Robust expansion of phylogeny for fast-growing genome sequence data.

Massive sequencing of SARS-CoV-2 genomes has urged novel methods that employ existing phylogenies to add new samples efficiently instead of de novo inference. 'TIPars' was developed for such challenge integrating parsimony analysis with pre-computed ancestral sequences. It took about 21 seconds to insert 100 SARS-CoV-2 genomes into a 100k-taxa reference tree using 1.4 gigabytes. Benchmarking on four datasets, TIPars achieved the highest accuracy for phylogenies of moderately similar sequences. For highly similar and divergent scenarios, fully parsimony-based and likelihood-based phylogenetic placement methods performed the best respectively while TIPars was the second best. TIPars accomplished efficient and accurate expansion of phylogenies of both similar and divergent sequences, which would have broad biological applications beyond SARS-CoV-2. TIPars is accessible from https://tipars.hku.hk/ and source codes are available at https://github.com/id-bioinfo/TIPars.

Characterization of an Emergent Chicken H3N8 Influenza Virus in Southern China: a Potential Threat to Public Health.

Although influenza A viruses of several subtypes have occasionally infected humans, to date only those of the H1, H2, and H3 subtypes have led to pandemics and become established in humans. The detection of two human infections by avian H3N8 viruses in April and May of 2022 raised pandemic concerns. Recent studies have shown the H3N8 viruses were introduced into humans from poultry, although their genesis, prevalence, and transmissibility in mammals have not been fully elucidated. Findings generated from our systematic influenza surveillance showed that this H3N8 influenza virus was first detected in chickens in July 2021 and then disseminated and became established in chickens over wider regions of China. Phylogenetic analyses revealed that the H3 HA and N8 NA were derived from avian viruses prevalent in domestic ducks in the Guangxi-Guangdong region, while all internal genes were from enzootic poultry H9N2 viruses. The novel H3N8 viruses form independent lineages in the glycoprotein gene trees, but their internal genes are mixed with those of H9N2 viruses, indicating continuous gene exchange among these viruses. Experimental infection of ferrets with three chicken H3N8 viruses showed transmission through direct contact and inefficient transmission by airborne exposure. Examination of contemporary human sera detected only very limited antibody cross-reaction to these viruses. The continuing evolution of these viruses in poultry could pose an ongoing pandemic threat. IMPORTANCE A novel H3N8 virus with demonstrated zoonotic potential has emerged and disseminated in chickens in China. It was generated by reassortment between avian H3 and N8 virus(es) and long-term enzootic H9N2 viruses present in southern China. This H3N8 virus has maintained independent H3 and N8 gene lineages but continues to exchange internal genes with other H9N2 viruses to form novel variants. Our experimental studies showed that these H3N8 viruses were transmissible in ferrets, and serological data suggest that the human population lacks effective immunological protection against it. With its wide geographical distribution and continuing evolution in chickens, other spillovers to humans can be expected and might lead to more efficient transmission in humans.

3D-Printing Multi-Component Multi-Domain Supramolecular Gels with Differential Conductivity.

We report the use of wet-spinning to 3D-print gels from low-molecular-weight gelators (LMWGs) based on the 1,3:2,4-dibenzylidenesorbitol (DBS) scaffold. Gel stripes assembled from DBS-CONHNH2 and DBS-COOH are printed, and their conductivities assessed. Printed gels based on DBS-CONHNH2 can be loaded with Au(III), which is reduced in situ to form embedded gold nanoparticles (AuNPs). The conductivity of these gels increases because of electron transport mediated by the AuNPs, whereas the conductivity of DBS-COOH, which does not promote AuNP formation, remains lower. We then fabricate multi-component gel patterns comprised of spatially well-defined domains of printed DBS-CONHNH2/AuNP (higher conductivity) and DBS-COOH (lower conductivity) resulting in soft multi-domain materials with differential conductivity. Such materials have future prospects in applications such as soft nanoelectronics or tissue engineering.

Fabricating Shaped and Patterned Supramolecular Multigelator Objects via Diffusion-Adhesion Gel Assembly.

