Bony-fish-like scales in a Silurian maxillate placoderm.

Major groups of jawed vertebrates exhibit contrasting conditions of dermal plates and scales. But the transition between these conditions remains unclear due to rare information on taxa occupying key phylogenetic positions. The 425-million-year-old fish Entelognathus combines an unusual mosaic of characters typically associated with jawed stem gnathostomes or crown gnathostomes. However, only the anterior part of the exoskeleton was previously known for this very crownward member of the gnathostome stem. Here, we report a near-complete post-thoracic exoskeleton of Entelognathus. Strikingly, its scales are large and some are rhomboid, bearing distinctive peg-and-socket articulations; this combination was previously only known in osteichthyans and considered a synapomorphy of that group. The presence in Entelognathus of an anal fin spine, previously only found in some stem chondrichthyans, further illustrates that many characters previously thought to be restricted to specific lineages within the gnathostome crown likely arose before the common ancestor of living jawed vertebrates.

Citrus dataset for image classification.

Citrus fruits are a specialty of the subtropical region and are currently the most widely cultivated and produced fruits in Taiwan. They contain a wealth of vitamins and minerals, including vitamin C, potassium, magnesium, and more, offering anti-inflammatory and antioxidant benefits. Citrus plants are among the economically significant fruits in Taiwan, and there are several citrus species that share a similar appearance. We have constructed a database containing the four most commonly purchased citrus varieties in the market. This database comprises a total of 1379 original images, which have been expanded to 7584 images using six different data augmentation methods. We have chosen three Convolutional Neural Network (CNN) models that have achieved an accuracy rate exceeding 95 % in classifying the four varieties of citrus fruits.

Antioxidant, Collagenase Inhibitory, and Antibacterial Effects of Bioactive Peptides Derived from Enzymatic Hydrolysate of Ulva australis.

The protein extract of Ulva australis hydrolyzed with Alcalase and Flavourzyme was found to have multi-functional properties, including total antioxidant capacity (TAC), collagenase inhibitory, and antibacterial activities. The #5 fraction (SP5) and #7 fraction (SP7) of U. australis hydrolysate from cation-exchange chromatography displayed significantly high TAC, collagenase inhibitory, and antibacterial effects against Propionibacterium acnes, and only the Q3 fraction from anion-exchange chromatography displayed high multi-functional activities. Eight of 42 peptides identified by MALDI-TOF/MS and Q-TOF/MS/MS were selected from the results for screening with molecular docking on target proteins and were then synthesized. Thr-Gly-Thr-Trp (TGTW) displayed ABTS [2,2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid)] radical scavenging activity. The effect of TAC as Trolox equivalence was dependent on the concentration of TGTW. Asn-Arg-Asp-Tyr (NRDY) and Arg-Asp-Arg-Phe (RDRF) exhibited collagenase inhibitory activity, which increased according to the increase in concentration, and their IC50 values were 0.95 mM and 0.84 mM, respectively. Peptides RDRF and His-Ala-Val-Tyr (HAVY) displayed anti-P. Acnes effects, with IC50 values of 8.57 mM and 13.23 mM, respectively. These results suggest that the U. australis hydrolysate could be a resource for the application of effective nutraceuticals and cosmetics.

NME3 binds to phosphatidic acid and mediates PLD6-induced mitochondrial tethering.

Mitochondria are dynamic organelles regulated by fission and fusion processes. The fusion of membranes requires elaborative coordination of proteins and lipids and is particularly crucial for the function and quality control of mitochondria. Phosphatidic acid (PA) on the mitochondrial outer membrane generated by PLD6 facilitates the fusion of mitochondria. However, how PA promotes mitochondrial fusion remains unclear. Here, we show that a mitochondrial outer membrane protein, NME3, is required for PLD6-induced mitochondrial tethering or clustering. NME3 is enriched at the contact interface of two closely positioned mitochondria depending on PLD6, and NME3 binds directly to PA-exposed lipid packing defects via its N-terminal amphipathic helix. The PA binding function and hexamerization confer NME3 mitochondrial tethering activity. Importantly, nutrient starvation enhances the enrichment efficiency of NME3 at the mitochondrial contact interface, and the tethering ability of NME3 contributes to fusion efficiency. Together, our findings demonstrate NME3 as a tethering protein promoting selective fusion between PLD6-remodeled mitochondria for quality control.

