Effects of temporal changes in resting heart rate on future diabetes-related outcomes.

Background and aims: Most studies have analyzed the relationship between resting heart rate (RHR) measured at only one time point and future clinical events. The current study aims to investigate the impact of long-term RHR changes on future clinical outcomes in a decade-long cohort with type 2 diabetes mellitus (T2DM). Methods: The two-staged follow-up involved 2,513 T2DM participants. The first stage (2008-2014) intended to identify levels and trends in RHR changes, while the second stage (2014-2018) attempted to collect new occurrence records of clinical results. Cox proportional hazards models were applied to predict hazard ratios (HRs), along with 95% confidence interval (CI) for the correlation between RHR changes and future events. Results: There is no significant correlation between baseline RHR levels and long-term clinical events. According to the range of RHR change, compared with the stable RHR group, the adjusted HRs for cardiovascular events and all-cause death in the large increase group were 3.40 (95% CI: 1.33-8.71, p=0.010) and 3.22 (95% CI: 1.07-9.64, p=0.037), respectively. While the adjusted HRs for all-cause death and major adverse cardiac and cerebrovascular events (MACCE) in the moderate decrease group were 0.55 (95% CI: 0.31-0.96, p=0.037) and 0.51 (95% CI: 0.26-0.98, p=0.046). According to the trend of RHR, compared with the normal-normal group, the adjusted HRs for composite endpoint events and cerebrovascular events in the normal-high group were 1.64 (95% CI: 1.00-2.68, p=0.047) and 2.82 (95% CI: 1.03-7.76, p=0.043), respectively. Conclusion: Changes in RHR had predictive value for long-term clinical events in diabetic populations. Individuals with significantly elevated RHR over a particular period of time showed an increased risk of adverse events.

Single Mn atom modulated molecular oxygen activation over TiO2 for photocatalytic formaldehyde oxidation.

In single-atom catalysts, the atomically dispersed metal sites are pivotal for oxygen molecule activation. We hypothesize that dispersing single Mn atoms on TiO2 nanosheets may improve the photocatalytic oxidation of formaldehyde (HCHO) in the gas phase under ambient conditions. Density function theory (DFT) and experimental experiments were carried out to single Mn atoms not only improved the transfer of localized electrons and photogenerated electrons but also enhanced the activation/dissociation of O2 to generate monoatomic oxygen ions (O-) as the final reactive oxygen species (ROS). In photocatalytic experiments, Mn/TiO2 photocatalyst removed 100 % of HCHO at a low concentration of 7.6 ppm, and reaching excellent mineralization efficiency of over 99.6 %. According to the proposed reaction mechanism, O2 spontaneously adsorbs onto the Mn/TiO2 surface, forming two adsorbed O- after electron donation into the π2p* antibonding orbitals of O2. The adsorbed O- then reacts with gaseous HCHO to produce the key intermediate dioxymethylene (DOM), finally fulfilling a more favorable oxidation process on the Mn/TiO2 surface. This research illustrates the key role of O- in HCHO oxidation and paves the way for practical HCHO removal using TiO2-based photocatalysts.

Plasma levels of Sirtuin 7 are decreased in patients with essential hypertension.

