Safety and efficacy of umbilical cord tissue-derived mesenchymal stem cells in the treatment of patients with aging frailty: a phase I/II randomized, double-blind, placebo-controlled study.

BACKGROUND: Mesenchymal stem cells (MSCs) hold a great promise for cell-based therapy in the field of regenerative medicine. In this study, we aimed to evaluate the safety and efficacy of intravenous infusion of human umbilical cord-derived MSCs (HUC-MSCs) in patients with aging frailty. METHODS: In this randomized, double-blind, placebo-controlled trial, participants diagnosed with aging frailty were randomly assigned to receive intravenous administrations of HUC-MSCs or placebo. All of serious adverse events and AEs were monitored to evaluate the safety of treatment during the 6-month follow-up. The primary efficacy endpoint was alteration of physical component scores (PCS) of SF-36 qualities of life at 6 months. The secondary outcomes including physical performance tests and pro-inflammatory cytokines, were also observed and compared at each follow-up visits. All evaluations were performed at 1 week, 1, 2, 3 and 6 months following the first intravenous infusion of HUC-MSCs. RESULTS: In the MSCs group, significant improvements in PCS of SF-36 were observed from first post-treatment visit and sustained throughout the follow-up period, with greater changes compared to the placebo group (p = 0.042). EQ-VAS scores of MSCs group improved significantly at 2 month (p = 0.023) and continued until the end of the 6-month visit (p = 0.002) in comparison to the placebo group. The timed up and go (TUG) physical performance test revealed significant group difference and showed continual enhancements over 6 months (p < 0.05). MSC transplantation improved the function of 4-m walking test (4MWT) compared with the placebo group with a decrease of 2.05 s at 6 months of follow-up (p = 0.21). The measurement of grip strength revealed group difference with MSCs group demonstrating better performance, particularly at 6 months (p = 0.002). Inflammatory cytokines (TNF-α, IL-17) exhibited declines in MSCs group at 6 months compared to the placebo group (p = 0.034 and 0.033, respectively). There was no difference of incidence of AEs between the two groups. CONCLUSION: Intravenous transplantation of HUC-MSCs is a safe and effective therapeutic approach on aging frailty. The positive outcomes observed in improving quality of life, physical performance, and reducing chronic inflammation, suggest that HUC-MSC therapy may be a promising potential treatment option for aging frailty. TRIAL REGISTRATION: Clinicaltrial.gov; NCT04314011; https://clinicaltrials.gov/ct2/show/NCT04314011 .

Severe photochemical pollution formation associated with strong HONO emissions from dew and guttation evaporation.

The unknown daytime source of HONO has been extensively investigated due to unexplained atmospheric oxidation capacity and current modelling bias, especially during cold seasons. In this study, abrupt morning increases in atmospheric HONO at a rural site in the North China Plain (NCP) were observed almost on daily basis, which were closely linked to simultaneous rises in atmospheric water vapor content and NH3 concentrations. Dew and guttation water formation was frequently observed on wheat leaves, from which water samples were taken and chemically analyzed for the first time. Results confirmed that such natural processes likely governed the daily nighttime deposition and daytime release of HONO and NH3, which have not been considered in the numerous HONO budget studies investigating its large missing daytime source in the NCP. The dissolved HONO and NH3 in leaf surface water droplets reached 1.4 and 23 mg L-1 during the morning on average, resulting in averaged atmospheric HONO and NH3 increases of 0.89 ± 0.61 and 43.7 ± 29.3 ppb during morning hours, with relative increases of 186 ± 212 % and 233 ± 252 %, respectively. The high atmospheric oxidation capacity contained within HONO was stored in near surface liquid water (such as dew, guttation and soil surface water) during nighttime, which prevented its atmospheric dispersion after sunset and protected it from photodissociation during early morning hours. HONO was released in a blast during later hours with stronger solar radiation, which triggered and then accelerated daytime photochemistry through the rapid photolysis of HONO and subsequent OH production, especially under high RH conditions, forming severe secondary gaseous and particulate pollution. Results of this study demonstrate that global ecosystems might play significant roles in atmospheric photochemistry through nighttime dew formation and guttation processes.

Epigenetic Regulation of Macrophage Polarization in Cardiovascular Diseases.

