APOE ε4-associated downregulation of the IL-7/IL-7R pathway in effector memory T cells: Implications for Alzheimer's disease.

INTRODUCTION: The apolipoprotein E (APOE) ε4 allele exerts a significant influence on peripheral inflammation and neuroinflammation, yet the underlying mechanisms remain elusive. METHODS: The present study enrolled 54 patients diagnosed with late-onset Alzheimer's disease (AD; including 28 APOE ε4 carriers and 26 non-carriers). Plasma inflammatory cytokine concentration was assessed, alongside bulk RNA sequencing (RNA-seq) and single-cell RNA sequencing (scRNA-seq) analysis of peripheral blood mononuclear cells (PBMCs). RESULTS: Plasma tumor necrosis factor α, interferon γ, and interleukin (IL)-33 levels increased in the APOE ε4 carriers but IL-7 expression notably decreased. A negative correlation was observed between plasma IL-7 level and the hippocampal atrophy degree. Additionally, the expression of IL-7R and CD28 also decreased in PBMCs of APOE ε4 carriers. ScRNA-seq data results indicated that the changes were mainly related to the CD4+ Tem (effector memory) and CD8+ Tem T cells. DISCUSSION: These findings shed light on the role of the downregulated IL-7/IL-7R pathway associated with the APOE ε4 allele in modulating neuroinflammation and hippocampal atrophy. HIGHLIGHTS: The apolipoprotein E (APOE) ε4 allele decreases plasma interleukin (IL)-7 and aggravates hippocampal atrophy in Alzheimer's disease. Plasma IL-7 level is negatively associated with the degree of hippocampal atrophy. The expression of IL-7R signaling decreased in peripheral blood mononuclear cells of APOE ε4 carriers Dysregulation of the IL-7/IL-7R signal pathways enriches T cells.

High-Speed Self-Powered PdSe2/Si 2D-3D PIN-like Photodetector with Broadband Response Based on PdSe2 Quantum Island Structure.

As a two-dimensional (2D) material, palladium diselenide (PdSe2) has attracted extensive research attention due to its unique asymmetric crystal structure and extraordinary optoelectronic properties, showing great potential in electronic, optoelectronic, and other application fields. Thinner PdSe2 exhibits semiconductor properties, while the photoresponse of the photodetectors based on this film is weaker. Although increasing the thickness of the PdSe2 film can improve the photoresponse, thicker PdSe2 exhibits metallic-like properties, which is not conducive to the formation of the heterojunction. In this work, a PdSe2 2D material with a quantum island structure is prepared by a simple thermal-assisted conversion method. A new type of photodetector with a PdSe2/n--Si/n+-Si vertical PIN-like structure is innovatively proposed. Broad spectral absorption from 532 to 2200 nm and a high rectification ratio (106) of the device are achieved. The introduced n--Si layer concentrates the electric field in the depletion region, thereby shortening the transit time and accelerating the separation and collection of the carriers, resulting in the enhancement of the responsivity and 3 dB frequency compared to the traditional device with a PN structure. A recorded highest 3 dB frequency of ∼25 kHz is achieved for the PdSe2 2D-3D PIN-like device.

Fully Optical Control of Polarization Current Direction in a Cyanide-Bridged Trinuclear Complex.

As a remote and non-contact stimulus, light offers the potential for manipulating the polarization of ferroelectric materials without physical contact. However, in current research, the non-contact write-read (erase) process lacks direct observation through the stable current as output signal. To address this limitation, we investigated the photoinduced polarization switching capabilities of the cyanide-bridged compound [Fe2Co] using visible light, leading to the achievement of rewritable polarization. By subjecting [Fe2Co] crystals to alternating irradiation with 785 nm and 532 nm light, the polarization changes exhibited a distinct square wave pattern, confirming the reliability of the writing and erasing processes. Initialization involved exposing specific crystal units to 532 nm light for storing "1" or "0" information, while reading was accomplished by scanning the units with 785 nm light, resulting in brief current pulses for "1" states and no current signal for "0" states. This research unveils new possibilities for optical storage systems, paving the way for efficient and rewritable data storage and retrieval technologies, such as the next-generation memories.

Benefit finding among family caregivers of patients with advanced cancer in a palliative treatment: a qualitative study.

