LDHA contributes to nicotine induced cardiac fibrosis through autophagy flux impairment.

Cardiac fibrosis is a typical feature of cardiac pathological remodeling, which is associated with adverse clinical outcomes and has no effective therapy. Nicotine is an important risk factor for cardiac fibrosis, yet its underlying molecular mechanism remains poorly understood. This study aimed to identify its potential molecular mechanism in nicotine-induced cardiac fibrosis. Our results showed nicotine exposure led to the proliferation and transformation of cardiac fibroblasts (CFs) into myofibroblasts (MFs) by impairing autophagy flux. Through the use of drug affinity responsive target stability (DARTS) assay, cellular thermal shift assay (CETSA), and surface plasmon resonance (SPR) technology, it was discovered that nicotine directly increased the stability and protein levels of lactate dehydrogenase A (LDHA) by binding to it. Nicotine treatment impaired autophagy flux by regulating the AMPK/mTOR signaling pathway, impeding the nuclear translocation of transcription factor EB (TFEB), and reducing the activity of cathepsin B (CTSB). In vivo, nicotine treatment exacerbated cardiac fibrosis induced in spontaneously hypertensive rats (SHR) and worsened cardiac function. Interestingly, the absence of LDHA reversed these effects both in vitro and in vivo. Our study identified LDHA as a novel nicotine-binding protein that plays a crucial role in mediating cardiac fibrosis by blocking autophagy flux. The findings suggest that LDHA could potentially serve as a promising target for the treatment of cardiac fibrosis.

On the need for standardized reporting of photophysical parameters of in vitro photodynamic therapy studies.

In vitro dose escalation experiments are one of the first gatekeepers in therapeutic evaluation and development. This also holds for evaluating novel photosensitizers (PS) and Photodynamic Therapy (PDT) co-therapies as needed to provide dose response guidelines before engaging in further pre-clinical studies. The dose needed to achieve 50% cell kill (LD50) is a standard metric to report the potency of a therapeutic agents that is widely accepted for single-drug therapies. In reporting results of PDT experiments, which involve delivery of both drug and light, it is inherently more complicated to identify such a convenient dose response metric that actually captures the larger space of treatment parameters. In addition to ubiquitous sources of biological variability that apply broadly in biomedical research, PDT treatment efficacy is determined by multiple key parameters that may or may not have been documented, including PS concentration and light fluence, where the latter is itself a function of the spectral properties of the light source used (often not described), not to mention dose rate, fractionation and other parameters that potentially vary between individual studies. It is impossible to compare results between two study when, for example one reports LD50 PS concentration without providing essential light dosimetry details. Motivated by this challenge in comparing outcomes and establishing reproducibility of in vitro PDT studies, we endeavored to perform a meta-analysis of the reporting of PDT results by converting, where possible, the disparately reported experimental details into a consistent metric that could be used to compare across studies. In this context we adopt here the number of photons absorbed by photosensitizers per unit volume to affect a 50% decline in cell survival as a standardized metric. By choosing this metric one can acknowledge the quantum-based generation of cytotoxins. While this metric does not cover every possible source of variability between any two studies, for a PS with known optical properties, this does encapsulate PS concentration as well as irradiance and spectral properties of light delivered. For the sake of focus we adopt this approach for study of reported results with two photosensitizers, Protoporphyrin IX, either synthesized in the cells by aminolevulinic acid or administered exogenously, and Chlorin e6. A literature search was performed to identify in vitro studies with these two photosensitizers and collect necessary information to calculate the absorbed photon LD50 threshold for each study. Only approximately 1/10 of the manuscripts reporting on in vitro studies provide the minimum required information to calculate the threshold values. While the majority of the determined threshold values are within a factor of 10, the range of threshold values spanned close to 7 orders of magnitude for both photosensitizers. To contrast with single-agent therapies, a similar exercise was performed for chemotherapeutic drugs targeting cellular mitosis or tyrosine kinase inhibitors resulted in an LD50 or IC50 range of 1-2 orders of magnitude, with LD50 or IC50 values for a single cell line being within a factor of 5. This review underscores challenges in the reporting of in vitro PDT efficacy. In many cases it takes considerable effort to extract the necessary methodology information to make meaningful comparison between PDT studies. Only when results between studies can be compared is it possible to begin to assess reproducibility which, as shown here, can be a major issue. Hence, guidelines need to be developed and enforced through the peer review process for meaningful reporting of preclinical PDT results in order for the most promising sensitizers and co-therapies to be identified and translated into the clinic.