BACKGROUND: Sirtuin 7 (SIRT7), as a nicotinamide adenine dinucleotide-dependent protein/histone deacetylase, has been implicated in the pathogenesis of cardiovascular diseases. However, whether SIRT7 is related to hypertension remains largely unclear. Thus, this study aims to explore the effects and correlation between SIRT7 and hypertension. METHODS: A total of 72 patients with essential hypertension and 82 controls with non-hypertension were recruited at Beijing Tongren Hospital Affiliated with Capital Medical University from July 2022 to June 2023. Plasma SIRT7 expression was measured using enzyme-linked immunosorbent assay analysis. Clinical baseline characteristics, laboratory measurements, echocardiographic data, and medical therapy were collected. RESULTS: Plasma levels of SIRT7 were lower in hypertensive patients compared with non-hypertensive patients [0.97 (0.58-1.30) vs. 1.24 (0.99-1.46) ng/mL, P < 0.001, respectively]. Furthermore, compared with the low SIRT7 group, there were lower levels of systolic blood pressure, hyperlipidemia, and the ultrasonic electrocardiogram parameters left ventricular end-diastolic diameter and left atrial in diastole in the high SIRT7 group (P < 0.05, respectively). More importantly, multivariate logistic regression analyses indicated that plasma SIRT7 was a predictor of hypertension [OR: 0.06, 95 % CI (0.02-0.19), P < 0.001]. Receiver operating characteristics curve analysis revealed that the optimal cutoff value for plasma SIRT7 levels in detecting hypertension was determined as 0.85 ng/mL with a sensitivity of 73.6 % and a specificity of 89.0 %. The area under the curve for SIRT7 was 0.821 (95 % CI, 0.751-0.878; P < 0.001). CONCLUSION: Plasma levels of SIRT7 are decreased in patients with essential hypertension, implying its potential as a biomarker for diagnosing essential hypertension..

Corticotropin-releasing hormone neurons control trigeminal neuralgia-induced anxiodepression via a hippocampus-to-prefrontal circuit.

Anxiety and depression are frequently observed in patients suffering from trigeminal neuralgia (TN), but neural circuits and mechanisms underlying this association are poorly understood. Here, we identified a dedicated neural circuit from the ventral hippocampus (vHPC) to the medial prefrontal cortex (mPFC) that mediates TN-related anxiodepression. We found that TN caused an increase in excitatory synaptic transmission from vHPCCaMK2A neurons to mPFC inhibitory neurons marked by the expression of corticotropin-releasing hormone (CRH). Activation of CRH+ neurons subsequently led to feed-forward inhibition of layer V pyramidal neurons in the mPFC via activation of the CRH receptor 1 (CRHR1). Inhibition of the vHPCCaMK2A-mPFCCRH circuit ameliorated TN-induced anxiodepression, whereas activating this pathway sufficiently produced anxiodepressive-like behaviors. Thus, our studies identified a neural pathway driving pain-related anxiodepression and a molecular target for treating pain-related psychiatric disorders.

Glia-derived adenosine in the ventral hippocampus drives pain-related anxiodepression in a mouse model resembling trigeminal neuralgia.

Glial activation and dysregulation of adenosine triphosphate (ATP)/adenosine are involved in the neuropathology of several neuropsychiatric illnesses. The ventral hippocampus (vHPC) has attracted considerable attention in relation to its role in emotional regulation. However, it is not yet clear how vHPC glia and their derived adenosine regulate the anxiodepressive-like consequences of chronic pain. Here, we report that chronic cheek pain elevates vHPC extracellular ATP/adenosine in a mouse model resembling trigeminal neuralgia (rTN), which mediates pain-related anxiodepression, through a mechanism that involves synergistic effects of astrocytes and microglia. We found that rTN resulted in robust activation of astrocytes and microglia in the CA1 area of the vHPC (vCA1). Genetic or pharmacological inhibition of astrocytes and connexin 43, a hemichannel mainly distributed in astrocytes, completely attenuated rTN-induced extracellular ATP/adenosine elevation and anxiodepressive-like behaviors. Moreover, inhibiting microglia and CD39, an enzyme primarily expressed in microglia that degrades ATP into adenosine, significantly suppressed the increase in extracellular adenosine and anxiodepressive-like behaviors. Blockade of the adenosine A2A receptor (A2AR) alleviated rTN-induced anxiodepressive-like behaviors. Furthermore, interleukin (IL)-17A, a pro-inflammatory cytokine probably released by activated microglia, markedly increased intracellular calcium in vCA1 astrocytes and triggered ATP/adenosine release. The astrocytic metabolic inhibitor fluorocitrate and the CD39 inhibitor ARL 67156, attenuated IL-17A-induced increases in extracellular ATP and adenosine, respectively. In addition, astrocytes, microglia, CD39, and A2AR inhibitors all reversed rTN-induced hyperexcitability of pyramidal neurons in the vCA1. Taken together, these findings suggest that activation of astrocytes and microglia in the vCA1 increases extracellular adenosine, which leads to pain-related anxiodepression via A2AR activation. Approaches targeting astrocytes, microglia, and adenosine signaling may serve as novel therapies for pain-related anxiety and depression.