Cardiovascular diseases (CVDs) are the leading cause of hospitalization and death worldwide, especially in developing countries. The increased prevalence rate and mortality due to CVDs, despite the development of several approaches for prevention and treatment, are alarming trends in global health. Chronic inflammation and macrophage infiltration are key regulators of the initiation and progression of CVDs. Recent data suggest that epigenetic modifications, such as DNA methylation, posttranslational histone modifications, and RNA modifications, regulate cell development, DNA damage repair, apoptosis, immunity, calcium signaling, and aging in cardiomyocytes; and are involved in macrophage polarization and contribute significantly to cardiac disease development. Cardiac macrophages not only trigger damaging inflammatory responses during atherosclerotic plaque formation, myocardial injury, and heart failure but are also involved in tissue repair, remodeling, and regeneration. In this review, we summarize the key epigenetic modifications that influence macrophage polarization and contribute to the pathophysiology of CVDs, and highlight their potential for the development of advanced epigenetic therapies.

Mixed Cu2 Se Hexagonal Nanosheets@Co3 Se4 Nanospheres for High-Performance Asymmetric Supercapacitors.

Rational designing and constructing multiphase hybrid electrode materials is an effective method to compensate for the performance defects of the single component. Based on this strategy, Cu2 Se hexagonal nanosheets@Co3 Se4 nanospheres mixed structures have been fabricated by a facile two-step hydrothermal method. Under the synergistic effect of the high ionic conductivity of Cu2 Se and the remarkable cycling stability of Co3 Se4 , Cu2 Se@Co3 Se4 can exhibit outstanding electrochemical performance as a novel electrode material. The as-prepared Cu2 Se@Co3 Se4 electrode displays high specific capacitance of 1005 F g-1 at 1 A g-1 with enhanced rate capability (56 % capacitance retention at 10 A g-1 ), and ultralong lifespan (94.2 % after 10 000 cycles at 20 A g-1 ). An asymmetric supercapacitor is assembled applying the Cu2 Se@Co3 Se4 as anode and graphene as cathode, which delivers a wide work potential window of 1.6 V, high energy density (30.9 Wh kg-1 at 0.74 kW kg-1 ), high power density (21.0 Wh kg-1 at 7.50 kW kg-1 ), and excellent cycling stability (85.8 % after 10 000 cycles at 10 A g-1 ).

Purification and characterization of chitinase from Paenibacillus sp. .

The chitinase-producing bacteria Paenibacillus sp. was isolated from soil samples. The chitinase was purified successively by ammonia sulfate fractional precipitation followed by chromatography on DEAE 52-cellulose column and then on Sephadex G-75 column. The chitinase has a molecular weight of ca. 30 kDa as measured by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) electrophoresis. Its optimum pH is 4.5, and its optimum temperature is 50 °C with colloidal chitin as a substrate. The enzyme is stable below 45 °C and in pH ranges between 4.5 and 5.5. It is activated by glucosamine, glucose, N-acetylglucosamine, and metal ions including Ca2+ , Fe2+ , Fe3+ , and Ni2+ . It is inhibited by SDS, H2 O2 , ascorbic acid, Cu2+ , Mg2+ , Ba2+ , Sn2+ , Cr3+ , and K+ . With colloidal chitin as substrate, the Km and the Vmax of the chitinase are 4.28 mg/mL and 14.29 µg/(Min·mL), respectively, whereas the end products of the enzymatic hydrolysis are 14.33% monomer and 85.67% dimer of N-acetylglucosamine. The viscosity of carboxymethyl chitin decreased rapidly at the initial stages when subjected to chitinase hydrolysis, which indicates that the chitinase acts in an endosplitting pattern.

CuO nanorods grown vertically on graphene nanosheets as a battery-type material for high-performance supercapacitor electrodes.

This work reports the preparation and characterization of the CuO nanorods grown vertically on graphene nanosheets, denoted as CuO/rGO@NF. Graphene is deposited by electrostatic attraction showing the morphology of folded nanosheets, which improves the electrical conductivity of the electrode, while CuO is modified by filtered cathodic vacuum arc technology and subsequent electrochemical oxidation presenting the morphology of nanorods, which increases the contact area of active sites and shortens the ion and electronic diffusion path. The results show that the CuO/rGO@NF electrode deliver an ultrahigh specific capacity (2.51 C cm-2 at 2 mA cm-2), remarkable rate performance (64.6%) and improved conductivity. A symmetrical supercapacitor is assembled by two identical electrodes, presenting the maximum energy density of 38.35 W h kg-1 at a power density of 187.5 W kg-1. Therefore, the CuO/rGO@NF electrode can be used as a prospective electrode for energy storage devices. In addition, the whole electrode preparation process is short in time, safe and environmentally friendly, which provides a new idea for the preparation of other electrode materials.

