Genetic evaluation in indeterminate acute liver failure: A post hoc analysis.

BACKGROUND AND STUDY AIMS: There are limited data regarding indeterminate acute liver failure (ALF). The study aims to perform a post hoc analysis using genetic methods for the ALF cases with indeterminate etiology. PATIENTS AND METHODS: Stored blood samples from these patients with indeterminate ALF were collected. Whole-exome sequencing (WES) was used to evaluate the pathogenesis of indeterminate ALF. RESULTS: A total of 16 samples from 11 adult patients and 5 pediatric patients with indeterminate ALF were available. Among the adult patients, one female patient was identified with two heterozygous variants (c.2333G > T (p.Arg778Leu) and c.2310C > G (p.Leu770 = )) in the adenosine triphosphatase copper-transporting beta (ATP7B) gene, and two male patients were found to harbor heterozygous and homozygous variants (c.686C > A (p.Pro229Gln) plus homozygousvariantA(TA)6TAAinsTA (-), andc.1456 T > G (p.Tyr486Asp) plus c.211G > A (p.Gly71Arg)) in the uridine diphosphate glucuronosyltransferase 1A1 (UGT1A1) gene. For the pediatric patients, single heterozygous variant (c.2890C > T (p.Arg964Cys)) in the polymerase gamma (POLG) gene was found in 1 male child, and two heterozygous variants (c.1909A > G (p.Lys637Glu) and c.3646G > A (p.Val1216Ile)) in the tetratricopeptide repeat domain 37 (TTC37) gene were found in 1 female child. No variants clinically associated with known liver diseases were revealed in the remaining patients. CONCLUSION: These results expand the knowledge of ALF with indeterminate etiology. WES is helpful to reveal possible candidate genes for indeterminate ALF, but incomplete consistency between the genotype and phenotype in some cases still challenge the accurate diagnosis.

Tumor Microenvironment-Regulating Two-Photon Probe Based on Bimetallic Post-Coordinated MOF Facilitating the Dual-Modal and Deep Imaging-Guided Synergistic Therapies.

The intricate tumor microenvironment (TME) always brings about unsatisfactory therapeutic effects for treatments, although nanomedicines have been demonstrated to be highly beneficial for synergistic therapies to avoid the side effects caused by the complexity and heterogeneity of cancer. Developing nanotheranostics with the functionalities of both synergistic therapies and TME regulation is a good strategy but is still in its infancy. Herein, an "all-in-one" nanoplatform for integrated diagnosis and treatment, namely, Carrier@ICG@DOX@FA (CIDF), is constructed. Benefiting from the bimetallic coordination of Eu3+-HTHA (4,4,4-trifluoro-1-(9-hexylcarbazol-3-yl)-1,3-butanedione) and Fe3+ with the ligands in UiO-67, CIDF can simultaneously achieve two-photon fluorescence imaging, fluorescent lifetime imaging in deep tumors, and regulation of TME. Owing to its porosity, CIDF can encapsulate indocyanine green as photosensitizers and doxorubicin as chemotherapeutic agent, further realizing light-controlled drug release. Moreover, CIDF exhibited good biocompatibility and tumor targeting by coating with folic-acid-modified polymers. Both in vitro and in vivo experiments demonstrate the excellent therapeutic efficacy of CIDF through dual-modal-imaging-guided synergistic photothermal-, photodynamic-, and chemotherapy. CIDF provides a new paradigm for the construction of TME-regulated synergistic nanotheranostics and realizes the complete elimination of tumors without recurrence.

In vitro differentiation of human induced pluripotent stem cells into temporomandibular joint disc like cells.

