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Aims To examine the association between alcohol consumption and mental health during the COVID-19 pandemic. Methods An anonymous online survey was distributed among US adults during May–August 2020 through social networks and ResearchMatch. We collected information on demographic, lifestyles and mental health symptoms including anxiety, depression, stress and post-traumatic stress disorder. Logistic regression models were used to examine the cross-sectional association between alcohol consumption and mental health symptoms. We also examined effect modification by race, age, gender, social support, financial insecurity and quarantine status. Results The analytical sample consists of 3623 adults. Stable drinking habits and regular drinking behaviors were found to co-exist with better mental health status. Participants who increased their alcohol use had higher odds of developing mental health disorders than those who maintained their pre-pandemic drinking habits. Additionally, participants who engaged in binge drinking during the pandemic had higher odds of depression and stress than those who did not. The associations regarding increased drinking and binge drinking in relation to adverse mental health outcomes were stronger among females, racial minorities, and individuals with financial concerns, poor social support and restricted quarantine status than their counterparts. Conclusions During the early stage of the COVID-19 pandemic, increased alcohol use and binge drinking are cross-sectionally associated with higher odds of mental health disorders, which highlighted the need for targeted intervention to address the mental health needs of individuals who have engaged in these behaviors, especially among females, minorities, those with insecurities or with restricted quarantine status.

Cadmium (Cd) is associated with telomere length and hypertension, respectively, but the mechanism behind its relationship is unclear. Our study aimed to clarify the role of telomere length in the relationship between Cd and hypertension. A 1:1 matched case-control study was conducted with 213 hypertensive patients and 213 normotensive controls in Taiyuan, Shanxi Province, China, from February and June 2016. General demographic characteristics information and lifestyle were collected using a structured questionnaire. Urine samples were collected to test urinary Cd (UCd) levels and corrected by urinary creatinine (UCr) levels. Peripheral leukocyte absolute telomere length (ATL) was measured using quantitative polymerase chain reaction. Logistic regression was used to screen the influencing factors of hypertension. A mediation effect analysis was used to explore the role of telomere length between Cd exposure and the risk of hypertension. We found that the hypertension group had a significantly higher UCd level compared to the control group (0.91 vs 0.80 μg/g Cr, P 0.01), while ATL showed the opposite relationship (2.36 vs 2.65 kb, P 0.01). The Regression analysis of hypertension identified these significant predictors: family history of hypertension (OR = 3.129, 95% confidence interval (95% CI): 1.767-5.540), Body mass index (BMI, OR = 1.088, 95% CI: 1.023-1.157), total cholesterol (TC, OR = 1.277, 95% CI: 1.024-1.592), UCd (OR = 2.092, 95% CI: 1.179-3.710), ATL (OR = 0.105, 95% CI: 0.025-0.453) and 8-hydroxy-2-deoxyguanosine (8-OHdG, OR = 7.864, 95% CI: 3.516-17.589). Mediating effect analysis revealed that ATL was a potential partial mediating factor between Cd and hypertension. Cd may induce hypertension by affecting telomere length, but this requires further exploration.

Subway transportation is being promoted worldwide to effectively solve urban congestion. However, the vibration induced by subway traffic has caused a major adverse impact on building safety, precision instrument operation and human health. Wave barriers have been proven effective in mitigating ground vibration, whereas they have some limitations in achieving ideal attenuation zone and high efficiency to cover the low-frequency vibration in underground railway system. Based on locally resonant phononic crystals theory, this paper designs three-component locally resonant periodic wave barriers (LRPWBs), and investigates the effects of geometrical and material parameters on the bandgap features in detail. The band structures are calculated using improved plane wave expansion (IPWE), the transmission spectra and vibration modes are obtained by finite element method (FEM). The results indicate LRPWBs are able to give lower and wider bandgap to cover the main frequency of subway environment, which is proved by time and frequency domain analysis. For the bandgap mechanism, the local resonance features of LRPWBs result in the energy conversion between kinetic energy and elastic strain energy, thus the elastic wave energy is localized in resonance unit and then the locally resonant bandgap is created. In addition, the bandgap can be adjusted by carefully selecting proper geometrical and material parameters to actualize low-frequency broadband attenuation. Further studies about multi-oscillator system indicate that the appropriate combination of multiple LRPWBs are conductive to diverse and broad bandgaps. The investigations can provide inspiration for periodic wave barriers design in multi-frequency vibration attenuation field.

