The microRNA408-plantacyanin module balances plant growth and drought resistance by regulating reactive oxygen species homeostasis in guard cells.

The conserved microRNA (miRNA) miR408 enhances photosynthesis and compromises stress tolerance in multiple plants, but the cellular mechanism underlying its function remains largely unclear. Here, we show that in Arabidopsis (Arabidopsis thaliana), the transcript encoding the blue copper protein PLANTACYANIN (PCY) is the primary target for miR408 in vegetative tissues. PCY is preferentially expressed in the guard cells, and PCY is associated with the endomembrane surrounding individual chloroplasts. We found that the MIR408 promoter is suppressed by multiple abscisic acid (ABA)-responsive transcription factors, thus allowing PCY to accumulate under stress conditions. Genetic analysis revealed that PCY elevates reactive oxygen species (ROS) levels in the guard cells, promotes stomatal closure, reduces photosynthetic gas exchange, and enhances drought resistance. Moreover, the miR408-PCY module is sufficient to rescue the growth and drought tolerance phenotypes caused by gain- and loss-of-function of MYB44, an established positive regulator of ABA responses, indicating that the miR408-PCY module relays ABA signaling for regulating ROS homeostasis and drought resistance. These results demonstrate that miR408 regulates stomatal movement to balance growth and drought resistance, providing a mechanistic understanding of why miR408 is selected during land plant evolution and insights into the long-pursued quest of breeding drought-tolerant and high-yielding crops.

Adhesin domains responsible for binding bacteria to surfaces they colonize project outwards from companion split domains.

Bacterial adhesins attach their hosts to surfaces that the bacteria will colonize. This surface adhesion occurs through specific ligand-binding domains located towards the distal end of the long adhesin molecules. However, recognizing which of the many adhesin domains are structural and which are ligand binding has been difficult up to now. Here we have used the protein structure modeling program AlphaFold2 to predict structures for these giant 0.2- to 1.5-megadalton proteins. Crystal structures previously solved for several adhesin regions are in good agreement with the models. Whereas most adhesin domains are linked in a linear fashion through their N- and C-terminal ends, ligand-binding domains can be recognized by budding out from a companion core domain so that their ligand-binding sites are projected away from the axis of the adhesin for maximal exposure to their targets. These companion domains are "split" in their continuity by projecting the ligand-binding domain outwards. The "split domains" are mostly ß-sandwich extender modules, but other domains like a ß-solenoid can serve the same function. Bioinformatic analyses of Gram-negative bacterial sequences revealed wide variety ligand-binding domains are used in their Repeats-in-Toxin adhesins. The ligands for many of these domains have yet to be identified but known ligands include various cell-surface glycans, proteins, and even ice. Recognizing the ligands to which the adhesins bind could lead to ways of blocking colonization by bacterial pathogens. Engineering different ligand-binding domains into an adhesin has the potential to change the surfaces to which bacteria bind.

Fungal Prenyltransferase AnaPT and Its F265 Mutants Catalyze the Dimethylallylation at the Nonaromatic Carbon of Phloretin.

Phloretin is widely found in fruit and shows various biological activities. Here, we demonstrate the dimethylallylation, geranylation, and farnesylation, particularly the first dimethylallylation at the nonaromatic carbon of phloretin (1) by the fungal prenyltransferase AnaPT and its mutants. F265 was identified as a key amino acid residue related to dimethylallylation at the nonaromatic carbon of phloretin. Mutants AnaPT_F265D, AnaPT_F265G, AnaPT_F265P, AnaPT_F265C, and AnaPT_F265Y were discovered to generally increase prenylation activity toward 1. AnaPT_F265G catalyzes the O-geranylation selectively at the C-2' hydroxyl group, which involves an intramolecular hydrogen bond with the carbonyl group of 1. Seven products, 1D5, 1D7-1D9, 1G2, 1G4, and 1F2, have not been reported prior to this study. Twelve compounds, 1D3-1D9, 1G1-1G3, and 1F1-1F2, exhibited potential inhibitory effects on α-glucosidase with IC50 values ranging from 11.45 ± 0.87 to 193.80 ± 6.52 µg/mL. Among them, 1G1 with an IC50 value of 11.45 ± 0.87 µg/mL was the most potential α-glucosidase inhibitor, which is about 30 times stronger than the positive control acarbose with an IC50 value of 346.63 ± 15.65 µg/mL.