BACKGROUND: Benefit finding is the search for positive meaning from traumatic events, such as cancer. It can help caregivers have a positive experience in the caregiving process, relieve negative emotions, and reduce caregiving stress. The aim of this study was to explore benefit finding among caregivers of patients with advanced cancer in their palliative caregiving journey. METHODS: An exploratory qualitative design of phenomenology was used. Semistructured interviews were conducted with 19 caregivers of palliative care patients with advanced cancer. The Colaizzi 7-step analysis was used to analyse, summarize, and extract themes from the interview data. RESULTS: The study identified five themes of caregiver benefit finding in the caregiving process: personal growth, strengthened relationships with patients, adjustment and adaptation, perceived social support, and perceived meaning in life. Most caregivers reported a closer, more dependent relationship with the patient, and only one caregiver did not report any positive changes. CONCLUSIONS: Caregivers of palliative care patients with advanced cancer can have positive experiences in their care. Healthcare professionals should focus on supporting caregivers and helping them find positive experiences to cope with the challenges of caregiving and improve their quality of life.

Interplay between mesenchymal stem cells and macrophages: Promoting bone tissue repair.

The repair of bone tissue damage is a complex process that is well-orchestrated in time and space, a focus and difficulty in orthopedic treatment. In recent years, the success of mesenchymal stem cells (MSCs)-mediated bone repair in clinical trials of large-area bone defects and bone necrosis has made it a candidate in bone tissue repair engineering and regenerative medicine. MSCs are closely related to macrophages. On one hand, MSCs regulate the immune regulatory function by influencing macrophages proliferation, infiltration, and phenotype polarization, while also affecting the osteoclasts differentiation of macrophages. On the other hand, macrophages activate MSCs and mediate the multilineage differentiation of MSCs by regulating the immune microenvironment. The cross-talk between MSCs and macrophages plays a crucial role in regulating the immune system and in promoting tissue regeneration. Making full use of the relationship between MSCs and macrophages will enhance the efficacy of MSCs therapy in bone tissue repair, and will also provide a reference for further application of MSCs in other diseases.

Thalamic Nucleus Reuniens Glutamatergic Neurons Mediate Colorectal Visceral Pain in Mice via 5-HT2B Receptors.

Irritable bowel syndrome (IBS) is a common functional bowel disorder characterized by abdominal pain and visceral hypersensitivity. Reducing visceral hypersensitivity is the key to effectively relieving abdominal pain in IBS. Increasing evidence has confirmed that the thalamic nucleus reuniens (Re) and 5-hydroxytryptamine (5-HT) neurotransmitter system play an important role in the development of colorectal visceral pain, whereas the exact mechanisms remain largely unclear. In this study, we found that high expression of the 5-HT2B receptors in the Re glutamatergic neurons promoted colorectal visceral pain. Specifically, we found that neonatal maternal deprivation (NMD) mice exhibited visceral hyperalgesia and enhanced spontaneous synaptic transmission in the Re brain region. Colorectal distension (CRD) stimulation induced a large amount of c-Fos expression in the Re brain region of NMD mice, predominantly in glutamatergic neurons. Furthermore, optogenetic manipulation of glutamatergic neuronal activity in the Re altered colorectal visceral pain responses in CON and NMD mice. In addition, we demonstrated that 5-HT2B receptor expression on the Re glutamatergic neurons was upregulated and ultimately promoted colorectal visceral pain in NMD mice. These findings suggest a critical role of the 5HT2B receptors on the Re glutamatergic neurons in the regulation of colorectal visceral pain.

A ResNet mini architecture for brain age prediction.

The brain presents age-related structural and functional changes in the human life, with different extends between subjects and groups. Brain age prediction can be used to evaluate the development and aging of human brain, as well as providing valuable information for neurodevelopment and disease diagnosis. Many contributions have been made for this purpose, resorting to different machine learning methods. To solve this task and reduce memory resource consumption, we develop a mini architecture of only 10 layers by modifying the deep residual neural network (ResNet), named ResNet mini architecture. To support the ResNet mini architecture in brain age prediction, the brain age dataset (OpenNeuro #ds000228) that consists of 155 study participants (three classes) and the Alzheimer MRI preprocessed dataset that consists of 6400 images (four classes) are employed. We compared the performance of the ResNet mini architecture with other popular networks using the two considered datasets. Experimental results show that the proposed architecture exhibits generality and robustness with high accuracy and less parameter number.