The structural expanded polystyrene (EPS) concrete (above 35 MPa) has the potential to be used as metro track bed to reduce and isolate vibration, but its bond behavior is still unclear. This inhibits its application because it is often used in combination with reinforcing bar. In this paper, a class of structural EPS concrete (above 35 MPa) was developed. Based on this, a series of pull-out tests were conducted and the bond behavior of deformed bars in these structural EPS concretes was investigated. In addition, effects of rebar bond length and rebar diameter were analyzed in detail. Experimental results indicate that the structural EPS concrete suffers splitting failure more easily than the conventional concrete (CC). Increase of EPS replacement, rebar bond length or rebar diameter tends to cause the splitting failure of structural EPS concrete. Moreover, with increase of EPS replacement, the failure process is less explosive and more gradual. The stress-slip relationships of the most specimens show three stages, namely linear ascending, non-linear progression, and descending stages. The bond strength of structural EPS concrete is found depended linearly on the power function of its compressive strength, relative cover thickness (c/d) and relative rebar bond length (L/d), respectively. Accordingly, a bond strength prediction model was formulated, and it can precisely predict the bond strength of deformed bars in structural EPS concrete, specimens failing in splitting or splitting-pull out modes, and no fiber added. The results can provide reference for the design of structural EPS concrete.

Previous studies have examined the associations between ambient fine particulate matter (PMTo examine the associations of prenatal ambient PMFrom July 2016 to October 2017, a birth cohort study was conducted in Beijing, China. Participants were interviewed in each trimester regarding demographics, lifestyle, living and working environment, and medical conditions. Participant's daily ambient PMOf 165 pregnant women, 23 (13.94%) developed GDM. After adjusting for potential confounders, PMAmbient PM

During the COVID-19 pandemic, social distancing measures often resulted in individual isolation, which can lead to adverse mental outcomes. We collected online questionnaires from 3,952 US adults to examine the impact of “shelter-in-place” guidelines on mental health, and to explore potential disparities and modifiable factors. Self-reported anxiety, depression, and PTSD symptoms were associated with more restrictive quarantine. Younger adults, women, those with lower income, more insecurity, more media exposure, reduced physical activity, or worsened family relationships were particularly affected. Targeted prevention on susceptible subpopulations, including young adults and lower SES groups, might help mitigate disparities in COVID-19-related mental health problems.

Locally resonant phononic crystals (LRPCs) have the capacity to adjust elastic waves with the structure sizes much smaller than the incident wavelengths, the unique property is called low-frequency bandgap, but it is not easily applied in practical engineering because of narrow bandgap width. Multilayered LRPCs are helpful in generating several bandgaps, in the meanwhile the designs of multilayered LRPCs proposed in previous study result in the larger filling fraction, whereas the bandwidth of LRPCs increases monotonically with filling fraction, thus the pure contribution of concentric ring configuration to the bandwidth extending is less involved. Keeping the filling fraction constant, this paper carefully designs the microstructure of concentric ring locally resonant phononic crystals, and investigates the effects of structure configuration on the bandgap property. To this end, an updated improved plane wave expansion (UIPWE) method is developed to calculate the band structure, and finite element method (FEM) is used to obtain transmission spectra and vibration mode. The results demonstrate that UIPWE method is valid and is able to give precise outcomes, which is verified by FEM. In addition, the concentric ring configuration equivalently produces dual-oscillator system, relative movements between the oscillators generate coupling effect, thus, the bandgaps can be extended by configurating rightly the microstructure of single cell. Further studies about different models indicate that the combination of smaller inner scatterers and larger inner coating layers are beneficial to wider bandgap. These conclusions presented herein provide insights in the design of three-component PCs in multi-frequency vibration control field.

Locally resonant phononic crystal (LRPC) has the extraordinary property to prohibit the wave propagation in specific low-frequency ranges, however it exists limitation in engineering application due to narrow band gap width. Extensive achievements have been obtained on the locally resonant band gap (LRBG) tunability, whereas existing investigations mainly concern the independent primitive cells structure, which have the limitation in obtaining low-frequency and broadband simultaneously. In this paper, the composited locally resonant phononic crystals (CLRPC) are proposed and the effects of primitive cells contact state on the LRBG properties are investigated. The dispersion curves are applied to obtain the LRBG, and the corresponding modal features are analyzed to explain the band gap formation mechanism. The band structure indicates the design of composite primitive cells is able to increase the band gap number and obtain lower band gap, which is verified by the frequency response function (FRF). For the band gap formation mechanism, the asymmetric vibration due to primitive cells contact leads to diverse and strong coupling response, which generates more band gaps and reduces the band gap starting frequency, therefore the band gaps can be tuned by designing carefully the geometry structure of CLRPC. Further researches on band gap optimization demonstrate that the smaller cell spacing, smaller lattice constant and larger damping of coating layer should be satisfied to obtain broader LRBG and considerable attenuation synchronously. This investigation can provide references for the locally resonant isolation structure design in the low-frequency vibration control field.

