Single-cell RNA sequencing analysis of the embryogenic callus clarifies the spatiotemporal developmental trajectories of the early somatic embryo in Dimocarpus longan.

Plant embryogenic calli (ECs) can undergo somatic embryogenesis to regenerate plants. This process is mediated by regulatory factors, such as transcription factors and specifically expressed genes, but the precise molecular mechanisms underlying somatic embryogenesis at the single-cell level remain unclear. In this study, we performed high-resolution single-cell RNA sequencing analysis to determine the cellular changes in the EC of the woody plant species Dimocarpus longan (longan) and clarify the continuous cell differentiation trajectories at the transcriptome level. The highly heterogeneous cells in the EC were divided into 12 putative clusters (e.g., proliferating, meristematic, vascular, and epidermal cell clusters). We determined cluster-enriched expression marker genes and found that overexpression of the epidermal cell marker gene GDSL ESTERASE/LIPASE-1 inhibited the hydrolysis of triacylglycerol. In addition, the stability of autophagy was critical for the somatic embryogenesis of longan. The pseudo-timeline analysis elucidated the continuous cell differentiation trajectories from early embryonic cell division to vascular and epidermal cell differentiation during the somatic embryogenesis of longan. Moreover, key transcriptional regulators associated with cell fates were revealed. We found that ETHYLENE RESPONSIVE FACTOR 6 was characterized as a heat-sensitive factor that negatively regulates longan somatic embryogenesis under high-temperature stress conditions. The results of this study provide new spatiotemporal insights into cell division and differentiation during longan somatic embryogenesis at single-cell resolution.

Genome-wide high-throughput chromosome conformation capture analysis reveals hierarchical chromatin interactions during early somatic embryogenesis.

Somatic embryogenesis (SE), like zygotic embryo development, is a progressive process. Early SE is the beginning of a switch from a somatic to an embryogenic state and is an important stage for initiating chromatin reprogramming of SE. Previous studies suggest that changes in chromatin accessibility occur during early SE, although information on the 3D structure of chromatin is not yet available. Here, we present a chromosome-level genome assembly of longan (Dimocarpus longan) using PacBio combined with high-through chromosome conformation capture scaffolding, which resulted in a 446 Mb genome assembly anchored onto 15 scaffolds. During early SE, chromatin was concentrated and then decondensed, and a large number of long terminal repeat retrotransposons (LTR-RTs) were enriched in the local chromatin interaction region, suggesting LTR-RTs were involved in chromatin reorganization. Early SE was accompanied by the transformation from A to B compartments, and the interactions between B compartments were enhanced. Results from chromatin accessibility, monomethylation of histone H3 at lysine 4 (H3K4me1) modification, and transcription analyses further revealed a gene regulatory network for cell wall thickening during SE. Particularly, we found that the H3K4me1 differential peak binding motif showed abnormal activation of ethylene response factor transcription factors and participation in SE. The chromosome-level genomic and multiomics analyses revealed the 3D conformation of chromatin during early SE, providing insight into the molecular mechanisms underlying cell wall thickening and the potential regulatory networks of TFs during early SE in D. longan. These results provide additional clues for revealing the molecular mechanisms of plant SE.

Genome-wide analysis of the GLP gene family and overexpression of GLP1-5-1 to promote lignin accumulation during early somatic embryo development in Dimocarpus longan.

