Genomic analysis reveals a cryptic pangolin species.

Eight extant species of pangolins are currently recognized. Recent studies found that two mitochondrial haplotypes identified in confiscations in Hong Kong could not be assigned to any known pangolin species, implying the existence of a species. Here, we report that two additional mitochondrial haplotypes identified in independent confiscations from Yunnan align with the putative species haplotypes supporting the existence of this mysterious species/population. To verify the new species scenario we performed a comprehensive analysis of scale characteristics and 138 whole genomes representing all recognized pangolin species and the cryptic new species, 98 of which were generated here. Our morphometric results clearly attributed this cryptic species to Asian pangolins (Manis sp.) and the genomic data provide robust and compelling evidence that it is a pangolin species distinct from those recognized previously, which separated from the Philippine pangolin and Malayan pangolin over 5 Mya. Our study provides a solid genomic basis for its formal recognition as the ninth pangolin species or the fifth Asian one, supporting a new taxonomic classification of pangolins. The effects of glacial climate changes and recent anthropogenic activities driven by illegal trade are inferred to have caused its population decline with the genomic signatures showing low genetic diversity, a high level of inbreeding, and high genetic load. Our finding greatly expands current knowledge of pangolin diversity and evolution and has vital implications for conservation efforts to prevent the extinction of this enigmatic and endangered species from the wild.

Alkaline Ionic Liquid Microphase Promotes Deep Reduction of CO2 on Copper.

Electrochemical reduction of CO2 to multicarbon (C2+) products using renewable energy sources is an important route to storing sustainable energy and achieving carbon neutrality. It remains a challenge to achieve high C2+ product faraday efficiency (FE) at ampere-level current densities. Herein, we propose the immobilization of an alkaline ionic liquid on copper for promoting the deep reduction of CO2. By this strategy, a C2+ FE of 81.4% can be achieved under a current density of 0.9 A·cm-2 with a half-cell energy conversion efficiency of 47.4% at -0.76 V vs reversible hydrogen electrode (RHE). Particularly, when the current density is as high as 1.8 A·cm-2, the C2+ FE reaches 71.6% at an applied potential of -1.31 V vs RHE. Mechanistic studies demonstrate that the alkaline ionic liquid plays multiple roles of improving the accumulation of CO2 molecules on the copper surface, promoting the activation of the adsorbed CO2, reducing the energy barrier of CO dimerization, stabilizing intermediates, and facilitating the C2+ product formation.

Cu3(BTC)2 nanoflakes synthesized in an ionic liquid/water binary solvent and their catalytic properties.

Low-dimensional metal-organic frameworks (MOFs) exhibit enhanced properties compared with three-dimensional (3D) geometry MOFs in many fields. In this work, we demonstrate the synthesis of Cu3(BTC)2 (BTC = benzene-1,3,5-tricarboxylate) nanoflakes in a binary solvent of ionic liquid (IL) and water. Such a MOF architecture has a high surface area and abundant unsaturated coordination metal sites, making them attractive for adsorption and catalysis. For example, in catalyzing the oxidation reactions of a series of alcohols, the Cu3(BTC)2 nanoflakes exhibit a high performance that is superior to Cu3(BTC)2 microparticles synthesized in a conventional solvent. Experimental and theoretical studies reveal that the IL accelerates the crystallization of Cu3(BTC)2, while water plays a role in stripping the Cu3(BTC)2 blocks that are formed at an early stage through its attack on the crystal plane of Cu3(BTC)2. Such an in situ crystallization-exfoliation process that uses an IL/water solvent opens a new route for producing low-dimensional MOFs.

Associations of multiple chronic disease and depressive symptoms with incident stroke among Chinese middle-aged and elderly adults: a nationwide population-based cohort study.

