Free amino acids, carbon and nitrogen isotopic compositions responses to cadmium stress in two castor (Ricinus communis L.) species.

Cadmium (Cd) toxicity induce various disturbances in metabolic processes and impair plant establishment. The composition of carbon and nitrogen stable isotopes (δ13C and δ15N) and free amino acids (FAAs) can reflect the response of plants to environmental stress. In the present study, a solution culture experiment was carried out, and the secretion characteristics of FAAs as well as δ13C and δ15N were evaluated as indicative of the functional performance of two castor species (Zibo-3 and Zibo-9) under various Cd concentrations stress (0, 1, 2, and 5 mg L-1). The results indicated that: 1) The treatment of the plants with 5 mg L-1 of a Cd solution resulted in a significant decline of biomasses by 22.4% and 11.6% in Zibo-3 and Zibo-9, respectively, relative to controls; additionally, the accumulation levels for Cd in Zibo-9 were higher than those in Zibo-3, thus Zibo-9 showed higher tolerance and enrichment ability to Cd. 2) The exposure of castor to Cd treatments results in significant modifications in individual FAAs, suggesting a differential sensitivity of each biosynthetic pathway to this stress; however, a positive correlation was found between the accumulation of total FAAs and Cd treatment dosages; higher proportion of asparagine and glutamate in total amino acids for Zibo-9, and abundant secretion of arginine in Cd treated Zibo-9 may be associated with the higher Cd-tolerance and Cd-accumulation in Zibo-9. 3) Cd stress increased leaf δ13C and δ15N values regardless of the castor species; δ13C and δ15N could be used as monitoring tools for heavy metal stress in plants.

Characteristics of cadmium translocation and isotope fractionation in Ricinus communis seedlings: Effects from split/cut-root and limited nutrients.

Studying cadmium (Cd) transport in plants will improve the current understanding of Cd tolerance mechanisms. Due to the influence of analytical techniques, the application of Cd isotopes in plants is still in its early stages. Therefore, the relationships between Cd isotope fractionation and Cd translocation in plants remain unclear. In this study, we cultured Ricinus communis in hydroponic solutions during split/cut-root experiments and limited and infinite nutrient experiments. To understand the Cd transport process, the Cd2+ and other ion concentrations in different tissues (i.e., roots, stems, and leaves) and nutrient solutions, Cd isotope composition and the soluble protein in tissues were measured. The results showed that although significant effects were evident in the top leaves, the principal roots had less pronounced effects on Cd2+ translocation in the stems. Moreover, Cd underwent homolateral transport before it was translocated from the principal roots to the leaves on the side without Cd. It was apparent that the stems were responsible for translocating Cd2+ in plants. In addition, the continuous supply of high Cd2+ concentrations inhibited the growth of the top leaves, while in low Cd2+ concentrations, it was gradually transferred to the top leaves. Moreover, the tissues of R. communis were enriched with lighter Cd isotopes compared with the solutions. The clear differences between the Cd isotope fractionation of leaves under infinite and limited nutrient experiments may be attributed to plant growth and Cd uptake rates. This study provides important information for understanding Cd2+ translocation in R. communis and furthers our understanding of its tolerance and hyperaccumulation.

Isotopic reconstruction of iron oxidation-reduction process based on an Archean Ocean analogue.

The chemical composition and redox conditions of the Precambrian ocean are key factors for reconstructing the temporal evolution of atmospheric oxygen through time. In particular, the isotopic composition of iron are useful proxies for reconstructing paleo-ocean environments. Yet, respective processes and related signatures are poorly constrained, hindering the reconstruction of iron redox mechanisms in the Archean ocean. This study centers on Sihailongwan Lake, a stratified water body with a euxinic lower water column considered as an Archean ocean analogue. Results show that the anaerobic oxidation layer is so different from other similar lakes in which dissolved Fe oxidation is present in redoxcline layer. And the fractionation factor between ferrous Fe and iron hydroxide observed in nature water body of Sihailongwan Lake reaches to 2.6‰, which would benefit the production of the oxidations of BIF in sediment. By the spatial distribution of Fe isotope, the benthic water in autumn and the hypolimnetic anoxic water in spring has been identified as iron sulfide zone, where iron isotopic fractionation factor during iron sulfide formation is 1.16‰, accounting for partial scavenging of dissolved Fe(II) with an associated isotopic fractionation. However, pyrite in the sediment records the iron isotopic signal from the redoxcline but not in the iron sulfide or oxide zones of the water column. Above findings indicate that neither the iron isotope fractionation during partial transfer of ferrous iron to iron sulfide nor the partial oxidation of ferrous iron are recorded as pyrite in sedimentary rock. Importantly, the signal of Fe isotopic fractionation in water was archived in the suspended particulate matter and transferred into the sediment, rather than via ferrous iron directly deposited in the sediment. This study reveals that Fe isotopes from modern natural environments are useful proxies for reconstructing iron oxidation-reduction process during Earth's early history.

