Protein acetylation and related potential therapeutic strategies in kidney disease.

Kidney disease can be caused by various internal and external factors that have led to a continual increase in global deaths. Current treatment methods can alleviate but do not markedly prevent disease development. Further research on kidney disease has revealed the crucial function of epigenetics, especially acetylation, in the pathology and physiology of the kidney. Histone acetyltransferases (HATs), histone deacetylases (HDACs), and acetyllysine readers jointly regulate acetylation, thus affecting kidney physiological homoeostasis. Recent studies have shown that acetylation improves mechanisms and pathways involved in various types of nephropathy. The discovery and application of novel inhibitors and activators have further confirmed the important role of acetylation. In this review, we provide insights into the physiological process of acetylation and summarise its specific mechanisms and potential therapeutic effects on renal pathology.

Improved Resolution and Cost Performance of Low-Cost MEMS Seismic Sensor through Parallel Acquisition.

In earthquake monitoring, an important aspect of the operational effect of earthquake intensity rapid reporting and earthquake early warning networks depends on the density and performance of the deployed seismic sensors. To improve the resolution of seismic sensors as much as possible while keeping costs low, in this article the use of multiple low-cost and low-resolution digital MEMS accelerometers is proposed to increase the resolution through the correlation average method. In addition, a cost-effective MEMS seismic sensor is developed. With ARM and Linux embedded computer technology, this instrument can cyclically store the continuous collected data on a built-in large-capacity SD card for approximately 12 months. With its real-time seismic data processing algorithm, this instrument is able to automatically identify seismic events and calculate ground motion parameters. Moreover, the instrument is easy to install in a variety of ground or building conditions. The results show that the RMS noise of the instrument is reduced from 0.096 cm/s2 with a single MEMS accelerometer to 0.034 cm/s2 in a bandwidth of 0.1-20 Hz by using the correlation average method of eight low-cost MEMS accelerometers. The dynamic range reaches more than 90 dB, the amplitude-frequency response of its input and output within -3 dB is DC -80 Hz, and the linearity is better than 0.47%. In the records from our instrument, earthquakes with magnitudes between M2.2 and M5.1 and distances from the epicenter shorter than 200 km have a relatively high SNR, and are more visible than they were prior to the joint averaging.

Correlation between the High Density Lipoprotein and its Subtypes in Coronary Heart Disease.

BACKGROUND/AIMS: To detect the changes of high density lipoprotein (HDL) and its subtypes in serum of patients with coronary heart disease (CHD). METHODS: 337 hospitalized patients were selected from our hospital during August, 2014 - January, 2015, and divided into CHD group (n = 190) and control group (n = 127). Lipoprint lipoprotein analyzer was used to classify low density lipoprotein (LDL) particle size and its sub-components, as well as HDL particle size and its sub-components. The changes of the subtypes in patients with CHD were statistically analyzed. The possible mechanism was explored. RESULTS: (1) Compared with the control group, the concentration of HDL in CHD patients reduced, HDLL significantly decreased (P < 0.001), while HDLS increased (P < 0.001); (2) In the patients with HDL less than 1.04 mmol/L among CHD, all HDL subtypes reduced, but HDLL had the most significant decreased; (3) HDL and all HDL subtypes were positively correlated with apolipoprotein A-I (apoA-I), of which, HDLL had the biggest correlation with apoA-I (P < 0.001); (4) HDL subtypes had good correlation with HDL, of which, HDLM had a maximum correlation with HDL (P < 0.001). CONCLUSION: HDL maturation disorders existed in the serum of CHD patients, HDLL may be protected factor for CHD, whose decrease was closely related wit the risk increase of CHD. The cardiovascular protection function of HDLL may be related with apoA-I content.

Temporal and Spatial Changes of Proarrhythmic Substrate in Premature Ventricular Contraction-Induced Cardiomyopathy.

