Spatially resolved land and grid model of carbon neutrality in China.

China has committed to achieve net carbon neutrality by 2060 to combat global climate change, which will require unprecedented deployment of negative emissions technologies, renewable energies (RE), and complementary infrastructure. At terawatt-scale deployment, land use limitations interact with operational and economic features of power systems. To address this, we developed a spatially resolved resource assessment and power systems planning optimization that models a full year of power system operations, sub-provincial RE siting criteria, and transmission connections. Our modeling results show that wind and solar must be expanded to 2,000 to 3,900 GW each, with one plausible pathway leading to 300 GW/yr combined annual additions in 2046 to 2060, a three-fold increase from today. Over 80% of solar and 55% of wind is constructed within 100 km of major load centers when accounting for current policies regarding land use. Large-scale low-carbon systems must balance key trade-offs in land use, RE resource quality, grid integration, and costs. Under more restrictive RE siting policies, at least 740 GW of distributed solar would become economically feasible in regions with high demand, where utility-scale deployment is limited by competition with agricultural land. Effective planning and policy formulation are necessary to achieve China's climate goals.

CD11b + CD43 hi Ly6C lo splenocyte-derived macrophages exacerbate liver fibrosis via spleen-liver axis.

BACKGROUND AND AIMS: Monocyte-derived macrophages (MoMFs), a dominant population of hepatic macrophages under inflammation, play a crucial role in liver fibrosis progression. The spleen serves as an extra monocyte reservoir in inflammatory conditions; however, the precise mechanisms of involvement of the spleen in the pathogenesis of liver fibrosis remain unclear. APPROACH AND RESULTS: By splenectomy and splenocyte transfusion, it was observed that splenic CD11b + cells accumulated intrahepatically as Ly6C lo MoMFs to exacerbate CCl 4 -induced liver fibrosis. The splenocyte migration into the fibrotic liver was further directly visualized by spleen-specific photoconversion with KikGR mice and confirmed by CD45.1 + /CD45.2 + spleen transplantation. Spleen-derived CD11b + cells purified from fibrotic livers were then annotated by single-cell RNA sequencing, and a subtype of CD11b + CD43 hi Ly6C lo splenic monocytes (sM-1s) was identified, which was markedly expanded in both spleens and livers of mice with liver fibrosis. sM-1s exhibited mature feature with high expressions of F4/80, produced much ROS, and manifested preferential migration into livers. Once recruited, sM-1s underwent sequential transformation to sM-2s (highly expressed Mif , Msr1 , Clec4d , and Cstb ) and then to spleen-derived macrophages (sMφs) with macrophage features of higher expressions of CX 3 CR1, F4/80, MHC class II, and CD64 in the fibrotic hepatic milieu. Furthermore, sM-2s and sMφs were demonstrated capable of activating hepatic stellate cells and thus exacerbating liver fibrosis. CONCLUSIONS: CD11b + CD43 hi Ly6C lo splenic monocytes migrate into the liver and shift to macrophages, which account for the exacerbation of liver fibrosis. These findings reveal precise mechanisms of spleen-liver axis in hepatic pathogenesis and shed light on the potential of sM-1 as candidate target for controlling liver diseases.

Lysyl oxidase like-1 deficiency in optic nerve head astrocytes elicits reactive astrocytosis and alters functional effects of astrocyte derived exosomes.

