Evolutionary history of the angiosperm flora of China.

High species diversity may result from recent rapid speciation in a 'cradle' and/or the gradual accumulation and preservation of species over time in a 'museum'. China harbours nearly 10% of angiosperm species worldwide and has long been considered as both a museum, owing to the presence of many species with hypothesized ancient origins, and a cradle, as many lineages have originated as recent topographic changes and climatic shifts-such as the formation of the Qinghai-Tibetan Plateau and the development of the monsoon-provided new habitats that promoted remarkable radiation. However, no detailed phylogenetic study has addressed when and how the major components of the Chinese angiosperm flora assembled to form the present-day vegetation. Here we investigate the spatio-temporal divergence patterns of the Chinese flora using a dated phylogeny of 92% of the angiosperm genera for the region, a nearly complete species-level tree comprising 26,978 species and detailed spatial distribution data. We found that 66% of the angiosperm genera in China did not originate until early in the Miocene epoch (23 million years ago (Mya)). The flora of eastern China bears a signature of older divergence (mean divergence times of 22.04-25.39 Mya), phylogenetic overdispersion (spatial co-occurrence of distant relatives) and higher phylogenetic diversity. In western China, the flora shows more recent divergence (mean divergence times of 15.29-18.86 Mya), pronounced phylogenetic clustering (co-occurrence of close relatives) and lower phylogenetic diversity. Analyses of species-level phylogenetic diversity using simulated branch lengths yielded results similar to genus-level patterns. Our analyses indicate that eastern China represents a floristic museum, and western China an evolutionary cradle, for herbaceous genera; eastern China has served as both a museum and a cradle for woody genera. These results identify areas of high species richness and phylogenetic diversity, and provide a foundation on which to build conservation efforts in China.

PGAM5 exacerbates acute renal injury by initiating mitochondria-dependent apoptosis by facilitating mitochondrial cytochrome c release.

Acute kidney injury (AKI) is a worldwide public health problem characterized by the massive loss of tubular cells. However, the precise mechanism for initiating tubular cell death has not been fully elucidated. Here, we reported that phosphoglycerate mutase 5 (PGAM5) was upregulated in renal tubular epithelial cells during ischaemia/reperfusion or cisplatin-induced AKI in mice. PGAM5 knockout significantly alleviated the activation of the mitochondria-dependent apoptosis pathway and tubular apoptosis. Apoptosis inhibitors alleviated the activation of the mitochondria-dependent apoptosis pathway. Mechanistically, as a protein phosphatase, PGAM5 could dephosphorylate Bax and facilitate Bax translocation to the mitochondrial membrane. The translocation of Bax to mitochondria increased membrane permeability, decreased mitochondrial membrane potential and facilitated the release of mitochondrial cytochrome c (Cyt c) into the cytoplasm. Knockdown of Bax attenuated PGAM5 overexpression-induced Cyt c release and tubular cell apoptosis. Our results demonstrated that the increase in PGAM5-mediated Bax dephosphorylation and mitochondrial translocation was implicated in the development of AKI by initiating mitochondrial Cyt c release and activating the mitochondria-dependent apoptosis pathway. Targeting this axis might be beneficial for alleviating AKI.

USP11 promotes renal tubular cell pyroptosis and fibrosis in UUO mice via inhibiting KLF4 ubiquitin degradation.

