Electrophysiological responses of the left atrial appendage during pulsed-field electrical isolation utilizing a novel device in a canine model.

BACKGROUND: The electrophysiological responses of the left atrial appendage (LAA) during pulsed-field electrical isolation have not been established. OBJECTIVE: This study aims to investigate the electrical responses of the LAA during pulsed-field electrical isolation using a novel device and their relations to acute isolation success. METHODS: Six canines were enrolled. The E-SeaLA™ device, which is able to perform LAA occlusion and ablation simultaneously, was deployed into the LAA ostium. LAA potentials (LAAp) were mapped via a mapping catheter, and the LAAp recovery time (LAAp RT, the time between the last pulsed spike and the first recovered LAAp) was measured after pulsed-train delivery. The initial pulse index (PI, corelated to pulsed-field intensity) was adjusted during the ablation procedure until LAAEI was achieved. Acute LAA electrical isolation (LAAEI) success was defined as LAAp disappearance or exit and entrance conduction block, confirmed through a drug test and a 60-minute waiting period. RESULT: All canines achieved successful LAA occlusion without peri-device leaks. Acute LAA electrical isolation (LAAEI) was achieved in five out of six canines (5/6, 83.3%). Very late LAAp recurrence (LAAp RT > 600 s) was observed during PFA. Early recurrence (LAAp RT < 30 s) was observed in two canines (2/6, 33.3%) post-PFA. Intermediate recurrence (LAAp RT ~ 120 s) was observed in three canines (3/6, 50%) post-PFA. The two canines with intermediate recurrence achieved LAAEI with higher PI ablations. The one canine with early LAAp recurrence had a peri-device leak and achieved LAAEI by the same PI after replacing with a larger size device and eliminating the peri-device leak. Another canine with early recurrence (1/6, 16.7%) failed to achieve LAAEI due to epicardial connection with persistent left superior vena cava. No coronary spasm, stenosis or other complications were observed. CONCLUSION: These results suggest that with proper device-tissue contact and pulse intensity, LAAEI can be achieved using this novel device without serious complications. The LAAp RT patterns observed in this study could inform and guide the adjustment of the ablation strategy.

Strontium-incorporated titanium implant surfaces treated by hydrothermal treatment enhance rapid osseointegration in diabetes: A preclinical vivo experimental study.

OBJECTIVES: The aim of the current study was to explore effects of strontium-incorporated titanium implant surfaces by hydrothermal treatment on osseointegration in diabetic rats. MATERIALS AND METHODS: The surface characteristics of SLA and SLA-Sr surfaces were detected by related instruments. Thirty-six male Sprague-Dawley rats were induced into diabetes, and thirty-six rats were normal. SLA and SLA-Sr implants were, respectively, inserted into bilateral tibial metaphysis of each rat. Percentage of bone-to-implant contact (BIC%) and percentage of bone area (BA%) were analyzed at 4 and 8 weeks after implantation. Immunohistochemistry of osteoprotegerin (OPG) and Wnt5a were conducted at 1 and 4 weeks. Gene expression levels of inflammatory cytokines and related signaling molecules in peri-implant bone tissue were detected at 3 and 7 days. RESULTS: Strontium was uniformly distributed on SLA-Sr surfaces, and it was released in an effective concentration range. SLA-Sr surfaces showed significantly higher BIC% in diabetic rats at 4 (p < .05) and 8 weeks (p < .05). Besides, it displayed higher BIC% at 4 weeks (p < .05) in normal rats. Also, SLA-Sr surfaces upregulated expression of OPG at 4 weeks (p < .05) in diabetic rats. What's more, SLA-Sr surfaces downregulated inflammation (TNF-α, IL-1ß, and IL-6; p < .01) in diabetic rats at 3 days. In addition, expression of Wnt5a and ROR2 was upregulated (p < .05) at 7 days after implantation under diabetes. CONCLUSION: It is suggested that strontium-incorporated titanium implant surfaces by hydrothermal treatment could enhance implant osseointegration as compared with SLA implant surfaces in diabetic rats.

Catalytically active gold clusters with atomic precision for noninvasive early intervention of neurotrauma.