Glaucoma is a multifactorial progressive ocular pathology that manifests clinically with damage to the optic nerve (ON) and the retina, ultimately leading to blindness. The optic nerve head (ONH) shows the earliest signs of glaucoma pathology, and therefore, is an attractive target for drug discovery. The goal of this study was to elucidate the effects of reactive astrocytosis on the elastin metabolism pathway in primary rat optic nerve head astrocytes (ONHA), the primary glial cell type in the unmyelinated ONH. Following exposure to static equibiaxial mechanical strain, we observed prototypic molecular and biochemical signatures of reactive astrocytosis that were associated with a decrease in lysyl oxidase like 1 (Loxl1) expression and a concomitant decrease in elastin (Eln) gene expression. We subsequently investigated the role of Loxl1 in reactive astrocytosis by generating primary rat ONHA cultures with ∼50% decreased Loxl1 expression. Our results suggest that reduced Loxl1 expression is sufficient to elicit molecular signatures of elastinopathy in ONHA. Astrocyte derived exosomes (ADE) significantly increased the length of primary neurites of primary neurons in vitro. In contrast, ADE from Loxl1-deficient ONHA were deficient of trophic effects on neurite outgrowth in vitro, positing that Loxl1 dysfunction and the ensuing impaired elastin synthesis during reactive astrocytosis in the ONH may contribute to impaired neuron-glia signaling in glaucoma. Our data support a role of dysregulated Loxl1 function in eliciting reactive astrocytosis in glaucoma subtypes associated with increased IOP, even in the absence of genetic polymorphisms in LOXL1 typically associated with exfoliation glaucoma. This suggests the need for a paradigm shift toward considering lysyl oxidase activity and elastin metabolism and signaling as contributors to an altered secretome of the ONH that may lead to the progression of glaucomatous changes. Future research is needed to investigate cargo of exosomes in the context of reactive astrocytosis and identify the pathways leading to the observed transcriptome changes during reactive astrocytosis.

Combined solar power and storage as cost-competitive and grid-compatible supply for China's future carbon-neutral electricity system.

As the world's largest CO2 emitter, China's ability to decarbonize its energy system strongly affects the prospect of achieving the 1.5 °C limit in global, average surface-temperature rise. Understanding technically feasible, cost-competitive, and grid-compatible solar photovoltaic (PV) power potentials spatiotemporally is critical for China's future energy pathway. This study develops an integrated model to evaluate the spatiotemporal evolution of the technology-economic-grid PV potentials in China during 2020 to 2060 under the assumption of continued cost degression in line with the trends of the past decade. The model considers the spatialized technical constraints, up-to-date economic parameters, and dynamic hourly interactions with the power grid. In contrast to the PV production of 0.26 PWh in 2020, results suggest that China's technical potential will increase from 99.2 PWh in 2020 to 146.1 PWh in 2060 along with technical advances, and the national average power price could decrease from 4.9 to 0.4 US cents/kWh during the same period. About 78.6% (79.7 PWh) of China's technical potential will realize price parity to coal-fired power in 2021, with price parity achieved nationwide by 2023. The cost advantage of solar PV allows for coupling with storage to generate cost-competitive and grid-compatible electricity. The combined systems potentially could supply 7.2 PWh of grid-compatible electricity in 2060 to meet 43.2% of the country's electricity demand at a price below 2.5 US cents/kWh. The findings highlight a crucial energy transition point, not only for China but for other countries, at which combined solar power and storage systems become a cheaper alternative to coal-fired electricity and a more grid-compatible option.

Comprehensive transcriptomics and metabolomics analyses reveal that hyperhomocysteinemia is a high risk factor for coronary artery disease in a chinese obese population aged 40-65: a prospective cross-sectional study.

BACKGROUND: Clinical observations suggest a complex relationship between obesity and coronary artery disease (CAD). This study aimed to characterize the intermediate metabolism phenotypes among obese patients with CAD and without CAD. METHODS: Sixty-two participants who consecutively underwent coronary angiography were enrolled in the discovery cohort. Transcriptional and untargeted metabolomics analyses were carried out to screen for key molecular changes between obese patients with CAD (CAD obese), without CAD (Non-CAD obese), and Non-CAD leans. A targeted GC-MS metabolomics approach was used to further identify differentially expressed metabolites in the validation cohorts. Regression and receiver operator curve analysis were performed to validate the risk model. RESULTS: We found common aberrantly expressed pathways both at the transcriptional and metabolomics levels. These pathways included cysteine and methionine metabolism and arginine and proline metabolism. Untargeted metabolomics revealed that S-adenosylhomocysteine (SAH), 3-hydroxybenzoic acid, 2-hydroxyhippuric acid, nicotinuric acid, and 2-arachidonoyl glycerol were significantly elevated in the CAD obese group compared to the other two groups. In the validation study, targeted cysteine and methionine metabolomics analyses showed that homocysteine (Hcy), SAH, and choline were significantly increased in the CAD obese group compared with the Non-CAD obese group, while betaine, 5-methylpropanedioic acid, S-adenosylmethionine, 4-PA, and vitamin B2 (VB2) showed no significant differences. Multivariate analyses showed that Hcy was an independent predictor of obesity with CAD (hazard ratio 1.7; 95%CI 1.2-2.6). The area under the curve based on the Hcy metabolomic (HCY-Mtb) index was 0.819, and up to 0.877 for the HCY-Mtb.index plus clinical variables. CONCLUSION: This is the first study to propose that obesity with hyperhomocysteinemia is a useful intermediate metabolism phenotype that could be used to identify obese patients at high risk for developing CAD.

