Association between Intake of Edible Mushrooms and Algae and the Risk of Cognitive Impairment in Chinese Older Adults.

Previous studies have investigated the association between diet and cognitive impairment, yet there is limited investigation into the link between edible mushrooms and algae intake and cognitive decline. This study aims to explore the association between edible mushrooms and algae intake and the risk of cognitive impairment in individuals aged 65 years and above in China. Cross-sectional data from the 2018 Chinese Longitudinal Healthy Longevity Survey (CLHLS) formed the basis of this study. Edible mushrooms and algae intake was evaluated using a simplified food frequency questionnaire (FFQ) and cognitive function was assessed using the Mini-Mental State Examination (MMSE). A binary logistic regression model was used to evaluate odds ratios (ORs) and 95% confidence intervals (CIs), with subgroup analysis conducted. Among 14,150 older adults, the average age was (85.33 ± 11.55), with a cognitive impairment prevalence of 22.7; multi-model adjustments showed a 25.3% lower probability of cognitive impairment for those occasionally consuming edible mushrooms and algae (OR: 0.747, 95% CI: 0.675~0.826). Furthermore, a 29% lower risk was observed in those with daily intake (OR: 0.710, 95% CI: 0.511~0.987). Subgroup analysis demonstrated significant risk reduction in women (OR: 0.589, 95% CI: 0.375~0.925, p = 0.022), individuals with disability in activities of daily living (OR: 0.568, 95% CI: 0.367~0.878, p = 0.011), and those with low social activity levels (OR: 0.671, 95% CI: 0.473~0.950, p = 0.025). This study concludes that edible mushrooms and algae intake significantly impacts the risk of cognitive impairment in older adults. These results provide insights and impetus for further research into this area. Additional cohort studies or intervention trials are necessary to confirm the potential benefits of edible mushrooms and algae in promoting cognitive health.

Macrophage ß-arrestin-1 deteriorates DSS-induced colitis through interaction with NF-κB signaling.

ß-arrestin-1 has been demonstrated to participate in the regulation of inflammatory reactions in several diseases. Thus, this study aimed to investigate the role of macrophage ß-arrestin-1 in the pathogenesis and progression of ulcerative colitis (UC). A myeloid ß-arrestin-1 conditional knockout mouse model was generated to explore the role of macrophage ß-arrestin-1. DSS was employed for the establishment of an ulcerative colitis mouse model, using TNF-α as an inflammatory stressor in vitro. The expression level of ß-arrestin-1 was detected via western blot and immunofluorescence assays, whilst disease severity was evaluated by clinical score and H&E staining in the DSS-induced colitis model. In the in vitro experiments, the levels of inflammatory cytokines were examined using real-time PCR. NF-κB activation was detected through the double luciferase reporter system, western blot, and electrophoretic mobility shift assay (EMSA). BAY11-7082 was used to inhibit NF-κB activation. Our results exposed that the level of ß-arrestin-1 was increased in monocytes/macrophages derived from DSS-induced colitis mice or under the TNF-α challenge. Moreover, conditionally knocking out the expression of myeloid ß-arrestin-1 alleviated disease severity, while knocking out the expression of ß-arrestin-1 decreased the levels of inflammatory cytokines. Additionally, NF-κB was identified as a central regulatory element of ß-arrestin-1 promoter, and using BAY11-7082 to inhibit NF-κB activation lowered the level of ß-arrestin-1 under TNF-α challenge. ß-arrestin-1 led to the activation of the NF-κB signaling pathway by enhancing binding to IκBα and IKK under the TNF-α challenge. Taken together, our findings demonstrated macrophage ß-arrestin-1 contributes to the deterioration of DSS-induced colitis through the interaction with NF-κB signaling, thus highlighting a novel target for the treatment of UC.

Combined administration of anisodamine and neostigmine alleviated colitis by inducing autophagy and inhibiting inflammation.