We report the use of acid-diffusion to assemble core-shell supramolecular gel beads with different low-molecular-weight gelators (LMWGs) in the core and shell. These gel beads grow a shell of dibenzylidenesorbitol-based DBS-COOH onto a core comprising DBS-CONHNH2 and agarose that has been loaded with acetic acid. Diffusion of the acid from the core triggers shell assembly. The presence of DBS-CONHNH2 enables the gel core to be loaded with metal nanoparticles (NPs) as acyl hydrazide reduces metal salts in situ. The pH-responsiveness of DBS-COOH allows responsive assembly of the shell with both temporal and spatial control. By fixing multiple gel beads in a Petri dish, the cores become linked to one another by the assembled DBS-COOH gel shell─a process we describe as diffusion-adhesion assembly. By controlling the geometry of the beads with respect to one another, it is possible to pattern the structures, and using a layer-by-layer approach, 3D objects can be fabricated. If some of the beads are loaded with basic DBS-carboxylate instead of CH3COOH, they act as a "sink" for diffusing protons, preventing DBS-COOH shell assembly in the close proximity. Those beads do not adhere to the remainder of the growing gel object and can be simply removed once diffusion-assembly is complete, acting as templates, and enabling the fabrication of 3D "imprinted" multigel architectures. Preloading the gel beads with AuNPs or AgNPs suspends these functional units within the cores at precisely defined locations within a wider gel object. In summary, this approach enables the dynamic fabrication of shaped and patterned gels with embedded metal NPs─such objects have potential next-generation applications in areas including soft nanoelectronics and regenerative medicine.

Supramolecular gels - a panorama of low-molecular-weight gelators from ancient origins to next-generation technologies.

Supramolecular gels, self-assembled from low-molecular-weight gelators (LMWGs), have a long history and a bright future. This review provides an overview of these materials, from their use in lubrication and personal care in the ancient world, through to next-generation technologies. In academic terms, colloid scientists in the 19th and early 20th centuries first understood such gels as being physically assembled as a result of weak interactions, combining a solid-like network having a degree of crystalline order with a highly mobile liquid-like phase. During the 20th century, industrial scientists began using these materials in new applications in the polymer, oil and food industries. The advent of supramolecular chemistry in the late 20th century, with its focus on non-covalent interactions and controlled self-assembly, saw the horizons for these materials shifted significantly beyond their historic rheological applications, expanding their potential. The ability to tune the LMWG chemical structure, manipulate hierarchical assembly, develop multi-component systems, and introduce new types of responsive and interactive behaviour, has been transformative. Furthermore, the dynamics of these materials are increasingly understood, creating metastable gels and transiently-fueled systems. New approaches to shaping and patterning gels are providing a unique opportunity for more sophisticated uses. These supramolecular advances are increasingly underpinning and informing next-generation applications - from drug delivery and regenerative medicine to environmental remediation and sustainable energy. In summary, this article presents a panorama over the field of supramolecular gels, emphasising how both academic and industrial scientists are building on the past, and engaging new fundamental insights and innovative concepts to open up exciting horizons for their future use.

Alignment free sequence comparison methods and reservoir host prediction.

MOTIVATION: The emergence and subsequent pandemic of the SARS-CoV-2 virus raised urgent questions about its origin and, particularly, its reservoir host. These types of questions are long-standing problems in the management of emerging infectious diseases and are linked to virus discovery programs and the prediction of viruses that are likely to become zoonotic. Conventional means to identify reservoir hosts have relied on surveillance, experimental studies and phylogenetics. More recently, machine learning approaches have been applied to generate tools to swiftly predict reservoir hosts from sequence data. RESULTS: Here, we extend a recent work that combined sequence alignment and a mixture of alignment-free approaches using a gradient boosting machines machine learning model, which integrates genomic traits and phylogenetic neighbourhood signatures to predict reservoir hosts. We add a more uniform approach by applying Machine Learning with Digital Signal Processing-based structural patterns. The extended model was applied to an existing virus/reservoir host dataset and to the SARS-CoV-2 and related viruses and generated an improvement in prediction accuracy. AVAILABILITY AND IMPLEMENTATION: The source code used in this work is freely available at https://github.com/bill1167/hostgbms. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Hind limb muscle reconstruction in the incipiently opisthopubic large therizinosaur Nothronychus (Theropoda; Maniraptora).

