Self-Aligned Ionic Doping of TiO2 Thin-Film Transistors for Enhanced Current Drivability via Postfabrication Superacid Treatment.

Oxide semiconductor thin-film transistors (TFTs) have shown great potential in emerging applications such as flexible displays, radio-frequency identification tags, sensors, and back-end-of-line compatible transistors for monolithic 3D integration beyond their well-established flat-plane display technology. To meet the requirements of these appealing applications, high current drivability is essential, necessitating exploration in materials science and device engineering. In this work, we report for the first time on a simple solution-based superacid (SA) treatment to enhance the current drivability of top-gate TiO2 TFTs with a gate-offset structure. The on-current of these transistors is limited by the relatively low mobility of TiO2 due to its d-orbital conduction nature. It is found that the on-current of TiO2 TFTs is nearly doubled via a quick dip in a SA solution at room temperature in ambient air. A series of experiments, including comparative I-V measurements of TFTs with different treatments and gate structures, C-V measurements, X-ray photoelectron spectroscopy, time-of-flight secondary ion mass spectrometry, and device simulation, were performed to uncover the underlying reason for the current enhancement. It is believed that the protons (H+) from SA are doped into the offset region of TiO2 TFTs, forming an electron double layer and thus boosting the on-current, with the top gate serving as a self-aligned mask for ionic doping. Furthermore, the ionic size and the proportion of the offset region to the channel play crucial roles in the effectiveness of ionic doping, while the position of the incorporated ions, whether in the channel or dielectric, may result in distinct shifts in the turn-on voltage (VON) and affect the functionality of ionic doping. This study provides a pathway for enhancing the current drivability of TiO2 TFTs via selective ionic doping enabled by SA treatment and deepens our understanding of ion incorporation in electronic devices. This approach could be applicable to other material systems and may also benefit TFTs with miniaturized dimensions, thus opening up unprecedented opportunities for TiO2 TFTs in future applications requiring high current drivability.

Dissecting the causal links between gut microbiome, immune traits and polyp using genetic evidence.

Background: Previous research has demonstrated an association between gut microbiota and immune status with the development of several diseases. However, whether these factors contribute to polyps remains unclear. This study aims to use Mendelian randomization (MR) to investigate the causal relationship between gut microbiota and 4 types of polyps (nasal, gallbladder, colon, and gastric polyps), as well as to analyze the mediating role of immune traits. Methods: This study utilized large-scale GWAS meta-analyses of gut microbiota (MiBioGen Consortium), 731 immune traits, and 4 types of polyps (one from the FinnGen Consortium and three from the NBDC Human Database). Univariate MR with the inverse variance weighted (IVW) estimation method was employed as the primary analytical approach. A two-step MR analysis was performed to identify potential mediating immune traits. Additionally, multivariable MR approach based on Bayesian model averaging (MR-BMA) was employed to further prioritize gut microbiota and immune traits associated with polyp development. Results: Based on IVW method in univariate MR analysis, we identified 39 gut microbial taxa and 135 immune traits significantly causally associated with at least one type of polyp. For nasal polyps, 13 microbial taxa and 61 immune traits were causally associated. After false discovery rate (FDR) correction, CD3 on Central Memory CD8+ T cells and CD3 on CD4 regulatory T cells remained significant. MR-BMA identified 4 gut microbial taxa and 4 immune traits as high priority. For gallbladder polyps, 9 microbial taxa and 30 immune traits were causally associated. MR-BMA identified 8 microbial taxa and 6 immune traits as higher importance. For colon polyps, 6 microbial taxa and 21 immune traits were causally associated. MR-BMA identified 4 microbial taxa and 3 immune traits as higher importance. For gastric polyps, 12 microbial taxa and 33 immune traits were causally associated. Actinobacteria remained significant after FDR correction, and MR-BMA identified 7 gut microbial taxa and 6 immune traits as high priority. We identified 16 causal pathways with mediator directions consistent with the direction of gut microbiome-polyp association. Of these, 6 pathways were associated with the mechanism of nasal polyps, 1 with gallbladder polyps, 2 with colon polyps, and 7 with gastric polyps. Conclusions: Our findings shed light on the causal relationships between gut microbiota, immune traits, and polyp development, underscoring the crucial roles of gut microbiota and immune status in polypogenesis. Furthermore, these findings suggest potential applications in polyp prevention, early screening, and the development of effective strategies to reduce polyp risk.