BACKGROUND: With the population aging, multiple chronic diseases, depressive symptoms, and stroke are increasingly common among middle-aged and elderly adults worldwide. This study aimed to explore the independent associations of multiple chronic diseases and depressive symptoms as well as their combination with incident stroke in a prospective cohort of Chinese middle-aged and elderly adults, and to sensitively estimate the association between each type of chronic disease and incident stroke. METHODS: This study used data from the China Health and Retirement Longitudinal Study (CHARLS). A total of 8389 participants meeting the inclusion criteria at baseline (between 2011 and 2012) survey were included, and 7108 eligible participants completed the follow-up survey over 8 years (Wave 4, in 2018). Questionnaire information, physical examination, and clinical and biochemical measurements were collected. RESULTS: The mean (SD) age at baseline was 58.5 (± 9.1) years. Multiple chronic disease and depressive symptoms were independently associated with incident stroke. After adjusting for control variables, patients having 1 type of chronic disease and depressive symptoms were at 1.943 (95% CI = 1.166-3.238) times higher risk of incident stroke than those without chronic disease and depressive symptoms, and patients having at least 2 types of chronic diseases and depressive symptoms were at 3.000 (95% CI = 1.846-4.877) times higher risk of incident stroke; the magnitudes of the associations increased by the numbers of having chronic diseases and depressive symptoms. Sensitivity analyses incorporating all five types of chronic disease (i.e., hypertension, dyslipidemia, heart disease, diabetes, and chronic kidney disease) showed that the magnitude of the associations between hypertension and incident stroke was most significant. CONCLUSIONS: We identified significant independent and combined longitudinal associations of multiple chronic diseases and depressive symptoms with incident stroke, and the combined associations reflected a dose-response relationship. The association between hypertension and incident stroke was strongest among the five chronic diseases.

Anchoring Ionic Liquid in Copper Electrocatalyst for Improving CO2 Conversion to Ethylene.

Electrochemical conversion of CO2 to valuable fuels is appealing for CO2 fixation and energy storage. The Cu-based catalysts feature unique superiorities, but achieving high ethylene selectivity is still restricted. In this study, we propose the anchoring of an ionic liquid (IL) on a Cu electrocatalyst for improving the electrochemical CO2 reduction to ethylene. In a water-based electrolyte and a commonly used H-type cell, a high ethylene Faradaic efficiency of 77.3 % was achieved at -1.49 V (vs. RHE). Experimental and theoretical studies reveal that an IL can modify the electronic structure of a Cu catalyst through its interaction with Cu, making it more conducive to *CO dimerization for ethylene formation.

Diverse phylogenomic datasets uncover a concordant scenario of laurasiatherian interordinal relationships.

Resolving the interordinal relationships in the mammalian superorder Laurasiatheria has been among the most intractable problems in higher-level mammalian systematics, with many conflicting hypotheses having been proposed. The present study collected three different sources of genome-scale data with comprehensive taxon sampling of laurasiatherian species, including two protein-coding datasets (4,186 protein-coding genes for an amino acid dataset comprising 2,761,247 amino acid residues and a nucleotide dataset comprising 5,516,340 nucleotides from 1st and 2nd codon positions), an intronic dataset (1,210 introns comprising 1,162,723 nucleotides) and an ultraconserved elements (UCEs) dataset (1,246 UCEs comprising 1,946,472 nucleotides) from 40 species representing all six laurasiatherian orders and 7 non-laurasiatherian outgroups. Remarkably, phylogenetic trees reconstructed with the four datasets using different tree-building methods (RAxML, FastTree, ASTRAL and MP-EST) all supported the relationship (Eulipotyphla, (Chiroptera, ((Carnivora, Pholidota), (Cetartiodactyla, Perissodactyla)))). We find a resolution of interordinal relationships of Laurasiatheria among all types of markers used in the present study, and the likelihood ratio tests for tree comparisons confirmed that the present tree topology is the optimal hypothesis compared to other examined hypotheses. Jackknifing subsampling analyses demonstrate that the results of laurasiatherian tree reconstruction varied with the number of loci and ordinal representatives used, which are likely the two main contributors to phylogenetic disagreements of Laurasiatheria seen in previous studies. Our study provides significant insight into laurasiatherian evolution, and moreover, an important methodological strategy and reference for resolving phylogenies of adaptive radiation, which have been a long-standing challenge in the field of phylogenetics.