Improved source localization in passive acoustic mapping using delay-multiply-and-sum beamforming with virtually augmented aperture.

High-intensity focused ultrasound (HIFU) is a promising non-invasive treatment method whose applications include tissue ablation, hemostasis, thrombolysis and blood-brain barrier opening etc. Its therapeutic effects come from the thermal necrosis and the mechanical destruction associated with acoustic cavitation. Passive acoustic mapping (PAM) is capable of simultaneous monitoring of HIFU-induced cavitation events using only receive beamforming. Nonetheless, conventional time exposure acoustics (TEA) algorithm has poor spatial resolution and suffers from the X-shaped artifacts. These factors lead to difficulties in precise localization of cavitation source. In this study, we proposed a novel adaptive PAM method which combines Delay-Multiply-and-Sum (DMAS) beamforming with virtual augmented aperture (VA) to overcome the problem. In DMAS-VA beamforming, the magnitude of each channel waveform is scaled by p-th root while the phase is multiplied by L. The p and L correspond respectively to the degree of signal coherence in DMAS beamforming and the augmentation factor of aperture size. After channel sum, p-th power is applied to restore the dimensionality of source strength and then the PAM image is reconstructed by accumulating the signal power over the observation time. Based on simulation and experimental results, the proposed DMAS-VA has better image resolution and image contrast compared with the conventional TEA. Moreover, since the VA method may introduce grating lobes into PAM because of the virtually augmented pitch size, DMAS coherent factor (DCF) is further developed to alleviate these image artifacts. Results indicate that, with DCF weighting, the PAM image of DMAS-VA beamforming could be constructed without detectable image artifacts from grating lobes and false main lobes.

Multi-Feature Transformer-Based Learning for Continuous Human Motion Recognition with High Similarity Using mmWave FMCW Radar.

Doppler-radar-based continuous human motion recognition recently has attracted extensive attention, which is a favorable choice for privacy and personal security. Existing results of continuous human motion recognition (CHMR) using mmWave FMCW Radar are not considered the continuous human motion with the high similarity problem. In this paper, we proposed a new CHMR algorithm with the consideration of the high similarity (HS) problem, called as CHMR-HS, by using the modified Transformer-based learning model. As far as we know, this is the first result in the literature to investigate the continuous HMR with the high similarity. To obtain the clear FMCW radar images, the background and target signals of the detected human are separated through the background denoising and the target extraction algorithms. To investigate the effects of the spectral-temporal multi-features with different dimensions, Doppler, range, and angle signatures are extracted as the 2D features and range-Doppler-time and range-angle-time signatures are extracted as the 3D features. The 2D/3D features are trained into the adjusted Transformer-encoder model to distinguish the difference of the high-similarity human motions. The conventional Transformer-decoder model is also re-designed to be Transformer-sequential-decoder model such that Transformer-sequential-decoder model can successfully recognize the continuous human motions with the high similarity. The experimental results show that the accuracy of our proposed CHMR-HS scheme are 95.2% and 94.5% if using 3D and 2D features, the simulation results also illustrates that our CHMR-HS scheme has advantages over existing CHMR schemes.

The oldest complete jawed vertebrates from the early Silurian of China.

Molecular studies suggest that the origin of jawed vertebrates was no later than the Late Ordovician period (around 450 million years ago (Ma))1,2. Together with disarticulated micro-remains of putative chondrichthyans from the Ordovician and early Silurian period3-8, these analyses suggest an evolutionary proliferation of jawed vertebrates before, and immediately after, the end-Ordovician mass extinction. However, until now, the earliest complete fossils of jawed fishes for which a detailed reconstruction of their morphology was possible came from late Silurian assemblages (about 425 Ma)9-13. The dearth of articulated, whole-body fossils from before the late Silurian has long rendered the earliest history of jawed vertebrates obscure. Here we report a newly discovered Konservat-Lagerstätte, which is marked by the presence of diverse, well-preserved jawed fishes with complete bodies, from the early Silurian (Telychian age, around 436 Ma) of Chongqing, South China. The dominant species, a 'placoderm' or jawed stem gnathostome, which we name Xiushanosteus mirabilis gen. et sp. nov., combines characters from major placoderm subgroups14-17 and foreshadows the transformation of the skull roof pattern from the placoderm to the osteichthyan condition10. The chondrichthyan Shenacanthus vermiformis gen. et sp. nov. exhibits extensive thoracic armour plates that were previously unknown in this lineage, and include a large median dorsal plate as in placoderms14-16, combined with a conventional chondrichthyan bauplan18,19. Together, these species reveal a previously unseen diversification of jawed vertebrates in the early Silurian, and provide detailed insights into the whole-body morphology of the jawed vertebrates of this period.