An integrated approach to quantify ecological and human health risks of soil heavy metal contamination around coal mining area.

Soil heavy metals harm ecological biodiversity and human health, and quantifying the risks more accurately is still obscure. In this study, a network environ analysis was applied to quantify risks between ecological communities based on control allocation and human health risk models to calculate human health exposure risks from soil heavy metals around Greenside coal mining in South Africa. Ecological and human health risks were apportioned using PMF model. Results showed assessed heavy metals (mean) exceeded local background content with a cumulative of moderately polluted using pollution load index (PLI). Total initial risk (Ri), the risk to biological organisms from direct soil exposure, was 0.656 to vegetation and 1.093 to soil microorganisms. Risk enters the food web via vegetation and harms the whole system. Integrated risks (initial, direct, and indirect) to vegetation, herbivores, soil microorganisms, and carnivores were 0.656, 0.125, 1.750, and 0.081, respectively, revealing that soil microorganisms are the most risk receptors. Total Hazard Index (HIT) was <1 for adults (0.574) whereas >1 for children (4.690), signifying severe non-cancer effects to children. Total cancer risk (TCR) to children and adults surpassed the unacceptable limit (1.00E-04). Comparatively, Cr is a high-risk metal accounted for 63.24% (adults) and 65.88% (children) of the HIT and 92.98% (adults) and 91.31% (children) of the TCR. Four sources were apportioned. Contributions to Ri (soil microorganisms and vegetation) from F3 (industrial), F4 (atmospheric), F2 (coal mining), and F1 (natural) were 42.20%, 24.56%, 23.55%, and 9.68%, respectively. The non-cancer risk from F3 (37.67% to adults and 38.40% to children) was dominant, and TCR to children from the sources except F1 surpassed the unacceptable limit. An integrated approach of risk quantification is helpful in managing risks and reducing high-risk pollution sources to better protect the environment and human health.

A review on analysis methods, source identification, and cancer risk evaluation of atmospheric polycyclic aromatic hydrocarbons.

Polycyclic aromatic hydrocarbons (PAHs) have gained attention because of their environmental persistence and effects on ecosystems, animals, and human health. They are mutagenic, carcinogenic, and teratogenic. The review provides background knowledge about their sources, metabolism, temporal variations, and size distribution in atmospheric particulate matter. The review article briefly discusses the analytical methods suitable for the extraction, characterization, and quantification of nonpolar and polar PAHs, addressing the challenges. Herein, we discussed the molecular diagnostic ratios (DRs), stable carbon isotopic analysis (SCIA), and receptor models, with much emphasis on the positive matrix factorization (PMF) model, for apportioning PAH sources. Among which, DRs and PCA identified as the most widely employed method, but their accuracy for PAH source identification has received global criticism. Therefore, the review recommends compound-specific isotopic analysis (CSIA) and PMF as the best alternative methods to provide detailed qualitative and quantitative source analysis. The compound-specific isotopic signatures are not affected by environmental degradation and are considered promising for apportioning PAH sources. However, isotopic fractions of co-eluted compounds like polar PAHs and aliphatic hydrocarbons make the PAHs isotopic fractions interpretation difficult. The interference of unresolved complex mixtures is a limitation to the application of CSIA for PAH source apportionment. Hence, for CSIA to further support PAH source apportionment, fast and cost-effective purification techniques with no isotopic fractionation effects are highly desirable. The present review explains the concept of stable carbon isotopic analysis (SCIA) relevant to PAH source analysis, identifying the techniques suitable for sample extract purification. We demonstrate how the source apportioned PAHs can be applied in assessing the health risk of PAHs using the incremental lifetime cancer risk (ILCR) model, and in doing so, we identify the key factors that could undermine the accuracy of the ILCR and research gaps that need further investigation.