Molecular Genetics Supports a Potential Fifth Asian Pangolin Species (Mammalia, Pholidota, Manis).

Recently, two mitochondrial haplotypes, H4 and H8, of Manis sp. were found in two seizures in Hong Kong that do not correspond to Manis javanica, Manis pentadactyla or Manis crassicaudata of Asian pangolin species or any African pangolin species. It was proposed that both haplotypes derived from Manis culionensis, an unknown lineage of M. javanica, or a thus far unidentified Asian pangolin species (Manis sp.). To further investigate these three hypotheses, we used two mitochondrial genes of all eight known extant pangolin species and conducted phylogenetic tree reconstructions, divergence time estimation, and species delimitation analyses. All analyses consistently confirmed that these two haplotypes of Manis sp. constitute a distinct lineage, potentially representing a fifth Asian pangolin species, which originated around the Late Miocene to Early Pliocene (6.95 [4.64-9.85] million years ago). Our study provides genetic support for a potential fifth Asian pangolin species and helps to better understand species diversity of Asian pangolins, which is urgently needed for effective conservation work.

PEG-PEI/siROCK2 Protects Against Aß42-Induced Neurotoxicity in Primary Neuron Cells for Alzheimer Disease.

Gene therapy that targets the ROCK2 gene has yielded promising results in the treatment of AD. Our previous study indicated that PEG-PEI/siROCK2 could effectively suppress ROCK2 mRNA expression and showed a promising prospect for the treatment of Alzheimer's disease. However, the ability of PEG-PEI/siROCK2 to reduce Aß-induced cytotoxicity is unknown. To investigate the effect of PEG-PEI/siROCK2 against Aß42-induced neurotoxicity, primary cultured cortical neurons were pretreated with PEG-PEI/siROCK2 for 24 h and then treated with 5 µM Aß42 for 24 h. We found that PEG-PEI/siROCK2 increased the cell viability and reduced the number of apoptotic cells induced by Aß42, as measured using an MTT assay and Annexin V/PI staining. A further study revealed that PEG-PEI/siROCK2 can activate p-Akt, and treatment with the PI3K inhibitor LY294002 attenuated the neuroprotective effects. These results suggest that PEG-PEI/siROCK2 prevents Aß42-induced neurotoxicity and that the activation of PI3K/Akt pathway is involved in neuroprotection. Taken together, these findings shed light on the role of PEG-PEI/siROCK2 as a potential therapeutic agent for AD.

Sertraline plus deanxit to treat patients with depression and anxiety in chronic somatic diseases: a randomized controlled trial.

BACKGROUND: Patients in chronic somatic diseases are often accompanied with depression and anxiety, remission of which may be observed in the third or fourth week after applying common antidepressant medications. We investigate the efficacy and safety of sertraline plus deanxit on patients with depression and anxiety in chronic somatic diseases. METHODS: 75 Patients who met the criteria were randomly assigned to deanxit group or placebo group: sertraline (75 mg/day) plus deanxit (one piece/day) (N = 38), or sertraline (75 mg/day) plus placebo (one piece/day) (N = 37) for 2 weeks, both groups received sertraline (75 mg/day) in the following 2 weeks. Changes from baseline to day 4, day 8, day 15, and day 29 in Hamilton Rating Scale for Depression (HAM-D) and Hamilton Rating Scale for Anxiety (HAM-A) total scores were the efficacy measures. Adverse events were monitored and registered systematically during the trial. RESULTS: Response rates for HAM-D scores in deanxit group and placebo group were significantly different on day 8(55.26% ± 2.56% VS 24.32% ± 2.19%, p = 0.006) and day 15(78.95% ± 3.89% VS 40.54% ± 4.18%, p = 0.001), while no statistical differences were observed on day 4 and day 29. Respectively, response rates for HAM-A scores on day 4 (34.21% ± 2.21% VS 8.11% ± 1.37%, p = 0.006), day 8 (57.89% ± 3.56% VS 18.92% ± 2.68%, p = 0.001) and day 15 (78.95% ± 4.37% VS 43.24% ± 4.68%, p = 0.002), favoring the deanxit group. However, HAM-A scores were not remarkably different at the end point. The overall safety profile of both groups was favorable with no distinct differences. CONCLUSIONS: The efficacy was exhibited in the deanxit group, with evidence for similar safety. The rapid onset of sertraline plus short-term deanxit indicated that it might be an inspiring strategy to manage depression and anxiety within the first two weeks in chronic somatic diseases.