Longan (Dimocarpus longan Lour.) is an economically important subtropical fruit tree. Its fruit quality and yield are affected by embryo development. As a plant seed germination marker gene, the germin-like protein (GLP) gene plays an important role in embryo development. However, the mechanism underlying the role of the GLP gene in somatic embryos is still unclear. Therefore, we conducted genome-wide identification of the longan GLP (DlGLP) gene and preliminarily verified the function of DlGLP1-5-1. Thirty-five genes were identified as longan GLP genes and divided into 8 subfamilies. Based on transcriptome data and qRT‒PCR results, DlGLP genes exhibited the highest expression levels in the root, and the expression of most DlGLPs was upregulated during the early somatic embryogenesis (SE) in longan and responded to high temperature stress and 2,4-D treatment; eight DlGLP genes were upregulated under MeJA treatment, and four of them were downregulated under ABA treatment. Subcellular localization showed that DlGLP5-8-2 and DlGLP1-5-1 were located in the cytoplasm and extracellular stroma/chloroplast, respectively. Overexpression of DIGLP1-5-1 in the globular embryos (GEs) of longan promoted the accumulation of lignin and decreased the H2O2 content by regulating the activities of ROS-related enzymes. The results provide a reference for the functional analysis of DlGLPs and related research on improving lignin accumulation in the agricultural industry through genetic engineering.

C-reactive protein inhibits C3a/C3aR-dependent podocyte autophagy in favor of diabetic kidney disease.

Numerous studies have reported the pathogenic roles of C-reactive protein (CRP) and complement activation in diabetic kidney disease (DKD) individually. However, considering the potent regulatory effect of CRP on complement activation, it remains unclear whether CRP participates in DKD pathogenesis by regulating complement activation. Moreover, this work focuses on complement activation in rats, which aims at settling the dispute that whether rat CRP can activate the complement system. To address this question, the complement effectors C3a, C5a, and C5b-9 were examined in human patients with diabetic nephropathy (DN) and wt, Crp-/- , and huCRPtg rats with STZ-diabetic DKD. The Crp-/- rats showed more C3a accumulation in blood and glomeruli than wt and huCRPtg rats. The balance between autophagy and apoptosis was evaluated in DKD rats, and Crp-/- rats showed increased podocyte autophagy compared with wt and huCRPtg rats. Meanwhile, stable CRP-overexpression and CRP-knockout cell lines were established and used to demonstrate that CRP suppresses C3a-induced podocyte autophagy under high-glucose conditions. We further verified that the inhibition of C3a-induced podocyte autophagy by CRP was dependent on C3aR expression and that this effect could be reversed with a C3aR antagonist and agonist. Therefore, our findings provide evidence that CRP suppresses podocyte autophagy to accelerate the development of DKD by inhibiting C3a/C3aR axis signaling, which may help in the development of a new therapeutic strategy for the management of podocyte autophagy and DKD. In addition, rat CRP has been shown to be identical to human CRP in the activation of autologous complement and interspecific complement.

Fabrication of Z-scheme Cd0.85Zn0.15S/Co9S8dual-functional photocatalyst for effective hydrogen evolution and organic pollutant degradation.

A Z-scheme Cd0.85Zn0.15S/Co9S8(CZS-CS) photocatalyst was reasonably fabricated by a simple solvothermal method for the effective visible-light-driven H2evolution and organic pollutants degradation. The precise construction of the CZS-CS composites provided an efficient heterogeneous contact interface and abundant reaction sites for the proposed photocatalytic reaction. The homogeneous Co9S8nanocrystals were uniformly wrapped on the surface of Cd0.85Zn0.15S nanorods, forming an intimate-contact interface, markedly contributed to the light collection and effectively inhibited the charge-carrier recombination. The optimized CZS-CS-15 composites exhibited a special H2production rate reaching 19.15 mmol·h-1·g-1, roughly 1915 and 4.5 times of pure Co9S8and Cd0.85Zn0.15S samples and 85% of tetracycline (TC) molecule within 15 min was degraded. Furthermore, trapping experiments confirmed that h+was the main active species for TC photodegradation. Moreover, the obtained photocatalysts manifested stability without apparent activity declines during the proposed reactions. Finally, the Z-scheme photocatalytic mechanism was verified to illustrate the characteristics of efficient charge transfer and high redox ability. This study provided a rational and learnable strategy for designing dual-functional Z-scheme heterojunction photocatalysts.

Unprecedented Neoverrucosane and Cyathane Diterpenoids with Anti-Neuroinflammatory Activity from Cultures of the Culinary-Medicinal Mushroom Hericium erinaceus.