Bioinformatic Analysis and Translational Validation of Psoriasis Candidate Genes for Precision Medicine.

Background: Psoriasis is a recurrent, chronic, inflammation- and immune-mediated skin disease with multiple causative factors. However, the genetic markers associated with recurrence have not yet been fully elucidated. Accordingly, in this study, we aimed to identify markers associated with the recurrence of psoriasis. Methods: We analyzed differentially expressed genes to determine which targets were associated with the recurrence of psoriasis and used these data to construct a protein-protein interaction network using Cytoscape software. The results were then validated by analysis of core targets using Gene Expression Omnibus (GEO) datasets and clinical samples. Functional enrichment analysis was used to explore the potential mechanisms mediating the recurrence of psoriasis. Results: We screened out six core targets that played important roles in recurrence of psoriasis, and validation of GEO datasets and clinical samples showed that the expression levels of five core targets were higher in patients with psoriasis than in healthy individuals. Functional enrichment analysis revealed that the cell cycle and oocyte meiosis signaling pathways were involved in the recurrence of psoriasis. Conclusion: Our findings provided insights into the mechanisms mediating the onset and recurrence of psoriasis.

DEFB126 polymorphisms and association with idiopathic asthenozoospermia in China.

Idiopathic asthenozoospermia, a common factor in male infertility, is characterized by altered sperm motility function in fresh ejaculate. Although the ß-defensin 126 (DEFB126) protein is associated with asthenozoospermia, DEFB126 gene polymorphisms have not been extensively studied. Therefore, the association between DEFB126 gene polymorphisms and asthenozoospermia requires further investigation. Screening was performed by semen analysis, karyotype analysis, and Y microdeletion detection, and 102 fertile men and 106 men with asthenozoospermia in Chengdu, China, were selected for DEFB126 gene sequence analyses. Seven nucleotide mutations and two nucleotide deletions in the DEFB126 gene were detected. rs11467417 (317-318 del/del), rs11467497 (163-166 wt/del), c.152T>C, and c.227A>G were significantly different between the control and asthenozoospermia groups, likely representing high-risk genetic factors for asthenozoospermia among males. DEFB126 expression was not observed in sperm with rs11467497 homozygous deletion and was unstable in sperm with rs11467417 homozygous deletion. The rs11467497 four-nucleotide deletion leads to truncation of DEFB126 at the carboxy-terminus, and the rs11467417 binucleotide deletion produces a non-stop messenger RNA (mRNA). The above deletions may be responsible for male hypofertility and infertility by reducing DEFB126 affinity to sperm surfaces. Based on in silico analysis, the amino acids 51M and 76K are located in the highly conserved domain; c.152T>C (M51T) and c.227A>G (K76R) are predicted to be damaging and capable of changing alternative splice, structural and posttranslational modification sites of the RNA, as well as the secondary structure, structural stability, and hydrophobicity of the protein, suggesting that these mutations are associated with asthenozoospermia.

Efficacy of hyaluronic acid on the prevention of intrauterine adhesion and the improvement of fertility: A meta-analysis of randomized trials.

BACKGROUND: and purpose:Intrauterine adhesion (IUA) and re-adhesion were common problems in women of childbearing age. The aim of our research was to evaluate the efficacy of hyaluronic acid gel on preventing IUA and improving the fertility. METHODS: A systematic search for randomized controlled trial (RCT) articles that tested the effectiveness of using hyaluronic acid gel during intrauterine surgery in prevention of IUA and improvement of fertility was performed in PubMed, Medline, Embase, the Cochrane Library and clinicaltrials.gov until December 2020. Data were extracted independently and analyzed using RevMan statistical software version 5.3. RESULTS: Twelve articles (11 studies) were deemed eligible for inclusion. There was a significantly reduced proportion of IUA after using hyaluronic acid gel during intrauterine operation (OR 0.39, 95% CI 0.29 to 0.52). It has significantly reduced the incidence of moderate-to-severe IUA after using hyaluronic acid gel, but no effect on the mild IUA. In addition, our analysis showed that the hyaluronic acid gel group was associated with a significant increased incidence of pregnancy (OR 1.64, 95% CI 1.08 to 2.50). CONCLUSION: Our analysis confirmed that using hyaluronic acid gel during intrauterine operation seemed to be more helpful for patients with high risk of IUA. However, larger and well-designed studies would be desired in the future to confirm its efficacy and safety in protecting fertility.