Probing invadosomes: technologies for the analysis of invadosomes.

Invadosomes are protrusive and mechanosensitive actin devices critical for cell migration, invasion, and extracellular matrix remodeling. The dynamic, proteolytic, and protrusive natures of invadosomes have made these structures fascinating and attracted many scientists to develop new technologies for their analysis. With these exciting methodologies, many biochemical and biophysical properties of invadosomes have been well characterized and appreciated, and those discoveries elegantly explained the biological and pathological effects of invadosomes in human health and diseases. In this review, we focus on these commonly used or newly developed methods for invadosome analysis and effort to reason some discrepancies among those assays. Finally, we explore the opposite regulatory mechanisms among invadosomes and focal adhesions, another actin-rich adhesive structures, and speculate a potential rule for their switch.

A new Silurian fish close to the common ancestor of modern gnathostomes.

The Silurian Period occupies a pivotal stage in the unfolding of key evolutionary events, including the rise of jawed vertebrates.1-4 However, the understanding of this early diversification is often hampered by the patchy nature of the Silurian fossil record,5 with the articulated specimens of jawed vertebrates only known in isolated localities, most notably Qujing, Yunnan, China.6-9 Here, we report a new Silurian maxillate placoderm, Bianchengichthys micros, from the Ludlow of Chongqing, with a near-complete dermatoskeleton preserved in articulation. Although geographically separated, the new taxon resembles the previously reported Qilinyu in possessing a unique combination of dermatoskeletal characters. However, the dermal bone of the mandible in Bianchengichthys unexpectedly differs from those in both Qilinyu and Entelognathus and displays a broad oral lamina carrying a line of tooth-like denticles, in addition to the marginal toothless flange. The external morphology of the pectoral fin is preserved and reveals an extensively scale-covered lobate part, flanked by a fringe of lepidotrichia-like aligned scales. The phylogenetic analysis reveals that Bianchengichthys is positioned immediately below Entelognathus plus modern gnathostomes. The discovery significantly widens the distribution of Silurian placoderm-grade gnathostomes in South China and provides a range of morphological disparity for the outgroup comparison to the earliest evolution of jaws, dentitions, and pectoral fins in modern gnathostomes. We also demonstrate that the previously reported Silurian placoderms from central Vietnam10 are maxillate placoderms close to Qilinyu, Silurolepis, and Bianchengichthys, corroborating the paleogeographic proximity between the Indochina and South China blocks during the Middle Paleozoic.11.

Endocast and Bony Labyrinth of a Devonian "Placoderm" Challenges Stem Gnathostome Phylogeny.

Our understanding of the earliest evolution of jawed vertebrates depends on a credible phylogenetic framework for the jawed stem gnathostomes collectively known as "placoderms".1 However, their relationships, and whether placoderms represent a single radiation or a paraphyletic array, remain contentious.2-13 This uncertainty is compounded by an uneven understanding of anatomy across the group, particularly of the phylogenetically informative braincase and brain cavity-endocast. Based on new tomographic data, we here describe the endocast and bony labyrinth of Brindabellaspis stensioi from the Early Devonian of New South Wales.14 The taxon was commonly recovered as branching near the base of placoderms.5-9,11,12,15-17 Previous studies of Brindabellaspis emphasized its resemblances with fossil jawless fishes in the braincase anatomy14 and endocast proportions1,18 and its distinctive features were interpreted as autapomorphies, such as the elongated premedian region.19 Although our three-dimensional data confirmed the resemblance of its endocast to those of jawless vertebrates, we discovered that the inner ear and endolymphatic complex display a repertoire of previously unrecognized characters close to modern or crown-group jawed vertebrates, including a pronounced sinus superior and a vertical duct that connects the endolymphatic sac and the labyrinth cavity. Both parsimony and Bayesian analyses suggest that prevailing hypotheses of placoderm relationships are unstable, with newly revealed anatomy pointing to a radical revision of early gnathostome evolution. Our results call into question the appropriateness of arthrodire-like placoderms as models of primitive gnathostome anatomy and raise questions of homology relating to key cranial features.

