Enantioselective Synthesis of ß-Aminoboronic Acids via Borylalkylation of Enamides.

Aminoboronic acids represent a class of significant compounds that have attracted significant attention in the fields of drug discovery and organic synthesis. Despite notable progress in their synthesis, the efficient construction of chiral ß-aminoboronic acids with alkyl side chains remains a challenging endeavor. Here, we introduce an unprecedented nickel-catalyzed asymmetric borylalkylation of enamides, employing a simple chiral diamine ligand, readily available B2pin2, and alkyl halides as coupling partners. This reaction serves as an efficient platform for assembling a diverse range of ß-aminoboronic acid derivatives with flexible alkyl side chains, displaying exceptional regio-, stereo-, and enantioselectivities. Moreover, this transformation exhibits a broad substrate scope and remarkable tolerance toward various functional groups. Theoretical calculations demonstrate that the benzyl group on the ligand is the key to the high enantiocontrol in this transformation. Additionally, we exemplify the practical application of this strategy through the concise synthesis of complex bioactive molecules.

Experimental and simulation investigation of stereo-DIC via a deep learning algorithm based on initial speckle positioning technology.

For the deep-learning-based stereo-digital image correlation technique, the initial speckle position is crucial as it influences the accuracy of the generated dataset and deformation fields. To ensure measurement accuracy, an optimized extrinsic parameter estimation algorithm is proposed in this study to determine the rotation and translation matrix of the plane in which the speckle is located between the world coordinate system and the left camera coordinate system. First, the accuracy of different extrinsic parameter estimation algorithms was studied by simulations. Subsequently, the dataset of stereo speckle images was generated using the optimized extrinsic parameters. Finally, the improved dual-branch CNN deconvolution architecture was proposed to output displacements and strains simultaneously. Simulation results indicate that DAS-Net exhibits enhanced expressive capabilities, as evidenced by a reduction in displacement errors compared to previous research. The experimental results reveal that the mean absolute percentage error between the stereo-DIC results and the generated dataset is less than 2%, suggesting that the initial speckle positioning technology effectively minimizes the discrepancy between the images in the dataset and those obtained experimentally. Furthermore, the DAS-Net algorithm accurately measures the displacement and strain fields as well as their morphological characteristics.

Enantioselective C-H Arylation for Axially Chiral Heterobiaryls.

An enantioselective palladium-catalyzed C-H arylation of functionalized pyrazoles/triazoles/imidazoles is developed, affording a variety of axially chiral ortho-nitro/formyl-substituted heterobiaryls with excellent enantioselectivities and good yields. The method features a deuterated P-chiral phosphorus ligand CD3-AntPhos, a broad substrate scope of functionalized heterobiaryls, mild reaction conditions, and low palladium loadings.

Model for Predicting Central Nervous System Relapse in Diffuse Large B-Cell Lymphoma and Discussion of Prophylaxis Measures.

OBJECTIVE: Relapse of the central nervous system (CNS) is a rare but fatal complication in diffuse large B-cell lymphoma (DLBCL). The purpose of this study is to learn how to identify high-risk patients and take effective preventive measures. METHODS: We retrospectively analyzed 1,290 adult patients with DLBCL at Peking University Cancer Hospital and Shanxi Bethune Hospital between 2010 and 2020. RESULTS: There were 55 patients with CNS relapse who had a median follow-up of 5 years. The risk of CNS relapse was 1.58% in the low-risk group, 5.66% in the moderate-risk group, and 11.67% in the high-risk group based on CNS International Prognostic Index (CNS-IPI). We found that CNS-IPI and testicular involvement were risk factors for CNS relapse, with OR 1.913 (95% CI: 1.036∼3.531; P = 0.038) versus. OR 3.526 (95% CI: 1.335∼9.313; P = 0.011), respectively. Intrathecal MTX and/or cytarabine prophylaxis was used in 166 patients (13.94%), intravenous (IV) high-dose methotrexate (HD-MTX) prophylaxis in 8 patients (0.67%), and intrathecal plus intravenous prophylaxis in 15 patients (1.26%). There was no significant difference in CNS relapse risk between IT, HD-MTX, and no prophylaxis recipients (12.7% vs. 0% vs. 23.6%, respectively, P = 0.170). The risk of CNS relapse was similar whether or not patients accepted prophylaxis (5-year risk 4.1% vs. 2.2%, P = 0.140). CONCLUSIONS: Central nervous system (CNS) relapse is associated with high risk CNS-IPI and testicular involvement. Therefore, it is necessary to pursue novel prophylactic strategies for CNS relapse.

