Discovery of a selective NLRP3-targeting compound with therapeutic activity in MSU-induced peritonitis and DSS-induced acute intestinal inflammation.

The aberrant activation of the nucleotide-binding oligomerization domain-like receptor family pyrin domain containing 3 (NLRP3) inflammasome is known to contribute to the pathogenesis of various human inflammation-related diseases. However, to date, no small-molecule NLRP3 inhibitor has been used in clinical settings. In this study, we have identified SB-222200 as a novel direct NLRP3 inhibitor through the use of drug affinity responsive target stability assay, cellular thermal shift assay, and surface plasmon resonance analysis. SB-222200 effectively inhibits the activation of the NLRP3 inflammasome in macrophages, while having no impact on the activation of NLRC4 or AIM2 inflammasome. Furthermore, SB-222200 directly binds to the NLRP3 protein, inhibiting NLRP3 inflammasome assembly by blocking the NEK7 - NLRP3 interaction and NLRP3 oligomerization. Importantly, treatment with SB-222200 demonstrates alleviation of NLRP3-dependent inflammatory diseases in mouse models, such as monosodium urate crystal-induced peritonitis and dextran sulfate sodium-induced acute intestinal inflammation. Therefore, SB-222200 holds promise as a lead compound for the development of NLRP3 inhibitors to combat NLRP3-driven disease and serves as a versatile tool for pharmacologically investigating NLRP3 biology.

Modeling insect growth regulators for pest management.

Insect growth regulators (IGRs) have been developed as effective control measures against harmful insect pests to disrupt their normal development. This study is to propose a mathematical model to evaluate the cost-effectiveness of IGRs for pest management. The key features of the model include the temperature-dependent growth of insects and realistic impulsive IGRs releasing strategies. The impulsive releases are carefully modeled by counting the number of implements during an insect's temperature-dependent development duration, which introduces a surviving probability determined by a product of terms corresponding to each release. Dynamical behavior of the model is illustrated through dynamical system analysis and a threshold-type result is established in terms of the net reproduction number. Further numerical simulations are performed to quantitatively evaluate the effectiveness of IGRs to control populations of harmful insect pests. It is interesting to observe that the time-changing environment plays an important role in determining an optimal pest control scheme with appropriate release frequencies and time instants.

Phylogenetic position of Bopyroides hippolytes, with comments on the rearrangement of the mitochondrial genome in isopods (Isopoda: Epicaridea: Bopyridae).

BACKGROUND: Classification of parasitic bopyrids has traditionally been based on morphological characteristics, but phylogenetic relationships have remained elusive due to limited information provided by morphological data and tendency for loss of morphological features as a result of parasitic lifestyle. Subfamily Argeiinae was separated from Bopyrinae based on morphological evidence, although the assignment of all genera has not been phylogenetically evaluated. Bopyroides hippolytes has been traditionally classified in Bopyrinae, but divergent morphological characters make this assignment questionable. To investigate the relationship of bopyrines, we sequenced the complete mitochondrial genome of B. hippolytes and four mitochondrial genes of two other Bopyrinae. RESULTS: The phylogenetic trees based on separate and combined cox1and 18S sequence data recovered Bopyridae as robustly monophyletic, but Bopyrinae as polyphyletic. Bopyroides hippolytes was a close sister to Argeia pugettensis, type species to Argeiinae. Mitochondrial phylogenomics also suggested that B. hippolytes was close to Argeiinae. We also found a novel gene order in B. hippolytes compared to other isopods. CONCLUSIONS: Bopyroides hippolytes should be excluded from the Bopyrinae and has a close affinity with Argeia pugettensis based on molecular and morphological data. The conserved syntenic blocks of mitochondrial gene order have distinctive characteristics at a subordinal level and may be helpful for understanding the higher taxonomic level relationships of Isopoda.

A reaction-advection-diffusion model of cholera epidemics with seasonality and human behavior change.