Clinical Significance of Upregulation of EZH1 Expression in Hepatocellular Carcinoma Tissues.

BACKGROUND AND AIMS: The incidence and mortality of hepatocellular carcinoma (HCC) are increasing. It is urgent to develop more effective HCC biomarkers for diagnosis and treatment. This project intends to verify the expression of enhancer of zeste 1 polycomb repressive complex 2 subunit (EZH1) and its mechanism in HCC. METHODS: This study integrates global microarray and high-throughput sequencing datasets, combined with internal immunohistochemistry, to analyze the expression and prognostic value of EZH1 in HCC. Functional enrichment analysis was conducted to investigate transcriptional targets, which were achieved by intersecting HCC over-expressed genes, EZH1 co-expressed genes and putative transcriptional targets. The relationship between EZH1 and anticancer drugs was detected by drug sensitivity analysis. RESULTS: In this study, 84 datasets from 40 platforms (3,926 HCC samples and 3,428 non-cancerous liver tissues) were included to show the high expression of EZH1 in HCC. Immunohistochemistry with 159 HCC samples and 62 non-HCC samples confirmed the high expression level. HCC patients with high EZH1 expression had worse survival prognoses. Gene ontology and Reactome analysis revealed that metabolism-related pathways, including autophagy, are critical for HCC. Interestingly, as one of the EZH1 potential transcriptional targets, autophagy-related 7 (ATG7) appeared in the above pathways. ATG7 was positively correlated with EZH1, upregulated in HCC, and mediated poor prognosis. Upregulation of EZH1 was found to be in contact with HCC anti-tumor drug resistance. CONCLUSIONS: The upregulation of EZH1 expression can promote the occurrence of HCC and lead to poor clinical progression and drug resistance; these effects may be mediated by regulating ATG7.

Identification and genetic characterization of a recently identified enterovirus C116 in China.

Enterovirus C116 (EV-C116) is a new member of the enterovirus C group which is closely associated with several infectious diseases. Although sporadic studies have detected EV-C116 in clinical samples worldwide, there is currently limited information available. In this study, two EV-C-positive fecal specimens were detected in apparently healthy children, which harbored low abundance, through meta-transcriptome sequencing. Based on the prototypes of several EV-Cs, two lineages were observed. Lineage 1 included many types that could not cause EV-like cytopathic effect in cell culture. Three genogroups of EV-C116 were divided in the maximum likelihood tree, and the two strains in this study (XZ2 and XZ113) formed two different lineages, suggesting that EV-C116 still diffuses worldwide. Obvious inter-type recombination events were observed in the XZ2 strain, with CVA22 identified as a minor donor. However, another strain (XZ113) underwent different recombination situations, highlighting the importance of recombination in the formation of EV-Cs biodiversity. The EV-C116 strains could propagate in rhabdomyosarcoma cell cultures at low titer; however, EV-like cytopathic effects were not observed. HEp-2, L20B, VERO, and 293T cell lines did not provide an appropriate environment for EV-C116 growth. These results challenge the traditional recognition of the uncultured nature of EV-C116 strains and explain the difficulty of clinical detection.

Spinal nerve transection-induced upregulation of SAP97 via promoting membrane trafficking of GluA1-containing AMPA receptors in the dorsal horn contributes to the pathogenesis of neuropathic pain.