Efficacy of lenvatinib combined with sequential transarterial chemoembolization for primary hepatocellular carcinoma and the effects on serum basic fibroblast growth factor and vascular endothelial growth factor.

Objective: The aim of this research was to investigate the therapeutic efficacy of lenvatinib combined with sequential transarterial chemoembolization (TACE) on primary hepatocellular carcinoma (HCC) and the effects on serum basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF). Method: A total of 104 patients with primary HCC, admitted to People's Hospital of Leshan from April 2018 to January 2021, were selected as the study subjects and were divided into the TACE-LEN group (n = 53) who were treated with lenvatinib combined with sequential TACE and the TACE group (n = 51) who were treated with TACE alone, according to the appropriate treatment modalities. The clinical efficacy 8 weeks after treatment; the serum levels of total bilirubin, conjugated bilirubin, and alanine aminotransferase (ALT); the prothrombin time (PT); the indocyanine green retention rate at 15 min (ICGR15); and the serum bFGF and VEGF levels before treatment and at 8 weeks after treatment were compared between the two groups. The incidence of adverse events and the survival rates at 18 months were also recorded for both groups. COX regression analysis was used to analyze the risk factors affecting the survival of patients. Results: Eight weeks after treatment, the objective response rate was higher in the TACE-LEN group than in the TACE group (77.36% vs. 56.36%, p < 0.05), but there were no statistically significant differences in the bilirubin and ALT levels, the PT, and the ICGR15 between the two groups (p > 0.05). The serum bFGF and VEGF levels post-therapeutic were lower in the TACE-LEN group than in the TACE group (p < 0.05). The differences in the incidence of postoperative adverse events and the survival rate within 6 months were not statistically significant between the two groups (p > 0.05). In addition, the survival rates within 12 and 18 months after treatment were higher in the TACE-LEN group than in the TACE group than in the TACE group (81.1% vs. 64.7%, 69.8% vs. 49.1%, p < 0.05). ICG-R15 and treatment regimen are risk factors for survival. Conclusion: The worse the liver reserve is, the worse the prognosis is. The combination of TACE and lenvatinib showed better efficacy and longer survival than TACE monotherapy for HCC patients and reduced the levels of bFGF and VEGF.

Essential Roles of Two FRQ Proteins (Frq1 and Frq2) in Beauveria bassiana's Virulence, Infection Cycle, and Calcofluor-Specific Signaling.