Association of Neutrophil and Albumin With Mortality Risk in Patients Receiving Peritoneal Dialysis.

OBJECTIVE: Inflammation and nutrition have been recognized as predicting mortality in patients receiving peritoneal dialysis (PD). Serum neutrophil and albumin are crucial factors in inflammation and nutrition status. Up until now, the synergistic effect of neutrophil and albumin on mortality prediction in PD patients is still being determined. Our study sought to assess the effect of the interaction between neutrophils and albumin on the risk of all-cause mortality and cardiovascular disease (CVD) mortality patients receiving PD. METHODS: A total of 1229 PD patients were recruited and divided into three categories in this cohort study. Their relationships with all-cause mortality and CVD mortality were analyzed in multivariable COX regression models adjusted for confounding factors. RESULTS: During the median follow-up of 34.2 months, 222 (18.1%) patients died, and 115 (51.8%) suffered from cardiovascular events. Patients with high neutrophil percentage-to-albumin ratio (NPAR) showed increased all-cause mortality and CVD mortality, with adjusted hazard ratios of 1.490 (95% confidence interval, 1.070-2.074, P = .018) and 1.633 (95% confidence interval, 1.041-2.561, P = .033), respectively, compared with those with low NPAR. Competitive risk models and sensitivity analyses further confirmed this association. In the receiver operating characteristic curve analysis, however, there was little evidence that NPAR is a better indicator than albumin and neutrophil count. CONCLUSIONS: Having a high NPAR is linked to a higher risk of mortality, especially when both high neutrophil and low albumin are present.

Highly Sensitive Genosensing Coupling Rolling Circle Amplification with Multiple DNAzyme Cores for DNA Walking.

Herein, a highly sensitive electrochemical genosensor is proposed by the construction of an innovative DNA walking machine. Generally, a number of tetrahedral DNA (TDNA)-supported tracks and walkers are comodified on the electrode surface. DNA walking is inhibited in the absence of target DNA. After the interaction between a DNA walker strand and target DNA, a single-stranded primer sequence could be released, which initiates subsequent rolling circle amplification (RCA). The generated long single-stranded product contains multiple DNAzyme cores, which facilitate highly efficient cleavage of track strands and subsequent DNA walking. The electrode then loses the ability to localize silver nanoparticles (AgNPs) as the electrochemical species. Thus, when the reduced silver stripping current is recorded, a highly sensitive method for the detection of DNA is fabricated. Under optimal conditions, it achieves an admirable sensitivity with the limit of detection as low as 0.1 fM. Satisfactory specificity is also guaranteed. In addition, the practicality is further confirmed by applying human serum samples, which show great potential utility for clinical diagnosis.

Nano-copper enhanced flexible device for simultaneous measurement of human respiratory and electro-cardiac activities.

BACKGROUND: Dysfunction of human respiratory and electro-cardiac activities could affect the ability of the heart to pump blood and the lungs to inhale oxygen. Thus, a device could simultaneously measure electro-cardiac signal and respiratory pressure could provide vital signs for predicting early warning of cardio-pulmonary function-related chronic diseases such as cardiovascular disease, and respiratory system disease. RESULTS: In this study, a flexible device integrated with piezo-resistive sensing element and voltage-sensing element was developed to simultaneously measure human respiration and electro-cardiac signal (including respiratory pressure, respiration frequency, and respiration rhythm; electro-cardio frequency, electro-cardio amplitude, and electro-cardio rhythm). When applied to the measurement of respiratory pressure, the piezo-resistive performance of the device was enhanced by nano-copper modification, which detection limitation of pressure can reduce to 100 Pa and the sensitivity of pressure can achieve to 0.053 ± 0.00079 kPa-1. In addition, the signal-to-noise ratio during bio-electrical measurement was increased to 10.7 ± 1.4, five times better than that of the non-modified device. CONCLUSION: This paper presents a flexible device for the simultaneous detection of human respiration and cardiac electrical activity. To avoid interference between the two signals, the layout of the electrode and the strain sensor was optimized by FEA simulation analysis. To improve the piezo-resistive sensitivity and bio-electric capturing capability of the device, a feather-shaped nano-copper was modified onto the surface of carbon fiber. The operation simplicity, compact size, and portability of the device open up new possibilities for multi-parameter monitoring.

