Geochemical Characteristics and Origin of Sinian-Cambrian Natural Gas in Penglai Gas Area, Sichuan Basin.

The Sichuan Basin in southern China is well-known for its large natural gas resource potential stored in Sinian-Cambrian systems. Recently, high-yield industrial gas flow has been discovered from the Dengying Formation (Sinian System) and Canglangpu Formation (Cambrian System) in the Penglai gas area, preluding the multilayer stereoscopic exploration in Sichuan Basin. However, the origin of the natural gas and its preserving mechanics is still debated, and thus, in this study the geochemical characteristics of the natural gas are systematically analyzed, based on the data from gas composition and hydrocarbon isotope of a series of local wells. On this basis, the geochemical characteristics of natural gas in different regions and layers are compared, and the reasons for these differences from the origin and influencing factors are analyzed. The results show the following: (1) The natural gas of the Penglai gas field is dry gas dominated by CH4, and the Sinian Dengying Formation gas has lower C2H6 content, larger dryness coefficient, heavier δ13C, and lighter δ2HCH4 than the Cambrian gas, which is associated with the high proportion of hydrocarbons from the high-maturity Dengying source rocks. (2) The natural gas from some wells in the lower part of the structure is characterized by high H2S content and low CH4 content, and heavy δ13C in the components, which seems to be affected by the thermochemical sulfate reduction (TSR) effect. (3) The natural gas from the Penglai gas area has a relatively low maturity, which appears to be attributed to the continuous sealing ability of the caprock, which can preserve both the early generated gas and the late thermal-cracked gas.

Human Pluripotent Stem Cells Derived Endothelial Cells Repair Choroidal Ischemia.

Choroidal atrophy is a common fundus pathological change closely related to the development of age-related macular degeneration (AMD), retinitis pigmentosa, and pathological myopia. Studies suggest that choroidal endothelial cells (CECs) that form the choriocapillaris vessels are the first cells lost in choroidal atrophy. It is found that endothelial cells derived from human pluripotent stem cells (hPSC-ECs) through the MESP1+ mesodermal progenitor stage express CECs-specific markers and can integrate into choriocapillaris. Single-cell RNA-seq (scRNA-seq) studies show that hPSC-ECs upregulate angiogenesis and immune-modulatory and neural protective genes after interacting with ex vivo ischemic choroid. In a rat model of choroidal ischemia (CI), transplantation of hPSC-ECs into the suprachoroidal space increases choroid thickness and vasculature density. Close-up examination shows that engrafted hPSC-ECs integrate with all layers of rat choroidal vessels and last 90 days. Remarkably, EC transplantation improves the visual function of CI rats. The work demonstrates that hPSC-ECs can be used to repair choroidal ischemia in the animal model, which may lead to a new therapy to alleviate choroidal atrophy implicated in dry AMD, pathological myopia, and other ocular diseases.

Exposure to copper induces endoplasmic reticulum (ER) stress-mediated apoptosis in chicken (Gallus gallus) myocardium.

Copper (Cu), an omnipresent environmental pollutant, can cause potential harm to the public and ecosystems. In order to study the cardiotoxicity caused by Cu, molecular biology techniques were used to analyze the effect of Cu on ER stress-mediated cardiac apoptosis. In vivo investigation, 240 1-day-old chickens were fed with Cu (11, 110, 220, and 330 mg/kg) diet for 7 weeks. The consequence showed that high-Cu can induce ER stress and apoptosis in heart tissue. The vitro experiments, the Cu treatment for 24 h could provoke ultrastructural damage and upregulate the apoptosis rate. Meanwhile, GRP78, GRP94, eIF2α, ATF6, XBP1, CHOP, Bax, Bak1, Bcl2, Caspase-12 and Caspase-3 genes levels, and GRP78, GRP94 and Caspase-3 proteins levels were increased, which indicated that ER stress and apoptosis in cardiomyocytes. But the mRNA level of Bcl2 were decreased after Cu exposure. Conversely, Cu-induced ER stress-mediated apoptosis can be alleviated by treatment with 4-PBA. These findings generally showed that Cu exposure can contribute to ER stress-mediated apoptosis in chicken myocardium, which clarifies the important mechanism link between ER stress and apoptosis, and provides a new perspective for Cu toxicology.