Two FRQ proteins (Frq1 and Frq2) distinct in molecular mass and structure coexist in Beauveria bassiana, an asexual insect-pathogenic fungus. Frq1 and Frq2 have been proven to have opposite nuclear rhythms that can persistently activate developmental activator genes and hence orchestrate nonrhythmic conidiation in vitro under light or in darkness. Here, we report the essentiality of either FRQ, but Frq2 being more important than Frq1, for the fungal virulence and infection cycle. The fungal virulence was attenuated significantly more in the absence of frq2 than in the absence of frq1 through either normal cuticle infection or cuticle-bypassing infection by intrahemocoel injection, accompanied by differentially reduced secretion of Pr1 proteases required for the cuticle infection and delayed development of hyphal bodies in vivo, which usually propagate by yeast-like budding in the host hemocoel to accelerate insect death from mycosis. Despite insignificant changes in radial growth under normal, oxidative, and hyperosmotic culture conditions, conidial yields of the Δfrq1 and Δfrq2 mutants on insect cadavers were sharply reduced, and the reduction increased with shortening daylight length on day 9 or 12 after death, indicating that both Frq1 and Frq2 are required for the fungal infection cycle in host habitats. Intriguingly, the Δfrq1 and Δfrq2 mutants showed hypersensitivity and high resistance to cell wall-perturbing calcofluor white, coinciding respectively with the calcofluor-triggered cells' hypo- and hyperphosphorylated signals of Slt2, a mitogen-activated protein kinase (MAPK) required for mediation of cell wall integrity. This finding offers a novel insight into opposite roles of Frq1 and Frq2 in calcofluor-specific signal transduction via the fungal Slt2 cascade.IMPORTANCE Opposite nuclear rhythms of two distinct FRQ proteins (Frq1 and Frq2) coexisting in an asexual fungal insect pathogen have been shown to orchestrate the fungal nonrhythmic conidiation in vitro in a circadian day independent of photoperiod change. This paper reports essential roles of both Frq1 and Frq2, but a greater role for Frq2, in sustaining the fungal virulence and infection cycle since either frq1 or frq2 deletion led to marked delay of lethal action against a model insect and drastic reduction of conidial yield on insect cadavers. Moreover, the frq1 and frq2 mutants display hypersensitivity and high resistance to cell wall perturbation and have hypo- and hyperphosphorylated MAPK/Slt2 in calcofluor white-triggered cells, respectively. These findings uncover a requirement of Frq1 and Frq2 for the fungal infection cycle in host habitats and provide a novel insight into their opposite roles in calcofluor-specific signal transduction through the MAPK/Slt2 cascade.

Value of the controlling nutritional status score and psoas muscle thickness per height in predicting prognosis in liver transplantation.

BACKGROUND: Patients with end-stage liver disease usually have varying degrees of malnutrition, and severe malnutrition may affect the prognosis of patients after liver transplantation (LT). However, there is no recommended standard for the nutrition assessment of patients waiting for LT, and it is unknown whether malnutrition has an impact on the occurrence of postoperative complications. AIM: The study aim was to investigate the value of the controlling nutritional status (CONUT) score and psoas muscle thickness per height (PMTH) in predicting prognosis in LT. METHODS: We retrospectively analyzed the clinical data of 313 patients who underwent classic orthotopic LT from January 2016 to December 2018 in Tianjin First Central Hospital affiliated with Tianjin Medical University. The CONUT score is derived from the preoperative serum albumin and total cholesterol levels, and total lymphocyte count. Patients were divided into low (≤ 4), medium (5-8), and high (9-12) CONUT score groups perioperative characteristics, Clavien-Dindo grade III/IV/V postoperative complications, graft loss and infection, and cumulative postoperative survival in the three groups were compared 3 mo after LT. PMTH was calculated as the ratio of the transverse thickness of the psoas muscle in the umbilical plane to the height of the patient. The cutoff values of receiver operating characteristic curves were determined separately for men and women. The values were 14.1 cm/m2 for women and 17.9 cm/m2 for men. The patients were then divided into low and high PMTH groups by the cutoff values. The comparison of data between the two groups was the same as above. RESULTS: Patients with medium and high CONUT scores had lower preoperative serum hemoglobin, more intraoperative red blood cell (RBC) transfusions, longer postoperative intensive care unit stay and hospital stays, higher 7 and 14 preoperative-day serum bilirubin levels, and a higher incidence of postoperative grade III/IV complications and infections than patients with low CONUT scores. Differences in the 3-mo cumulative survival among the three groups were not significant. Patients with a low PMTH had higher preoperative serum urea nitrogen, more intraoperative packed RBC and frozen plasma transfusions, longer times to postoperative ventilator extubation, higher incidence of total postoperative complications, and a lower 3-mo cumulative survival than those with a high PMTH. CONCLUSION: A CONUT score ≥ 5 and a low PMTH were both associated with poor prognosis in LT. The CONUT score had no predictive value for short-term patient survival after LT, but the PMTH was predictive of short-term patient survival after LT.