The pyroptosis of renal tubular epithelial cells leads to tubular loss and inflammation and then promotes renal fibrosis. The transcription factor Krüppel-like factor 4 (KLF4) can bidirectionally regulate the transcription of target genes. Our previous study revealed that sustained elevation of KLF4 is responsible for the transition of acute kidney injury (AKI) into chronic kidney disease (CKD) and renal fibrosis. In this study, we explored the upstream mechanisms of renal tubular epithelial cell pyroptosis from the perspective of posttranslational regulation and focused on the transcription factor KLF4. Mice were subjected to unilateral ureteral obstruction (UUO) surgery and euthanized on D7 or D14 for renal tissue harvesting. We showed that the pyroptosis of renal tubular epithelial cells mediated by both the Caspase-1/GSDMD and Caspase-3/GSDME pathways was time-dependently increased in UUO mouse kidneys. Furthermore, we found that the expression of the transcription factor KLF4 was also upregulated in a time-dependent manner in UUO mouse kidneys. Tubular epithelial cell-specific Klf4 knockout alleviated UUO-induced pyroptosis and renal fibrosis. In Ang II-treated mouse renal proximal tubular epithelial cells (MTECs), we demonstrated that KLF4 bound to the promoter regions of Caspase-3 and Caspase-1 and directly increased their transcription. In addition, we found that ubiquitin-specific protease 11 (USP11) was increased in UUO mouse kidneys. USP11 deubiquitinated KLF4. Knockout of Usp11 or pretreatment with the USP11 inhibitor mitoxantrone (3 mg/kg, i.p., twice a week for two weeks before UUO surgery) significantly alleviated the increases in KLF4 expression, pyroptosis and renal fibrosis. These results demonstrated that the increased expression of USP11 in renal tubular cells prevents the ubiquitin degradation of KLF4 and that elevated KLF4 promotes inflammation and renal fibrosis by initiating tubular cell pyroptosis.

The Sino-Himalayan flora evolved from lowland biomes dominated by tropical floristic elements.

BACKGROUND: The Sino-Himalayan flora harbors highly diverse high-elevation biotas, but our understanding of its evolutionary history in temporal and spatial dimensions is limited. In this study, we integrated a dated phylogenetic tree with comprehensive species distribution data to investigate changes over time and space in floristic elements, including the tropical, Tethys, northern temperate, and East Asian floristic elements, across the entire Sino-Himalaya and its three floristic regions: the Yunnan Plateau, Hengduan Mountains, and East Himalaya regions. RESULTS: Our results revealed that the Sino-Himalayan flora developed from lowland biomes and was predominantly characterized by tropical floristic elements before the collision between the Indian subcontinent and Eurasia during the Early Cenozoic. Subsequently, from the Late Eocene onwards, the uplifts of the Himalaya and Hengduan Mountains transformed the Sino-Himalayan region into a wet and cold plateau, on which harsh and diverse ecological conditions forced the rapid evolution of local angiosperms, giving birth to characteristic taxa adapted to the high altitudes and cold habitat. The percentage of temperate floristic elements increased and exceeded that of tropical floristic elements by the Late Miocene. CONCLUSIONS: The Sino-Himalayan flora underwent four significant formation periods and experienced a considerable increase in endemic genera and species in the Miocene, which remain crucial to the present-day patterns of plant diversity. Our findings support the view that the Sino-Himalayan flora is relatively young but has ancient origins. The three major shifts in the divergence of genera and species during the four formation periods were primarily influenced by the uplifts of the Himalaya and Hengduan Mountains and the onset and intensification of the Asian monsoon system. Additionally, the temporal patterns of floristic elements differed among the three floristic regions of the Sino-Himalaya, indicating that the uplift of the Himalaya and surrounding areas was asynchronous. Compared to the Yunnan Plateau region, the East Himalaya and Hengduan Mountains experienced more recent and drastic uplifts, resulting in highly intricate topography with diverse habitats that promoted the rapid radiation of endemic genera and species in these regions.

Deubiquitinating enzyme USP11 promotes renal tubular cell senescence and fibrosis via inhibiting the ubiquitin degradation of TGF-ß receptor II.