Therizinosaurs are highly modified, probably herbivorous, theropods from the Upper Cretaceous of Asia and North America. They are characterized by an extensively pneumatized axial skeleton, and in the derived forms, an incipiently opisthopubic pelvis. The evolution of such a pelvis is expected to be associated with extensive modification of the muscular system. The muscular system is reconstructed using observed muscle scars, reconstructions of the theropods Staurikosaurus and Tyrannosaurus, the ornithischian Maiasaura, and extant crocodilians and birds. The results indicate convergence with birds and ornithischian dinosaurs, such that the retroverted pubis in some maniraptorans can be regarded as analogous with the postacetabular bar in ornithischians. Functional implications also make derived therizinosaurs, such as Nothronychus, in some respects convergent with birds as the pubis is retroverted, becoming fused with the ischium, a laterally flaring synsacrum, and an avian-like pes.

Forelimb musculature and function in the therizinosaur Nothronychus (Maniraptora, Theropoda).

Therizinosaurs are unusual theropods from the Upper Cretaceous of Asia and North America. North American representatives include Falcarius utahensis from central Utah, Nothronychus mckinleyi from west central New Mexico, and N. graffami from southern Utah. Nothronychus was quite large, with well-developed forelimbs and pectoral girdle. In many respects, however, these structures were typical for conventional carnivorous theropods, although therizinosaurs have been hypothesized to be herbivorous using anatomical and functional inferences. There is no indication of increased range of motion within the forelimbs, as might be predicted for derived non-avian theropods. The muscular anatomy of the pectoral girdle and forelimb of Nothronychus is reconstructed using visible muscle scars, data from extant birds and crocodilians, and models for other theropods. The osteology and inferred musculature is a mosaic of primitive and derived characters for theropods. A fossa pneumotricipitales may have been present in the proximal humerus. There was a well-developed fossa brachialis in the distal humerus. The epicleidium of the furcula is deflected, reflecting either taphonomic deformation or possibly accommodation of M. supracoracoideus in a triosseal canal, but such a development has yet to be described in any non-avian theropod. In many respects, the other muscular results were quite similar to those inferred for dromaeosaurs.

Vertebral pneumaticity of the North American therizinosaur Nothronychus.

Nothronychus was a large, derived therizinosaur from the Upper Cretaceous of Utah and New Mexico. The genus is known from elements that have been referred to single individuals. Therizinosaurs were unusual maniraptoran theropods close to the origin of birds. The axial skeleton is extensively pneumatized, but CT scans reveal an apneumatic synsacrum. Inferred air sacs invade the basicranium, the presacral vertebrae, and the proximal caudal vertebrae, but bypassed the sacrum resulting in a caudosacral hiatus similar to some sauropods and reflecting the development of multiple diverticula from the abdominal air sac. The vertebral pneumatic chambers are described here and compared with those observed in the theropod Allosaurus and the recent avian Dinornis. The vertebrae of Nothronychus are intermediate between those two theropods. It is inferred to have possessed avian-like abdominal air sacs. This theropod would have had unidirectional lungs, as in birds, but this character cannot be related to endothermy.

Self-Propelling Hybrid Gels Incorporating an Active Self-Assembled, Low-Molecular-Weight Gelator.

Hybrid gel beads based on combining a low-molecular-weight gelator (LMWG) with a polymer gelator (PG) demonstrate an enhanced ability to self-propel in water, with the LMWG playing an active role. Hybrid gel beads were loaded with ethanol and shown to move in water owing to the Marangoni effect changes in surface tension caused by the expulsion of ethanol - smaller beads move farther and faster than larger beads. Flat shapes of the hybrid gel were cut using a "stamp" - circles moved the furthest, whereas stars showed more rotation on their own axes. Comparing hybrid LMWG/PG gel beads with PG-only beads demonstrated that the LMWG speeds up the beads, enhancing the rate of self-propulsion. Self-assembly of the LMWG into a "solid-like" network prevents its leaching from the gel. The LMWG also retains its own unique function - specifically, remediating methylene blue pollutant dye from basic water as a result of noncovalent interactions. The mobile hybrid beads accumulate this dye more effectively than PG-only beads. Self-propelling gel beads have potential applications in removal/delivery of active agents in environmental or biological settings. The ability of self-assembling LMWGs to enhance mobility and control removal/delivery suggests that adding them to self-propelling systems can add significant value.