BACKGROUND: Neurotrauma is a worldwide public health problem which can be divided into primary and secondary damge. The primary damge is caused by external forces and triggers the overproduction of peroxides and superoxides, leading to long-lasting secondary damage including oxidative stress, wound infection and immunological reactions. The emerging catalysts have shown great potential in the treatment of brain injury and neurogenic inflammation, but are limited to biosafety issues and delivery efficiency. RESULTS: Herein, we proposed the noninvasive delivery route to brain trauma by employing highly active gold clusters with enzyme-like activity to achieve the early intervention. The decomposition rate to H2O2 of the ultrasmall gold clusters is 10 times that of glassy carbon (GC) electrodes, indicating excellent catalytic activity. The gold clusters can relieve the oxidative stress and decrease the excessive O2·- and H2O2 both in vitro and in vivo. Besides, gold clusters can accelerate the wound healing of brain trauma and alleviate inflammation via inhibiting the activation of astrocytes and microglia through noninvasive adminstration. decrease the peroxide and superoxide of brain tissue. CONCLUSIONS: Present work shows noninvasive treatment is a promising route for early intervention of brain trauma.

Preparation and evaluation of HPMC-based pirfenidone solution in vivo.

CONTEXT: Pirfenidone (PFD) has exhibited therapeutic potential in the treatment of cell proliferative disorders. The previously developed 0.5% water-based PFD eye drops by our team exhibited antiscarring effectiveness and ocular safety but with a limit of short half-life and poor bioavailability. OBJECTIVE: To increase bioavailability of the water-based PFD eye drops, we prepared a viscous solution by adding hydroxypropyl methylcellulose (HPMC, F4M), which acted as a viscosity-enhancer. Subsequently, we compared the HPMC-based PFD solution with the water-based PFD eye drops. MATERIALS AND METHODS: PFD solution with 1% HPMC (w/v) was prepared, and the viscosities at different shear rates were measured to investigate its rheology. PFD concentrations in the tear, aqueous humor, conjunctiva, cornea, and sclerae of New Zealand rabbits were detected at different time points with high-performance liquid chromatography (HPLC) following single instillation of the 0.5% PFD (w/v) water-based eye drops or HPMC-based solution. RESULTS: Compared with the 0.5% water-based PFD eye drops, the HPMC-based solution increased the PFD levels in tears and prolonged the residence time from 10 to more than 20 min (p < .01). Consequently, the concentrations of PFD in aqueous humor, conjunctiva, cornea, and sclera were elevated to varying degrees until 90 min after topical administration. CONCLUSIONS: The developed formulation possesses a same readily administration and simple preparation as the PFD eye drops; however, the HPMC-based solution exhibited the higher bioavailability.

Prevalence, types and awareness of glaucoma in a multi-ethnic population in rural China: the Yunnan Minority Eye Study.

PURPOSE: To determine the prevalence, types and awareness of glaucoma in a rural community in China and to examine possible ethnic variations. METHODS: The Yunnan Minority Eye Study was a multi-ethnic community-based eye survey using random cluster sampling strategies. 2133 Bai, 2205 Han and 2208 Yi Chinese aged 50 years or older participated in this study. Glaucoma including primary open-angle glaucoma (POAG), primary angle-closure glaucoma (PACG) and secondary glaucoma was defined based on the International Society of Geographical and Epidemiological Ophthalmology criteria. RESULTS: The overall age-standardized prevalence of all glaucoma was 2.6% (95% confidence interval [CI]: 2.2-3.1%) in this population. It was 1.8% (95% CI: 1.1-1.9%) for POAG and 0.5% (95% CI: 0.9-1.6%) for PACG, respectively. Among 29 people with secondary glaucoma, 27 (93%) were blind in at least one eye. The presence of primary open-angle glaucoma was associated with male gender (odds ratio [OR] = 2.94; comparing men with women), Yi ethnicity (OR = 2.27; comparing Yi with Han people), higher IOP (OR = 1.09 per mmHg increase), and the presence of myopia (OR = 1.84). Of the 212 participants with glaucoma, only 38 (18%) were aware of the disease and had been diagnosed previously as having glaucoma or suspected glaucoma. Patients who were better educated tended to be aware of the disease. CONCLUSIONS: Significant ethnic difference in the prevalence of POAG was observed in this study. The low awareness of glaucoma highlights the pressing need to increase public awareness of this potentially blinding condition in rural China.

[A prospective randomized study of selective laser trabeculoplasty (SLT) as a replacement for medical therapy in primary open-angle glaucoma].

