The Role of Deformation and Microstructure Evolution on Texture Formation of a TA15 Alloy Subjected to Plane Strain Compression.

In this study, the texture formation mechanism of a TA15 titanium alloy under different plane strain compression conditions was investigated by analyzing the slipping, dynamic recrystallization (DRX) and phase transformation behaviors. The results indicated that the basal texture component basically appears under all conditions, since the dominant basal slip makes the C-axis of the α grain rotate to the normal direction (ND, i.e., compression direction), but it has a different degree of deflection. With an increase in deformation amount, temperature or strain rate, {0001} poles first approach the ND and then deviate from it. Such deviation is mainly caused by a change in slip behaviors and phase transformation. At a smaller deformation amount and higher strain rate, inhomogeneous deformation easily causes a basal slip preferentially arising from the grain with a soft orientation, resulting in a weak basal texture component. A greater deformation amount can increase the principal strain ratio, thereby promoting other slip systems to be activated, and a lower temperature can increase the critical shear stress of the basal slip, further causing a dispersive orientation under these conditions. At a higher temperature and a lower strain rate, apparent phase transformation will induce the occurrence of lamellar α whose orientation obeys the Burgers orientation of the ß phase, thereby disturbing and weakening the deformation texture. As for DRX, continuous-type (CDRX) is most common under most conditions, whereas CDRX grains have a similar orientation to deformed grains, so DRX has little effect on overall texture. Moreover, the microhardness of samples is basically inversely proportional to the grain size, and it can be significantly improved as lamellar α occurs. In addition, deformed samples with a weaker texture present a higher microhardness due to the smaller Schmidt factors of the activated prism slip at ambient loading.

Evolutionary Adaptation of KPC-2-Producing Pseudomonas aeruginosa High-Risk Sequence Type 463 in a Lung Transplant Patient.

OBJECTIVES: KPC-2-producing Pseudomonas aeruginosa high-risk sequence type (ST) 463 is increasingly prevalent in China and poses severe threats to public health. In this study, we aimed to investigate within-host adaptive evolution of this clone during therapy. METHODS: Using nine serial respiratory isolates from a post-lung transplantation patient undergoing multiple antibiotic treatments, we conducted genomic, transcriptomic, and phenotypic analyses to uncover the adaptive mechanisms of a KPC-2-producing ST463 P. aeruginosa strain. RESULTS: The early-course isolates exhibited low-level resistance to ceftazidime/avibactam (CZA), facilitated by the blaKPC-2 gene's presence on both chromosome and plasmid, and its overexpression. Comparative genomic analysis revealed that chromosomal integration of blaKPC-2 resulted from intracellular replicative transposition of the plasmid-derived IS26-blaKPC-2-IS26 composite transposon. As the infection progressed, selective pressures, predominantly from antibiotic interventions and host immune response, led to significant genomic and phenotypic changes. The late-course isolates developed a Δ242-GT-243 deletion in plasmid-encoded blaKPC-2 (blaKPC-14) after sustained CZA exposure, conferring high-level CZA resistance. Increased expression of pili and extracellular polysaccharides boosted biofilm formation. A D143N mutation in the global regulator vfr rendered the strain aflagellate by abrogating the ability of fleQ to positively regulate flagellar gene expression. The enhancement of antibiotic resistance and immune evasion collaboratively facilitated the prolonged survival of ST463 P. aeruginosa within the host. CONCLUSIONS: Our findings highlight the remarkable capacity of ST463 P. aeruginosa in adapting to the dynamic host pressures, supporting its persistence and dissemination in healthcare.

MOSGAT: Uniting Specificity-Aware GATs and Cross Modal-Attention to Integrate Multi-Omics Data for Disease Diagnosis.

With the advancement of sequencing methodologies, the acquisition of vast amounts of multi-omics data presents a significant opportunity for comprehending the intricate biological mechanisms underlying diseases and achieving precise diagnosis and treatment for complex disorders. However, as diverse omics data are integrated, extracting sample-specific features within each omics modality and exploring potential correlations among different modalities while avoiding mutual interference becomes a critical challenge in multi-omics data integration research. In the context of this study, we proposed a framework that unites specificity-aware GATs and cross-modal attention to integrate different omics data (MOSGAT). To be specific, we devise Graph Attention Networks (GATs) tailored for each omics modality data to perform feature extraction on samples. Additionally, an adaptive confidence attention weighting technique is incorporated to enhance the confidence in the extracted features. Finally, a cross-modal attention mechanism was devised based on multi-head self-attention, thoroughly uncovering potential correlations between different omics data. Extensive experiments were conducted on four publicly available medical datasets, highlighting the superiority of the proposed framework when compared to state-of-the-art methodologies, particularly in the realm of classification tasks. The experimental results underscore MOSGAT's effectiveness in extracting features and exploring potential inter-omics associations.