A transcription factor complex in Dictyostelium enables adaptive changes in macropinocytosis during the growth-to-development transition.

Macropinocytosis, an evolutionarily conserved endocytic pathway, mediates nonselective bulk uptake of extracellular fluid. It is the primary route for axenic Dictyostelium cells to obtain nutrients and has also emerged as a nutrient-scavenging pathway for mammalian cells. How cells adjust macropinocytic activity in various physiological or developmental contexts remains to be elucidated. We discovered that, in Dictyostelium cells, the transcription factors Hbx5 and MybG form a functional complex in the nucleus to maintain macropinocytic activity during the growth stage. In contrast, during starvation-induced multicellular development, the transcription factor complex undergoes nucleocytoplasmic shuttling in response to oscillatory cyclic adenosine 3',5'-monophosphate (cAMP) signals, which leads to increased cytoplasmic retention of the complex and progressive downregulation of macropinocytosis. Therefore, by coupling macropinocytosis-related gene expression to the cAMP oscillation system, which facilitates long-range cell-cell communication, the dynamic translocation of the Hbx5-MybG complex orchestrates a population-level adjustment of macropinocytic activity to adapt to changing environmental conditions.

Arabidopsis G-protein ß subunit AGB1 represses abscisic acid signaling via attenuation of the MPK3-VIP1 phosphorylation cascade.

Heterotrimeric G proteins play key roles in cellular processes. Although phenotypic analyses of Arabidopsis Gß (AGB1) mutants have implicated G proteins in abscisic acid (ABA) signaling, the AGB1-mediated modules involved in ABA responses remain unclear. We found that a partial AGB1 protein was localized to the nucleus where it interacted with ABA-activated VirE2-interacting protein 1 (VIP1) and mitogen-activated protein kinase 3 (MPK3). AGB1 acts as an upstream negative regulator of VIP1 activity by initiating responses to ABA and drought stress, and VIP1 regulates the ABA signaling pathway in an MPK3-dependent manner in Arabidopsis. AGB1 outcompeted VIP1 for interaction with the C-terminus of MPK3, and prevented phosphorylation of VIP1 by MPK3. Importantly, ABA treatment reduced AGB1 expression in the wild type, but increased in vip1 and mpk3 mutants. VIP1 associates with ABA response elements present in the AGB1 promoter, forming a negative feedback regulatory loop. Thus, our study defines a new mechanism for fine-tuning ABA signaling through the interplay between AGB1 and MPK3-VIP1. Furthermore, it suggests a common G protein mechanism to receive and transduce signals from the external environment.

PANI/MCM-41 adsorption for removal of Cr(VI) ions and its application in enhancing electrokinetic remediation of Cr(VI)-contaminated soil.

In this study, a polyaniline/mesoporous silica (PANI/MCM-41) composite material that can be used as a filler for permeable reactive barrier (PRB) was prepared by in situ polymerization. Firstly, the adsorption capacity of PANI/MCM-41 on Cr (VI) in solution was investigated. The results show that the prepared PANI/MCM-41 exhibits a significant Cr (VI) adsorption capacity (~ 340 mg/g), and the adsorption process is more accurately described by the Langmuir isotherm and pseudo-second-order kinetic model. The thermodynamic functions evidenced that the Cr(VI) adsorption was an endothermic spontaneous process. In addition, adsorption-desorption cycle experiments proved the excellent reusability of the material. Subsequently, the material was utilized as a filler in the PRB for the remediation of Cr(VI)-contaminated soil using electrokinetic-permeable reactive barrier (EK-PRB) technology. The results show that compared with traditional electrokinetic remediation, the use of PANI/MCM-41 as an active filler can enlarge the current during remediation and enhance the conductivity of soil, which increases the removal rates of total Cr and Cr(VI) in soil (17.4% and 10.2%).

Development and validation of a risk prediction model for osteoporosis in elderly patients with type 2 diabetes mellitus: a retrospective and multicenter study.