Cholera is a water- and food-borne infectious disease caused by V. cholerae. To investigate multiple effects of human behavior change, seasonality and spatial heterogeneity on cholera spread, we propose a reaction-advection-diffusion model that incorporates human hosts and aquatic reservoir of V. cholerae. We derive the basic reproduction number [Formula: see text] for this system and then establish a threshold type result on its global dynamics in terms of [Formula: see text]. Further, we show that the bacterial loss at the downstream end of the river due to water flux can reduce the disease risk, and describe the asymptotic behavior of [Formula: see text] for small and large diffusion in a special case (where the diffusion rates of infected human and the pathogen are constant). We also study the transmission dynamics at the early stage of cholera outbreak numerically, and find that human behavior change may lower the infection level and delay the disease peak. Moreover, the relative rate of bacterial loss, together with convection rate, plays an important role in identifying the severely infected areas. Meanwhile spatial heterogeneity may dilute or amplify cholera infection, which in turn would increase the complexity of disease spread.

A novel gene arrangement among the Stylommatophora by the complete mitochondrial genome of the terrestrial slug Meghimatium bilineatum (Gastropoda, Arionoidea).

Stylommatophora is a main clade of Gastropoda that encompasses approximately 112 gastropod families and may exceed a total of 30,000 species. Twenty-four complete stylommatophoran mitogenomes have been sequenced to date, yet our understanding of mitochondrial evolution in stylommatophorans is still in its infancy. To further expand the set of available mitogenomes, we sequenced the mitogenome of Meghimatium bilineatum (Arionoidea: Philomycidae), a widespread land slug in East Asia. This is the first report on a mitogenome of the superfamily Arionoidea, and indeed on a terrestrial slug. The mitogenome of Meghimatium bilineatum comprises 13,972 bp and exhibits a novel, highly distinctive gene arrangement among the Stylommatophora. Phylogenetic reconstructions based on the sequences of all protein-coding genes consistently recovered Meghimatium bilineatum as sister-group of the Succineidae. A phylogenetic reconstruction based on gene order, however, suggested a highly divergent tree topology, which is less credible when taking into account prior knowledge of stylommatophoran relationships. Our CREx (Common interval Rearrangement Explorer) analysis suggested that three successive events of tandem duplication random loss (TDRL) best explain the evolutionary process of gene order rearrangement in Meghimatium bilineatum from an ancestral stylommatophoran mitogenome. The present example offers new insights into the mechanisms of mitogenome rearrangements in gastropods at large and into the usefulness of mitogenomic gene order as a phylogenetic marker.

Reclassification of Lamprotula rochechouartii as Margaritifera rochechouartiicomb. nov. (Bivalvia: Margaritiferidae) revealed by time-calibrated multi-locus phylogenetic analyses and mitochondrial phylogenomics of Unionoida.

The family Margaritiferidae encompasses 12 valid species, which are distributed widely but disjunctively in the Northern Hemisphere. A lack of a well resolved and temporally calibrated phylogenetic framework of Margaritiferidae has made it difficult to discuss the evolutionary pattern and process. Phylogenetic relationships between five major clades, which were revealed in earlier studies, remain elusive and unresolved. Lamprotula rochechouartii has long been classified within the family Unionidae based on shell morphology, but our preliminary molecular study on this species made us hypothesize that it has an affinity with margaritiferids. Hence, five loci (COI, 16S, 18S, 28S and histone H3) were used to investigate the phylogenetic position of L. rochechouartii and intra-familial relationships within Margaritiferidae using various partitioning strategies. Moreover, two mitochondrial genomes were newly obtained to further resolve and validate the five-clade relationships within Margaritiferidae in a broad view of Unionoida evolution. Both five-gene and mitogenome datasets strongly advocated treating Lamprotula rochechouartii as Margaritifera rochechouartiicomb. nov. Maximum likelihood and Bayesian inference analyses using partitioned five-gene dataset resulted in various topologies, but five well-supported clades were obtained. The most probable cladistic relationships generated by five-gene dataset analyses were identical to subsequent whole mitogenome analyses except the position of M. monodonta. M. rochechouartii and M. laosensis had a well-supported sister relationship and formed a basal clade splitting from the rest of the family. Based on six reliable fossils, crown age of the extant Margaritiferidae was estimated during the Late Cretaceous at 88.3 Ma (95% HPD = 66.2-117.4). But we hypothesized a much earlier origin of this family due to the Permian stem age (mean = 257 Ma, 95% HPD = 230.0-296.0) and a high extinction rate in the whole order. Biogeographic scenarios supported a Laurasian origin of extant Margaritiferidae during the Late Cretaceous, and suggested that Asian margaritiferids may have had two origins, having either Asia (M. rochechouartii, M. laosensis) or North America (M. dahurica, M. laevis, and M. middendorffi) as ancestral. The newly added Margaritiferidae species M. rochechouartii expands our recognized distribution range of modern margaritiferids. Our results indicate that whole mitogenome sequences can be used to reconstruct robust phylogenetic relationships for freshwater mussels, especially with the help of adding M-type mitogenomes.