Robust Ti3C2Tx MXene foam modified with natural antioxidants for long-term effective electromagnetic interference shielding.

MXenes have been proven to be outstanding lossy phase of advanced electromagnetic interference (EMI) shielding materials. However, their poor tolerance to oxygen and water results in fast degradation of the pristine two-dimensional (2D) nanostructure and fading of the functional performance. Herein, in this research, natural antioxidants (e.g., melatonin, tea polyphenols, and phytic acid) were employed to protect the Ti3C2Tx MXene from its degradation in order to achieve a long-term stability of the EMI shielding performance. The results showed that the synthesized composites comprised of antioxidants and Ti3C2Tx exhibited a decelerating degradation rate resulting in an improved EMI shielding effective (SE) stability. The antioxidation mechanism of the applied antioxidants is discussed with respect to the nanostructure evolution of the Ti3C2Tx MXene. This work contributes to the basic foundations for the further development of advanced MXenes for stable applications in the EM field.

Clinical Efficiency of Fixed-Bearing Unicompartmental Knee Arthroplasty Versus Total Knee Arthroplasty For Lateral Compartment Knee Osteoarthritis and the Effect on Recovery of Motor Function.

Objective: To evaluate the clinical efficiency of fixed-bearing unicompartmental knee arthroplasty (UKA) versus total knee arthroplasty (TKA) for lateral compartment knee osteoarthritis and the effect on the recovery of motor function. Methods: A total of 54 patients who underwent surgery for lateral compartment knee osteoarthritis and satisfied the inclusion criteria from September 2018 to February 2021 at our hospital were recruited and assigned to receive either UKA (UKA group, n=30) or TKA (TKA group, n=24) via random number table method. Among them, the randomization was carried out using an online web-based randomization tool (freely available at http://www.randomizer.org/). Inclusion criteria: 1) patients with lateral compartment knee osteoarthritis diagnosed by clinically relevant tests; 2) patients with structural and functional integrity of the knee ligaments; 3) all with a single knee lesion. Outcome measures included operative time, the reduction ratio of Hb 1d postoperatively, visual analog scale (VAS) score 7d postoperatively, length of hospital stay, postoperative Keen society score (KSS), Oxford knee score (OKS), range of motion (ROM), forgotten joint score (FJS), motor function recovery, and adverse events. Results: All patients were followed up postoperatively for 12-33 (21.71±7.45) months. Patients in the UKA group showed significantly shorter operative indices, a lower reduction ratio of Hb 1d postoperatively, and VAS scores of 7d postoperatively (P < .05). At 1 month and 6 months postoperatively, UKA resulted in significantly better KSS scores, OKS scores, ROM, and motor function recovery versus TKA (P < .05), while the difference of the above indices did not come up to the statistical standard at 1 year postoperatively (P < .05). At 1 year postoperatively, patients receiving UKA were associated with significantly higher FJS scores versus those given TKA. No documented thrombosis, knee, or prosthesis-related adverse events were observed during hospitalization and follow-up. Conclusion: In comparison to TKA, UKA resulted in smaller surgical incisions, improved postoperative healing, and greater restoration of knee function. Both arthroplasties are successful in alleviating pain and increasing knee function, although they are less effective in recovering patients' motor capabilities.

Hierarchical NiCo@NiOOH@CoMoO4 Core-Shell Heterostructure on Carbon Cloth for High-Performance Asymmetric Supercapacitors.

