The U-shape relationship between insulin resistance-related indexes and chronic kidney disease: a retrospective cohort study from National Health and Nutrition Examination Survey 2007-2016.

BACKGROUND: There is ongoing debate on the correlation between chronic kidney disease (CKD) and insulin resistance (IR)-related indices. Our objective was to explore the prognostic ability of IR-related indexes for the prevalence of CKD, as well as the mortality from all causes and cardiovascular disease (CVD) in CKD patients. METHODS: The data used in this study came from the National Health and Nutrition Examination Survey (NHANES). Binary logistic regression analysis, Cox proportional hazards model, and restricted cubic spline (RCS) were used to analyze the relationship between IR-related indexes, including metabolic score of IR (METS-IR), homeostatic model assessment for IR (HOMA-IR), triglyceride glucose index (TyG), triglyceride glucose-waist-to-height ratio (TyG-WHtR), triglyceride glucose-body mass index (TyG-BMI), with CKD and its all-cause mortality and CVD mortality. Subgroup analysis was performed to test the stability of the results. Finally, the predictive power of IR-related indexes for CKD was tested by the receiver operating characteristic (ROC) curve. RESULTS: Among the recruited 10,660 participants, 15.42% were CKD patients. All IR-related indexes were found to be nonlinearly correlated to the prevalence of CKD in the study. When the TyG index was higher than 9.05, it was positively associated with CKD (OR: 1.77, 95% CI 1.44-2.18). Moreover, increased TyG-WHtR level was correlated with a greater prevalence of CKD when it was higher than 4.3 (OR: 1.31, 95% CI 1.19-1.45). Other IR-related indexes (METS-IR, HOMA-IR, and TyG-BMI) showed fewer notable correlations with CKD. The association of IR-related indexes and the prevalence of CKD remained consistent in most subgroups (P for interactions > 0.05). TyG-WHtR was also the predictor of all-cause mortality in CKD patients (HR: 1.34, 95% CI 1.14-1.58), while other IR-related indexes were not correlated with the all-cause mortality or CVD mortality in CKD patients (P > 0.05). Otherwise, ROC curves showed that TyG-WHtR had more robust diagnostic efficacy than other IR-related indexes (METS-IR, HOMA-IR, TyG, and TyG-BMI) in predicting CKD (area under the curve: 0.630, 95% CI 0.615-0.644). CONCLUSIONS: IR-related biomarkers (METS-IR, HOMA-IR, TyG, and TyG-BMI) were positively correlated with the prevalence of CKD. Moreover, TyG-WHtR enhanced CKD and its all-cause mortality prediction. In patients with elevated levels of IR-related indexes, the early detection and intervention of IR may reduce the occurrence of CKD and the prognosis of CKD patients.

Effects of contralateral nephrectomy timing and ischemic conditions on kidney fibrosis after unilateral kidney ischemia-reperfusion injury.

Acute kidney injury (AKI) is an important cause of chronic kidney disease (CKD), but the underlying mechanisms are unclear. Animal models are tools for studying the AKI-CKD progression. Kidney ischemia-reperfusion injury (IRI) models, especially the unilateral IRI (uIRI) model with delayed contralateral kidney resection, are commonly used to induce fibrotic progression to CKD after AKI. However, in previous studies, we found that details of the operation had a significant impact on the long-term outcomes of the kidney in this uIRI model. In this study, we investigated the effects of resection timing of the contralateral intact kidney, core body temperatures during ischemia, and time length of kidney ischemia on kidney function, histological injury and kidney fibrosis after AKI, using a mouse uIRI model with delayed contralateral nephrectomy. The results showed that all these parameters significantly affected the AKI-CKD transition. The post-AKI fibrosis worsened and the survival rate declined with a longer interval between contralateral nephrectomy and uIRI, higher ischemic body temperature, or longer ischemic duration when the other two variables were fixed. In conclusion, in the uIRI model with delayed contralateral nephrectomy, kidney fibrosis after AKI is influenced by many factors. Strictly controlling the experimental conditions is very important for the stability and consistency of the model.

Exploring the Regional Coordination Relationship between Water Utilization and Urbanization Based on Decoupling Analysis: A Case Study of the Beijing-Tianjin-Hebei Region.

Understanding the potential association between the urbanization process and regional water shortage/pollution is conducive to promoting the intensive utilization of local water resources. In this study, the water footprint model was used to estimate water utilization status in terms of both water quantity (virtual water footprint (VWF)) and water quality (grey water footprint (GWF)) in the Beijing-Tianjin-Hebei region (China) during 2004-2017. Their potential coordination relationship with the local urbanization process represented by the gross domestic product (GDP), population (POP), and built-up area (BA) was examined using the Tapio decoupling model. The results showed that from 2004 to 2017, (1) VWF in Beijing and Tianjin showed non-significant decreasing trends, with reductions of 1.08 × 109 and 1.56 × 109 m3, respectively, while that in Hebei showed a significant increasing trend, with an increase of 5.74 × 109 m3. This indicated a gradually increasing water demand in Hebei and decreasing demand in Beijing and Tianjin. In all three regions, the agricultural sector accounted for a relatively high proportion of VWF compared to other sectors. (2) GWF in Beijing, Tianjin, and Hebei all showed declining trends, with reductions of 2.19 × 1010, 2.32 × 1010, and 1.66 × 1011 m3, respectively, indicating considerable local water quality improvement. The domestic sector contributed as the main component of GWF in Beijing, while agriculture was the main contributor in Hebei. The major contributor in Tianjin transitioned from the domestic (before 2015) to the agricultural sector. (3) We found good coordination between VWF and GDP in all three regions, as their local economic development was no longer overly dependent on water consumption. However, the expansion of urban built-up area or population would bring about accelerated depletion of water resources. (4) GWF in the three provinces showed good coordination with GDP, POP, and BA in most years, implying that the development of urbanization no longer strongly caused the pollution of water resources. In sum, policymakers should focus on improving agricultural irrigation efficiency and residents' awareness of water conservation, so as to gradually achieve sustainable water resource management in the BTH region.