Hybrid Self-Assembled Gel Beads for Tuneable pH-Controlled Rosuvastatin Delivery.

This article describes the fabrication of new pH-responsive hybrid gel beads combining the polymer gelator calcium alginate with two different low-molecular-weight gelators (LMWGs) based on 1,3 : 2,4-dibenzylidene-d-sorbitol: pH-responsive DBS-COOH and thermally responsive DBS-CONHNH2 , thus clearly demonstrating that different classes of LMWG can be fabricated into gel beads by using this approach. We also demonstrate that self-assembled multicomponent gel beads can be formed by using different combinations of these gelators. The different gel bead formulations exhibit different responsiveness - the DBS-COOH network can disassemble within those beads in which it is present upon raising the pH. To exemplify preliminary data for a potential application for these hybrid gel beads, we explored aspects of the delivery of the lipid-lowering active pharmaceutical ingredient (API) rosuvastatin. The release profile of this statin from the hybrid gel beads is pH-dependent, with greater release at pH 7.4 than at pH 4.0 - primary control of this process results from the pKa of the API. The extent of pH-mediated API release is also significantly further modified according to gel bead composition. The DBS-COOH/alginate beads show rapid, highly effective drug release at pH 7.4, whereas the three-component DBS-COOH/DBS-CONHNH2 /alginate system shows controlled slow release of the API under the same conditions. These initial results indicate that such gel beads constitute a promising, versatile and easily tuned platform suitable for further development for controlled drug-delivery applications.

Dissemination, divergence and establishment of H7N9 influenza viruses in China.

Since 2013 the occurrence of human infections by a novel avian H7N9 influenza virus in China has demonstrated the continuing threat posed by zoonotic pathogens. Although the first outbreak wave that was centred on eastern China was seemingly averted, human infections recurred in October 2013 (refs 3-7). It is unclear how the H7N9 virus re-emerged and how it will develop further; potentially it may become a long-term threat to public health. Here we show that H7N9 viruses have spread from eastern to southern China and become persistent in chickens, which has led to the establishment of multiple regionally distinct lineages with different reassortant genotypes. Repeated introductions of viruses from Zhejiang to other provinces and the presence of H7N9 viruses at live poultry markets have fuelled the recurrence of human infections. This rapid expansion of the geographical distribution and genetic diversity of the H7N9 viruses poses a direct challenge to current disease control systems. Our results also suggest that H7N9 viruses have become enzootic in China and may spread beyond the region, following the pattern previously observed with H5N1 and H9N2 influenza viruses.

Catalytic Gels for a Prebiotically Relevant Asymmetric Aldol Reaction in Water: From Organocatalyst Design to Hydrogel Discovery and Back Again.

This paper reports an investigation into organocatalytic hydrogels as prebiotically relevant systems. Gels are interesting prebiotic reaction media, combining heterogeneous and homogeneous characteristics with a structurally organized active "solid-like" catalyst separated from the surrounding environment, yet in intimate contact with the solution phase and readily accessible via "liquid-like" diffusion. A simple self-assembling glutamine amide derivative 1 was initially found to catalyze a model aldol reaction between cyclohexanone and 4-nitrobenzaldehyde, but it did not maintain its gel structure during reaction. In this study, it was observed that compound 1 could react directly with the benzaldehyde to form a hydrogel in situ based on Schiff base 2 as a low-molecular-weight gelator (LMWG). This new dynamic gel is a rare example of a two-component self-assembled LMWG hydrogel and was fully characterized. It was demonstrated that glutamine amide 1 could select an optimal aldehyde component and preferentially assemble from mixtures. In the hunt for an organocatalyst, reductive conditions were applied to the Schiff base to yield secondary amine 3, which is also a highly effective hydrogelator at very low loadings with a high degree of nanoscale order. Most importantly, the hydrogel based on 3 catalyzed the prebiotically relevant aldol dimerization of glycolaldehyde to give threose and erythrose. In buffered conditions, this reaction gave excellent conversions, good diastereoselectivity, and some enantioselectivity. Catalysis using the hydrogel of 3 was much better than that using non-assembled 3-demonstrating a clear benefit of self-assembly. The results suggest that hydrogels offer a potential strategy by which prebiotic reactions can be promoted using simple, prebiotically plausible LMWGs that can selectively self-organize from complex mixtures. Such processes may have been of prebiotic importance.