Transforming growth factor-ß1 (TGF-ß1) is regarded as a key factor in promoting renal fibrosis during chronic kidney disease (CKD). Signaling transduction of TGF-ß1 starts with binding to TGF-ß type II receptor (Tgfbr2), a constitutively activated kinase that phosphorylates TGF-ß type I receptor (Tgfbr1), and then activates downstream Smad2/3 or noncanonical pathways. Previous studies show that cellular senescence is associated with the progression of CKD, and accelerated tubular cell senescence is implicated in promoting renal fibrosis. In the present study we investigated the renal parenchymal cell senescence in fibrosis from the sight of posttranslational regulation and focused on Tgfbr2, the important gatekeeper for TGF-ß1 downstream signaling. In mice with unilateral ureteral obstruction (UUO) and folic acid (FA)-induced fibrotic kidneys, we found that Tgfbr2 was markedly elevated without obvious change in its mRNA levels. As an important member of deubiquitinating enzymes, ubiquitin-specific protease 11 (Usp11) was also significantly increased in fibrotic kidneys, and co-distributed with Tgfbr2 in tubular epithelial cells. Pretreatment with Usp11 inhibitor mitoxantrone (MTX, 30 mg · kg-1 · d-1, i.p.) twice a week, for 2 weeks significantly attenuated the elevation of Tgfbr2, activation in downstream senescence-related signaling pathway, as well as renal senescence and fibrosis. In cultured mouse tubular epithelial cells (MTECs), treatment with angiotensin II (Ang-II, 10-7, 10-6 M) dose-dependently elevated both Tgfbr2 and Usp11 levels. Inhibition or knockdown on Usp11 attenuated Ang-II-induced elevation in Tgfbr2 level, and attenuated the activation of downstream senescent-related signaling pathway and as well as cell senescence. We conducted Co-IP experiments, which revealed that Usp11 was able to interact with Tgfbr2, and inhibition of Usp11 increased the ubiquitination of Tgfbr2. Taken together, these results demonstrate that the elevation of Usp11 under pathological condition is implicated in promoting renal fibrosis. Usp11 promotes the development of renal fibrosis by deubiquitinating Tgfbr2, reducing Tgfbr2 ubiquitination degradation, and then facilitating the activation of downstream senescent signaling pathway.

Electrochemical determination of benomyl using MWCNTs interspersed graphdiyne as enhanced electrocatalyst.

Graphdiyne (GDY) has attracted a lot of interest in electrochemical sensing application with the advantages of a large conjugation system, porous structure, and high structure defects. Herein, to further improve the sensing effect of GDY, conductive MWCNTs were chosen as the signal accelerator. To get a stable composite material, polydopamine (PDA) was employed as connecting bridge between GDY and MWCNTs-NH2, where DA was firstly polymerized onto GDY, followed by covalently linking MWCNTs-NH2 with PDA through Michael-type reaction. The formed GDY@PDA/MWCNTs-NH2 composite was then explored as an electrochemical sensor for benomyl (Ben) determination. GDY assists the adsorption and accumulation of Ben molecules to the sensing surface, while MWCNTs-NH2 can enhance the electrical conductivity and electrocatalytic activity, all of which contributing to the significantly improved performance. The proposed sensor displays an obvious oxidation peak at 0.72 V (vs. Hg|Hg2Cl2) and reveals a wide linear range from 0.007 to 10.0 µM and a low limit of detection (LOD) of 1.8 nM (S/N = 3) toward Ben detection. In addition, the sensor shows high stability, repeatability, reproducibility, and selectivity. The feasibility of this sensor was demonstrated by detecting Ben in apple and cucumber samples with a recovery of 94-106% and relative standard deviations (RSDs) less than 2.3% (n = 5). A sensitive electrochemical sensing platform was reported for benomyl (Ben) determination based on a highly stable GDY@PDA/MWCNTs-NH2 composite.

Caspase-11 promotes NLRP3 inflammasome activation via the cleavage of pannexin1 in acute kidney disease.

Ischemia/reperfusion (I/R) injury is a major cause of acute kidney injury (AKI) in clinic. The activation of NLRP3 inflammasome is associated with inflammation and renal injury in I/R-induced AKI. In the current study we explored the molecular and cellular mechanisms for NLRP3 inflammasome activation following renal I/R. Mice were subjected to I/R renal injury by clamping bilateral renal pedicles. We showed that I/R injury markedly increased caspase-11 expression and the cleavage of pannexin 1 (panx1) in the kidneys accompanied by NLRP3 inflammasome activation evidenced by the activation of caspase-1 and interlukin-1ß (IL-1ß) maturation. In Casp-11-/- mice, I/R-induced panx1 cleavage, NLRP3 inflammasome activation as well as renal functional deterioration and tubular morphological changes were significantly attenuated. In cultured primary tubular cells (PTCs) and NRK-52E cells, hypoxia/reoxygenation (H/R) markedly increased caspase-11 expression, NLRP3 inflammasome activation, IL-1ß maturation and panx1 cleavage. Knockdown of caspase-11 attenuated all those changes; similar effects were observed in PTCs isolated from Casp-11-/- mice. In NRK-52E cells, overexpression of caspase-11 promoted panx1 cleavage; pretreatment with panx1 inhibitor carbenoxolone or knockdown of panx1 significantly attenuated H/R-induced intracellular ATP reduction, extracellular ATP elevation and NLRP3 inflammasome activation without apparent influence on H/R-induced caspase-11 increase; pretreatment with P2X7 receptor inhibitor AZD9056 also attenuated NLRP3 inflammasome activation. The above results demonstrate that the cleavage of panx1 by upregulated caspase-11 is involved in facilitating ATP release and then NLRP3 inflammasome activation in I/R-induced AKI. This study provides new insight into the molecular mechanism of NLRP3 inflammasome activation in AKI.