Short-chain fatty acids regulate erastin-induced cardiomyocyte ferroptosis and ferroptosis-related genes.

Background: Ferroptosis has been proven to contribute to the progression of myocardial ischemia/reperfusion (I/R) injury and can be inhibited or promoted by ATF3. Short-chain fatty acids (SCFAs) have shown benefits in various cardiovascular diseases with anti-inflammatory and antioxidant effects. However, the impact of SCFAs on ferroptosis in ischemic-stimulated cardiomyocytes remains unknown. This study aimed to investigate the effect of SCFAs on cardiomyocyte ferroptosis, the expression of ATF3, and its potential upstream regulators. Methods and results: The expression of ATF3, ferroptosis pathway geneset (FPG), and geneset of potential regulators for ATF3 (GPRA, predicted by the PROMO database) was explored in the public human myocardial infarction single-cell RNA-seq (sma) dataset. Cardiomyocyte data was extracted from the dataset and re-clustered to explore the FPG, ATF3, and GPRA expression patterns in cardiomyocyte subclusters. A dose-dependent toxic experiment was run to detect the suitable dose for SCFA treatment. The erastin-induced ferroptosis model and hypoxia-reoxygenation (H/R) model (10 h of hypoxia followed by 6 h of reoxygenation) were adopted to assess the effect of SCFAs via the CCK8 assay. Gene expression was examined via RT-PCR and western blot. Ferroptosis markers, including lipid peroxides and Fe2+, were detected using the liperfluo and ferroOrange probes, respectively. In the sma dataset, upregulated ferroptosis pathway genes were mainly found in the infarction-stimulated cardiac cells (border zone and fibrotic zone), particularly the cardiomyocytes and adipocytes. The ATF3 and some of its potential transcription factors (VDR, EGR3, PAX5, and SP1) can be regulated by SCFA. SCFA can attenuate erastin-induced lipid peroxidation in cardiomyocytes. SCFA treatment can also reverse erastin-induced Fe2+ increase but may strengthen the Fe2+ in the H/R model. We also precisely defined a ferroptosis subcluster of cardiomyocytes (CM09) that highly expressed FPG, ATF3, and GPRA. Conclusion: The ATF3 and the ferroptosis pathway are elevated in cardiomyocytes of injury-related cardiac regions (border zone, ischemic zone, and fibrotic zone). SCFA can attenuate cardiomyocyte ferroptosis and regulate the expression of ATF3. Our study offers novel insights into the potential targets of SCFAs in the cardiovascular system.

Application of nanomaterials in heart transplantation: a narrative review.

Background and Objective: Heart transplantation (HT) is a therapeutic option for end-stage heart disease. Still, it faces many challenges, especially the shortage of donor sources and the poor durability of grafts, which are the two critical issues. In this review, we generalize the application of existing nanomedicine technologies in donor management as well as prevention and diagnosis of post-transplantation complications, also including the current preclinical studies of nanomaterials in cardiac tissue engineering and gene-editing xeno-donor grafts. Finally, we discuss the remaining problems and future directions of nanomaterials in the field of HT. Methods: A narrative review using current search of the most recent literature on the topic. The terms "nanomaterials", "nano medicine'', "Heart transplantation (HT)", "Nano-drug delivery system (NDDS)" or their combination were searched in PubMed and Google Scholar. The specified timeframe began from 1990, and we prioritized publications mainly from the last 10 years. Key Content and Findings: Nano-systems integrating therapeutic and diagnostic functions have been applied to cardiovascular diseases (CVDs) with their unique advantages in multiple fields such as drug delivery, tissue engineering, gene editing, imaging, biomarker editing, and many other aspects. In terms of transplantation, the preservation, transportation, and pretreatment of donor hearts machine perfusion (MP) provide the possibility for nano-systems with unique features, and therapeutic and diagnostic functions to be directly and passively targeted in order to improve the functional status of the transplanted organs or to increase the ability to tolerate the graft of patients. The development of nano-imaging, nanosensor, and nano biomarker technologies are also being applied to monitor the status of transplant recipients for early prevention and treatment of post-transplantation-related complications. Nanomaterials combined with cardiac tissue engineering and gene editing technologies could also expand graft sources and alleviate donor shortages. Conclusions: Although the overall research on nanomaterial applications in the field of HT is in its infancy, its role in improving the prognosis of transplant recipients and breaking the current dilemma of HT is clear. However, before nanotechnologies can be translated into clinical applications in the future, they must be aimed at ensuring the drug delivery system's safety and pose a challenge in the direction of the ability to intervene with multiple drugs in combination.

