Impact of stage-specific limb function exercises guided by a self-management education model on arteriovenous fistula maturation status.

BACKGROUND: The exercise of limb function is the most economical and safe method to promote the maturation of arteriovenous fistula (AVF). However, due to the lack of a unified exercise standard in China, many patients have insufficient awareness of the importance of AVF, leading to poor effectiveness of limb function exercise. The self-management education model can effectively promote patients to take proactive health-related actions. This study focuses on the characteristics of patients during the peri-AVF period and conducts a phased limb function exercise under the guidance of the self-management education model to observe changes in factors such as the maturity of AVF. AIM: To assess the impact of stage-specific limb function exercises, directed by a self-management education model, on the maturation status of AVFs. METHODS: This study is a randomized controlled trial involving 74 patients with forearm AVFs from the Nephrology Department of a tertiary hospital in Sichuan Province, China. Patients were randomly divided into an observation group and a control group using a random number table method. The observation group underwent tailored stage-specific limb function exercises, informed by a self-management education model which took into account the unique features of AVF at various stages, in conjunction with routine care. Conversely, the control group was given standard limb function exercises along with routine care. The assessment involves the maturity of AVFs post-intervention, postoperative complications, and the self-management level of the fistula in both groups patients. Analyses were conducted using SPSS version 23.0. Count data were represented by frequency and percentage and subjected to chi-square test comparisons. Measurement data adhering to a normal distribution were presented as mean ± SD. The independent samples t-test was utilized for inter-group comparisons, while the paired t-test was used for intra-group comparisons. For measurement data not fitting a normal distribution, the median and interquartile range were presented and analyzed using the Wilcoxon rank sum test. RESULTS: At the 8-wk postoperative mark, the observation group demonstrated significantly higher scores in AVF symptom recognition, symptom prevention, and self-management compared to the control group (P < 0.05). However, the variance in symptom management scores between the observation and control groups lacked statistical significance (P > 0.05). At 4 wk after the operation, the observation group displayed a superior vessel diameter and depth from the skin of the drainage vessels in comparison to the control group (P < 0.05). While the observation group did manifest elevated blood flow rates in the drainage vessels relative to the control group, this distinction was not statistically significant (P > 0.05). By the 8-wk postoperative interval, the observation group outperformed the control group with notable enhancements in blood flow rates, vessel diameter, and depth from the skin of drainage vessels (P < 0.01). Seven days following the procedure, the observation group manifested significantly diminished limb swelling and an overall reduced complication rate in contrast to the control group (P < 0.05). The evaluation of infection, thrombosis, embolism, arterial aneurysm stenosis, and incision bleeding showed no notable differences between the two groups (P > 0.05). By the 4-wk postoperative juncture, complications between the observation and control groups were statistically indistinguishable (P > 0.05). CONCLUSION: Stage-specific limb function exercises, under the guidance of a self-management education model, amplify the capacity of AVF patients to discern and prevent symptoms. Additionally, they expedite AVF maturation and mitigate postoperative limb edema, underscoring their efficacy as a valuable method for the care and upkeep of AVF in hemodialysis patients.

Ntsr1 contributes to pulmonary hypertension by enhancing endoplasmic reticulum stress via JAK2-STAT3-Thbs1 signaling.

Pulmonary hypertension (PH) is a severe clinical syndrome with pulmonary vascular remodeling and poor long-term prognosis. Neurotensin receptor 1 (Ntsr1), serve as one of the G protein-coupled receptors (GPCRs), implicates in various biological processes, but the potential effects of Ntsr1 in PH development are unclear. The Sugen/Hypoxia (SuHx) or monocrotaline (MCT) induced rat PH model was used in our study and the PH rats showed aggravated pulmonary artery remodeling and increased right ventricular systolic pressure (RVSP). Our results revealed that Ntsr1 induced endoplasmic reticulum (ER) stress response via ATF6 activation contributed to the development of PH. Moreover, RNA-sequencing (RNA-seq) and phosphoproteomics were performed and the Ntsr1-JAK2-STAT3-thrombospondin 1 (Thbs1)-ATF6 signaling was distinguished as the key pathway. In vitro, pulmonary artery smooth muscle cells (PASMCs) under hypoxia condition showed enhanced proliferation and migration properties, which could be inhibited by Ntsr1 knockdown, JAK2 inhibitor (Fedratinib) treatment, STAT3 inhibitior (Stattic) treatment, Thbs1 knockdown or ATF6 knockdown. In addition, adeno-associated virus 1 (AAV1) were used to knockdown the expression of Ntsr1, Thbs1 or ATF6 in rats and reversed the phenotype of PH. In summary, our results reveal that Ntsr1-JAK2-STAT3-Thbs1 pathway can induce enhanced ER stress via ATF6 activation and increased PASMC proliferation and migration capacities, which can be mechanism of the pulmonary artery remodeling and PH. Targeting Ntsr1 might be a novel therapeutic strategy to ameliorate PH.