Our previous work demonstrated that the anisodamine (ANI) and neostigmine (NEO) combination produced an antiseptic shock effect and rescued acute lethal crush syndrome by activating the α7 nicotinic acetylcholine receptor (α7nAChR). This study documents the therapeutic effect and underlying mechanisms of the ANI/NEO combination in dextran sulfate sodium (DSS)-induced colitis. Treating mice with ANI and NEO at a ratio of 500:1 alleviated the DSS-induced colitis symptoms, reduced body weight loss, improved the disease activity index, enhanced colon length, and alleviated colon inflammation. The combination treatment also enhanced autophagy in the colon of mice with DSS-induced colitis and lipopolysaccharide/DSS-stimulated Caco-2 cells. Besides, the ANI/NEO treatment significantly reduced INF-γ, TNF-α, IL-6, and IL-22 expression in colon tissues and decreased TNF-α, IL-1ß, and IL-6 mRNA levels in Caco-2 cells. Meanwhile, the autophagy inhibitor 3-methyladenine and ATG5 siRNA attenuated these effects. Furthermore, 3-methyladenine (3-MA) and the α7nAChR antagonist methyllycaconitine (MLA) weakened the ANI/NEO-induced protection on DSS-induced colitis in mice. Overall, these results indicate that the ANI/NEO combination exerts therapeutic effects through autophagy and α7nAChR in a DSS-induced colitis mouse model.

OBJECTIVE QUANTIFICATION OF DEPTH-OF-FIELD ADVANTAGE IN 3D SURGICAL VIDEO SYSTEM FOR VITREORETINAL SURGERY: Safety and Efficacy in Macular Diseases.

PURPOSE: The objective of this study was to demonstrate, based on objective clinical indicators, the advantages of depth of field provided by the 3D surgical video system compared with the traditional microscope during vitrectomy for treating epiretinal membranes or macular holes. METHODS: A total of 38 patients were included in this study and randomly assigned to either the 3D surgical video group or the conventional microscope group. Surgical parameters, such as the focal plane adjustment frequency, membrane peeling time, and number of attempts to peel the membrane, were recorded for each patient. In addition, patients were followed up for 3 months postoperatively. RESULTS: No significant differences were observed in age, sex, operated eyes, or follow-up rates between the groups. The 3D group had significantly lower focal plane adjustment frequency in macular hole surgery and epiretinal membrane surgery. No significant differences were observed in peeling maneuvers, time, or total surgical time. Postoperative follow-up data showed no significant differences. CONCLUSION: In conclusion, the 3D surgical video system exhibits potential advantages in depth of field. The 3D surgical video system is a safe and effective technology in vitrectomy for macular diseases.

Lupus-associated innate receptors drive extrafollicular evolution of autoreactive B cells.

In systemic lupus erythematosus, recent findings highlight the extrafollicular (EF) pathway as prominent origin of autoantibody-secreting cells (ASCs). CD21loCD11c+ B cells, associated with aging, infection, and autoimmunity, are contributors to autoreactive EF ASCs but have an obscure developmental trajectory. To study EF kinetics of autoreactive B cell in tissue, we adoptively transferred WT and gene knockout B cell populations into the 564Igi mice - an autoreactive host enriched with autoantigens and T cell help. Time-stamped analyses revealed TLR7 dependence in early escape of peripheral B cell tolerance and establishment of a pre-ASC division program. We propose CD21lo cells as precursors to EF ASCs due to their elevated TLR7 sensitivity and proliferative nature. Blocking receptor function reversed CD21 loss and reduced effector cell generation, portraying CD21 as a differentiation initiator and a possible target for autoreactive B cell suppression. Repertoire analysis further delineated proto-autoreactive B cell selection and receptor evolution toward self-reactivity. This work elucidates receptor and clonal dynamics in EF development of autoreactive B cells, and establishes modular, native systems to probe mechanisms of autoreactivity.

Enhanced neuroprotective activity of ophthalmic delivered nerve growth factor conjugated with cell penetrating peptide against optic nerve injury.

Aims: Nerve growth factor is a well characterised neurotrophic factor that play a critical role in the survival, growth and differentiation of neurons both in central and peripheral nervous system. However, it is difficult for the conventional exogenous nerve growth factor administration delivery to the central nervous system due to the biological barrier in human bodies.Results: We validated a series of cell penetrating peptides and found that L-PenetraMax significantly enhanced the efficiency of recombinant human nerve growth factor entry into the rat retina. In the optic nerve crush mice model, eye drop administration of recombinant human nerve growth factor alone promoted retinal ganglion cell survival and axon regeneration at high dose, while the combination of recombinant human nerve growth factor with L-PenetraMax significantly enhanced the neuroprotective efficacy at lower dose, thus potentially enhancing the availability of recombinant human nerve growth factor eye drops in patients with optic neuropathy.Conclusions: This study provides the evidence that the noncovalent coadministration of recombinant human nerve growth factor with L-PenetraMax could be a potent strategy for the non-invasive and sustained ocular delivery of therapeutic proteins for improving the optic nerve injury.

