the laboratory poses challenges. A recent study has introduced a capillary force-driven membrane filtration technique to accurately separate small plasma volumes. This method efficiently isolates 100-200 µL of pure human whole blood with a 48% hematocrit, resulting in 5-30 µL of plasma with less than a 10% margin of error. The entire process is completed within 20 min, offering a simple and cost-effective approach to blood separation. This study has successfully addressed the bottleneck in self-service POCT, ensuring testing accuracy. This innovative method shows promise for clinical diagnostics and point-of-care testing.

Rapid Fabrication of Large-Grain Opal Films and Photonic Crystal Hydrogel Sensors by a Filter Paper-Enhanced Evaporation Chip.

Developing a rapid fabrication method for crack-free opal films is a significant challenge with broad applications. We developed a microfluidic platform known as the "filter paper-enhanced evaporation microfluidic chip" (FPEE-chip) for the fabrication of photonic crystal and inverse opal hydrogel (IOPH) films. The chip featured a thin channel formed by bonding double-sided adhesive poly(ethylene terephthalate) with a polymethyl methacrylate cover and a glass substrate. This channel was then filled with nanosphere colloids. The water was guided to evaporate rapidly at the surface of the filter paper, allowing the nanospheres to self-assemble and accumulate within the channel under capillary forces. Experimental results confirmed that the self-assembly method based on the FPEE-chip was a rapid platform for producing high-quality opal, with centimeter-sized opal films achievable in less than an hour. Furthermore, the filter paper altered the stress release mechanism of the opal films during drying, resulting in fewer cracks. This platform was proven capable of producing large-grain, crack-free opal films of up to 30 mm2 in size. We also fabricated crack-free IOPH pH sensors that exhibited color and size responsiveness to pH changes. The coefficient of variation of the gray color distribution for crack-free IOPH ranged from 0.03 to 0.07, which was lower than that of cracked IOPH (ranging from 0.07 to 0.14). Additionally, the grayscale peak value in 1 mm2 of the crack-free IOPH was more than twice that of the cracked IOPH at the same pH. The FPEE-chip demonstrated potential as a candidate for developing vision sensors.

A compact microfluidic laser-induced fluorescence immunoassay system using avalanche photodiode for rapid detection of alpha-fetoprotein.

Alpha-fetoprotein (AFP), commonly employed for early diagnosis of liver cancer, serves as a biomarker for cancer screening and diagnosis. Combining the high sensitivity and specificity of fluorescence immunoassay (FIA), developing a low-cost and efficient immunoassay system for AFP detection holds significant importance in disease diagnosis. In this work, we developed a miniaturized oblique laser-induced fluorescence (LIF) immunoassay system, coupled with a microfluidic PMMA/paper hybrid chip, for rapid detection of AFP. The system employed an avalanche photodiode (APD) as the detector, and implemented multi-level filtering in the excitation light channel using the dichroic mirror and optical trap. At first, we employed the Savitzky-Golay filter and baseline off-set elimination methods to denoise and normalize the original data. Then the cutoff frequency of the low-pass filter and the reverse voltage of the APD were optimized to enhance the detection sensitivity of the system. Furthermore, the effect of laser power on the fluorescence excitation efficiency was investigated, and the sampling time during the scanning process was optimized. Finally, a four-parameter logistic (4PL) model was utilized to establish the concentration-response equation for AFP. The system was capable of detecting concentrations of AFP standard solution within the range of 1-500 ng/mL, with a detection limit of 0.8 ng/mL. The entire immunoassay process could be completed within 15 min. It has an excellent potential for applications in low-cost portable diagnostic instruments for the rapid detection of biomarkers.

The Shape Effect of Acoustic Micropillar Array Chips in Flexible Label-Free Separation of Cancer Cells.

The precise isolation of circulating tumor cells (CTCs) from blood samples is a potent tool for cancer diagnosis and clinical prognosis. However, CTCs are present in extremely low quantities in the bloodstream, posing a significant challenge to their isolation. In this study, we propose a non-contact acoustic micropillar array (AMPA) chip based on acoustic streaming for the flexible, label-free capture of cancer cells. Three shapes of micropillar array chips (circular, rhombus, and square) were fabricated. The acoustic streaming characteristics generated by the vibration of microstructures of different shapes are studied in depth by combining simulation and experiment. The critical parameters (voltage and flow rate) of the device were systematically investigated using microparticle experiments to optimize capture performance. Subsequently, the capture efficiencies of the three micropillar structures were experimentally evaluated using mouse whole blood samples containing cancer cells. The experimental results revealed that the rhombus microstructure was selected as the optimal shape, demonstrating high capture efficiency (93%) and cell activity (96%). Moreover, the reversibility of the acoustic streaming was harnessed for the flexible release and capture of cancer cells, facilitating optical detection and analysis. This work holds promise for applications in monitoring cancer metastasis, bio-detection, and beyond.