OBJECTIVE: To evaluate the efficacy and safety of selective laser trabeculoplasty (SLT) as a replacement for medical therapy in primary open-angle glaucoma (POAG). METHODS: A prospective, randomized, controlled study.SLT treatment with SOLO SLT Nd: YAG laser was provided to 45 participants with advanced POAG (67 eyes, IOP ≤ 21 mmHg, 1 mmHg = 0.133 kPa) under anti-glaucomatous medications control). A table of random numbers was created by simple randomization method. Participants were randomly divided into two groups: the standard-energy group (34 eyes), which received a 270° standard-energy SLT treatment and the sub-threshold energy group (33 eyes), which received a 360° sub-threshold energy treatment. The intraocular pressure (IOP) before and after SLT, daytime IOP curve, dosage of anti-glaucoma drugs and treatment complications were observed, which were be followed up for 6-9 months (average 6.4 months). Two-tailed t-test or paired t test was used when the continuous variables were normal distribution, such as the basic data, daily fluctuations of IOP, laser energy. Non-parametric Mann-Whitney U test or Wilcoxon rank test was used when data was not distributed normally, such as drug category. Chi-square or Fisher's exact test was used when count variables such as success rate and complications were analyzed. RESULTS: The number of anti-glaucomatous drugs used in the standard-energy group and the sub-threshold energy group before SLT was (2.3 ± 0.5) and (2.1 ± 0.4), respectively; whereas, after the last treatment, it reduced to (1.3 ± 0.5) and (1.1 ± 0.3), respectively (Z = -5.477, -5.396; P < 0.05). The success rate of the standard-energy group and the sub-threshold energy group was 91.1%, and 87.9%, respectively, which was not significant different (P = 0.70). Laser treatment was found to reduce the IOP fluctuation during the daytime.IOP fluctuation decreased from (3.6 ± 1.0) mmHg to (2.3 ± 1.0) mmHg in the standard-energy group, and decreased from (3.9 ± 1.4) mmHg to (2.4 ± 0.9) mmHg in the sub-threshold energy group, which was significant different (t = 4.911, 4.679; P < 0.05). The total laser energy of the standard-energy group (47.8 ± 6.0) mJ was higher than the sub-threshold energy group (43.2 ± 5.1) mJ (t = 12.006, 3.233; P < 0.05). However, there was no significant difference in the daily IOP fluctuations, success rate, reduction of medication categories, preoperative and postoperative IOP, and adverse reactions between the two groups. CONCLUSIONS: SLT is a safe and effective replacement for medical therapy in primary open-angle glaucoma treatment. SLT could reduce the applications of anti-glaucoma drugs. There was no significant difference between therapeutic effects of which eyes received 360° sub-threshold energy and 270° standard-energy.

Pooled-analysis of the association between TIM-1 5383_5397 insertion/deletion polymorphism and asthma susceptibility.

The T cell immunoglobulin (Ig) domain and mucin domain 1 (TIM-1) gene play an important role in pathogenesis of asthma. We investigate the association between the TIM-1 5383_5397 insertion/deletion polymorphism (rs45623443) and the risk of asthma in an asthma case-control study, and added these data to a literature-based meta-analysis. The TIM-1 5383_5397 insertion/deletion polymorphism genotype was analyzed in 156 asthma patients and 162 healthy subjects from Han Chinese population. We combined our data with that from previously published studies and performed a meta-analysis to evaluate the effect of the gene. Through regression model, we found no significant association for TIM-1 5383_5397 insertion/deletion polymorphism in our cohort. Meta-analysis, comprising a total of 1,577 asthma cases and 1,781 controls, revealed that no significant association between and asthma susceptibility was observed (OR = 0.99, 95 % CI = 0.83-1.20 for Ins vs. Del; OR = 1.01, 95 % CI = 0.74-1.37 for Ins/Ins vs. Ins/Del + Del/Del; OR = 0.96, 95 % CI = 0.78-1.18 for Ins/Ins + Ins/Del vs. Del/Del). The present meta-analysis suggested that TIM-1 5383_5397 insertion/deletion polymorphism may not substantially contribute to asthma susceptibility. However, gene-gene and gene-environment interaction effects and other considerations involving this polymorphism may exit.

A universal framework for determining the effect of operating parameters on piezoionic voltage generation.

The piezoionic effect, the generation of a transient voltage in a polymer matrix infused with ion embedded solvent upon the application of a mechanical stimulus, has demonstrated potential applications in ionic sensing, actuation, interfaces, and energy harvesting. Considerable progress has been made to increase voltage output based on optimizing the morphology and composition of materials. However, regardless of the materials used, in order to design and operate piezoionic devices efficiently, the effect of operating parameters, for example, the strength, speed, and location of the mechanical stimulus, as well as the collection of the piezoionic signal using electrodes are of equal importance. Yet, there has not been any systematic exploration of such operating parameters, leading to the present ad hoc approaches to the design, operation, and performance evaluation of piezoionic systems. In this work, we systematically show the effect of operating parameters on piezoionic voltage generation and provide a universal framework to describe new observations. To elucidate the relationship between the piezoionic response and the underlying mechanism, we propose a novel spatial-temporal strategy for characterizing the piezoionic effect. To ensure generality, newfound insights are modeled and cross-validated over a wide range of experimental data. New observations and new theoretical attributions resulting from this work provide the first systematic method towards optimizing the structure, geometry, and test of piezoionic devices.