P-type Na+/K+ ATPases essential and nonessential for cellular homeostasis and insect pathogenicity of Beauveria bassiana.

ENA1 and ENA2 are P-type IID/ENA Na+/K+-ATPases required for cellular homeostasis in yeasts but remain poorly understood in filamentous fungal insect pathogens. Here, we characterized seven genes encoding five ENA1/2 homologues (ENA1a-c and ENA2a/b) and two P-type IIC/NK Na+/K+-ATPases (NK1/2) in Beauveria bassiana, an insect-pathogenic fungus serving as a main source of fungal insecticides worldwide. Most of these genes were highly responsive to alkaline pH and Na+/K+ cues at transcription level. Cellular Na+, K+ and H+ homeostasis was disturbed only in the absence of ena1a or ena2b. The disturbed homeostasis featured acceleration of vacuolar acidification, elevation of cytosolic Na+/K+ level at pH 5.0 to 9.0, and stabilization of extracellular H+ level to initial pH 7.5 during a 5-day period of submerged incubation. Despite little defect in hyphal growth and asexual development, the Δena1a and Δena2b mutants were less tolerant to metal cations (Na+, K+, Li+, Zn2+, Mn2+ and Fe3+), cell wall perturbation, oxidation, non-cation hyperosmolarity and UVB irradiation, severely compromised in insect pathogenicity via normal cuticle infection, and attenuated in virulence via hemocoel injection. The deletion mutants of five other ENA and NK genes showed little change in vacuolar pH and all examined phenotypes. Therefore, only ENA1a and ENA2b evidently involved in both transmembrane and vacuolar activities are essential for cellular cation homeostasis, insect pathogenicity and multiple stress tolerance in B. bassiana. These findings provide a novel insight into ENA1a- and ENA2b-dependent vacuolar pH stability, cation-homeostatic process and fungal fitness to host insect and environment.

Subtilisin-like Pr1 proteases marking the evolution of pathogenicity in a wide-spectrum insect-pathogenic fungus.

Subtilisin-like Pr1 proteases of insect-pathogenic fungi are a large family of extracellular cuticle-degrading enzymes that presumably determine a capability of hyphal invasion into insect hemocoel through normal cuticle infection, but remain poorly understood although often considered as virulence factors for genetic improvement of fungal potential against pests. Here, we report that not all of 11 Pr1 family members necessarily function in Beauveria bassiana, an ancient wide-spectrum pathogen evolved insect pathogenicity ~200 million years ago. These Pr1 proteases are phylogenetically similar to or distinct from 11 homologues (Pr1A-K) early named in Metarhizium anisopliae complex, a young entomopathogen lineage undergoing molecular evolution toward Pr1 diversification, and hence renamed Pr1A1/A2, Pr1B1-B3, Pr1 C, Pr1F1-F4,4 and Pr1 G, respectively. Multiple analyses of all single gene-deleted and rescued mutants led to the recognition of five conserved members (Pr1C, Pr1G, Pr1A2, Pr1B1, and Pr1B2) contributing significantly to the fungal pathogenicity to insect. The conserved Pr1 proteases were proven to function only in cuticle degradation, individually contribute 19-29% to virulence, but play no role in post-infection cellular events critical for fungal killing action. Six other Pr1 proteases were not functional at all in either cuticle degradation during host infection or virulence-related cellular events post-infection. Therefore, only the five conserved proteases are collectively required for, and hence mark evolution of, insect pathogenicity in B. bassiana. These findings provide the first referable base for insight into the evolution of Pr1 family members in different lineages of fungal insect pathogens.