N-acetyl-L-cysteine alleviates FUNDC1-mediated mitophagy by regulating mitochondrial dynamics in type 1 diabetic nephropathy canine.

Diabetic nephropathy (DN) is a major complication of type 1 diabetes mellitus, and hyperglycemia and hypertension are the main risk factors for the development of DN. N-Acetyl-Cysteine (NAC) has a variety of effects, interfering with the production and scavenging of free radicals and regulating the metabolic activity of tissue cells. However, the efficacy of NAC on DN treatment is unclear. Thus, this study investigated the protective mechanism of NAC combined with insulin on renal injury in dogs with DN. The forty dogs were selected and divided into control group, DM group, INS group, INS + NAC group and NAC group to establish the model for a trial period of 4 months. The results revealed that INS + NAC was effective in reducing and stabilizing blood glucose levels. Biochemical results showed that INS + NAC treatment significantly regulated the stability of UREA, CREA and fructosamine indicators. Meanwhile, histopathology staining showed significant glomerular wrinkling and fibrosis in the DM group, which could be reversed after INS + NAC treatment. In addition, INS + NAC could restore mitochondria homeostasis by upregulating the levels of mitochondrial fission (MFN1, MFN2 and OPA1) and inhibiting of mitochondrial fusion (DRP1, FIS1 and MFF) related indicators. Further studies revealed that INS + NAC regulated the expression levels of renal BNIP3, NIX and FUNDC1 in the DM group, thereby alleviating mitophagy. Collectively, these results suggested that NAC combined with insulin protects DN by regulating the mitochondrial dynamics and FUNDC1-mediated mitophagy.

MitomiR-504 alleviates the copper-induced mitochondria-mediated apoptosis by suppressing Bak1 expression in porcine jejunal epithelial cells.

Copper (Cu), an environmental heavy metal pollutant, has been widely researched in its toxicology. Recently, an increasing number of mitochondrial microRNAs (mitomiRs) have been shown to involve in the metabolic regulation. However, the underlying mechanisms of mitomiRs on regulating apoptosis under Cu exposure are still unclear. Here, we proved that Cu induced mitochondria-mediated apoptosis in porcine jejunal epithelial cells, concomitant with distinct reduction of mitomiR-504 in vivo and in vitro. The miR-504 mimic notably enhanced the mRNA and protein expressions of Bak1, Bax, Cleaved-caspase3 and Caspase-9, and significantly decreased the apoptosis rate and Bcl-2 mRNA and protein levels, indicating that overexpression of mitomiR-504 attenuated the Cu-induced mitochondria-mediated apoptosis. Besides, Bak1 was confirmed as a direct target of mitomiR-504 by the bioinformatics analysis and dual-luciferase reporter assay. Subsequently, transfection of siRNA targeting Bak1 significantly enhanced the alleviating effect of miR-504 mimic on the Cu-induced mitochondria-mediated apoptosis. Overall, these suggested that overexpression of mitomiR-504 alleviated the Cu-induced mitochondria-mediated apoptosis in jejunal epithelial cells by suppressing Bak1 expression. These findings are conducive to elucidating the mechanism of Cu-induced jejunal epithelial pathologies, providing a new research idea for the Cu toxicology.

N-acetylcysteine combined with insulin alleviates the oxidative damage of cerebrum via regulating redox homeostasis in type 1 diabetic mellitus canine.

Neurodegenerative diseases are one of the major complications of type 1 diabetes mellitus (T1DM). The effect of insulin monotherapy on controlling blood glucose and neurodegeneration associated with diabetes is unsatisfactory. It is revealed that oxidative stress is a key element in T1DM. Therefore, N-acetylcysteine (NAC) was used together with insulin to investigate the therapeutic effect on neuronal damage in T1DM in this study. A total of 40 beagles were randomly divided into 5 groups (control group, DM group, insulin monotherapy group, NAC combined with insulin group, and NAC monotherapy group) to explore the effects of NAC on alleviating the oxidative damage in cerebrum. Our results showed that the contents of H2O2, 8-OHdg and MDA were apparently increased in DM group, while DNA and lipid oxidative damage was alleviated by the treatment of NAC and insulin. Histopathology revealed the sparse of neurofibrils and vacuolar degeneration in DM group. Additionally, compared with the control group, the mRNA expression levels of HO-1, nqo1, GCLC and GSTM1 were significantly decreased in DM group, while the opposite trend could be shown under NAC combined with insulin treatment. Meanwhile, the tight junction proteins of ZO-1, occludin and Claudin-1 were up-regulated with the treatment of NAC combined with insulin. Additionally, NAC further alleviated oxidative damage by enhancing the activity of GSH, Trx and TrxR and reducing the activity of catalase, GSSG and Grx to maintain redox homeostasis. These results demonstrated that NAC combined with insulin exerted protective effects against T1DM-induced cerebral injury via maintaining cerebral redox homeostasis.