Cadmium isotope constraints on heavy metal sources in a riverine system impacted by multiple anthropogenic activities.

Heavy metals pollutants are global concern due to their toxicities and persistence in the environment. Cd isotope signatures in soils and sediments change during weathering, and it remains unclear if Cd isotopes can effectively trace Cd sources in a riverine system. In this study, we investigate Cd concentration and its isotope compositions, as well as other heavy metals of sediments and related potential Cd sources in a riverine system. The results showed that the two river sediments evaluated were moderately polluted by Zn, Cr, and Cd, while the source samples (soil, sludge, waste, and raw materials) were seriously polluted by heavy metals derived from anthropogenic activities. According to comprehensive ecological risks, the two sediments have a moderate to low potential risk and more than half of all anthropogenic activities in the study area were at considerable or moderate potential risk. We determined that Cd pollution in river sediments was primarily derived from sewage treatment and outlets based on river flow direction and the isotope geochemical behaviors of the Cd isotope in nature conditions. This study further confirmed that analyzing Cd isotopes could be a powerful tool for tracing the source and destination of environmental Cd for multiple sources with similar Cd concentrations.

Sulfur dioxide derivatives produce antidepressant- and anxiolytic-like effects in mice.

Sulfur dioxide (SO2) can be endogenously generated from sulfur-containing amino acids in animals and humans. Increasing evidence shows that endogenous SO2 may act as a gaseous molecule to participate in many physiological and pathological processes. However, the role of SO2 and its derivatives in the central nervous system remains poorly understood. The present study explored the protective effects of exogenous SO2 derivatives (Na2SO3:NaHSO3, 3:1 M/M) on cellular injury in vitro by using the cell proliferation assay (MTS), cell counting kit 8 assay (CCK-8), and cyto-flow assay in the corticosterone (CORT)-induced PC12 cell injury model. We also examined the antidepressant and anxiolytic effects of SO2 derivatives on the chronic mild stress (CMS)-induced depression mouse model by using the open field test, novelty suppressed feeding test, forced swimming test, tail suspension test, and sucrose preference test. In the MTS and CCK-8 assays, we found that preexposure of SO2 derivatives significantly blocked CORT-induced decrease of cellular survival without causing any negative effects. Results from the cyto-flow assay indicated that treatment with SO2 derivatives could reverse CORT-induced early and late apoptosis of PC12 cells. Systemic treatment with SO2 derivatives produced markedly antidepressant- and anxiolytic-like activities in mice under normal condition and rapidly reversed CMS-induced depressive- and anxiety-like behaviors. In conclusion, these findings indicate that exogenous SO2 derivatives show protective properties against the detrimental effects of stress and exert antidepressant- and anxiolytic-like actions. The present study suggests that exogenous SO2 derivatives are potential therapeutic agents for the treatment of depression, anxiety, and other stress-related diseases.

Effects and mechanism of stem cells from human exfoliated deciduous teeth combined with hyperbaric oxygen therapy in type 2 diabetic rats.

