Molecular Comparison Research Articles

SperMD: the expression atlas of sperm maturation

The impairment of sperm maturation is one of the major pathogenic factors in male subfertility, a serious medical and social problem affecting millions of global couples. Regrettably, the existing research on sperm maturation is slow, limited, and fragmented, largely attributable to the lack of a global molecular view. To fill the data gap, we newly established a database, namely the Sperm Maturation Database (SperMD, http://bio-add.org/SperMD). SperMD integrates heterogeneous multi-omics data (170 transcriptomes, 91 proteomes, and five human metabolomes) to illustrate the transcriptional, translational, and metabolic manifestations during the entire lifespan of sperm maturation. These data involve almost all crucial scenarios related to sperm maturation, including the tissue components of the epididymal microenvironment, cell constituents of tissues, different pathological states, and so on. To the best of our knowledge, SperMD could be one of the limited repositories that provide focused and comprehensive information on sperm maturation. Easy-to-use web services are also implemented to enhance the experience of data retrieval and molecular comparison between humans and mice. Furthermore, the manuscript illustrates an example application demonstrated to systematically characterize novel gene functions in sperm maturation. Nevertheless, SperMD undertakes the endeavor to integrate the islanding omics data, offering a panoramic molecular view of how the spermatozoa gain full reproductive abilities. It will serve as a valuable resource for the systematic exploration of sperm maturation and for prioritizing the biomarkers and targets for precise diagnosis and therapy of male subfertility.

Translation into Clinical Practice of the G1-G7 Molecular Subgroup Classification of Glioblastoma: Comprehensive Demographic and Molecular Pathway Profiling.

Glioblastoma is the most frequent and malignant primary neoplasm of the central nervous system. In a recent breakthrough study on a prospective Discovery cohort, I proposed the first all-inclusive molecular classification of glioblastoma into seven subgroups, G1-G7, based on MAPK pathway activation. New data from a WHO-grade-4 diffuse glioma prospective Validation cohort offers, in this study, an integrated demographic-molecular analysis of a 213-patient Combined cohort. Despite cohort differences in the median age and molecular subgroup distribution, all the prospectively-acquired cases from the Validation cohort mapped into one of the G1-G7 subgroups defined in the Discovery cohort. A younger age of onset, higher tumor mutation burden and expanded G1/EGFR-mutant and G3/NF1 glioblastoma subgroups characterized the glioblastomas from African American/Black relative to Caucasian/White patients. The three largest molecular subgroups were G1/EGFR, G3/NF1 and G7/Other. The fourth largest subgroup, G6/Multi-RTK, was detailed by describing a novel gene fusion ST7-MET, rare PTPRZ1-MET, LMNA-NTRK1 and GOPC-ROS1 fusions and their overexpression mechanisms in glioblastoma. The correlations between the MAPK pathway G1-G7 subgroups and the PI3-kinase/PTEN, TERT, cell cycle G1 phase and p53 pathways defined characteristic subgroup pathway profiles amenable to personalized targeted therapy. This analysis validated the first all-inclusive molecular classification of glioblastoma, showed significant demographic and molecular differences between subgroups, and provided the first ethnic molecular comparison of glioblastoma.

A new deep-sea species of golden gorgonian (Octocorallia: Scleralcyonacea: Chrysogorgiidae) from Antarctic waters

The Southern Ocean harbours rich deep-sea ecosystems with local hotspots of benthic biodiversity. Still, many species, including deep-water octocorals, remain undescribed despite the fact that the exploration of the deep-sea has improved thanks to recent technological advances. In this context, a new species of golden gorgonian has been collected at 1407–1581 m depth during a recent cruise to Dronning Maud Land in the Eastern Weddell Sea. Currently, after recent changes in Chrysogorgia taxonomy, Chrysogorgia lunae sp. nov. (Octocorallia: Scleralcyonacea) is the only known representative of the genus in Antarctic waters. It corresponds to the "Squamosae typicae" and is characterized by a bushy colony with branching sequence of 2/5L and bell-shaped polyps. A molecular comparison with published sequences of Chrysogorgia species is provided based on a concatenated sequence of two mitochondrial genes, mtMutS and COI, as well as the 28S nuclear ribosomal gene.