KOH Activated Carbon Coated 3D Wood Solar Evaporator with Highest Water Transport Height and Evaporation Rate for Clean Water Production.

The water evaporation rate of 3D solar evaporator heavily relies on the water transport height of the evaporator. In this work, a 3D solar evaporator featuring a soil capillary-like structure is designed by surface coating native balsa wood using potassium hydroxide activated carbon (KAC). This KAC-coated wood evaporator can transport water up to 32 cm, surpassing that of native wood by ≈8 times. Moreover, under 1 kW m-2 solar radiation without wind, the KAC-coated wood evaporator exhibits a remarkable water evaporation rate of 25.3 kg m-2 h-1, ranking among the highest compared with other reported evaporators. The exceptional water transport capabilities of the KAC-coated wood should be attributed to the black and hydrophilic KAC film, which creates a porous network resembling a soil capillary structure to facilitate efficient water transport. In the porous network of coated KAC film, the small internal pores play a pivotal role in achieving rapid capillary condensation, while the larger interstitial channels store condensed water, further promoting water transport up more and micropore capillary condensation. Moreover, this innovative design demonstrates efficacy in retarding phenol from wastewater through absorption onto the coated KAC film, thus presenting a new avenue for high-efficiency clean water production.

Green synthesis of a superhydrophobic porous organic polymer for the removal of volatile organic compounds at high humidity.

Superhydrophobic porous organic polymers are potential sorbents for volatile organic compounds (VOCs) pollution control by suppressing the competition of water molecules on their surfaces. However, the synthesis of superhydrophobic reagents usually requires large amounts of organic solvents and a long reaction time (≥ 24 h). Herein, a green mechanochemical method was developed to synthesize a superhydrophobic polymer (MSHMP-1) with the advantages of using a small amount of organic solvents (5 mL/g) and a short reaction time (2 h). Meanwhile, MSHMP-1 with a water contact angle (WCA) of 162° exhibited a dramatically rich pore structure as revealed by its specific surface area (SSA) of 1780 m2/g. The decrease in the adsorption of benzene on MSHMP-1 due to the competition of water molecules, even at relative humidity of 90 %, was nonsignificant (<10 %), indicating the great application potential of MSHMP-1 in hydrophobic adsorption. Moreover, the adsorption capacity of MSHMP-1 was maintained after at least five adsorption-desorption cycles. Therefore, MSHMP-1 can be a remarkable adsorbent for the removal of hazardous VOCs, especially at high humidity levels.

Decomposition strategy for surface EMG with few channels: a simulation study.

Objective.In the specific use of electromyogram (EMG) driven prosthetics, the user's disability reduces the space available for the electrode array. We propose a framework for EMG decomposition adapted to the condition of a few channels (less than 30 observations), which can elevate the potential of prosthetics in terms of cost and applicability.Approach.The new framework contains a peel-off approach, a refining strategy for motor unit (MU) spike train and MU action potential and a re-subtracting strategy to adapt the framework to few channels environments. Simulated EMG signals were generated to test the framework. In addition, we quantify and analyze the effect of strategies used in the framework.Main results.The results show that the new algorithm has an average improvement of 19.97% in the number of MUs identified compared to the control algorithm. Quantitative analysis of the usage strategies shows that the re-subtracting and refining strategies can effectively improve the performance of the framework under the condition of few channels.Significance.These prove that the new framework can be applied to few channel conditions, providing a optimization space for neural interface design in cost and user adaptation.

Identification of SMC2 and SMC4 as prognostic markers in breast cancer through bioinformatics analysis.