The fabrication of low-cost, effective, and highly integrated nanostructured materials through simple and reproducible methods for high-energy-density supercapacitors is highly desirable. Herein, an activated carbon cloth (ACC) is designed as the functional scaffold for supercapacitors and treated hydrothermally to deposit NiCo nanoneedles working as internal core, followed by a dip-dry coating of NiOOH nanoflakes core-shell and uniform hydrothermal deposition of CoMoO4 nanosheets serving as an external shell. The structured core-shell heterostructure ACC@NiCo@NiOOH@CoMoO4 electrode resulted in exceptional specific areal capacitance of 2920 mF cm-2 and exceptional cycling stability for 10 000 cycles. Moreover, the fabricated electrode is developed into an asymmetric supercapacitor which demonstrates excellent areal capacitance, energy density, and power density within the broad potential window of 1.7 V with a cycling life of 92.4% after 10 000 charge-discharge cycles, which reflects excellent cycle life. The distinctive core-shell structure, highly conductive substrate, and synergetic effect of coated material results in more electrochemical active sites and flanges for effective electrons and ion transportation. This unique technique provides a new perspective for cost-efficient supercapacitor applications.

Huangqi Jianzhong Tang treats chronic atrophic gastritis rats by regulating intestinal flora and conjugated bile acid metabolism.

Huangqi Jianzhong Tang (HQJZ) is effective for treating chronic atrophic gastritis (CAG). The present study was carried out to reveal the mechanism of HQJZ in CAG rats. The metabolism and microbial composition of the cecal contents in CAG rats were analyzed through the integration of an untargeted metabolomic approach using ultra-high-performance liquid chromatography coupled with the quadrupole-time of flight mass spectrometry (UHPLC-QTOF-MS) and 16S rRNA gene sequencing, respectively. Finally, MetOrigin analyses were performed to explore the relationship between differential metabolites and intestinal flora. The results showed that HQJZ could significantly regulate metabolic disorders, especially conjugated acid metabolites. 16S rRNA gene sequencing analysis illustrated that HQJZ decreased the abundance of Acetobacter, Desulfovibrio, Escherichia, and Shigella. MetOrigin metabolite traceability analysis showed that the six bile acids associated with HQJZ efficacy included three bacteria-host cometabolites, which were involved in the primary bile acid biosynthesis pathway. Research presented here confirmed that conjugated bile acid metabolism was key to the treatment of CAG by HQJZ and correlates strongly with Bacteroides acidifaciens and Prevotella copri. These findings provide new insights into the mechanisms to explain the efficacy of HQJZ.

Plasma levels of bone morphogenic protein-4 are downregulated in elderly hypertensive patients with heart failure with preserved ejection fraction.

OBJECTIVE: This study aimed to evaluate the association between plasma bone morphogenic protein-4 (BMP-4) levels and heart failure (HF) with preserved ejection fraction (HFpEF) or mildly reduced ejection fraction (HFmrEF) in elderly hypertensive patients. METHODS: A total of 222 hypertensive individuals meeting the inclusion criteria were enrolled from October 2021 to July 2022. Data were collected including clinical characteristics, laboratory tests and echocardiogram measurements. Plasma BMP-4 levels were tested using enzyme-linked immunosorbent assay analysis. RESULTS: Among 222 elderly hypertensive patients, 149 were without HF, 59 had HFpEF, and 14 had HFmrEF. Plasma BMP-4 levels were strikingly downregulated in hypertensive patients with HFpEF/HFmrEF [median (25th, 75th percentile): 15.89 (7.69, 23.12) pg/mL vs. 19.67 (10.60, 33.04) pg/mL; P = 0.002]. After univariate and multivariate logistic regression analysis, the risk of HFpEF/HFmrEF was declined in the 4th quartile BMP-4 group when compared with the 1st quartile BMP-4 group (odds ratio, 0.20, 95% confidence interval (CI), 0.04 to 1.00; P = 0.050, P for trend = 0.025). Receiver operating characteristic curve analysis revealed that BMP-4 ≤ 28.5 pg/mL exhibited a sensitivity of 95.9% and a specificity of 28.2% in HFpEF/HFmrEF diagnosis. Furthermore, the area under the curve (AUC) was 0.619 (95% CI:0.540-0.698, P < 0.001). The corresponding AUC for brain natriuretic peptide (BNP) was 0.781 (95% CI: 0.710-0.852), P < 0.001. Adding BMP-4 to BNP increased the AUC to 0.790 (95% CI: 0.724-0.856), vs. BMP-4, P < 0.001; vs. BNP, P = 0.730, respectively. CONCLUSIONS: Plasma BMP-4 levels are downregulated in elderly hypertensive patients with HFpEF. BMP-4 is a promising biomarker for diagnosing HFpEF/HFmrEF during hypertension.