Temporomandibular joint discs (TMJ discs) are unable to repair themselves in disease states, while induced stem cell differentiation is a common method to repair tissue defects. Nowadays, kinds of stem cells are attempted for tissue regeneration of TMJ disc, but these methods have several downsides, which limit their wide application. The proliferation and differentiation ability of human induced pluripotent stem cells (hiPSC) provides a new research direction for TMJ disc tissue regeneration. In this study, we investigated the feasibility of induced differentiation of hiPSC into TMJ disc cells in vitro and the differentiation efficiency of different methods to clarify the possibility and conditions of hiPSC application in TMJ disc tissue engineering. We collected sheep TMJ disc cells cultures for adding in hiPSC culture environment and treated hiPSC by both direct induction and Transwell co-culture for 7 days, 14 days and 21 days. The secretion of extracellular matrix in TMJ disc cells was detected by Sirius Red and Safranin O staining. Collagen Ⅰ and Collagen Ⅱ were qualitatively detected by immunohistochemical staining. The expression of extracellular matrix genes (type I collagen (COL1A1), type II collagen(COL2), glycosaminoglycan (GAG)), chondrogenic differentiation gene SOX9 and pluripotency gene OCT4 were detected by RT-qPCR. Our results showed that hiPSC had the ability to differentiate to TMJ disc cells by direct induction in TMJ disc cell culture medium and by Transwell co-culture method. The highest degree of differentiation was observed after 14 days of direct induction, while Transwell co-culture showed significant differentiation at different times and with different major directions. Meanwhile, Transwell co-culture not only differentiates hiPSC but also promotes the growth and proliferation of TMJ disc cells. Our study is valuable to investigate the possibility of differentiation of hiPSC toward TMJ disc cells and to determine the time of differentiation. It provides new ideas for the selection of seed cells for TMJ disc tissue engineering.

A 10-micrometer-thick nanomesh-reinforced gas-permeable hydrogel skin sensor for long-term electrophysiological monitoring.

Hydrogel-enabled skin bioelectronics that can continuously monitor health for extended periods is crucial for early disease detection and treatment. However, it is challenging to engineer ultrathin gas-permeable hydrogel sensors that can self-adhere to the human skin for long-term daily use (>1 week). Here, we present a ~10-micrometer-thick polyurethane nanomesh-reinforced gas-permeable hydrogel sensor that can self-adhere to the human skin for continuous and high-quality electrophysiological monitoring for 8 days under daily life conditions. This research involves two key steps: (i) material design by gelatin-based thermal-dependent phase change hydrogels and (ii) robust thinness geometry achieved through nanomesh reinforcement. The resulting ultrathin hydrogels exhibit a thickness of ~10 micrometers with superior mechanical robustness, high skin adhesion, gas permeability, and anti-drying performance. To highlight the potential applications in early disease detection and treatment that leverage the collective features, we demonstrate the use of ultrathin gas-permeable hydrogels for long-term, continuous high-precision electrophysiological monitoring under daily life conditions up to 8 days.

Cognition of nursing translational medical research among nursing practitioners in China.

BACKGROUND: Nursing translational research (TR) begins with clinical discovery and medical research and leads to clinical application in patients. TR is key to improving nursing quality and developing the nursing profession. However, its development in China remains limited, and the reasons for this are unclear. We aim to enhance the recognition of nursing TR among nursing practitioners in China by exploring their cognition about nursing TR and associated influences. METHODS: We distributed an internet-based questionnaire to 683 nursing practitioners between February 13 and March 15, 2023. We analyzed the characteristics and cognition of nursing TR using descriptive statistics, the chi-squared test, Fisher's exact test, the Wilcoxon rank-sum test, Kruskal-Wallis H test, and stepwise logistic regression analysis. The majority (79.65%) of nursing practitioners who responded to the questionnaire were willing to participate in nursing TR. FINDINGS: Nursing practitioners with a higher educational level, stronger recognition of the importance of nursing TR, and stronger recognition of transdisciplinary nursing TR were more willing to participate in nursing TR. DISCUSSION: The results of this study can accelerate nursing practitioners' willingness to participate in nursing TR. APPLICATION TO PRACTICE: We identified strategies to promote TR: provide further education, optimize courses in higher education, disseminate information, provide guidance on the importance of nursing TR, and establish a nursing TR platform with appropriate potential collaborators.