Emerging evidence has implicated an important role of synapse-associated protein-97 (SAP97)-regulated GluA1-containing AMPARs membrane trafficking in cocaine restate and in contextual episodic memory of schizophrenia. Herein, we investigated the role of SAP97 in neuropathic pain following lumbar 5 spinal nerve transection (SNT) in rats. Our results showed that SNT led to upregulation of SAP97, enhanced the interaction between SAP97 and GluA1, and increased GluA1-containing AMPARs membrane trafficking in the dorsal horn. Microinjection of AAV-EGFP-SAP97 shRNA in lumbar 5 spinal dorsal horn inhibited SAP97 production, decreased SAP97-GluA1 interaction, reduced the membrane trafficking of GluA1-containing AMPARs, and partially attenuated neuropathic pain following SNT. Intrathecal injections of SAP97 siRNA or NASPM, an antagonist of GluA1-containing AMPARs, also partially reversed neuropathic pain on day 7, but not on day 14, after SNT. Spinal overexpression of SAP97 by AAV-EGFP-SAP97 enhanced SAP97-GluA1 interaction, increased the membrane insertion of GluA1-containing AMPARs, and induced abnormal pain in naïve rats. In addition, treatment with SAP97 siRNA or NASPM i.t. injection alleviated SNT-induced allodynia and hyperalgesia and exhibited a longer effect in female rats. Together, our results indicate that the SNT-induced upregulation of SAP97 via promoting GluA1-containing AMPARs membrane trafficking in the dorsal horn contributes to the pathogenesis of neuropathic pain. Targeting spinal SAP97 might be a promising therapeutic strategy to treatment of chronic pain.

Sensitive, Robust, Wide-Range, and High-Consistency Capacitive Tactile Sensors with Ordered Porous Dielectric Microstructures.

Flexible capacitive tactile sensors show great promise in personalized healthcare monitoring and human-machine interfaces, but their practical application is normally hindered because they rarely possess the required comprehensive performance, that is, high pressure sensitivity and fast response within a broad pressure range, high structure robustness, performance consistency, etc. This paper aims to engineer flexible capacitive pressure sensors with highly ordered porous dielectric microstructures and a 3D-printing-based fully solution-processable fabrication process. The proposed dielectric layer with uniformly distributed interior microporous can not only increase its compressibility and dynamic response within an extended pressure range but also enlarge its contact area with electrodes, contributing to a simultaneous improvement in the sensitivity, response speed, detection range, and structure robustness. Meanwhile, owing to its superior abilities in complex structure manufacturing and dimension controlling, the proposed 3D-printing-based fabrication process enables the consistent fabrication of the porous microstructure and thus guarantees device consistency. As a result, the prepared pressure sensors exhibit a high sensitivity of 0.21 kPa-1, fast response and relaxation times of 112 and 152 ms, an interface bonding strength of more than 455.2 kPa, and excellent performance consistency (≤5.47% deviation among different batches of sensors) and tunability. Encouraged by this, the pressure sensor is further integrated with a wireless readout circuit and realizes wireless wearable monitoring of various biosignals (pulse waves and heart rate) and body movements (from slight finger touch to large knee bending). Finally, the influence law of the feature parameters of the porous microstructure on device performance is established by the finite element method, paving the way for sensor optimization. This study motivates the development of flexible capacitive pressure sensors toward practical application.

Self-Healing Hydrogel Bioelectronics.

Hydrogels have emerged as powerful building blocks to develop various soft bioelectronics because of their tissue-like mechanical properties, superior bio-compatibility, the ability to conduct both electrons and ions, and multiple stimuli-responsiveness. However, hydrogels are vulnerable to mechanical damage, which limits their usage in developing durable hydrogel-based bioelectronics. Self-healing hydrogels aim to endow bioelectronics with the property of repairing specific functions after mechanical failure, thus improving their durability, reliability, and longevity. This review discusses recent advances in self-healing hydrogels, from the self-healing mechanisms, material chemistry, and strategies for multiple properties improvement of hydrogel materials, to the design, fabrication, and applications of various hydrogel-based bioelectronics, including wearable physical and biochemical sensors, supercapacitors, flexible display devices, triboelectric nanogenerators (TENGs), implantable bioelectronics, etc. Furthermore, the persisting challenges hampering the development of self-healing hydrogel bioelectronics and their prospects are proposed. This review is expected to expedite the research and applications of self-healing hydrogels for various self-healing bioelectronics.

Rab27a-mediated exosome secretion in anterior cingulate cortex contributes to colorectal visceral pain in adult mice with neonatal maternal deprivation.