OBJECTIVES: Mesenchymal stem cells (MSCs) are potentially ideal for type 2 diabetes treatment, owing to their multidirectional differentiation ability and immunomodulatory properties. Here we investigated whether the stem cells from human exfoliated deciduous teeth (SHED) in combination with hyperbaric oxygen (HBO) could treat type 2 diabetic rats, and explored the underlying mechanism. METHODS: SD rats were used to generate a type 2 diabetes model, which received stem cell therapy, HBO therapy, or both together. Before and after treatment, body weight, blood glucose, and serum insulin, blood lipid, pro-inflammatory cytokines (tumor necrosis factor-alpha and interleukin-6), and urinary proteins were measured and compared. After 6 weeks, rats were sacrificed and their organs were subjected to hematoxylin and eosin staining and immunofluorescence staining for insulin and glucagon; apoptosis and proliferation were analyzed in islet cells. Structural changes in islets were observed under an electron microscope. Expression levels of Pdx1, Ngn3, and Pax4 mRNAs in the pancreas were assessed by real-time quantitative polymerase chain reaction (RT-qPCR). RESULTS: In comparison with diabetic mice, those treated with the combination or SHE therapy showed decreased blood glucose, insulin resistance, serum lipids, and pro-inflammatory cytokines and increased body weight and serum insulin. The morphology and structure of pancreatic islets improved, as evident from an increase in insulin-positive cells and a decrease in glucagon-positive cells. Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining of islet cells revealed the decreased apoptosis index, while Ki67 and proliferating cell nuclear antigen staining showed increased proliferation index. Pancreatic expression of Pdx1, Ngn3, and Pax4 was upregulated. CONCLUSION: SHED combined with HBO therapy was effective for treating type 2 diabetic rats. The underlying mechanism may involve SHED-mediated increase in the proliferation and trans-differentiation of islet ß-cells and decrease in pro-inflammatory cytokines and apoptosis of islets.

Pioglitazone Metformin Complex Improves Polycystic Ovary Syndrome Comorbid Psychological Distress via Inhibiting NLRP3 Inflammasome Activation: A Prospective Clinical Study.

OBJECTIVE: This study aimed at investigating the therapeutic effect and mechanism of pioglitazone metformin complex preparation (PM) in polycystic ovary syndrome (PCOS) comorbid psychological distress. METHODS: Seventy-five patients with PCOS comorbid psychological distress were randomly allocated into the PM, metformin, and placebo groups. The primary efficacy measure was the change from baseline to week 12 on the Symptom Checklist 90-R (SCL-90-R) scores. NLRP3 inflammasome, IL-1ß, IL-6, TNF-α, and biochemical parameters were determined at baseline and at week 12. The participants were required to meet the criteria for PCOS (Rotterdam, NIH) and psychological distress (any factor scores of SCL - 90 - R > 2). RESULTS: The participants had significantly high scores on the SCL-90-R scales of anxiety and depression. PM significantly decreased anxiety and depression symptom severity (from 2.31 ± 0.75 to 1.65 ± 0.38, p < 0.001, and from 2.08 ± 0.74 to 1.61 ± 0.46, p = 0.010, at week 12, respectively). PM significantly decreased the expression of NRPL3 and caspase-1. Patients in the PM group experienced a significant reduction in IL-1ß (from 98.42 ± 14.38 to 71.76 ± 13.66, p = 0.02), IL-6 (from 87.51 ± 8.74 to 71.98 ± 15.87, p = 0.02), and TNF-α (from 395.33 ± 88.55 to 281.98 ± 85.69, p = 0.04). PM was superior to metformin in reducing total testosterone (2.24 ± 0.74 versus 3.06 ± 0.83, p = 0.024, at week 12). CONCLUSIONS: This study is the first to reveal that PM alleviates psychological distress via inhibiting NLRP3 inflammasome and improves several markers, including total testosterone.

Complex liver retransplantation to treat graft loss due to long-term biliary tract complication after liver transplantation: A case report.

BACKGROUND: Loss of graft function after liver transplantation (LT) inevitably requires liver retransplant. Retransplantation of the liver (ReLT) remains controversial because of inferior outcomes compared with the primary orthotopic LT (OLT). Meanwhile, if accompanied by vascular complications such as arterial and portal vein (PV) stenosis or thrombosis, it will increase difficulties of surgery. We hereby introduce our center's experience in ReLT through a complicated case of ReLT. CASE SUMMARY: We report a patient who suffered from hepatitis B-associated cirrhosis and underwent LT in December 2012. Early postoperative recovery was uneventful. Four months after LT, the patient's bilirubin increased significantly and he was diagnosed with an ischemic-type biliary lesion caused by hepatic artery occlusion. The patient underwent percutaneous transhepatic cholangial drainage and repeatedly replaced intrahepatic biliary drainage tube regularly for 5 years. The patient developed progressive deterioration of liver function and underwent liver re-transplant in January 2019. The operation was performed in a classic OLT manner without venous bypass. Both the hepatic artery and PV were occluded and could not be used for anastomosis. The donor PV was anastomosed with the recipient's left renal vein. The donor hepatic artery was connected to the recipient's abdominal aorta. The bile duct reconstruction was performed in an end-to-end manner. The postoperative process was very uneventful and the patient was discharged 1 mo after retransplantation. CONCLUSION: With the development of surgical techniques, portal thrombosis and arterial occlusion are no longer contraindications for ReLT.