In this paper, the effects of material parameters on the band gaps of two-dimensional (2D) three-component phononic crystals (PCs) are investigated based on improved plane wave expansion method (IPWE). The theoretical derivation is based on the elastic wave equations, and the effects on band gaps for both in-plane (xy-mode) and anti-plane modes (z-mode) are discussed in detail. Results show that the material parameters directly determining the band gaps include mass density ratio, shear modulus ratio, and Poisson’s ratio for xy-mode, and mass density ratio and shear modulus ratio for z-mode; for the three-component PCs with Bragg gaps, wide band gap appears in the case of large density mismatches and large shear modulus ratio of scatterer to matrix, and the Poisson’s ratio of the matrix has more influence on the band gap; for the three-component PCs with local resonance gaps, wide band gap appears in the case of large mass density ratio of scatterer to matrix and small mass density ratio of coating layer to matrix, large shear modulus ratio of scatterer to matrix and small shear modulus ratio of coating layer to matrix. These conclusions can be used to guide the band gap designing of the three-component PCs.

Phononic crystals (PCs) provide a new method for vibration insulation and noise reduction. PCs commonly have small bandgap width, and understanding how to expand this bandgap, including the ultra-low band gap, is crucial for applying PCs to vibration reduction in engineering structures. A new periodic structure composite material quasi-PCs is proposed and the high polymer concrete with quasi-PCs structure is conducted. Vibration measurements for the new periodic structure composite material demonstrate that quasi-PC behavior can open the ultra-low frequency band gap. The new periodic structure composite material can be used to reduce vibrations in engineering field.

Neuroprotective strategies using diazoxide (DZX) have been demonstrated to limit ischemia/reperfusion (I/R)‑induced injury and cell apoptosis. In type 2 diabetes mellitus, DZX has been reported to improve β‑cell function and reduce their apoptosis, through suppressing endoplasmic reticulum (ER) stress. However, the effects of DZX on ER stress during I/R‑induced neuronal apoptosis in the hippocampus remains to be elucidated. In the present study, pretreatment of hippocampal neurons with DZX was revealed to inhibit oxygen‑glucose deprivation (OGD)‑stimulated apoptosis in vitro and to alleviate I/R‑induced hippocampal injury and behavioral deficits in rats in vivo. Furthermore, OGD and I/R were demonstrated to induce ER stress via upregulating the expression of ER stress‑associated proteins, including C/EBP homologous protein, 78 kDa glucose‑regulated protein and caspase‑12, whereas the exogenous administration of DZX effectively downregulated ER stress‑associated protein expression following OGD and I/R. In addition, DZX was revealed to significantly increase the protein expression of B‑cell lymphoma (Bcl)‑2 and suppress the expression of caspase‑3 and Bcl‑2‑associated X protein. These findings suggested that DZX may protect cells against apoptosis via regulating the expression of ER stress‑associated proteins in vitro and in vivo, thus enhancing the survival of hippocampal cells. The present results suggested a novel mechanism that may underlie the protective effect of DZX administration in the central nervous system.

The red-emitting Ca9Eu(PO4)7 nanophosphors have been successfully synthesized by a facile hydrothermal method. X-ray diffraction (XRD), photoluminescence (PL) spectroscopy, GSAS structural refinement and scanning electron microscopy (SEM) were used to characterize the materials. Rietveld refinement of powder X-ray diffraction patterns of Ca9Eu(PO4)7 demonstrated that the structure of Ca9Eu(PO4)7 consisted of [PO4] tetrahedra. Ca/Eu atoms filled the space between the tetrahedral groups with Eu3+ ions distributed randomly on three individual Ca crystallographic sites. The major red emission peak located at 616 nm under 397 nm excitation attributed to the electric dipole transition 5D0 → 7F2 of Eu3+ was a parity forbidden f–f configuration transition, which would only occur when Eu3+ occupied lattice sites without inversion symmetry. Introducing Gd, La, and Y ions into samples made luminescence properties of Ca9Eu1−xLnx(PO4)7 (Ln = Gd, La, Y) phosphors decrease. pH value plays a key role in the formation of Ca9Eu(PO4)7 nanophosphor morphology. With increasing pH in the initial reaction solution, the morphology of samples changed from rod to sphere and their aspect ratio also decreased. Different morphologies have different photoluminescence properties, and samples prepared at pH 7 manifested better photoluminescence properties relative to other samples. This novel red-emitting phosphor could be applied in white light-emitting diodes.