Solid pseudopapillary neoplasm (SPN) of the pancreas presenting with ascites misdiagnosed as pancreatic tuberculosis: a case report and literature review.

INTRODUCTION: Solid pseudopapillary neoplasm (SPN) is a rare pancreatic tumor that mainly affects young women. It is a low-grade malignant neoplasm, with an excellent prognosis after surgical treatment. We report herein a case of SPN presenting with ascites that was misdiagnosed as pancreatic tuberculosis (TB). CASE REPORT: A 16-year-old female initially presented with a large volume of ascites. Contrast-enhanced ultrasound and computed tomography found a heterogeneous lesion in the pancreatic body, which had slight contrast enhancement on the arterial phase. Analysis of ascites showed it was exudative. Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) of the mass only revealed a few blood clots. The diagnosis was highly suggestive of a pancreatic TB. However, after 6 months of anti-TB therapy, the pancreatic lesion remained essentially unchanged. Subsequently, magnetic resonance imaging indicated a mixed solid and cystic lesion with a well-defined margin in the pancreatic body. Further EUS-FNA showed monomorphic neoplastic cells with papillary architecture and immunohistochemical analysis revealed that the tumor cells were positive for ß-catenin, CD10, vimentin, cytokeratin, and synaptophysin. These findings were consistent with SPN. After distal pancreatectomy with splenectomy, postoperative pathology and immunohistochemical staining confirmed the diagnosis of SPN. CONCLUSION: Clinicians should consider the possibility of SPN for pancreatic heterogeneous masses. Multiple diagnostic imaging modalities and EUS-FNA may contribute to the preoperative diagnosis of this disease.

The DUF1996 and WSC domain-containing protein Wsc1I acts as a novel sensor of multiple stress cues in Beauveria bassiana.

Wsc1I homologues featuring both an N-terminal DUF1996 (domain of unknown function 1996) and a C-terminal WSC (cell wall stress-responsive component) domain exist in filamentous fungi but have never been functionally characterized. Here, Wsc1I is shown to localize in the vacuoles and cell wall/membrane of the insect mycopathogen Beauveria bassiana and hence linked to cell membrane- and vacuole-related cellular events. In B. bassiana, deletion of Wsc1I resulted in marked increases of hyphal and conidial sensitivities to hyperosmotic agents, oxidants, cell wall perturbing chemicals, and metal cations (Cu2+ , Zn2+ , Fe2+ , and Mg2+ ) despite slight impact on normal growth and conidiation. Conidia produced by the deletion mutant showed not only reduced tolerance to both 45°C heat and UVB irradiation but also attenuated virulence to a susceptible insect through normal cuticle infection or cuticle-bypassing infection. Importantly, phosphorylation of the mitogen-activated protein kinase Hog1 was largely attenuated or nearly abolished in the Wsc1I-free cells triggered with hyperosmotic, oxidative, or cell wall perturbing stress. All changes were well restored by targeted gene complementation. Our findings highlight a novel role of Wsc1I in sensing multiple stress cues upstream of the Hog1 signalling pathway and its pleiotropic effects in B. bassiana.

Downregulation of VEGFA inhibits proliferation, promotes apoptosis, and suppresses migration and invasion of renal clear cell carcinoma.