Nickel Nanoparticles Anchored onto Ni Foam for Supercapacitors with High Specific Capacitance.

Supercapacitors are regarded as a promising energy storage system. Transition metal compounds have been widely used as electrode materials for pseudocapacitors, which possess variable oxidation valence states. Among them, Ni-based materials have drawn a substantial amount of attention. In this work, Ni nanoparticles (NiNPs/NiF) were successfully synthesized on Ni foam by a facile ion implantation method and first studied for the supercapacitor application. At the same time, NiO nanofibers were grown on a Ni foam (NiOF/NiF) for comparison. The NiNPs/NiF electrode delivered a better performance than the NiOF/NiF. The NiNPs/NiF electrode showed a high specific capacitance of 3862 F g-1 at 5 A g-1 and good long-term endurance at a current density of 50 A g-1 after a charge-discharge test of 1000 cycles. The good performance can be attributed to the uniform deposition of the Ni nanoparticles, which provided abundant active sites for the Faradaic reaction. Moreover, the three-dimensional (3D) structure of Ni foam facilitated the electron transfer between the electrode and electrolyte. The excellent performance and facile fabrication make the NiNPs/NiF electrode a promising candidate for high-performance supercapacitors.

Formaldehyde regulates vascular tensions through nitric oxide-cGMP signaling pathway and ion channels.

Formaldehyde (FA) has been linked to the detrimental cardiovascular effects. Here, we explored the effects and mechanisms of FA on rat aortas both in vivo and in vitro. The results presented that FA evidently lowered the blood pressures of rats. The expression levels of BKCa subunits α and ß1 and iNOS of the aortas were up-regulated by FA in vivo. However, FA markedly reduced the levels of Cav1.2 and Cav1.3, which are the subunits of L-Ca2+ channel. Furthermore, the contents of NO, cGMP and iNOS in the aortas were augmented by FA. To further confirm these findings, the mechanisms accredited to these effects were examined in vitro. The data showed that FA contracted the isolated aortic rings at low concentrations (<300 µM), while it relaxed the rings at high concentrations (>500 µM). The FA-induced vasoconstriction at low concentrations was blocked partly by an inhibitor of ACE. The relaxation caused by FA at high concentrations was attenuated by the inhibitors of NO-cGMP pathway, L-Ca2+ channel and BKCa channel, respectively. Similarly, the expression of iNOS was strongly enhanced by FA in vitro. The effects of FA on the aortic rings with endothelium were significantly greater than those on the rings without endothelium. Our results indicate that the vasoconstriction of FA at low concentrations might be partially pertinent to endothelin, and the FA-caused vasorelaxation at high concentrations is possibly associated with the NO-cGMP pathway, L-Ca2+ channel and BKCa channel. This study will improve our understanding of the pathogenic mechanisms for FA-related cardiovascular diseases.

Cadmium exposure and its health effects: a 19-year follow-up study of a polluted area in China.