Repeated endoscopic treatment of gastric antral vascular ectasia.

GAVE is a relatively rare acquired vascular disease. The most common treatment for GAVE is endoscopic therapy. Argon plasma coagulation（APC） is usually the first-line choice for endoscopic GAVE treatment, but its recurrence rate is high and often requires multiple repeated treatments. In this case, the GAVE patient recurred after two APC treatments. The results suggest that APC-treated patients with GAVE are prone to relapse. In conclusion, clinicians should regularly follow up patients who received APC treatment.

An optical-based multipoint 3-axis pressure sensor with a flexible thin-film form.

Multipoint 3-axis tactile pressure sensing by a high-resolution and sensitive optical system provides rich information on surface pressure distribution and plays an important role in a variety of human interaction-related and robotics applications. However, the optical system usually has a bulky profile, which brings difficulties to sensor mounting and system integration. Here, we show a construction of thin-film and flexible multipoint 3-axis pressure sensor by optical methods. The sensor can detect the distribution of 3-axis pressure on an area of 3 centimeter by 4 centimeter, with a high-accuracy normal and tangential pressure sensing up to 360 and 100 kilopascal, respectively. A porous rubber is used as a 3-axis pressure-sensitive optical modulator to omit the thick and rigid focusing system without sacrificing the sensitivity. In addition, by integrating thin and flexible backlight and imager, the sensor has a total thickness of 1.5 milimeter, making it function properly even when bent to a radius of 18 milimeter.

Alcoholic cardiomyopathy in patients with alcoholic liver cirrhosis: a study across 10†years.

BACKGROUND AND OBJECTIVES: Available data regarding cardiomyopathy in patients with alcoholic liver cirrhosis (ALC) are very limited because it often requires multidisciplinary assessments. The study aims to evaluate the prevalence of alcoholic cardiomyopathy in ALC and their clinical correlations. METHODS: Adult ALC patients without a previous diagnosis of cardiovascular diseases between January 2010 and December 2019 were included in the study. The prevalence rate of alcoholic cardiomyopathy in patients with ALC was calculated together with a 95% confidence interval (CI) using the Clopper-Pearson exact method. RESULTS: A total of 1022 ALC patients were included. Male patients predominated (90.5%). ECG abnormalities were observed in 353 patients (34.5%). Prolonged QT interval was most common in ALC patients with ECG abnormalities, which occurred in 109. Thirty-five ALC patients underwent the cardiac MRI examination and only one patient was found with cardiomyopathy. The estimated prevalence rate of alcoholic cardiomyopathy in all the ALC patients was 0.0286 (95% CI, 0.0007-0.1492). There was no statistical difference regarding the prevalence rate between the group of patients with ECG abnormalities and the group without ECG abnormalities (0.0400 vs. 0.0000, P  = 1.000). CONCLUSION: Although ECG abnormalities, especially QT prolongation, existed in a proportion of ALC patients, cardiomyopathy in the patient population was not common. Further larger-sample studies based on cardiac MRI are needed to verify our results.

Hepatocyte proliferation favours viral clearance in young children with chronic hepatitis B virus infection.

AIM: The aim of this study is to explore the correlation between hepatocyte proliferation and hepatitis B virus (HBV) clearance in young children with chronic HBV infection. METHODS: We collected liver biopsy samples and clinical data corresponding to paediatric patients with chronic HBV infection. Ki-67 expression in liver tissues was evaluated by immunohistochemical staining. RESULTS: Eighteen patients were included and were divided into two groups based on different antiviral outcomes. Group I achieved hepatitis B surface antigen (HBsAg) loss within 48 weeks. Group II did not develop seroconversion from hepatitis B e (HBe) antigen to anti-HBe after 48 weeks. There were 10 patients in Group I and 8 in Group II, respectively. Demographical data and baseline virological and biochemical characteristics in serum across Group I and Group II were not statistically different. Histologically, mean Ki-67 expression index in Group I was 15%, while the mean index in Group II was 5%. There was a significant difference between the two groups (p < 0.01). CONCLUSION: High Ki-67 expression can contribute to viral clearance in young children with chronic HBV infection. This is the first confirmation of the association between hepatocyte proliferation and HBV clearance in vivo and has implications for novel therapeutic strategies against hepatitis B.