Chronic visceral pain is a common symptom of irritable bowel syndrome (IBS). Exosomes are involved in the development of pain. Rab27a can mediate the release of exosomes. The purpose of this study is to investigate how Rab27a-mediated exosome secretion in the anterior cingulate cortex (ACC) regulates visceral hyperalgesia induced with neonatal maternal deprivation (NMD) in adult mice. The colorectal distension method was adopted to measure visceral pain. The BCA protein assay kit was applied to detect the exosome protein concentration. Western blotting, quantitative PCR, and immunofluorescence technique were adopted to detect the expression of Rab27a and the markers of exosomes. Exosomes extracted from ACC were more in NMD mice than in control (CON) mice. Injection of the exosome-specific inhibitor GW4869 in ACC attenuated colorectal visceral pain of NMD mice. Injection of NMD-derived exosomes produced colorectal visceral pain in CON mice. Rab27a was upregulated in ACC of NMD mice. Rab27a was highly expressed in ACC neurons of NMD mice, rather than astrocytes and microglia. Injection of Rab27a-siRNA reduced the release of exosomes and attenuated the colorectal visceral pain in NMD mice. This study suggested that overexpression of Rab27a increased exosome secretion in ACC neurons, thus contributing to visceral hyperalgesia in NMD mice.NEW & NOTEWORTHY This work demonstrated that the expression of Rab27a in the anterior cingulate cortex was upregulated, which mediated multivesicular bodies trafficking to the plasma membrane and led to the increased release of neuronal exosomes, thus contributing to colorectal visceral pain in neonatal maternal deprivation (NMD) mice. Blocking the release of exosomes or downregulation of Rab27a could alleviate colorectal visceral pain in NMD mice. These data may provide a promising strategy for the treatment of visceral pain in irritable bowel syndrome patients.

Neuralized1-Mediated CPEB3 Ubiquitination in the Spinal Dorsal Horn Contributes to the Pathogenesis of Neuropathic Pain in Rats.

Compelling evidence has shown that Neuralized1 (Neurl1) facilitates hippocampal-dependent memory storage by modulating cytoplasmic polyadenylation element-binding protein 3 (CPEB3)-dependent protein synthesis. In the current study, we investigated the role of Neurl1 in the pathogenesis of neuropathic pain and the underlying mechanisms. The neuropathic pain was evaluated by lumbar 5 spinal nerve ligation (SNL) in rats. Immunofluorescence staining, Western blotting, qRT-PCR, and coimmunoprecipitation (Co-IP) were performed to investigate the underlying mechanisms. Our results showed that SNL led to an increase of Neurl1 in the spinal dorsal horn. Spinal microinjection of AAV-EGFP-Neurl1 shRNA alleviated mechanical allodynia; decreased the level of CPEB3 ubiquitination; inhibited the production of GluA1, GluA2, and PSD95; and reduced GluA1-containing AMPA receptors in the membrane of the dorsal horn following SNL. Knockdown of spinal CPEB3 decreased the production of GluA1, GluA2, and PSD95 in the dorsal horn and attenuated abnormal pain after SNL. Overexpression of Neurl1 in the dorsal horn resulted in pain-related hypersensitivity in naïve rats; raised the level of CPEB3 ubiquitination; increased the production of GluA1, GluA2, and PSD95; and augmented GluA1-containing AMPA receptors in the membrane in the dorsal horn. Moreover, spinal Neurl1 overexpression-induced mechanical allodynia in naïve rats was partially reversed by repeated intrathecal injections of CPEB3 siRNA. Collectively, our results suggest that SNL-induced upregulation of Neurl1 through CPEB3 ubiquitination-dependent production of GluA1, GluA2, and PSD95 in the dorsal horn contributes to the pathogenesis of neuropathic pain in rats. Targeting spinal Neurl1 might be a promising therapeutic strategy for the treatment of neuropathic pain.

Upregulation of lysine-specific demethylase 6B aggravates inflammatory pain through H3K27me3 demethylation-dependent production of TNF-α in the dorsal root ganglia and spinal dorsal horn in rats.