The culinary medicinal mushroom Hericium erinaceus holds significant global esteem and has garnered heightened interest within increasingly ageing societies due to its pronounced neuroprotective and anti-neuroinflammatory properties. Within this study, two novel diterpenes, 16-carboxy-13-epi-neoverrucosane (1) and Erinacine L (2); three known xylosyl cyathane diterpenoids, Erinacine A (3), Erinacine C (4), and Erinacine F (5); and four lanostane-type triterpenoids, and three cyclic dipeptides (10-12), in addition to orcinol (13), were isolated from the rice-based cultivation medium of H. erinaceus. Their structures were determined by NMR, HR-ESI-MS, ECD, and calculated NMR. Compound 1 marks a pioneering discovery as the first verrucosane diterpene originating from basidiomycetes, amplifying the scope of fungal natural product chemistry, and the intricate stereochemistry of Compound 5 has been comprehensively assessed for the first time. Compounds 2-5 not only showed encouraging neurotrophic activity in rat adrenal pheochromocytoma PC-12 cells, but also significantly inhibited lipopolysaccharide (LPS)-induced nitric oxide (NO) production in BV2 microglia cell cultures with IC50 values as low as 5.82 ± 0.18 µM. To elucidate the mechanistic underpinnings of these bioactivities, molecular docking simulation was used to analyze and support the interaction of 1 and 2 with inducible NO synthase (iNOS), respectively. In particular, compound 2, a cyathane-xyloside containing an unconventional hemiacetal moiety, is a compelling candidate for the prevention of neurodegenerative diseases. In summation, this investigation contributes substantively to the panorama of fungal diterpene structural diversity, concurrently furnishing additional empirical substantiation for the role of cyathane diterpenes in the amelioration of neurodegenerative afflictions.

Antigen-Down PEC Immunosensor for CYFRA21-1 Detection Based on Photocurrent Polarity Switching Strategy.

In this work, an antigen-down photoelectrochemical (PEC) immunosensor based on a signal polarity switching strategy for the detection of cytokeratin 19 fragment 21-1 (CYFRA21-1) was proposed. 3,4,9,10-Perylene tetracarboxylic acid (PTCA) is a conjugated organic dye containing five benzene nuclei, which has excellent film-forming and optical properties. PTCA sensitized by SnS2 can further improve the basal signal and the stability of the PEC immunosensor. Moreover, avidin-functionalized CuInS2 as a signal probe can convert the basal anodic photocurrent to a cathodic photocurrent. Therefore, the PEC sensor realized the photocurrent polarity conversion before and after labeling. With avidin-functionalized CuInS2, the polarity of the photocurrent was changed once CYFRA21-1 was detected. Therefore, the PEC immunosensor owns high sensitivity. The linear range of the immunosensor for the detection of CYFRA21-1 is 0.00001-500 ng·mL-1, and the detection limit is 3.5 fg·mL-1. The PEC immunosensor has good stability, high selectivity, and good repeatability. This work may provide a new way for the detection of CYFRA21-1 and other proteins.

Self-powered photoelectrochemical aptasensor based on AgInS2@Co/Ni-UiO-66@CDs photoelectrode for estradiosl detection.

A self-powered photoelectrochemical (PEC) aptasensor was constructed to sensitively detect 17ß-estradiol (E2). Firstly, a reasonable AgInS2@Co/Ni-UiO-66@Carbon Nanodots (CDs) photoelectrode with excellent photoelectrochemical performance was built by a simple two-step preparation method. The Co and Ni doping markedly improved the activity of UiO-66; the matched energy level of AgInS2 and Co/Ni-UiO-66 promoted the separation of electron-hole pairs, and the coupling of CDs further enhanced the conductivity and light utilization. Therefore, a steady anode-photocurrent signal output was obtained in 0.0 V bias voltage, providing a reliable photoelectric translating platform for assembling a self-powered PEC aptasensor. The E2-aptamer was adopted as a recognition unit to enhance the selectivity and sensitivity of the proposed aptasensor. The specific recognition reaction between E2 and aptamer administering to a raised photocurrent signal and the concentration of E2 was quantified by counting the fluctuation of the anode-photocurrent signal. The linear response range of the PEC aptasensor was 1.0 × 10-5-10 nmol/L, and the detection limit (S/N = 3) was lower than 3.0 fmol/L under optimal conditions. The fabricated aptasensor exhibited admirable selectivity, high sensitivity, rapid response, and wide linear range, demonstrating an extensive application prospect for environmental endocrine disruptor detection.