Spatial phylogenetics of the Chinese angiosperm flora provides insights into endemism and conservation.

The flora of China is well known for its high diversity and endemism. Identifying centers of endemism and designating conservation priorities are essential goals for biodiversity studies. However, there is no comprehensive study from a rigorous phylogenetic perspective to understand patterns of diversity and endemism and to guide biodiversity conservation in China. We conducted a spatial phylogenetic analysis of the Chinese angiosperm flora at the generic level to identify centers of neo- and paleo-endemism. Our results indicate that: (i) the majority of grid cells in China with significantly high phylogenetic endemism (PE) were located in the mountainous regions; (ii) four of the nine centers of endemism recognized, located in northern and western China, were recognized for the first time; (iii) arid and semiarid regions in Northwest China were commonly linked to significant PE, consistent with other spatial phylogenetic studies worldwide; and (iv) six high-priority conservation gaps were detected by overlaying the boundaries of China's nature reserves on all significant PE cells. Overall, we conclude that the mountains of southern and northern China contain both paleo-endemics (ancient relictual lineages) and neo-endemics (recently diverged lineages). The areas we highlight as conservation priorities are important for broad-scale planning, especially in the context of evolutionary history preservation.

[Acute kidney injury and regulated cell death].

Acute kidney injury (AKI) refers to a clinical syndrome in which renal function declines rapidly in a short period of time caused by various pathological factors. During the development of AKI, renal tubules with the functions of reabsorption and excretion are prone to cell death due to external pathological stimuli, which is an important cause of impaired renal function. In recent years, a variety of new cell death pathways have been gradually recognized. Researchers have now found that regulated cell death (RCD), such as necroptosis, pyroptosis and ferroptosis, are important regulatory mechanisms of AKI. This article will summarize the research advances of various types of RCD involved in the process of AKI, aiming to deepen the understanding of AKI and provide innovative thoughts for the clinical treatment of AKI.

Historical biogeography of Tetrastigma (Vitaceae): Insights into floristic exchange patterns between Asia and Australia.

Biodiversity exchanges across the Malesian region, linking the distinct biotas of Asia and Australia, have long attracted the curiosity of biologists. Tetrastigma (Vitaceae) has a wide distribution in Asia through the Sunda archipelago to Australia and provides a good case to elucidate floristic exchange between Asia and Australia. Tetrastigma species have fleshy fruits that are consumed by birds, representing a lineage with a predictable dispersal across island chains. We herein estimate the divergence times and reconstruct the biogeographic history of Tetrastigma with intensive taxon sampling (96 of approximately 120 species; >80%) using 10 chloroplast loci. The biogeographic history of Tetrastigma was reconstructed with 4-area and 6-area divisions by delineating the Sunda region into one or three areas of endemism based on a phylogenetic bioregionalization analysis and the geological history of Malesia. The 4-area division shows that Tetrastigma originated in continental Asia and diverged from the recently segregated genus Pseudocayratia in the early Eocene (49.43 Ma). Dispersal from continental Asia might have started in the late Eocene but mainly occurred in the last 10 Myr. Continental Asia is indicated to be the most important source area while Sunda is the biggest sink, with 16 of the 27 dispersal events inferred from continental Asia to Sunda. Only seven dispersal events are inferred arriving in the Sahul plate and one reverse dispersal from Sahul back to Asia. The 6-area division suggests that the Philippines have been an active junction between Asia and Australia. The biogeographic history of Tetrastigma illustrates an asymmetric floristic exchange between Asia and Australia in this genus, which has been facilitated by the formation of terrestrial connections in the late Miocene and the expansion of wet tropical forests across Wallace's Line and beyond.