Lycopene Ameliorate Atrazine-Induced Oxidative Damage in the B Cell Zone via Targeting the miR-27a-3p/Foxo1 Axis.

Lycopene, a natural bioactive component, has potential to reduce the risk of environmental factors inducing chronic diseases. It is important to explore lycopene's health benefits and its mechanism. The uncontrolled use of atrazine in agriculture causes critical environmental pollution issues worldwide. Exposure to atrazine through water and food chains is a risk to humans. In this study, mice were orally treated with lycopene and/or different concentrations of atrazine for 21 days to explore the influence of atrazine on the spleen and the role of lycopene's protection in atrazine exposure. The work found that atrazine exerted its toxic role in the B cell zone of the spleen by inducing Foxo1 deficiency. Atrazine caused ROS generation and Pink1/Parkin dysfunction via inducing Foxo1 deficiency, which led to apoptosis in the B cell zone. Additionally, the work revealed that lycopene ameliorates atrazine-induced apoptosis in the B cell zone of the spleen via regulating the miR-27a-3p/Foxo1 pathway. The finding also underscored a novel target of lycopene in maintaining homeostasis during B cell maturation.

N-acetyl-L-cysteine ameliorates hepatocyte pyroptosis of dog type 1 diabetes mellitus via suppression of NLRP3/NF-κB pathway.

Type 1 diabetes mellitus (T1DM) is a chronic and represented by insulin-causing pancreatic ß-cell disruption and hyperglycemia. N-Acetyl-Cysteine (NAC) is regarded as facilitating endothelial cell function and angiogenesis and may have treatment effect in the case of diabetes. However, the impact of NAC on T1DM are unknown. Here we reported that inflammatory pathogenesis of canine type 1 diabetes liver disease and the therapeutic effect of NAC combined with insulin. For this purpose, the model was established by intravenous injection of streptozotocin (20 mg/kg). Forty adult dogs were used and divided into 5 groups: control group, DM group, insulin treatment group, NAC combined with insulin therapy, and NAC group, while study lasted for 16 weeks. Results showed that the level of liver function enzyme activity were apparently increased in DM group, while the NAC with insulin treatment remarkable decreased liver function enzyme levels. Histopathology revealed that obvious changes in liver structure of all DM group, as evidenced by hepatocyte disorder and cellular swelling. Liver structure was evaluated by Periodic Acid Schiff (PAS) and Masson staining, the tissues appeared glycogen deposition and collagen deposition, indicating that DM aggravated liver injury. Compared with control group, the protein and mRNA expression of NLRP3, Caspase-1, ASC, and GSDMD were significantly induced in the DM group, while INS and NAC combined with INS treatment reversed the above changes. The levels of NF-κB P65, p-NF-κB, and IFN γ were availably enhanced in the DM group, which decreased through insulin and NAC combined with insulin treatment. This study demonstrated that NAC combined with INS exerted protective effects against STZ-induced liver injury by inhibiting the NLRP3/NF-κB pathway. The findings indicated that NAC combined with INS may serve as a potential candidate therapy for the treatment of T1DM.

Integrative epigenomic and transcriptomic analysis reveals the requirement of JUNB for hematopoietic fate induction.

Human pluripotent stem cell differentiation towards hematopoietic progenitor cell can serve as an in vitro model for human embryonic hematopoiesis, but the dynamic change of epigenome and transcriptome remains elusive. Here, we systematically profile the chromatin accessibility, H3K4me3 and H3K27me3 modifications, and the transcriptome of intermediate progenitors during hematopoietic progenitor cell differentiation in vitro. The integrative analyses reveal sequential opening-up of regions for the binding of hematopoietic transcription factors and stepwise epigenetic reprogramming of bivalent genes. Single-cell analysis of cells undergoing the endothelial-to-hematopoietic transition and comparison with in vivo hemogenic endothelial cells reveal important features of in vitro and in vivo hematopoiesis. We find that JUNB is an essential regulator for hemogenic endothelium specialization and endothelial-to-hematopoietic transition. These studies depict an epigenomic roadmap from human pluripotent stem cells to hematopoietic progenitor cells, which may pave the way to generate hematopoietic progenitor cells with improved developmental potentials.

