Late-onset Cholestasis with Paucity of Portal Area Secondary to HNF1ß Deficiency in Adulthood: A Case Report.

Hepatocyte nuclear factor 1ß (HNF1ß) is essential for biliary development, while its genetic defect triggers the dysplasia of interlobular bile ducts, leading to life-threatening hepatitis and cholestasis. To date, this disorder has mainly been documented in neonates. Here, we report a case of cholestasis in an adult patient caused by a de novo HNF1ß mutation. A liver biopsy revealed remarkable shrinkage of the portal area accompanied by a decrease or absence of interlobular bile ducts, veins, and arteries in the portal area. Our case showed that an HNF1ß defect could induce late-onset cholestasis with paucity of the portal area in adulthood.

How Positioning Wearable Haptic Interfaces on Limbs Influences Virtual Embodiment.

With increasing use of computer applications and robotic devices in our everyday life, and with the advent of metaverse, there is an urgent need of developing new types of interfaces that facilitate a more intuitive interaction in physical and virtual space. In this work, we investigate the influence of the location of haptic feedback devices on embodiment of virtual hands and user load during an interactive pick-and-place task. To do this, we conducted a user study with a 3x2 repeated measure experiment design: feedback position is varied between the distal phalanx of the index finger and the thumb, the proximal phalanx of the index finger and the thumb, and the wrist. These conditions of feedback are tested with the stimuli applied synchronously to the participant in one case, and with an additional delay of 350 ms in the second case. The results show that the location of the haptic feedback device does not affect embodiment, whereas the delay, i.e., whether the feedback is applied synchronously or asynchronously, affects embodiment. This suggests that for pick-and-place tasks, haptic feedback devices can be placed on the user's wrist without compromising performance making the hands to remain free, allowing unobstructed hand visibility for precise motion tracking, thereby improving accuracy.

TIGIT reverses IFN-α-promoted Th1-like Tregs via in-sequence effects dependent on STAT4.

OBJECTIVES: The induction direction of interferon (IFN)-α in T-cell phenotype and function varies depending on the activation state of the cell and the time of stimulation. To assess the effects of elevated IFN-α on regulatory T cells (Tregs) in systemic lupus erythematosus (SLE) patients, we investigated the differentiation of Th1-like Tregs under in-sequence and out-of-sequence conditions and the reversal effect of activating TIGIT on immune suppression. METHODS: Phenotypes and activation levels of Tregs from SLE patients and healthy controls were analyzed using flow cytometry. In vitro culture conditions based on the sequence of TCR activation and IFN-α stimulation simulated in-sequence or out-of-sequence effects. CD4+T cells and Tregs were cultured under the above conditions with or without TIGIT agonist. Expression of related characteristic markers and phosphorylation levels of AKT, mTOR, and STATs were detected using flow cytometry and ELISA. RESULTS: The frequency of Th1-like Tregs and activation levels of Tregs increased, but TIGIT expression in Tregs decreased in SLE patients. IFN-α promoted the conversation of Tregs to Th1-like Tregs while reducing immunosuppressive function under in-sequence conditions. The STAT4 pathway, but not the STAT1 pathway, was crucial for the IFN-α-mediated in-sequence effects. Reactivation of TIGIT reversed Th1 polarization of Tregs by suppressing AKT/mTOR and STAT4 signaling. CONCLUSIONS: Our findings suggest that IFN-α mediated in-sequence effects on Tregs may be responsible for the expansion of Th1-like Tregs in SLE. TIGIT can restore immune suppression damage in Tregs and represents a potential therapeutic target for SLE.

The optimization of an EV decommissioned battery recycling network: A third-party approach.