Caspase-11/4 and gasdermin D-mediated pyroptosis contributes to podocyte injury in mouse diabetic nephropathy.

Diabetic nephropathy (DN) is characterized by sterile inflammation with continuous injury and loss of renal inherent parenchyma cells. Podocyte is an essential early injury target in DN. The injury and loss of podocytes are closely associated with proteinuria, the early symptom of renal injury in DN. However, the exact mechanism for podocyte injury and death in DN remains ambiguous. In this study we investigated whether pyroptosis, a newly discovered cell death pathway was involved in DN. Diabetic mice were generated by high-fat diet/STZ injections. We showed that the expression levels of caspase-11 and cleavage of gasdermin D (GSDMD-N) in podocytes were significantly elevated, accompanied by reduced expression of podocyte makers nephrin and podocin, loss and fusion in podocyte foot processes, increased inflammatory cytokines NF-κB, IL-1ß, and IL-18, macrophage infiltration, glomerular matrix expansion and increased urinary albumin to creatinine ratio (UACR). All these changes in diabetic mice were blunted by knockout of caspase-11 or GSDMD. Cultured human and mouse podocytes were treated with high glucose (30 mM), which significantly increased the expression levels of caspase-11 or caspase-4 (the homolog of caspase-11 in human), GSDMD-N, NF-κB, IL-1ß, and IL-18, and decreased the expression of nephrin and podocin. Either caspase-4 or GSDMD knockdown by siRNA significantly blunted these changes. In summary, our results demonstrate that caspase-11/4 and GSDMD-mediated pyroptosis is activated and involved in podocyte loss under hyperglycemia condition and the development of DN.

KLF4 initiates sustained YAP activation to promote renal fibrosis in mice after ischemia-reperfusion kidney injury.

Acute renal injury (AKI) causes a long-term risk for progressing into chronic kidney disease (CKD) and interstitial fibrosis. Yes-associated protein (YAP), a key transcriptional cofactor in Hippo signaling pathway, shuttles between the cytoplasm and nucleus, which is required for the renal tubular epithelial cells repair in the acute phase of AKI. In this study we investigated the role of YAP during ischemia-reperfusion (IR)-induced AKI to CKD. Mice were subjected to left kidney IR followed by removal of the right kidney on the day before tissue harvests. Mouse shRNA expression adenovirus (Ad-shYAP or Ad-shKLF4) and mouse KLF4 expression adenovirus (Ad-KLF4) were delivered to mice by intrarenal injection on D7 after IR. We showed that the expression and nucleus distribution of YAP were persistently increased until the end of experiment (D21 after IR). The sustained activation of YAP in post-acute phase of AKI was accompanied by renal dysfunction and interstitial fibrosis. Knockdown of YAP significantly attenuated IR-induced renal dysfunction and decreased the expression of fibrogenic factors TGF-ß and CTGF in the kidney. We showed that the expression of the transcription factor KLF4, lined on the upstream of YAP, was also persistently increased. Knockdown on KLF4 attenuated YAP increase and nuclear translocation as well as renal functional deterioration and interstitial fibrosis in IR mice, whereas KLF4 overexpression caused opposite effects. KLF4 increased the expression of ITCH, and ITCH facilitated YAP nuclear translocation via degrading LATS1. Furthermore, we demonstrated in primary cultured renal tubular cells that KLF4 bound to the promoter region of YAP and positively regulates YAP expression. In biopsy sample from CKD patients, we also observed increased expression and nuclear distribution of YAP. In conclusion, the activation of YAP in the post-acute phase of AKI is implicated in renal functional deterioration and fibrosis although it exhibits beneficial effect in acute phase. Reprogramming factor KLF4 is responsible for the persistent activation of YAP. Blocking the activation of KLF4-YAP pathway might be a way to prevent the transition of AKI into CKD.