Effects and mechanism of stem cells from human exfoliated deciduous teeth combined with hyperbaric oxygen therapy in type 2 diabetic rats

OBJECTIVES: Mesenchymal stem cells (MSCs) are potentially ideal for type 2 diabetes treatment, owing to their multidirectional differentiation ability and immunomodulatory properties. Here we investigated whether the stem cells from human exfoliated deciduous teeth (SHED) in combination with hyperbaric oxygen (HBO) could treat type 2 diabetic rats, and explored the underlying mechanism. METHODS: SD rats were used to generate a type 2 diabetes model, which received stem cell therapy, HBO therapy, or both together. Before and after treatment, body weight, blood glucose, and serum insulin, blood lipid, pro-inflammatory cytokines (tumor necrosis factor-alpha and interleukin-6), and urinary proteins were measured and compared. After 6 weeks, rats were sacrificed and their organs were subjected to hematoxylin and eosin staining and immunofluorescence staining for insulin and glucagon; apoptosis and proliferation were analyzed in islet cells. Structural changes in islets were observed under an electron microscope. Expression levels of Pdx1, Ngn3, and Pax4 mRNAs in the pancreas were assessed by real-time quantitative polymerase chain reaction (RT-qPCR). RESULTS: In comparison with diabetic mice, those treated with the combination or SHE therapy showed decreased blood glucose, insulin resistance, serum lipids, and pro-inflammatory cytokines and increased body weight and serum insulin. The morphology and structure of pancreatic islets improved, as evident from an increase in insulin-positive cells and a decrease in glucagon-positive cells. Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining of islet cells revealed the decreased apoptosis index, while Ki67 and proliferating cell nuclear antigen staining showed increased proliferation index. Pancreatic expression of Pdx1, Ngn3, and Pax4 was upregulated. CONCLUSION: SHED combined with HBO therapy was effective for treating type 2 diabetic rats. The underlying mechanism may involve SHED-mediated increase in the proliferation and trans-differentiation of islet β-cells and decrease in pro-inflammatory cytokines and apoptosis of islets.

[A twenty-year review of clinical liver transplantation].