In this paper, we solve the urgent problem to construct a recycling network of decommissioned batteries of Electric Vehicles (EVs) and clarify the recycling entities that will be responsible for its reverse logistics (RL) process. We consider the third-party recycling entities to develop a recycling network and conduct a case-study of Xi'an, a key industry of EVs in China to provide a reference for the government and enterprises to develop recycling plans. We scientifically optimize our recycling network, which will have a significant impact on the environmental and economic benefits of electric vehicles (EVs) in Xi'an in the future. Specifically, we consider the costs of transportation, construction, operation, recycling, packaging, and emission, as well as the profits achieved through sales revenue and subsidy offerings. We collect the actual data of potential facility locations in Xi'an, predict the quantity of decommissioned batteries in the future, and develop a fuzzy-based model to solve the optimal results of battery traveling path and distribution in the recycling process network. Our results show that with the rapid growth of the number of decommissioned batteries, third-party revenues will reach about 53.08 billion by 2035. When the facilities split the recycling process load appropriately, the network has increase in revenue while the utilization rate of facilities will decrease. We expect that splitting will be a major trend in the future development of recycling network in Xi'an. Finally, a sensitivity analysis finds that with the environmentally conscious and safe operation of recycling, the negative impact on the third-party enterprises' revenue will be small. Our proposed methodology can serve as a critical framework for other cities and governments to plan their recycling networks and formulate regulations, reflecting on the realistic projection of the scale of decommissioned batteries of EVs and the potential siting and sizing of the recycling facilities.

Identification of key genes and imbalance of immune cell infiltration in immunoglobulin A associated vasculitis nephritis by integrated bioinformatic analysis.

Background: IgAV, the most common systemic vasculitis in childhood, is an immunoglobulin A-associated immune complex-mediated disease and its underlying molecular mechanisms are not fully understood. This study attempted to identify differentially expressed genes (DEGs) and find dysregulated immune cell types in IgAV to find the underlying pathogenesis for IgAVN. Methods: GSE102114 datasets were obtained from the Gene Expression Omnibus (GEO) database to identify DEGs. Then, the protein-protein interaction (PPI) network of the DEGs was constructed using the STRING database. And key hub genes were identified by cytoHubba plug-in, performed functional enrichment analyses and followed by verification using PCR based on patient samples. Finally, the abundance of 24 immune cells were detected by Immune Cell Abundance Identifier (ImmuCellAI) to estimate the proportions and dysregulation of immune cell types within IgAVN. Result: A total of 4200 DEGs were screened in IgAVN patients compared to Health Donor, including 2004 upregulated and 2196 downregulated genes. Of the top 10 hub genes from PPI network, STAT1, TLR4, PTEN, UBB, HSPA8, ATP5B, UBA52, and CDC42 were verified significantly upregulated in more patients. Enrichment analyses indicated that hub genes were primarily enriched in Toll-like receptor (TLR) signaling pathway, nucleotide oligomerization domain (NOD)-like receptor signaling pathway, and Th17 signaling pathways. Moreover, we found a diversity of immune cells in IgAVN, consisting mainly of T cells. Finally, this study suggests that the overdifferentiation of Th2 cells, Th17 cells and Tfh cells may be involved in the occurrence and development of IgAVN. Conclusion: We screened out the key genes, pathways and maladjusted immune cells and associated with the pathogenesis of IgAVN. The unique characteristics of IgAV-infiltrating immune cell subsets were confirmed, providing new insights for future molecular targeted therapy and a direction for immunological research on IgAVN.

A Design Framework of Medical Wayfinding Signs for the Elderly: Based on the Situational Cognitive Commonness.

Older people in China have a poor understanding of hospital signage. To address this problem, in this study, we combined the theories of situated cognition and cognitive commonness in order to introduce the three main factors that affect the generation of situational cognitive commonness: composition of the situation, familiarity, and concreteness. We used these theories to construct a methodological framework for the design of geriatric hospital wayfinding signs that were based on situational cognitive commonness. The design of nine healthcare signs for Chinese national standards were used as examples in the study. First, users who were familiar with medical scenarios were asked to draw concrete cognitive conception graphics for the purposes of individual wayfinding targets from both physical and social situations. Next, we coded and grouped the generated graphics based on their situational features in order to extract groups of representative common graphics. Finally, we reorganized the common graphics and developed concrete designs, which were tested by the judgment test. The wayfinding signs designed according to the methodological framework of this study effectively improved the understanding of hospital signage among older Chinese people. This study took geriatric hospital wayfinding signs as the examples to provide a feasible theoretical basis and research reference for symbol design.