c-Myc promotes tubular cell apoptosis in ischemia-reperfusion-induced renal injury by negatively regulating c-FLIP and enhancing FasL/Fas-mediated apoptosis pathway.

c-Myc plays an important role in cell proliferation, differentiation, and cell apoptosis. FasL/Fas pathway is a key regulator of cell apoptosis. This study was aimed to investigate the effects of c-Myc on the FasL/Fas pathway in ischemia-reperfusion (I/R)-induced renal injury. Rats were objected to bilateral renal ischemia for 60 min and reperfused for 24 or 48 h. NRK-52E cells were treated with hypoxia-reoxygenation (H/R) or FasL. Immunohistochemistry was used to identify the distribution of c-Myc. Cell apoptosis was assessed by TUNEL staining. Ad-c-Myc and recombinant pcDAN 3.0 were used to overexpress c-Myc and c-FLIP, respectively. ChIP assay and luciferase assay were used to detect the binding of c-Myc to c-FLIP promoter. In I/R rats, c-Myc was increased significantly and mainly located in renal tubular epithelial cells; meanwhile, c-FLIP was decreased, cleaved caspase-8, cleaved caspase-3 and TUNEL-positive staining cells were increased. Treatment of I/R rats with c-Myc inhibitor 10058-F4 significantly attenuated the decrease in c-FLIP, the increase in cleaved caspase-8, cleaved caspase-3, TUNEL-positive cells, Scr and BUN in I/R rats. In NRK-52E cells, hypoxia and reoxygen induced the increase in c-Myc and decrease in c-FLIP. ChIP and luciferase assay results indicated that c-Myc binds to the promoter region of c-FLIP gene. Overexpression of c-Myc markedly decreased c-FLIP. Overexpression of c-FLIP inhibited the increase in cleaved caspase-8 and caspase-3 induced by FasL. Data indicated that c-Myc is increased in kidneys of I/R rats and negatively regulates the expression of c-FLIP, then enhanced FasL-induced cell apoptosis in I/R stress.

Caspase-11 promotes renal fibrosis by stimulating IL-1ß maturation via activating caspase-1.

Caspase-11 is a key upstream modulator for activation of inflammatory response under pathological conditions. In this study, we investigated the roles of caspase-11 in the maturation of interleukin-1ß (IL-1ß) and development of renal interstitial fibrosis in vivo and in vitro. Mice were subjected to unilateral ureteral obstruction (UUO). The mice were treated with either caspase-11 inhibitor wedelolactone (Wed, 30 mg/kg/day, ig) for 7 days or caspase-11 siRNA (10 nmol/20 g body weight per day, iv) for 14 days. The mice were euthanized on day 14, their renal tissue and blood sample were collected. We found that the obstructed kidney had significantly higher caspase-11 levels and obvious tubular injury and interstitial fibrosis. Treatment with Wed or caspase-11 siRNA significantly mitigated renal fibrosis in UUO mice, evidenced by the improved histological changes. Furthermore, caspase-11 inhibition significantly blunted caspase-1 activation, IL-1ß maturation, transforming growth factor-ß (TGF-ß), fibronectin, and collagen I expressions in the obstructed kidney. Renal tubular epithelial NRK-52E cells were treated in vitro with angiotensin (Ang, 1 µmol/L), which stimulated caspase-11 activation and IL-1ß maturation. Treatment with IL-1ß (20 ng/ml) significantly increased the expression of TGF-ß, fibronectin, and collagen I in the cells. Ang II-induced expression of TGF-ß, fibronectin, and collagen I were suppressed by caspase-11 siRNA or Wed. Finally, we revealed using co-immunoprecipitation that caspase-11 was able to interact with caspase-1 in NRK-52E cells. These results suggest that caspase-11 is involved in UUO-induced renal fibrosis. Elevation of caspase-11 in the obstructed kidney promotes renal fibrosis by stimulating caspase-1 activation and IL-1ß maturation.

Boreotropical range expansion and long-distance dispersal explain two amphi-Pacific tropical disjunctions in Sabiaceae.