Knockout of Canopy 2 activates p16INK4a pathway to impair cardiac repair.

BACKGROUND: Cardiac repair depends on angiogenesis and cell proliferation. Previously we identified Canopy 2 (CNPY2) as a secreted angiogenic growth factor which promotes neovascularization. We investigated the role of CNPY2 in cardiac repair following myocardial infarction (MI) and the possible mediators involved using Cnpy2 knockout (KO) mice and human cardiac tissue. METHODS AND RESULTS: Cardiac tissue from patients with end-stage heart failure had significantly lower endogenous CNPY2 expression compared to samples from control patients. CNPY2 expression in mouse hearts significantly decreased following MI. Significantly less leukocyte and endothelial cell proliferation was found in Cnpy2 KO than wild-type (WT) mice post MI which contributed to impaired angiogenesis, tissue repair, and decreased cardiac function (fractional shortening: WT: 21.1 ±â€¯2.1% vs. KO: 16.4 ±â€¯1.6%, p < .01 at day 28 post MI). RT-qPCR revealed significantly increased p16INK4a expression in Cnpy2 KO mouse hearts (WT: 1.0 ±â€¯0.04 vs. KO: 2.33 ±â€¯0.11 [relative expression of p16 INK4a], p < .01) which was confirmed by immunostaining (WT: 8.47 ±â€¯1.22 vs. KO: 12.9 ±â€¯1.22 [% total cells], p < .05) for the p16INK4a protein. Expression of cell cycle-related proteins, cyclin D1, cyclin-dependent kinases 4 and 6, and phosphorylated retinoblastoma protein (pRb) was significantly decreased in Cnpy2 KO mouse hearts. The up-regulation of the p16INK4a/cyclin D1/Rb pathway by knockout of Cnpy2 was accompanied by attenuation of PDK1/Akt phosphorylation. MI exacerbated the detrimental effects of p16INK4a on tissue repair in Cnpy2 KO mice. Overexpression of CNPY2 in the cardiac tissue of transgenic mice reversed the inhibition of cell proliferation through suppression of the p16INK4a pathway. CONCLUSIONS: Cardiac injury and progressive heart failure were associated with decreased CNPY2 levels in both humans and mice. Knockout of Cnpy2 resulted in up-regulation of p16INK4a which impaired cardiac function and tissue repair. These data suggest that CNPY2 is an important regulator of p16INK4a and promotes cell proliferation and tissue repair through inhibition of the p16INK4a pathway. CNPY2 treatment may offer a new approach to restore cardiac function after an MI.

Prognostic Significance of Serum Cysteine-Rich Protein 61 in Patients with Acute Heart Failure.