New polymerized sesquiterpene lactones from Ainsliaea yunnanensis and their activity evaluation.

Two new dimeric and trimeric sesquiterpene lactones (1-2), and nine known sesquiterpene lactones (3-11) were isolated from the EtOAc phase of the ethanolic extract of Ainsliaea yunnanensis. Their structures were identified by NMR, IR and HR-ESIMS spectroscopic methods, and compound 1 was confirmed by single crystal X-ray diffraction experiment. All the compounds were tested for their cytotoxic, anti-microbial and anti-inflammatory activities. Compounds 1, 2, 3, 5, 7, 9 and 11 showed very significant selective cytotoxic activities on MDA-MB-468, PANC-1, HEPG2 or A549 cells. Compounds 6 and 11 showed very significant inhibiting effect on Epicoccum sp. (CPCC 400307), Fusarium solani (CPCC 800013) or Bacillus subtilis. Meanwhile, compounds 6 and 7 can inhibit the NLRP3 inflammasome's activation at the concentration of 10 µM.

Effect of exercise rehabilitation on exercise capacity and quality of life in children with bronchial asthma: a systematic review. / 运动康复训练对支气管哮喘儿童运动能力和生活质量干预效果的系统评价.

OBJECTIVES: To systematically evaluate the effect of exercise rehabilitation on exercise capacity and quality of life in children with bronchial asthma. METHODS: PubMed, Cochrane Library, Web of Science, EBSCO, China National Knowledge Infrastructure, Weipu Data, and Wanfang Data were searched for randomized controlled trials (RCTs) on the effect of exercise rehabilitation on children with bronchial asthma published up to February 2021. RevMan 5.3 was used to perform a Meta analysis. RESULTS: A total of 14 studies were included, with 990 subjects in total. The Meta analysis showed that compared with the conventional treatment group, the exercise rehabilitation group had significantly better exercise capacity (distance covered in the 6-minute walk test: MD=108.13, P<0.01; rating of perceived effort: MD=-2.16, P<0.001; peak power: MD=0.94, P=0.001) and significantly higher total score of quality of life (SMD=1.28, P=0.0002), activity score (SMD=1.38, P=0.0002), symptom score (SMD=1.02, P<0.001), and emotional score (SMD=0.86, P<0.001) assessed by the Pediatric Asthma Quality of Life Questionnaire. CONCLUSIONS: Current evidence shows that exercise rehabilitation has a positive effect in improving exercise capacity and quality of life in children with bronchial asthma. Due to limited number and quality of studies included in the analysis, further research is needed.

Comparative effectiveness of herb-partitioned moxibustion plus lifestyle modification treatment for patients with simple obesity: A study protocol for a randomized controlled trial.

INTRODUCTION: Obesity is a global public health issue, which results in many health complications. Moxibustion may serve as an alternative management for simple obesity, where pharmacological therapy is always difficult to be accepted by the majority of obese patients based on its safety. However, the effects of herb-partitioned moxibustion as obesity intervention have not been confirmed. This study is designed as a single-blinded, 3-dummy randomized controlled trial to evaluate the efficacy and safety of herb-partitioned moxibustion plus lifestyle modification treatment in patients with simple obesity. METHODS AND ANALYSIS: This study will be a randomized, controlled trial conducted from April, 2019 to April, 2021 that includes 108 participants who have simple obesity and meet the eligibility criteria. The participants will be randomly divided into 3 treatment groups: heat application group, medicated plaster group, or herb-partitioned moxibustion group. Each treatment will last 4 weeks. The primary outcomes will be the clinical effectiveness. The secondary outcome measures include participants' obesity-related indicators, the IWQOL-Lite scale, and the syndrome score of Traditional Chinese Medicine. Adverse events will be recorded during the intervention period. ETHICS AND DISSEMINATION: Ethical approval of this study was granted by the Ethics Committee of Hubei Provincial Hospital of Traditional Chinese Medicine on 15 November 2018 (Ethics Reference No: HBZY2018-C24-01). Written informed consents will be provided by all participants before they were enrolled in this study. TRIAL REGISTRATION NUMBER: NCT04606680.