High-yield and crystalline graphitic carbon nitride photocatalyst: One-step sodium acetate-mediated synthesis and improved hydrogen-evolution performance.

To avoid the drawbacks (such as multi-step operations and causing big quality loss) of currently reported molten salt-assisted strategy for the preparation of crystalline graphitic carbon nitride (g-C3N4) photocatalysts, in this study, an innovative and one-step sodium acetate (CH3COONa)-mediated synthesis strategy has been designed to synthesize a high-yield and crystalline g-C3N4 photocatalyst. It is found that CH3COONa can strongly combine with dicyandiamide (DCDA) to availably prevent the massive sublimation of DCDA and the following intermediates, causing the high-efficiency transformation of DCDA into g-C3N4 with a high yield (52.2 wt%). In addition to the promoted denitrification and quick polymerization of DCDA via CH3COONa, the produced Na2CO3 from CH3COONa decomposition at a higher temperature can further accelerate the polymerization reaction of 3-s-triazine units, leading to the final production of highly ordered and crystalline g-C3N4. Consequently, the resultant high-yield and crystalline g-C3N4 shows an obviously strengthened hydrogen (H2)-evolution rate, about 2.4 times higher than that of bulk g-C3N4, which is due to the synergetic function of highly crystalline structure, reduced band gap and cyano-groups. The current one-step CH3COONa-mediated synthesis strategy may open a novel horizon for the facile preparations and various applications of crystalline g-C3N4 materials.

A comparison of radiological and clinical outcomes between robotic-assisted and conventional total hip arthroplasty: A meta-analysis.

BACKGROUND: The purpose of this study was to investigate whether robotic-assisted total hip arthroplasty (RATHA) is superior to conventional total hip arthroplasty (CTHA) in terms of radiological and clinical outcomes. METHODS: Three databases (PubMed, Cochrane Library, and Embase) were searched for articles published before 11 May 2021. The comparison outcomes of interest included radiological and clinical outcomes. RESULTS: Eighteen studies involving 2845 hips that compared the radiological and clinical outcomes of RATHA and CTHA were included in this study. There was no significant difference between RATHA and CTHA in cup anteversion or complications. However, RATHA showed better outcomes in terms of leg-length discrepancy, stem alignment, cup inclination, the Lewinnek safe zone, Callanan safe zone, total complications, and intraoperative complications. Robotic-assisted total hip arthroplasty was inferior to CTHA in terms of operative time and dislocations (all p-values < 0.05). CONCLUSIONS: The radiological and clinical outcomes of RATHA were comparable and even better than those of CTHA, except for operative time and dislocation outcomes.

The bZIP Transcription Factors in Current Jasmine Genomes: Identification, Characterization, Evolution and Expressions.

Jasmine, a recently domesticated shrub, is renowned for its use as a key ingredient in floral tea and its captivating fragrance, showcasing significant ornamental and economic value. When cultivated to subtropical zone, a significant abiotic stress adaptability occurs among different jasmine varieties, leading to huge flower production changes and plantlet survival. The bZIP transcription factors (TFs) are reported to play indispensable roles in abiotic stress tolerance. Here, we performed a genome-level comparison of bZIPs using three-type jasmine genomes. Based on their physicochemical properties, conserved motif analysis and phylogenetic analysis, about 63 bZIP genes were identified and clustered in jasmine genomes, noting a difference of one member compared to the other two types of jasmines. The HTbZIP genes were categorized into 12 subfamilies compared with A. thaliana. In cis-acting element analysis, all genes contained light-responsive elements. The abscisic acid response element (ABRE) was the most abundant in HTbZIP62 promoter, followed by HTbZIP33. Tissue-specific genes of the bZIPs may play a crucial role in regulating the development of jasmine organs and tissues, with HTbZIP36 showing the most significant expressions in roots. Combined with complicated protein interactions, HTbZIP62 and HTbZIP33 might play a crucial role in the ABA signaling pathway and stress tolerance. Combined with RT-qPCR analysis, SJbZIP37/57/62 were more sensitive to ABA response genes compared with other bZIPs in DJ amd HT genomes. Our findings provide a useful resource for further research on the regulation of key genes to improve abiotic stress tolerance in jasmine.