Expansion and systematics redefinition of the most threatened freshwater mussel family, the Margaritiferidae.

Two Unionida (freshwater mussel) families are present in the Northern Hemisphere; the Margaritiferidae, representing the most threatened of unionid families, and the Unionidae, which include several genera of unresolved taxonomic placement. The recent reassignment of the poorly studied Lamprotula rochechouartii from the Unionidae to the Margaritiferidae motivated a new search for other potential species of margaritiferids from members of Gibbosula and Lamprotula. Based on molecular and morphological analyses conducted on newly collected specimens from Vietnam, we here assign Gibbosula crassa to the Margaritiferidae. Additionally, we reanalyzed all diagnostic characteristics of the Margaritiferidae and examined museum specimens of Lamprotula and Gibbosula. As a result, two additional species are also moved to the Margaritiferidae, i.e. Gibbosula confragosa and Gibbosula polysticta. We performed a robust five marker phylogeny with all available margaritiferid species and discuss the taxonomy within the family. The present phylogeny reveals the division of Margaritiferidae into four ancient clades with distinct morphological, biogeographical and ecological characteristics that justify the division of the Margaritiferidae into two subfamilies (Gibbosulinae and Margaritiferinae) and four genera (Gibbosula, Cumberlandia, Margaritifera, and Pseudunio). The systematics of the Margaritiferidae family is re-defined as well as their distribution, potential origin and main biogeographic patterns.

Taxonomic revision of two species in the genus Ptychorhynchus Simpson, 1900 (Bivalvia: Unionidae: Gonideinae), with description of a new species.

Accurate identification and precise classification of freshwater mussel species that are among the most threatened freshwater taxa in the world, play a crucial role in informing conservation and management efforts for these organisms. However, due to the variability in shell morphology, relying solely on shell characteristics for species taxonomy poses significant challenges, thereby impeding effective conservation planning and management. The freshwater mussel genus Ptychorhynchus Simpson, 1900 is one such group in need of study. We integrate molecular phylogeny, shell morphology and soft-body anatomy to examine the classification of Ptychorhynchus denserugata (Haas, 1910) and Ptychorhynchus resupinatus (von Martens, 1902). The COI barcoding data support the clustering of P. denserugata and Nodularia douglasiae within a single clade, and P. denserugata shares the diagnostic feature of the genus Nodularia , i.e. knobs or bumps on the inner mantle surface in the excurrent aperture. Therefore, by integrating molecular data and anatomical characteristics, we confirm that the nominal species P. denserugata syn. nov. is a new synonym for N. douglasiae . The multi-locus (COI + ND1 + 16S rRNA + 18S rRNA + 28S rRNA ) phylogeny and mitochondrial phylogenomics support the transfer of P. resupinatus from Ptychorhynchus to the newly elevated genus Cosmopseudodon stat. rev., as Cosmopseudodon resupinatus stat. rev. that is still considered the designated type species. We also describe a new species based on integrative taxonomy, i.e. Cosmopseudodon wenshanensis sp. nov. The comprehensive understanding of the taxonomy and diversity of the revised Cosmopseudodon species, and shell heteromorphism of N. douglasiae (=P. denserugata syn. nov.), will serve as a crucial foundation for further scientific assessment and conservation strategies pertaining to these taxa. ZooBank: urn:lsid:zoobank.org:pub:E48968B1-DF0F-42AD-8F31-B8C95F23CE57.

Discovery of a dual-acting inhibitor of interleukin-1ß and STATs for the treatment of inflammatory bowel disease.