Supramolecular Non-Helical One-Dimensional Channels and Microtubes Assembled from Enantiomers of Difluorenol.

The design and assembly of photoelectro-active molecular channel structures is of great importance because of their advantages in charge mobility, photo-induced electron transfer, proton conduction, and exciton transport. Herein, we report the use of racemic 9,9'-diphenyl-[2,2'-bifluorene]-9,9'-diol (DPFOH) enantiomers to produce non-helical 1D channel structures. Although the individual molecule does not present any molecular symmetry, two pairs of racemic DPFOH enantiomers can form a C2 -symmetric closed loop via the stereoscopic herringbone assembly. Thanks to the special symmetry derived from the enantiomer pairs, the multiple supramolecular interactions, and the padding from solvent molecules, this conventionally unstable topological structure is achieved. The etching of solvent in 1D channels leads to the formation of microtubes, which exhibit a significant lithium-ion conductivity of 1.77×10-4  S cm, indicating the potential research value of this novel 1D channel structure.

Clinical effect of catgut implantation at acupoints for the treatment of simple obesity: A multicentre randomized controlled trial.

BACKGROUND: Catgut implantation at acupoints (CIA) is a subtype of acupuncture that has been widely used to treat simple obesity, but evidence for its effectiveness remains scarce. The aim of this study is to evaluate the efficacy and safety of treating simple obesity with CIA. OBJECTIVE: This clinical trial aims to evaluate the effectiveness and safety of CIA used for treatment of simple obesity. METHODS: This is a multicentre, randomized, parallel, sham-controlled clinical trial. A total of 216 patients with simple obesity will be recruited. They will be randomly assigned in a 1:1 ratio to either the CIA group or the sham control group. All treatments will be given once every 2 weeks. The primary outcome measure is the rate of waistline reduction. Secondary outcome measures are the rates of reduction of body measurements, including weight, body mass index (BMI), hipline, waist-hip-ratio (WHR) and body fat percentage (BFP), the changes in scores on scales, including the Impact of Weight on Quality of Life Questionnaire (IWQOL-Lite), Short Form 36 (SF-36), the Hospital Anxiety and Depression Scale (HAD) and the Self-Esteem Scale (SES), Outcomes will be evaluated at baseline and at weeks 4, 8, 12, 16, 28, and 40, respectively. All adverse events that occur during this study will be recorded. If any participant withdraws from the trial, an intention-to-treat analysis (ITT) will be performed. CONCLUSION: This is a randomized, sham-controlled trial of CIA treatment for simple obesity. The results of this trial will provide more evidence on whether CIA is efficacious and safe for treating obesity. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02936973. Registered on October 18, 2016.

[Moxibustion therapy in prevention and treatment of coronavirus disease 2019 (COVID-19): construction and application of non-contact diagnosis and treatment mode].