Whole Genome Analysis of SLs Pathway Genes and Functional Characterization of DlSMXL6 in Longan Early Somatic Embryo Development.

Strigolactones (SLs), a new class of plant hormones, are implicated in the regulation of various biological processes. However, the related family members and functions are not identified in longan (Dimocarpus longan Lour.). In this study, 23 genes in the CCD, D27, and SMXL family were identified in the longan genome. The phylogenetic relationships, gene structure, conserved motifs, promoter elements, and transcription factor-binding site predictions were comprehensively analysed. The expression profiles indicated that these genes may play important roles in longan organ development and abiotic stress responses, especially during early somatic embryogenesis (SE). Furthermore, GR24 (synthetic SL analogue) and Tis108 (SL biosynthesis inhibitor) could affect longan early SE by regulating the levels of endogenous IAA (indole-3-acetic acid), JA (jasmonic acid), GA (gibberellin), and ABA (abscisic acid). Overexpression of SMXL6 resulted in inhibition of longan SE by regulating the synthesis of SLs, carotenoids, and IAA levels. This study establishes a foundation for further investigation of SL genes and provides novel insights into their biological functions.

Melatonin attenuates diabetic cardiomyopathy and reduces myocardial vulnerability to ischemia-reperfusion injury by improving mitochondrial quality control: Role of SIRT6.

Targeting mitochondrial quality control with melatonin has been found promising for attenuating diabetic cardiomyopathy (DCM), although the underlying mechanisms remain largely undefined. Activation of SIRT6 and melatonin membrane receptors exerts cardioprotective effects while little is known about their roles during DCM. Using high-fat diet-streptozotocin-induced diabetic rat model, we found that prolonged diabetes significantly decreased nocturnal circulatory melatonin and heart melatonin levels, reduced the expressions of cardiac melatonin membrane receptors, and decreased myocardial SIRT6 and AMPK-PGC-1α-AKT signaling. 16 weeks of melatonin treatment inhibited the progression of DCM and the following myocardial ischemia-reperfusion (MI/R) injury by reducing mitochondrial fission, enhancing mitochondrial biogenesis and mitophagy via re-activating SIRT6 and AMPK-PGC-1α-AKT signaling. After the induction of diabetes, adeno-associated virus carrying SIRT6-specific small hairpin RNA or luzindole was delivered to the animals. We showed that SIRT6 knockdown or antagonizing melatonin receptors abolished the protective effects of melatonin against mitochondrial dysfunction as evidenced by aggravated mitochondrial fission and reduced mitochondrial biogenesis and mitophagy. Additionally, SIRT6 shRNA or luzindole inhibited melatonin-induced AMPK-PGC-1α-AKT activation as well as its cardioprotective actions. Collectively, we demonstrated that long-term melatonin treatment attenuated the progression of DCM and reduced myocardial vulnerability to MI/R injury through preserving mitochondrial quality control. Melatonin membrane receptor-mediated SIRT6-AMPK-PGC-1α-AKT axis played a key role in this process. Targeting SIRT6 with melatonin treatment may be a promising strategy for attenuating DCM and reducing myocardial vulnerability to ischemia-reperfusion injury in diabetic patients.

CT-Guided Autologous Blood Patch for High-Level Cervical Cerebrospinal Fluid Leakage: Imaging Characteristics and Treatment Safety and Efficiency.