DNA barcoding of the supergiant isopods from Bathynomuskensleyi Lowry & Dempsey, 2006 (Cirolanidae) and a molecular biology comparison of B.jamesi Kou, Chen & Li, 2017.

DNA was extracted from tissue samples from specimens of newly-collected Bathynomuskensleyi from Queensland and subsequently the COI and 16S rRNA sequences were successfully cloned. The holotype of B.kensleyi was also sampled for COI only. Comparison of the sequences showed that, for the COI sequences, B.jamesi and B.kensleyi have more than 59 different DNA positions amongst 596 known reading sequences. The Kimura two parameter (K2P) distance analysis confirmed that B.jamesi and B.kensleyi are two species. Indian records of Bathynomus are reviewed and three of the four identified species from India are shown to be misidentifications. Bathynomusdecemspinosus, B.doederlini and B.kensleyi are found to not occur in India and the only accepted record is that of Bathynomuskeablei Lowry & Dempsey, 2006. We conclude that, based on molecular analysis and morphological comparisons, the correct species identity of Indian species other than Bathynomuskeablei remains unknown.

A new species of Ancistrus (Siluriformes: Loricariidae), with a redescription of Ancistrus brevipinnis and further evidence of hidden diversity in the laguna dos Patos system, Brazil

Abstract A new species of Ancistrus is described from the rio Vacacaí drainage, rio Jacuí basin, laguna dos Patos system, southern Brazil. The new species differs from A. brevipinnis, the common species in the laguna dos Patos system, by having a dark brown to black background body color and dorsal and caudal fins plain dark, without lighter spots or bands. A morphometric and molecular comparison of different populations of A. brevipinnis from the laguna dos Patos system suggests that previously undetected species diversity is present in that basin. The type-locality of A. brevipinnis, originally described as Rio Grande do Sul State, is herein restricted to the rio Camaquã sub-basin of the laguna dos Patos system, and a redescription of A. brevipinnis is provided based on that population.

Development and Comprehensive Benchmark of a High-Quality AMBER-Consistent Small Molecule Force Field with Broad Chemical Space Coverage for Molecular Modeling and Free Energy Calculation.

Biomolecular simulations have become an essential tool in contemporary drug discovery, and molecular mechanics force fields (FFs) constitute its cornerstone. Developing a high quality and broad coverage general FF is a significant undertaking that requires substantial expert knowledge and computing resources, which is beyond the scope of general practitioners. Existing FFs originate from only a limited number of groups and organizations, and they either suffer from limited numbers of training sets, lower than desired quality because of oversimplified representations, or are costly for the molecular modeling community to access. To address these issues, in this work, we developed an AMBER-consistent small molecule FF with extensive chemical space coverage, and we provide Open Access parameters for the entire modeling community. To validate our FF, we carried out benchmarks of quantum mechanics (QM)/molecular mechanics conformer comparison and free energy perturbation calculations on several benchmark data sets. Our FF achieves a higher level of performance at reproducing QM energies and geometries than two popular open-source FFs, OpenFF2 and GAFF2. In relative binding free energy calculations for 31 protein-ligand data sets, comprising 1079 pairs of ligands, the new FF achieves an overall root-mean-square error of 1.19 kcal/mol for ΔΔG and 0.92 kcal/mol for ΔG on a subset of 463 ligands without bespoke fitting to the data sets. The results are on par with those of the leading commercial series of OPLS FFs.

A cluster of three extrapulmonary Mycobacterium abscessus infections linked to well-maintained water-based heater-cooler devices.