Clinical values of different specimen preparation methods for the diagnosis of lung cancer by EBUS-TBNA.

BACKGROUND AND OBJECTIVE: EBUS-TBNA has emerged as an important minimally invasive procedure for the diagnosis and staging of lung cancer. Our objective was to evaluate the effect of different specimen preparation from aspirates on the diagnosis of lung cancer. METHODS: 181 consecutive patients with known or suspected lung cancer accompanied by hilar / mediastinal lymphadenopathy underwent EBUS-TBNA from January 2019 to December 2022. Specimens obtained by EBUS-TBNA were processed by three methods: Traditional smear cytology of aspirates (TSC), liquid-based cytology of aspirates (LBC) and histopathology of core biopsies. RESULTS: EBUS-TBNA was performed in 181 patients on 213 lymph nodes, the total positive rate of the combination of three specimen preparation methods was 80.7%. The diagnostic positive rate of histopathology was 72.3%, TSC was 68.1%, and LBC was 65.3%, no significant differences was observed (p = 0.29); however, statistically significant difference was noted between the combination of three preparation methods and any single specimen preparation methods (p = 0.002). The diagnostic sensitivity of histopathology combined with TSC and histopathology combined with LBC were 96.5 and 94.8%, the specificity was 95.0% and 97.5%, the PPV was 98.8% and 99.4%, the NPV was 86.4% and 81.2%, the diagnostic accuracy was 96.2% and 95.3%, respectively; The sensitivity and accuracy of above methods were higher than that of single specimen preparation, but lower than that of combination of three preparation methods. CONCLUSION: When EBUS-TBNA is used for the diagnosis and staging of lung cancer, histopathology combined with TSC can achieve enough diagnostic efficiency and better cost-effectiveness.

Correlation Between Impaired Sensitivity to Thyroid Hormones and Serum Uric Acid in Female Patients With Obesity and After Laparoscopic Sleeve Gastrectomy.

OBJECTIVE: An alterable risk factor for hyperuricemia is obesity. Additionally, obese people may have a moderate form of acquired resistance to thyroid hormones. Thyrotropin, thyroid hormones, and obesity all interact subtly. However, the connection between thyroid hormone sensitivity and hyperuricemia in obese patients both before and after laparoscopic sleeve gastrectomy (LSG) has not yet been clarified. The objective of our study was to investigate the connection between impaired thyroid hormone sensitivity and elevated uric acid (UA) levels before and after LSG. METHODS: In total, 1054 euthyroid patients with obesity (481 males, 573 females), 248 (143 female patients) of whom underwent subsequent LSG, were enrolled in this retrospective study. Anthropometric measurements and thyroid hormone and UA levels were taken before and 3 months after LSG. RESULTS: Female patients with obesity with impaired sensitivity to thyroid hormones had higher UA levels (P for trend <.01). The odds ratio of the fourth vs first quartile of thyroid feedback quantile index, thyrotropin index, and thyrotropin-thyroxine resistance index were 4.285 (confidence interval: 1.360-13.507), 3.700 (confidence interval: 1.276-10.729), and 2.839 (confidence interval: 1.014-7.948), respectively, with robust relationships with female hyperuricemia (all P < .05). However, there was only a positive correlation between the decline in UA levels and thyroid feedback quantile index, thyrotropin, and thyrotropin-thyroxine resistance index in female patients following LSG. CONCLUSION: Female hyperuricemia is correlated with higher thyroid hormone resistance index scores. Resistance to thyroid hormones was greatly improved by LSG. The decrease in UA levels after surgery is correlated with the improvement of thyroid hormone resistance after LSG.

Microstructural abnormality of white matter tracts in rheumatoid arthritis.