OBJECTIVE: The aim of this study was to investigate the effects of vascular endothelial growth factor A (VEGFA) on cell proliferation, apoptosis, migration, and invasion in renal clear cell carcinoma (RCCC). METHODS: Between June 2012 and June 2015, RCCC tissues were obtained for the experimental group, and RCCC adjacent tumor-free kidney parenchyma tissues were obtained for the control group. VEGFA mRNA and protein expressions and phosphoinositide 3-kinase, serine/threonine-specific protein kinase (AKT), and phosphorylated-AKT protein expressions were detected. The chemically synthesized specific siRNA using RNA interference technology was used to inhibit VEGFA gene expression in human RCCC 786-O cells. The negative control (NC) group was transfected with NC sequence, and the blank group was transfected with no sequence. Flow cytometry, scratch test, and cell-penetrating experiment were used to detect cell proliferation, apoptosis, migration, and invasion of 786-O cells. RESULTS: Positive expression of VEGFA protein was 60.62% in RCCC tissue and 18.34% in adjacent tissue with statistically significant difference (P<0.001). VEGFA protein and mRNA expressions were higher in RCCC tissue than those in adjacent tissue (both P<0.01). VEGF expression in RCCC tissue was associated with Fuhrman grading and American Joint Committee on Cancer staging (both P<0.05). After RCCC 786-O cells transfecting the VEGFA siRNA, the VEGFA mRNA and protein expressions and phosphoinositide 3-kinase and phosphorylated-AKT protein expressions were significantly decreased, cell proliferation was remarkably inhibited, cell apoptotic ratio was obviously increased, and migration distance and invasive cell number were markedly decreased compared to those in the NC group and the blank group (all P<0.05). CONCLUSION: Inhibition of VEGFA inhibited proliferation, promoted apoptosis, and suppressed migration and invasion of RCCC 786-O cells. VEGF has a potential role in diagnosis and therapy of RCCC.

Proteomic Analysis of Embryonic and Young Human Vitreous.

PURPOSE: The proteomic profile of vitreous from second-trimester human embryos and young adults was characterized using mass spectrometry and analyzed for changes in protein levels that may relate to structural changes occurring during this time. This vitreous proteome was compared to previous reports to confirm proteins already identified and reveal novel ones. METHODS: Vitreous from 17 human embryos aged 14 to 20 weeks gestation (WG) and from a 12-, a 14-, a 15-, and a 28-year-old was individually analyzed using tandem mass spectrometry-based proteomics. Peptide spectral count associations with embryonic age were assessed using a general linear model of fold changes and Spearman's rank correlation. Differences between embryonic and young adult vitreous proteomes were also compared. Immunohistochemistry was used to evaluate three proteins in five additional fetal (10-18 WG) human eyes. RESULTS: There were 1217 proteins identified in fetal and young adult human vitreous, 206 after quantile normalization and variance filtering. In embryos, the peptide counts of 37 proteins changed significantly from 14 to 20 WG: 75.7% increased, 24.3% decreased. Immunohistochemistry confirmed the absence of clusterin and cadherin in 10 and 14 WG eyes and their presence at 18 WG. Comparing embryonic to young adult vitreous, 47 proteins were significantly higher or lower. A total of 768 proteins not previously identified in the literature are presented. CONCLUSIONS: Proteins previously unreported in the human vitreous were identified. The human vitreous proteome undergoes significant changes during embryogenesis and young adulthood. A number of protein levels change considerably during the second trimester, with the majority decreasing.

Intraocular hemorrhage causes retinal vascular dysfunction via plasma kallikrein.

PURPOSE: Retinal hemorrhages occur in a variety of sight-threatening conditions including ocular trauma, high altitude retinopathy, and chronic diseases such as diabetic and hypertensive retinopathies. The goal of this study is to investigate the effects of blood in the vitreous on retinal vascular function in rats. METHODS: Intravitreal injections of autologous blood, plasma kallikrein (PK), bradykinin, and collagenase were performed in Sprague-Dawley and Long-Evans rats. Retinal vascular permeability was measured using vitreous fluorophotometry and Evans blue dye permeation. Leukostasis was measured by fluorescein isothiocyanate-coupled concanavalin A lectin and acridine orange labeling. Retinal hemorrhage was examined on retinal flatmounts. Primary cultures of bovine retinal pericytes were cultured in the presence of 25 nM PK for 24 hours. The pericyte-conditioned medium was collected and the collagen proteome was analyzed by tandem mass spectrometry. RESULTS: Intravitreal injection of autologous blood induced retinal vascular permeability and retinal leukostasis, and these responses were ameliorated by PK inhibition. Intravitreal injections of exogenous PK induced retinal vascular permeability, leukostasis, and retinal hemorrhage. Proteomic analyses showed that PK increased collagen degradation in pericyte-conditioned medium and purified type IV collagen. Intravitreal injection of collagenase mimicked PK's effect on retinal hemorrhage. CONCLUSIONS: Intraocular hemorrhage increases retinal vascular permeability and leukostasis, and these responses are mediated, in part, via PK. Intravitreal injections of either PK or collagenase, but not bradykinin, induce retinal hemorrhage in rats. PK exerts collagenase-like activity that may contribute to blood-retinal barrier dysfunction.