Various water-based heater-cooler devices (HCDs) have been implicated in nontuberculous mycobacteria outbreaks. Ongoing rigorous surveillance for healthcare-associated M. abscessus (HA-Mab) put in place following a prior institutional outbreak of M. abscessus alerted investigators to a cluster of 3 extrapulmonary M. abscessus infections among patients who had undergone cardiothoracic surgery. Investigators convened a multidisciplinary team and launched a comprehensive investigation to identify potential sources of M. abscessus in the healthcare setting. Adherence to tap water avoidance protocols during patient care and HCD cleaning, disinfection, and maintenance practices were reviewed. Relevant environmental samples were obtained. Patient and environmental M. abscessus isolates were compared using multilocus-sequence typing and pulsed-field gel electrophoresis. Smoke testing was performed to evaluate the potential for aerosol generation and dispersion during HCD use. The entire HCD fleet was replaced to mitigate continued transmission. Clinical presentations of case patients and epidemiologic data supported intraoperative acquisition. M. abscessus was isolated from HCDs used on patients and molecular comparison with patient isolates demonstrated clonality. Smoke testing simulated aerosolization of M. abscessus from HCDs during device operation. Because the HCD fleet was replaced, no additional extrapulmonary HA-Mab infections due to the unique clone identified in this cluster have been detected. Despite adhering to HCD cleaning and disinfection strategies beyond manufacturer instructions for use, HCDs became colonized with and ultimately transmitted M. abscessus to 3 patients. Design modifications to better contain aerosols or filter exhaust during device operation are needed to prevent NTM transmission events from water-based HCDs.

Molecular Characterization and Genetic Subclassification Comparison of Diffuse Large B-Cell Lymphoma: Real-Life Experience with 74 Cases

Introduction: Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous entity. Lately, several algorithms achieving therapeutically and prognostically relevant DLBCL subclassification have been published. Methods: A cohort of 74 routine DLBCL cases was broadly characterized by immunohistochemistry (IHC), fluorescence in situ hybridization (FISH) of the BCL2, BCL6, and MYC loci, and comprehensive high-throughput sequencing (HTS). Based on the genetic alterations found, cases were reclassified using two probabilistic tools – LymphGen and Two-step classifier, allowing for comparison of the two models. Results: Hans and Tally’s overall IHC-based subclassification success rate was 96% and 82%, respectively. HTS and FISH data allowed the LymphGen algorithm to successfully classify 11/55 cases (1 – BN2, 7 – EZB, 1 – MCD, and 2 – genetically composite EZB/N1). The total subclassification rate was 20%. On the other hand, the Two-step classifier categorized 36/55 cases, with 65.5% success (9 – BN2, 12 – EZB, 9 – MCD, 2 – N1, and 4 – ST2). Clinical correlations highlighted MCD as an aggressive subtype associated with higher relapse and mortality. Conclusions: The Two-step algorithm has a better success rate at subclassifying DLBCL cases based on genetic differences. Further improvement of the classifiers is required to increase the number of classifiable cases and thus prove their applicability in routine diagnostics.

A new species of stygobitic Hyalella Smith, 1874 (Amphipoda: Hyalellidae) from Ash Meadows National Wildlife Refuge, Nevada, USA, with discussion of the unique presence of the species in the Nearctic groundwater fauna

Abstract A new species of stygobitic hyalellid amphipod, Hyalella cretaen. sp., is described from Ash Meadows National Wildlife Refuge, Nye County, Nevada, USA, based on both morphological and molecular comparisons to congeners. These data identify H. cretaen. sp. as distinct when compared to allied species. Along with the similar Hyalella muertaBaldinger, Shepard & Threloff, 2000, H. cretaen. sp. marks the second described stygobitic species of Hyalella from the Nearctic. The occurrence of the genus in groundwater in the Nearctic is enigmatic, especially when compared to other more wide-ranging stygobites (e.g., Stygobromus spp., Hadziidae spp.). The biogeographic implications of the occurrence of species like H. muerta and H. cretaen. sp. in relation to other Nearctic stygobites is discussed.

TAXONOMIC REASSESSMENT AND MORPHOLOGICAL REDESCRIPTION OF NEMATOSTRIGEA SERPENS ANNULATA (DIGENEA: STRIGEIDAE) FROM OSPREY IN NORTH AMERICA.