BACKGROUND: This study aimed to construct a risk prediction model to estimate the odds of osteoporosis (OP) in elderly patients with type 2 diabetes mellitus (T2DM) and evaluate its prediction efficiency. METHODS: This study included 21,070 elderly patients with T2DM who were hospitalized at six tertiary hospitals in Southwest China between 2012 and 2022. Univariate logistic regression analysis was used to screen for potential influencing factors of OP and least absolute shrinkage. Further, selection operator regression (LASSO) and multivariate logistic regression analyses were performed to select variables for developing a novel predictive model. The area under the receiver operating characteristic curve (AUROC), calibration curve, decision curve analysis (DCA), and clinical impact curve (CIC) were used to evaluate the performance and clinical utility of the model. RESULTS: The incidence of OP in elderly patients with T2DM was 7.01% (1,476/21,070). Age, sex, hypertension, coronary heart disease, cerebral infarction, hyperlipidemia, and surgical history were the influencing factors. The seven-variable model displayed an AUROC of 0.713 (95% confidence interval [CI]:0.697-0.730) in the training set, 0.716 (95% CI: 0.691-0.740) in the internal validation set, and 0.694 (95% CI: 0.653-0.735) in the external validation set. The optimal decision probability cut-off value was 0.075. The calibration curve (bootstrap = 1,000) showed good calibration. In addition, the DCA and CIC demonstrated good clinical practicality. An operating interface on a webpage ( https://juntaotan.shinyapps.io/osteoporosis/ ) was developed to provide convenient access for users. CONCLUSIONS: This study constructed a highly accurate model to predict OP in elderly patients with T2DM. This model incorporates demographic characteristics and clinical risk factors and may be easily used to facilitate individualized prediction.

Microspore-expressed SCULP1 is required for p-coumaroylation of sporopollenin, exine integrity, and pollen development in wheat.

Sporopollenin is one of the most structurally sophisticated and chemically recalcitrant biopolymers. In higher plants, sporopollenin is the dominant component of exine, the outer wall of pollen grains, and contains covalently linked phenolics that protect the male gametes from harsh environments. Although much has been learned about the biosynthesis of sporopollenin precursors in the tapetum, the nutritive cell layer surrounding developing microspores, little is known about how the biopolymer is assembled on the microspore surface. We identified SCULP1 (SKS clade universal in pollen) as a seed plant conserved clade of the multicopper oxidase family. We showed that SCULP1 in common wheat (Triticum aestivum) is specifically expressed in the microspore when sporopollenin assembly takes place, localized to the developing exine, and binds p-coumaric acid in vitro. Through genetic, biochemical, and 3D reconstruction analyses, we demonstrated that SCULP1 is required for p-coumaroylation of sporopollenin, exine integrity, and pollen viability. Moreover, we found that SCULP1 accumulation is compromised in thermosensitive genic male sterile wheat lines and its expression partially restored exine integrity and male fertility. These findings identified a key microspore protein in autonomous sporopollenin polymer assembly, thereby laying the foundation for elucidating and engineering sporopollenin biosynthesis.

Analysis of the Dose-Response Relationship Between the International Normalized Ratio and Hepatic Encephalopathy in Patients With Liver Cirrhosis Using Restricted Cubic Spline Functions.

Background: The International Normalized Ratio (INR) is significantly associated with Hepatic Encephalopathy (HE) in patients with liver cirrhosis. However, the dose-response relationship between continuous INR changes and HE risk has not been clearly defined. Thus, our goal was to explore the continuous relationship between HE and INR among patients hospitalized with liver cirrhosis and to evaluate the role of the INR as a risk factor for HE in these patients. Methods: A total of 6,266 people were extracted from the Big Data Platform of the Medical Data Research Institute of Chongqing Medical University. In this study, unconditional logistic regression and restricted cubic spline (RCS) model were used to analyze the dose-response association of INR with HE. Alcoholic liver disease, smoking status, and drinking status were classified for subgroup analysis. Results: The prevalence of HE in the study population was 8.36%. The median INR was 1.4. After adjusting for alcoholic liver disease, age, smoking status, drinking status, total bilirubin, neutrophil percentage, total hemoglobin, aspartate aminotransferase, serum sodium, albumin, lymphocyte percentage, serum creatinine, red blood cell, and white blood cell, multivariate logistic regression analysis revealed that INR ≥ 1.5 (OR = 2.606, 95% CI: 2.072-3.278) was significantly related to HE risk. The RCS model showed a non-linear relationship between the INR and HE (non-linear test, χ2 = 30.940, P < 0.001), and an increased INR was an independent and adjusted dose-dependent risk factor for HE among patients with liver cirrhosis. Conclusion: This finding could guide clinicians to develop individualized counseling programs and treatments for patients with HE based on the INR risk stratification.