Zbtb16 increases susceptibility of atrial fibrillation in type 2 diabetic mice via Txnip-Trx2 signaling.

Atrial fibrillation (AF) is the most prevalent sustained cardiac arrhythmia, and recent epidemiological studies suggested type 2 diabetes mellitus (T2DM) is an independent risk factor for the development of AF. Zinc finger and BTB (broad-complex, tram-track and bric-a-brac) domain containing 16 (Zbtb16) serve as transcriptional factors to regulate many biological processes. However, the potential effects of Zbtb16 in AF under T2DM condition remain unclear. Here, we reported that db/db mice displayed higher AF vulnerability and Zbtb16 was identified as the most significantly enriched gene by RNA sequencing (RNA-seq) analysis in atrium. In addition, thioredoxin interacting protein (Txnip) was distinguished as the key downstream gene of Zbtb16 by Cleavage Under Targets and Tagmentation (CUT&Tag) assay. Mechanistically, increased Txnip combined with thioredoxin 2 (Trx2) in mitochondrion induced excess reactive oxygen species (ROS) release, calcium/calmodulin-dependent protein kinase II (CaMKII) overactivation, and spontaneous Ca2+ waves (SCWs) occurrence, which could be inhibited through atrial-specific knockdown (KD) of Zbtb16 or Txnip by adeno-associated virus 9 (AAV9) or Mito-TEMPO treatment. High glucose (HG)-treated HL-1 cells were used to mimic the setting of diabetic in vitro. Zbtb16-Txnip-Trx2 signaling-induced excess ROS release and CaMKII activation were also verified in HL-1 cells under HG condition. Furthermore, atrial-specific Zbtb16 or Txnip-KD reduced incidence and duration of AF in db/db mice. Altogether, we demonstrated that interrupting Zbtb16-Txnip-Trx2 signaling in atrium could decrease AF susceptibility via reducing ROS release and CaMKII activation in the setting of T2DM.

In-situ-sprayed therapeutic hydrogel for oxygen-actuated Janus regulation of postsurgical tumor recurrence/metastasis and wound healing.

Surgery is the mainstay of treatment modality for malignant melanoma. However, the deteriorative hypoxic microenvironment after surgery is recognized as a stemming cause for tumor recurrence/metastasis and delayed wound healing. Here we design and construct a sprayable therapeutic hydrogel (HIL@Z/P/H) encapsulating tumor-targeted nanodrug and photosynthetic cyanobacteria (PCC 7942) to prevent tumor recurrence/metastasis while promote wound healing. In a postsurgical B16F10 melanoma model in female mice, the nanodrug can disrupt cellular redox homeostasis via the photodynamic therapy-induced cascade reactions within tumor cells. Besides, the photosynthetically generated O2 by PCC 7942 can not only potentiate the oxidative stress-triggered cell death to prevent local recurrence of residual tumor cells, but also block the signaling pathway of hypoxia-inducible factor 1α to inhibit their distant metastasis. Furthermore, the long-lasting O2 supply and PCC 7942-secreted extracellular vesicles can jointly promote angiogenesis and accelerate the wound healing process. Taken together, the developed HIL@Z/P/H capable of preventing tumor recurrence/metastasis while promoting wound healing shows great application potential for postsurgical cancer therapy.