Digenean trematodes in the strigeid genus Nematostrigea are parasites of various birds, most often ospreys (Pandion haliaetus). Nematostrigea currently contains 2 species, Nematostrigea serpens and Nematostigea hepatica. Nematostrigea serpens is divided into 2 subspecies: N. serpens serpens from the Palearctic and Indomalayan realms and N. serpens annulata from the Nearctic realm. In the present work, we studied the type material of N. serpens annulata and collected new specimens from an osprey in Wisconsin close to the type locality. The original description and illustration of N. serpens annulata were incomplete. Herein we provide a detailed redescription and new illustrations of N. serpens annulata on the basis of the type material as well as newly collected and sequenced specimens. Nematostrigea serpens annulata has a distinct tegumental thickening near the mid-length of the genital cone, which is absent in its congeners. Partial sequences of the large ribosomal subunit (28S) DNA and cytochrome c oxidase subunit 1 (COI) mitochondrial DNA gene sequences were generated from our specimens of N. serpens annulata. Comparisons with previously published sequences of N. serpens serpens from the Palearctic demonstrated 2.2% difference in 28S and 3.7% in COI. On the basis of morphological and molecular comparisons, we elevate N. serpens annulata to species status and recognize it as Nematostrigea annulata Dubois and Rausch, 1948.

Extraction, purification and characterization of amylose from sago and corn: Morphological, structural and molecular comparison

In the present work, a comprehensive study was carried out to better understand the molecular characteristics of amylose extracted from sago starch, using butanol as the extraction solvent. The sago derived amylose was compared with amylose extracted from corn starch and both characterized through different techniques, i.e. size exclusion chromatography, X-ray diffraction (XRD), Fourier transform infrared spectroscopy, Raman spectroscopy, Scanning electron microscopy, Atomic force microscopy and Zeta potential measurements. The purity of the amylose extracted from sago and corn was 99.20 % and 93.46 %, respectively. From XRD results, it was revealed that sago amylose had more crystallinity with high thermal stability compared to corn amylose. Based on Raman spectra, single and double helices formed in both extracted amyloses, but due to their intrinsic differences, the intensities associated with these helices varied for sago and corn amylose. Purified amyloses were shown to have two different forms of spherulite morphology: torus and spherical shapes with varying degrees of roughness. Our findings demonstrated that sago starch is a novel and low-cost source for supplying amylose, a promising polymer for different applications.

Design, Synthesis, and Bioactivity of Novel 2-(Arylformyl)cyclohexane-1,3-dione Derivatives as HPPD Inhibitors.

4-Hydroxyphenylpyruvate dioxygenase inhibitors (Echinochloa crus-galli 1.13.11.27, HPPD) have gained significant popularity as one of the best-selling herbicides worldwide. To identify highly effective HPPD inhibitors, a rational design approach utilizing bioisosterism was employed to create a series of 2-(arylformyl)cyclohexane-1,3-dione derivatives. A total of 29 novel compounds were synthesized and characterized through various techniques, including IR, 1H NMR, 13C NMR, and HRMS. Evaluation of their inhibitory activity against Arabidopsis thaliana HPPD (AtHPPD) revealed that certain derivatives exhibited superior potency compared to mesotrione (IC50 = 0.204 μM). Initial herbicidal activity tests demonstrated that compounds 27 and 28 were comparable to mesotrione in terms of weed control and crop safety, with compound 28 exhibiting enhanced safety in canola crops. Molecular docking analyses indicated that the quinoline rings of compounds 27 and 28 formed more stable π-π interactions with the amino acid residues Phe-360 and Phe-403 in the active cavity of AtHPPD, surpassing the benzene ring of mesotrione. Molecular dynamics simulations and molecular structure comparisons confirmed the robust binding capabilities of compounds 27 and 28 to AtHPPD. This study provides a valuable reference for the development of novel triketone herbicide structures, serving as a blueprint for future advancements in this field.