Supplemental Digital Content is available in the text, Background: Chimeric antigen receptor (CAR) T-cell therapy has produced promising response rates in patients with B cell malignancies. However, previous meta-analyses have demonstrated that CAR T-cell efficacy is unsatisfactory in patients with lymphoma unlike in patient with other hematological malignancies, but these studies included insufficient numbers of studies and patients with lymphoma. Furthermore, clinicians are interested in the effects of infusion dose, CAR structure, interleukin-2 (IL-2), and conditioning therapy regimen. Methods: All clinical trials administering autologous CAR T-cell therapy in lymphoma patients were searched in medical databases. A traditional meta-analysis was performed to assess the safety and efficacy of CAR T-cells in lymphoma treatment. Subgroup analysis was performed to determine the relationships between potential factors and efficacy. The best overall response rate (ORR), 6 month ORR (6m ORR), and severe cytokine release syndrome (sCRS) rate were calculated by Stata 14.0. Results: A total of 411 patients across all the studies were included. Our analysis showed a best ORR of 0.71, a 6m ORR of 0.63, and an overall CRS (grade ≥ 3) rate of 0.18. The subgroup analysis showed that increased response rates and reduced CRS (grade ≥ 3) rates were associated with a low dose of CAR T-cells. No IL-2 administration and the use of a fludarabine-containing lymphodepletion regimen led to improved efficacy, while anti-CD19 CAR T cells led to a more successful outcome than anti-CD20 CAR T cells. In addition, 2nd- and 3rd-generation CAR T cells exhibited increased effectiveness in clinical studies, and no significant effect diversity was found between the 2nd- and 3rd-generation CAR T cells. sCRS was associated with a high dose of infused CAR T cells when IL-2 and fludarabine were excluded from the positive factors for sCRS. Conclusion: CAR T cells are promising in the treatment of relapsed or refractory lymphoma. Doses lower than 108/m2, no IL-2 administration, fludarabine administration, and anti-CD19 CAR T cells were related to improved efficacy and safety.

Cadmium exposure may be associated with high risk of hypertension. But inconsistent results have been reported. In this study, the association of blood pressure (BP) with blood cadmium (BCd) and the possible influencing factors were investigated. A total of 181 persons (71 men and 110 women) living near a cadmium smelter participated in this study. The participants completed a questionnaire and BP, BCd and related biochemical indicators were measured. The geometric mean of BCd was 3.84μg/L and 3.32μg/L for women and men. The systolic blood pressure (SBP) and diastolic blood pressure both increased with the increasing of BCd. The BP in women was positively correlated with BCd (p

Blood lead concentration (B-Pb), the main biomarker of lead exposure and risk, is curvi-linearily related to exposure. We assessed plasma lead (P-Pb) as a marker for both lead exposure and toxic effects. We examined claims that delta-aminolevulinic acid dehydratase genotype (ALAD) can modify lead toxicity. In 290 lead-exposed and 91 unexposed Chinese workers, we determined P-Pb, B-Pb, urinary lead (U-Pb), AMD polymorphism (rs1800435, ALAD112; TaqMan assay), and also toxic effects on heme synthesis (blood zinc protoporphyrin and hemoglobin, urinary delta-aminolevulic acid), on the kidneys (urinary albumin, beta(2)microglobulin and N-acetyl-beta-D-glucosaminidase) and on the peripheral nervous system (sensory and motor conduction velocities).In exposed workers, median P-Pb was 4.10 (range 0.35-27) mu g/L, B-Pb 401 (110-950) mu g/L, and U-Pb 188 (22-590) mu g/g creatinine. P-Pb had a higher ratio between exposed and unexposed workers (median 39, range 18-110) than B-Pb (19, 15-36; p

Alteration of mitochondrial DNA (mtDNA) copy number, which reflects oxidant-induced cell damage, has been observed in a wide range of human diseases. However, whether it correlates with hypertension has not been elucidated. We aimed to explore the association between mtDNA copy number and the risk of hypertension in Chinese coal miners. A case–control study was performed with 378 hypertension patients and 325 healthy controls in a large coal mining group located in North China. Face-to-face interviews were conducted by trained staffs with necessary medical knowledge. The mtDNA copy number was measured by a quantitative real-time PCR assay using DNA extracted from peripheral blood. No significant differences in mtDNA copy number were observed between hypertension patients and healthy controls. However, in both case and control groups, the mtDNA copy number was statistically significantly lower in the elder population (≥45 years old) compared with the younger subjects (

Our early toxicological studies showed that metallothionein (MT) is a protein that carries cadmium (Cd) to the kidney, explaining why Cd exposures during long time periods may give rise to kidney dysfunction. This dysfunction is usually considered to be the critical effect, i.e. the adverse effect that occurs at the lowest exposure level. MT also provides intracellular protection against cadmium toxicity. In studies of population groups in cadmium contaminated areas in China, we investigated factors that affected the relationship between internal dose of Cd, as indicated by blood Cd (BCd) or urinary Cd (UCd), and the prevalence of kidney dysfunction. We found dose-response relationships between UCd and the prevalence of increased levels of biomarkers of renal tubular dysfunction (urinary beta-2-microglobulin, B2M, or N-acetyl-beta-d-glucosaminidase - NAG) or urinary albumin (UAlb), a biomarker of glomerular kidney dysfunction. Two years after Cd intake from contaminated rice was diminished, renal tubular dysfunction appeared unchanged or aggravated among those with higher UCd; Another 8 years later, i.e. 10 years after Cd intake was decreased, the prevalence of renal tubular dysfunction was still increased but UAlb had returned to normal. Factors that influenced the dose-response relationships were: (1) time after maximum exposure. (2) Concomitant exposure to other nephrotoxic agents such as inorganic arsenic. (3) Cd induced metallothionein mRNA levels in peripheral blood lymphocytes, used as a biomarker of the ability of each person, to synthesize MT. (4) The occurrence of increased levels in blood plasma of autoantibodies against MT. The two last points further support a role in humans of MT as a protective protein against tissue damage from cadmium and gives support to previous ideas developed partly in experimental systems.