The carboxy terminal transmembrane domain of SPL7 mediates interaction with RAN1 at the endoplasmic reticulum to regulate ethylene signalling in Arabidopsis.

In Arabidopsis, copper (Cu) transport to the ethylene receptor ETR1 mediated using RAN1, a Cu transporter located at the endoplasmic reticulum (ER), and Cu homeostasis mediated using SPL7, the key Cu-responsive transcription factor, are two deeply conserved vital processes. However, whether and how the two processes interact to regulate plant development remain elusive. We found that its C-terminal transmembrane domain (TMD) anchors SPL7 to the ER, resulting in dual compartmentalisation of the transcription factor. Immunoprecipitation coupled mass spectrometry, yeast-two-hybrid assay, luciferase complementation imaging and subcellular co-localisation analyses indicate that SPL7 interacts with RAN1 at the ER via the TMD. Genetic analysis revealed that the ethylene-induced triple response was significantly compromised in the spl7 mutant, a phenotype rescuable by RAN1 overexpression but not by SPL7 without the TMD. The genetic interaction was corroborated by molecular analysis showing that SPL7 modulates RAN1 abundance in a TMD-dependent manner. Moreover, SPL7 is feedback regulated by ethylene signalling via EIN3, which binds the SPL7 promoter and represses its transcription. These results demonstrate that ER-anchored SPL7 constitutes a cellular mechanism to regulate RAN1 in ethylene signalling and lay the foundation for investigating how Cu homeostasis conditions ethylene sensitivity in the developmental context.

The PCY-SAG14 phytocyanin module regulated by PIFs and miR408 promotes dark-induced leaf senescence in Arabidopsis.

Leaf senescence is a critical process in plants and has a direct impact on many important agronomic traits. Despite decades of research on senescence-altered mutants via forward genetics and functional assessment of senescence-associated genes (SAGs) via reverse genetics, the senescence signal and the molecular mechanism that perceives and transduces the signal remain elusive. Here, using dark-induced senescence (DIS) of Arabidopsis leaf as the experimental system, we show that exogenous copper induces the senescence syndrome and transcriptomic changes in light-grown plants parallel to those in DIS. By profiling the transcriptomes and tracking the subcellular copper distribution, we found that reciprocal regulation of plastocyanin, the thylakoid lumen mobile electron carrier in the Z scheme of photosynthetic electron transport, and SAG14 and plantacyanin (PCY), a pair of interacting small blue copper proteins located on the endomembrane, is a common thread in different leaf senescence scenarios, including DIS. Genetic and molecular experiments confirmed that the PCY-SAG14 module is necessary and sufficient for promoting DIS. We also found that the PCY-SAG14 module is repressed by a conserved microRNA, miR408, which in turn is repressed by phytochrome interacting factor 3/4/5 (PIF3/4/5), the key trio of transcription factors promoting DIS. Together, these findings indicate that intracellular copper redistribution mediated by PCY-SAG14 has a regulatory role in DIS. Further deciphering the copper homeostasis mechanism and its interaction with other senescence-regulating pathways should provide insights into our understanding of the fundamental question of how plants age.

Similar long-term survival after isolated bioprosthetic versus mechanical aortic valve replacement: A propensity-matched analysis.

OBJECTIVES: Improved durability and preference to avoid anticoagulation have led to increasing use of bioprostheses in younger patients despite the need for eventual reoperation. Therefore, we compared in-hospital complications, reoperation, and survival after bioprosthetic and mechanical aortic valve replacement. METHODS: From January 1990 to January 2020, 6143 patients underwent isolated aortic valve replacement at Cleveland Clinic; 637 patients received a mechanical prosthesis and 5506 a bioprosthesis. Propensity matching identified 527 well-matched pairs (83% of possible matches) for comparison of perioperative outcomes. The average age of patients was 54 years in the bioprosthesis group and 55 years in the mechanical prosthesis group. Random Forest machine-learning analysis was performed to compare survival using the entire cohort of 6143 patients. RESULTS: Among matched patients, major in-hospital complications, including stroke, deep sternal wound infection, and reoperation for bleeding, were similar, as was in-hospital mortality (2 in the bioprosthesis group [0.38%] vs 3 in the mechanical prosthesis group [0.57%]; P > .9). Patients receiving a bioprosthesis had shorter hospital stays (median 6 vs 7 days, P < .0001). Fifty-one patients (32% at 14 years) in the bioprosthesis group and 17 patients in the mechanical prosthesis group (8% at 14 years) underwent reoperation (P [log-rank] < .0001); 5-year survival after reoperation was 85% versus 82% (P = .6). Risk-adjusted Random Forest prediction of 18-year survival was 60% in the bioprosthetic group and 58% in the mechanical prosthesis group. CONCLUSIONS: Aortic valve bioprostheses are associated with excellent short-term outcomes and 18-year survival similar to that of patients receiving mechanical valves. Reoperation does not adversely affect survival. These results suggest that risk for reoperation alone should not deter the use of bioprostheses in younger patients.