BACKGROUND: The changes in proarrhythmic substrates and malignant ventricular arrhythmia mechanisms caused by premature ventricular contraction-induced cardiomyopathy (PVCCM) remain unclear. OBJECTIVES: The goal of this study was to establish the electrophysiological mechanism of how high-load PVC causes malignant arrhythmia. METHODS: Thirteen swine were exposed to 50% paced PVC from the right ventricular apex for 12 weeks (PVCCM, n = 6) and no pacing for 12 weeks (control, n = 7). Cardiac function was quantified biweekly with echocardiography. Computed tomography scans and electrophysiological examinations were performed monthly to dynamically evaluate the changes in the cardiac structure and the arrhythmogenic substrate. RESULTS: The decreases in the cardiac function and ventricular enlargement in the PVCCM group were significant after 12 weeks of PVC stimulation compared with the control group (P < 0.001). Electrophysiological examination found that the ventricular effective refractory period dispersion (0.071 ± 0.008), area of the low-voltage zone (9.41 ± 1.55 cm2), and malignant ventricular arrhythmia inducibility (33.3%) of the PVCCM group increased significantly at week 8 after pacing (P < 0.001 vs the control group); these changes slowed down after 8 weeks. Moreover, the distribution of the low-voltage zone presented obvious spatial heterogeneity, especially in the anterior wall of the right ventricle, accompanied by delayed activation in the sinus rhythm (67 ± 13 milliseconds). Consistently, the proportion of ventricular fibrosis- and expression-related proteins were significantly increased in the PVCCM group (P < 0.001), especially in the right ventricle. Moreover, proteomic analysis confirmed the spatial profile of these fibrotic changes in the PVCCM group. CONCLUSIONS: High-burden PVC can cause significant temporal and spatial heterogeneity changes in proarrhythmic substrates, which are potentially related to the upregulation of calcium signaling caused by asynchronous activation.

Synthesis of MnOOH and its application in a supporting hexagonal Pd/C catalyst for the oxygen reduction reaction.

With the expansion of global energy problems and the deepening of research on oxygen reduction reaction (ORR) in alkaline media, the development of low cost and high electrocatalytic performance catalysts has become a research hotspot. In this study, a hexagonal Pd-C-MnOOH composite catalyst was prepared by using the triblock copolymer P123 as the reducing agent and protective agent, sucrose as the carbon source and self-made MnOOH as the carrier under hydrothermal conditions. When the Pd load is 20% and the C/MnOOH ratio is 1 : 1, the 20% Pd-C-MnOOH-1 : 1 catalyst obtained by the one-step method has the highest ORR activity and stability in the alkaline system. At 1600 rpm, the limiting diffusion current density and half-wave potential of the 20% Pd-C-MnOOH-1 : 1 electrocatalyst are -4.78 mA cm-2 and 0.84 V, respectively, which are better than those of the commercial 20%Pd/C catalyst. According to the Koutecky-Levich (K-L) equation and the linear fitting results, the electron transfer number of the 20%Pd-C-MnOOH-1 : 1 electrocatalyst for the oxygen reduction reaction is 3.8, which is similar to that of a 4-electron process. After 1000 cycles, the limiting diffusion current density of the 20%Pd-C-MnOOH-1 : 1 catalyst is -4.61 mA cm-2, which only decreases by 3.7%, indicating that the 20%Pd-C-MnOOH-1 : 1 catalyst has good stability. The reason for the improvement of the ORR performance of the Pd-C-MnOOH composite catalyst is the improvement of the conductivity of the carbon layer formed by original carbonization, the regular hexagonal highly active Pd particles and the synergistic catalytic effect between Pd and MnOOH. The method of introducing triblock copolymers in the synthesis of oxides and metal-oxide composite catalysts is expected to be extended to other electrocatalysis fields.

Novel insights into STAT3 in renal diseases.