Background and objective: Long-term exposure to cadmium (Cd) causes renal dysfunction, but the change in renal function with exposure is unknown. We assessed the evolution of Cd-induced renal effects after a reduction in dietary exposure to Cd in rice. Methods: Four hundred twelve residents in previously Cd-polluted and nonpolluted areas were examined twice, in 1998 and in 2006. Changes in blood Cd, urinary Cd, and kidney function [N-acetyl-β-d-glucosaminidase (NAG), β2-microglobulin, and albumin in urine] were measured. Results: In the most polluted area, mean blood Cd was 8.9 μg/L and 3.3 μg/L in 1998 and in 2006, respectively, and urinary Cd was 11.6 and 9.0 μg/g creatinine. Urinary albumin in 1998 increased with urinary Cd, but no such exposure–response relation appeared for 2006 albumin versus urinary Cd 1998, indicating recovery. Other biomarkers of kidney function were also elevated in 1998. Partial recovery was observed for NAG among women and was suggested for β2-microglobulin among young individuals. The probability of having β2-microglobulin levels above the 95th percentile in 2006 was high in those with elevated β2-microglobulin in 1998 [odds ratio (OR) = 24.8; 95% confidence interval (CI): 11.2, 55.3] compared with albumin (OR = 3.0; 95% CI: 1.2, 7.5) and NAG (OR = 2.6; 95% CI: 1.6, 4.4). Conclusions: Results suggest that a Cd-mediated increase in urinary albumin excretion is reversible upon substantial reduction of exposure. For markers of tubular effects, we observed a tendency toward improvement but not complete recovery. Data from repeated observations suggest that β2-microglobulin may be more informative than NAG as an indicator for an individual’s future tubular function.

There is a wide variation in sensitivity to lead (Pb) exposure, which may be due to genetic susceptibility towards Pb. We investigated whether a polymorphism (rs1800435) in the δ-aminolevulinic acid dehydratase (ALAD) gene affected the toxicokinetics and toxicodynamics of Pb. Among 461 Chinese Pb-exposed storage battery and 175 unexposed workers, allele frequencies for the ALAD1 and ALAD2 alleles were 0.968 and 0.032, respectively. The Pb-exposed workers had a higher fraction of the ALAD1-2/2-2 genotype than unexposed workers (7.8% vs. 2.3%, p=0.01). The Pb levels in blood (B-Pb) and urine (U-Pb) were higher in Pb-exposed workers carrying the ALAD2 allele compared to homozygotes for ALAD1 (median B-Pb: 606 vs. 499 μg/L; U-Pb: 233 vs. 164 μg/g creatinine), while there was no statistically significant difference in the unexposed controls (median: 24 vs. 37 μg/L, and 3.9 vs. 6.4μg/g creatinine, respectively). High B-Pb and U-Pb were associated with statistically significantly lower sensory and motor conduction velocities in the median, ulnar and peroneal nerves. At the same B-Pb and U-Pb, ALAD1 homozygotes had lower conduction velocities than the ALAD2 carriers. There were similar trends for toxic effects on haem synthesis (zinc protoporphyrin and haemoglobin in blood) and renal function (albumin and N-acetyl-d-β-acetylglucosaminidase in urine), but without statistical significance. There was no difference in Pb toxicokinetics and toxicodynamics associated with VDR BsmI polymorphism. Our results show that the ALAD genotype modifies the relationship between Pb and its toxic effects on the peripheral nervous system. This must be considered in the assessment of risks at Pb exposure.

The main focus of this study was to evaluate the long-term effects of Cd on forearm bone mineral density after the cessation of the ingestion of Cd-polluted rice. A total of 458 persons (294 women, 164 men) from three Cd exposure areas (low, moderately, and heavy) participated in this study. Those living in the moderate and heavy exposure areas ceased ingesting Cd-polluted rice (0.51 and 3.7mg/kg, respectively) in 1996 (10 years prior to present analysis). The participants completed a questionnaire and bone mineral density (BMD) was measured by dual energy X-ray absorptiometry (DXA) at the proximal radius and ulna. The changes and change percentage in forearm bone density and the prevalence of osteoporosis between 1998 and 2006 were used as markers of bone recovery. The Cd concentrations in urine (UCd) and blood (BCd) in 1998 were used as Cd exposure markers. The values of the BMD change and change percentage of groups in which UCd was above 5microg/g creatinine (microg/g crea) and BCd was above 10microg/L were significantly higher than those of the low-exposure groups (in women, p0.001; in men, p0.05). The BMD change and change percentage correlated positively with the UCd and BCd (in women, p0.01; in men, p0.05). Analysis of the Z-score revealed that the prevalence of osteoporosis in 2006 was higher than that in 1998 and increased along with the level of UCd and BCd in both women and men, especially for those subjects with the higher BCd [BCd5microg/L, OR=3.45 (0.95-13.6); BCd10microg/L, OR=4.51(1.57-13.54)] and UCd [UCd10microg/g crea, OR=4.74 (1.82-12.81)] in women. It is concluded that decreasing dietary cadmium exposure at the population level is not associated with bone recovery at the individual level, and the adverse bone effects of Cd exposure persisted after the main source of Cd exposure had been blocked, especially in women.