Sabiaceae comprises three genera and ca. 80 species with an amphi-Pacific tropical disjunct distribution. It has been unclear whether the family is monophyletic, where the family belongs within the angiosperm phylogeny, and when and how is present-day disjunct distribution originated. To address these questions, we conducted a phylogenetic analysis of Sabiaceae with comprehensive sampling of the family and basal eudicots using six chloroplast DNA loci (atpB, rbcL, matK, ndhF, atpB-rbcL and trnL-trnF). Our results support the monophyly of Sabiaceae s. l. that includes three genera: Meliosma Blume, Ophiocaryon Endl. and Sabia Colebr. The placement of Sabiaceae as sister to Proteales receives moderate bootstrap support, and is corroborated by various alternative hypothesis tests. Within Sabiaceae, Ophiocaryon and Sabia were resolved as strongly supported clades, whereas Meliosma was paraphyletic with Ophiocaryon nested within it. The biogeographically disjunct accessions of Meliosma alba (which is alternatively known as Kingsboroughia alba (Schltdl.) Liebm.) sampled from southwestern China and Mexico form a monophyletic group. Molecular dating and ancestral area reconstruction suggest a Eurasian origin of Sabiaceae in the late Cretaceous and a boreotropical range expansion during Paleogene. Southward migrations were inferred from continental Eurasia to the Malesian region in Sabia and in the Asian Meliosma, and from Central America to South America in the Neotropical clade of Meliosma in response to climatic cooling after the late Miocene. A long distance dispersal from Central America to tropical Asia was suggested during the time at the Neogene and Quaternary boundary in Meliosma alba (now recognized as Kingsboroughia alba). Our results also support the recognition of Kingsboroughia Liebm. as a distinct genus to maintain the monophyly of each of the genera: Meliosma, Ophiocaryon and Sabia. Kingsboroughia along with Meliosma and Ophiocaryon constitutes the subfamily Meliosmoideae Mast., while Sabia is the sole genus of Sabioideae Y.W. Law & Y.F. Wu.

Combining complete chloroplast genome sequences with target loci data and morphology to resolve species limits in Triplostegia (Caprifoliaceae).

Species represent the most basic unit of taxonomy. As such, species delimitation represents a crucial issue for biodiversity conservation. Taxonomic practices were revolutionized in the last three decades due to the increasing availability of molecular phylogenetic data. The genus Triplostegia (Caprifoliaceae) traditionally consists of two species, T. glandulifera and T. grandiflora, distinguishable mainly based on quantitative morphological features. In this study, we sequenced nine chloroplast loci (i.e., accD, psbK-psbI, rbcL-accD, rpoB-trnC, rps16-trnQ, trnE-trnT, trnF-ndhJ, trnH-psbA, trnS-trnG) and one nuclear locus (ITS) of 16 individuals of Triplostegia representing the entire distribution range of both species recognized. Furthermore, we also obtained whole chloroplast sequences for 11 of the 16 individuals for which silica gel-dried leaves were available. Our phylogenetic analyses integrating chloroplast genome sequences and multiple loci data revealed that Triplostegia includes four main clades that largely match geography. Neither T. grandiflora nor T. glandulifera was recovered as monophyletic and no diagnosable differences in leaf, flower, and pollen traits were detected between the two species, indicating the need for a revised species circumscription within Triplostegia. Our study highlights the importance of combining data from different sources while defining species limits.

SND p102 promotes extracellular matrix accumulation and cell proliferation in rat glomerular mesangial cells via the AT1R/ERK/Smad3 pathway.

SND p102 was first described as a transcriptional co-activator, and subsequently determined to be a co-regulator of Pim-1, STAT6 and STAT5. We previously reported that SND p102 expression was increased in high glucose-treated mesangial cells (MCs) and plays a role in the extracellular matrix (ECM) accumulation of MCs by regulating the activation of RAS. In this study, we further examined the roles of SND p102 in diabetic nephropathy (DN)-induced glomerulosclerosis. Rats were injected with STZ (50 mg/kg, ip) to induce diabetes. MCs or isolated glomeruli were cultured in normal glucose (NG, 5.5 mmol/L)- or high glucose (HG, 25 mmol/L)-containing DMEM. We found that SND p102 expression was significantly increased in the diabetic kidneys, as well as in HG-treated isolated glomeruli and MCs. In addition, HG treatment induced significant fibrotic changes in MCs evidenced by enhanced protein expression of TGF-ß, fbronectin and collagen IV, and significantly increased the proliferation of MCs. We further revealed that overexpression of SND p102 significantly increased the protein expression of angiotensin II (Ang II) type 1 receptor (AT1R) in MCs by increasing its mRNA levels via directly targeting the AT1R 3'-UTR, which resulted in activation of the ERK/Smad3 signaling and subsequently promoted the up-regulation of fbronectin, collagen IV, and TGF-ß in MCs, as well as the cell proliferation. These results demonstrate that SND p102 is a key regulator of AT1R-mediating ECM synthesis and cell proliferation in MCs. Thus, small molecule inhibitors of SND p102 may be a novel therapeutic strategy for DN.