OBJECTIVE: To review the development of adult and pediatric liver transplantation in Tianjin First Center Hospital, and to enhance academic exchanges, improve technological innovation, and jointly promote the progress and maturity in the field of liver transplantation. METHODS: The development of liver transplantation in Tianjin First Center Hospital was analyzed. The clinical data of adult and pediatric liver transplantation from September 1998 to September 2018 were collected. The important events and technological innovation achievements of liver transplantation during the 20 years were summarized. RESULTS: The first clinical liver transplantation was attempted in Tianjin First Central Hospital in April 1980. The first long-term survival adult liver transplantation in China was completed in 1994 (11 years survival after the operation). The specialized team of liver transplantation was formally established in September 1998. The 20-year clinical exploration and progress reflected the characteristics of era changes and technological innovation during the rapid development of liver transplantation in China. Our center performed liver re-transplantation in January 1999, reduced-size pediatric liver transplantation in August 2000. In May 2001, we organized the formulation for the preventive and treatment plan for hepatitis B recurrence after liver transplantation. We performed combined liver and kidney transplantation in July 2002, split liver transplantation (SLT) in April 2004, the first domino liver transplantation (DLT) in August 2005. Pediatric living donor liver transplantation (LDLT) was initiated in October 2006, adult LDLT was carried out in August 2007. In September 2007, the first living donor combined liver and kidney transplantation from the same donor in Asia was performed. The first domino+living donor double grafts liver transplantation in the world was performed in January 2009. In March 2011, we performed laparoscopically assisted right hepatic lobe liver transplantation (LDLT) with middle hepatic vein. In May 2014, living donor laparoscopic left lateral lobe procurement was successfully established. In April 2016, simultaneous liver, pancreas and kidney multi-organ transplantation was completed. Domino donor-auxiliary liver transplantation was performed in February 2017. In December 2017, extracorporeal membrane oxygenation (ECMO)-supported liver transplantation in a patient with severe pulmonary hypertension was successfully completed. Liver transplantation combined with partial splenectomy was established in April 2018. Cross-domino liver transplantation (hypersensitive kidney transplantation with auxiliary liver transplantation+pediatric liver transplantation) was performed in May 2018. During the 20 years, the team has performed or assisted other centers in Beijing, Shanghai, Guangzhou and Shenzhen to carry out more than 10 000 cases of liver transplantations. A total of 7 043 cases of various types of liver transplantation were performed in the single center of the hospital (6 005 adult liver transplantations and 1 038 pediatric liver transplantations). Concerning adult liver transplantation, the cumulative 1-year, 3-year and 5-year survival rate from September 1998 to March 2003 were 83.1%, 73.0% and 69.0%, from April 2003 to March 2009 were 85.3%, 76.2% and 72.1% and from April 2009 to September 2018 were 87.5%, 79.2% and 75.1%, respectively. The cumulative 1-year, 3-year and 5-year survival rate for pediatric liver transplantation were 93.5%, 92.2% and 90.2%, respectively. The nucleoside (acid) analogue combined with low dose hepatitis B immunoglobulin (HBIG) was developed to prevent the recurrence of hepatitis B after liver transplantation, this plan has reduced the recurrence rate of hepatitis B and the 5-year re-infection rate of hepatitis B virus (HBV) after liver transplantation significantly. The risk assessment system for tumor recurrence after liver transplantation was established and individual treatment method was established based on this assessment system. Continuous exploration and improvement of liver transplantation for liver cancer, liver re-transplantation, liver transplantation with portal vein thrombosis, SLT, DLT and multi-organ combined transplantation have significantly improved the clinical efficacy of patients and the post-operative survival rate. CONCLUSIONS: The liver transplantation team of Tianjin First Center Hospital has carried out a scientific and technological exploration on the key problems and technical difficulties of clinical liver transplantation. This work strongly has initiated and promoted the rapid development of liver transplantation in China. The restrictive barrier of hepatitis B recurrence after liver transplantation has been overcome. The risk prevention and control system of tumor recurrence after liver transplantation has been established. A series of innovative achievements that can be popularized have been achieved in the field of complex liver transplantation and expansion of donor liver source. The iterative progress and sustainable development of liver transplantation have been realized.

Characteristics of cadmium accumulation and isotope fractionation in higher plants.

Cadmium (Cd) pollution of the soil is an important global environmental issue owing to its great toxicity. The study of metal isotope fractionation is a novel technique that could be used to identify and quantify metal uptake and transport mechanisms in plant. In this study, cadmium tolerant Ricinus communis and hyperaccumulator Solanum nigrum have been cultured in different Cd concentration nutrient solutions. The Cd isotope values, metal elements concentrations in the organs (root, stem and leaf) in the two plant species have been measured during the growth periods (10d, 15d, 20d, 25d, and 30d). The results indicate that the organs of S. nigrum could be enriched with lighter Cd isotopes compared with R. communis. In addition, the Cd isotope fractionation become smaller when the plants were subjected to high Cd toxicity, which indicates that Cd isotope fractionation reflected the extent of Cd toxicity to plants. This study advances our current view of Cd translocation machination in plants.

Identification of the Pathogenic Biomarkers for Hepatocellular Carcinoma Based on RNA-seq Analyses.

The purpose of this study was to explore potential biomarkers in the diagnosis of hepatocellular carcinoma (HCC) based on RNA-seq. The microarray data GSE98269 were downloaded from the GEO database, including the miRNA, mRNA and lncRNA expression profiles of 3 HCC tissues and 3 normal liver tissues from 3 HCC patients. The limma package was used to identify the differentially expressed miRNAs (DEMs) and the differentially expressed lncRNAs in HCC tissues compared with normal liver tissues. Database of DAVID, KEGG PATHWAY and Reactome were used to perform the functional and pathway enrichment. Putative targets for DEMs, and the miRNA-gene pairs were predicted via the miRWalk V2.0 database. The protein-protein pairs of DEGs were screened via String software. The expression features of the differentially expressed lncRNAs were analyzed. The regulated network of DEGs and DEMs were constructed, and related genes and miRNAs were detected in the HCC tissues and normal liver samples with Q-PCR. A total of 678 DEGs, 32 DEMs and 411 differential expressed lncRNAs were identified. The DEGs were enriched in 196 GO terms and 79 pathways. 38 negative regulation miRNA-gene pairs and 1205 protein-protein interactions were screened out, and the regulated network was constructed based on them. KNG1, CDK1, EHHADH, CYP3A4, hsa-miR-199a-5p and hsa-miR-455-3p might be biomarkers in the occurrence of HCC.