NAC alleviative ferroptosis in diabetic nephropathy via maintaining mitochondrial redox homeostasis through activating SIRT3-SOD2/Gpx4 pathway.

Diabetic nephropathy (DN) is known as a major microvascular complication in type 1 diabetes. The effect of insulin treatment alone on controlling blood glucose is unsatisfactory. N-acetylcysteine (NAC), a chemical agent with thiol group, is found to confer a protective effect in renal injury. However, whether NAC combined with insulin treatment can further enhance the therapeutic effect in DN remains unclear. Here, we firstly used large mammal beagle as DN model to explore the effect of NAC combined with insulin treatment on DN during 120 d. Our results showed that NAC further alleviated mitochondrial oxidative damage and ferroptosis by enhancing activity of mitochondria GSH and maintaining mitochondrial redox homeostasis in DN. Additionally, the upregulated acetylation level of SOD2 was further abrogated by NAC treatment. In MDCK cells, NAC reduced high glucose (HG)-caused ferroptosis via activating Gpx4 expression. Of note, inhibition of Gpx4 by FIN56 abolished the protective effects of NAC on HG-induced ferroptosis. More importantly, 3-TYP reversed the effect of NAC on the mitochondria ROS under HG treatment, as well as eliminated its following beneficial effects for ferroptosis against HG-stimulated cells. These results reveal that NAC attenuated ferroptosis in DN via maintaining mitochondrial redox homeostasis through activating SIRT3-SOD2-Gpx4 signaling pathway.

Royal Jelly Protected against Dextran-Sulfate-Sodium-Induced Colitis by Improving the Colonic Mucosal Barrier and Gut Microbiota.

Royal jelly (RJ) is a natural bee product that contains a variety of biologically active ingredients and has antitumor, antiallergic, antibacterial and immune-regulating effects. Inflammatory bowel disease (IBD) is a chronic inflammatory disease of the intestine that can cause abdominal pain and diarrhea. With this study, we aimed to explore the protective effect of RJ on DSS-induced colitis in mice. The physiochemical parameters (water, protein, 10-hydroxy-2-decenoic acid, total sugar, starch, ash and acidity) of the RJ samples used in this study met the requirements of the international and Chinese national standards. Treatment with RJ improved symptoms and colonic cell apoptosis and decreased intestinal permeability by increasing the expression of tight-junction protein, goblet cells and their secretion mucin, MUC2, in DSS-induced ulcerative colitis mice. RJ also reduced the expression of proinflammatory cytokine IL-6 and increased the expression of anti-inflammatory cytokine IL-10 and sIgA. DSS resulted in an increase in the relative abundance of Parabacteroides, Erysipelotrichaceae, Proteobacteria (Gammaproteobacteria, Enterobacteriales and Enterobacteriaceae) and Escherichia Shigella in the colon and a decrease in the relative abundance of Muribaculum. In the RJ treatment group, the relative abundance of the above intestinal flora was improved by treatment with 2.0 g/kg RJ. These results suggested that RJ alleviated DSS-induced colitis by improving the colonic mucosal barrier.

Toxicological mechanism of large amount of copper supplementation: Effects on endoplasmic reticulum stress and mitochondria-mediated apoptosis by Nrf2/HO-1 pathway-induced oxidative stress in the porcine myocardium.