Structural and Functional Analyses of Hub MicroRNAs in An Integrated Gene Regulatory Network of Arabidopsis.

MicroRNAs (miRNAs) are trans-acting small regulatory RNAs that work coordinately with transcription factors (TFs) to shape the repertoire of cellular mRNAs available for translation. Despite our growing knowledge of individual plant miRNAs, their global roles in gene regulatory networks remain mostly unassessed. Based on interactions obtained from public databases and curated from the literature, we reconstructed an integrated miRNA network in Arabidopsis that includes 66 core TFs, 318 miRNAs, and 1712 downstream genes. We found that miRNAs occupy distinct niches and enrich miRNA-containing feed-forward loops (FFLs), particularly those with miRNAs as intermediate nodes. Further analyses revealed that miRNA-containing FFLs coordinate TFs located in different hierarchical layers and that intertwined miRNA-containing FFLs are associated with party and date miRNA hubs. Using the date hub MIR858A as an example, we performed detailed molecular and genetic analyses of three interconnected miRNA-containing FFLs. These analyses revealed individual functions of the selected miRNA-containing FFLs and elucidated how the date hub miRNA fulfills multiple regulatory roles. Collectively, our findings highlight the prevalence and importance of miRNA-containing FFLs, and provide new insights into the design principles and control logics of miRNA regulatory networks governing gene expression programs in plants.

Predictive model for diabetic retinopathy under limited medical resources: A multicenter diagnostic study.

Background: Comprehensive eye examinations for diabetic retinopathy is poorly implemented in medically underserved areas. There is a critical need for a widely available and economical tool to aid patient selection for priority retinal screening. We investigated the possibility of a predictive model for retinopathy identification using simple parameters. Methods: Clinical data were retrospectively collected from 4, 159 patients with diabetes admitted to five tertiary hospitals. Independent predictors were identified by univariate analysis and least absolute shrinkage and selection operator (LASSO) regression, and a nomogram was developed based on a multivariate logistic regression model. The validity and clinical practicality of this nomogram were assessed using concordance index (C-index), area under the receiver operating characteristic curve (AUROC), calibration curves, decision curve analysis (DCA), and clinical impact curves (CIC). Results: The predictive factors in the multivariate model included the duration of diabetes, history of hypertension, and cardiovascular disease. The three-variable model displayed medium prediction ability with an AUROC of 0.722 (95%CI 0.696-0.748) in the training set, 0.715 (95%CI 0.670-0.754) in the internal set, and 0.703 (95%CI 0.552-0.853) in the external dataset. DCA showed that the threshold probability of DR in diabetic patients was 17-55% according to the nomogram, and CIC also showed that the nomogram could be applied clinically if the risk threshold exceeded 30%. An operation interface on a webpage (https://cqmuxss.shinyapps.io/dr_tjj/) was built to improve the clinical utility of the nomogram. Conclusions: The predictive model developed based on a minimal amount of clinical data available to diabetic patients with restricted medical resources could help primary healthcare practitioners promptly identify potential retinopathy.

The PIF1-miR408-PLANTACYANIN repression cascade regulates light-dependent seed germination.