BACKGROUND: Structural and functional brain imaging studies have reported abnormalities of gray matter morphology and functional activities in patients with rheumatoid arthritis (RA). However, it is largely unknown whether patients with RA show alterations of white matter microstructural organization. OBJECTIVES: To automatically identify alteration of white matter microstructure in patients with RA and further examine how this alteration associates with clinical characteristics. METHODS: This single-institutional prospective study included 66 participants (33 patients with RA [52 ± 9 years, 29 women] and 33 sex/age-matched healthy controls [53 ± 12 years, 27 women]), who underwent diffusion MRI scan from January 2021 to December 2021. The white matter microstructure was assessed using fractional anisotropy, mean diffusivity, axial diffusivity, and radial diffusivity. Voxelwise analyses were conducted on white matter skeleton using an automated, observer-independent tract-based spatial statistics analysis. The relationship between white matter microstructural alterations and clinical and neuropsychological variables was evaluated using correlation analysis. RESULTS: Compared with healthy controls, patients with RA exhibited lower fractional anisotropy in several major white matter tracts (threshold-free cluster enhancement at P < 0.05 for multiple comparison correction, permutation test), involving the forceps minor, bilateral inferior fronto-occipital fasciculus, bilateral anterior thalamic radiation, and bilateral uncinate fasciculus. Lower fractional anisotropy values in the patients with RA were significantly associated with pain-related assessments, including tender joint count (r = -0.43, P = 0.015), Clinical Disease Activity Index score (r = -0.36, P = 0.049), pain severity rated through visual analogue scale (r = -0.45, P = 0.012), and Simplified Disease Activity Index score (r = -0.36, P = 0.045). No significant group difference was found in mean diffusivity, axial diffusivity, and radial diffusivity. CONCLUSIONS: We report the first anatomical evidence for aberrant microstructure organization of several major white matter tracts and its associations with pain processing in patients with rheumatoid arthritis.

Shared and distinct prefrontal cortex alterations of implicit emotion regulation in depression and anxiety: An fNIRS investigation.

BACKGROUND: Emotion regulation deficits, particularly in cognitive reappraisal, are crucial in depression and anxiety. However, research on the neural mechanisms of implicit emotion regulation is lacking, and it remains unclear whether these mechanisms are shared or distinct between the two disorders. METHODS: We investigated the neural mechanisms of implicit cognitive reappraisal in 28 individuals with major depressive disorder (MDD), 25 with generalized anxiety disorder (GAD), and 30 healthy controls (HC) using functional near-infrared spectroscopy (fNIRS). Participants completed an implicit cognitive reappraisal task and underwent neuropsychological and clinical assessments. RESULTS: We found that MDD patients reported higher levels of rumination and lower utilization of cognitive reappraisal, while GAD patients reported reduced use of perspective-taking. Notably, both MDD and GAD patients exhibited decreased activation in the dorsolateral prefrontal cortex (DLPFC) and orbitofrontal cortex (OFC) compared to HC participants during implicit cognitive reappraisal. Specifically, inadequate OFC activation was observed in MDD patients, while GAD patients demonstrated OFC deactivation during the task. Furthermore, DLPFC activation showed a negative correlation with depression severity in MDD patients, while OFC activation was positively correlated with perspective-taking in GAD patients. LIMITATIONS: fNIRS has limited depth and spatial resolution. CONCLUSION: Our fNIRS study is the first to reveal shared and distinct neurobiological profiles of depression and anxiety in implicit emotion regulation. These findings underscore the significance of reduced DLPFC/OFC activation in emotion regulation impairment and highlight unique OFC activation patterns in these disorders. These insights have potential implications for developing cognitive-behavioral therapy and transcranial magnetic stimulation as treatment approaches.

Three-dimensional array of microbubbles sonoporation of cells in microfluidics.

Sonoporation is a popular membrane disruption technique widely applicable in various fields, including cell therapy, drug delivery, and biomanufacturing. In recent years, there has been significant progress in achieving controlled, high-viability, and high-efficiency cell sonoporation in microfluidics. If the microchannels are too small, especially when scaled down to the cellular level, it still remains a challenge to overcome microchannel clogging, and low throughput. Here, we presented a microfluidic device capable of modulating membrane permeability through oscillating three-dimensional array of microbubbles. Simulations were performed to analyze the effective range of action of the oscillating microbubbles to obtain the optimal microchannel size. Utilizing a high-precision light curing 3D printer to fabricate uniformly sized microstructures in a one-step on both the side walls and the top surface for the generation of microbubbles. These microbubbles oscillated with nearly identical amplitudes and frequencies, ensuring efficient and stable sonoporation within the system. Cells were captured and trapped on the bubble surface by the acoustic streaming and secondary acoustic radiation forces induced by the oscillating microbubbles. At a driving voltage of 30 Vpp, the sonoporation efficiency of cells reached 93.9% ± 2.4%.