Competitive binding of transcription factors underlies flexibility of T peripheral helper cells and T follicular helper cells in SLE.

OBJECTIVE: Peripheral helper T (Tph) cells interact with B cells and promote immune responses at sites of ectopic lymphoid structures (ELSs). To assess the characteristics of Tph cells, we investigated the phenotype of T helper (Th) cells in patients with SLE and the underlying competitive binding mechanisms using cytokine-mediated signal transducer and activator of transcription (STAT) factors. METHODS: Peripheral blood mononuclear cells from SLE patients and healthy controls were analysed for phenotypic identification. Serum cytokine levels were detected using Luminex assays. In vitro culture was performed to assess cytokine-induced conversion of phenotypes and transcriptional regulation using flow cytometry and PCR. Chromatin immunoprecipitation was used to evaluate STAT binding and histone modifications. RESULTS: CXCR5-PD-1+Tph-like cells were increased in SLE patients and showed strong association with disease activity and renal involvement. Serum IFN-α levels were increased and associated with Tph frequency. IFN-α promoted the differentiation of IL-10-producing CXCR5-PD-1+Tph-like cells, increased the responsiveness of IL-2 and induced the conversion of Tfh-like cells to Tph-like cells. STAT5 gained a competitive advantage and bound to the BCL6 locus at the expense of STAT1, accompanied by suppression of H3K4me3. Finally, anti-IFNAR1 decreased the differentiation of Tph-like cells, thereby suppressing the generation of CD38highCD27highplasmablasts. CONCLUSION: Tph cells might be crucial makers to effectively reflect disease activity level in SLE patients. The finding that synergy of IFN-α and IL-2 increases Tph cells through competitive transcriptional regulation could be one of the mechanisms responsible for pathological formation of ELSs and helpful for selection of individualized therapeutic approaches for SLE.

A Self-Sustained Wireless Multi-Sensor Platform Integrated with Printable Organic Sensors for Indoor Environmental Monitoring.

A self-sustained multi-sensor platform for indoor environmental monitoring is proposed in this paper. To reduce the cost and power consumption of the sensing platform, in the developed platform, organic materials of PEDOT:PSS and PEDOT:PSS/EB-PANI are used as the sensing films for humidity and CO2 detection, respectively. Different from traditional gas sensors, these organic sensing films can operate at room temperature without heating processes or infrared transceivers so that the power consumption of the developed humidity and the CO2 sensors can be as low as 10 µW and 5 µW, respectively. To cooperate with these low-power sensors, a Complementary Metal-Oxide-Semiconductor (CMOS) system-on-chip (SoC) is designed to amplify and to read out multiple sensor signals with low power consumption. The developed SoC includes an analog-front-end interface circuit (AFE), an analog-to-digital convertor (ADC), a digital controller and a power management unit (PMU). Scheduled by the digital controller, the sensing circuits are power gated with a small duty-cycle to reduce the average power consumption to 3.2 µW. The designed PMU converts the power scavenged from a dye sensitized solar cell (DSSC) module into required supply voltages for SoC circuits operation under typical indoor illuminance conditions. To our knowledge, this is the first multiple environmental parameters (Temperature/CO2/Humidity) sensing platform that demonstrates a true self-powering functionality for long-term operations.

A wireless bio-MEMS sensor for C-reactive protein detection based on nanomechanics.

A quick wireless label-free detection of disease-related C-reactive proteins (CRPs) using a 200-microm-long microelectromechanical systems (MEMS) microcantilever housed in a 7 x 7 mm(2) reaction chamber with a safe reusable feature is reported. The assay time ranges from about 30 min to 3 h, depending on accuracy. The deflection of the microcantilever due to specific CRP-antiCRP binding is detected using a position-sensitive detector. The converted bio-signal is transmitted by a custom designed wireless amplitude-shift-keying (ASK) transceiver IC fabricated in a 0.18 microm CMOS process. CRP concentrations from 1 microg/mL to 500 microg/mL can be detected. A 0.2-Hz 1-V ac signal instead of traditional bases/acids is applied to the bio-MEMS sensor to unbind the CRP from the microcantilever for reusability.