Light-dependent seed germination is a vital process for many seed plants. A decisive event in light-induced germination is degradation of the central repressor PHYTOCHROME INTERACTING FACTOR 1 (PIF1). The balance between gibberellic acid (GA) and abscisic acid (ABA) helps to control germination. However, the cellular mechanisms linking PIF1 turnover to hormonal balancing remain elusive. Here, employing far-red light-induced Arabidopsis thaliana seed germination as the experimental system, we identified PLANTACYANIN (PCY) as an inhibitor of germination. It is a blue copper protein associated with the vacuole that is both highly expressed in mature seeds and rapidly silenced during germination. Molecular analyses showed that PIF1 binds to the miR408 promoter and represses miR408 accumulation. This in turn posttranscriptionally modulates PCY abundance, forming the PIF1-miR408-PCY repression cascade for translating PIF1 turnover to PCY turnover during early germination. Genetic analysis, RNA-sequencing, and hormone quantification revealed that PCY is necessary and sufficient to maintain the PIF1-mediated seed transcriptome and the low-GA-high-ABA state. Furthermore, we found that PCY domain organization and regulation by miR408 are conserved features in seed plants. These results revealed a cellular mechanism whereby PIF1-relayed external light signals are converted through PCY turnover to internal hormonal profiles for controlling seed germination.

MicroRNA-29a inhibits glioblastoma stem cells and tumor growth by regulating the PDGF pathway.

BACKGROUND AND PURPOSE: microRNAs are small noncoding RNAs that play important roles in cancer regulation. In this study, we investigated the expression, functional effects and mechanisms of action of microRNA-29a (miR-29a) in glioblastoma (GBM). METHODS: miR-29a expression levels in GBM cells, stem cells (GSCs) and human tumors as well as normal astrocytes and normal brain were measured by quantitative PCR. miR-29a targets were uncovered by target prediction algorithms, and verified by immunoblotting and 3' UTR reporter assays. The effects of miR-29a on cell proliferation, death, migration and invasion were assessed with cell counting, Annexin V-PE/7AAD flow cytometry, scratch assay and transwell assay, respectively. Orthotopic xenografts were used to determine the effects of miR-29a on tumor growth. RESULTS: Mir-29a was downregulated in human GBM specimens, GSCs and GBM cell lines. Exogenous expression of miR-29a inhibited GSC and GBM cell growth and induced apoptosis. miR-29a also inhibited GBM cell migration and invasion. PDGFC and PDGFA were uncovered and validated as direct targets of miR-29a in GBM. miR-29a downregulated PDGFC and PDGFA expressions at the transcriptional and translational levels. PDGFC and PDGFA expressions in GBM tumors, GSCs, and GBM established cell lines were higher than in normal brain and human astrocytes. Mir-29a expression inhibited orthotopic GBM xenograft growth. CONCLUSIONS: miR-29a is a tumor suppressor miRNA in GBM, where it inhibits cancer stem cells and tumor growth by regulating the PDGF pathway.

The p53 Pathway in Glioblastoma.

The tumor suppressor and transcription factor p53 plays critical roles in tumor prevention by orchestrating a wide variety of cellular responses, including damaged cell apoptosis, maintenance of genomic stability, inhibition of angiogenesis, and regulation of cell metabolism and tumor microenvironment. TP53 is one of the most commonly deregulated genes in cancer. The p53-ARF-MDM2 pathway is deregulated in 84% of glioblastoma (GBM) patients and 94% of GBM cell lines. Deregulated p53 pathway components have been implicated in GBM cell invasion, migration, proliferation, evasion of apoptosis, and cancer cell stemness. These pathway components are also regulated by various microRNAs and long non-coding RNAs. TP53 mutations in GBM are mostly point mutations that lead to a high expression of a gain of function (GOF) oncogenic variants of the p53 protein. These relatively understudied GOF p53 mutants promote GBM malignancy, possibly by acting as transcription factors on a set of genes other than those regulated by wild type p53. Their expression correlates with worse prognosis, highlighting their potential importance as markers and targets for GBM therapy. Understanding mutant p53 functions led to the development of novel approaches to restore p53 activity or promote mutant p53 degradation for future GBM therapies.

Contributions of Basal Glucose and Postprandial Glucose Concentrations to Hemoglobin A1c in the Newly Diagnosed Patients with Type 2 Diabetes--the Preliminary Study.