INTRODUCTION: Epidural blood patches (EBPs) are rarely performed at the high-level cervical levels. The aim of the study was to investigate the imaging features, safety, and effectiveness of CT-guided percutaneous EBPs for high-level cervical cerebrospinal fluid (CSF) leakage. METHODS: Twenty-five patients with spontaneous high-level (C1-C3) CSF leakage on MRI and CT imaging, including 2 patients with intracranial epidural hematoma caused by CSF, were treated with EBP. Two needles were inserted into the C1-3 bilateral epidural space. The needle location was confirmed by injection of both 3-5mL sterile air and a diluted iodinated contrast agent to delineate its spatial diffusion. The patient's blood 11.1 ± 3.1 mL was slowly injected to make a patch; the distribution in epidural space was monitored with intermittent CT scanning. RESULTS: The typical manifestation of CSF leakage was the high signal outside the C1-3 cervical dura on MR T2W fat inhibition images and low density in cervical muscle space on CT images. Twenty patients suffered from headaches and were able to sit and walk 24 h after the operation. Four patients, with partial relief of headache and a small but persistent CSF leakage, were re-treated with EBS. One patient underwent a third operation because of a persistent CSF leakage on MRI. CONCLUSIONS: Imaging of water at the surrounding epidural space of high cervical level is a typical feature of dural rupture on both MRI and CT. CT-guided EBP is safe and efficient for the high-level cervical CSF leakage, especially for cases in which conservative treatments failed.

An Efficient System for Ds Transposon Tagging in Brachypodium distachyon.

Transposon tagging is a powerful tool that has been widely applied in several species for insertional mutagenesis in plants. Several efforts have aimed to create transfer-DNA (T-DNA) insertional mutant populations in Brachypodium distachyon, a monocot plant used as a model system to study temperate cereals, but there has been a lack of research aimed at using transposon strategies. Here, we describe the application of a maize (Zea mays) Dissociation (Ds) transposon tagging system in B distachyon The 35S::AcTPase cassette and Ds element were constructed within the same T-DNA and transformed into B distachyon plants. The Ds element was readily transposed to other chromosomes or to the same chromosome under the function of Activator (Ac) transposase. Through homologous chromosome synapsis, recombination, and segregation, the Ds element separated from the Ac element. We selected stable Ds-only plants using G418 and GFP assays and analyzed 241 T0 lines, some of which were highly efficient at producing Ds-only progeny. Through thermal asymmetric interlaced PCR, we isolated 710 independent Ds flanking sequences from Ds-only plants. Furthermore, we identified a large collection of mutants with visible developmental phenotypes via this transposon tagging system. The system is relatively simple and rapid in comparison to traditional T-DNA insertion strategies, because once efficiency lines are obtained they can be reused to generate more lines from nontransposed plants without the use of time-consuming tissue culture steps.

Effects of interfacial adsorption configurations on dye-sensitized solar cell performance at the stoichiometric and defective TiO2 anatase (101) surfaces: a theoretical investigation.

Interfacial adsorption configuration plays a crucial role in influencing the photovoltaic performance of dye-sensitized solar cells (DSSCs), and thus, theoretical investigations are needed to further understand the impacts of different absorption configurations on stoichiometric and defective TiO2(101) surfaces on the short-circuit photocurrent density (JSC) and open-circuit voltage (VOC) of DSSCs. Herein, calculations of isolated dyes and dye/TiO2 systems were performed on the donor-π bridge-acceptor (D-π-A) type porphyrin sensitizers bearing different donor moieties and an α-cyanoacrylic acid anchoring group (T1-3), using DFT and TD-DFT methods. And, for the first time, comparative analysis of interfacial electron transfer (IET) and density of states (DOS) were carried out on dye/TiO2 systems with stoichiometric and defective surfaces to provide further insight into the electronic factors influencing the efficiency of DSSCs, which can well explain the experimental variation trends of JSC and VOC values. It turned out that attachment via the carboxyl and cynao groups in a tridentate binding mode can result in more efficient IET rates and an upshifted conduction band in comparison with those of the bidentate attachment. More interestingly, we found that the adsorption configuration on defective surfaces containing an O2c vacancy induced more upshifted CBM and relatively fast IET, especially for the bonding mode through two O atoms of the carboxyl group.