Signal transducer and activator of transcription 3 (STAT3) is a cell-signal transcription factor that has attracted considerable attention in recent years. The stimulation of cytokines and growth factors can result in the transcription of a wide range of genes that are crucial for several cellular biological processes involved in pro- and anti-inflammatory responses. STAT3 has attracted considerable interest as a result of a recent upsurge in study because of their role in directing the innate immune response and sustaining inflammatory pathways, which is a key feature in the pathogenesis of many diseases, including renal disorders. Several pathological conditions which may involve STAT3 include diabetic nephropathy, acute kidney injury, lupus nephritis, polycystic kidney disease, and renal cell carcinoma. STAT3 is expressed in various renal tissues under these pathological conditions. To better understand the role of STAT3 in the kidney and provide a theoretical foundation for STAT3-targeted therapy for renal disorders, this review covers the current work on the activities of STAT3 and its mechanisms in the pathophysiological processes of various types of renal diseases.

[Correlation between blood T-cell receptor rearrangement excision circles levels and severe infection in children with acute lymphoblastic leukemia].

OBJECTIVE: This study quantitatively examined signal joint T-cell receptor rearrangement excision circles (sjTRECs) levels in peripheral blood of children with acute lymphoblastic leukemia (ALL) at different stages in order to evaluate the role of sjTRECs in predicting severe infection postchemotherapy. METHODS: sjTRECs levels in peripheral blood were measured by fluorescent quantitation-polymerase chain reaction in 30 children with newly diagnosed ALL, 36 children with ALL who accepted chemotherapy but were not infected, 30 children with ALL who had severe infection after chemotherapy, and 50 normal children. RESULTS: Blood sjTRECs levels in the normal group (394 ± 270 copies/103 MNC) were significantly higher than those in the other three groups (P<0.05). Blood sjTRECs levels in the chemotherapy group without infection (96 ± 78 copies/103 MNC) were significantly lower than those in the newly diagnosed ALL group (210 ± 219 copies/103 MNC) (P<0.05). The chemotherapy group with severe infection showed the lowest blood sjTRECs levels (48 ± 40 copies/103 MNC) in the four groups. CONCLUSIONS: The measurement of blood sjTRECs levels might be helpful for predicting the occurrence of severe infection postchemotherapy in children with ALL.

Evaluation of a new frequency-volume chart for children with primary monosymptomatic nocturnal enuresis: a prospective, comparative study.

INTRODUCTION: To improve compliance with voiding diaries in children with primary monosymptomatic nocturnal enuresis (PMNE), a new modified 3-day weekend frequency-volume chart (FVC) was designed, and the compliance and validity of this modified FVC was evaluated by comparing with the International Children's Continence Society (ICCS) recommended voiding diary. METHODS: A total of 1200 patients with PMNE were enrolled in the study from 13 centers in China and were randomly assigned to record this modified FVC or the ICCS-recommended voiding diary. The primary outcome measure was the compliance, assessed by comparing the completing index and the quality score of diaries between two groups. The secondary outcome measure was the validity, evaluated by comparing the constituent of subtypes, micturition parameters and response rate to desmopressin. RESULTS: Among the 1200 participants enrolled in the study, 447 patients completed the ICCS-recommended voiding diary and 469 completed the modified diary. The diurnal completing index and the quality score of the modified FVC group were better than those of the ICCS group. In addition, there was no significant difference between these two groups in the subtype classification, or in the response rate to desmopressin. CONCLUSIONS: The modified FVC could be applied to obtain the voiding characteristics of children with PMNE as the ICCS-recommended voiding diary does and offers a reasonable and better choice for children with PMNE from the unselected population in the future.

Real world effectiveness of PCSK-9 inhibitors combined with statins versus statins-based therapy among patients with very high risk of atherosclerotic cardiovascular disease in China (RWE-PCSK study).