BACKGROUND/AIMS: Cyr61-cysteine-rich protein 61 (CCN1/CYR61) is a multifunctional matricellular protein involved in the regulation of fibrogenesis. Animal experiments have demonstrated that CCN1 can inhibit cardiac fibrosis in cardiac hypertrophy. However, no study has been conducted to assess the relation between serum CCN1 and prognosis of acute heart failure (AHF). METHODS: We measured the serum CCN1 levels of 183 patients with AHF, and the patients were followed up for 6 months. The associations between CCN1 levels and some clinical covariates, especially left ventricular ejection fraction (LVEF), estimated glomerular filtration rate (eGFR), atrial fibrillation and age, were estimated. The AHF patients were followed up for 6 months. The endpoint was all-cause mortality. Kaplan-Meier curve analysis and multivariable Cox proportional hazards analysis were employed to evaluate the prognostic ability of CCN1. We used calibration, discrimination and reclassification to assess the mortality risk prediction of adding CCN1. RESULTS: Serum CCN1 concentrations in AHF patients were significantly increased compared with those in individuals without AHF (237 pg/ml vs. 124.8 pg/ml, p< 0.001). CCN1 level was associated with the level of NT-proBNP (r=0.349, p< 0.001) and was not affected by LVEF, eGFR, age or atrial fibrillation in AHF patients. Importantly, Kaplan-Meier curve analysis illustrated that the AHF patients with serum CCN1 level > 260 pg/ ml had a lower survival rate (p< 0.001). Multivariate Cox hazard analysis suggests that CCN1 functions as an independent predictor of mortality for AHF patients (LgCCN1, hazard ratio 5.825, 95% confidence interval: 1.828-18.566, p=0.003). In addition, the inclusion of CCN1 in the model with NT-proBNP significantly improved the C-statistic for predicting death (0.758, p< 0.001). The integrated discrimination index was 0.019 (p< 0.001), and the net reclassification index increased significantly after addition of CCN1 (23.9%, p=0.0179). CONCLUSIONS: CCN1 is strongly predictive of 6-month mortality in patients with AHF, suggesting serum CCN1 as a promising candidate prognostic biomarker for AHF patients.

Dual specificity phosphatase 15 regulates Erk activation in Schwann cells.

Schwann cells and oligodendrocytes are the myelinating cells of the peripheral and central nervous system, respectively. Despite having different myelin components and different transcription factors driving their terminal differentiation there are shared molecular mechanisms between the two. Sox10 is one common transcription factor required for several steps in development of myelinating glia. However, other factors are divergent as Schwann cells need the transcription factor early growth response 2/Krox20 and oligodendrocytes require Myrf. Likewise, some signaling pathways, like the Erk1/2 kinases, are necessary in both cell types for proper myelination. Nonetheless, the molecular mechanisms that control this shared signaling pathway in myelinating cells remain only partially characterized. The hypothesis of this study is that signaling pathways that are similarly regulated in both Schwann cells and oligodendrocytes play central roles in coordinating the differentiation of myelinating glia. To address this hypothesis, we have used genome-wide binding data to identify a relatively small set of genes that are similarly regulated by Sox10 in myelinating glia. We chose one such gene encoding Dual specificity phosphatase 15 (Dusp15) for further analysis in Schwann cell signaling. RNA interference and gene deletion by genome editing in cultured RT4 and primary Schwann cells showed Dusp15 is necessary for full activation of Erk1/2 phosphorylation. In addition, we show that Dusp15 represses expression of several myelin genes, including myelin basic protein. The data shown here support a mechanism by which early growth response 2 activates myelin genes, but also induces a negative feedback loop through Dusp15 to limit over-expression of myelin genes.

Comparison of the Inhibitory Mechanisms of Diethyl Citrate, Sodium Citrate, and Phosphonoformic Acid on Calcification Induced by High Inorganic Phosphate Contents in Mouse Aortic Smooth Muscle Cells.

OBJECTIVE: This study aimed to investigate the differences and inhibitory effects of diethyl citrate (Et2Cit), sodium citrate (Na3Cit), and phosphonoformic acid (PFA) on calcification induced by high inorganic phosphate (Pi) contents in mouse aortic smooth muscle cells (MOVAS) and to develop drugs that can induce anticoagulation and inhibit vascular calcification (VC). METHODS: Alive and fixed MOVAS were assessed for 14 days in the presence of high Pi with increasing Et2Cit, Na3Cit, and PFA concentrations. Calcification on MOVAS was measured through Alizarin red staining and the deposited calcium amount; apoptosis was detected by annexin V staining; and cell transdifferentiation was examined by measuring smooth muscle lineage gene (α-SMA) expression and alkaline phosphatase activity. RESULTS: Coincubation of MOVAS with Et2Cit, Na3Cit, and PFA significantly decreased Pi-induced VC in live MOVAS, and the apoptotic rate was reduced by low inhibitor concentrations. The 3 inhibitors could prevent the alkaline phosphatase activity induced by high Pi contents and increased the expression of α-smooth muscle actin genes. Thus, the transdifferentiation of MOVAS into osteoblast-like cells was blocked. Their inhibitory effects exhibited concentration dependence. The inhibitory effect of each inhibitor at the same concentration showed the following trend: PFA > Na3Cit > Et2Cit. CONCLUSIONS: Et2Cit, Na3Cit, and PFA prevented the calcification of MOVAS and inhibited the osteochondrocytic conversion of vascular smooth muscle cells. Thus, Et2Cit and Na3Cit as anticoagulants may alleviate VC in clinical applications.