Exploring Psoriasis Inflammatory Microenvironment by NanoString Technologies.

Psoriasis is a chronic inflammatory skin disease whose molecular mechanisms and microenvironment are poorly understood. We performed gene expression analysis through the nCounter® PanCancer Immune Profiling Panel (NanoString Technologies, Seattle, WA, USA) on 22 FFPE punch biopsies from 19 psoriasis-affected patients. A subset of five cases was analyzed before (T0) and after 6 months (T6) of treatment with dimethyl fumarate (DMF) to address immune microenvironment changes. Molecular comparisons according to biopsy site and age of onset showed a different distribution of innate immune cells (mast cells, macrophages, NK cells, and DC cells) and pathways (complement regulation and transporter functions). The analysis according to PASI (Psoriasis Area and Severity Index) led to non-significant results, suggesting no link between molecular expression profile and clinical amount of skin disease. In DMF-treated patients, we observed a strong immunomodulatory effect after treatment: A subversion of exhausted CD8 T cells, NK CD56dim cells, Tregs, neutrophils, CD45+ cells, T cells, B cells, and macrophages was reported between the two analyzed time-points, as well as the reduction in pro-inflammatory pathways and molecules, including cytotoxicity, pathogen defense, antigen processing, adhesion, cell cycle, chemokines, cytokines, and interleukins. The inflammatory psoriatic microenvironment can be modulated using DMF with encouraging results, achieving an immune-tolerant and non-inflammatory condition through the regulation of both innate and adaptive immunity.

New distribution of Reticulitermes speratus speratus (Blattodea: Rhinotermitidae) in Korea.

Reticulitermes speratus (Kolbe) is economically important pest in East Asia including Korea, Japan, and China where they infest wooden structures in urban areas. Previously, it has been reported that R. speratus consists of 5 subspecies, R. speratus kyushuensis Morimoto, R. speratus speratus Kolbe, R. speratus leptolabralis Morimoto, R. speratus okinawanus Morimoto, R. speratus yaeyamanus Morimoto, while only R. speratus kyushuensis was recorded in Korea in the past. However, it remains elusive if different subspecies of R. speratus other than R. speratus kyushuensis are present in Korea. In this study, we report the first record of R. speratus speratus from Korea, which was verified using soldier morphology and molecular characteristics obtained from a mitochondrial gene. R. speratus speratus Kolbe, 1885 (Blattodea: Rhinotermitidae) are found in several provinces, mainly southern regions in Korea, whereas R. speratus kyushuensis are distributed throughout the country. Our morphological comparison showed that R. speratus speratus can be distinguishable from R. speratus kyushuensis by the ratio of the posterior postmentum width to length. In the molecular comparison, R. speratus speratus revealed genetic differences of 3.06% (range 2.60-4.10%) from R. speratus kyushuensis using cytochrome oxidase subunit II gene sequences.

Design, Synthesis, Insecticidal Activity, and SAR of Aryl Isoxazoline Derivatives Containing Pyrazole-5-carboxamide Motif.

It is important to develop new insecticides with a new mode of action because of increasing pesticide resistance. In this study, a series of novel aryl isoxazoline derivatives containing the pyrazole-5-carboxamide motif were designed and synthesized. Their structures were confirmed by 1H NMR, 13C NMR, and HRMS. Bioassays indicated that the 24 compounds synthesized possessed excellent insecticidal activity against Mythimna separate and no activity against Aphis craccivora and Tetranychus cinnabarinus. Among these aryl isoxazoline derivatives, 3-(5-(3,5-dichlorophenyl)-5-(trifluoromethyl)-4,5-dihydrozol-3-yl)-N-(4-fluorophenyl)-1-methyl-1H-pyrazole-5-carboxamide (IA-8) had the best insecticidal activity against M. separate, which is comparable with the positive control fluralaner. The molecular docking results of compound IA-8 and fluralaner with the GABA model demonstrated the same docking mode between compound IA-8 and positive control fluralaner in the active site of GABA. Molecular structure comparisons and ADMET analysis can potentially be used to design more active compounds. The structure-activity relationships are also discussed. This work provided an excellent insecticide for further optimization.