Self-Assembled Supramolecular Hybrid Hydrogel Beads Loaded with Silver Nanoparticles for Antimicrobial Applications.

This Full Paper reports the formation of silver (Ag) NPs within spatially resolved two-component hydrogel beads, which combine a low-molecular-weight gelator (LMWG) DBS-CONHNH2 and a polymer gelator (PG) calcium alginate. The AgNPs are formed through in situ reduction of AgI , with the resulting nanoparticle-loaded gels being characterised in detail. The antibacterial activity of the nanocomposite gel beads was tested against two drug-resistant bacterial strains, often associated with hospital-acquired infections: vancomycin-resistant Enterococcus faecium (VRE) and Pseudomonas aeruginosa (PA14), and the AgNP-loaded gels showed good antimicrobial properties against both types of bacteria. It is suggested that the gel bead format of these AgNP-loaded hybrid hydrogels makes them promising versatile materials for potential applications in orthopaedics or wound healing.

Self-Assembling Supramolecular Hybrid Hydrogel Beads.

With the goal of imposing shape and structure on supramolecular gels, we combine a low-molecular-weight gelator (LMWG) with the polymer gelator (PG) calcium alginate in a hybrid hydrogel. By imposing thermal and temporal control of the orthogonal gelation methods, the system either forms an extended interpenetrating network or core-shell-structured gel beads-a rare example of a supramolecular gel formulated inside discrete gel spheres. The self-assembled LMWG retains its unique properties within the beads, such as remediating PdII and reducing it in situ to yield catalytically active Pd0 nanoparticles. A single PdNP-loaded gel bead can catalyse the Suzuki-Miyaura reaction, constituting a simple and easy-to-use reaction-dosing form. These uniquely shaped and structured LMWG-filled gel beads are a versatile platform technology with great potential in a range of applications.

Sequential Assembly of Mutually Interactive Supramolecular Hydrogels and Fabrication of Multi-Domain Materials.

A two-component self-sorting hydrogel based on acylhydrazide and carboxylic acid derivatives of 1,3:2,4-dibenzylidene-d-sorbitol (DBS-CONHNH2 and DBS-COOH) is reported. A heating-cooling cycle induces the self-assembly of DBS-CONHNH2 , followed by the self-assembly of DBS-COOH induced by decreasing pH. Although the networks are formed sequentially, there is spectroscopic evidence of interactions between them, which impact on the mechanical properties and significantly enhance the ability of these low-molecular-weight gelators (LMWGs) to form gels when mixed. The DBS-COOH network can be switched "off" and "on" within the two-component gel through a pH change. By using a photo-acid generator, the two-component gel can be prepared combining the thermal trigger with photo-irradiation. Photo-patterned self-assembly of DBS-COOH within a pre-formed DBS-CONHNH2 gel under a mask yields spatially controlled multi-domain gels. Different gel domains can have different functions, for example, controlling the rate of release of heparin incorporated into the gel, or directing gold nanoparticle assembly. Such photo-patterned multi-component hydrogels have potential applications in regenerative medicine or bio-nano-electronics.

Tuning gelled lyotropic liquid crystals (LLCs) - probing the influence of different low molecular weight gelators on the phase diagram of the system H2O/NaCl-Genapol LA070.