S1P Signaling Pathways in Pathogenesis of Type 2 Diabetes.

The pathogenesis of type 2 diabetes mellitus (T2DM) is very complicated. The currently well-accepted etiology is the "Ominous Octet" theory proposed by Professor Defronzo. Since presently used drugs for T2DM have limitations and harmful side effects, studies regarding alternative treatments are being conducted. Analyzing the pharmacological mechanism of biomolecules in view of pathogenesis is an effective way to assess new drugs. Sphingosine 1 phosphate (S1P), an endogenous lipid substance in the human body, has attracted increasing attention in the T2DM research field. This article reviews recent study updates of S1P, summarizing its effects on T2DM with respect to pathogenesis, promoting ß cell proliferation and inhibiting apoptosis, reducing insulin resistance, protecting the liver and pancreas from lipotoxic damage, improving intestinal incretin effects, lowering basal glucagon levels, etc. With increasing research, S1P may help treat and prevent T2DM in the future.

Overexpression and characterization of two types of nitrile hydratases from Rhodococcus rhodochrous J1.

Nitrile hydratase (NHase) from Rhodococcus rhodochrous J1 is widely used for industrial production of acrylamide and nicotinamide. However, the two types of NHases (L-NHase and H-NHase) from R. rhodochrous J1 were only slightly expressed in E. coli by routine methods, which limits the comprehensive and systematic characterization of the enzyme properties. We successfully expressed the two types of recombinant NHases in E. coli by codon-optimization, engineering of Ribosome Binding Site (RBS) and spacer sequences. The specific activity of the purified L-NHase and H-NHase were 400 U/mg and 234 U/mg, respectively. The molecular mass of L-NHase and H-NHase was identified to be 94 kDa and 504 kDa, respectively, indicating that the quaternary structure of the two types of NHases was the same as those in R. rhodochrous J1. H-NHase exhibited higher substrate and product tolerance than L-NHase. Moreover, higher activity and shorter culture time were achieved in recombinant E. coli, and the whole cell catalyst of recombinant E. coli harboring H-NHase has equivalent efficiency in tolerance to the high-concentration product relative to that in R. rhodochrous J1. These results indicate that biotransformation of nitrile by R. rhodochrous J1 represents a potential alternative to NHase-producing E. coli.

[Study on the status of infection and distribution of rabies virus in China].

OBJECTIVE: To investigate the status of infection and distribution of rabies virus (RV) in different epidemic areas in China. METHODS: Brain specimens from animals and suspected patients were collected at the districts of high-, medium- and low incidence rates of human rabies and detected by both direct Immunofluorescence assay (DFA) and RT-PCR. RESULTS: 254 of 3007 specimens of dog brains showed RV positive by DFA (positive rate of 8.4%). Among these 254 samples, 78 showed positive (positive rate of 30.7%) by RT-PCR. 93 specimens from dogs and cats that had attacked human beings, 63 of them showed positive by DFA (positive rate of 67.7%) and all of them were also positive by RT-PCR. In addition, RV could also be detected in Apodemus agrarius, ferret badger, and suspected patients specimens from the districts under survey. There was no statistical difference between the infection rates of RV in different provinces and regions with different incidence of rabies. CONCLUSION: There might be a relatively high infection rate of RV among the domestic dogs/cats in the endemic areas in China. Wild animals might have been infected with RV in the districts under survey.

[Molecular epidemiology investigation of rabies virus nucleoprotein genes in China].

OBJECTIVE: To study the relationship between the distribution of rabies virus and genetic variation, the genetic characterization and variation of rabies virus strains in China were analyzed. METHODS: The downstream 720 nucleotides of Nucleoprotein (N) gene coding region of the rabies specimens from different areas and host animals were sequenced, and then homology and phylogenesis were analyzed. RESULTS: Nucleotide similarities of 34 N gene sequences were 87.5%-100%, and the deduced amino acid similarities were 93.3%-99.6%. Most of the nucleotide variations were synonymous mutations. CONCLUSION: The 34 rabies specimens all belong to genotype I and are of regional characteristic. The rabies viruses in high-incidence areas in China are of various origins and present the transmission tendency from high-incidence areas to surrounding regions. There may be cross-infection and mutual spread of rabies virus between wildlife and domestic animals as well as native and foreign animals.

[Study on the feasibility of a cell-culture inoculation test in the detection and isolation of street rabies virus].

OBJECTIVE: Feasibility of using MNA cell-culture inoculation test to detect and isolate the street rabies virus. METHODS: Using MNA cell-culture inoculation test, fluorescent antibody test (FAT) and sandwich ELISA with double-antibodies to detect 33 specimens of street rabies virus, 20 specimens of negative canine brains and 4 specimens of healthy mice brains. RESULTS: 33 specimens of street rabies virus were positive to the cell-culture inoculation test but the others were negative. The concordances of MNA cell-cultured inoculation test with FAT and sandwich ELISA with double-antibodies were both 100%. CONCLUSION: MNA cell-culture inoculation test appeared to be both highly sensitive and specific in detecting the street rabies virus, and could be used in detection and isolation of the virus.