Higher Sodium Channel Excitability in Cardiac Purkinje Fibers: Implications for Multifocal Ectopic Purkinje-Related Premature Contractions.

BACKGROUND: Multifocal ectopic Purkinje-related premature contractions (MEPPCs) are associated with SCN5A variants. However, it is not well understood why Purkinje fibers, but not ventricular myocardium, play a predominant role in arrhythmogenesis. OBJECTIVES: This study sought to explore the underlying mechanisms of MEPPC. METHODS: Whole-cell patch-clamp and molecular biology techniques were used in the present study. RESULTS: Clinical data from one patient with R814W variant showed MEPPC syndrome, which is well responsive to amiodarone. Compared with canine ventricular myocytes, Purkinje cells (PCs) had significantly larger sodium current (INa), leftward shift of INa activation and inactivation curves, suggesting higher sodium channel excitability in PCs. Real-time polymerase chain reaction and Western blot analysis showed that the mRNA and protein expression of NaVß1 and NaVß3 was higher in canine Purkinje fibers than in ventricular myocardium. INa in heterologous Chinese hamster ovary cell expression system co-expressing NaV1.5 and NaVß1/NaVß3 exhibited similar biophysical properties of INa in PCs. R814W variant shifted INa activation in a hyperdepolarized direction, caused a larger window current, and generated an outward-gating pore current at depolarized voltages. Coexpression of NaVß1/NaVß3 with Nav1.5-R814W further left-shifted INa activation and caused an even larger window current and gating pore current, suggesting higher susceptibility of Purkinje fibers to R814W variant. Amiodarone inhibited INa, shifted its inactivation to more negative voltages, and significantly decreased the window current. CONCLUSIONS: A higher expression of ß1 and ß3 subunits contributes to higher sodium channel excitability in cardiac Purkinje fibers, making them more susceptible to MEPPC.

Conductive Nanofibers-Enhanced Microfluidic Device for the Efficient Capture and Electrical Stimulation-Triggered Rapid Release of Circulating Tumor Cells.

The effective detection and release of circulating tumor cells (CTCs) are of great significance for cancer diagnosis and monitoring. The microfluidic technique has proved to be a promising method for CTCs isolation and subsequent analysis. However, complex micro-geometries or nanostructures were often constructed and functionalized to improve the capture efficiency, which limited the scale-up for high-throughput production and larger-scale clinical applications. Thus, we designed a simple conductive nanofiber chip (CNF-Chip)-embedded microfluidic device with a herringbone microchannel to achieve the efficient and specific capture and electrical stimulation-triggered rapid release of CTCs. Here, the most used epithelial cell adhesion molecule (EpCAM) was selected as the representative biomarker, and the EpCAM-positive cancer cells were mainly studied. Under the effects of the nanointerface formed by the nanofibers with a rough surface and the herringbone-based high-throughput microfluidic mixing, the local topographic interaction between target cells and nanofibrous substrate in the microfluidic was synergistically enhanced, and the capture efficiency for CTCs was further improved (more than 85%). After capture, the sensitive and rapid release of CTCs (release efficiency above 97%) could be conveniently achieved through the cleavage of the gold-sulfur bond by applying a low voltage (-1.2 V). The device was successfully used for the effective isolation of CTCs in clinical blood samples from cancer patients, indicating the great potential of this CNF-Chip-embedded microfluidic device in clinical applications.

Tumor Microenvironment-Inspired Glutathione-Responsive Three-Dimensional Fibrous Network for Efficient Trapping and Gentle Release of Circulating Tumor Cells.