Reappraisal of the Silurian placoderm Silurolepis and insights into the dermal neck joint evolution.

Silurolepis platydorsalis, a Silurian jawed vertebrate originally identified as an antiarch, is here redescribed as a maxillate placoderm close to Qilinyu and is anteroposteriorly reversed as opposed to the original description. The cuboid trunk shield possesses three longitudinal cristae, obstanic grooves on the trunk shield and three median dorsal plates, all uniquely shared with Qilinyu. Further preparation reveals the morphology of the dermal neck joint, with slot-shaped articular fossae on the trunk shield similar to Qilinyu and antiarchs. However, new tomographic data reveal that Qilinyu uniquely bears a dual articulation between the skull roof and trunk shield, which does not fit into the traditional 'ginglymoid' and 'reverse ginglymoid' categories. An extended comparison in early jawed vertebrates confirms that a sliding-type dermal neck joint is widely distributed and other types are elaborated in different lineages by developing various laminae. Nine new characters related to the dermal neck joint are proposed for a new phylogenetic analysis, in which Silurolepis forms a clade with Qilinyu. The current phylogenetic framework conflicts with the parsimonious evolution of dermal neck joints in suggesting that the shared trunk shield characters between antiarchs and Qilinyu are independently acquired, and the sliding-type joint in Entelognathus is reversely evolved from the dual articulation in Qilinyu.

An acute decrease in plasma membrane tension induces macropinocytosis via PLD2 activation.

Internalization of macromolecules and membrane into cells through endocytosis is critical for cellular growth, signaling and plasma membrane (PM) tension homeostasis. Although endocytosis is responsive to both biochemical and physical stimuli, how physical cues modulate endocytic pathways is less understood. Contrary to the accumulating discoveries on the effects of increased PM tension on endocytosis, less is known about how a decrease of PM tension impacts on membrane trafficking. Here, we reveal that an acute decrease of PM tension results in phosphatidic acid (PA) production, F-actin and phosphatidylinositol (4,5)-bisphosphate [PI(4,5)P2]-enriched dorsal membrane ruffling and subsequent macropinocytosis in myoblasts. The PA production induced by decreased PM tension depends on phospholipase D2 (PLD2) activation via PLD2 nanodomain disintegration. Furthermore, the 'decreased PM tension-PLD2-macropinocytosis' pathway is prominent in myotubes, reflecting a potential mechanism of PM tension homeostasis upon intensive muscle stretching and relaxation. Together, we identify a new mechanotransduction pathway that converts an acute decrease in PM tension into PA production and then initiates macropinocytosis via actin and PI(4,5)P2-mediated processes.

Organocatalytic Atroposelective Friedländer Quinoline Heteroannulation.

An atroposelective Friedländer heteroannulation reaction of 2-aminoaryl ketones with α-methylene carbonyl derivatives has been developed for the first time with chiral phosphoric acid as an efficient organocatalyst. The desired enantioenriched axially chiral polysubstituted 4-arylquinoline architectures were prepared with good to high yields and enantioselectivities (up to 94% yield and up to 97% ee). Furthermore, the products can be readily derivatized to afford an array of new quinoline-containing heteroatropisomers, which hold great potential in asymmetric catalysis and drug discovery.

Tks5 and Dynamin-2 enhance actin bundle rigidity in invadosomes to promote myoblast fusion.

Skeletal muscle development requires the cell-cell fusion of differentiated myoblasts to form muscle fibers. The actin cytoskeleton is known to be the main driving force for myoblast fusion; however, how actin is organized to direct intercellular fusion remains unclear. Here we show that an actin- and dynamin-2-enriched protrusive structure, the invadosome, is required for the fusion process of myogenesis. Upon differentiation, myoblasts acquire the ability to form invadosomes through isoform switching of a critical invadosome scaffold protein, Tks5. Tks5 directly interacts with and recruits dynamin-2 to the invadosome and regulates its assembly around actin filaments to strengthen the stiffness of dynamin-actin bundles and invadosomes. These findings provide a mechanistic framework for the acquisition of myogenic fusion machinery during myogenesis and reveal a novel structural function for Tks5 and dynamin-2 in organizing actin filaments in the invadosome to drive membrane fusion.

HIF1α regulates single differentiated glioma cell dedifferentiation to stem-like cell phenotypes with high tumorigenic potential under hypoxia.