MiR-29c-3p inhibits proliferation and migration in rat primary cardiac fibroblasts via interacting with STAT3.

BACKGROUND: The aim of this study was to elucidate the influence and molecular mechanism of microRNA-29c-3p (miR-29c-3p) on cell functions of cardiac fibroblasts. METHODS: Rat primary cardiac fibroblasts were induced with high-level glucose (HG), followed by determination of miR-29c-3p and signal transducer and activator of transcription 3 (STAT3) levels. The regulatory effects of miR-29c-3p and STAT3 (AG490) on proliferative and migratory potentials in HG-induced cardiac fibroblasts were examined by cell counting kit-8 (CCK-8) and Transwell assay, respectively. The interaction between miR-29c-3p and STAT3 was assessed by bioinformatics analysis and dual-luciferase reporter assay. RESULTS: MiR-29c-3p was downregulated, and STAT3 was upregulated in HG-induced cardiac fibroblasts. HG induction stimulated proliferative and migratory potentials in cardiac fibroblasts, which were attenuated by overexpression of miR-29c-3p. STAT3 was the target gene binding miR-29c-3p. Application of AG490, the STAT3 inhibitor, was able to reverse the promoted proliferative and migratory potentials in HG-induced cardiac fibroblasts with miR-29c-3p knockdown. CONCLUSIONS: MiR-29c-3p weakens the over-proliferative and over-migratory potentials in HG-induced cardiac fibroblasts via inactivating the STAT3 signaling.

Vitamin D3 eradicates Helicobacter pylori by inducing VDR-CAMP signaling.

Background: Vitamin D3 [VitD3, 1,25 (OH)2D3] is known to have immunomodulatory and anti-microbial properties; however, its activity against Helicobacter pylori is unclear. In this study, we established H. pylori infection models in wild-type and VitD3 receptor (VDR) knockdown mice and analyzed the effects of VitD3 and their underlying mechanisms. Methods: VDR+/+ and VDR+/- mice were intragastrically infected with the H. pylori SS1 strain. After confirmation of H. pylori infection, mice were treated with different doses of VitD3. The infection levels in stomach tissues were quantified using the colony-forming assay, and the expression levels of the VDR and cathelicidin antimicrobial peptide (CAMP) in the gastric mucosa were analyzed by immunohistochemistry and western blotting. Results: The gastric mucosa of VDR+/- mice was more susceptible to H. pylori colonization and had lower levels of VDR and CAMP expression than that of VDR+/+ mice. H. pylori infection upregulated VDR and CAMP expression in the stomach of both wild-type and mutant mice, and VitD3 treatment resulted in further increase of VDR and CAMP levels, while significantly and dose-dependently decreasing the H. pylori colonization rate in both mouse groups, without affecting blood calcium or phosphorus levels. Conclusion: Our data indicate that oral administration of VitD3 reduces the H. pylori colonization rate and upregulates VDR and CAMP expression in the gastric mucosa, suggesting a role for VitD3/VDR/CAMP signaling in the eradication of H. pylori in the stomach. These findings provide important insights into the mechanism underlying the anti-H. pylori activity of VitD3 and should be useful in the development of measures to eradicate H. pylori.

Follow-Up of Newborns with Hepatitis B Antigenemia.