Enhancing surgical precision and efficiency: a study and comparison of a three-dimensional surgical video system in proliferative diabetic retinopathy surgery.

Purpose: This study aimed to investigate the safety and efficacy of three-dimensional (3D) surgical video systems for proliferative diabetic retinopathy (PDR). Methods: This retrospective clinical case study included 30 patients (30 eyes) with PDR. Patients were divided into two groups: one underwent surgery using a 3D surgical video system (14 cases, 14 eyes), while the other underwent traditional microscope surgery (16 cases, 16 eyes). Safety and efficacy were assessed through predetermined surgical parameters, including surgical duration, intraoperative membrane removal rate, and occurrences during intraoperative and postoperative phases. Results: Our study revealed noteworthy differences in various aspects between the 3D surgical video system group and the traditional microscope surgery group. Specifically, the mean surgical time was 30.25 ± 14.43 mins in the 3D surgical video system group, while it was 38.56 ± 18.71 mins in the traditional microscope surgery group (p = 0.051). Furthermore, the mean membrane removal time was significantly shorter in the 3D group at 2.53 ± 1.52 mins, as compared to 3.23 ± 1.76 mins in the traditional group (p = 0.042). Importantly, the membrane removal rate also displayed a significant difference, with the 3D group at 0.55 ± 0.07 and the traditional group at 0.41 ± 0.11 (p = 0.018). However, no notable differences were observed between the two groups in terms of intraoperative and postoperative incidences. Conclusion: The safety and efficacy obtained using the 3D surgical video system in PDR surgery were comparable to those obtained in traditional microscopic surgery.

Depletion of ß-arrestin-1 in macrophages enhances atherosclerosis in ApoE-/- mice.

Autophagy in atherosclerotic plaque macrophage contributes to the alleviation of atherosclerosis through the promotion of lipid metabolism. ß-arrestins are multifunctional proteins participating various kinds of cellular signaling pathways. Here we aimed to determine the role of ß-arrestin-1, an important member of ß-arrestin family, in atherosclerosis, and whether autophagy was involved in this process. ApoE-/-ß-arrestin-1fl/flLysM-Cre mice were created through bone marrow transplantation for the atherosclerosis model with conditional myeloid knocking out ß-arrestin-1. Bone marrow-derived macrophages (BMDMs) were used for the in vitro studies. Oil red O staining was used to detect the lesional area. F4/80, Masson trichrome and picro-Sirius red staining were applied for the determination of plaque stability. Real-time PCR was used for the detection of levels of lipid metabolism-related receptors. Electron microscopy and tandem fluorescent mRFP-GFP-LC3 plasmid was applied to test autophagy level. We found that ß-arrestin-1 was highly increased in expression in plaque macrophage on the occurrence of atherosclerosis. Conditional myeloid knocking out ß-arrestin-1 largely promotes plaque formation and vulnerability. In murine macrophage with lipid loading, knocking down ß-arrestin-1 enhanced foam cell formation and levels of plasma and cellular cholesterol, while overexpressing ß-arrestin-1 led to the opposite effects. The alleviative effects induced by macrophage ß-arrestin-1 in atherosclerosis were involved in autophagy, based on the reduction of autophagy level with the knocking down of macrophage ß-arrestin-1 and administration of autophagy inhibitors which largely attenuated the decreasing effect on foam cell formation. Our results demonstrated for the first time that macrophage ß-arrestin-1 protected against atherosclerosis through the induction of autophagy.

[Spatial Distribution, Source Analysis, and Health Risk Assessment of Metal Elements in Karst Water in Southeastern Chongqing].