OBJECTIVE: To establish and promote the non-contact doctor-patient interactive diagnosis and treatment mode based on mobile internet for the treatment of coronavirus disease 2019 (COVID-19) with moxibustion therapy, and to observe the feasibility and effectiveness of the model in the pandemic. METHODS: A total of 43 first-line medical staff and 149 suspected and confirmed cases with COVID-19 [18 cases in medical observation period, 17 cases of mild type (cold dampness and stagnation in the lung), 24 cases of ordinary type (cold-dampness accumulated in the lung) and 90 cases in recovery period (qi deficiency of spleen and lung)] were included. A non-contact doctor-patient interactive diagnosis and treatment platform was established for the treatment of COVID-19 with indirect moxibustion plaster based on mobile internet. By the platform, the patients were instructed to use indirect moxibustion plaster in treatment. For the first-line medical staff and patients in the medical observation period, Zusanli (ST 36), Qihai (CV 6) and Zhongwan (CV 12) were selected. For the mild cases (cold dampness and stagnation in the lung) and the cases of ordinary type (cold-dampness accumulated in the lung), Hegu (LI 4), Taichong (LR 3), Zusanli (ST 36) and Guanyuan (CV 4) were selected. In the recovery period (qi deficiency of spleen and lung), Dazhui (GV 14), Feishu (BL 13), Geshu (BL 17), Zusanli (ST 36) and Kongzui (LU 6) were used. The treatment was given once daily for 40 min each time. The intervention lasted for 10 days. After intervention, the infection rate and the improvement in the symptoms and psychological status of COVID-19 were observed in clinical first-line medical staff and COVID-19 patients. RESULTS: In 10 days of intervention with indirect moxibustion plaster, there was "zero" infection among medical staff. Of 43 first-line physicians and nurses, 33 cases had some physical symptoms and psychological discomforts, mainly as low back pain, poor sleep and anxiety. After treatment, regarding the improvements in the symptoms and psychological discomforts, the effective rate was 78.8% (26/33) and the curative rate was 36.4% (12/33). Regarding the improvements in psychological discomforts, the effective rate was 58.3% (14/24) and the curative rate was 37.5 (9/24). Of 149 patients, 133 cases had the symptoms and psychological discomforts. After treatment, regarding the improvements in the symptoms and psychological discomforts, the effective rate was 81.2% (108/133) and the curative rate was 34.6% (46/133). Regarding the improvements in psychological discomforts, the effective rate was 76.5% (52/68) and the curative rate was 57.4 % (39/68). CONCLUSION: It is feasible to apply the indirect moxibustion plaster technique based on mobile internet to the treatment COVID-19. This mode not only relieves the symptoms such as cough and fatigue, improves psychological state, but also possibly prevents the first-line medical staff from COVID-19.

The Dimensionality Transition between Three-Dimensional and Two-Dimensional Organic Microcrystals: Specific Symmetry and Selective Adhesion.

A three-dimensional-two-dimensional dimensionality transition of organic microcrystals was performed via elongated octahedrons, oblique octahedrons, diamond-like particles, and parallelograms using nonplanar 2,7-di(9H-carbazol-9-yl)spiro[fluorene-9,9'-xanthene] molecules. The specific crystal symmetry and selective adhesion of P123 on the {11-1}s facet are supposed to induce the morphological transition.

Mechanisms of Acupuncture Therapy for Simple Obesity: An Evidence-Based Review of Clinical and Animal Studies on Simple Obesity.

Simple obesity is a worldwide epidemic associated with rapidly growing morbidity and mortality which imposes an enormous burden on individual and public health. As a part of Traditional Chinese Medicine (TCM), acupuncture has shown the positive efficacy in the management of simple obesity. In this article, we comprehensively review the clinical and animal studies that demonstrated the potential mechanisms of acupuncture treatment for simple obesity. Clinical studies suggested that acupuncture regulates endocrine system, promotes digestion, attenuates oxidative stress, and modulates relevant molecules of metabolism in patients of simple obesity. Evidence from laboratory indicated that acupuncture regulates lipid metabolism, modulates inflammatory responses, and promotes white adipose tissue browning. Acupuncture also suppresses appetite through regulating appetite regulatory hormones and the downstream signaling pathway. The evidence from clinical and animal studies indicates that acupuncture induces multifaceted regulation through complex mechanisms and moreover a single factor may not be enough to explain the beneficial effects against simple obesity.

Supramolecular steric hindrance effect on morphologies and photophysical behaviors of spirocyclic aromatic hydrocarbon nanocrystals.

Three pyrene-based spirocyclic aromatic hydrocarbons (Py-SAHs) were prepared to clarify the roles of molecular segments in regulating the morphologies and photophysical properties of organic microcrystals. Due to the different supramolecular steric hindrance (SSH) effect between bulky groups and pyrene rings, distinct nanocrystal morphologies with unique photoluminescence properties were realized.

Double-balloon catheter versus dinoprostone insert for labour induction: a meta-analysis.