Copper (Cu) is an essential micronutrient that is required by all living organisms. However, Cu can also be a potentially toxic metal if excessive dietary supplementation occurs. The current study aimed to investigate the mechanism of Cu toxicity in the cardiomyocytes of large mammal pigs. Here, we used pigs to explore Cu toxicity in the control group (10 mg/kg Cu) and treatment groups (125 mg/kg and 250 mg/kg Cu) for a period of 80 days. Consequently, we identified that large amount intake of Cu led to in oxidative damage, and activation of the nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1)-mediated antioxidant pathway, indicating an imbalanced redox status in the myocardium. Furthermore, Cu exposure activated endoplasmic reticulum (ER) stress through upregulating levels of glucose-regulated protein 78 (GRP78), c-Jun N-terminal kinase (JNK), glucose-regulated protein 94 (GRP94), X-box binding protein 1 (XBP1), and C/EBP homologous protein (CHOP). Additionally, mitochondrial fission and fusion homeostasis was disrupted and the copy number of mitochondrial DNA (mtDNA) was reduced under Cu exposure. Furthermore, Cu exposure could induce apoptosis, evidenced by the increased terminal deoxynucleotidyl transferase biotin-d UTP nick end labeling (TUNEL)-positive staining, the upregulated expression levels of Cytoplasm-cytochrome C (Cytc), Bcl-2-associated X protein (Bax), and Cleaved-caspase3, and decreased expression level of B-cell lymphoma-2 (Bcl-2) and Mitochondrial-cytc. In summary, large amount of Cu could trigger Nrf2/HO-1 pathway-mediated oxidative stress, which promotes ER stress and mitochondrial damage pathways, causing apoptosis in cardiomyocytes.

Endoplasmic Reticulum Stress Contributes to Copper-Induced Pyroptosis via Regulating the IRE1α-XBP1 Pathway in Pig Jejunal Epithelial Cells.

Copper (Cu) is a common additive in food products, which poses a potential concern to animal and human health when it is in excess. Here, we investigated the relationship between endoplasmic reticulum (ER) stress and pyroptosis in Cu-induced toxicity of jejunum in vivo and in vitro. In in vivo experiments, excess intake of dietary Cu caused ER cavity expansion, elevated fluorescence signals of GRP78 and Caspase-1, and increased the mRNA and protein expression levels related to ER stress and pyroptosis in pig jejunal epithelium. Simultaneously, similar effects were observed in IPEC-J2 cells under excess Cu treatment. Importantly, 4-phenylbutyric acid (ER stress inhibitor) and MKC-3946 (IRE1α inhibitor) significantly inhibited the ER stress-triggered IRE1α-XBP1 pathway, which also alleviated the Cu-induced pyroptosis in IPEC-J2 cells. In general, these results suggested that ER stress participated in regulating Cu-induced pyroptosis in jejunal epithelial cells via the IRE1α-XBP1 pathway, which provided a novel view into the toxicology of Cu.

The potential risks of herbicide butachlor to immunotoxicity via induction of autophagy and apoptosis in the spleen.

Butachlor being an important member of chloroacetanilide herbicides, is frequently used in agriculture to control unwanted weeds. Exposure to butachlor can induce cancer, human lymphocyte aberration, and immunotoxic effects in animals. The current experimental trial was executed to determine the potential risks of herbicide butachlor to immunotoxicity and its mechanism of adverse effects on the spleen. For this purpose, mice were exposed to 8 mg/kg butachlor for 28 days, and the toxicity of butachlor on the spleen of mice was evaluated. We found that butachlor exposure led to an increase in serum ALB, GLU, TC, TG, and TP and changes in the morphological structure of the spleen of mice. More importantly, results showed that butachlor significantly increased the expression level of ATG-5, decreased the protein expression of LC3B and M-TOR, and significantly decreased the mRNA content of M-TOR and p62. Results revealed that the mRNA contents of APAF-1, CYTC, and CASP-9 related genes were significantly decreased after butachlor treatment. Subsequently, the mRNA levels of inflammatory cytokines (IL-1ß, TNF-α, IL-10) were reduced in the spleen of treated mice. This study suggested that butachlor induce spleen toxicity and activate the immune response of spleen tissue by targeting the CYTC/BCL2/M-TOR pathway and caspase cascading activation of spleen autophagy and apoptosis pathways which may ultimately lead to immune system disorders.

Mitochondrial miR-1285 regulates copper-induced mitochondrial dysfunction and mitophagy by impairing IDH2 in pig jejunal epithelial cells.