Dispersed karst water is an important water supply source, or even the only water supply source, for some districts and counties in Chongqing City. It is particularly necessary to understand the distribution characteristics of metal elements in karst water and the health risks exposed. In this study, the scattered karst water in the southeastern part of Chongqing was taken as the main research object, and the concentrations of Al, Cu, Pb, Zn, Cr, Cd, Ni, Mn, As, and Hg in 42 groups of karst spring water samples were determined. The spatial distribution of metal elements with a high detection rate was revealed using the ordinary kriging interpolation method, and the spatial distribution characteristics, sources, and health risks of metal elements were analyzed using multivariate statistical methods and health risk models. The results showed that the quality of dispersed karst water in southeastern Chongqing was generally good, and the spatial scale variability in the occurrence of metal elements in karst water was strong, especially for Ni and As. The sources of Cu, Pb, As, Zn, and Cr were mainly affected by the regional geological background; Al and Mn were mainly affected by human industrial, agricultural, and mining activities; and Ni was affected by both the natural background and human activities. The total health risk of exposure through the drinking route was higher than that of the skin infiltration route, which was the main exposure route of the human body. The total health risk of children exposed through the drinking route was higher than that of adults, and the total health risk of adults exposed through the skin infiltration route was higher than that of children. It is worth noting that Cr was the determinant of total health risk. From the perspective of drinking water safety, local residents need to pay certain attention to water quality when drinking distributed karst groundwater, in order to reduce the health risk of the population.

Regulated control of virus replication by 4-hydroxytamoxifen-induced splicing.

Designing a modified virus that can be controlled to replicate will facilitate the study of pathogenic mechanisms of virus and virus-host interactions. Here, we report a universal switch element that enables precise control of virus replication after exposure to a small molecule. Inteins mediate a traceless protein splicing-ligation process, and we generate a series of modified vesicular stomatitis virus (VSV) with intein insertion into the nucleocapsid, phosphoprotein, or large RNA-dependent RNA polymerase of VSV. Two recombinant VSV, LC599 and LY1744, were screened for intein insertion in the large RNA-dependent RNA polymerase of VSV, and their replication was regulated in a dose-dependent manner with the small molecule 4-hydroxytamoxifen, which induces intein splicing to restore the VSV replication. Furthermore, in the presence of 4-hydroxytamoxifen, the intein-modified VSV LC599 replicated efficiently in an animal model like a prototype of VSV. Thus, we present a simple and highly adaptable tool for regulating virus replication.

A wideband high-power microwave radiation source based on gyromagnetic nonlinear transmission line and Vlasov antenna.

The gyromagnetic nonlinear transmission line (GNLTL) is a special kind of coaxial transmission line partially loaded with the ferrite material. A GNLTL system can modulate the input high-power pulses into wideband high-power microwaves without relying on the electron beam and confining magnetic field. The unique working mechanism gives the GNLTL system the potential to be a small portable wideband high-power microwave radiation source. In this study, a wideband high-power microwave radiation source based on a GNLTL system is designed and constructed. In order to effectively radiate the wideband microwaves into the air, a high-power wideband Vlasov antenna and a special absorption high-pass filter are developed. The designs of key subsystems and high-power radiation experiments have been introduced and discussed in detail. In the test experiments, a radiated pulse with a peak electric field strength of 23 kV/m was measured at 20 m away from the transmitting antenna and the effective potential of radiation is 460 kV/m. The pulse width of the radiation pulse is about 4 ns, the center frequency is about 2.25 GHz, and the highest repetition rate can reach 25 Hz.

Application of the hydrochemistry, stable isotopes and MixSIAR model to identify nitrate sources and transformations in surface water and groundwater of an intensive agricultural karst wetland in Guilin, China.