Detection of circulating tumor cells (CTCs) is important for early cancer diagnosis, prediction of postoperative recurrence, and individualized treatment. However, it is still challenging to achieve efficient capture and gentle release of CTCs from the complex peripheral blood due to their rarity and fragility. Herein, inspired by the three-dimensional (3D) network structure and high glutathione (GSH) level of the tumor microenvironment (TME), a 3D stereo (3D-G@FTP) fibrous network is developed by combining the liquid-assisted electrospinning method, gas foaming technique, and metal-polyphenol coordination interactions to achieve efficient trapping and gentle release of CTCs. Compared with the traditional 2D@FTP fibrous scaffold, the 3D-G@FTP fibrous network could achieve higher capture efficiency (90.4% vs 78.5%) toward cancer cells in a shorter time (30 min vs 90 min). This platform showed superior capture performance toward heterogeneous cancer cells (HepG2, HCT116, HeLa, and A549) in an epithelial cell adhesion molecule (EpCAM)-independent manner. In addition, the captured cells with high cell viability (>90.0%) could be gently released under biologically friendly GSH stimulus. More importantly, the 3D-G@FTP fibrous network could sensitively detect 4-19 CTCs from six kinds of cancer patients' blood samples. We expect this TME-inspired 3D stereo fibrous network integrating efficient trapping, broad-spectrum recognition, and gentle release will promote the development of biomimetic devices for rare cell analysis.

Tough Porous Silk Nanofiber-Derived Cryogels with Osteogenic and Angiogenic Capacity for Bone Repair.

Tough porous cryogels with angiogenesis and osteogenesis features remain a design challenge for utility in bone regeneration. Here, building off of the recent efforts to generate tough silk nanofiber-derived cryogels with osteogenic activity, deferoxamine (DFO) is loaded in silk nanofiber-derived cryogels to introduce angiogenic capacity. Both the mechanical cues (stiffness) and the sustained release of DFO from the gels are controlled by tuning the concentration of silk nanofibers in the system, achieving a modulus above 400 kPa and slow release of the DFO over 60 days. The modulus of the cryogels and the released DFO induce osteogenic and angiogenic activity, which facilitates bone regeneration in vivo in femur defects in rat, resulting in faster regeneration of vascularized bone tissue. The tunable physical and chemical cues derived from these nanofibrous-microporous structures support the potential for silk cryogels in bone tissue regeneration.

Loss-of-function CFTR p.G970D missense mutation might cause congenital bilateral absence of the vas deferens and be associated with impaired spermatogenesis.

Congenital bilateral absence of the vas deferens (CBAVD) is observed in 1%-2% of males presenting with infertility and is clearly associated with cystic fibrosis transmembrane conductance regulator (CFTR) mutations. CFTR is one of the most well-known genes related to male fertility. The frequency of CFTR mutations or impaired CFTR expression is increased in men with nonobstructive azoospermia (NOA). CFTR mutations are highly polymorphic and have established ethnic specificity. Compared with F508Del in Caucasians, the p.G970D mutation is reported to be the most frequent CFTR mutation in Chinese patients with cystic fibrosis. However, whether p.G970D participates in male infertility remains unknown. Herein, a loss-of-function CFTR p.G970D missense mutation was identified in a patient with CBAVD and NOA. Subsequent retrospective analysis of 122 Chinese patients with CBAVD showed that the mutation is a common pathogenic mutation (4.1%, 5/122), excluding polymorphic sites. Furthermore, we generated model cell lines derived from mouse testes harboring the homozygous Cftr p.G965D mutation equivalent to the CFTR variant in patients. The Cftr p.G965D mutation may be lethal in spermatogonial stem cells and spermatogonia and affect the proliferation of spermatocytes and Sertoli cells. In spermatocyte GC-2(spd)ts (GC2) Cftr p.G965D cells, RNA splicing variants were detected and CFTR expression decreased, which may contribute to the phenotypes associated with impaired spermatogenesis. Thus, this study indicated that the CFTR p.G970D missense mutation might be a pathogenic mutation for CBAVD in Chinese males and associated with impaired spermatogenesis by affecting the proliferation of germ cells.

The novel BRDT inhibitor NHWD870 shows potential as a male contraceptive in mice.

Small molecule inhibitors of the bromodomain and extraterminal domain (BET) family proteins have emerged as promising options not only for the treatment of multiple cancers but also for disturbing the process of sperm maturation with potential for use as viable contraceptive targets. In this study, we find that the BET family inhibitor NHWD870 and BRDT can bind well in vitro through bioinformatics software prediction and protein binding inhibition experiments. NHWD870 can produce a good contraceptive effect through animal experiments in vivo, and the fertility can be restored to normal after drug withdrawal. Transcriptomics and proteomics results suggest that NHWD870 affects pathways related to spermatogenesis and maturation, further contributing to the male infertility phenotype. Our results show that NHWD870 can induce a complete and reversible contraceptive effect in mice, which is stronger than that of JQ1 and its synthesized derivatives. This study is expected to eventually lead to clinical trials.