Copper (Cu), a hazardous heavy metal, can lead to toxic effects on host physiology. Recently, specific mitochondria-localized miRNAs (mitomiRs) were shown to modulate mitochondrial function, but the underlying mechanisms remain undefined. Here, we identified mitomiR-1285 as an important molecule regulating mitochondrial dysfunction and mitophagy in jejunal epithelial cells under Cu exposure. Mitochondrial dysfunction and mitophagy were the important mechanisms of Cu-induced pathological damage in jejunal epithelial cells, which were accompanied by significant increase of mitomiR-1285 in vivo and in vitro. Knockdown of mitomiR-1285 significantly attenuated Cu-induced mitochondrial respiratory dysfunction, ATP deficiency, mitochondrial membrane potential reduction, mitochondrial reactive oxygen species accumulation, and mitophagy. Subsequently, bioinformatics analysis and luciferase reporter assay demonstrated that IDH2 was a direct target of mitomiR-1285. RNA interference of IDH2 dramatically reversed the effect that mitomiR-1285 knockdown relieved mitochondrial dysfunction and mitophagy induced by Cu, and the opposite effect was shown by overexpression of IDH2. Therefore, our results suggested that mitomiR-1285 aggravated Cu-induced mitochondrial dysfunction and mitophagy via suppressing IDH2 expression. These findings identified the important mechanistic connection between mitomiRs and mitochondrial metabolism under Cu exposure, providing a new insight into Cu toxicology.

A mixed-method evaluation of the relationship between Oxford classification scores and longitudinal changes in proteinuria in patients with immunoglobulin A nephropathy.

Introduction: This study aimed to investigate the relationship between Oxford Classification scores and longitudinal changes in proteinuria in patients with immunoglobulin A nephropathy (IgAN). Methods: The study was a single-center retrospective cohort study involving 358 patients with primary IgAN who were treated at the Shenzhen Second People's Hospital, China, between January 2011 and May 2021. Multivariate linear regression and generalized additive mixed models (GAMMs), adjusted for traditional risk confounders, were used to evaluate the correlation between scores for mesangial hypercellularity (M), endocapillary hypercellularity (E), segmental glomerulosclerosis (S), tubular atrophy/interstitial fibrosis (T), and crescents (C) (known as the Oxford Classification MEST-C score system), with proteinuria/creatinine ratio (PCR) at the time of renal biopsy and longitudinal changes in PCR, respectively. Results: The median PCR was 1061 mg/g, and it increased on average by 68.82 mg/g per year in these patients. Among patients with renal insufficiency, compared with patients without relative lesions, those with E present (E1) (1153.44; 95% confidence interval [CI], 188.99-2117.89 mg/g) and C > 0 (C1/2) (1063.58; 95% CI, 185.25-1941.90 mg/g) were associated with increased PCR levels at the time of renal biopsy. What's more, S present (S1) (194.96; 95% CI, 54.50-335.43 mg/g per year) was associated with the fastest PCR increase; C > 0 (C1/2) (147.59; 95% CI, 8.32-286.86 mg/g per year) and T >25% (T1/2) (77.04; 95% CI, 7.18-146.89 mg/g per year), were also correlated with a faster PCR increase. In patients with normal kidney function, associations between S1 (55.46; 95% CI, 8.93-101.99 mg/g per year) and E1 (94.02; 95% CI, 21.47-166.58 mg/g per year) and PCR change could be observed. Additionally, in patients with overweight/obesity, S1 (156.09; 95% CI, 52.41-259.77 mg/g per year), E1 (143.34; 95% CI, 35.30-251.38 mg/g per year), T1/2 (116.04; 95% CI, 22.58-209.51 mg/g per year), as well as C1/2 (134.03; 95% CI, 41.73-226.32 mg/g per year) were associated with noticeably quicker PCR increase. Conclusions: Overall, E1 and C1/2 were independently associated with raised proteinuria levels at the time of renal biopsy, and S1, E1, T1/2, C1/2 were independently associated with a longitudinal increase in proteinuria in the patients with IgAN, especially in those with renal insufficiency or overweight/obesity, suggesting that currently available treatments might not be satisfactory, and weight control might be beneficial. Individual therapy development might benefit from the use of the Oxford Classification system.

Multiple organ dysfunction due to a rare complication of Nuss procedure for pectus excavatum: A case report.