Integrated oral microgel system ameliorates renal fibrosis by hitchhiking co-delivery and targeted gut flora modulation.

BACKGROUND: Renal fibrosis is a progressive process associated with chronic kidney disease (CKD), contributing to impaired kidney function. Active constituents in traditional Chinese herbs, such as emodin (EMO) and asiatic acid (AA), exhibit potent anti-fibrotic properties. However, the oral administration of EMO and AA results in low bioavailability and limited kidney accumulation. Additionally, while oral probiotics have been accepted for CKD treatment through gut microbiota modulation, a significant challenge lies in ensuring their viability upon administration. Therefore, our study aims to address both renal fibrosis and gut microbiota imbalance through innovative co-delivery strategies. RESULTS: In this study, we developed yeast cell wall particles (YCWPs) encapsulating EMO and AA self-assembled nanoparticles (NPYs) and embedded them, along with Lactobacillus casei Zhang, in chitosan/sodium alginate (CS/SA) microgels. The developed microgels showed significant controlled release properties for the loaded NPYs and prolonged the retention time of Lactobacillus casei Zhang (L. casei Zhang) in the intestine. Furthermore, in vivo biodistribution showed that the microgel-carried NPYs significantly accumulated in the obstructed kidneys of rats, thereby substantially increasing the accumulation of EMO and AA in the impaired kidneys. More importantly, through hitchhiking delivery based on yeast cell wall and positive modulation of gut microbiota, our microgels with this synergistic strategy of therapeutic and modulatory interactions could regulate the TGF-ß/Smad signaling pathway and thus effectively ameliorate renal fibrosis in unilateral ureteral obstruction (UUO) rats. CONCLUSION: In conclusion, our work provides a new strategy for the treatment of renal fibrosis based on hitchhiking co-delivery of nanodrugs and probiotics to achieve synergistic effects of disease treatment and targeted gut flora modulation.

Neuroprotective effects of anti-TRAIL-ICG nanoagent and its multimodal imaging evaluation in cerebral ischemia-reperfusion injury.

Cerebral ischemia-reperfusion injury (CIRI) is a major challenge to neuronal survival in acute ischemic stroke (AIS). However, effective neuroprotective agents remain to be developed for the treatment of CIRI. In this work, we have developed an Anti-TRAIL protein-modified and indocyanine green (ICG)-responsive nanoagent (Anti-TRAIL-ICG) to target ischemic areas and then reduce CIRI and rescue the ischemic penumbra. In vitro and in vivo experiments have demonstrated that the carrier-free nanoagent can enhance drug transport across the blood-brain barrier (BBB) in stroke mice, exhibiting high targeting ability and good biocompatibility. Anti-TRAIL-ICG nanoagent played a better neuroprotective role by reducing apoptosis and ferroptosis, and significantly improved ischemia-reperfusion injury. Moreover, the multimodal imaging platform enables the dynamic in vivo examination of multiple morphofunctional information, so that the dynamic molecular events of nanoagent can be detected continuously and in real time for early treatment in transient middle cerebral artery occlusion (tMCAO) models. Furthermore, it has been found that Anti-TRAIL-ICG has great potential in the functional reconstruction of neurovascular networks through optical coherence tomography angiography (OCTA). Taken together, our work effectively alleviates CIRI after stoke by blocking multiple cell death pathways, which offers an innovative strategy for harnessing the apoptosis and ferroptosis against CIRI.

Huang Qin decoction increases SLC6A4 expression and blocks the NFκB-mediated NLRP3/Caspase1/GSDMD pathway to disrupt colitis-associated carcinogenesis.