Melatonin protects diabetic heart against ischemia-reperfusion injury, role of membrane receptor-dependent cGMP-PKG activation.

It has been demonstrated that the anti-oxidative and cardioprotective effects of melatonin are, at least in part, mediated by its membrane receptors. However, the direct downstream signaling remains unknown. We previously found that melatonin ameliorated myocardial ischemia-reperfusion (MI/R) injury in diabetic animals, although the underlying mechanisms are also incompletely understood. This study was designed to determine the role of melatonin membrane receptors in melatonin's cardioprotective actions against diabetic MI/R injury with a focus on cGMP and its downstream effector PKG. Streptozotocin-induced diabetic Sprague-Dawley rats and high-glucose medium-incubated H9c2 cardiomyoblasts were utilized to determine the effects of melatonin against MI/R injury. Melatonin treatment preserved cardiac function and reduced oxidative damage and apoptosis. Additionally, melatonin increased intracellular cGMP level, PKGIα expression, p-VASP/VASP ratio and further modulated myocardial Nrf-2-HO-1 and MAPK signaling. However, these effects were blunted by KT5823 (a selective inhibitor of PKG) or PKGIα siRNA except that intracellular cGMP level did not changed significantly. Additionally, our in vitro study showed that luzindole (a nonselective melatonin membrane receptor antagonist) or 4P-PDOT (a selective MT2 receptor antagonist) not only blocked the cytoprotective effect of melatonin, but also attenuated the stimulatory effect of melatonin on cGMP-PKGIα signaling and its modulatory effect on Nrf-2-HO-1 and MAPK signaling. This study showed that melatonin ameliorated diabetic MI/R injury by modulating Nrf-2-HO-1 and MAPK signaling, thus reducing myocardial apoptosis and oxidative stress and preserving cardiac function. Importantly, melatonin membrane receptors (especially MT2 receptor)-dependent cGMP-PKGIα signaling played a critical role in this process.

Diallyl trisulfide ameliorates myocardial ischemia-reperfusion injury by reducing oxidative stress and endoplasmic reticulum stress-mediated apoptosis in type 1 diabetic rats: role of SIRT1 activation.

Diallyl trisulfide (DATS) protects against apoptosis during myocardial ischemia-reperfusion (MI/R) injury in diabetic state, although the underlying mechanisms remain poorly defined. Previously, we and others demonstrated that silent information regulator 1 (SIRT1) activation inhibited oxidative stress and endoplasmic reticulum (ER) stress during MI/R injury. We hypothesize that DATS reduces diabetic MI/R injury by activating SIRT1 signaling. Streptozotocin (STZ)-induced type 1 diabetic rats were subjected to MI/R surgery with or without perioperative administration of DATS (40 mg/kg). We found that DATS treatment markedly improved left ventricular systolic pressure and the first derivative of left ventricular pressure, reduced myocardial infarct size as well as serum creatine kinase and lactate dehydrogenase activities. Furthermore, the myocardial apoptosis was also suppressed by DATS as evidenced by reduced apoptotic index and cleaved caspase-3 expression. However, these effects were abolished by EX527 (the inhibitor of SIRT1 signaling, 5 mg/kg). We further found that DATS effectively upregulated SIRT1 expression and its nuclear distribution. Additionally, PERK/eIF2α/ATF4/CHOP-mediated ER stress-induced apoptosis was suppressed by DATS treatment. Moreover, DATS significantly activated Nrf-2/HO-1 antioxidant signaling pathway, thus reducing Nox-2/4 expressions. However, the ameliorative effects of DATS on oxidative stress and ER stress-mediated myocardial apoptosis were inhibited by EX527 administration. Taken together, these data suggest that perioperative DATS treatment effectively ameliorates MI/R injury in type 1 diabetic setting by enhancing cardiac SIRT1 signaling. SIRT1 activation not only upregulated Nrf-2/HO-1-mediated antioxidant signaling pathway but also suppressed PERK/eIF2α/ATF4/CHOP-mediated ER stress level, thus reducing myocardial apoptosis and eventually preserving cardiac function.