BACKGROUND: The efficacy and safety of proprotein convertase subtilisin/kexin type 9 (PCSK-9) inhibitors were confirmed by several clinical trials, but its effectiveness in routine clinical practice in China has not been evaluated. This study aims to describe the real world effectiveness of PCSK-9 inhibitors combined with statins compared with statins-based therapy among patients with very high risk of atherosclerotic cardiovascular disease (ASCVD). METHODS: This is a multi-center observational study, enrolled patients from 32 hospitals who underwent percutaneous coronary intervention (PCI) from January to June in 2019. There are 453 patients treated with PCSK-9 inhibitors combined with statins in PCSK-9 inhibitor group and 2,610 patients treated with statins-based lipid lowering therapies in statins-based group. The lipid control rate and incidence of major adverse cardiovascular events (MACE) over six months were compared between two groups. A propensity score-matched (PSM) analysis was used to balance two groups on confounding factors. Survival analysis using Kaplan-Meier methods was applied for MACE. RESULTS: In a total of 3,063 patients, 89.91% of patients had received moderate or high-intensity statins-based therapy before PCI, but only 9.47% of patients had low-density lipoprotein cholesterol (LDL-C) levels below 1.4 mmol/L at baseline. In the PSM selected patients, LDL-C level was reduced by 42.57% in PCSK-9 inhibitor group and 30.81% (P < 0.001) in statins-based group after six months. The proportion of LDL-C ≤ 1.0 mmol/L increased from 5.29% to 29.26% in PCSK-9 inhibitor group and 0.23% to 6.11% in statins-based group, and the proportion of LDL-C ≤ 1.4 mmol/L increased from 10.36% to 47.69% in PCSK-9 inhibitor group and 2.99% to 18.43% in statins-based group ( P < 0.001 for both). There was no significant difference between PCSK-9 inhibitor and statins-based treatment in reducing the risk of MACE (hazard ratio = 2.52, 95% CI: 0.49-12.97, P = 0.250). CONCLUSIONS: In the real world, PCSK-9 inhibitors combined with statins could significantly reduce LDL-C levels among patients with very high risk of ASCVD in China. The long-term clinical benefits for patients received PCSK-9 inhibitor to reduce the risk of MACE is still unclear and requires further study.

[Sulfur Sources and Oxidation Pathways in Summer Aerosols from Nanjing Northern Suburbs Using S and O Isotopes].

The sulfur and oxygen isotopic compositions of sulfate in PM2.5 were determined by EA-IRMS to study the sulfur sources and oxidation formation pathways of sulfates in PM2.5 from Nanjing northern suburbs during July 2014. The results indicated that δ34 S values of sulfate ranged from 1.7‰ to 4.8‰ with an average of 3.2‰±1.0‰, while δ18O values ranged from 7.5‰ to 12.9‰ with an average of 9.3‰±1.7‰. Comparing the δ34 S values of aerosol sulfate and potential pollution sources, we concluded that the sulfur source of PM2.5 was mainly local coal combustion and vehicle exhaust. In addition, the secondary sulfate was dominant in PM2.5, and 59.3% of the formation of the secondary sulfate was caused by SO2 homogeneous oxidation. In addition, the heterogeneous oxidation of SO2 in the atmosphere was dominated by ferrous iron oxidation in excess O2. The main mechanisms of homogeneous oxidation include oxidation in the presence of electric discharge (presumably forming O3) and NO2.

[Chemical Constitution and Carbon Isotopic Compositions of PM2.5 in the Northern Suburb of Nanjing in Spring].

PM2.5 is an important atmospheric pollution component and has a complicated composition. The chemical constitution of PM2.5 in Nanjing northern region during March 2016 was analyzed using the Dinoex ICS-3000 and ICS-2000 ion chromatograph and DRI Model 2001A thermal/optical carbon analyzer, and the carbon isotopic compositions were analyzed using EA-IRMS from Thermo Scientific in order to explore pollution behaviors and source apportionment of PM2.5. The results showed that the mean concentration of atmospheric PM2.5 was (106.16±48.70) µg·m-3, which equated with heavy pollution. Meanwhile, 88% of the samples exhibited the presence of the secondary organic pollutants. The average concentration of secondary organic carbon (SOC) was (3.58±2.78) µg·m-3 and this high concentration was attributed to the reaction of O3 with atmospheric hydrocarbons under ultraviolet light on sunny days. In addition, δ13CTC in PM2.5 ranged from -26.56‰ to -23.75‰ and the mean was (-25.47‰±0.63‰). Combining the various analyses, we concluded that atmospheric PM2.5 for the study area was mainly derived from coal combustion, vehicle exhaust, geology (natural sources) and biomass burning.