AIMS: Lysine-specific demethylase 6B (KDM6B) serves as a key mediator of gene transcription. It regulates expression of proinflammatory cytokines and chemokines in variety of diseases. Herein, the role and the underlying mechanisms of KDM6B in inflammatory pain were studied. METHODS: The inflammatory pain was conducted by intraplantar injection of complete Freund's adjuvant (CFA) in rats. Immunofluorescence, Western blotting, qRT-PCR, and chromatin immunoprecipitation (ChIP)-PCR were performed to investigate the underlying mechanisms. RESULTS: CFA injection led to upregulation of KDM6B and decrease in the level of H3K27me3 in the dorsal root ganglia (DRG) and spinal dorsal horn. The mechanical allodynia and thermal hyperalgesia following CFA were alleviated by the treatment of intrathecal injection of GSK-J4, and by microinjection of AAV-EGFP-KDM6B shRNA in the sciatic nerve or in lumbar 5 dorsal horn. The increased production of tumor necrosis factor-α (TNF-α) following CFA in the DRGs and dorsal horn was inhibited by these treatments. ChIP-PCR showed that CFA-induced increased binding of nuclear factor κB with TNF-α promoter was repressed by the treatment of microinjection of AAV-EGFP-KDM6B shRNA. CONCLUSIONS: These results suggest that upregulated KDM6B via facilitating TNF-α expression in the DRG and spinal dorsal horn aggravates inflammatory pain.

Genome editing HLA alleles for a pilot immunocompatible hESC line in a Chinese hESC bank for cell therapies.

Robust allogeneic immune reactions after transplantation impede the translational pace of human embryonic stem cells (hESCs)-based therapies. Selective genetic editing of human leucocyte antigen (HLA) molecules has been proposed to generate hESCs with immunocompatibility, which, however, has not been specifically designed for the Chinese population yet. Herein, we explored the possibility of customizing immunocompatible hESCs based on Chinese HLA typing characteristics. We generated an immunocompatible hESC line by disrupting HLA-B, HLA-C, and CIITA genes while retaining HLA-A*11:01 (HLA-A*11:01-retained, HLA-A11R ), which covers ~21% of the Chinese population. The immunocompatibility of HLA-A11R hESCs was verified by in vitro co-culture and confirmed in humanized mice with established human immunity. Moreover, we precisely knocked an inducible caspase-9 suicide cassette into HLA-A11R hESCs (iC9-HLA-A11R ) to promote safety. Compared with wide-type hESCs, HLA-A11R hESC-derived endothelial cells elicited much weaker immune responses to human HLA-A11+ T cells, while maintaining HLA-I molecule-mediated inhibitory signals to natural killer (NK) cells. Additionally, iC9-HLA-A11R hESCs could be induced to undergo apoptosis efficiently by AP1903. Both cell lines displayed genomic integrity and low risks of off-target effects. In conclusion, we customized a pilot immunocompatible hESC cell line based on Chinese HLA typing characteristics with safety insurance. This approach provides a basis for establishment of a universal HLA-AR bank of hESCs covering broad populations worldwide and may speed up the clinical application of hESC-based therapies.

The incremental significance of heart rate recovery as a predictor during exercise-stress myocardial perfusion SPECT imaging in individuals with suspected coronary artery disease.

Background: Major adverse cardiac events (MACE) are more likely to occur when abnormal heart rate recovery (HRR). This study aimed to assess the incremental predictive significance of HRR over exercise stress myocardial perfusion single-photon emission computed tomography (MPS) results for MACE in individuals with suspected coronary artery disease (CAD). Methods: Between January 2014 and December 2017, we continually gathered data on 595 patients with suspected CAD who received cycling exercise stress MPS. HRR at 1, 2, 3, and 4 min were used as study variables to obtain the optimal cut-off values of HRR for MACE. The difference between the peak heart rate achieved during exercise and the heart rate at 1, 2, 3, and 4 min was used to calculate the HRR, as shown in HRR3. Heart rate variations between two locations in time, such as HRR2 min-1 min, were used to establish the slope of HRR. All patients were followed for a minimum of 4 years, with MACE as the follow-up goal. The associations between HRR and MACE were assessed using Cox proportional hazards analyses. Results: Patients with MACE were older (P = 0.001), and they also had higher rates of hypertension, dyslipidemia, diabetes, abnormal MPS findings (SSS ≥ 5%), medication history (all P < 0.001), and lower HRR values (all P < 0.01). Patients with and without MACE did not significantly vary in their HRR4 min-3 min. The optimal cut-off of HRR1, 2, and 3 combined with SSS can stratify the risk of MACE in people with suspected CAD (all P < 0.001). HRR 1, 2, and 3 and its slope were linked to MACE in multivariate analysis, where HRR3 was the most significant risk predictor. With a global X2 increase from 101 to 126 (P < 0.0001), HRR3 demonstrated the greatest improvement in the model's predictive capacity, incorporating clinical data and MPS outcomes. Conclusions: HRR at 3 min has a more excellent incremental prognostic value for predicting MACE in patients with suspected CAD following cycling exercise stress MPS. Therefore, incorporating HRR at 3 min into known predictive models may further improve the risk stratification of the patients.