Karst water as the vital water supply source is generally suffered from NO3- contamination in intensive agricultural areas worldwide. Identifying NO3- sources and transformations is the key for understanding nitrogen pathways, and also for effectively controlling diffuse NO3- pollution. In this study, chemical variables and stable isotopes (δ2H-H2O, δ18O-H2O, δ15N-NO3- and δ18O-NO3-) were measured in 10 surface water (SW) samples and 13 groundwater (GW) samples collected from the Huixian karst wetland, with the application of a Bayesian stable isotope mixing model (MixSIAR) to identified NO3- sources and biogeochemical transformations. The results showed that the NO3- concentrations ranged from the below detection limit to 117 mg/L, with 30.8% of GW samples obtained from the north central part of the study area exceeding the maximum permissible limit for drinking water, and posing significant non-carcinogenic health risks for native people through drinking water pathway. Moreover, based on characteristics of the hydrochemistry and stable isotopes, different biogeochemical fates were evaluated in SW and GW: nitrification process was a dominant factor in GW, as a result of high NO3- levels, and this microbial process was unlikely occurred in SW associated with relatively anaerobic condition and low NO3- levels; however, the denitrification might not be a main process of degradation NO3- levels throughout the study area. The MixSIAR outputs revealed that the long-term application of synthetic NH4+ fertilizer (36.6%) and soil organic nitrogen (28.0%) were the main contributors to NO3- pollution, followed by synthetic NO3- fertilizer (16.8%) and domestic sewage and manure (15.1%), whereas NO3- in precipitation (3.44%) played a less important role. Additionally, NO3- concentration was significantly influenced by agricultural activities rather than NO3- source's contribution between SW and GW. This work suggests that synthetic NH4+ fertilizer should be the primary target for control to prevent further NO3- pollution of the karst groundwater.

A human-airway-on-a-chip for the rapid identification of candidate antiviral therapeutics and prophylactics.

The rapid repurposing of antivirals is particularly pressing during pandemics. However, rapid assays for assessing candidate drugs typically involve in vitro screens and cell lines that do not recapitulate human physiology at the tissue and organ levels. Here we show that a microfluidic bronchial-airway-on-a-chip lined by highly differentiated human bronchial-airway epithelium and pulmonary endothelium can model viral infection, strain-dependent virulence, cytokine production and the recruitment of circulating immune cells. In airway chips infected with influenza A, the co-administration of nafamostat with oseltamivir doubled the treatment-time window for oseltamivir. In chips infected with pseudotyped severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), clinically relevant doses of the antimalarial drug amodiaquine inhibited infection but clinical doses of hydroxychloroquine and other antiviral drugs that inhibit the entry of pseudotyped SARS-CoV-2 in cell lines under static conditions did not. We also show that amodiaquine showed substantial prophylactic and therapeutic activities in hamsters challenged with native SARS-CoV-2. The human airway-on-a-chip may accelerate the identification of therapeutics and prophylactics with repurposing potential.

[Pollution and Irrigation Applicability of Surface Water from Wet, Normal, and Dry Periods in the Huixian Karst Wetland, China].

To reveal the hydrochemical characteristics of karst wetland located in a subtropical area and at lower elevations in China, 27 surface water samples were collected during three periods (wet, normal, and dry) in the Huixian karst wetland to investigate the distributions, pollution, and irrigation application of 12 inorganic ions and 10 heavy metals. Based on their concentrations, the Nemerow index and the four evaluation systems of the sodium adsorption ratio (SAR), sodium concentration (SC), permeability index (PI), and residual sodium carbonate (RSC) were applied to evaluate the pollution characteristics and irrigation application. It was found that the water type in this area was Ca2+-HCO3- and weakly alkaline. Regarding the 12 inorganic ions and 10 heavy metals, NH4+ exceeded the Chinese standards for drinking water with an exceedance rate of 25.93%, and the exceedance rates of Al, Mn, and Hg were 11.11%, 44.44%, and 37.04%, respectively. The spatiotemporal scaling effect on inorganic ions was lower than that of heavy metals, and the distributions of the inorganic ions and heavy metals were in the order of wet period > normal period > dry period. However, the surface water quality in the Huixian karst wetland was generally well-protected based on the pollution assessment. The Nemerow index ranged from 0.75 to 2.69, which recognized the main pollution contributors as NH4+, Mn, Al, and Hg with the contamination grade from slight pollution to moderate pollution, especially in the core area during the wet period. According to the limits of standards for irrigation water quality and environmental quality for surface water, as well as the evaluation results of the SAR, SC, PI, and RSC, the surface water in the Huixian karst wetland was generally suitable for irrigation, and the water quality in the dry period was better than that in the wet and normal periods. The surface water from site PH1 during the normal period with 19.1 µg·L-1 of Hg and site FH8 during the wet period with 13.7 mg·L-1 of NH4+ were not suitable for agricultural irrigation.