Huang Qin decoction (HQD) is a traditional Chinese medicine formula for treating colitis, but the effects and molecular mechanism of action of HQD in colitis-associated carcinogenesis (CAC) are still unclear. Therefore, we aimed to determine the beneficial effects of HQD on CAC in mice and to reveal the underlying mechanism involved. AOM/DSS was used to induce CAC in mice, and the effects of HQD on tumorigenesis in mice were examined (with mesalazine serving as a positive control). Mesalazine or HQD treatment alleviated body weight loss and decreased the disease activity index in mice induced by AOM/DSS. Mesalazine or HQD treatment also suppressed the shortening of colon tissue length, the number of tumors, and the infiltration of inflammatory cells. The genes targeted by HQD were predicted and verified, followed by knockout experiments. Elevated SLC6A4 and inhibited serotonin production and inflammation were observed in HQD-treated mice. HQD inhibited the NFκB and NLRP3/caspase1/GSDMD pathways. The therapeutic effect of HQD was diminished in SLC6A4-deficient AOM/DSS mice. Additionally, the downregulation of SLC6A4 mitigated the inhibitory effect of HQD-containing serum on MODE-K cell pyroptosis. Our findings suggest that SLC6A4 is a pivotal regulator of HQD-alleviated CAC via its modulation of the NLRP3/caspase1/GSDMD pathway.

Effect of NiO Addition on the Sintering and Electrochemical Properties of BaCe0.55Zr0.35Y0.1O3-δ Proton-Conducting Ceramic Electrolyte.

Proton ceramic fuel cells offer numerous advantages compared with conventional fuel cells. However, the practical implementation of these cells is hindered by the poor sintering activity of the electrolyte. Despite extensive research efforts to improve the sintering activity of BCZY, the systematic exploration of the utilization of NiO as a sintering additive remains insufficient. In this study, we developed a novel BaCe0.55Zr0.35Y0.1O3-δ (BCZY) electrolyte and systematically investigated the impact of adding different amounts of NiO on the sintering activity and electrochemical performance of BCZY. XRD results demonstrate that pure-phase BCZY can be obtained by sintering the material synthesized via solid-state reaction at 1400 °C for 10 h. SEM analysis revealed that the addition of NiO has positive effects on the densification and grain growth of BCZY, while significantly reducing the sintering temperature required for densification. Nearly fully densified BCZY ceramics can be obtained by adding 0.5 wt.% NiO and annealing at 1350 °C for 5 h. The addition of NiO exhibits positive effects on the densification and grain growth of BCZY, significantly reducing the sintering temperature required for densification. An anode-supported full cell using BCZY with 0.5 wt.% NiO as the electrolyte reveals a maximum power density of 690 mW cm-2 and an ohmic resistance of 0.189 Ω cm2 at 650 °C. Within 100 h of long-term testing, the recorded current density remained relatively stable, demonstrating excellent electrochemical performance.

Design of a Zn-based nanozyme injectable multifunctional hydrogel with ROS scavenging activity for myocardial infarction therapy.

The existing strategies for myocardial infarction therapy mainly focus on reinstating myocardial blood supply, often disregarding the intrinsic and intricate microenvironment created by elevated levels of reactive oxygen species (ROS) that accompanies myocardial infarction. This microenvironment entails cardiomyocytes apoptosis, substantial vascular cell death, excessive inflammatory infiltration and fibrosis. In such situation, the present study introduces a zinc-based nanozyme injectable multifunctional hydrogel, crafted from ZIF-8, to counteract ROS effects after myocardial infarction. The hydrogel exhibits both superoxide dismutase (SOD)-like and catalase (CAT)-like enzymatic activities, proficiently eliminating surplus ROS in the infarcted region and interrupting ROS-driven inflammatory cascades. Furthermore, the hydrogel's exceptional immunomodulatory ability spurs a notable transformation of macrophages into the M2 phenotype, effectively neutralizing inflammatory factors and indirectly fostering vascularization in the infarcted region. For high ROS and demanding for zinc of the infarcted microenvironment, the gradual release of zinc ions as the hydrogel degrades further enhances the bioactive and catalytic performance of the nanozymes, synergistically promoting cardiac function post myocardial infarction. In conclusion, this system of deploying catalytic nanomaterials within bioactive matrices for ROS-related ailment therapy not only establishes a robust foundation for biomedical material development, but also promises a holistic approach towards addressing myocardial infarction complexities. STATEMENT OF SIGNIFICANCE: Myocardial infarction remains the leading cause of death worldwide. However, the existing strategies for myocardial infarction therapy mainly focus on reinstating myocardial blood supply. These therapies often ignore the intrinsic and intricate microenvironment created by elevated levels of reactive oxygen species (ROS). Hence, we designed an injectable Zn-Based nanozyme hydrogel with ROS scavenging activity for myocardial infarction therapy. ALG-(ZIF-8) can significantly reduce ROS in the infarcted area and alleviate the ensuing pathological process. ALG-(ZIF-8) gradually releases zinc ions to participate in the repair process and improves cardiac function. Overall, this multifunctional hydrogel equipped with ZIF-8 makes full use of the characteristics of clearing ROS and slowly releasing zinc ions, and we are the first to test the therapeutic efficacy of Zinc-MOFs crosslinked-alginate hydrogel for myocardial infarction.