Currently, a significant proportion of inflammatory bowel disease (IBD) patients fail to respond to conventional drug therapy such as immunosuppressants and biologic agents. Interference with the JAK/STAT pathway and blocking of IL-1 signaling are two promising therapeutic strategies for these unresponsive IBD patients. This work describes the discovery of an inhibitor 10v that not only blocks NLRP3 and AIM-2 inflammasome-mediated IL-1ß signaling, but also reduces the expression of STAT1 and STAT5 in the JAK/STAT pathway. Importantly, 10v exhibits a significant anti-IL-1ß effect and decreases the levels of STAT1 and STAT5 in a mouse model of colitis. As a result, a novel small molecule is identified with a dual inhibitory capacity towards both inflammasomes/IL-1ß and STAT pathways, which supports further exploration of the therapeutic potential for IBD patients that do not respond to current drug therapy.

Chlorquinaldol Alleviates Lung Fibrosis in Mice by Inhibiting Fibroblast Activation through Targeting Methionine Synthase Reductase.

Idiopathic pulmonary fibrosis (IPF) is a progressive interstitial lung disease with limited treatment options. Thus, it is essential to investigate potential druggable targets to improve IPF treatment outcomes. By screening a curated library of 201 small molecules, we have identified chlorquinaldol, a known antimicrobial drug, as a potential antifibrotic agent. Functional analyses have demonstrated that chlorquinaldol effectively inhibits the transition of fibroblasts to myofibroblasts in vitro and mitigates bleomycin-induced pulmonary fibrosis in mice. Using a mass spectrometry-based drug affinity responsive target stability strategy, we revealed that chlorquinaldol inhibited fibroblast activation by directly targeting methionine synthase reductase (MTRR). Decreased MTRR expression was associated with IPF patients, and its reduced expression in vitro promoted extracellular matrix deposition. Mechanistically, chlorquinaldol bound to the valine residue (Val-467) in MTRR, activating the MTRR-mediated methionine cycle. This led to increased production of methionine and s-adenosylmethionine, counteracting the fibrotic effect. In conclusion, our findings suggest that chlorquinaldol may serve as a novel antifibrotic medication, with MTRR-mediated methionine metabolism playing a critical role in IPF development. Therefore, targeting MTRR holds promise as a therapeutic strategy for pulmonary fibrosis.

Molecular and morphological evidence reveals a hidden new taxon in the endemic genus Pseudocuneopsis (Bivalvia, Unionidae) from China.

A new species of freshwater mussel belonging to the genus Pseudocuneopsis, namely Pseudocuneopsiswuanasp. nov., is diagnosed and described from Guangxi Province, China. This paper provides a detailed shell morphological description, soft-body anatomical characteristics, and partial sequences of mitochondrial COI as DNA barcode data for the novel species. The new species can be distinguished from its congeners (Pseudocuneopsissichuanensis, P.yangshuoensis, and P.capitata) by shell shape, beak position, and surface sculpture. Phylogenetic analyses based on the mitochondrial COI gene reveal that Pseudocuneopsiswuanasp. nov. forms a sister group with P.yangshuoensis and exhibits an interspecific genetic distance of 5.1%. Therefore, we provide robust morphological and molecular evidence to support the validity of this new species.

Highly efficient removal of aqueous Hg(II) by FeS micro-flakes.

FeS (mackinawite) is known to be effective in the sorption of aqueous Hg(II). However, FeS nanoparticles are apt to aggregate and easy to be oxidized, which limits their wide applications. Here, we have synthesized FeS micro-flakes which can be uniformly dispersed in water without aggregation. Owing to the good stability and dispersibility, FeS micro-flakes exhibit high efficiency in the removal of Hg(II) from water. The sorption of Hg(II) on the FeS micro-flakes is more consistent with the pseudo-second-order kinetic model and Langmuir model, indicating that the sorption of Hg(II) is mainly monolayer sorption dominated by chemical sorption. The maximum sorption capacity is 2680 mg/g at pH 5.6 and 30 °C, significantly higher than those of FeS nanoparticles and other Hg(II) scavengers. The pH studies indicate that FeS (0.31 g/L) can effectively remove >97.6 % of 200 mg/L Hg(II) in the pH range of 2-12 at 30 °C. Powder X-ray diffraction, elemental and sorption analyses suggest that Hg(II) is removed via chemical precipitation and surface adsorption. This study demonstrates the potential and viability of FeS micro-flakes for efficient removal of aqueous Hg(II).