A Nanounit Strategy Disrupts Energy Metabolism and Alleviates Immunosuppression for Cancer Therapy.

Aberrant energy metabolism not only endows tumor cells with unlimited proliferative capacity but also contributes to the establishment of the glucose-deficient/lactate-rich immunosuppressive tumor microenvironment (ITM) impairing antitumor immunity. Herein, a novel metabolic nanoregulator (D/B/CQ@ZIF-8@CS) was developed by enveloping 2-deoxy-d-glucose (2-DG), BAY-876, and chloroquine (CQ) into zeolitic imidazolate framework-8 (ZIF-8) to simultaneously deprive the energy/nutrition supply of tumor cells and relieve the ITM for synergetic tumor starvation-immunotherapy. Aerobic glycolysis, glucose uptake, and autophagy flux could be concurrently blocked by D/B/CQ@ZIF-8@CS, cutting off the nutrition/energy supply and the source of lactate. Furthermore, inhibition of glucose uptake and aerobic glycolysis could effectively reverse the glucose-deficient/lactate-rich ITM, thus functionally inactivating regulatory T cells and augmenting anti-CTLA-4 immunotherapy. Such a two-pronged strategy would provide new insights for the design of metabolic intervention-based synergistic cancer therapy.

Heparin-Induced Thrombocytopenia Caused by Preventive Anticoagulation After Femoral Intertrochanteric Fracture Surgery: a Case Report.

BACKGROUND: Heparin-induced thrombocytopenia (HIT) is a severe complication caused by heparin. It is characterized by occult onset and missed diagnosis. Misdiagnosis easily occurs. METHODS: This paper reported an 85-year-old woman with an intertrochanteric fracture of the femur which was treated with low molecular weight heparin (LMWH) and fondaparinux sodium to prevent venous thrombosis. Then, the patient developed HIT. This is the first case report of HIT induced by LMWH and fondaparinux in a patient with a hip fracture. This case highlights the severity of HIT in elderly patients with hip fractures using LMWH and fondaparinux and the need for platelet monitoring in these patients. RESULTS: LMWH was ceased in this HIT-confirmed patient, and non-heparin treatment was begun instead. Apixaban was given twice daily for therapeutic anticoagulation therapy. In the end, the platelet levels gradually returned to normal. CONCLUSIONS: We should pay more attention to HIT and platelets during the perioperative period of orthopedic surgery, especially in elderly patients. Once the disease is confirmed, it is necessary to stop heparin-related drugs immediately and administer oral anticoagulants instead.

Development of a Localized Drug Delivery System with a Step-by-Step Cell Internalization Capacity for Cancer Immunotherapy.

How to precisely reprogram tumor-associated macrophages (TAMs) and combine them with immunogenic cell death (ICD) is still a great challenge in enhancing the antitumor immunotherapeutic effect. Here, we developed a localized drug delivery system with a step-by-step cell internalization ability based on a hierarchical-structured fiber device. The chemotherapeutic agent-loaded nanomicelles are encapsulated in the internal chambers of the fiber, which could first be internalized by actively targeting tumor cells to induce ICD. Next, the rod-like microparticles can be gradually formed from long to short shape through hydrolysis of the fiber matrix in the tumor microenvironment and selectively phagocytosed by TAMs but not to tumor cells when the length becomes less than 3 µm. The toll-like receptors 7 (TLR7) agonist imiquimod could be released from these microparticles in the cytoplasm to reprogram M2-like TAMs. The in vivo results exhibit that this localized system can synergistically induce an antitumor immune response and achieve an excellent antitumor efficiency. Therefore, this system will provide a promising treatment platform for cancer immunotherapy.

Antibacterial surfaces: Strategies and applications.