Intracranial injection of PEG-PEI/ROCK II-siRNA improves cognitive impairment in a mouse model of Alzheimer's disease.

PURPOSE: A plenty of studies have demonstrated that the Rho/ROCK pathway is involved in the neuronal loss and inhibition of axonal regeneration observed in Alzheimer's disease (AD). Therefore, we conducted this study to evaluate whether intracranial injection of PEG-PEI/ROCK II siRNA (PPRS) would improve the cognitive impairments in a senescence-accelerated mouse (SAM) model of AD. MATERIALS AND METHODS: Five male senescence-resistant inbred strain (SAMR1) mice and 15 male senescence-accelerated mouse prone-8 (SAMP8) strain mice were divided into the following three groups:PPRS group, PEG-PEI/ ROCK II-Scramble (PPRScr) siRNA group, and normal group (SAMR1). Total volumes of 2.3 µl of nanoparticles or saline were intracranially injected under the guidance of a stereotaxic apparatus. The injections were performed every three days and lasted for two weeks. Four weeks after injection, the Morris water maze (MWM) was used to evaluate the spatial learning and memory functions of the mice. Choline acetyltransferase (ChAT) activity was detected by immunohistochemistry. RESULTS: Mice in the PPRS-treated group exhibited decreases in escape latencies over the three successive days of navigating the test and crossing the target quadrant during the spatial probe test more frequently than did the mice in the PPRScr-treated group. Analyses of ChAT activity revealed that greater numbers of ChAT-positive cells were present in the hippocampal regions of the PPRS-treated mice than in the PPRScr group. CONCLUSIONS: Intracranial injection of PPRS improved the cognitive impairments of SAM mice, and this improvement may have been mediated by enhancement of ChAT activity in the hippocampus.

Evolution and conservation genetics of pangolins.

Pangolins (Pholidota, Manidae) are classified as an evolutionarily distinct and globally endangered mammal due to their unique morphology (nail-like scales and a myrmecophagous diet) and being the victim of heavy poaching and worldwide trafficking. As such, pangolins serve as a textbook example for studying the special phenotypic evolutionary adaptations and conservation genetics of an endangered species. Recent years have demonstrated significant advancements in the fields of molecular genetics and genomics, which have translated to a series of important research achievements and breakthroughs concerning the evolution and conservation genetics of pangolins. This review comprehensively presents the hitherto advances in phylogeny, adaptive evolution, conservation genetics, and conservation genomics that are related to pangolins, which will provide an ample understanding of their diversity, molecular adaptation mechanisms, and evolutionary potentials. In addition, we highlight the priority of investigating species/population diversity among pangolins and suggest several avenues of research that are highly relevant for future pangolin conservation.

Green solvent systems for material syntheses and chemical reactions.

It is of great significance to develop environmentally benign, non-volatile and recyclable green solvents for different applications. This feature article overviews the properties of green solvent systems (e.g., ionic liquids, supercritical carbon dioxide, deep eutectic solvents and mixed green solvent systems) and their applications in (1) framework material syntheses, including metal-organic frameworks, covalent organic frameworks and hydrogen-bonded organic frameworks, and (2) CO2 conversion reactions, including photocatalytic and electrocatalytic reduction reactions. Finally, the future perspective for research on green solvent systems is proposed from different aspects.