Intraoperative management during liver transplantation in the child with mitochondrial depletion syndrome: A case report.

INTRODUCTION: Mitochondrial DNA depletion syndrome (MDS) is a kind of autosomal recessive genetic disorder associated with a reduction in mitochondrial DNA (mtDNA) copy number caused by mutations in nuclear genes during nucleotide synthesis, which affects the energy production of tissues and organs. Changes in hemodynamics during liver transplantation may lead to high energy-demanding organs and tissues being vulnerable. This report described the intraoperative management during liver transplantation in a child with MDS. Ultimately, the child was discharged smoothly without any complications. PRESENTATION OF THE CASE: A five-year-old boy was diagnosed with mitochondrial depletion syndrome preoperatively and scheduled for living donor liver transplantation. The incidence of postreperfusion syndrome (PRS) could not be avoided for 30 min after opening, despite our best efforts to aggressively prevent it before opening. While ensuring hemodynamic stability, we actively prevented and adopted high-energy-demand organ protection strategies to reduce the incidence of postoperative complications. Finally, the child was discharged 28 days after the operation, and no other complications were found. DISCUSSION: Liver transplantation can be performed for liver failure in this disease to improve the quality of life and prolong the life of patients. As this child has mitochondrial DNA depletion syndrome, the disruption of cellular energy generation caused by mitochondrial malfunction puts high-energy-demanding organs and tissues at risk during surgery. It motivates us to pay closer attention to the prevention and treatment of PRS in anesthetic management to minimize damage to the child's organs and tissues with high energy demands. CONCLUSIONS: This report describes the intraoperative management during liver transplantation in a child with mitochondrial depletion syndrome. To increase the safety of perioperative anesthesia and reduce mortality in patients with mitochondrial disease, for such patients, maintaining an acid-base balance and a stable internal environment is essential. We should also pay attention to protecting body temperature, using vasoactive drugs beforehand to lessen the incidence of PRS, and protecting high-energy-demanding organs afterward.

Identifying potential key ferroptosis-related genes and therapeutic drugs in sepsis-induced ARDS by bioinformatics and experimental verification.

BACKGROUND: Acute respiratory distress syndrome (ARDS) is a serious pathological process with high mortality. Ferroptosis is pivotal in sepsis, whose regulatory mechanisms in sepsis-induced ARDS remains unknown. We aimed to determine key ferroptosis-related genes in septic ARDS and investigate therapeutic traditional Chinese medicine (TCM). METHOD: Sepsis-induced ARDS dataset obtained from Gene Expression Omnibus (GEO) was analyzed to identify ferroptosis-related differentially expressed genes (FRDEGs). Enrichment analysis and protein-protein interaction (PPI) network construction were performed to identify hub genes. Immune cells infiltration was analyzed and competitive endogenous RNA (ceRNA) network was constructed. The diagnostic value of hub genes in septic ARDS was analyzed and the occurrence of ferroptosis and the expression of hub genes were detected. TCM targeting hub genes was predicted via SymMap database and was verified. RESULTS: 16 FRDEGs were obtained, among which the top four genes (IL1B, TXN, MAPK3, HSPB1) were selected as hub genes, which may be potential diagnostic markers of septic ARDS. Immunoassay showed that sepsis-induced ARDS and hub genes were closely related to immune cells. The ceRNA network showed 26 microRNAs and 38 long noncoding RNA (lncRNAs). Ferroptosis occurred and the expressions of IL1B, MAPK3 and TXN were increased in septic ARDS mice and LPS-challenged human pulmonary alveolar epithelial cells (HPAEpiCs). Sea buckthorn alleviated septic lung injury and affected hub genes expression. CONCLUSIONS: Ferroptosis-related genes of IL1B, MAPK3 and TXN serve as potential diagnostic genes for sepsis-induced ARDS. Sea buckthorn may be therapeutic medication for ARDS. This study provides a new direction for septic ARDS treatment.

The Impact of Intraocular Pressure Changes on Corneal Biomechanics in Primary Open-angle Glaucoma.