Hyperglycemia-induced cerebral hematoma expansion is mediated by plasma kallikrein.

Hyperglycemia is associated with greater hematoma expansion and poor clinical outcomes after intracerebral hemorrhage. We show that cerebral hematoma expansion triggered by intracerebral infusion of autologous blood is greater in diabetic rats and mice compared to nondiabetic controls and that this augmented expansion is ameliorated by plasma kallikrein (PK) inhibition or deficiency. Intracerebral injection of purified PK augmented hematoma expansion in both diabetic and acutely hyperglycemic rats, whereas injection of bradykinin, plasmin or tissue plasminogen activator did not elicit such a response. This response, which occurs rapidly, was prevented by co-injection of the glycoprotein VI agonist convulxin and was mimicked by glycoprotein VI inhibition or deficiency, implicating an effect of PK on inhibiting platelet aggregation. We show that PK inhibits collagen-induced platelet aggregation by binding collagen, a response enhanced by elevated glucose concentrations. The effect of hyperglycemia on hematoma expansion and PK-mediated inhibition of platelet aggregation could be mimicked by infusing mannitol. These findings suggest that hyperglycemia augments cerebral hematoma expansion by PK-mediated osmotic-sensitive inhibition of hemostasis.

Waterlogging and salinity effects on two Suaeda salsa populations.

Adaptations to combined salinity and waterlogging stress were evaluated in two Suaeda salsa populations from different saline environments. Seedlings were exposed to 1, 200 and 600 mM NaCl in drained or waterlogged sand for 22 days in a glasshouse. Waterlogging did not significantly affect the K(+) /Na(+) ratio or Cl(-) concentration in leaves of either population. Adventitious roots were produced only by the inland population and under the waterlogged condition. X-ray microanalysis showed that S. salsa roots of the intertidal population accumulated more [Na(+) ] and [Cl(-) ] in both the cortex and stele than the roots of the inland population. The ability of roots to exclude Na(+) and Cl(-) was greater in the intertidal population than in the inland population, which may explain why leaves of the intertidal population accumulated less Na(+) and Cl(-) than the leaves of the inland population. The lower level of Cl(-) than Na(+) in leaves of both populations may result from the greater ability of roots to exclude Cl(-) than Na(+) . These traits may help the two S. salsa populations adapt to their different saline environments.

Vitreous proteomics and diabetic retinopathy.

Diabetic retinopathy is the major cause of acquired blindness in working-age adults. Studies of the vitreous proteome have provided insights into the etiology of diabetic retinopathy and suggested potential molecular targets for treatments. Further characterization of the protein changes associated with the progression of this disease may suggest additional therapeutic approaches as well as reveal novel factors that may be useful in predicting risk and functional outcomes of interventional therapies. This article provides an overview of the various techniques used for proteomic analysis of the vitreous and details results from various studies evaluating vitreous of diabetic patients using the proteomic approach.

Proteomic identification of novel plasma kallikrein substrates in the astrocyte secretome.