BACKGROUND: Breast cancer (BRCA) is one of the most common malignant tumors. The structural maintenance of chromosome (SMC) gene family has been shown to play an important role in human cancers. However, the role of SMC families in BRCA is unclear. This study aimed to explore the role and potential clinical value of whole SMCs in BRCA. METHODS: TIMER and UALCAN database were used to analysis the expression level. Genetic variations were analyzed by cBioPortal. Promoter methylation and protein level were analyzed by UCLCAN. GO and KEGG were analyzed by Metascape database. Prognostic value of SMCs was analyzed by Kaplan-Meier and multivariate cox regression analyses. Immune infiltration analysis was conducted by CIBERSORT. Immunotherapy outcome prediction was conducted by Cancer Immunome Atlas. Targeted drug therapy outcome prediction was taken by GDSC and R language. The cell viability was tested by CCK8 and migration was tested by wound healing assay. Xenograft model was used to investigate the in vivo role of SMC2. RESULTS: Expression levels of SMC1A, SMC2, SMC4, SMC5 and SMC6 mRNA were increased in BRCA tissues, and negatively correlated with promoter methylation. Overexpression of SMC2 and SMC4 was negatively correlated with survival. Function of SMCs family regulatory genes was mainly related to ATPase activity. Expression of most SMCs was negatively correlated with immunotherapy and drug therapy outcomes. Interfere SMC2 and SMC4 decreased IC50 values of 5-fluorouracil and oxaliplatin and inhibited the migration of MCF7 cells. Tumor growth and weights were significantly decreased in si-SMC2 groups. CONCLUSIONS: Combined bioinformatics and clinical specimen analysis verified SMC2 and SMC4 as independent prognostic factors in BRCA, suggesting their significance for the diagnosis and treatment of BRCA.

5-Hydroxytryptamine Enhances the Pacemaker Activity of Interstitial Cells of Cajal in Mouse Colon.

We examined the localization of the 5-hydroxytryptamine (5-HT) receptor and its effects on mouse colonic interstitial cells of Cajal (ICCs) using electrophysiological techniques. Treatment with 5-HT increased the pacemaker activity in colonic ICCs with depolarization of membrane potentials in a dose-dependent manner. Hyperpolarization-activated cyclic nucleotide-gated (HCN) channel blockers blocked pacemaker activity and 5-HT-induced effects. Moreover, an adenylate cyclase inhibitor inhibited 5-HT-induced effects, and cell-permeable 8-bromo-cAMP increased the pacemaker activity. Various agonists of the 5-HT receptor subtype were working in colonic ICCs, including the 5-HT4 receptor. In small intestinal ICCs, 5-HT depolarized the membrane potentials transiently. Adenylate cyclase inhibitors or HCN blockers did not show any influence on 5-HT-induced effects. Anoctamin-1 (ANO1) or T-type Ca2+ channel blockers inhibited the pacemaker activity of colonic ICCs and blocked 5-HT-induced effects. A tyrosine protein kinase inhibitor inhibited pacemaker activity in colonic ICCs under controlled conditions but did not show any influence on 5-HT-induced effects. Among mitogen-activated protein kinase (MAPK) inhibitors, a p38 MAPK inhibitor inhibited 5-HT-induced effects on colonic ICCs. Thus, 5-HT's effect on pacemaker activity in small intestinal and colonic ICCs has excitatory but variable patterns. ANO1, T-type Ca2+, and HCN channels are involved in 5-HT-induced effects, and MAPKs are involved in 5-HT effects in colonic ICCs.

Advances in tumor microenvironment and underlying molecular mechanisms of bladder cancer: a systematic review.

Bladder cancer is one of the most frequent malignant tumors of the urinary system. The prevalence of bladder cancer among men and women is roughly 5:2, and both its incidence and death have been rising steadily over the past few years. At the moment, metastasis and recurrence of advanced bladder cancer-which are believed to be connected to the malfunction of multigene and multilevel cell signaling network-remain the leading causes of bladder cancer-related death. The therapeutic treatment of bladder cancer will be greatly aided by the elucidation of these mechanisms. New concepts for the treatment of bladder cancer have been made possible by the advancement of research technologies and a number of new treatment options, including immunotherapy and targeted therapy. In this paper, we will extensively review the development of the tumor microenvironment and the possible molecular mechanisms of bladder cancer.

Double-walled Al-based MOF with large microporous specific surface area for trace benzene adsorption.

Double-walled metal-organic frameworks (MOFs), synthesized using Zn and Co, are potential porous materials for trace benzene adsorption. Aluminum is with low-toxicity and abundance in nature, in comparison with Zn and Co. Therefore, a double-walled Al-based MOF, named as ZJU-520(Al), with large microporous specific surface area of 2235 m2 g-1, pore size distribution in the range of 9.26-12.99 Å and excellent chemical stability, was synthesized. ZJU-520(Al) is consisted by helical chain of AlO6 clusters and 4,6-Di(4-carboxyphenyl)pyrimidine ligands. Trace benzene adsorption of ZJU-520(Al) is up to 5.98 mmol g-1 at 298 K and P/P0 = 0.01. Adsorbed benzene molecules are trapped on two types of sites. One (site I) is near the AlO6 clusters, another (site II) is near the N atom of ligands, using Grand Canonical Monte Carlo simulations. ZJU-520(Al) can effectively separate trace benzene from mixed vapor flow of benzene and cyclohexane, due to the adsorption affinity of benzene higher than that of cyclohexane. Therefore, ZJU-520(Al) is a potential adsorbent for trace benzene adsorption and benzene/cyclohexane separation.