PURPOSE: To investigate the relationship between intraocular pressure (IOP) changes and corneal biomechanical properties, determine the quantitative relationship between IOP changes and corneal biomechanical properties in patients with glaucoma and observe the differences among different types of glaucoma when the effects of high-level IOP were excluded. DESIGN: Prospective clinical cohort study. METHODS: Setting: Institutional. PATIENTS: Treatment-naive patients with primary open-angle glaucoma or ocular hypertension (OHT) were included. OBSERVATION PROCEDURES: IOP was measured using a Goldmann applanation tonometer. Corneal biomechanics were evaluated using a corneal indentation device and corneal visualization Scheimpflug technology. Medication therapy was used for IOP reduction. Repeated measurements were taken at the baseline visit and each week thereafter within a month. Paired t tests were used to compare IOP and corneal biomechanical metrics before and after IOP-lowering therapy. One-way analysis of variance was employed to investigate potential differences across groups, with a Bonferroni post hoc correction administered for multiple intergroup comparisons. MAIN OUTCOME MEASURES: Corneal biomechanical parameters following IOP changes. RESULTS: Eighty-one participants (mean age, 41.63 ± 17.33 years) were included in this study. The cohort comprised 20 patients with normal-tension glaucoma (NTG), 47 with high-tension glaucoma (HTG), and 14 with OHT. The baseline corneal stiffness (88.58 ± 18.30 N/m) and corneal modulus (0.71 ± 0.16 MPa) were greater than the post-IOP reduction values (67.15 ± 9.24 N/m and 0.54 ± 0.08 MPa, respectively; P < .001). The relationships between changes in IOP and changes in corneal biomechanical parameters were Δ corneal stiffness = 2.06*ΔIOP+6.47 (P < .001) and Δ corneal modulus = 0.017*ΔIOP+0.051 (P < .001). After IOP reduction, the mean corneal stiffness at the 4th week in the NTG group was significantly lower (60.97 ± 6.36 N/m) than that in the HTG (67.25 ± 9.01 N/m) and OHT (75.62 ± 6.52 N/m, P < .001) groups. Additionally, the stiffness of HTG patients was lower than that of OHT patients (P = .003). CONCLUSIONS: Changes in IOP have an impact on corneal biomechanical parameters. Decreases in corneal stiffness and modulus were observed after IOP reduction. When the effect of high-level IOP was excluded, corneal biomechanics varied according to the type of glaucoma. The HTG corneas were softer than the OHT corneas, and the NTG corneas were even softer.

Efficacy and Safety of Surgical Peripheral Iridectomy, Goniosynechialysis, and Goniotomy for Advanced Primary Angle Closure Glaucoma Without Cataract: 1-Year Results of a Multicenter Study.

PRCIS: The combination of surgical peripheral iridectomy, goniosynechialysis, and goniotomy is a safe and effective surgical approach for advanced primary angle closure glaucoma without cataract. PURPOSE: To evaluate the efficacy and safety of surgical peripheral iridectomy (SPI), goniosynechialysis (GSL), and goniotomy (GT) in advanced primary angle closure glaucoma (PACG) eyes without cataract. PATIENTS AND METHODS: A prospective multicenter observational study was performed for patients who underwent combined SPI, GSL, and GT for advanced PACG without cataract. Patients were assessed before and after the operation. Complete success was defined as achieving intraocular pressure (IOP) between 6 and 18 mm Hg with at least a 20% reduction compared with baseline, without the use of ocular hypotensive medications or reoperation. Qualified success adopted the same criteria but allowed medication use. Factors associated with surgical success were analyzed using logistic regression. RESULTS: A total of 61 eyes of 50 advanced PACGs were included. All participants completed 12 months of follow-up. Thirty-six eyes (59.0%) achieved complete success, and 56 eyes (91.8%) achieved qualified success. Preoperative and postsurgical at 12 months mean IOPs were 29.7±7.7 and 16.1±4.8 mm Hg, respectively. The average number of ocular hypotensive medications decreased from 1.9 to 0.9 over 12 months. The primary complications included IOP spike (n=9), hyphema (n=7), and shallow anterior chamber (n=3). Regression analysis indicated that older age (odds ratio [OR]=1.09; P =0.043) was positively associated with complete success, while a mixed angle closure mechanism (OR=0.17; P =0.036) reduced success rate. CONCLUSIONS: The combination of SPI, GSL, and GT is a safe and effective surgical approach for advanced PACG without cataract. It has great potential as a first-line treatment option for these patients.

Phacogoniotomy versus phacotrabeculectomy for advanced primary angle-closure glaucoma with cataract: A randomized non-inferiority trial.