OBJECTIVE: To assess the efficacy and safety of a double-balloon catheter versus dinoprostone insert for labour induction. STUDY DESIGN: PubMed, MEDLINE, Embase, ClinicalTrials.gov, and the Cochrane Central Register of Clinical Trials databases were searched from 1985 to April 2018. Randomized controlled trials that compared a double-balloon catheter and dinoprostone insert for cervical ripening were identified. Eligible study populations consisted of women with singleton pregnancies that had any indication for labour induction and were randomly assigned to undergo induction with a double-balloon catheter or dinoprostone insert. The main outcomes were incidence of vaginal delivery within 24 h and caesarean section, and neonatal outcomes. RESULTS: Five randomized trials (603 women; 305 with a double-balloon catheter and 298 with a dinoprostone insert) were eligible for inclusion. No differences were observed between the two groups in terms of vaginal delivery within 24 h [relative risk (RR) 1.21, 95% confidence interval (CI) 0.93-1.59] and incidence of caesarean section (RR 0.99, 95% CI 0.77-1.27). Compared with the double-balloon catheter, the dinoprostone insert was associated with a reduced need for oxytocin administration in the process of labour induction (RR 1.95, 95% CI 1.45-2.62). However, there was a higher incidence of excessive uterine activity (RR 0.17, 95% CI 0.06-0.54) and neonatal umbilical cord arterial blood pH < 7.1 (RR 0.36, 95% CI 0.15-0.84) in the dinoprostone insert group. CONCLUSION: This review showed that the efficacy of labour induction using both the double-balloon catheter and dinoprostone insert was similar. However, the double-balloon catheter seemed to be a safer method.

Flexible Thermo-Optic Variable Attenuator based on Long-Range Surface Plasmon-Polariton Waveguides.

A flexible thermo-optic variable attenuator based on long-range surface plasmon-polariton (LRSPP) waveguide for microwave photonic application was investigated. Low-loss polymer materials and high-quality silver strip were served as cladding layers and core layer of the LRSPP waveguide, respectively. By using finite element method (FEM), the thermal distribution and the optical field distribution have been carefully optimized. The fabricated device was characterized by end-fire excitation with a 1550 nm laser. The transmission performance of high-speed data and microwave modulated optical signal was measured while using a broadband microwave photonics link. The results indicated that the propagation loss of the LRSPP waveguide was about 1.92 dB/cm. The maximum attenuation of optical signal was about 28 dB at a driving voltage of 4.17 V, and the variable attenuation of microwave signals was obviously observed by applying different driving voltage to the heater. This flexible plasmonic variable attenuator is promising for chip-scale interconnection in high-density photonic integrated circuits and data transmission and amplitude control in microwave photonic systems.

Seeds screening aqueous synthesis, multiphase interfacial separation and in situ optical characterization of invisible ultrathin silver nanowires.

We report a multi-step synthetic method to obtain ultrathin silver nanowires (Ag NWs) from an aqueous solution with a ∼17 nm diameter average, and where some of them decreased down to 9 nm. Carefully designed seed screening processes including LED irradiation at high temperature for a short time, and then continuous H2O2 etching, and relative growth mechanisms of high-yield five-twinned pentagonal seeds and ultrathin Ag NWs in aqueous environment are detailed. Then, a rapid and simple multiphase interfacial assembly method particularly suitable for the separation of ultrathin Ag NWs from various by-products was demonstrated with a clear mechanism explanation. Next, a unique optical interaction between light and individual AG NWs, as well as feature structures in the AG NWs film, was investigated by a micro-domain optical confocal microscope measurement in situ together with a theoretical explanation using modal transmission theory. That revealed that the haze problem of AG NWs films was not only arising from the interaction between light and individual or crossed Ag NWs but was also greatly dependent on a weak coupling effect of leaky modes supported by adjacent Ag NWs with large distances which had not been considered before. We then provided direct experimental evidence and concluded how to obtain haze-free films with 100% transparency in the whole visible range based on ultrathin Ag NWs. This breakthrough in diameter confinement and purification of Ag NWs is a highly expected step to overcome the well-focused light diffusion and absorption problems of Ag NWs-based devices applied in various fields such as flexible electronics, high-clarity displays, visible transparent heaters, photovoltaics and various optoelectronic technologies.

