Analysis of the Spatial-Temporal Distribution Characteristics of Climate and Its Impact on Winter Wheat Production in Shanxi Province, China, 1964-2018.

The possible influence of global climate changes on agricultural production is becoming increasingly significant, necessitating greater attention to improving agricultural production in response to temperature rises and precipitation variability. As one of the main winter wheat-producing areas in China, the temporal and spatial distribution characteristics of precipitation, accumulated temperature, and actual yield and climatic yield of winter wheat during the growing period in Shanxi Province were analysed in detail. With the utilisation of daily meteorological data collected from 12 meteorological stations in Shanxi Province in 1964-2018, our study analysed the change in winter wheat yield with climate change using GIS combined with wavelet analysis. The results show the following: (1) Accumulated temperature and precipitation are the two most important limiting factors among the main physical factors that impact yield. Based on the analysis of the ArcGIS geographical detector, the correlation between the actual yield of winter wheat and the precipitation during the growth period was the highest, reaching 0.469, and the meteorological yield and accumulated temperature during this period also reached its peak value of 0.376. (2) The regions with more suitable precipitation and accumulated temperature during the growth period of winter wheat in the study area had relatively high actual winter wheat yields. Overall, the average actual yield of the entire region showed a significant increasing trend over time, with an upward trend of 47.827 kg ha-1 yr-1. (3) The variation coefficient of winter wheat climatic yield was relatively stable in 2008-2018. In particular, there were many years of continuous reduction in winter wheat yields prior to 2006. Thereafter, the impact of climate change on winter wheat yields became smaller. This study expands our understanding of the complex interactions between climate variables and crop yield but also provides practical recommendations for enhancing agricultural practices in this region.

Lead intoxication-induced exosomes promote autophagy and apoptosis in renal proximal tubule cells by activating the adenosine 5'-monophosphate-activated protein kinase signaling.

Lead (Pb) intoxication is known to damage the proximal tubules of kidney. Autophagy and apoptosis have been shown to be involved in a variety of renal injuries, but the underlying mechanisms remain largely unknown. In this study, we constructed a mice model of Pb intoxication and validated it against lead concentrations in blood and urine. Electron microscopy revealed that Pb promoted the accumulation of autophagosomes. Subsequent immunofluorescence and western blotting revealed that Pb intoxication suppressed the autophagic flux. Next, exosomes were isolated and extracted through ultracentrifugation, and were further identified by diameter analysis and marker detection. We also demonstrated that autophagy and apoptosis were enhanced in renal cells with exosomes of Pb expose. Furthermore, the specific mechanisms were explored by RNA sequencing and it was found that several targeted genes regulated by differential exosomal miRNAs and lncRNAs. Target genes accumulated in several signaling pathways, especially the adenosine 5'-monophosphate-activated protein kinase (AMPK) signaling. We found that Pb intoxication-induced exosomes activated the AMPK signaling in renal proximal tubule cells. Furthermore, autophagy and apoptosis assays showed that GSK-690693, an AMPK inhibitor, significantly alleviated exosome-induced renal injuries by Pb intoxication. In conclusion, Pb-mediated exosome-induced autophagy and apoptosis via activating the AMPK signaling contributing to Pb-induced nephrotoxicity in renal cells.

Deep learning approach identified a gene signature predictive of the severity of renal damage caused by chronic cadmium accumulation.

Epidemiology studies have indicated that environmental cadmium exposure, even at low levels, will result in chronic cadmium accumulation in the kidney with profound adverse consequences and that the diabetic population is more susceptible. However, the underlying mechanisms are yet not fully understood. In the present study, we applied an animal model to study chronic cadmium exposure-induced renal injury and performed whole transcriptome profiling studies. Repetitive CdCl2 exposure resulted in cadmium accumulation and remarkable renal injuries in the animals. The diabetic ob/ob mice manifested increased severity of renal injury compared with the wild type C57BL/6 J littermate controls. RNA-Seq data showed that cadmium treatment induced dramatic gene expression changes in a dose-dependent manner. Among the differentially expressed genes include the apoptosis hallmark genes which significantly demarcated the treatment effects. Pathway enrichment and network analyses revealed biological oxidation (mainly glucuronidation) as one of the major stress responses induced by cadmium treatment. We next implemented a deep learning algorithm in conjunction with cloud computing and discovered a gene signature that can predict the degree of renal injury induced by cadmium treatment. The present study provided, for the first time, a comprehensive mechanistic understanding of chronic cadmium-induced nephrotoxicity in normal and diabetic populations at the whole genome level.

Analysis of cadmium accumulation in community adults and its correlation with low-grade albuminuria.

OBJECTIVE: To investigate the effects of chronic non-occupational exposure to cadmium (Cd) on renal injury in residents living in the urban areas of China. METHODS: In this cross-sectional study, we recruited 1000 participants in Shanghai from August 2015 to August 2017 and collected data on their socio-demographic characteristics, lifetime occupation, and lifestyle factors. The urinary Cd, urinary albumin, urinary creatinine, serum creatinine, urea, and uric acid levels were tested, and 683 participants completed those measurements. RESULTS: The median urinary Cd concentration of this study population was 0.77 µg/g. The urinary Cd concentration was significantly higher in the female, older, and lower body mass index populations. There were 148 participants with dominant albuminuria who had higher urinary Cd levels than those without dominant albuminuria (0.98 vs. 0.72 µg/g; P < 0.001). Among participants without dominant albuminuria, there were 134 participants with low-grade albuminuria (13.84 ≤ ACR < 30 mg/g) and 401 participants who had normal urinary albumin excretion (ACR < 13.84 mg/g). Compared with those who had normal urinary albumin excretion, those with low-grade albuminuria had significantly higher urinary Cd levels (0.83 vs. 0.69 µg/g; P < 0.001). Among those without dominant albuminuria, participants in the highest quartile of urinary Cd were more likely to have low-grade albuminuria than those in the lowest quartile (Odd's ratio = 2.98; P < 0.001). Further adjustment for age, sex, and BMI or other potential confounding factors did not change the magnitudes of the associations. Moreover, we conducted multivariable stepwise linear regression analysis within 134 low-grade albuminuria participants and demonstrated that urinary Cd concentration (P < 0.001) were independent determinants of urine albumin after adjusting for relevant confounders. CONCLUSION: The urinary Cd levels observed in Chinese urban adults are substantial and associated with an increased risk of low-grade albuminuria. Our findings suggest that potential sources of environmental Cd exposure should be explored, and the associated renal toxicity should be studied in more detail in future.