Molecular comparison of organic matter removal from shale gas flowback wastewater: Ozonation versus Fenton process

Shale gas extraction process generates a large amount of shale gas flowback wastewater (SGFW) containing refractory organic compounds, which can pose serious environmental threats if not properly treated. However, the extremely complex compositions of organics in SGFW are still unknown and their transformation pathways in O3- and •OH-dominated systems are not well recognized, which restrain the selection of treatment technology and optimization of operational parameters. The removal characteristics and reaction mechanism of dissolved organic matter (DOM) in SGFW treated by ozonation and Fenton processes were comparatively investigated using electrospray ionization Fourier transform ion cyclotron resonance mass spectrometry. The results showed that both processes could degrade low-oxygen highly unsaturated and phenolic organics, polyphenolics and polycyclic aromatics, and transform them into aliphatic organics and high-oxygen highly unsaturated and phenolic organics. With increasing action of reactive oxygen species (O3 for ozonation and •OH for Fenton process), the degradation products (mainly aliphatic organics) increased during ozonation. However, in Fenton process, a wider range of DOM was removed without aliphatic organics accumulation. The degradation mechanisms of DOM during ozonation and Fenton processes included oxygen addition reactions (+3O, +H2O2, and +2O) as dominant pathways. However, ozonation showed more violent oxygenation, hydroxylation, and carboxylation, while Fenton process presented more violent chain-breaking reactions. These results revealed the selective oxidation of ozone and nonselective oxidation of •OH during SGFW treatment, and provided theoretical support for selecting SGFW treatment approaches.

Single-cell multiomics of human fetal hematopoiesis define a developmental-specific population and a fetal signature.

Knowledge of human fetal blood development and how it differs from adult blood is highly relevant to our understanding of congenital blood and immune disorders and childhood leukemia, of which the latter can originate in utero. Blood formation occurs in waves that overlap in time and space, adding to heterogeneity, which necessitates single-cell approaches. Here, a combined single-cell immunophenotypic and transcriptional map of first trimester primitive blood development is presented. Using CITE-seq (cellular indexing of transcriptomes and epitopes by sequencing), the molecular profile of established immunophenotype-gated progenitors was analyzed in the fetal liver (FL). Classical markers for hematopoietic stem cells (HSCs), such as CD90 and CD49F, were largely preserved, whereas CD135 (FLT3) and CD123 (IL3R) had a ubiquitous expression pattern capturing heterogenous populations. Direct molecular comparison with an adult bone marrow data set revealed that the HSC state was less frequent in FL, whereas cells with a lymphomyeloid signature were more abundant. An erythromyeloid-primed multipotent progenitor cluster was identified, potentially representing a transient, fetal-specific population. Furthermore, differentially expressed genes between fetal and adult counterparts were specifically analyzed, and a fetal core signature was identified. The core gene set could separate subgroups of acute lymphoblastic leukemia by age, suggesting that a fetal program may be partially retained in specific subgroups of pediatric leukemia. Our detailed single-cell map presented herein emphasizes molecular and immunophenotypic differences between fetal and adult blood cells, which are of significance for future studies of pediatric leukemia and blood development in general.

Development and circuitry of the tunicate larval Motor Ganglion, a putative hindbrain/spinal cord homolog.

The Motor Ganglion (MG) is a small collection of neurons that control the swimming movements of the tunicate tadpole larva. Situated at the base of the tail, molecular and functional comparisons suggest that may be a homolog of the spinal cord and/or hindbrain ("rhombospinal" region) of vertebrates. Here we review the most current knowledge of the development, connectivity, functions, and unique identities of the neurons that comprise the MG, drawn mostly from studies in Ciona spp. The simple cell lineages, minimal cellular composition, and comprehensively mapped "connectome" of the Ciona MG all make this an excellent model for studying the development and physiology of motor control in aquatic larvae.