The standard treatment for Glioblastoma multiforme (GBM) is surgical resection and subsequent radiotherapy and chemotherapy. Surgical resection of GBM is typically restricted because of its invasive growth, which results in residual tumor cells including glioma stem cells (GSCs) and differentiated cells. Recurrence has been previously thought to occur as a result of these GSCs, and hypoxic microenvironment maintains the GSCs stemness also plays an important role. Summarizing traditional studies and we find many researchers ignored the influence of hypoxia on differentiated cells. We hypothesized that the residual differentiated cells may be dedifferentiated to GSC-like cells under hypoxia and play a crucial role in the rapid, high-frequency recurrence of GBM. Therefore, isolated CD133-CD15-NESTIN- cells were prepared as single-cell culture and treated with hypoxia. More than 95% of the surviving single differentiated CD133-CD15-NESTIN- cell dedifferentiated into tumorigenic CD133+CD15+NESTIN+ GSCs, and this process was regulated by hypoxia inducible factor-1α. Moreover, the serum also played an important role in this dedifferentiation. These findings challenge the traditional glioma cell heterogeneity model, cell division model and glioma malignancy development model. Our study also highlights the mechanism of GBM recurrence and the importance of anti-hypoxia therapy. In addition to GSCs, residual differentiated tumor cells also substantially contribute to treatment resistance and the rapid, high recurrence of GBM.

Risk factors analysis and prognosis of the microvascular invasion of hepatocellular carcinoma / 中华消化外科杂志

Objective To explore the risk factors and prognosis of the microvascular invasion of hepatocellular carcinoma (HCC).Methods The retrospective case-control study was conducted.The clinicopathological data of 220 patients with HCC who were admitted to the Nanfang Hospital of Southern Medical University from July 2012 to July 2015 were collected.Among 220 patients,63 were confirmed with microvascular invasion of HCC by postoperative pathological examination after radical resection of HCC and 157 were not confirmed with microvascular invasion of HCC.Observation indicators:(1) univariate and multivariate analyses affecting microvascular invasion of HCC;(2) follow-up and survival situations.Follow-up using outpatient examination and telephone interview was performed to detect patients' survival and tumor recurrence up to July 2016.The univariate and multivariate analyses were done using the Logistic regression model.The survival curve and survival rate were respectively drawn and calculated by the Kaplan-Meier method,and the Log-rank test was used for survival analysis.Results (1) Univariate and multivariate analyses affecting microvascular invasion of HCC:the results of univariate analysis showed that maximum diameter of tumor,preoperative alpha-fetoprotein (AFP) and preoperative platelet (PLT) were related factors affecting microvascular invasion of HCC [OR =4.542,1.576,3.655,95％ confidence interval (CI):2.433-8.470,1.084-2.292,1.985-6.831,P＜0.05].The results of multivariate analysis showed that maximum diameter of tumor,preoperative AFP and preoperative PLT were independent factors affecting microvascular invasion of HCC (RR=3.386,1.563,2.247,95％CI:1.703-6.729,1.054-2.318,1.135-4.451,P＜0.05).(2) Follow-up and survival situations:220 patients were followed up for 12-48 months,with a median time of 26 months.The postoperative overall 1-and 2-year survival rates,postoperative 1-and 2-year tumor-free survival rates were 77.3％,50.0％,47.3％,38.0％ in 63 patients with microvascular invasion of HCC and 92.4％,77.2％,74.5％,69.4％ in 157 patients without microvascular invasion of HCC,with statistically significant differences (x2 =10.480,19.605,14.677,18.461,P＜ 0.05).Conclusion The maximum diameter of tumor,preoperative AFP and preoperative PLT are independent factors affecting microvascular invasion of HCC,and patients with microvascular invasion of HCC have poor clinical prognosis.

Risk factors analysis and prognosis of the microvascular invasion of hepatocellular carcinoma / 中华消化外科杂志