[Effect of Carbon and Nitrogen Forms on Decomposition of Organic Matter in Sediments from Urban Polluted River].

To reveal the controlling mechanism of urban polluted river,four trophic level urban river was studied. The change of distribution of organic matter and nitrogen in the sediment was studied while the organic matter was disposed. High level of organic matter is the significant feature of urban city rivers. the humin (HM) was the major fraction of humus, accounting for more than 65% of OM. The most proportion of the total nitrogen (TN) was organic nitrogen which accounted for more than 50%. The amount of organic matter removal increased after the sediment adsorbed the saturated ammonia, which suggested ammonia as the main limited factor for the decomposition of organic matter. The most of Ammonia was adsorbed onto unstable humins. The HM was more stable than other organic matter which was disposed by Hydrogen peroxide (H2O2).

The Effect of Acupuncture to SP6 on Skin Temperature Changes of SP6 and SP10: An Observation of "Deqi".

Background. Deqi sensation is a complex but an important component for acupuncture effect. In this study, we tried to observe the relationship between Deqi and skin temperature changes and whether there was some relativity between Deqi and needle stimulations on cold congealing and dysmenorrhea rat model. Thirty-two female Sprague Dawley (SD) rats were randomly divided into four groups (Saline Control Group, Model Group, Group A with strong stimulation, and Group B with small stimulation). Group A and Group B were performed with different stimulations. We found that, compared with saline control group, model group, and Group B, Group A showed that the skin temperature changes on right acupoint SP6 and SP10 increased significantly at 5 min-10 min interval. The skin temperature changes on left SP6 decreased at instant-5 min interval. The skin temperature changes on right SP10 decreased significantly at instant-5 min interval and 10 min-20 min interval. Thermogenic action along Spleen Meridian of Foot Greater Yin was manifested as simultaneous skin temperature increase on right SP6 and SP10 at 5 min-10 min interval after needling SP6, which was helpful to illustrate the relationship between the characteristic of Deqi and needle stimulations.

Effects of acupuncture applied to sanyinjiao with different stimuli on uterine contraction and microcirculation in rats with dysmenorrhea of cold coagulation syndrome.

In this study, we try to evaluate the effects of acupuncture stimulation with different amounts at Sanyinjiao (SP6) on uterine contraction and uterus microcirculation in rats with dysmenorrhea of cold coagulation syndrome and to explore whether there is direct relativity between "De qi" and needle stimulus intensity. Diestrus female rats were randomly divided into 4 groups, including saline control group, model control group, "A" stimulus group (with strong stimulus), and "B" stimulus group (with weak stimulus). We found that dysmenorrhea rats of the cold coagulation syndrome present a high intensity in uterine tension and high contraction of microvascular diameter. Acupuncture applied with two different stimuli could relieve the symptoms, but, compared with "B" stimulus, "A" stimulus leads to better outcomes on reducing uterine contraction and increasing diameter of uterine microvascular; moreover, hand manipulation during needling mediates the curative effect on the microvascular diameter. Our finding indicates that using thick needles and deep insertion with hand manipulation are more effective and achieve desired level of "De qi" in dysmenorrhea rats.

Acupuncture De-qi: From Characterization to Underlying Mechanism.

De-qi refers to the participant's subjective sensations and objective body responses as well as the acupuncturist's perceptions while the acupuncturist needles certain acupoints in the participant's body. In recent years, De-qi is getting increasing attention of the researchers and many efforts have been made to understand its mechanism. By the broad literature survey, this paper explores the subjective De-qi sensation of the patients, its influencing factors, and the resulting physiological responses. The purpose of this paper is expected to find out a possible mechanism of De-qi and to provide certain scientific evidence for acupuncture fundamental research and clinical practice.