Cu/Cu2O nanocrystals for electrocatalytic carbon dioxide reduction to multi-carbon products.

We demonstrate the electrochemical conversion of carbon dioxide into multi-carbon products catalyzed by Cu/Cu2O nanocrystals, with a maximum C2+ faradaic efficiency of 75% in 0.10 M K2SO4 aqueous solution at -2.0 V versus Ag/AgCl and a partial current density of 34 mA cm-2.

Hologenomic insights into mammalian adaptations to myrmecophagy.

Highly specialized myrmecophagy (ant- and termite-eating) has independently evolved multiple times in species of various mammalian orders and represents a textbook example of phenotypic evolutionary convergence. We explored the mechanisms involved in this unique dietary adaptation and convergence through multi-omic analyses, including analyses of host genomes and transcriptomes, as well as gut metagenomes, in combination with validating assays of key enzymes' activities, in the species of three mammalian orders (anteaters, echidnas and pangolins of the orders Xenarthra, Monotremata and Pholidota, respectively) and their relatives. We demonstrate the complex and diverse interactions between hosts and their symbiotic microbiota that have provided adaptive solutions for nutritional and detoxification challenges associated with high levels of protein and lipid metabolisms, trehalose degradation, and toxic substance detoxification. Interestingly, we also reveal their spatially complementary cooperation involved in degradation of ants' and termites' chitin exoskeletons. This study contributes new insights into the dietary evolution of mammals and the mechanisms involved in the coordination of physiological functions by animal hosts and their gut commensals.

Co(NO3)2/covalent organic framework nanoparticles for high-efficiency photocatalytic oxidation of thioanisole.

Herein, we demonstrated a highly efficient photocatalytic sulfide oxidation reaction at ambient conditions without a sacrificial reagent or redox mediator, by using Co(NO3)2/covalent organic framework nanoparticles as a photocatalyst.

LcCCL28-25, Derived from Piscine Chemokine, Exhibits Antimicrobial Activity against Gram-Negative and Gram-Positive Bacteria In Vitro and In Vivo.

Antimicrobial peptides (AMPs) are currently recognized as potentially promising antibiotic substitutes. Fish are an important seawater/freshwater medicinal biological resource, and the antimicrobial peptides and proteins that are key components of their innate immune systems are potential candidates for the development of novel antibacterial agents. The rainbow trout Oncorhynchus mykiss chemokine CK11 (omCK11), classified in the C-C motif chemokine ligand 27/28 (CCL27/28) family, is the only CC-type chemokine reported to play a direct antibacterial role in the immune response; however, its antibacterial domain remains unknown. In this study, we analyzed the structure-activity relationship of omCK11 and identified the antibacterial C-terminal domain. Additionally, we performed structure-function analyses of CCL27/28 proteins from different, representative freshwater and seawater fishes, revealing their shared C-terminal antibacterial domains. Surprisingly, a synthesized cationic peptide (named lcCCL28-25), derived from the large yellow croaker Larimichthys crocea CCL28, exhibited broad-spectrum and the most acceptable bactericidal activity, as well as antibiofilm activity and negligible hemolytic and cytotoxic activity in vitro. Additionally, lcCCL28-25 conferred a protective effect in the thighs of neutropenic mice infected with Staphylococcus aureus. SYTOX green fluorescence and electron microscopy experiments revealed that lcCCL28-25 was capable of rapidly destroying the integrity and permeability of the bacterial cell membrane. Overall, this study aided in the advancement of antibacterial CC-type chemokine research and also suggested a new strategy for exploring novel AMPs. Additionally, the efficacy of lcCCL28-25 in in vivo antibacterial activity in a mammalian model revealed that this compound could be a promising agent for the development of peptide-based antibacterial therapeutics. IMPORTANCE The primary function of chemokines has been described as recruiting and activating leukocytes to participate in the immune response. Some chemokines are also broad-spectrum antibacterial proteins in mammals. The Oncorhynchus mykiss chemokine CK11 (omCK11) is the first reported and currently the only CC-type antibacterial chemokine. The present study identified the antibacterial domain of omCK11. Structure-function analysis of various fish CCL27/28 proteins identified a novel antibacterial peptide (lcCCL28-25) from Larimichthys crocea CCL28 that exhibited broad-spectrum and the most acceptable bactericidal activity in vitro, as well as a protective effect in a Staphylococcus aureus infection mouse model. The antibacterial mechanisms included membrane disruption and permeation. This study advanced the field of antibacterial chemokine research in fish and also suggested a new strategy for exploring novel AMPs. The novel peptide lcCCL28-25 may prove to be an effective antibacterial agent.