New species of the genus Pseudocuneopsis Huang, Dai, Chen & Wu, 2022 (Bivalvia, Unionidae) from Guangxi Province, China.

A new species of freshwater mussel belonging to the genus Pseudocuneopsis, namely Pseudocuneopsisyangshuoensissp. nov., is diagnosed and described from Guangxi Province, China. This paper provides a detailed morphological description, photograph of the type specimen, and anatomical characteristics along with partial sequences of mitochondrial COI as DNA barcode data for this novel species. The new species can be distinguished from its congeners (Pseudocuneopsissichuanensis and Pseudocuneopsiscapitata) by shell shape, beak position and surface sculpture. The interspecies genetic distance based on the COI barcode between P.yangshuoensissp. nov. and P.sichuanensis is 8%, while it reaches 9% with P.capitata. Therefore, we provide robust morphological and molecular evidence to support the validity of this new species.

DNA barcoding, multilocus phylogeny, and morphometry reveal phenotypic plasticity in the Chinese freshwater mussel Lamprotula caveata (Bivalvia: Unionidae).

Accurate species identification is crucial for developing conservation strategies for freshwater mussels, one of the most imperiled faunas in the world. Traditionally, mussel species description primarily relied on conchological characters. However, shell morphology has great variability, which leads to the complexity of species delimitation. As endemic species to China, Lamprotula caveata was originally described by Heude (1877). Lamprotula quadrangulosus and Lamprotula contritus were considered for synonymization of L. caveata based on shell variants in the early 20th century, which has been long debated due to lack of rigorous molecular analysis. Moreover, great morphological variation caused doubt whether there are cryptic species. In this study, we used a combined phylogenetic and morphometric approach to verify the validity of the synonymization of L. caveata. The results of molecular species delimitation showed that two molecular operational taxonomic units (MOTUs) were identified in Lamprotula spp., including the L. leaii lineage and the complex lineage (L. quadrangulosa, L. cornuumlunae, L. contritus, and L. caveata). Phylogenetic analyses revealed that L. cornuumlunae formed a basal monophyletic clade, whose divergence time was relatively recent (4.26 Ma [95% HPD = 1.91-7.22 Ma]), and L. contritus, L. caveata, and L. quadrangulosa formed a large polytomy group with very shallow branches. In the previous study, we have demonstrated the validity of L. cornuumlunae. The molecular evidences supported that the complex (L. quadrangulosa + L. contritus + L. caveata) was a valid species; L. quadrangulosa and L. contritus were synonyms of L. caveata. In addition, three morphospecies (L. quadrangulosa, L. contritus, and L. caveata) were aggregated without clear differentiation based on shell morphometric analysis. We confirmed multiple phenotypes in L. caveata for species identification and presumed that the phenotypic plasticity was a response to specific habitats. This study clarified the diversity and phylogeny of the Lamprotula group, which is a crucial step for developing new conservation and management strategies for this imperiled group.

New species of the genus Inversidens Haas, 1911 (Unionoida, Unionidae, Gonideinae) from Jiangxi Province, China.

We diagnose and describe a new freshwater mussel species of the genus Inversidens, I.rentianensis sp. nov. from Jiangxi Province, China based on morphological characters and molecular data. This paper includes a morphological description and photograph of the holotype, and partial sequences of mitochondrial COI as DNA barcode data.

Declining freshwater mussel diversity in the middle and lower reaches of the Xin River Basin: Threat and conservation.

Freshwater mussels provide important functions and services for aquatic ecosystems, but populations of many species have been extirpated. Information on biodiversity plays an important role in the conservation and management of freshwater mussels. The Xin River Basin is a biodiversity hotspot for freshwater mussels in China, with more than 43 species known, but populations of which are decreasing. Here, we quantify the diversity of freshwater mussels in the middle and lower reaches of the Xin River Basin and study the correlation of habitat characteristics and freshwater mussel diversity. Compared to the historical period, the number of species, density, and biomass of freshwater mussels decreased 33%, 83%, and 82% in the current period, respectively. Fifty two percent of recorded species were empty shells, and 14 native freshwater mussels were not found in the study area. Four species are currently listed as vulnerable species using IUCN criteria and their global status. The assemblage structure of freshwater mussels exhibits significant spatial differences, and there was a correlation with substrate and physicochemical parameters. The main tributary of the Xin River with higher freshwater mussel diversity should be established as one large protected area because the nestedness component was the main pattern of beta diversity. These results indicated freshwater mussel diversity was declining rapidly, which can help focus conservation effort for freshwater mussel biodiversity.