OBJECTIVE: The aim of this preliminary study is to investigate contributions of basal glucose (BG) and postprandial glucose (PPG) increments to overall hyperglycemia in newly diagnosed patients with type 2 diabetes mellitus (T2DM). RESEARCH DESIGN AND METHODS: We evaluated the relative contributions of BG and PPG to overall hyperglycemia in 59 newly diagnosed T2DM patients according to BG baseline value of 6.1 mmol/L and 24-h glucose profiles of normal glucose tolerance (NGT) subjects obtained by continuous glucose monitoring as baseline, respectively. RESULTS: When the baseline was 24-h glucose profiles of the NGT subjects, the relative contributions of PPG in the T2DM patients with hemoglobin A1c (HbA1c) levels of ≤ 7.0%, 7.0-9.0%, and >9.0% were 57.58%, 44.69%, and 21.56%, respectively. When the baseline value was equal to 6.1 mmol/L, the relative contributions of PPG in the T2DM patients with HbA1c levels of ≤ 7.0%, 7.0-9.0%, and >9.0% were 77.23%, 53.43%, and 22.78%, respectively. Compared with the 24-h glucose profiles of the NGT subjects as the baseline, the relative contribution of PPG was overestimated by about 10-20% in the T2DM patients with HbA1c levels of ≤ 9.0% when 6.1 mmol/L was chosen as the baseline. CONCLUSIONS: In the newly diagnosed T2DM patients with mild hyperglycemia, PPG is a predominant contributor, whereas the relative contributions of BG gradually increase from mild to severe hyperglycemia and obviously exceed PPG in the T2DM patients with HbA1c levels of >9.0%. This finding implies that the initial pharmacotherapy may target PPG in those patients with mild hyperglycemia and target BG in those patients with severe hyperglycemia.

Autologous platelet-rich gel for treatment of diabetic chronic refractory cutaneous ulcers: A prospective, randomized clinical trial.

The purpose of the study is to examine the safety and effectiveness of topical autologous platelet-rich gel (APG) application on facilitating the healing of diabetic chronic refractory cutaneous ulcers. The study was designed as a prospective, randomized controlled trial between January 1, 2007 and December 31, 2011. Eligible inpatients at the Diabetic Foot Care Center of West China Hospital, Sichuan University (China) were randomly prescribed with a 12-week standard treatment of ulcers (the control group) or standard treatment plus topical application APG (the APG group). The wound healing grades (primary endpoint), time to complete healing, and healing velocity within 12 weeks were monitored as short-term effectiveness measurements, while side effects were documented safety endpoints. The rates of survival and recurrence within the follow up were recorded as long-term effectiveness endpoints. Analysis on total diabetic ulcers (DUs) (n = 117) and subgroup analysis on diabetic foot ulcers (DFUs) (n = 103) were both conducted. Standard treatment plus APG treatment was statistically more effective than standard treatment (p < 0.05 in both total DUs and subgroup of DFUs). The subjects defined as healing grade 1 were 50/59 (84.8%) in total DUs and 41/48 (85.4%) in DFUs in the APG group compared with 40/58 (69.0%) and 37/55 (67.3%) in the control group from intent to treat population. The Kaplan-Meier time-to-healing were significantly different between the two groups (p < 0.05 in both total DUs and subgroup of DFUs). No side effects were identified after topical APG application. The long-term survival and recurrence rates were comparative between groups (p > 0.05). This study shows that topical APG application plus standard treatment is safe and quite effective on diabetic chronic refractory cutaneous ulcers, compared with standard treatment.

Fine structure of Delia platura (Meigen) (Diptera: Anthomyiidae) revealed by scanning electron microscopy.

Delia platura (Meigen) is a phytophagous fly that can cause significant crop losses. To obtain a better understanding of the external morphology of this species, adult D. platura is studied using scanning electron microscopy. Organs or structures that are important for taxonomy, such as the compound eyes, spiracles, pulvilli, wings, and genitalia are highlighted to complement previous description based on light microscope. Mesothoracic and metathoracic spiracles of D. platura that provide efficiency in preventing entrance of fine materials or dust into the tracheal system are morphologically different. In addition, the elongate-oval pulvillus is densely covered with tenent setae with spoon-like tip, which can increase the number of contact points for attachment to a surface. Four types of sensilla are observed on the male genitalia of D. platura including: trichoid sensilla, chaetic sensilla, three subtypes of campaniform sensilla, and basiconic sensilla. Long bristles and microtrichiae are observed on the female genitalia of D. platura. The possible function of sensilla located in the genitalia of D. platura is discussed. Microsc. Res. Tech. 77:619-630, 2014. © 2014 Wiley Periodicals, Inc.