ZIF-9(III) nanosheets synthesized in ionic liquid/ethanol mixture for efficient photocatalytic hydrogen production.

To improve the photocatalytic performance of metal-organic frameworks is of great importance. We synthesized the nanosheets of a zeolitic imidazolate framework (ZIF-9(III)) in ionic liquid/ethanol solution, with an average thickness of 4.6 nm. The as-synthesized ZIF-9(III) nanosheets have optoelectronic properties superior to the three-dimensional ZIF-9(III) synthesized by the conventional solvothermal method. The ZIF-9(III) nanosheets exhibit high activity for photocatalytic hydrogen production under visible light irradiation. The maximum hydrogen production rate can reach 112.37 mmol g-1 h-1, while that by three-dimensional ZIF-9(III) is 29.64 mmol g-1 h-1 under the same experimental conditions.

Periodically nanoporous hydrogen-bonded organic frameworks for high performance photocatalysis.

The development of highly catalytic hydrogen-bonded organic frameworks (HOFs) is of great importance, but remains challenging. Herein, we demonstrate the fabrication of a periodically nanoporous HOF for high performance photocatalysis. Compared with the conventional microporous HOFs, the nanoporous HOF architecture has a larger number of free carboxyl groups on the surface and presents greatly improved photoelectrochemical properties. It exhibits high catalytic activity for the photo-oxidative coupling of amines under mild conditions such as air atmosphere and room temperature and without any co-catalysts, sacrificial reagents or photosensitizers. The relationship between the structure, properties and catalytic performance of the nanoporous HOF was studied by experimental and theoretical investigations. It shows that such a HOF structure facilitates reactant adsorption and O2 dissociation, thus promoting the oxidative coupling reaction. This work provides a new way for improving the catalytic performance of a single HOF.

SnS2/polypyrrole for high-efficiency photocatalytic oxidation of benzylamine.

Here, SnS2/polypyrrole (PPy) was synthesized, which shows high catalytic activity for the photocatalytic oxidation of benzylamine under mild conditions (at 25 °C, in air and without adding an additional sacrificial reagent, redox mediator and photosensitizer).

Comparative study of gut microbiota from captive and confiscated-rescued wild pangolins.

Pangolins are among the most critically endangered animals due to widespread poaching and worldwide trafficking. Captive breeding is considered to be one way to protect them and increase the sizes of their populations. However, comparative studies of captive and wild pangolins in the context of gut microbiota are rare. Here, the gut microbiome of captive and confiscated-rescued wild pangolins is compared, and the effects of different periods of captivity and captivity with and without antibiotic treatment are considered. We show that different diets and periods of captivity, as well as the application of antibiotic therapy, can alter gut community composition and abundance in pangolins. Compared to wild pangolins, captive pangolins have an increased capacity for chitin and cellulose/hemicellulose degradation, fatty acid metabolism, and short-chain fatty acid synthesis, but a reduced ability to metabolize exogenous substances. In addition to increasing the ability of the gut microbiota to metabolize nutrients in captivity, captive breeding imposes some risks for survival by resulting in a greater abundance of antibiotic resistance genes and virulence factors in captive pangolins than in wild pangolins. Our study is important for the development of guidelines for pangolin conservation, including health assessment, disease prevention, and rehabilitation of wild pangolin populations.