Renal outcomes with sodium-glucose cotransporters 2 inhibitors.

Diabetic nephropathy (DN) is one of the most serious complications of diabetes. Therefore, delaying and preventing the progression of DN becomes an important goal in the clinical treatment of type 2 diabetes mellitus. Recent studies confirm that sodium-glucose cotransporters 2 inhibitors (SGLT2is) have been regarded as effective glucose-lowering drugs with renal protective effect. In this review, we summarize in detail the present knowledge of the effects of SGLT2is on renal outcomes by analyzing the experimental data in preclinical study, the effects of SGLT2is on estimated glomerular flitration rates (eGFRs) and urinary albumin-creatinine ratios (UACRs) from clinical trials and observational studies, and renal events (such as renal death or renal failure requiring renal replacement therapy) in some large prospective cardiovaslucar outcomes trials. The underlying mechanisms for renoprotective activity of SGLT2is have been demondtrated in multiple diabetic and nondiabetic animal models including kidney-specific effects and secondary kidney effects related to amelioration in blood glucose and blood pressure. In conclusion, these promising results show that SGLT2is act beneficially in terms of the kidney for diabetic patients.

Association between Cardio-Ankle Vascular Index and Masked Uncontrolled Hypertension in Hypertensive Patients: A Cross-Sectional Study.

Detection of masked uncontrolled hypertension (MUCH) that was defined for treated hypertensive individuals who had normal office blood pressure (BP) but elevated ambulatory BP remains largely challenging. Arterial stiffness is one of the leading risk markers for hypertension and can be clinically assessed by the cardio-ankle vascular index (CAVI). This study aimed to evaluate the association between CAVI and MUCH. A total of 155 hypertensive patients were included with their office BP levels and ambulatory BP monitoring measurements, which were divided into controlled hypertension (CH), MUCH, and sustained uncontrolled hypertension (SUCH) groups, respectively. There were 48 patients with CH, 56 patients with MUCH, and 51 patients with SUCH. Both MUCH and SUCH groups had a significantly higher CAVI than the CH group (9.05 (8.20-9.91) vs. 8.33 (7.75-9.15), p = 0.017, and 9.75 (8.35-10.50) vs. 8.33 (7.75-9.15), p = 0.002, respectively). There was no significant difference in CAVI values between the MUCH and SUCH groups. Multinomial logistic regression analysis exhibited that compared with the CH group, increased CAVI levels were positively associated with the presence of MUCH and SUCH (OR 2.046, 95% CI (1.239-3.381), p = 0.005; OR 2.215, 95% CI (1.310-3.747), p = 0.003) after adjusting for confounders. However, there was a similar trend of the CAVI in the MUCH and SUCH groups (OR 0.924, 95% CI (0.629-1.356), p = 0.686). In summary, our findings support, for the first time, the novel notion that CAVI as an arterial stiffness parameter is an independent risk factor for MUCH, being equally important to MUCH and SUCH. When the assessed CAVI is high in hypertensive patients with normotensive office BP levels, it is necessary to further investigate with a 24 h ambulatory BP monitoring to estimate the longstanding BP control. CAVI may be used as a noninvasive indicator to identify patients with MUCH earlier.

Heterogeneously integrated InGaN-based green microdisk light-emitters on Si (100).