An Intrinsically Magnetic Epicardial Patch for Rapid Vascular Reconstruction and Drug Delivery.

Myocardial infarction (MI) is a major cause of mortality worldwide. The major limitation of regenerative therapy for MI is poor cardiac retention of therapeutics, which results from an inefficient vascular network and poor targeting ability. In this study, a two-layer intrinsically magnetic epicardial patch (MagPatch) prepared by 3D printing with biocompatible materials like poly (glycerol sebacate) (PGS) is designed, poly (ε-caprolactone) (PCL), and NdFeB. The two-layer structure ensured that the MagPatch multifariously utilized the magnetic force for rapid vascular reconstruction and targeted drug delivery. MagPatch accumulates superparamagnetic iron oxide (SPION)-labelled endothelial cells, instantly forming a ready-implanted organization, and rapidly reconstructs a vascular network anastomosed with the host. In addition, the prefabricated vascular network within the MagPatch allowed for the efficient accumulation of SPION-labelled therapeutics, amplifying the therapeutic effects of cardiac repair. This study defined an extendable therapeutic platform for vascularization-based targeted drug delivery that is expected to assist in the progress of regenerative therapies in clinical applications.

Localized delivery of anti-inflammatory agents using extracellular matrix-nanostructured lipid carriers hydrogel promotes cardiac repair post-myocardial infarction.

A challenge in treating cardiac injury is the low heart-specificity of the drugs. Nanostructured lipid carriers (NLCs) are a relatively new format of lipid nanoparticles which have been used to deliver RNA and drugs. However, lipid nanoparticles exhibit higher affinity to the liver than the heart. To improve the delivery efficiency of NLCs into the heart, NLCs can be embedded into a scaffold and be locally released. In this study, a cardiac extracellular matrix (ECM) hydrogel-NLC composite was developed as a platform for cardiac repair. ECM-NLC composite gels at physiological conditions and releases payloads into the heart over weeks. ECM-NLC hydrogel carrying colchicine, an anti-inflammation agent, improved cardiac repair after myocardial infarction in mice. Transcriptome analysis indicated that Egfr downstream effectors participated in ECM-NLC-colchicine induced heart repair. In conclusion, ECM-NLC hydrogel is a potential platform for sustained and localized delivery of biomolecules into the heart, and loading appropriate medicines further increases the therapeutic efficacy of ECM-NLC hydrogel for cardiovascular diseases.

Risk factors for major adverse cardiovascular events after coronary artery bypass grafting using radial artery grafts.