PURPOSE: To investigate the effectiveness and safety of phacogoniotomy versus phacotrabeculectomy (PVP) among patients with advanced primary angle-closure glaucoma (PACG) and cataracts. DESIGN: Multicenter, randomized controlled, non-inferiority trial. METHODS: A total of 124 patients (124 eyes) with advanced PACG and cataracts were enrolled, with 65 in the phacogoniotomy group and 59 in the phacotrabeculectomy group. Patients were followed up for 12 months with standardized evaluations. The primary outcome was the reduction in intraocular pressure (IOP) from baseline to 12 months postoperatively, of which a non-inferiority margin of 4 mmHg was evaluated. Secondary outcomes included the cumulative surgical success rate, postoperative complications, and changes in the number of glaucoma medications. RESULTS: After 12 months, phacogoniotomy demonstrated non-inferiority to phacotrabeculectomy in terms of IOP reduction, with mean IOP reductions of - 26.1 mmHg and - 25.7 mmHg (P = 0.383), respectively, from baseline values of around 40 mmHg. Both groups experienced a significant reduction in the mean number of medications used postoperatively (P < 0.001). The cumulative success rate was comparable between the groups (P = 0.890). However, phacogoniotomy had a lower rate of postoperative complications and interventions (12.3% and 4.6%) compared to phacotrabeculectomy (23.7% and 20.3% respectively). The phacogoniotomy group reported shorter surgery time (22.1 ± 6.5 vs. 38.8 ± 11.1 min; P = 0.030) and higher quality of life (EQ-5D-5 L) improvement at 12 months (7.0 ± 11.5 vs. 3.0 ± 12.9, P = 0.010) than the phacotrabeculectomy group. CONCLUSIONS: Phacogoniotomy was non-inferior to phacotrabeculectomy in terms of IOP reduction for advanced PACG and cataracts. Additionally, phacogoniotomy provided a shorter surgical time, lower postoperative complication rate, fewer postoperative interventions, and better postoperative quality of life.

Pirfenidone inhibits migration, differentiation, and proliferation of human retinal pigment epithelial cells in vitro.

PURPOSE: To investigate the effects of pirfenidone (PFD) on the migration, differentiation, and proliferation of retinal pigment epithelial (RPE) cells and demonstrate whether the drug induces cytotoxicity. METHODS: Human RPE cells (line D407) were treated with various concentrations of PFD. Cell migration was measured with scratch assay. The protein levels of fibronectin (FN), connective tissue growth factor (CTGF), α-smooth muscle actin (α-SMA), transforming growth factor beta (TGFßS), and Smads were assessed with western blot analyses. Levels of mRNA of TGFßS, FN, and Snail1 were analyzed using reverse transcriptase-polymerase chain reaction. Cell apoptosis was detected with flow cytometry using the Annexin V/PI apoptosis kit, and the percentages of cells labeled in different apoptotic stage were compared. A Trypan Blue assay was used to assess cell viability. RESULTS: PFD inhibited RPE cell migration. Western blot analyses showed that PFD inhibited the expression of FN, α-SMA, CTGF, TGFß1, TGFß2, Smad2/3, and Smad4. Similarly, PFD also downregulated mRNA levels of Snail1, FN, TGFß1, and TGFß2. No significant differences in cell apoptosis or viability were observed between the control and PFD-treated groups. CONCLUSIONS: PFD inhibited RPE cell migration, differentiation, and proliferation in vitro and caused no significant cytotoxicity.

Atomic Plasma Grafting: Precise Control of Functional Groups on Ti3C2Tx MXene for Room Temperature Gas Sensors.

Gas sensing properties of two-dimensional (2D) materials are derived from charge transfer between the analyte and surface functional groups. However, for sensing films consisting of 2D Ti3C2Tx MXene nanosheets, the precise control of surface functional groups for achieving optimal gas sensing performance and the associate mechanism are still far from well understood. Herein, we present a functional group engineering strategy based on plasma exposure for optimizing the gas sensing performance of Ti3C2Tx MXene. For performance assessment and sensing mechanism elucidation, we synthesize few-layered Ti3C2Tx MXene through liquid exfoliation and then graft functional groups via in situ plasma treatment. Functionalized Ti3C2Tx MXene with large amounts of -O functional groups shows NO2 sensing properties that are unprecedented among MXene-based gas sensors. Density functional theory (DFT) calculations reveal that -O functional groups are associated with increased NO2 adsorption energy, thereby enhancing charge transport. The -O functionalized Ti3C2Tx sensor shows a record-breaking response of 13.8% toward 10 ppm NO2, good selectivity, and long-term stability at room temperature. The proposed technique is also capable of improving selectivity, a well-known challenge in chemoresistive gas sensing. This work paves the way to the possibility of using plasma grafting for precise functionalization of MXene surfaces toward practical realization of electronic devices.