Heterogeneous integration of nitrides on Si (100) is expected to open the door to the new possibilities for this material system in the fields of high-speed integrated photonics and information processing. In this work, GaN epitaxial layer grown on the patterned sapphire substrate is transferred onto Si (100) by a combination of wafer bonding, laser lift-off and chemical mechanical polishing (CMP) processes. The GaN epilayer transferred is uniformly thinned down to 800 nm with a root mean square surface roughness as low as 2.33 Å. The residual stress within the InGaN quantum wells transferred is mitigated by 79.4% after the CMP process. Accordingly, its emission wavelength exhibits a blue shift of 8.8 nm, revealing an alleviated quantum-confined Stark effect. Based on this platform, an array of microcavities with diverse geometrics and sizes are fabricated, by which optically-pumped green lasing at ∼505.8 nm is achieved with a linewidth of ∼0.48 nm from ∼12 µm microdisks. A spontaneous emission coupling factor of around 10-4 is roughly estimated based on the light output characteristics with increasing the pumping densities. Lasing behaviors beyond the threshold suggest that the microdisk suffers less thermal effects as compared to its undercut counterparts. The electrically-injected microdisks are also fabricated, with a turn-on voltage of ∼2.0 V and a leakage current as low as ∼2.4 pA at -5 V. Being compatible with traditional semiconductor processing techniques, this work provides a feasible solution to fabricate large-area heterogeneously integrated optoelectronic devices based on nitrides.

MiR-199a-5p promotes ferroptosis-induced cardiomyocyte death responding to oxygen-glucose deprivation/reperfusion injury via inhibiting Akt/eNOS signaling pathway.

Myocardial ischemia/reperfusion (I/R) injury is associated with the poor outcome and higher mortality after myocardial infarction. Recent studies have revealed that miR-199a-5p participates in the process of myocardial I/R injury, but the precise roles and molecular mechanisms of miR-199a-5p in myocardial I/R injury remain not well-studied. Ferroptosis has been proposed to promote cardiomyocyte death, closely associated with myocardial I/R injury. Herein, the present study aimed to explore the function and mechanisms by which miR-199a-5p regulates whether miR-199a-5p contributes to ferroptosis-induced cardiomyocyte death responding to oxygen-glucose deprivation/reoxygenation (OGD/R) injury, an in vitro model of myocardial I/R injury focusing on Akt/eNOS signaling pathway. The results found that ferroptosis-induced cardiomyocyte death occurs and is accompanied by an increase in miR-199a-5p level in OGD/R-treated H9c2 cells. MiR-199a-5p inhibitor ameliorated ferroptosis-induced cardiomyocyte death as evidenced by the increased cell viability, the reduced reactive oxygen species (ROS) generation, lactate dehydrogenase (LDH) activity, malondialdehyde (MDA) and Fe2+ contents, and the up-regulated glutathione (GSH)/glutathione disulphide (GSSG) ratio as well as glutathione peroxidase 4 (Gpx4) protein expression in H9c2 cells-exposed to OGD/R, while miR-199a-5p mimic had the opposite effects. In addition, OGD/R led to the inhibition of Akt/eNOS signaling pathway, which was also blocked by miR-199a-5p inhibitor and aggravated by miR-199a-5p mimic. Furthermore, LY294002, an inhibitor of Akt/eNOS signaling pathway, abrogated miR-199a-5p inhibitor-induced the reduction of ferroptosis-induced cardiomyocyte death. In summary, our findings demonstrated that miR-199a-5p plays a central role in stimulating ferroptosis-induced cardiomyocyte death during ischemic/hypoxic injury via inhibiting Akt/eNOS signaling pathway.

Association of plasma bone morphogenetic protein-4 levels with arterial stiffness in hypertensive patients.