Melatonin rescues cardiac thioredoxin system during ischemia-reperfusion injury in acute hyperglycemic state by restoring Notch1/Hes1/Akt signaling in a membrane receptor-dependent manner.

Stress hyperglycemia is commonly observed in patients suffering from ischemic heart disease. It not only worsens cardiovascular prognosis but also attenuates the efficacies of various cardioprotective agents. This study aimed to investigate the protective effect of melatonin against myocardial ischemia-reperfusion (MI/R) injury in acute hyperglycemic state with a focus on Notch1/Hes1/Akt signaling and intracellular thioredoxin (Trx) system. Sprague Dawley rats were subjected to MI/R surgery and high-glucose (HG, 500 g/L) infusion (4 mL/kg/h) to induce temporary hyperglycemia. Rats were treated with or without melatonin (10 mg/kg/d) during the operation. Furthermore, HG (33 mmol/L)-incubated H9c2 cardiomyoblasts were treated in the presence or absence of luzindole (a competitive melatonin receptor antagonist), DAPT (a γ-secretase inhibitor), LY294002 (a PI3-kinase/Akt inhibitor), or thioredoxin-interacting protein (Txnip) adenoviral vectors. We found that acute hyperglycemia aggravated MI/R injury by suppressing Notch1/Hes1/Akt signaling and intracellular Trx activity. Melatonin treatment effectively ameliorated MI/R injury by reducing infarct size, myocardial apoptosis, and oxidative stress. Moreover, melatonin also markedly enhanced Notch1/Hes1/Akt signaling and rescued intracellular Trx system by upregulating Notch1, N1ICD, Hes1, and p-Akt expressions, increasing Trx activity, and downregulating Txnip expression. However, these effects were blunted by luzindole, DAPT, or LY294002. Additionally, Txnip overexpression not only decreased Trx activity, but also attenuated the cytoprotective effect of melatonin. We conclude that impaired Notch1 signaling aggravates MI/R injury in acute hyperglycemic state. Melatonin rescues Trx system by reducing Txnip expression via Notch1/Hes1/Akt signaling in a membrane receptor-dependent manner. Its role as a prophylactic/therapeutic drug deserves further clinical study.

The transcriptome responses of cardiomyocyte exposed to hypothermia.

Hypothermia has positive and negative consequences on the body. Hypothermia depresses myocardial contraction, conduction, and metabolic rate in the heart. However, little is known about the underlying molecular mechanisms. Herein, we compared the gene expression of human adult ventricular cardiomyocytes (AC16) under hypothermia to find differences between different temperatures, and elucidate the candidate genes that may play important roles in the response to hypothermia. A total of 2413 differentially expressed genes (DEGs) were identified by microarray hybridization, which provided abundant data for further analysis. Gene Ontology (GO) enrichment analysis revealed that genes related to transcription, and protein and lipid metabolism were significantly enriched. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed that DEGs were significantly enriched in TGF-ß pathway and cytokine-cytokine receptor interaction, which may play important roles in changes affected by hypothermia. A set of transcription factors (TFs) (CPBP, Churchill, NF-AT1, GKLF, SRY, ZNF333, ING4, myogenin, DRI1 and CRX) was recognized to be the functional layer of key nodes, which mapped the signal of hypothermia to transcriptome. The identified DEGs, pathways and predicted TFs could facilitate further investigations of the detailed molecular mechanisms.

Application-oriented computational studies on a series of D-π-A structured porphyrin sensitizers with different electron-donor groups.