Operation analysis of the wideband high-power microwave sources based on the gyromagnetic nonlinear transmission lines.

The wideband High-Power Microwave (HPM) sources, which combine the advantages of narrowband and ultrawideband sources, have drawn much attention. As a kind of wideband source, the gyromagnetic nonlinear transmission lines (GNLTLs) can directly modulate the incident pulses into radio frequency pulses without relying on the interaction between e-beam and microwaves. Due to the special working mechanism of gyromagnetic precession, the center frequency of the GNLTL can also be adjusted in a certain range. Based on classical magnetism and a simplified model of the GNLTL, this paper semi-quantitatively and theoretically analyzed the generation mechanism of HPM and illustrated the influences of the variations of parameters on the output microwaves. Then, a simple simulation based on 1-dimensional transmission line modeling method was carried out to study the performance of the GNLTL quantitatively, with the coupling of 1D telegraphist equations and the 3D Landau-Lifshitz-Gilbert equation. Simulation results preliminarily verified the conclusions derived from the theoretical analysis, and some working characteristics of the GNLTL were also obtained. This paper may help to understand the special working mechanism of the GNLTL and provide certain guidance for related simulations and experiments.

[Major Ionic Characteristics and Factors of Karst Groundwater at Huixian Karst Wetland, China].

To investigate the major ionic chemical characteristics and seasonal variations, 27 groundwater samples were collected from the wet season, flat season, and dry season during 2018-2019 in the Huixian Karst wetland, which is the largest low-altitude karst wetland in China. The single pollution standard index was applied to evaluate the groundwater pollution during different periods, and the major ionic factors of the karst groundwater were analyzed using the statistical analysis method, Gibbs diagram, and ion ratio. The results revealed that the groundwater samples were a weakly alkaline fresh water that were rich in Ca2+ and HCO3-. The average concentrations of the primary ions followed the order of flat season > wet season > dry season; meanwhile, the water quality in the dry season was better than that in the wet and flat seasons. The K+ and NO3- in the karst groundwater were mostly affected by the spatial distributions of the aquifers, and the Mg2+, SO42-, NO2-, NH4+, and TDS were related to the space-season scale. Na+, Ca2+, HCO3-, and Cl- were relatively stable ions in the karst groundwater. The hydrochemical characteristics were primarily determined by carbonate rock dissolution and were found to be the HCO3-Ca type, which accounted for 77.78%, 77.78%, and 88.89% in the wet season, flat season, and dry season, respectively. The karst groundwater was predominantly polluted by SO42-, NO3-, and NO2-; particularly, NO3- exhibited serious pollution points, and SO42- had heavy pollution points in the wet and flat seasons. The chemical composition of the karst groundwater was controlled mostly by water-rock interactions. Ca2+ and HCO3- primarily came from calcite dissolution, and the high concentrations of Mg2+ and SO42- in a few number of points were controlled by dolomite, dolomitic limestone, and pyrite. K+, Na+, SO42-, NO3-, and Cl- partly came from atmospheric precipitation, and Na+ and Cl- partly came from human activities; K+ was related to potash fertilizer, and the main source of NO3- was chemical fertilizer.

[Metal Pollutions and Human Health Risks in Groundwater from Wet, Normal, and Dry Periods in the Huixian Karst Wetland, China].