Cadmium is a well-known nephrotoxic agent with extremely long biological half-time of 10-30 years in human. To investigate the evolution of cadmium-induced renal effects in the population, a number of 148 residents who lived in cadmium-polluted area were followed-up for 3 years after the reduction of cadmium exposure in rice. Urinary cadmium (UCd), beta(2)-microglobulin (B2M) and albumin (ALB) were analyzed in 1995 and 1998, respectively. The results demonstrated that the changes of renal effects of residents depended on the levels of UCd before inflow of cadmium to human body declined. In cases where UCd were less than 10 microg/g creatinine in 1995, evidence was found indicating significant decreases in proteinuria (i.e., B2M and ALB) 3 years later, whereas, in cases where the excretion of UCd exceeded 10 microg/g creatinine in 1995, progression was observed. The study of dose-response relationships between UCd and B2M or ALB also showed that the cadmium-induced renal dysfunction might be reversible if UCd concentration was low-level before exposure decreasing, otherwise it might be irreversible or aggravated.

Background Recent studies indicate that lead may exert actions both directly on osteoblast and osteoclast function, and indirectly via kidney dysfunction on bone turnover. The main focus of this study was to investigate whether occupational lead exposure is associated with low bone mass in a population working in a storage battery plant. Methods Monophoton absorptiometry was used to measure bone mineral density (BMD) in the population and the Z score was introduced to define osteoporosis (Z score

The present study aimed to investigate the neuroprotective effect of lycopene in a mouse model of bilateral common carotid artery occlusion (BCCAO) and the role of the Nrf2/HO‑1 signaling pathway. A total of 60 male C57BL/6 mice, aged 12 weeks and weighing 20‑24 g, were used in the present study. The mice were randomly assigned to three groups: Control, BCCAO and BCCAO + lycopene. The neurological score was assessed 24, 48 or 72 h following BCCAO. Hematoxylin and eosin staining, and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) were performed to detect neuronal death and survival. The production of glutathione (GSH) and reactive oxygen species were detected to investigate the oxidative stress. The expression levels of nuclear factor erythroid 2‑related factor (Nrf2) and Heme oxygenase‑1 (HO‑1) were determined by western blotting. Lycopene significantly improved the neurological score in the BCCAO mice. It attenuated neuronal apoptosis, as indicated by TUNEL staining, and attenuated the oxidative stress induced by global ischemia. Lycopene increased the expression levels of Nrf2 and HO‑1, indicating that the Nrf2/HO‑1 signaling pathway may be involved in the neuroprotective effect of lycopene. The present study revealed that lycopene protects the brain from global ischemic injury, which is associated with its antiapoptotic effect and the activation of the Nrf2/HO‑1 signaling pathway.

OBJECTIVE—It has been reported that diabetes may increase the risk of cadmium-induced kidney damage. The presence of metallothionein antibody (MT-Ab) increased the susceptibility for tubular damage among cadmium workers. This study focused on the relationships between levels of MT-Ab, urinary cadmium, and kidney function in a Chinese type 2 diabetic population. RESEARCH DESIGN AND METHODS—A cross-sectional study was performed on 229 type 2 diabetic patients (92 men and 137 women) who were recruited from two community centers in one district of Shanghai City in China. Information was obtained from interviews, health records, and blood and urine samples. RESULTS—Levels of the tubular biomarker β2-microglobulin increased significantly when the levels of MT-Ab and urinary cadmium were elevated in male and female subjects; in contrast, the levels of urinary albumin, a glomerular biomarker, did not display such a pattern. After adjusting for potential confounding covariates, logistic regression showed that the odds ratios (ORs) of tubular dysfunction increased upon 1) increasing the MT-Ab concentration from a low to high level (OR 5.56 [95% CI 2.25–13.73]) and 2) increasing the level of urinary cadmium from CONCLUSIONS—This study proves that the presence of MT-Ab can potentiate tubular dysfunction among diabetic subjects and that patients with high MT-Ab levels are more prone to development of tubular damage.