A series of D-π-A zinc porphyrin sensitizers bearing a substituted iminodibenzyl group at the porphyrin meso position, which is expected to have different electron-donating abilities, were designed. Theoretical studies were performed to examine the photovoltaic properties of these molecules in dye-sensitized solar cells (DSSCs). In particular, the important concepts, the Fukui function and the extended condensed Fukui function, are employed to describe the electron-donating abilities accurately at the quantitative level. Tangui Le Bahers model was adopted to analyze charge transfer (CT) during electron transition. A correlation between the electron donating abilities of the derived iminodibenzyl group and CT was built to evaluate the cell performance based on sensitizers . The theoretical studies showed that porphyrins bearing an extremely strong electron-donating group (EDG) would fail in the generation of photocurrent in the closed circuit when applied in DSSCs due to the higher level of the HOMO energy than the redox potential of the redox couple (I(-)/I3(-)). The one with a weaker EDG () is expected to show better photovoltaic performance than porphyrin with an unsubstituted iminodibenzyl group. This study demonstrates a reliable method involving the employment of the Fukui function, the extended condensed Fukui function and the Tangui Le Bahers model for the evaluation of newly designed D-π-A type porphyrin sensitizers for use in DSSCs, and as guidance for future molecular design.

Repetitive transcranial magnetic stimulation (rTMS) for the treatment of depression in Parkinson disease: a meta-analysis of randomized controlled clinical trials.

The objective of this meta-analysis was to evaluate the effects of repetitive transcranial magnetic stimulation (rTMS) for the treatment of depression in patients with Parkinson disease in order to arrive at qualitative and quantitative conclusions about the efficacy of rTMS. We included randomized controlled trials examining the effects of rTMS compared with sham-rTMS or selective serotonin re-uptake inhibitors (SSRIs). The quality of included studies was strictly evaluated. Data analyses were performed using the RevMan5.1 software. Eight studies including 312 patients met all inclusion criteria. The results showed that rTMS could evidently improve the HRSD score compared with sham-rTMS (p < 0.00001). However, we found similar antidepressant efficacy between rTMS and SSRIs groups in terms of HRSD and BDI score (p = 0.65; p = 0.75, respectively). Furthermore, patients who received rTMS could evidently show improvement on the unified Parkinson's disease rating scale (UPDRS), ADL score, and UPDRS motor score compared with sham-rTMS or SSRIs (p < 0.05, p = 0.05, respectively). The subgroup analysis by frequency of rTMS evidenced that the efficacy of low-frequency rTMS was superior to sham-rTMS (p < 0.0001) in terms of the outcome measure according to HAMD scale. Meanwhile, the high-frequency rTMS has the same antidepressant efficacy as SSRIs (p = 0.94). The current meta-analysis provided evidence that rTMS was superior to sham-rTMS and had similar antidepressant efficacy as SSRIs, and may have the additional advantage of some improvement in motor function.

Quantifying the average of the time-varying hazard ratio via a class of transformations.

The hazard ratio derived from the Cox model is a commonly used summary statistic to quantify a treatment effect with a time-to-event outcome. The proportional hazards assumption of the Cox model, however, is frequently violated in practice and many alternative models have been proposed in the statistical literature. Unfortunately, the regression coefficients obtained from different models are often not directly comparable. To overcome this problem, we propose a family of weighted hazard ratio measures that are based on the marginal survival curves or marginal hazard functions, and can be estimated using readily available output from various modeling approaches. The proposed transformation family includes the transformations considered by Schemper et al. (Statist Med 28:2473-2489, 2009) as special cases. In addition, we propose a novel estimate of the weighted hazard ratio based on the maximum departure from the null hypothesis within the transformation family, and develop a Kolmogorov[Formula: see text]Smirnov type of test statistic based on this estimate. Simulation studies show that when the hazard functions of two groups either converge or diverge, this new estimate yields a more powerful test than tests based on the individual transformations recommended in Schemper et al. (Statist Med 28:2473-2489, 2009), with a similar magnitude of power loss when the hazards cross. The proposed estimates and test statistics are applied to a colorectal cancer clinical trial.