BACKGROUND: Dayu County, which is located in southwestern Jiangxi Province in China, has been a cadmium (Cd)-contaminated area since the 1960s. A series of studies about Cd pollution were carried out in the 1980s. However, no further studies of the area were conducted during the following 19 years. AIM: To observe cadmium (Cd) exposure levels and its health risks among residents living in contaminated areas that have been exposed to environmental cadmium pollution for 45 years. METHODS: Subjects involved in the survey in 1987 were interviewed again in 2006. Rice and urine samples from surviving subjects were collected to assess the level of cadmium exposure. Urinary Cd (U-Cd), urinary ß2-microglobulin (U-ß2-M) and urinary N-acetyl-ß-d-glucosaminidase (U-NAG) were used as biomarkers to evaluate renal function. A medical examination was also performed on all subjects to diagnose clinical symptoms of Cd-exposure. RESULT: Of the 96 subjects of the 1987 study who were alive in 2006, a total of 76 subjects were successfully recruited to this study. The average cadmium concentration in rice from the exposed areas was 0.59 ± 0.41 mg/kg in 2006, the average concentration of U-Cd, U-ß2-M and U-NAG from cadmium-exposed areas was 25.82 ± 0.20 µg/g Cr, 6525.71 ± 0.93 µg/g Cr and 13.65 ± 0.24 µmol/g Cr, respectively, in 2006. Compared with the 1987 results, the 2006 results showed that the U-ß2-M level in the exposed areas increased significantly after 19 years (p<0.05). The levels of U-Cd and U-NAG did not significantly change over time. CONCLUSION: The concentration of Cd in polluted areas in 2006 is higher than it was in 1987. Renal dysfunction has worsened after 45 years of continuous exposure. Thus, environmental protection and special procedures to remove cadmium in these areas require urgent consideration.

[The quantitative classification and survey of sanitation of urban secondary water supply in Haidian district of Beijing].

OBJECTIVE: To investigate the sanitary status of urban secondary water supply facilities in Haidian district of Beijing. METHODS: Adopting the quantitative classification table drafted by the Bureau for Sanitation Inspection and Supervision of Haidian district, we carried quantitative classification (A, B, C grade) on all 1725 secondary water supply facilities in Haidian district for two times. At the same time, we collected 20 residential areas with stratified random sampling method. As the public points in the first quantitative classification, the effect of level publicity on changing the sanitary grade of the secondary water supply facilities were observed. RESULTS: In the first two times of quantitative classification, A-level and B-level secondary water supply facilities took up 81.04% (1398/1725) and 89.04% (1536/1725) of all secondary water supply facilities respectively; the ratio of effective sanitary permits achieved 86.14% (1486/1725) and 92.35% (1593/1725) respectively; and the ratio of effective water quality test reports achieved 86.60% (1494/1725) and 97.10% (1675/1725) respectively. There were 52 secondary water supply facilities in 20 collected areas, including 8 A-level, 27 B-level and 17 C-level secondary water supply facilities before level publicity, and 19, 29 and 4 after level publicity. The impact of level publicity on changing the sanitary grade of the secondary water supply facilities was statistically significant (χ(2) = 12.60, P = 0.002). CONCLUSION: The city secondary water supply facilities in Haidian district are overall in good sanitary conditions. Quantitative classification and level publicity can effectively improve the sanitary status of secondary water supply facilities.

[A following up survey on cadmium level in rice in contaminated area, Jiangxi Province].

OBJECTIVE: To observe rice cadmium level in a contaminated area where has being continuously polluted for 19 years since last investigation. METHODS: Samples of late rice (polished) grown in 2006 were collected from farmer household in contaminated and control area and its cadmium concentration were detected with IPC-MS. RESULTS: Samples of polished rice from the polluted and control areas were detected. The average cadmium concentration from last investigation area 19 years before was 0.59 mg/kg (0.05 mg/kg for rice from control area), it upraises about 30% corresponding to average of rice from the same areas detected before 19 years. The average cadmium level of rice from whole contaminated areas (including last investigation and expanding areas) was 0.26 mg/kg and it is greater than that in control areas (0.06 mg/kg) and the limited value of national hygiene standard (< 0.20 mg/kg). There was about 64%, 23.17% and 11% of samples have higher level than 0.20 mg/kg (the limited value of national hygiene standard), 0.4 mg/kg (the limited value of Codex General Standard) and 1.0 mg/kg (cadmium-rice) respectively. There was a higher percentage (36.8%) of Cadmium-rice (greater than 1.0 mg/kg) in some heavy contamination villages. CONCLUSION: Environmental cadmium pollution has being existing for 19 years since last investigation. Average cadmium concentration of rice from whole country polluted areas was higher than that of national hygiene standard. Percentage of "cadmium-rice" might be higher in some villages.

[Research advance of environmental cadmium exposure on human health damage].

Based on the available data of population survey, we review the research situation of health hazards on the environment cadmium polluted population from the threshold study of cadmium burden on human body, the chronic hazards of cadmium pollution on human health, the identification diagnosis of cadmium hazards. The information in this review could provide ideas for future study goal and development trend of health hazards in environmental cadmium pollution.