Antibacterial surfaces are surfaces that can resist bacteria, relying on the nature of the material itself. It is significant for safe food and water, human health, and industrial equipment. Biofilm is the main form of bacterial contamination on the material surface. Preventing the formation of biofilm is an efficient way to develop antibacterial surfaces. The strategy for constructing the antibacterial surface is divided into bacteria repelling and bacteria killing based on the formation of the biofilm. Material surface wettability, adhesion, and steric hindrance determine bacteria repelling performance. Bacteria should be killed by surface chemistry or physical structures when they are attached to a material surface irreversibly. Killing approaches are usually in the light of the cell membrane of bacteria. This review summarizes the fabrication methods and applications of antibacterial surfaces from the view of the treatment of the material surfaces. We also present several crucial points for developing long-term stability, no drug resistance, broad-spectrum, and even programable antibacterial surfaces.

A Hierarchical-Structured Mineralized Nanofiber Scaffold with Osteoimmunomodulatory and Osteoinductive Functions for Enhanced Alveolar Bone Regeneration.

Alveolar bone resorption is a major cause of teeth loss and jeopardizes the osseointegration of dental implants, greatly affecting patient's quality of life and health. It is still a great challenge to completely regenerate the alveolar bone defect through traditional guided bone regeneration (GBR) membranes due to their limited bioactivity and regeneration potential. Herein, a new hierarchical-structured mineralized nanofiber (HMF) scaffold, which is combined with both anisotropic and isotropic nanofibrous surface topography and the mineralized particles, is fabricated via a simple template-assisted electrospinning technology and in situ mineralization method. This HMF scaffold can not only directly induce osteogenic differentiation of bone mesenchymal stem cells (osteoinduction), but also stimulate macrophage toward pro-healing (M2) phenotype-polarization with an elevated secretion of the pro-healing cytokines, eventually enhancing the osteogenesis (osteoimmunomodulation). The results of in vivo rat alveolar bone defect repair experiments demonstrate that as compared with the combination of commercial Bio-Gide and Bio-Oss, the single HMF scaffold shows comparable or even superior bone repair effect, with better tissue-integration and more suitable degradation time and accompanied by a simplified operation.

pH-Sensitive Polymeric Vesicles for GOx/BSO Delivery and Synergetic Starvation-Ferroptosis Therapy of Tumor.

Typical glucose oxidase (GOx)-based starvation therapy is a promising strategy for tumor treatment; however, it is still difficult to achieve an effective therapeutic effect via a single starvation therapy. Herein, we designed a pH-sensitive polymeric vesicle (PV) self-assembled by histamine-modified chondroitin sulfate (CS-his) for codelivery of GOx and l-buthionine sulfoximine (BSO). GOx can consume glucose to induce the starvation therapy after the PVs reach cancer cell. Moreover, the product H2O2 will be reduced by a high concentration of glutathione (GSH) in the tumor cell, resulting in a reduction of the GSH content. The released BSO finally further reduced the GSH level. As a result, the signaling pathway of the ferroptosis will be activated. The in vivo results demonstrated that GOx/BSO@CS PVs exhibit a good inhibitory effect on the growth of 4T1 tumors in mice. Thus, this work provides a facile strategy to prepare pH-sensitive nanomedicine for synergistic starvation-ferroptosis therapy of tumor.

Engineered multifunctional metal-phenolic nanocoatings for label-free capture and "self-release" of heterogeneous circulating tumor cells.

Immunomagnetic beads have been widely explored as an important analytical tool for the rapid and sensitive detection of circulating tumor cells (CTCs). However, their clinical application is seriously hindered by the tedious preparation procedures and heterogeneous nature of CTCs. To this end, a designed multifunctional platform named Fe3O4@TA/CuII superparamagnetic nanoparticles (SPMNPs) is expected to have the following features: (i) the formation of a tannic acid-copper (II) ion (TA/CuII) coating which could be accomplished by a one-step method is very simple; (ii) the TA/CuII coating shows high affinity for heterogeneous CTCs and good resistance to nonspecific adhesion of blood cells; (iii) "self-release" of the captured cells could be achieved as the TA/CuII coating gradually degrades in the cell culture environment without any additional interventions. Therefore, the resulting Fe3O4@TA/CuII SPMNPs could capture various CTCs (MCF-7, HepG2 and HeLa cells) with different expression levels of the epithelial cell adhesion molecule (EpCAM). And the capture efficiency and cell purity can reach 88% and 87%, respectively. In addition, 68% of the captured cells are self-released after 6 h of incubation and most of the released cells show high cell proliferation activity. In particular, Fe3O4@TA/CuII SPMNPs can successfully detect 1-13 CTCs from 1 mL of blood of 14 patients with 6 types of cancers. Hence, we expect that the as-prepared Fe3O4@TA/CuII SPMNPs with simple, efficient, and universal yet cost-efficient characteristics could act as a promising analytical tool for clinical CTC detection.