Gelled lyotropic liquid crystals (LLCs) are highly tunable multi-component materials. By studying a selection of low molecular weight gelators (LMWGs), we find gelators that form self-assembled gels in LLCs without influencing their phase boundaries. We studied the system H2O/NaCl-Genapol LA070 in the presence of (a) the organogelators 12-hydroxyoctadecanoic acid (12-HOA) and 1,3:2,4-dibenzylidene-d-sorbitol (DBS) and (b) the hydrogelators N,N'-dibenzoyl-l-cystine (DBC) and a tris-amido-cyclohexane derivative (HG1). Visual phase studies and oscillation shear frequency sweeps confirmed that 12-HOA acts as co-surfactant (stabilizing the lamellar Lα phase and destabilizing the hexagonal H1 phase), thus preventing gelation. Conversely, DBS was a potent gelator for LLCs, with the phase boundaries un-influenced by the presence of DBS; gelled lamellar Lα, and softly-gelled hexagonal H1 phases are formed. For the hydrogelator DBC, the LLC phase boundaries were only slightly altered, but no gelled LLCs were formed. For the hydrogelator HG1, however, the phase boundaries were unaffected while gelled lamellar Lα and softly-gelled hexagonal H1 phases were formed. Temperature-dependent rheology measurements demonstrated that by changing the DBS or the HG1 concentration, the sol-gel transition temperature of the gelled lamellar Lα phase can be adjusted such that (a) Tsol-gel is below the Lα-isotropic phase transition (DBS, HG1 mass fraction η = 0.0075) and (b) Tsol-gel is above the gelled Lα-isotropic phase transition (DBS, HG1 η = 0.015). This opens the possibility of temporal materials control by addressing phase transitions in different orders. As this system contains oil and water, both the organogelator DBS and the hydrogelator HG1 can gel these LLCs, but this clearly does not apply to all organogelators/hydrogelators. The study indicates that careful optimization of LMWGs is required to avoid interaction with the surfactant layer and to optimize the Tsol-gel value, which is important for the application of LMWGs in gelled LLCs.

The genesis and source of the H7N9 influenza viruses causing human infections in China.

A novel H7N9 influenza A virus first detected in March 2013 has since caused more than 130 human infections in China, resulting in 40 deaths. Preliminary analyses suggest that the virus is a reassortant of H7, N9 and H9N2 avian influenza viruses, and carries some amino acids associated with mammalian receptor binding, raising concerns of a new pandemic. However, neither the source populations of the H7N9 outbreak lineage nor the conditions for its genesis are fully known. Using a combination of active surveillance, screening of virus archives, and evolutionary analyses, here we show that H7 viruses probably transferred from domestic duck to chicken populations in China on at least two independent occasions. We show that the H7 viruses subsequently reassorted with enzootic H9N2 viruses to generate the H7N9 outbreak lineage, and a related previously unrecognized H7N7 lineage. The H7N9 outbreak lineage has spread over a large geographic region and is prevalent in chickens at live poultry markets, which are thought to be the immediate source of human infections. Whether the H7N9 outbreak lineage has, or will, become enzootic in China and neighbouring regions requires further investigation. The discovery here of a related H7N7 influenza virus in chickens that has the ability to infect mammals experimentally, suggests that H7 viruses may pose threats beyond the current outbreak. The continuing prevalence of H7 viruses in poultry could lead to the generation of highly pathogenic variants and further sporadic human infections, with a continued risk of the virus acquiring human-to-human transmissibility.

Self-Assembled Gels Formed in Deep Eutectic Solvents: Supramolecular Eutectogels with High Ionic Conductivity.

1,3:2,4-Dibenzylidene-d-sorbitol (DBS), a simple, commercially relevant compound, was found to self-assemble as a result of intermolecular noncovalent interactions into supramolecular gels in deep eutectic solvents (DESs) based on choline chloride combined with alcohols/ureas. DBS formed gels at a loading of 5 % w/v. Rheology confirmed the gel-like nature of the materials, electron microscopy and X-ray diffraction indicated underpinning nanofibrillar DBS networks, and differential scanning calorimetry showed the DES nature of the liquid-like phase was retained. The ionic conductivities of the gels were similar to those of the unmodified DESs, thus proving the deep eutectic nature of the ionic liquid-like phase. Gelation was tolerant of ionic additives Li+ , Mg2+ , and Ca2+ ; the resulting gels had similar conductivities to electrolyte dissolved in the native DES. The low-molecular-weight gelator DBS is thus a low-cost additive that forms gels in DESs from readily available constituents, with conductivity levels suitable for practical applications.

Commercially Relevant Orthogonal Multi-Component Supramolecular Hydrogels for Programmed Cell Growth.

This study reports the ability of synthetically simple, commercially viable sugar-derived 1,3:2,4-dibenzylidenesorbitol-4',4"-diacylhydrazide (DBS-CONHNH2 ) to support cell growth. Simple mixing and orthogonal self-sorting can formulate heparin, agarose, and heparin-binding micelles into these gels-easily incorporating additional function. Interestingly, the components used in the gel formulation, direct the ability of cells to grow, meaning the chemical programming of these multi-component gels is directly translated to the biological systems in contact with them. This simple approach has potential for future development in regenerative medicine.