The concentrations of 10 metals (Cd, Cr, As, Al, Cu, Pb, Zn, Mn, Hg, and Fe) in 27 groundwater samples collected during different periods (wet, normal, and dry) in the Huixian Karst wetland, the largest subtropical low-altitude karst wetland in China, were detected and analyzed to investigate pollution and health risks. The pollution characteristics, distribution, and health risks of the metals in groundwater were revealed by a comprehensive pollution assessment, multivariate statistical analysis, and health risk assessment model, respectively. The results showed that the average concentrations of metals in groundwater were followed the order of Mn > Fe > Zn > Al > Hg > Cr > Cu > Cd > As > Pb. The maximum concentration of Mn (1022.00 µg·L-1) was found in the wet season, while that of Hg (42.40 µg·L-1) was found in the normal season, and both were over the corresponding standard limits. The results of the pollution assessment indicated that only Mn pollution reached level Ⅵ in the wet season, while Cd, Al, Zn, and Fe pollution were at the level of Ⅲ. Only the Hg pollution level reached level Ⅵ while Al pollution reached the level of Ⅲ in the normal water period. According to the above results, the water quality in the dry season was better than that in the wet and normal seasons in terms of the 10 metals. The concentrations of Zn, Cd, Mn, and Al in groundwater were affected by human activities, while the time-scale characteristics of these were not obvious. The concentrations of As, Fe, Cu, and Cr were all affected by human activities and the time-scale, while the concentrations of Hg and Pb were mainly manifested in time-scale characteristics. The results of the health risk assessment of the water due to drinking and the skin penetration pathway indicated that the total health risks followed the order of normal season > the wet season > the dry season. The carcinogenic risks caused by Cr for adults and children through drinking pathway in the wet season (8.03×10-5 a-1 and 8.76×10-5 a-1), normal season (1.15×10-4 a-1 and 1.26×10-4 a-1),and dry season (8.72×10-5 a-1 and 9.51×10-5 a-1) exceeded the maximum allowed level (5.0×10-5 a-1) in all periods. Hence, Cr was the main metal element that caused carcinogenic risks. For the sake of drinking water safety, the concentrations of Mn, Hg, and Cr in groundwater should be controlled before drinking.

Therapeutic Effects of Simultaneous Delivery of Nerve Growth Factor mRNA and Protein via Exosomes on Cerebral Ischemia.

Stroke is the leading neurological cause of death and disability all over the world, with few effective drugs. Nerve growth factor (NGF) is well known for its multifaceted neuroprotective functions post-ischemia. However, the lack of an efficient approach to systemically deliver bioactive NGF into ischemic region hinders its clinical application. In this study, we engineered the exosomes with RVG peptide on the surface for neuron targeting and loaded NGF into exosomes simultaneously, with the resultant exosomes denoted as NGF@ExoRVG. By systemic administration of NGF@ExoRVG, NGF was efficiently delivered into ischemic cortex, with a burst release of encapsulated NGF protein and de novo NGF protein translated from the delivered mRNA. Moreover, NGF@ExoRVG was found to be highly stable for preservation and function efficiently for a long time in vivo. Functional study revealed that the delivered NGF reduced inflammation by reshaping microglia polarization, promoted cell survival, and increased the population of doublecortin-positive cells, a marker of neuroblast. The results of our study suggest the potential therapeutic effects of NGF@ExoRVG for stroke. Moreover, the strategy proposed in our study may shed light on the clinical application of other neurotrophic factors for central nervous system diseases.

Dendritic Cells Therapy with Cytokine-Induced Killer Cells and Activated Cytotoxic T Cells Attenuated Th2 Bias Immune Response.

THE AIM OF THIS STUDY: The purpose of this study is to investigate whether the DC cells combined with CIK cells (DC/CIK) and DC activated cytotoxic T cells (DC-ACT) treatment can promote antitumor response and change the immune indicators by targeting the heterogeneous tumor cell populations at a system level. METHODS: In this study, 112 patients with cancer were assigned to the DC/CIK treatment and 116 patients received the DC-ACT therapy. We detected the lymphocyte subsets and other immune indicators pre- and post-treatment to evaluate the changes of patient's immunity and compare the differences in immune status between two adoptive cellular immunotherapies. RESULTS: DC/CIK therapy elevated the percentage of CD3+ HLA-DR+ T cells, NK cells and several serological cytokines such as IL-2, IL-6 after cell infusion (p < .05). DC-ACT therapy could increase the total CD3 + T cells, CD8 + T cells, CD3+ HLA-DR+ cells and IL-12 cytokines after cell infusion (p < .05). The levels of IL-4/IFN-γ, IL-4/IL-12 and IL-6/IL-12 were reduced significantly in the DC-ACT group compared with DC/CIK group. These observations suggested that DC-ACT therapy has more dominance to induce Th1 cytokine response instead of skewing toward the Th2 cytokine profile based on the immunomodulatory properties. CONCLUSIONS: These results indicated that DC, CIK, and DC-ACT cells exert anti-tumor activity through the different pathways. Thus, this work may provide valuable insights into the clinical curative effect evaluation of immunocyte therapy and the design of combined immunotherapeutic strategies for malignant tumors.