Icotinib inhibits the proliferation of hepatocellular carcinoma cells in vitro and in vivo dependently on EGFR activation and PDL1 expression.

PURPOSE: Hepatocellular carcinoma (HCC) accounts for one of the most prevalent tumor types in the world and still lacks an effective treatment regimen. The EGFR tyrosine-kinase inhibitor icotinib is capable of inhibiting proliferation of several kinds of cancer cells, but its anticancer effect in HCC is still not verified. METHODS: In the current study, ten HCC cell lines were selected to test their original EGFR-activation status and PDL1 protein level, and in vitro antiproliferation assays were also conducted to analyze the IC50 and further investigate the correlation between IC50 and protein level of phosphorylated EGFR and PDL1. A in vivo nude mouse xenograft animal model was used as well to analyze its anticancer effect. RESULTS: Icotinib showed significant inhibitory effects only on HCC cell lines that had both higher p-EGFR and PDL1 protein level. This specific HCC cell line was subcutaneously injected to establish the in vivo xenograft tumor model, and icotinib reduced tumor weight remarkably and growth dose dependently. Molecular mechanism study revealed that icotinib inhibited the phosphorylation of EGFR and PDL1 expression in cancer cells and activated apoptosis. Knocking down PDL1 significantly reduced the inhibitory effect of icotinib on HCC, and knocking in PDL1 increased the sensitivity of icotinib in HCC. CONCLUSION: The current research suggests that icotinib has an inhibitory effect on a subgroup of HCC cells that have both higher p-EGFR and PDL1. This hints at the potential clinical usage of icotinib in HCC based on PDL1-biomarker examination.

Hydrogen-Rich Water Ameliorates Autistic-Like Behavioral Abnormalities in Valproic Acid-Treated Adolescent Mice Offspring.

Due to its anti-inflammatory and anti-oxidative effects, recent research has demonstrated that molecular hydrogen can serve as a new medical approach for depression, anxiety and traumatic brain injury. However, its potential effects on neurodevelopmental diseases, such as autism are still elusive. The present study aims to investigate the potential effects of hydrogen-rich water (HRW) administration on valproic acid (VPA)-induced autistic-like behavioral deficits, and the associated underlying mechanism in adolescent mice offspring. Pregnant ICR mice were randomly divided into five groups (n = 6). One group was injected with saline (NAV group) and provided hydrogen-free water. The other four groups were injected with VPA (600 mg/kg, intraperitoneally, i.p.) on pregnant day (PND) 12.5. One group was provided with hydrogen-free water (VEH group) and the other three groups were provided HRW at different segments, postnatal day 1 (PND 1) to PND 21 (PHV group), PND 13 to PND 21 (PVS group) or from PND 13 to postnatal day 42 (PVL group). Behavioral tests, including open field, novelty suppressed feeding (NSF), hot plate, social interaction (SI) and contextual fear memory tests were conducted between postnatal day 35-42. We found that HRW administration significantly reversed the autistic-like behaviors induced by maternal VPA exposure in the adolescent offspring of both male and female adolescent offspring. Furthermore, HRW administration significantly reversed the alternation of serum levels of interleukin 6 (IL-6) and tumor necrosis factor-α (TNF-α), but without any effects on the BDNF levels in maternal VPA-exposed mice offspring. These data suggest the need for additional research on HRW as a potential preventive strategy for autism and related disorders. Lay Summary: Maternal VPA injection induces autistic-like behavioral deficits in adolescent mice offspring. HRW administration ameliorates autistic-like behavioral deficits. HRW administration reverses the alternation of serum levels of IL-6 and TNF-α induced by VPA.

Effects of cadmium stress on growth and amino acid metabolism in two Compositae plants.