DNMT1 involved in the analgesic effect of folic acid on gastric hypersensitivity through downregulating ASIC1 in adult offspring rats with prenatal maternal stress.

AIMS: Gastric hypersensitivity (GHS) is a characteristic pathogenesis of functional dyspepsia (FD). DNA methyltransferase 1 (DNMT1) and acid-sensing ion channel 1 (ASIC1) are associated with GHS induced by prenatal maternal stress (PMS). The aim of this study was to investigate the mechanism of DNMT1 mediating the analgesic effect of folic acid (FA) on PMS-induced GHS. METHODS: GHS was quantified by electromyogram recordings. The expression of DNMT1, DNMT3a, DNMT3b, and ASIC1 were detected by western blot, RT-PCR, and double-immunofluorescence. Neuronal excitability and proton-elicited currents of dorsal root ganglion (DRG) neurons were determined by whole-cell patch clamp recordings. RESULTS: The expression of DNMT1, but not DNMT3a or DNMT3b, was decreased in DRGs of PMS rats. FA alleviated PMS-induced GHS and hyperexcitability of DRG neurons. FA also increased DNMT1 and decreased ASIC1 expression and sensitivity. Intrathecal injection of DNMT1 inhibitor DC-517 attenuated the effect of FA on GHS alleviation and ASIC1 downregulation. Overexpression of DNMT1 with lentivirus not only rescued ASIC1 upregulation and hypersensitivity, but also alleviated GHS and hyperexcitability of DRG neurons induced by PMS. CONCLUSIONS: These results indicate that increased DNMT1 contributes to the analgesic effect of FA on PMS-induced GHS by reducing ASIC1 expression and sensitivity.

The remarkable enhancement of photo-stability and antioxidant protection of lutein coupled with carbon-dot.

Lutein is a carotenoid that is beneficial to human health. However, its low stability and bioavailability have limited its application in the pharmaceutical and food industries. Herein, lutein has been successfully modified with carbon-dots (CDs) via a simple and mild solvent-ultrasonic method at room temperature. The synthesized lutein/CDs composites (LCs) showed 3.4 times higher photostability than the pristine lutein under UV irradiation, and 3.5 times higher than that under visible light, and the retention rate of lutein in the air rose from 3.6 % to 68 % over 25 days. Meanwhile, the antioxidant capacity of lutein has been improved by 6.4 times. Based on the photoluminescence (PL) measurements, a possible mechanism for the enhanced photostability and antioxidant ability of LCs has been proposed. The work provides a simple but effective approach to enhancing the stability and antioxidant capacity of lutein, and is expected to extend its application in food and biomedical fields.

A Tale of Two Social Insurance Systems in South Korea and Taiwan: A Financial Risk Protection Perspective.

Universal Health Coverage (UHC) is a widespread policy goal in the 21st century. The aim is to protect people from financial risk while promoting their access to good-quality care. This study examined the social insurance systems of South Korea and Taiwan to explore the critical challenges of achieving effective UHC. By assessing the impact of UHC on financial risk protection (measured by out-of-pocket payment share and catastrophic payment headcount), we found that when South Korea inaugurated its National Health Insurance (NHI) program with a limited benefits package and high cost sharing, it did not reduce the financial burden. Meanwhile, we observed a drop of 5 to 6 percentage points in the catastrophic payment headcount in Taiwan, which offered a universal and rather comprehensive benefits package with a modest cost-sharing design under its single-payer NHI system. The political-economic context of the UHC policy evolution was further explored through an in-depth discussion. We conclude that to provide sufficient financial risk protection against unexpected medical expenses, the design of the insurance scheme, in particular the risk-sharing mechanism, not only matters but is also the key to success.