Background: Beta-site Amyloid precursor protein Cleaving Enzyme 1 (BACE1) is conceived as a potential target for therapies against Alzheimer disease (AD) which is characterized by the accumulation of plaques formed of short β-amyloid (APPβ) peptides. Recently, such microRNAs, as miR-29a, miR-29b-1 have been shown to correlate with abnormally high levels of BACE1 and APPβ in sporadic AD. Methods: In order to confirm whether miR-29c correlates with the BACE1 upregulation in sporadic AD, we firstly evaluated the expression of miR-29c and BACE1, the APPβ accumulation in sporadic AD brain tissues and analyzed the correlation of miR-29c with BACE1. Then we determined the regulation of miR-29c in human heuroblastoma SH-SY5Y cells on the BACE1 expression and APPβ accumulation. And finally we determined the targeting to 3’ UTR of BACE1 by miR-29c by a luciferase reporter. Results: It was demonstrated that miR-29c was downregulated in sporadic AD brains, in an association with an upregulation of BACE1 in both mRNA and protein level of BACE1, and also an elevated APPβ accumulation. And the manipulated high level of miR-29c with miR-29c mimics transfection significantly reduced the protein level of BACE1 and APPβ accumulation in human neuroblastoma SH-SY5Y cells. Further luciferase reporter assay demonstrated that miR-29c targets the 3’ UTR of BACE1 and downregulated the BACE1 in HEK293 cells. Conclusion: Present study indicated that miR-29c was downregulated in sporadic AD brains, and it targeted the 3’ UTR of BACE1, reduced the BACE1 expression, and downregulated the APPβ accumulation in vitro.

Exposure to cadmium (Cd) can affect both DNA methylation and renal function, but there are few examples of the association between epigenetic markers and Cd-induced kidney damage. It has been suggested that hypermethylation of the genes RASAL1 and KLOTHO is associated with renal fibrogenesis. To investigate whether hypermethylation of RASAL1 and KLOTHO in peripheral blood DNA can be associated with Cd exposure and/or Cd-induced renal dysfunction, the degrees of methylation of RASAL1 and KLOTHO in peripheral blood DNA from 81 residents in Cd-polluted and non-polluted areas were measured using bisulfate-PCR-pyrosequencing. Changes in blood cadmium (BCd), urinary cadmium (UCd), and kidney parameters were measured, and the glomerular filtration rate (eGFR) was estimated. The levels of BCd and UCd correlated positively with the levels of DNA methylation in RASAL1 and in KLOTHO. The more heavily exposed residents (BCd, 4.23–13.22 μg/L; UCd, 8.65–32.90 μg/g creatinine) exhibited obvious renal dysfunction. Notably, when Cd concentration in blood and urine was adjusted, the increased methylation level in RASAL1 was inversely correlated with eGFR (P

Cadmium (Cd) effect on bone varies between individuals. We investigated whether genetic variation in metallothionein (MT)1A and MT2A associated with Cd induced bone loss in this study. A total of 465 persons (311 women and 154 men), living in control, moderately and heavily polluted areas, participated. The participants completed a questionnaire and the bone mineral density (BMD) was measured by dual energy x-ray absorptiometry (DXA) at the proximal radius and ulna. Samples of urine and blood were collected for determination of Cd in urine (UCd) and blood (BCd). Genotypes for polymorphisms in MT1A (rs11076161) and MT2A (rs10636) were determined by Taqman allelic discrimination assays. BCd had a weak association with variant alleles for MT1A (rs11076161) and MT2A (rs10636) in female living in the highly polluted group ( p = 0.08 and 0.05, respectively). A weak association was found between bone mineral density and MT2A polymorphisms variation ( p = 0.06) in female living in the highly polluted group. Only a weak association was found between bone mineral density and MT1A polymorphisms variation in female. Genetic variation in the MT1A and MT2A genes may not associate with bone loss caused by cadmium exposure.

Relationship between bone mineral density (BMD) and previous renal dysfunction caused by cadmium exposure was investigated. A total of 457 persons, living in polluted and control areas, were followed up in this study. The inhabitants living in exposure areas ceased ingesting cadmium-contaminated rice in 1996. Blood and urinary cadmium levels and BMD in 1998 and 2006 were measured. Urinary N-acetyl-β-d-glucosaminidase and albumin determined in 1998 and 2006 were used to evaluate kidney status. BMD of subjects with tubular damage was significant lower than those without damage in female (p < 0.05). The prevalence of osteoporosis was significantly different between those with and without kidney damage (p = 0.003, in total population; p = 0.039, in female) and those with and without tubular damage (p = 0.0005, in total population; p = 0.007, in female). The results suggested that BMD was correlated with previous kidney impairment caused by cadmium exposure, especially to tubular damage and especially for female.