An HPLC method for simultaneous quantitative determination of seven secoiridoid glucosides separated from the roots of Ilex pubescens.

A simple and specific high-performance liquid chromatographic method has been developed and validated to simultaneously determine seven secoiridoid glucosides for the first time. Three of them were separated from the ethanolic extract of the roots of Ilex pubescens for the first time, namely nuezhenide A, ligusides B and oleonuezhenide. In quantitative analysis, all of the calibration curves showed good linear regression (r > 0.999) within the tested ranges, and the mean recoveries of three different concentrations ranged from 97.6 to 101.2%. The limit of detection and limit of quantification were <4.18 and 11.63 ng mL-1 , respectively. The relative standard deviation for repeatability and the precision of seven analytes were <3.4 and 1.9%, respectively. The established method was successfully applied to simultaneous determination of seven secoiridoid glucosides in 11 batches of samples collected from different habitats in China.

[Application of lymphography in the location and treatment decision of chyle leakage: an analysis of 177 cases].

OBJECTIVE: To identify the value of lymphography in the location and treatment decision of chyle leakage. METHODS: The clinic data of 177 patients suffered from chyle leakage admitted in 6 medical centers in Shanghai from February 1998 to December 2014 was analyzed retrospectively. There were 94 male and 83 female patients aging from 9 to 84 years with a mean of 49 years, including 128 cases of chyluria, 34 cases of primary chylothorax and 15 cases of other chyle leakage. All patients had failed to conservative treatment more than 2 weeks. Pedal lymphography was performed in every patient to investigate the site and range of chyle leakage. Effect of surgical or conservative management was compared according to the different results of lymphography. RESULTS: No serious complication was noticed. For all 177 patients, lymphography showed localized lymphatic diseases in 148 cases (83.6%), including 125 cases of lymphatic renal pelvic leaks, 14 cases of unilateral identified leak within thorax and 9 cases of chyle leakage in neck, heart, abdomen or scrotum. Among these patients, surgical treatment cured 129 and improved 3 patients but failed in 2 patients, while the remaining 14 cases had their leaks decreased after lymphography and cured by conservative management. For those 15 patients having disseminated lymphatic diseases or 14 with no abnormality under lymphography, surgery only cured 2 and improved 1 patient but failed in 8 patients (with 3 death), whereas continuous conservative treatment cured 11 patients, improved 5 patients but only failed in 2 patients (with one death). For localized leakage, surgical treatment showed better efficacy (98.5% vs. 3/11), whereas conservative treatment had significantly higher successful rate than surgical interventions in patients with disseminated lymphatic diseases or no abnormality under lymphography (16/18 vs. 3/11). CONCLUSIONS: Lymphography could identify the location and range of complicate chyle leakage failed to primary conservative management. Patients with disseminated lymphatic diseases or no abnormality under lymphography would be better managed by continuous non-operative treatment partly due to therapeutic effect of lymphography, while surgical intervention could be a good option for patients having localized lymphatic etiology.

The advantages of unilateral pedal lymphography in the diagnosis of chyluria.

OBJECTIVES: To evaluate the efficacy and safety of pedal lymphography (PLG) in the localization diagnosis of chyluria. METHODS: Cystoscopy was performed in 153 patients and PLG in 121 cases. Unilateral or staged bilateral ligation and stripping of renal lymphatic vessel were performed according to the results of cystoscopy and/or PLG. RESULTS: Unilateral and bilateral urinary excretion of chyle was detected in 123 and 1 case by cystoscopy, respectively. In 121 cases receiving PLG, 100 cases of unilateral fistulous connection between the renal pelvis and the lymphatic system, 18 cases of bilateral fistulas and 1 case of lymphatic bladder fistula were demonstrated. PLG has a higher diagnostic rate for the detection of bilateral lymphatic renal pelvis fistulas than cystoscopy (p<0.05). 28 cases received renal pedicle lymphatic disconnection only according to the results of cystoscopy, and 3 of them failed (10.1%). While 121 cases had the same operation according to the results of PLG, only 1 case failed the operation (0.8%). CONCLUSIONS: PLG was efficient and safe for the localization diagnosis of chyluria, with a higher detection rate of bilateral fistulas than cystoscopy. PLG might benefit the selection of appropriate therapy and improve the surgical effect.