Late restoration of renal function in patients with severe ANCA-associated glomerulonephritis who were dialysis-dependent at presentation.

In antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), many patients with severe renal dysfunction are on dialysis at presentation. Among those who got rid of dialysis finally, renal restoration happened mostly within the first 3 months of treatment. However, in clinical practice, we occasionally encountered patients who got rid of dialysis after 3 months. The current study investigated clinical and pathological features of AAV patients with so-called delayed renal function restoration. A total of 156 patients with ANCA-associated glomerulonephritis who were on dialysis at presentation were retrospectively recruited. Clinical and pathological data as well as treatment and outcomes were analyzed. Among these 156 patients, 58 and 12 patients got rid of dialysis within and after 3 months, respectively. Among the 12 patients with delayed renal function restoration, 8 and 4 patients got rid of dialysis within and after 6 months, respectively. Among the 72 patients who were still on dialysis at the end of 3 months since the initiation of immunosuppressive therapy, those receiving intravenous cyclophosphamide therapy over 3 months had significantly higher proportion of renal function restoration than those receiving intravenous cyclophosphamide for only 3 months (8/14 versus 4/58, P < 0.001). For patients with ANCA-associated glomerulonephritis who were on dialysis at presentation, there is an unnegligible proportion of patients who had their renal function restoration beyond 3 months since the initiation of immunosuppressive therapy. Further studies are needed to investigate whether, and for whom, cyclophosphamide prescription should be prolonged for more than 3 months.

mROS-TXNIP axis activates NLRP3 inflammasome to mediate renal injury during ischemic AKI.

Ischemia/reperfusion (I/R) is a critical risk factor for acute kidney injury (AKI). Recent studies provided evidence that tubular epithelial cells (TEC)-associated inflammation aggravates kidney injury and impairs tissue repair after I/R injury. Here we demonstrated that the Nod-like receptor protein 3 (NLRP3) inflammasome is activated by mitochondrial reactive oxygen species (mROS) during I/R injury via direct interactions between the inflammasome and thioredoxin-interacting protein (TXNIP). Firstly, we found that NLRP3 inflammasome activation was induced by I/R injury, peaking at day 3 after reperfusion. Consistent with this observation, NLRP3 deletion significantly attenuated I/R-induced kidney damage and markers of inflammasome activation. Then, we observed mitochondrial dysfunction, characterized by ultrastructural changes and cytochrome C (Cyt c) redistribution. Mitochondria-targeted antioxidant MitoTEMPO prevented mROS overproduction and the decline in mitochondrial membrane potential (MMP) in vitro. MitoTEMPO treatment also inhibited NLRP3 inflammasome activation and co-localization of NLRP3 and TXNIP after simulated ischemia/reperfusion (SI/R) injury. Finally, we transfected HK-2 cells with TXNIP siRNA to explore the role of TXNIP in mROS-induced NLRP3 inflammasome activation. We found that TXNIP siRNA significantly inhibited NLRP3 inflammasome activation. These results demonstrate that NLRP3 inflammasome is activated through the mROS-TXNIP-NLRP3 pathway and provide a potential therapeutic target in ischemic AKI.

Hybrid fiber resonator employing LRSPP waveguide coupler for gyroscope.

Polarization error and temperature noise are two main limits to the performance of resonant fiber optic gyroscope (RFOG). To overcome these limits, we demonstrated a hybrid resonator consisting of a polymer-based long-range surface plasmon polariton (LRSPP) waveguide coupler and a silica fiber. Single-polarization property of LRSPP waveguide and the offsetting of the opposite thermo-optical characteristics between the polymer-based LRSPP waveguide and the silica fiber can effectively inhibit both the polarization error and the temperature noise of RFOG. The measured resonance spectrum of the hybrid resonator shows the absence of polarization noise. The temperature dependence of wavelength shift (TDWS) of resonator dropped to about 2 pm/°C, or even to 0 pm/°C with optimal structure, which dramatically improves the temperature stability of gyroscope system. In addition, the hybrid resonator also shows tremendous application potential in rate-grade and tactical-grade gyroscopes.