Analysis of mitochondrial genomes resolves the phylogenetic position of Chinese freshwater mussels (Bivalvia, Unionidae).

The Yangtze River basin is one of the most species-rich regions for freshwater mussels on Earth, but is gravely threatened by anthropogenic activities. However, conservation planning and management of mussel species has been hindered by a number of taxonomic uncertainties. In order to clarify the taxonomic status and phylogenetic position of these species, mitochondrial genomes of four species (Acuticostachinensis, Schistodesmuslampreyanus, Cuneopsisheudei and Cuneopsiscapitatus) were generated and analyzed along with data from 43 other mitogenomes. The complete F-type mitogenomes of A.chinensis, S.lampreyanus, C.heudei, and C.capitatus are 15652 bp, 15855 bp, 15892 bp, and 15844 bp, respectively, and all four F-type mitogenomes have the same pattern of gene arrangement. ML and BI trees based on the mitogenome dataset are completely congruent, and indicate that the included Unionidae belong to three subfamilies with high bootstrap and posterior probabilities, i.e., Unioninae (Aculamprotula, Cuneopsis, Nodularia, and Schistodesmus), Anodontinae (Cristaria, Arconaia, Acuticosta, Lanceolaria, Anemina, and Sinoanodonta), and Gonideinae (Ptychorhynchus, Solenaia, Lamprotula, and Sinohyriopsis). Results also indicate that A.chinensis has affinities with Arconaialanceolata and Lanceolariagrayii and is a member of the subfamily Anodontinae.

Complete mitochondrial genome of the radicine pond snail Radix plicatula (Gastropoda: Lymnaeidae).

Radix plicatula is broadly distributed in China, as well as Russia. It is one of the intermediate hosts of Fasciola species which leads to the spread of fascioliasis. Here, we first described the complete mitochondrial genome of R. plicatula. The mitogenome is 13,751 bp in length, containing 13 protein-coding genes, 22 tRNA genes, and 2 rRNA genes. The contents of each base are 30.7% A, 39.6% T, 15.7% G, and 13.9% C. The sequence is AT rich (70.3%). Mitochondrial phylogenomic analysis showed that R. plicatula is close to R. auricularia.

Testing the utility of DNA barcodes and a preliminary phylogenetic framework for Chinese freshwater mussels (Bivalvia: Unionidae) from the middle and lower Yangtze River.

The middle and lower portions of the Yangtze River basin is the most species-rich region for freshwater mussels in Asia. The management and conservation of the taxa in this region has been greatly hampered by the lack of a well-developed phylogeny and species-level taxonomic framework. In this study, we tested the utility of two mitochondrial genes commonly used as DNA barcodes: the first subunit of the cytochrome oxidase c gene (COI) and the first subunit of the NADH dehydrogenase gene (ND1) for 34 putative species representing 15 genera, and also generated phylogenetic hypotheses for Chinese unionids based on the combined dataset of the two mitochondrial genes. The results showed that both loci performed well as barcodes for species identification, but the ND1 sequences provided better resolution when compared to COI. Based on the two-locus dataset, Bayesian Inference (BI) and Maximum Likelihood (ML) phylogenetic analyses indicated 3 of the 15 genera of Chinese freshwater mussels examined were polyphyletic. Additionally, the analyses placed the 15 genera into 3 subfamilies: Unioninae (Aculamprotula, Cuneopsis, Nodularia and Schistodesmus), Gonideninae (Lamprotula, Solenaia and Ptychorhychus) and Anodontinae (Cristaria, Arconaia, Acuticosta, Lanceolaria, Anemina and Sinoanodonta). Our results contradict previous taxonomic classification that placed the genera Arconaia, Acuticosta and Lanceolaria in the Unioninae. This study represents one of the first attempts to develop a molecular phylogenetic framework for the Chinese members of the Unionidae and will provide a basis for future research on the evolution, ecology, and conservation of Chinese freshwater mussels.