Effect of HSP90 inhibitor in pheochromocytoma PC12 cells: an experimental investigation.

This study aims to investigate whether the expression of heat shock protein 90 (HSP90) is associated with the malignant pheochromocytoma (PHEO) and the effects of 17-allylamino-17-demethoxygeldanamcyin (17-AAG) on the expression of vascular endothelial growth factor (VEGF) in PHEO cell line PC12. The expression of HSP90 was investigated in 38 paraffin-embedded samples of PHEO patients using immunohistochemistry. The time and concentration effects of 17-AAG were investigated in PHEO PC12 cells. Cell proliferation was measured by MTT assay and cell counting. Apoptosis was detected by flow cytometry. Positive staining for HSP90 was found in 14 of 17 malignant (82.35%) and in 5 of 21 (23.81%) benign PHEOs. There existed a significant statistical difference between the malignant group and the benign ones (P < 0.001). 17-AAG inhibited the proliferation of HCC cells in a time- and concentration-dependent manner. The apoptosis rates of PC12 cells after treatment with 0.1 µmol/L for 6, 12, 24, and 48 h were significantly higher than that in blank control group. 17-AAG significantly downregulated VEGF-165 protein level in PC12 cells. This study has confirmed that the specific HSP90 inhibitor 17-AAG can play a therapeutic role in malignant PHEO treatment, and HSP90 qualifies as a promising new target in malignant PHEO.

The role of unilateral adrenalectomy in corticotropin-independent bilateral adrenocortical hyperplasias.

BACKGROUND: The objective of the present study was twofold: to demonstrate our experience with unilateral adrenalectomy in the treatment of adrenocorticotropic hormone (ACTH)-independent Cushing syndrome (CS) caused by bilateral adrenocortical hyperplasias, and to evaluate the long-term results as evidenced by the main laboratory and clinical findings. METHODS: From February 2000 to August 2009, unilateral adrenalectomy was performed on 27 patients with ACTH-independent CS and bilateral adrenocortical hyperplasias, including 14 patients with ACTH-independent macronodular adrenal hyperplasia (AIMAH) and 13 patients with primary pigmented nodular adrenocortical disease (PPNAD). Signs and symptoms of CS, endocrine examinations, and radiographic imaging were evaluated preoperatively and postoperatively. RESULTS: At a median follow-up of 69 months (range: 23-120 months) for AIMAH and 47 months (range: 16-113 months) for PPNAD, 25 patients were cured by unilateral adrenalectomy. Serum cortisol level, daily urinary free cortisol (UFC), and plasma ACTH regained the normal range in both AIMAH and PPNAD patients at monthly follow-up visits; the circadian serum cortisol rhythm returned to normal, and a normal responsiveness to overnight low-dose dexamethasone administration (LDDST) became obvious. Both systolic and diastolic blood pressure (BP) levels were significantly reduced: 85 % of patients recovered normal BP levels, and the remaining patients need antihypertensive drugs, but at a reduced dose. No surgery-related morbidity occurred, and there was no sign of further enlargement of the residual adrenal gland after successful unilateral adrenalectomy. One patient with PPNAD and another patient with AIMAH with similar weights and sizes of the bilateral adrenals needed contralateral adrenalectomy. CONCLUSIONS: Unilateral adrenalectomy may be the suitable treatment for selected patients with AIMAH and PPNAD. It can achieve long-term remission of CS and improve glycemic control and BP values.

Chitosan-induced self-assembly of montmorillonite nanosheets along the end-face for methylene blue removal from water.