INTRODUCTION: There is a need for data to evaluate hepatitis B antigenemia in newborns of mothers with hepatitis B virus (HBV) infection. This study aims to investigate this. METHODS: Newborns with positive serum hepatitis B surface antigen (HBsAg) and/or e antigen (HBeAg) were enrolled in the study. RESULTS: One hundred and one newborns from 98 HBV-infected mothers were included. Median maternal serum HBV DNA level was 23,200 IU/mL at delivery. Among the newborns, 48 were boys and 53 were girls. Mean birth weight was 3190.5 g. Twenty-one newborns had concurrent seropositive HBsAg and HBeAg, nine had seropositive HBsAg and seronegative HBeAg, and 71 had seronegative HBsAg and seropositive HBeAg. Eight newborns had detectable serum HBV DNA. In the follow-up, serum HBsAg and HBeAg in the newborns with undetectable HBV DNA became negative before 6 months of age. Two infants with detectable HBV DNA were diagnosed with immunoprophylaxis failure, one of whom developed active hepatitis at 3 months of age. Liver biopsy in this case showed significant interface hepatitis, fibrous septa formation, and expansion of portal areas with occasional bridging fibrosis. CONCLUSIONS: Concurrent HBV viremia and antigenemia in newborns of HBV-infected mothers requires attention, while antigenemia without viremia is often transient.

The influence of moral identity on green consumption.

Existing studies show that moral identity promotes green consumption, but its influence mechanism and boundary conditions remain unidentified. However, moral identity includes internalization and symbolization, which affect green consumption in different ways. Advertising goal framing also has an impact on green consumption. Existing studies often focus on moral identity internalization but neglect the role of moral identity symbolization and fail to fully consider the interaction, mechanism, and boundary conditions between moral identity and advertising goal framing. This study assumes that advertising goal framing includes both intrinsic and extrinsic goals. We attempt to verify the combined influence of internalization and symbolization of moral identity, advertising goal framing, and moral awareness on green purchasing intention. Through two experiments, we found that: (1) the internalization and symbolization of moral identity can promote consumers' green purchasing intention; (2) consumers with high internalization of moral identity have more positive responses to intrinsic goal advertising; (3) moral awareness can enhance the combined influence of moral identity internalization and intrinsic goal advertising on consumers' green purchasing intention; and (4) self-consistency and social approval mediate the combined impact of moral identity and advertising goal framing on consumers' green purchasing intention. This study enriches the literature on the influence of moral identity on green consumption. Businesses can also draw on these findings to improve the effectiveness of green marketing.

Cardiac involvement in Wilson's disease: a retrospective cohort study.

BACKGROUND AND OBJECTIVES: Wilson's disease (WD) is an inherited disorder with perturbations in copper metabolism and can cause multiorgan damage. This study aims to explore cardiac findings mainly based on electrocardiography (ECG) in WD patients. METHODS: We retrospectively enrolled adult patients who were diagnosed with WD between January 2011 and December 2020. Demographic and clinical data were collected and reevaluated. RESULTS: A total of 126 patients were included. There were 71 men and 55 women. The mean age was 27.2 years. Ninety-nine had hepatic presentation as the initial symptom and 27 had neuropsychiatric presentation as the initial symptom. Thirty-seven patients (29.4%) had cardiac manifestations. Of these patients, nine presented apparent cardiac symptoms (three with discontinuous chest tightness, three with dizziness, two with palpitation and one with atypical chest pain) and 28 had asymptomatic electrocardiography (ECG) abnormalities. Among the nine patients, four had second- or third-degree atrioventricular block, three had ST-segment change and two had ventricular tachycardia. ECG abnormalities in the 28 patients included increase in the width of the QRS complex in 8, atrial premature beats in 8, T-wave inversion in 5, P-wave inversion in 2, sinus bradycardia in 2, ST-segment change in 2, and coexistence of sinus bradycardia and T-wave inversion in 1. No statistical difference (P = 0.32) existed in the occurrence of ECG abnormalities between patients with hepatic presentation (27/99) and those with neuropsychiatric presentation (10/27). CONCLUSION: Cardiac involvement is not rare in adult WD patients. We suggest that cardiac evaluation should be routinely performed in the population.

Antimicrobial second skin using copper nanomesh.