BACKGROUND: Arterial stiffness interacts with hypertension, becoming an early marker of hypertension-mediated target organ damage. This study aimed to assess the association between plasma concentrations of bone morphogenetic protein-4 (BMP-4) and arterial stiffness during hypertension. METHODS: Using cardio-ankle vascular index (CAVI) to determine arterial stiffness status, 204 individuals with essential hypertension were classified into two groups, high CAVI (abnormal) group (n = 94) and low (normal) CAVI group (n = 110). Data were collected including clinical characteristics and laboratory measurements. Plasma levels of BMP-4 were tested by using ELISA analysis. RESULTS: Plasma levels of BMP-4 were substantially greater in high CAVI group than that in low CAVI group [38.51 (31.79-50.83) pg/mL vs. 31.15 (29.38-32.37) pg/mL; p < 0.001]. As shown by spearman correlation analysis, BMP-4 concentrations were correlated with CAVI values in hypertensive individuals (r = 0.406, p < 0.001). After adjustment for potential confounders, elevated BMP-4 levels were related with high CAVI (OR, 1.070; 95% CI, 1.003-1.108; p < 0.001). The best BMP-4 cutoff value for identifying high CAVI, as determined by ROC curve analysis, was 33.34 pg/mL (AUC, 0.751; 95% CI, 0.683-0.818; p < 0.001). CONCLUSION: Plasma levels of BMP-4 are increased in hypertensive individuals with high CAVI. Elevated BMP-4 levels are strongly correlated with higher CAVI values, implying a predictive value of BMP-4 in arterial stiffness during hypertension.

Influencing Factors and Improvement Path of Synergistic Value Creation Efficiency of Emerging Enterprises.

The cooperation between emerging enterprises and different enterprises can stimulate innovation enthusiasm and realize synergistic value creation. At present, there is no regular pattern and rules for synergistic value creation among emerging enterprises, which cannot achieve effective synergistic value creation. Based on the complex network relationship and dynamic model of game evolution among multiple entities of value creation within emerging enterprises, the factors that affect the efficiency of synergistic value creation in the aspect of input, benefit assignment, and interaction mechanism of synergistic value creation are analyzed and then the path of the promotion of synergistic value creation among the entities of new enterprises is studied. The results show that the core enterprises play a leading role in the cooperation input among emerging enterprises, and if the balance of interests among cooperative enterprises is guaranteed, the revenue effect is the best, and the network cooperation density is the strongest. The game evolution shows that, in order to improve the efficiency of synergistic value creation, it is necessary to improve the expected coefficient and number of synergies between enterprises and establish a mechanism for equitable distribution of synergies by strengthening information exchange among enterprises in emerging industries, so as to build an atmosphere of synergies, the complementarity of assets and synergies.

Bohring-Opitz syndrome caused by a novel ASXL1 mutation (c.3762delT) in an IVF baby: A case report.

RATIONALE: Bohring-Opitz syndrome is a severe congenital disorder associated with a de novo mutation in the additional sex combs-like 1 (ASXL1) gene, and it is characterized by symptoms that include developmental delay and musculoskeletal and neurological features. PATIENT CONCERNS: The patient was a girl, an in vitro fertilization (IVF) baby, with delayed motor development, drooling, short stature, slow growth, low muscle tone, image diagnosis of hypoplasia of the corpus callosum, delayed tooth eruption, high palatal arch, adduction of the thumb, drooling, not chewing, excessive joint activity, and ligament relaxation. DIAGNOSIS: Whole-exome sequencing analysis detected 1 novel disruptive frameshift mutation in ASXL1 in the proband but wild-type ASXL1 in both parents. INTERVENTIONS: Approximately 1 year of rehabilitation training, which included exercise therapy, toy imitation operation, cognition of daily objects, daily living skills training, gesture language training, oral muscle training, and hand movement training. OUTCOMES: After approximately 1 year of training, the patient was 3 years old and able to eat normally without drooling. She was able to grasp objects and pick them up after they fell. She was able to grasp small objects and actively played with toys. In addition, she was able to crawl on the floor (at slow speed, with poor initiative), stand with assistance, and walk with assistance; she was unstable when standing unassisted (standing unassisted for 8 seconds at most during training). LESSON: ASXL1 c.3762delT is a novel mutation that may be caused by IVF. This finding suggests that appropriate gene mutation detection approaches may be necessary for IVF technology.