Characteristics and phylogenetic distribution of megaplasmids and prediction of a putative chromid in Pseudomonas aeruginosa.

Research on megaplasmids that contribute to the spread of antimicrobial resistance (AMR) in Pseudomonas aeruginosa strains has grown in recent years due to the now widely used technologies allowing long-read sequencing. Here, we systematically analyzed distinct and consistent genetic characteristics of megaplasmids found in P. aeruginosa. Our data provide information on their phylogenetic distribution and hypotheses tracing the potential evolutionary paths of megaplasmids. Most of the megaplasmids we found belong to the IncP-2-type, with conserved and syntenic genetic backbones carrying modules of genes associated with chemotaxis apparatus, tellurite resistance and plasmid replication, segregation, and transmission. Extensively variable regions harbor abundant AMR genes, especially those encoding ß-lactamases such as VIM-2, IMP-45, and KPC variants, which are high-risk elements in nosocomial infection. IncP-2 megaplasmids act as effective vehicles transmitting AMR genes to diverse regions. One evolutionary model of the origin of megaplasmids claims that chromids can develop from megaplasmids. These chromids have been characterized as an intermediate between a megaplasmid and a chromosome, also containing core genes that can be found on the chromosome but not on the megaplasmid. Using in silico prediction, we identified the "PABCH45 unnamed replicon" as a putative chromid in P. aeruginosa, which shows a much higher similarity and closer phylogenetic relationship to chromosomes than to megaplasmids while also encoding plasmid-like partition genes. We propose that such a chromid could facilitate genome expansion, allowing for more rapid adaptations to novel ecological niches or selective conditions, in comparison to megaplasmids.

Sub-high amylose maize starch: an ideal substrate to generate starch with lower digestibility by fermentation of Qu.

BACKGROUND: The fermentation of Qu (FQ) is a novel method to modify the properties of starch to expand its application and especially to increase the resistant starch (RS) content. Using waxy maize starch (WMS) as a fermentation substrate can increase the RS content significantly but it may be time consuming and not cost effective due to the almost negligible RS content of WMS. To solve this problem, we hypothesized that sub-high amylose starch (s-HAMS), with an amylose content close to 50% could be an ideal substrate for FQ. RESULTS: The results showed that FQ did not change the shape and the particle size of starch granules, the gelatinization peak (Tp), or the conclusion temperature (Tc), but the slowly digested starch content declined. Rapidly digested starch content fluctuated during FQ and the amylose content decreased within 36 h and then increased. Within 24h, FQ significanlty increased these values: the RS content, relative crystallinity (RC), the ratio of FTIR absorbances at 1047/1022cm-1, the diffraction peak at 19.8° in X-ray diffraction (XRD), and the gelatinization onset temperature (To) increased significantly, within 24 h of FQ. However, after 24 h of fermentation, the RS content, RC, the ratio of FTIR absorbances at 1047/1022 cm-1, and gelatinization enthalpy (ΔH) decreased significantly. CONCLUSION: Sub-high amylose starch is more suitable for FQ to produce low digestibility starch, and the increase in RS may be due to the formation of 'amylose-lipid' complexes (RS5). © 2024 Society of Chemical Industry.

Simultaneous adsorption of fulvic acid and organic contaminants by KOH activated mesoporous biochar with large surface area.

Returning carbon materials from biomass to soil is a potential technology to retard organic contaminants or dissolved organic matter (DOM) in soil by adsorption, as well as to store carbon in soil for carbon sequestration. However, DOM was widely reported to inhibit adsorption of organic contaminants on carbon materials by competition and by enhancing contaminants' solubility. In this study, a KOH activated carbon material (KAC), pyrolyzed from bamboo chips, with high surface area (3108 m2/g), micropores volumes (0.964 cm3/g), mesopores volumes (1.284 cm3/g), was observed that it can adsorb fulvic acid (FA) and organic contaminants (e.g., nitrobenzene, phenols, and anilines) simultaneously with weak competition and high adsorption capacity. With 50 mg TOC/L FA, for example, the average competition suppressing rate (ΔKf/Kf-m) of organic contaminants on KAC was lower than 5%, the adsorption for organic contaminants and FA were higher than 1100 mg/g and 90 mg TOC/g, respectively. The weak competition on KAC could be attributed to the low micropore blockage (<35%) and the weak adsorption sites competition on mesopores of KAC, as well as the minimal solubility enhancement of organic contaminants by FA because most FA is adsorbed on KAC but is not dissolved in the solution. In addition, adsorption of organic contaminants with high hydrogen-bonding donor ability (αm) and adsorption affinity was less suppressed by FA because of the heterogeneous nature of hydrophilic sites on KAC's surface. Therefore, KAC could be a potential carbon material to be produced to implement to soil for carbon storage and simultaneous retarding organic contaminants and DOM.