In this study, chitosan-induced self-assembly of montmorillonite nanosheets (MMTNS) along the end-face to form the layered and porous structured composite with high adsorption capacity towards MB dye wastewater was investigated. The self-assembly process was driven by the hydrogen-bond interaction among -OH groups distributed along the end-face of MMTNS and -NH2 groups on chitosan (CS) chain, which finally formed the infinite two-dimensional lamellae. This technology remained the exposed adsorption sites on MMTNS surface, and solved the separation issue of spent MMTNS from water, making MMTNS/CS an excellent adsorption material for macromolecular MB dye. The maximum adsorption capacity of MMTNS/CS towards MB reached 243 mg/g, which was achieved via the Na+- exchange, hydrogen-bond and n-π stacking interactions with MB molecules. This work aimed at breaking through the bottleneck of small adsorption capacity of traditional MMT adsorbents, solving the problem of solid-liquid separation of nanosheets, and effectively reducing the adsorption cost, which might guide an important direction for adsorption material design and development in the future.

[Corrigendum] FPR2 serves a role in recurrent spontaneous abortion by regulating trophoblast function via the PI3K/AKT signaling pathway.

Subsequently to the publication of the above paper, an interested reader drew to the authors' attention that the '0 h/si-NC + Solvent' and '0 h/si-FPR2 + Solvent' data panels shown in Fig. 4B on p. 7 appeared to contain overlapping sections of data, such that they were potentially derived from the same original source where these panels was intended to show the results from differently performed experiments. After having conducted an independent investigation of the figures in the Editorial Office, it was identified that sections of the 'si-NC + Solvent' and 'si-FPR2 + LY294002' data panels in Fig. 4C also contained overlapping data. After having asked the authors to provide an explanation of these data, they realized that this figure was inadvertently assembled incorrectly. They were, however, able to consult their original data, and the revised version of Fig. 4, containing the correct data panel for the 'si-FPR2 + LY294002' experiment in Fig. 4C and complete data from one of the alternatively performed experiments in Fig. 4B, is shown on the next page. Note that these errors did not adversely affect either the results or the overall conclusions reported in this study. All the authors agree with the publication of this corrigendum, and are grateful to the Editor of Molecular Medicine Reports for allowing them the opportunity to publish this. They also wish to apologize to the readership of the Journal for any inconvenience caused. [Molecular Medicine Reports 24: 838, 2021; DOI: 10.3892/mmr.2021.12478].

[Experience in reducing intraoperative blood loss in radical retropubic prostatectomy].

OBJECTIVE: To search for an effective method of reducing intraoperative blood loss in radical retropubic prostatectomy (RRP). METHODS: We performed RRP for 100 patients with prostate cancer, 50 (group A) with the Walsh or Poor method for handling the dorsal venous complex (DVC), and the other 50 (group B) through the following three additional procedures for hemostasis: first placing a #7 prophylactic suture in the distal position of DVC, then ligating the vascular bundle of the prostatic apex with continuous 4-0 Vicryl sutures, and lastly placing a 4-0 absorbable suture followed by freeing the neurovascular bundle (NVB) or freeing NVB before suturing the remained levator ani myofascia and the deep layer of Denovilliers' fascia above the rectal serosa with 4-0 Vicryl. We assessed the effects of the three hemostatic methods in RRP by comparing the volumes of intraoperative blood loss and transfusion, operation time and perioperative levels of hemoglobin. RESULTS: There were no significant differences between groups A and B in age, PSA, Gleason score, clinical stage, prostate volume, operation time and perioperative hemoglobin levels (P>0.05). The volumes of intraoperative blood loss and transfusion were markedly higher in group A ([1103.00 +/- 528.03] ml and [482.00 +/- 364.60] ml) than in B ([528.00 +/- 258.96] ml and [140.00 +/- 266.28] ml) (P<0.05). CONCLUSION: Intraoperative blood loss in RRP could be significantly decreased by placing a prophylactic hemostatic suture in the distal position of DVC, continuous suture of the vascular bundle of the prostatic apex after cutting off the urethra, and placing a fine absorbable suture above NVB or continuous suture of the remained levator ani mony fascia and the deep layer of Denovilliers'fascia above the rectal serosa with absorbable sutures after freeing NVB.