Dysregulation of striatal dopamine D2/D3 receptor-mediated by hypocretin induces depressive behaviors in rats.

BACKGROUND: The dysregulation of the dopamine system contributes to depressive-like behaviors in rats, and the neurological functions regulated by hypocretin are severely affected in depression. However, whether suvorexant plays a role in alleviating depression by affecting the dopamine system is unclear. METHODS: To preliminarily explore the mechanism of suvorexant (10 mg/kg) in the treatment of depression, the mRNA and protein expression of TH, Drd2, Drd3, GluN2A, DAT, and GluN2B in the striatum of rats was quantified by qPCR and western blotting. The plasma hypocretin-1 and dopamine levels and the striatal dopamine levels were determined by ELISA. RESULTS: i) Compared to those of the control group, chronic unpredictable mild stress (CUMS) rats showed depressive-like behaviors, which were subsequently reversed by treatment with suvorexant. ii) The mRNA and protein expressions of TH, Drd2, Drd3, GluN2A, and GluN2B in the striatum of CUMS were significantly increased compared with those in the controls, but decreased after suvorexant treatment. iii) Compared with those in the control group, the plasma and striatal dopamine levels of CUMS decreased while plasma hypocretin-1 levels increased, which was reversed after suvorexant treatment. LIMITATIONS: i) The suvorexant is a dual hypocretin receptor antagonist; however, the responsible receptor is unclear. ii) We only focused on related factors in the striatum but did not explore other brain regions, nor did we directly explore the relationship among these factors. CONCLUSION: Depressive-like behaviors induced by CUMS can be reversed by suvorexant, and the therapeutic effects of suvorexant may be mediated by affecting the dopamine system.

Refinement of sensitive azides via in situ generated azole-based metal-organic frameworks towards stable energetic materials.

Energetic materials (EMs) have been widely employed in both military and civilian areas for nearly two centuries. The introduction of high-energy azide anions to assemble energetic metal-organic frameworks (EMOFs) is an efficient strategy to enhance energetic properties. However, azido-based EMOFs always suffer low stabilities to external mechanical stimulation. Herein, we employed an in situ hydrothermal reaction as a technique to refine azide anions with a neutral triazole-cyano-based ligand TrzAt (TrzAt = 2-(1H-1,2,4-triazol-1-yl)acetonitrile) to yield two tetrazole-based EMOFs, namely, [ZnBr(trmetz)]n1 and [Cd(trmetz)2]n2 (Htrmetz = 5-(1,2,4-triazol-1-ylmethyl)-1H-tetrazole). Compound 1 features a closely packed 2D layered network, while compound 2 exhibits a 3D architecture. With azide anions inlaid into a nitrogen-rich and chelating ligand in the EMOFs, compounds 1 and 2 present remarkable decomposition temperatures (Tdec ≥ 300 °C), low impact sensitivities (IS ≥ 32 J) and low friction sensitivities (FS ≥ 324 N). The calculated heat of detonation (ΔHdet) values of 1 and 2 are 3.496 and 4.112 kJ g-1, respectively. In particular, the ΔHdet value of 2 is higher than that of traditional secondary explosives such as 2,4,6-trinitrotoluene (TNT, ΔHdet = 3.720 kJ g-1). These results indicate that EMOFs 1 and 2 may serve as potential replacements for traditional secondary explosives. This work provides a simple and effective strategy to obtain two EMOFs with satisfactory energy densities and reliable stabilities through an in situ hydrothermal technique for desensitization of azide anions.

Coordination polymerization of nitrogen-rich linkers and dicyanamide anions toward energetic coordination polymers with low sensitivities.

The design and synthesis of energetic materials (EMs) with high energy and reliable stabilities has attracted much attention in the field of EMs. In this work, we employed a strategy of the coordination polymerization of mild dicyanamide ions (DCA-), two isomeric ligands 1-methyl-5-aminotetrazole (1-MAT) and 2-methyl-5-aminotetrazole (2-MAT) to construct energetic coordination polymers (ECPs). Four new ECPs {[Co(DCA)2(1-MAT)2]·H2O}n1, [Cu(DCA)2(1-MAT)]n2, [Cd(DCA)2(1-MAT)2]n3 and [Cd(DCA)2(2-MAT)2]n4 were successfully synthesized through solvent evaporation routes. Compounds 1 and 4 display 1D chains, while 2 and 3 exhibit 2D-layered structures. Compounds 1-3 with the 1-MAT ligand all exhibit reliable thermal stabilities (> 200 °C). The calculated heats of detonation (ΔHdet) of 1-3 are all higher than 1.4 kJ g-1, which are higher than traditional explosive TNT (1.22 kJ g-1) and the reported ECP AgMtta (HMtta = 5-methyl-1H-tetrazole, ΔHdet = 1.32 kJ g-1). Furthermore, sensitivity testing demonstrates that 1-4 features low mechanical sensitivity to external mechanical action in contrast with the extremely sensitive azide-based ECPs [Cu3(2-MAT)2(N3)6]n. In addition, compound 2 shows hypergolic properties via an 'oxidizer-fuel' drop experiment, demonstrating its application prospects in the field of propellants. This work details an approach of synthesizing multipurpose ECPs with reliable stabilities by introducing mild dicyanamide anions into nitrogen-rich skeletons.