The functional support and advancement of our body while preserving inherent naturalness is one of the ultimate goals of bioengineering. Skin protection against infectious pathogens is an application that requires common and long-term wear without discomfort or distortion of the skin functions. However, no antimicrobial method has been introduced to prevent cross-infection while preserving intrinsic skin conditions. Here, we propose an antimicrobial skin protection platform copper nanomesh, which prevents cross-infectionmorphology, temperature change rate, and skin humidity. Copper nanomesh exhibited an inactivation rate of 99.99% for Escherichia coli bacteria and influenza virus A within 1 and 10 min, respectively. The thin and porous nanomesh allows for conformal coating on the fingertips, without significant interference with the rate of skin temperature change and humidity. Efficient cross-infection prevention and thermal transfer of copper nanomesh were demonstrated using direct on-hand experiments.

On-skin paintable biogel for long-term high-fidelity electroencephalogram recording.

Long-term high-fidelity electroencephalogram (EEG) recordings are critical for clinical and brain science applications. Conductive liquid-like or solid-like wet interface materials have been conventionally used as reliable interfaces for EEG recording. However, because of their simplex liquid or solid phase, electrodes with them as interfaces confront inadequate dynamic adaptability to hairy scalp, which makes it challenging to maintain stable and efficient contact of electrodes with scalp for long-term EEG recording. Here, we develop an on-skin paintable conductive biogel that shows temperature-controlled reversible fluid-gel transition to address the abovementioned limitation. This phase transition endows the biogel with unique on-skin paintability and in situ gelatinization, establishing conformal contact and dynamic compliance of electrodes with hairy scalp. The biogel is demonstrated as an efficient interface for long-term high-quality EEG recording over several days and for the high-performance capture and classification of evoked potentials. The paintable biogel offers a biocompatible and long-term reliable interface for EEG-based systems.

Skin bioelectronics towards long-term, continuous health monitoring.

Skin bioelectronics are considered as an ideal platform for personalised healthcare because of their unique characteristics, such as thinness, light weight, good biocompatibility, excellent mechanical robustness, and great skin conformability. Recent advances in skin-interfaced bioelectronics have promoted various applications in healthcare and precision medicine. Particularly, skin bioelectronics for long-term, continuous health monitoring offer powerful analysis of a broad spectrum of health statuses, providing a route to early disease diagnosis and treatment. In this review, we discuss (1) representative healthcare sensing devices, (2) material and structure selection, device properties, and wireless technologies of skin bioelectronics towards long-term, continuous health monitoring, (3) healthcare applications: acquisition and analysis of electrophysiological, biophysical, and biochemical signals, and comprehensive monitoring, and (4) rational guidelines for the design of future skin bioelectronics for long-term, continuous health monitoring. Long-term, continuous health monitoring of advanced skin bioelectronics will open unprecedented opportunities for timely disease prevention, screening, diagnosis, and treatment, demonstrating great promise to revolutionise traditional medical practices.

Robust, self-adhesive, reinforced polymeric nanofilms enabling gas-permeable dry electrodes for long-term application.

Robust polymeric nanofilms can be used to construct gas-permeable soft electronics that can directly adhere to soft biological tissue for continuous, long-term biosignal monitoring. However, it is challenging to fabricate gas-permeable dry electrodes that can self-adhere to the human skin and retain their functionality for long-term (>1 d) health monitoring. We have succeeded in developing an extraordinarily robust, self-adhesive, gas-permeable nanofilm with a thickness of only 95 nm. It exhibits an extremely high skin adhesion energy per unit area of 159 µJ/cm2 The nanofilm can self-adhere to the human skin by van der Waals forces alone, for 1 wk, without any adhesive materials or tapes. The nanofilm is ultradurable, and it can support liquids that are 79,000 times heavier than its own weight with a tensile stress of 7.82 MPa. The advantageous features of its thinness, self-adhesiveness, and robustness enable a gas-permeable dry electrode comprising of a nanofilm and an Au layer, resulting in a continuous monitoring of electrocardiogram signals with a high signal-to-noise ratio (34 dB) for 1 wk.