[Advances in mechanism of autophagy in renal tubular injury].

Autophagy is a lysosome-dependent degradation process that eliminates damaged macromolecular proteins and aging organelles to maintain intracellular homeostasis. Autophagy is observed in almost all eukaryotic cells and plays important roles in many cellular physiological processes, including the cell proliferation and growth, cellular functional alteration and phenotypical transition. Renal tubule is an important target for renal injury under different pathological conditions. Following the discoveries of the molecular basis of autophagy, accumulated lines of evidence have indicated that autophagy dysfunction in tubule is involved in the pathogenesis of many renal diseases. This review will summarize the recent progress in molecule mechanism of autophagy and its roles in renal tubular injury.

Vitamin K3 inhibits mouse uterine contraction in vitro via interference with the calcium transfer and the potassium channels.

Previous studies have demonstrated vitamin K3 had a great relief to smooth muscle spastic disorders, but no researches have yet pinpointed its possible anti-contractile activity in the uterus. Here, we evaluated the effect of vitamin K3 on myometrial contractility and explored the possible mechanisms of vitamin K3 action. Myograph apparatus were used to record the changes in contractility of isolated mouse uterine strips in a tissue bath. Uterine strips were exposed to vitamin K3 or vehicle. Vitamin K3 suppressed spontaneous contractions in a concentration dependent manner. It significantly decreased the contractile frequency induced by PGF2ɑ but not their amplitude (expect 58.0 µM). Prior incubation with vitamin K3 reduced the effectiveness of PGF2ɑ-induced contraction. The antispasmodic effect of vitamin K3 was also sensitive to potassium channel blockers, such as tetraethylammonium, 4-aminopyridine, iberiotoxin) but not to the nitric oxide related pathway blockers. High concentrations (29.0, 58.0 µM) of vitamin K3 weakened the Ca(2+) dose response and inhibited phase 1 contraction (intracellular stored calcium release). These dates suggest that vitamin K3 specifically suppresses myometrial contractility by affecting calcium and potassium channels; thus, this approach has potential therapy for uterine contractile activity related disorders.

Label-free electrochemical immunosensor based on Nile blue A-reduced graphene oxide nanocomposites for carcinoembryonic antigen detection.

In this article, a novel, label-free, and inherent electroactive redox immunosensor for carcinoembryonic antigen (CEA) based on gold nanoparticles (AuNPs) and Nile blue A (NB) hybridized electrochemically reduced graphene oxide (NB-ERGO) is proposed. The composite of NB-graphene oxide (NB-GO) was prepared by π-π stacking interaction. Then, chronoamperometry was adopted to simultaneously reduce HAuCl4 and nanocomposites of NB-GO for synthesizing AuNPs/NB-ERGO. The immunosensor was fabricated by capturing CEA antibody (anti-CEA) at this nanocomposite modified electrode. The immunosensor determination was based on the fact that, due to the formation of antigen-antibody immunocomplex, the decreased response currents of NB were directly proportional to the concentrations of CEA. Under optimal conditions, the linear range of the proposed immunosensor was estimated to be from 0.001 to 40 ng ml(-1) and the detection limit was estimated to be 0.00045 ng ml(-1). The proposed immunosensor was used to determine CEA in clinical serum samples with satisfactory results. The proposed method may provide promising potential application in clinical immunoassays with the properties of facile procedure, stability, high sensitivity, and selectivity.