Heme oxygenase-1 enhances autophagy by modulating the AMPK/mTORC1 signaling pathway as a renoprotective mechanism to mitigate lead-induced nephrotoxicity.

Lead (Pb), a highly poisonous heavy metal and an important occupational hazard, is currently a widespread environmental pollutant. The kidney is especially susceptible to the toxic effects of Pb because of its major role in Pb excretion. Heme oxygenase-1 (HO-1) is an inducible antioxidant enzyme that can mitigate cellular injury. However, its role in Pb-elicited nephrotoxicity remains uncertain. This study was designed to examine the role of HO-1 in lead acetate (PbAc)-induced renal tubular cell injury in vitro. PbAc injury was found to suppress HO-1 expression and impair cell viability, with concomitant depletion of the autophagy proteins LC3-II and Beclin 1. Overexpression of HO-1 dramatically restored autophagy and protected cells against PbAc-induced apoptosis. In addition, pretreatment with 3-methyladenine, an inhibitor of autophagy, aggravated apoptosis and abolished renoprotection by HO-1, suggesting that the anti-apoptotic effect of HO-1 in Pb-induced nephrotoxicity is dependent on enhanced autophagy. Furthermore, HO-1 overexpression abrogated the inhibitory effect of PbAc on the adenosine monophosphate-activated protein kinase (AMPK)/mammalian target of rapamycin (mTORC1) signaling pathway. Pretreatment with an AMPK agonist, 5-aminoimidazole-4-carboxamide-1-ß-D ribofuranoside, markedly enhanced autophagic activity and diminished apoptosis. Conversely, inhibition of AMPK phosphorylation abolished the pro-autophagic and anti-apoptotic effects of HO-1 in PbAc-injured cells. Our findings suggest that HO-1 alleviates Pb-induced nephrotoxicity via enhanced autophagy, which involves activation of the AMPK/mTORC1 signaling pathway.

Urinary KIM-1: a novel biomarker for evaluation of occupational exposure to lead.

Chronic occult lead poisoning often develops ensuing occupational lead exposure. Early diagnosis of lead poisoning is critical for timely discontinuation of lead exposure and for prognosis. This study explored the value of urinary kidney injury molecule-1 (KIM-1) in diagnosing renal injury induced by lead at an early stage. We retrospectively analyzed 92 workers exposed to occupational lead and demonstrated a better correlation ship between blood lead levels and urine excretion of KIM-1 than other traditional renal injury biomarkers following creatinine adjustment. Receiver operating characteristic curve analysis of the ability of diverse biomarkers for predicting kidney injury in lead-exposed workers demonstrated that the order of predicting accuracy of the studied biomarkers is as follows: urinary KIM-1-to-creatinine ratio > urinary N-acetyl-ß-(D)-glucosaminidase-to-creatinine ratio > urinary ß2-microglobulin-to-creatinine ratio > urinary α1-microglobulin-to-creatinine ratio, with the Youden index being 16.59 ng/g, 14.01 U/g, 0.15 mg/g, and 4.63 mg/g, respectively. Collectively, our findings suggest that short-period occupational lead exposure may cause injury of renal tubules. Urinary excretion of KIM-1 correlates with blood lead levels better than other traditional renal injury biomarkers, including N-acetyl-ß-(D)-glucosaminidase, α1-microglobulin, and ß2-microglobulin. Longitudinal surveillance of urinary KIM-1 may aid for early diagnosis of renal tubular injury in workers with occupational lead exposure.

Study on lead-induced activation of rat renal interstitial fibroblasts and the related mechanisms.

CONTEXT: Lead is a common industrial toxicant and has been proved to be associated with the kidney damage. OBJECTIVE: To investigate the effect and mechanism of lead on expression of rat renal interstitial fibroblast activation related protein. MATERIALS AND METHODS: The expression of activation related protein mRNA was measured by real-time PCR in the NRK/49F treated by lead acetate with different concentrations (0, 0.5, 1 and 2 µmol/L). The effects of lead acetate on the level of fibronectin (FN) and signal transduction factors (Smads protein) expression were observed by Western blot. RESULTS: The mRNA expression of activation-related protein increased significantly after the cells were stimulated by lead acetate for 24 h. The lead acetate-treated group could upregulate the p-Smad2, p-Smad3 and FN protein expression compared with the control group. The level of Smad2/3 protein expression did not change in all groups, the expression of SnoN decreased significantly compared with the control group. DISCUSSION AND CONCLUSION: Lead acetate could increase the mRNA expression of activation-related factors. It could promote inflammatory reaction induced by TGF-ß via Smad signaling pathway. Lead acetate has the effect on inducing the renal fibrosis.