We investigated the role of metallothionein (MT) in tissues after cessation of cadmium (Cd) exposure. Wistar rats of both genders were given CdCl(2) in drinking water at daily doses of 0, 2.5, 5.0 or 10.0 mg Cd/kg body-weight for 12 weeks. Half of the animals were then killed; the others were given Cd-free water for the following 16 weeks, i.e. until 28 weeks after start of the experiment (28-week rats). We observed dose-dependent increases in the levels of MT in the tissues of rats 12 weeks after beginning the experiment (12-week rats). After the exposure ceased, levels of MT in the 28-week rats changed in three ways: an increase in the liver, persistence in the kidney cortex and a decrease in the medulla, relative to those levels in their 12-week counterparts. Biomarkers of kidney dysfunction were determined to be urinary MT (UMT) and urinary N-acetyl-beta-D-glucosaminidase (UNAG). After 12 weeks, we observed dose-related statistically significant increases in UMT and UNAG in all of the Cd-exposed groups. A statistically significant decrease for UNAG between the 12- and 28-week rats occurred among males at the lowest Cd dose and for UMT in all of the Cd-exposed groups. The unchanged tissue levels of MT in the kidney cortex suggest that decreased UMT is a sign either of (i) decreased transport of Cd-MT from the liver via blood plasma to the renal tubules or (ii) increased tubular reabsorption and recovery of renal tubular function.

Long term cadmium (Cd) exposure in occupational and general environments may give rise to kidney dysfunction. This effect is usually considered to be the critical effect, i. e. the effect that occurs at relatively low level of exposure. The present review focused on studies of the prevalence of cadmium-related kidney dysfunction among population groups residing in cadmium contaminated areas in China. Dose-response relationships were shown between UCd and the prevalence of increased levels of biomarkers in urine of renal tubular dysfunction such as urinary beta-2-microglobulin or N-acetyl-beta-d-glucosaminidase - NAG or urinary albumin, a biomarker of glomerular kidney dysfunction. Factors that influence these dose-response relationships include: 1) Metallothionein mRNA levels in peripheral blood lymphocytes, used as a biomarker of the ability of each person, to synthesize metallothionein (a protein known to provide intracellular protection against cadmium toxicity). 2) The occurrence of increased levels in blood plasma of autoantibodies against metallothionein. 3) Concomitant changes in glucose metabolism i e Type II diabetes. 4) Concomitant exposure to other nephrotoxic agents such as inorganic arsenic. Increased susceptibility in diabetics has been shown also in population groups in Europe. In persons with type II diabetes and increased levels of autoantibodies against metallothionein in blood plasma or in persons with concomitant exposure to environmental inorganic arsenic, indications of Cd-related kidney dysfunction was observed at UCd levels around 1 microg/g creatinine, levels found among "unexposed" population groups in many countries.

Objectives: The aim of this study was to examine a possible relationship between lead nephropathy and its effects on the skeleton in male population occupationally exposed to lead in China. Methods: One hundred and fifty-five lead-exposed male workers in a storage battery plant in Shanghai were selected as the exposed subjects while the 36 healthy male officers in the plant who were not occupationally exposed to lead were treated as the control. Blood lead (BPb) and urine lead were used as biomarkers for exposure. Z score, urine hydroxyproline (HYP), serum alkaline phosphatase (bone isoenzyme) (BALP) and serum osteocalcin (BGP) were used as biomarkers for bone effects. Urine N-acetyl-b-D-glucosaminidase (UNAG) and urine albumin (UALB) were applied as biomarkers of renal tubular and glomerular dysfunction. Bone mineral density was measured by the monophoton absorptiometry (SPA-4). Results: It was found that there were linear correlate relationships between lead exposure and NAG, ALB, BALP, BGP, HYP, Z score (P < 0.01), after controlling confounders such as age and work year. NAG, ALB, BALP, BGP and HYP would increase with the increase of lead exposure. Z score would decrease with the increase of lead exposure. Of 21 subjects with osteoporosis, nine subjects were suffering from renal dysfunction. The prevalence of renal dysfunction (42.86%) was significantly higher in the subjects with osteoporosis than in those without osteoporosis (17.65%) (x 2 5 7.310, P 5 0.007). The prevalence of osteoporosis had relationship with renal tubular damage, but not with renal glomerular damage. This showed that glomerular dysfunction plays a smaller role than tubular dysfunction in the causation of bone damage. Benchmark dose in terms of BPb was calculated using Benchmark Dose Software Version 1.3.2 software. The benchmark dose lower limit of a one-sided 95% confidence interval (BMDL) for 10% excess risk was also determined. It was found that BMDL205 for BALP, UNAG, BGP, HYP, Z score and UALB of BPb increased sequentially. The BMDL values for UNAG (10.13 m gd L 21 ) were lower than those of Z score (14.17 m gd L 21 ). Conclusions: The present study has thus demonstrated the combined adverse effects (osteoporosis and renal dysfunction) caused by occupational exposure to lead. There was a dose‐ response relationship between lead exposure and prevalence of osteoporosis, renal dysfunction and bone metabolism. The renal dysfunction might develop earlier than osteoporosis. Osteoporosis caused by lead was related to the change of bone metabolism and renal dysfunction, which was especially to tubular damage but not to glomerular damage.