Molecular characterization and comparison of bla NDM-1-carrying and bla NDM-5-harboring IncX3-type plasmids in carbapenem-resistant Klebsiella pneumoniae.

Carbapenem-resistant Klebsiella pneumoniae (CRKP), which harbors the bla NDM plasmid, has been reported extensively and is considered a global threat clinically. However, characterization and comparisons of bla NDM-1-carrying and bla NDM-5-harboring IncX3-type plasmids in CRKP are lacking. Here, we systematically compared the differences in the characteristics, genetic backgrounds, transferability, and fitness costs between bla NDM-1-carrying and bla NDM-5-carrying plasmids in K. pneumoniae isolates. Fifteen NDM-producing CRKP isolates were recovered from 1376 CRKP isolates between 2019 and 2021, of which 4 were positive for bla NDM-1 and 11 were positive for bla NDM-5. All strains were highly resistant to carbapenem but remained susceptible to tigecycline and colistin. Core-genome-based phylogenetic analyses revealed that these strains were not clonally related. Whole-genome sequencing showed that bla NDM-1 and bla NDM-5 were located on ~54 kb and ~46 kb IncX3-type plasmids, respectively. The backbone, genetic context, and fitness cost of the bla NDM-1-bearing plasmid were highly similar to those of the bla NDM-5-carrying plasmid, but the transferability of the bla NDM-1-positive plasmid was greater than that of the bla NDM-5-positive plasmid. In conclusion, the transmission of bla NDM-1 or bla NDM-5 is mainly disseminated by plasmids rather than clonal spread. The high transfer frequency of the IncX3 plasmid facilitates the prevalence and dissemination of NDM-KP among Enterobacteriaceae. IMPORTANCE The emergence of NDM-producing Klebsiella pneumoniae is a severe challenge to public health. The widespread presence of bla NDM-1 and bla NDM-5 in Enterobacteriaceae has aroused broad concern. In this study, we performed molecular characterization of bla NDM-1-carrying and bla NDM-5-harboring IncX3-type plasmids in carbapenem-resistant Klebsiella pneumoniae (CRKP) and compared their phenotypes between strains with different bla NDM subtype. Our findings highlight the importance of IncX3-type plasmids in the transfer of the bla NDM-1 and bla NDM-5 genes and demonstrate that the bla NDM-1 plasmid possesses higher transfer ability. These data will provide important insights into carbapenem resistance gene transfer via plasmids and their further spread in clinical settings.

A network pharmacology and molecular docking investigation on the mechanisms of Shanyaotianhua decoction (STT) as a therapy for psoriasis.

Psoriasis is an immune-mediated inflammatory skin disease with a complex etiology involving environmental and genetic factors. Psoriasis patients often require long-term treatment. Shanyaotianua decoction (STT), a typical traditional Chinese medicine prescription, positively affects psoriasis, although its molecular targets remain unknown. To elucidate its molecular mechanisms, a combination of network pharmacology, bioinformatics analysis, and drug similarity comparisons were employed. Participants were separated into 3 groups: non-lesional (NL), lesions after medication (LM), and psoriasis lesion groups (LS). Based on the Gene Ontology/kyoto encyclopedia of genes and genomes enrichment analyses, the key targets were mainly enriched for biological processes (immuno-inflammatory responses, leukocyte differentiation, lipid metabolic disorders, and viral infection) with the relevant pathways (Janus kinase/signal transducers and activators of transcription and adipocytokine signaling and T-helper 17 cell differentiation), thus identifying the possible action mechanism of STT against psoriasis. Target prediction for 18 STT compounds that matched the screening criteria was performed. Then, the STT compounds were intersected with the differentially expressed genes of the psoriatic process, and 5 proteins were potential targets for STT. Based on the open-source toolkit RDKit and DrugBank database, and through molecular docking and drug similarity comparisons, spinasterol, diosgenin, and 24-Methylcholest-5-enyl-3belta-O-glucopyranoside_qt may be potential drugs for psoriasis.