A 19-year-old male patient who suffered from sudden and repeated multiple organ dysfunction syndrome one month after the bar removal procedure of Nuss surgery for pectus excavatum was admitted to our department. With organ function supportive treatment, the etiology was finally identified to be a bone spur located at the inner border of the left costa due to repeated friction between the implanted steel bar and the rib, which damaged the heart repeatedly and induced the consequent acute cardiac tamponade. After operation, the patient was successfully managed and discharged. Follow-ups till three years indicated a good recovery.

HSP60-knockdown suppresses proliferation in colorectal cancer cells via activating the adenine/AMPK/mTOR signaling pathway.

Colorectal cancer (CRC) is the fourth most lethal cancer in the world. Heat shock protein 60 (HSP60), a mitochondrial chaperone that maintains mitochondrial proteostasis, is highly expressed in tumors compared with in paracancerous tissues, suggesting that high HSP60 expression benefits tumor growth. To determine the effects of HSP60 expression on tumor progression, stable HSP60-knockdown HCT116 cells were constructed in the present study, revealing that knockdown of HSP60 inhibited cell proliferation. Proteomic analysis demonstrated that mitochondrial proteins were downregulated, indicating that knockdown of HSP60 disrupted mitochondrial homeostasis. Metabolomic analysis demonstrated that cellular adenine levels were >30-fold higher in HSP60-knockdown cells than in control cells. It was further confirmed that elevated adenine activated the AMPK signaling pathway, which inhibited mTOR-regulated protein synthesis to slow down cell proliferation. Overall, the current results provide a valuable resource for understanding mitochondrial function in CRC, suggesting that HSP60 may be a potential target for CRC intervention.

AQP2 as a target of lycopene protects against atrazine-induced renal ionic homeostasis disturbance.

Atrazine (ATR), a ubiquitous environmental contaminant in water and soil, causes environmental nephrosis. To reveal the toxic effect of ATR on the kidney and the potential chemical nephroprotective effect of lycopene (LYC), Kun-Ming mice of specific pathogen-free (SPF) grade were treated with LYC (5 mg kg-1) and/or ATR (50 mg kg-1 or 200 mg kg-1) for 21 days. The degree of renal injury was evaluated by measuring the ion concentration, ATPase activities and the mRNA expressions/levels of associated ATPase subunits. In addition, the expression of renal aquaporins (AQPs) was analyzed. The results showed that the renal tubular epithelial cells of ATR-exposed mice were swollen, the glomeruli were significantly atrophied, and the ion concentrations were obviously changed. The activity of Na+-K+-ATPase and the transcription of its subunits were downregulated. The activity of Ca2+-Mg2+-ATPase and the transcription of its subunits were upregulated. The expression of AQPs, especially the critical AQP2, was affected. Notably, ATR-induced nephrotoxicity was significantly improved by LYC supplementation. Therefore, LYC could protect the kidney against ATR-induced nephrotoxicity via maintaining ionic homeostasis, reversing the changes in ATPase activity and controlling the expression of AQPs on the cell membrane. These results suggested that AQP2 was a target of LYC and protected against ATR-induced renal ionic homeostasis disturbance.

Prognostic nomograms for patients undergoing radical operation for stage I-III appendiceal adenocarcinoma: A surveillance, epidemiology, and end results database analysis.

Objective: To develop nomograms for effective prediction of cause-specific survival (CSS) and overall survival (OS) of patients who underwent radical operation for stage I-III appendiceal adenocarcinoma. Methods: Clinical information from the surveillance, epidemiology, and end results database was retrieved from 2004 to 2015 and subjected to multivariate analysis to explore variables that affect the OS and CSS. Results were used to construct nomograms to assess the 1-, 3-, and 5-year OS and CSS rates, then their calibration accuracy and discriminative power were examined using Kaplan-Meier curves, calibration plots, and C statistics. Results: Overall, 1,241 patients were included in the analysis. We found 7 and 5 factors that could independently alter the prognosis, then used for creating nomograms for evaluating the OS and CSS, respectively, with respective C-index values of 0.741 (95% confidence interval [CI]: 0.729-0.754) and 0.747 (95% CI: 0.733-0.762). Calibration and receiver operating characteristic curves further revealed excellent predictive performance. Conclusions: We successfully built highly accurate nomograms for evaluating the 1-, 3-, and 5-year CSS and OS rates in subjects who underwent radical operation for stage I-III appendiceal adenocarcinoma. Further studies, involving prospective validations, are required to validate these nomograms.