[Dynamic aspects of corneal lymphatic vessels after keratoplasty in rats].

OBJECTIVE: To study the development of lymphatic vessels after keratoplasty and to explore the molecular mechanisms of corneal lymphangiogenesis in transplanted corneas. METHODS: Experimental research. The development of corneal lymphangiogenesis was examined by LYVE-1 immunohistochemistry and whole mount immunofluorescence 1, 3, 7, 10, 14, 30 and 60 days after corneal transplantation, then lymphatic vessels counting (LVC)was evaluated. The expression of vascular endothelial growth factor-C (VEGF-C) in transplanted corneas was examined by immunohistochemistry, enzyme-linked immunosorbent assay (ELISA), and real time-PCR at same time. In addition, the inflammatory index (IF) was recorded at each time point. The association of VEGF-C and IF with LVC in transplanted corneas was examined. Analysis of the significance of differences between two groups was performed using paired Student's t-test. Pearson's analysis was used to analyze the correlation between VEGF-C, IF and LVC. RESULTS: Corneal lymphangiogenesis occurred in the stroma with LVC (1.8 ± 0.3) on Day 3, then developed and reached the peak with LVC (9.1 ± 1.5) on Day 14 after corneal transplantation. Both VEGF-C protein and mRNA up-regulated dramatically in rat transplanted corneas. The immunoreactivity reached the peak on the 3(rd) day and the 14(th) day after keratoplasty. Compared with the expression of VEGF-C mRNA (1.62 ± 0.08 copies/g) on Day 3, the expression of VEGF-C mRNA (2.48 ± 0.03 copies/g) significantly increased 14 days after the transplantation (t = 4.296, P = 0.02). LVC was strongly and positively correlated with IF (r = 0.55, P = 0.003) and the expression of VEGF-C mRNA (r = 0.51, P = 0.003). CONCLUSIONS: Corneal lymphangiogenesis correlates closely with corneal inflammation. The increased expression of VEGF-C in the cornea may be one of the important molecular mechanisms in the occurrence of corneal lymphangiogenesis after keratoplasty.

Analysis of implant loss risk factors after simultaneous guided bone regeneration: A retrospective study of 5404 dental implants.

PURPOSE: The purpose was to analyze the risk factors for implant loss after simultaneous guided bone regeneration (GBR). MATERIALS AND METHODS: Patients who underwent implant placement with simultaneous GBR between January 2011 and December 2018 were screened for this study. The cumulative survival rate (CSR) was calculated using the life table method. Log-rank test and Kaplan-Meier survival estimates were used to identify potential risk factors for implant loss. The association between the investigated variables and implant loss was determined using hazard ratios (HRs) obtained from a multivariate Cox regression analysis. RESULTS: A total of 3973 patients with 5404 implants were included in this study. The CSRs of the implants at 1, 5, and 10 years were 99.6%, 98.9%, and 98.7%, respectively. Male patient (HR = 2.94, 95% CI: 1.41-6.14), periodontitis (HR = 4.26, 95% CI: 2.05-9.86), tissue-level implants (HR = 3.02, 95% CI: 1.30-6.98), narrow implants (HR = 2.71, 95% CI: 1.12-6.57), and implant length ≤10 mm (HR = 2.91, 95% CI: 1.41-6.02) significantly increased the risk of implant loss (p < 0.05). The risk of implant loss was significantly higher in the maxillary posterior region (HR = 2.26, 95% CI: 1.04-4.90) than in the maxillary anterior region (p < 0.05). Compared to Straumann, Nobel (HR = 4.07, 95% CI: 1.75-9.44) and other implant systems (HR = 14.23, 95% CI: 4.32-46.85) showed a significantly higher risk of implant loss (p < 0.05). CONCLUSION: Male patient, periodontitis, maxillary posterior region, Nobel implant system, other implant systems, tissue-level implants, narrow implants, and implant length ≤10 mm were considered risk factors for implant loss after simultaneous GBR.