Background: Coronary artery bypass grafting using radial artery grafts (RA-CABG) has improved long-term outcomes. However, major adverse cardiovascular events (MACE-4, including all-cause death, myocardial infarction, stroke, and repeat revascularization) after RA-CABG still occur and the predictors remain uncertain. This study aimed to detect independent risk factors of MACE-4 after RA-CABG. Methods: This is a retrospective case-control study (NCT04935086) conducted among patients who underwent primary isolated RA-CABG between 2009 and 2019 in our center. Baseline characteristics, procedure characteristics, and medication use were compared to identify the independent predictors of MACE-4, all-cause death, and myocardial infarction (MI) with univariate and then multivariate logistic regression. Results: A total of 370 patients were analyzed using a mean follow-up duration of 48.8 ± 41.0 months. MACE-4, all-cause death, and MI occurred in 102 (27.6%), 27 (7.3%), and 66 patients (17.8%), respectively. Multivariate analysis revealed prior MI (OR = 2.12, 95%CI 1.05-4.25, P = 0.04) and RA to the left anterior descending artery (LAD) (non-left internal mammary artery to LAD) (OR = 4.87, 95%CI 1.41-16.82, P = 0.01) as independent predictors of MACE-4 after surgery. Female (OR = 4.53, 95%CI 1.06-19.41, P = 0.04), left ventricular ejection fraction (LVEF) <40% (OR = 21.00, 95%CI 1.20-368.35, P = 0.04), and RA to LAD (OR = 8.55, 95%CI 1.35-54.10, P = 0.02) were independent predictors of all-cause death. Prior MI (OR = 3.11, 95%CI 1.40-6.94, P = 0.006) emerged as an independent predictor of MI. Conclusion: Our data suggested that prior MI and RA to LAD were independent predictors of MACE-4 after RA-CABG. Being female, having an LVEF < 40% and RA to LAD indicated death. Prior MI indicated new MI.

Highly Stable Protonic Ceramic Electrolysis Cells Based on Air Electrodes with Finger-Like Pores Current Collection Layers Running in High-Steam-Content Air.

The steam content in the air electrode is one of the major factors determining the efficiency and stability of protonic ceramic electrolysis cells (PCECs). In this work, the La0.6Sr0.4Co0.2Fe0.8O3-δ (LSCF) current collection layer (CCL) film with unique finger-like pores was successfully prepared by the phase-inversion tape-casting technique (PT), which promoted the gas diffusion inside the electrode and effectively improved the stability of the single cell in high-humidity air. A screen-printed LSCF-BaCe0.7Zr0.1Y0.1Yb0.1O3 catalytic active layer (CAL) was also applied to match the thermal expansion coefficient (TEC) values and improve the interface combination. The electrochemical impedance spectroscopy (EIS) and distribution of relaxation time (DRT) studies of the symmetric cells showed that when the film was used to match different CALs as an air electrode, the gas diffusion inside the electrode was no longer restricted by the increasing steam content in air. The single cell exhibited a high electrolysis current density of 1 A cm-2 (1.25 V) at 650 °C; furthermore, no performance degradation was observed in this high current density when electrolyzed in air with 40 and 60% humidity for more than 250 h. These results present a simplified and economical scheme to develop air electrodes with high stability in wet air with a high steam content.

Rational design of a polysaccharide-based viral mimicry nanocomplex for potent gene silencing in inflammatory tissues.

Rational design and fabrication of small interfering RNA (siRNA) delivery system with simple production scheme, specific targeting capability, responsiveness to endogenous stimuli and potential multi-functionalities remains technically challenging. Herein, we screen and design a virus-mimicking polysaccharide nanocomplex that shows specific gene delivery capability in a selective subset of leukocytes. A virus-inspired poly (alkyl methacrylate-co-methacrylic acid) fragment was conjugated on barley ß-glucans (EEPG) to endow the nanocomplex with pH-dependent endosomal membrane destabilization capabilities, as confirmed both biologically and computationally. siRNA loaded EEPG nanocomplex is feasibly fabricated in a single-step manner, which exhibit efficient gene silencing efficacy towards Dectin-1+ monocytes/macrophages. The inherent targeting affinity and feasible gene silencing potency of EEPG nanocomplex are investigated in three independent murine inflammation models, including myocardial infarction, lung fibrosis and acute liver damage. Significant enhanced accumulation level of EEPG nanocomplex is observed in cardiac lesion site, indicating its exclusive targeting capability for ischemic heart diseases. As a proof of concept, siTGF-ß based gene therapy is confirmed in murine model with heart fibrosis. Overall, our findings suggest the designed EEPG nanocomplex is favorable for siRNA delivery, which might have translational potential as a versatile platform in inflammation-related diseases.

Hydroxychloroquine protects against autoimmune premature ovarian insufficiency by modulating the Treg/Th17 cell ratio in BALB/c mice.