Plasma kallikrein (PK) is activated during hemorrhage and has been implicated in cerebral vascular permeability and edema. To further characterize the potential effects of PK on the brain that may follow cerebral vascular injury, we have utilized a proteomics approach to search for novel PK substrates in the astrocyte secretome. Extracellular proteins released by astrocytes are critical mediators of cerebral homeostasis, including roles in synapse function and vascular integrity. We identified 1,108 proteins in astrocyte condition medium and 295 of these were annotated as secreted proteins. The total abundance of nine proteins was changed after treatment with PK. Characterization of the secreted proteins revealed low molecular weight fragments for 59 proteins in conditioned media exposed to PK that were not observed in untreated controls. The most striking finding from this study was the appearance of fragmentation of 26 extracellular matrix-associated proteins including collagen isoforms 1-6 and11, nidogen-1 and -2, lysyl oxidase-like protein 1, and matrix metalloproteinase 19 in the presence of PK. We also demonstrated that PK induced the fragmentation of non-matrix proteins, including apolipoprotein E. This report further characterizes the astrocyte secretome and identifies novel potential targets of PK-induced proteolysis that may contribute to its effects on the brain following vascular injury.

Angiotensin AT1 receptor antagonism ameliorates murine retinal proteome changes induced by diabetes.

Diabetic retinopathy is the most common microvascular complication caused by diabetes mellitus and is a leading cause of vision loss among working-age adults in developed countries. Understanding the effects of diabetes on the retinal proteome may provide insights into factors and mechanisms responsible for this disease. We have performed a comprehensive proteomic analysis and comparison of retina from C57BL/6 mice with 2 months of streptozotocin-induced diabetes and age-matched nondiabetic control mice. To explore the role of the angiotensin AT1 receptor in the retinal proteome in diabetes, a subgroup of mice were treated with the AT1 antagonist candesartan. We identified 1792 proteins from retinal lysates, of which 65 proteins were differentially changed more than 2-fold in diabetic mice compared with nondiabetic mice. A majority (72%) of these protein changes were normalized by candesartan treatment. Most of the significantly changed proteins were associated with metabolism, oxidative phosphorylation, and apoptotic pathways. An analysis of the proteomics data revealed metabolic and apoptotic abnormalities in the retina from diabetic mice that were ameliorated with candesartan treatment. These results provide insight into the effects of diabetes on the retina and the role of the AT1 receptor in modulating this response.

Detection of unsaturated disaccharides, pyridinoline, and hydroxyproline in urine of patients with Kashin-Beck disease: comparison with controls in an endemic area.

OBJECTIVE: To investigate the pathologic status of adult patients with Kashin-Beck disease (KBD) in an endemic area of China through detection of 5 biochemical markers in their urine, and to study the correlations between these markers and KBD. METHODS: A total of 55 patients with KBD over age 40 years were recruited and divided into groups, Grade 1 and Grade 2, according to clinical diagnosis criteria for KBD and our inclusion criteria; 25 healthy persons were enrolled into a control group. The first-time urine of the 80 participants was collected in the morning. Three unsaturated disaccharides, pyridinoline (PYD), and hydroxyproline (HYP) were detected in urine samples with high performance liquid chromatography, ELISA, and a chemical kit. Mean levels of these markers were compared in the 3 groups. RESULTS: The mean concentrations of 3 unsaturated disaccharides and PYD in the Grade 2 group were significantly higher than levels in the Grade 1 group and controls (p<0.05). There was no significant difference between findings in the Grade 1 group and controls. Levels of 3 unsaturated disaccharides correlated with each other (p<0.01). The correlation coefficient between PYD and HYP was 0.470 (p<0.01). Except for HYP, the other markers all correlated with grade of KBD, rather than age or sex of subjects. CONCLUSION: The cartilage degradation of patients with Grade 2 KBD was more severe than that of Grade 1 patients and controls. The pathologic condition of Grade 1 patients was mild. Except for HYP, the markers we investigated specifically reflected the pathologic bone metabolism of adult patients with KBD. Trial registration number ChiCTR-TRC-00000140.