Cadmium, a high toxic heavy metal, is one of the most serious contaminants in soil and a potential threat to plant growth and human health. Amino acid metabolism has the central role in heavy metal stress resistance of plants. In this paper, a pot experiment was carried out to study the effects of different concentrations of cadmium (0, 3, 6, 12, 30 mg kg-1) on the growth, Cd accumulation and amino acid metabolism in two Compositae plants (Ageratum conyzoides L. and Crassocephalum crepidioides). The results showed that under cadmium stress, C. crepidioides accumulated more Cd in its shoot and was tolerant to Cd, whereas its low Cd-accumulating relative, A. conyzoides, suffered reduced growth. The Cd content in the aerial part of C. crepidioides exceeded the threshold of Cd-hyperaccumulator. Furthermore, the bioaccumulation factor (BCF) and biological transfer factor (BTF) values for Cd in C. crepidioides were > 1. Thus, C. crepidioides can be regarded as Cd-hyperaccumulator. The comparison between both studied plants indicated that Cd stress resulted in a differential but coordinated response of amino acid levels, which are playing a significant role in plant adaptation to Cd stress. Glu, Gln, Asp, Asn, Gaba, Val and Ala dominated the major amino acids. Higher Cd tolerance and Cd accumulation in C. crepidioides was associated with greater accumulation of free amino acids, especially for Gln and Asn, in C. crepidioides than in A. conyzoides.

Stable isotope fractionation during uptake and translocation of cadmium by tolerant Ricinus communis and hyperaccumulator Solanum nigrum as influenced by EDTA.

The isotopic fractionation could contribute to understanding the Cd accumulation mechanisms in plant species. However, there are few of systematical investigations with regards to the Cd isotope fractionation in hyperaccumulator plants. The Cd tolerant Ricinus communis and hyperaccumulator Solanum nigrum were cultivated in nutrient solutions with varying Cd and EDTA concentrations. Cd isotope ratios were determined in the solution, root, stem and leaf. The two investigated plants were systematically enriched in light isotopes relative to their solutions (Δ114/110Cdplant-solution = -0.64‰ to -0.29‰ for R. communis and -0.84‰ to -0.31‰ for S. nigrum). Cd isotopes were markedly fractionated among the plant tissues. For both plant species, an enrichment in light Cd isotopes from solution to root was noted, followed by a slight depletion in light Cd isotopes from root to shoot. Noticeably, the chelation process has caused lighter Cd isotope enrichment in the root of R. communis and S. nigrum. Further, the good fits between △114/110Cdroot-plant and ln Froot (or between △114/110Cdshoot-plant and ln Fshoot) indicate that Cd isotopic signatures can be used to study Cd transportation during the metabolic process of plants. This study suggests that knowledge of the Cd isotope ratios could also provide new tool for identifying the Cd-avoiding crop cultivars.

Molecular hydrogen increases resilience to stress in mice.

The inability to successfully adapt to stress produces pathological changes that can lead to depression. Molecular hydrogen has anti-oxidative and anti-inflammatory activities and neuroprotective effects. However, the potential role of molecular hydrogen in stress-related disorders is still poorly understood. The present study aims to investigate the effects of hydrogen gas on resilience to stress in mice. The results showed that repeated inhalation of hydrogen-oxygen mixed gas [67%:33% (V/V)] significantly decreased both the acute and chronic stress-induced depressive- and anxiety-like behaviors of mice, assessed by tail suspension test (TST), forced swimming test (FST), novelty suppressed feeding (NSF) test, and open field test (OFT). ELISA analyses showed that inhalation of hydrogen-oxygen mixed gas blocked CMS-induced increase in the serum levels of corticosterone, adrenocorticotropic hormone, interleukin-6, and tumor necrosis factor-α in mice exposed to chronic mild stress. Finally, inhalation of hydrogen gas in adolescence significantly increased the resilience to acute stress in early adulthood, which illustrates the long-lasting effects of hydrogen on stress resilience in mice. This was likely mediated by inhibiting the hypothalamic-pituitary-adrenal axis and inflammatory responses to stress. These results warrant further exploration for developing molecular hydrogen as a novel strategy to prevent the occurrence of stress-related disorders.