Discharge-Induced Enhancement of the Oxygen Evolution Reaction.

The fundamental understanding of the surface reconstruction induced by the applied potential is of great significance for enhancing the oxygen evolution reaction (OER). Here, we show that a previously overlooked discharge current in the low applied potential region also leads to in situ electrochemical activation of a nitrogen-doped nickel oxyhydroxide surface. We exploit the fact that doping of heteroatoms weakens the surface structure, and hence, a weak discharge current originating from the capacitive nature of nickel oxyhydroxide has a strong structure-reforming ability to promote the formation of nitrogen and oxygen vacancies. The current density at 1.4 V (vs. Hg/HgO) can dramatically increase by as much as 31.3 % after discharge in the low applied potential region. This work provides insight into in situ enhancement of the OER and suggests that the low applied potential region must be a primary consideration in evaluating the origin of the activity of electrocatalysts.

Activin receptor-like kinase 4 haplodeficiency alleviates the cardiac inflammation and pacing-induced ventricular arrhythmias after myocardial infarction.

BACKGROUND: Inflammation process is an important determinant for subsequent changes in cardiac function and remodeling after acute myocardial infarction (MI). Recent studies have implicated that ALK4 haplodeficiency improves cardiac function after MI. However, it remains unknown if the beneficial effects are partly attributed to ALK4 haplodeficiency-induced modulation on inflammatory response in the inflammatory phase of MI. In this research, we aimed to explore the mechanism of ALK4 haplodeficiency in the inflammatory stage of MI. METHODS: ALK4, CD16, and CD14 were detected in peripheral blood mononuclear cells (PBMCs) isolated from MI patients and healthy volunteers. ALK4 haplodeficiency (ALK4+/-) mice and wild-type (WT) littermates were randomly divided into the sham group and the MI group. Inflammation cytokines and chemokines were measured. Echocardiography and intracardiac electrophysiological recordings were performed on the 3rd day and the 7th day after MI operation. ALK4 expression and inflammation cytokines were also detected in LPS- or IL-4-stimulated bone marrow-derived macrophages (BMDM) from the ALK4+/- mice and WT littermates. RESULTS: ALK4 gene expression in circulating monocytes of MI patients was higher than that in those of healthy volunteers. Cardiac inflammation and vulnerability of ventricular arrhythmia after acute myocardial injury are significantly alleviated in ALK4+/- mice as compared to WT littermates. On the 3rd day post-MI, the level of M1 macrophages were decreased in ALK4+/- mice as compared to WT littermates, while the level of M2 macrophages were increased on the 7th day post-MI. BMDM isolated from ALK4+/- mice displayed reduced secretion of pro-inflammation cytokines after stimulation by LPS in hypoxic condition and increased secretion of anti-inflammation cytokines after stimulation by IL-4. As a result, the haplodeficiency of ALK4 might be responsible for reduced inflammation response in the post-MI stage. CONCLUSIONS: ALK4 haplodeficiency reduces cardiac inflammation, improves cardiac function, and finally reduces the vulnerability of ventricular arrhythmia in the inflammatory stage after MI.

A dual-site controlled pH probe revealing the pH of sperm cytoplasm and screening for healthy spermatozoa.

A dual-site controlled pH probe, which is composed of gold nanoparticles and modified with rhodamine and fluorescein derivatives, was applied to sensitively monitor intracellular pH changes in sperm. The pH probe revealed the intracellular pH of sperm under different conditions and demonstrated the lower pH in asthenozoospermia patients as compared to healthy individuals. Importantly, the pH probe can help screen for healthy sperm.