Objective To explore the risk factors and prognosis of the microvascular invasion of hepatocellular carcinoma (HCC).Methods The retrospective case-control study was conducted.The clinicopathological data of 220 patients with HCC who were admitted to the Nanfang Hospital of Southern Medical University from July 2012 to July 2015 were collected.Among 220 patients,63 were confirmed with microvascular invasion of HCC by postoperative pathological examination after radical resection of HCC and 157 were not confirmed with microvascular invasion of HCC.Observation indicators:(1) univariate and multivariate analyses affecting microvascular invasion of HCC;(2) follow-up and survival situations.Follow-up using outpatient examination and telephone interview was performed to detect patients' survival and tumor recurrence up to July 2016.The univariate and multivariate analyses were done using the Logistic regression model.The survival curve and survival rate were respectively drawn and calculated by the Kaplan-Meier method,and the Log-rank test was used for survival analysis.Results (1) Univariate and multivariate analyses affecting microvascular invasion of HCC:the results of univariate analysis showed that maximum diameter of tumor,preoperative alpha-fetoprotein (AFP) and preoperative platelet (PLT) were related factors affecting microvascular invasion of HCC [OR =4.542,1.576,3.655,95％ confidence interval (CI):2.433-8.470,1.084-2.292,1.985-6.831,P＜0.05].The results of multivariate analysis showed that maximum diameter of tumor,preoperative AFP and preoperative PLT were independent factors affecting microvascular invasion of HCC (RR=3.386,1.563,2.247,95％CI:1.703-6.729,1.054-2.318,1.135-4.451,P＜0.05).(2) Follow-up and survival situations:220 patients were followed up for 12-48 months,with a median time of 26 months.The postoperative overall 1-and 2-year survival rates,postoperative 1-and 2-year tumor-free survival rates were 77.3％,50.0％,47.3％,38.0％ in 63 patients with microvascular invasion of HCC and 92.4％,77.2％,74.5％,69.4％ in 157 patients without microvascular invasion of HCC,with statistically significant differences (x2 =10.480,19.605,14.677,18.461,P＜ 0.05).Conclusion The maximum diameter of tumor,preoperative AFP and preoperative PLT are independent factors affecting microvascular invasion of HCC,and patients with microvascular invasion of HCC have poor clinical prognosis.

A Devonian predatory fish provides insights into the early evolution of modern sarcopterygians.

Crown or modern sarcopterygians (coelacanths, lungfishes, and tetrapods) differ substantially from stem sarcopterygians, such as Guiyu and Psarolepis, and a lack of transitional fossil taxa limits our understanding of the origin of the crown group. The Onychodontiformes, an enigmatic Devonian predatory fish group, seems to have characteristics of both stem and crown sarcopterygians but is difficult to place because of insufficient anatomical information. We describe the new skull material of Qingmenodus, a Pragian (~409-million-year-old) onychodont from China, using high-resolution computed tomography to image internal structures of the braincase. In addition to its remarkable similarities with stem sarcopterygians in the ethmosphenoid portion, Qingmenodus exhibits coelacanth-like neurocranial features in the otic region. A phylogenetic analysis based on a revised data set unambiguously assigns onychodonts to crown sarcopterygians as stem coelacanths. Qingmenodus thus bridges the morphological gap between stem sarcopterygians and coelacanths and helps to illuminate the early evolution and diversification of crown sarcopterygians.

Discovery of APD334: Design of a Clinical Stage Functional Antagonist of the Sphingosine-1-phosphate-1 Receptor.

APD334 was discovered as part of our internal effort to identify potent, centrally available, functional antagonists of the S1P1 receptor for use as next generation therapeutics for treating multiple sclerosis (MS) and other autoimmune diseases. APD334 is a potent functional antagonist of S1P1 and has a favorable PK/PD profile, producing robust lymphocyte lowering at relatively low plasma concentrations in several preclinical species. This new agent was efficacious in a mouse experimental autoimmune encephalomyelitis (EAE) model of MS and a rat collagen induced arthritis (CIA) model and was found to have appreciable central exposure.

The largest Silurian vertebrate and its palaeoecological implications.

An apparent absence of Silurian fishes more than half-a-metre in length has been viewed as evidence that gnathostomes were restricted in size and diversity prior to the Devonian. Here we describe the largest pre-Devonian vertebrate (Megamastax amblyodus gen. et sp. nov.), a predatory marine osteichthyan from the Silurian Kuanti Formation (late Ludlow, ~423 million years ago) of Yunnan, China, with an estimated length of about 1 meter. The unusual dentition of the new form suggests a durophagous diet which, combined with its large size, indicates a considerable degree of trophic specialisation among early osteichthyans. The lack of large Silurian vertebrates has recently been used as constraint in palaeoatmospheric modelling, with purported lower oxygen levels imposing a physiological size limit. Regardless of the exact causal relationship between oxygen availability and evolutionary success, this finding refutes the assumption that pre-Emsian vertebrates were restricted to small body sizes.