AIMS: The role of hydroxychloroquine (HCQ) in premature ovarian insufficiency (POI) remains unclear. The purpose of this study was to evaluate the effect of HCQ on ovarian function in mice with POI and to clarify its potential mechanisms. METHODS: POI was induced in mice by injection with zona pellucida 3 peptide (pZP3), and HCQ was administered intragastrically. Stages of the estrous cycle were determined using vaginal cytology. The ovarian structure was observed under a microscope after hematoxylin-eosin staining. The levels of serum hormones and anti-ZP antibody (aZPAb) were measured using enzyme-linked immunosorbent assay (ELISA). The expression levels of CD4, CD45, and ZP2, ZP3 were determined using immunofluorescence and immunohistochemistry, respectively. The T regulatory (Treg)/ T helper 17 (Th17) cell ratio was analyzed using flow cytometry analysis. Western blotting was performed to assess the expression levels of proteins, transcription factors and cytokines. RESULTS: Administration of HCQ to mice with POI greatly restored their estrus cycle. In the treatment group compared to the POI group, estradiol (E2 ) levels were higher, and follicle stimulating hormone (FSH) levels were lower. In addition, following pZP3, HCQ treatment increased ZP2 and ZP3 expression. Additionally, by inhibiting the activation of the TLR7 signaling pathway, HCQ attenuated the infiltration of inflammatory cells and prevented the activated naive CD4+ T cells from developing into Th17 cells. CONCLUSION: Our findings showed that HCQ effectively restored ovarian function by altering the Treg/Th17 cell ratio in mice with POI, indicating that HCQ maybe a promising therapeutic method for patients with POI.

Optical coherence tomography enhanced depth imaging of chorioretinal folds in patients with orbital tumors.

AIM: To characterize spectral-domain optical coherence tomography (SD-OCT) features of chorioretinal folds in orbital mass imaged using enhanced depth imaging (EDI). METHODS: Prospective observational case-control study was conducted in 20 eyes of 20 patients, the uninvolved eye served as a control. All the patients underwent clinical fundus photography, computed tomography, EDI SD-OCT imaging before and after surgery. Two patients with cavernous hemangiomas underwent intratumoral injection of bleomycin A5; the remaining patients underwent tumor excision. Patients were followed 1 to 14mo following surgery (average follow up, 5.8mo). RESULTS: Visual acuity prior to surgery ranged from 20/20 to 20/200. Following surgery, 5 patients' visual acuity remained unchanged while the remaining 15 patients had a mean letter improvement of 10 (range 4 to 26 letters). Photoreceptor inner/outer segment defects were found in 10 of 15 patients prior to surgery. Following surgical excision, photoreceptor inner/outer segment defects fully resolved in 8 of these 10 patients. CONCLUSION: Persistence of photoreceptor inner/outer segment defects caused by compression of the globe by an orbital mass can be associated with reduced visual prognosis. Our findings suggest that photoreceptor inner/outer segment defects on EDI SD-OCT could be an indicator for immediate surgical excision of an orbital mass causing choroidal compression.

Mechanism of Acupuncture and Moxibustion on Promoting Mucosal Healing in Ulcerative Colitis.

The latest guideline about ulcerative colitis (UC) clinical practice stresses that mucosal healing, rather than anti-inflammation, is the main target in UC clinical management. Current mucosal dysfunction mainly closely relates to the endoscopic intestinal wall (mechanical barrier) injury with the imbalance between intestinal epithelial cells (IECs) regeneration and death, as well as tight junction (TJ) dysfunction. It is suggested that biological barrier (gut microbiota), chemical barrier (mucus protein layer, MUC) and immune barrier (immune cells) all take part in the imbalance, leading to mechanical barrier injury. Lots of experimental studies reported that acupuncture and moxibustion on UC recovery by adjusting the gut microbiota, MUC and immune cells on multiple targets and pathways, which contributes to the balance of IEC regeneration and death, as well as TJ structure recovery in animals. Moreover, the validity and superiority of acupuncture and moxibustion were also demonstrated in clinic. This study aims to review the achievements of acupuncture and moxibustion on mucosal healing and analyse the underlying mechanisms.