Omental fibroma combined with right indirect inguinal hernia masquerades as a scrotal tumor: A case report.

BACKGROUND: The most common causes of scrotal enlargement in patients include primary tumor of the scrotum, inflammation, hydrocele of the tunica vaginalis, and indirect inguinal hernia; scrotal enlargement caused by external tumors of the scrotum is rare. The patient had both a greater omentum tumor and an inguinal hernia, and the tumor protruded into the scrotum through the hernia sac, which is even rarer. Moreover, omental tumors are mostly metastatic, and primary omental fibroma is rare. CASE SUMMARY: Here, we report a rare case of a 25-year-old young man with scrotal enlargement and pain for 3 months. Preoperative examination and multidisciplinary discussions considered intra-abdominal tumor displacement and inguinal hernia, and intraoperative exploration confirmed that the greater omentum tumor protruded into the scrotum. Therefore, tumor resection and tension-free inguinal hernia repair were performed. The final diagnosis was benign fibroma of the greater omentum accompanied by an indirect inguinal hernia. CONCLUSION: This unusual presentation of a common inguinal hernia disease illustrates the necessity of performing detailed history taking, physical examination, and imaging before surgery.

Linear adsorption of organic compounds on mesoporous activated carbon in bi-solute system.

Knowledge of organic compounds adsorption by adsorbents is essential for evaluating the environmental fates of organic compounds and removing them from the environment. Linear adsorption, as a supplement to the traditionally nonlinear adsorption, was previously proposed for the linear sorption of organic compounds on the mesoporous surface of carbon nanotubes (CNTs) in multi-solute system. However, CNTs are not the ideal adsorbent to verify the linear adsorption mechanism, because of their partition-like phase components such as mobile graphene layers that could be responsible for the linear sorption through linear partition mechanism instead, and thus the linear adsorption theory was argued. In this study, therefore, mesoporous activated carbon (MAC), widely accepted as the model free of partition phase components, was selected as an adsorbent to investigate the adsorption of typical organic compounds in the bi-solute system for verifying whether the linear adsorption phenomenon existed or not. The isotherm of nitrobenzene on MAC was changed from nonlinear to linear with 4-nitrophenol up to 1400 mg/L, and the linear isotherm slope decreased more as 4-nitrophenol concentration increased until 4000 mg/L. It agreed with the characteristics of adsorption (i.e., competition) but not partition (i.e., noncompetition), confirming the existence of linear adsorption. The isotherm linearity was attributed to the reduction of adsorption interactions by displacement and multilayer adsorption. Moreover, linear adsorption of apolar compounds on MAC could occur with apolar or polar competitors, while for polar compounds, linear adsorption could occur with only polar competitors. The observed linear sorption and the competition of organic compounds in the bi-solute system on MAC free of partition phase components verified that the linear adsorption existed, which gives a new insight into the adsorption theory for organic compounds. The results could provide better fundamental theory of adsorption for improving the accuracy of environmental risk assessment of organic pollution and enhancing the efficiency of organic pollution control in the environment.

Role of biochar pyrolysis temperature on intracellular and extracellular biodegradation of biochar-adsorbed organic compounds.

Immobilizing organic pollutants by adsorption of biochar in farmland soil is a cost-effective remediation method for contaminated soil. As the adsorption capacity of biochar is limited, biodegradation of biochar-adsorbed organic pollutants was a potential way to regenerate biochars and maintain the adsorption performance of biochars to lower the cost. It could be affected by the biochar pyrolysis temperature, but was not evaluated yet. In this study, biodegradation of adsorbed phenanthrene on a series of biochars with pyrolysis temperatures from 150 to 700 °C by Sphingobium yanoikuyae B1 was investigated using batch experiments of biodegradation kinetics at 30 °C, to explore the role of biochar pyrolysis temperature on biodegradation of biochar-adsorbed organic compounds. It was observed that 37.5-47.9% of adsorbed phenanthrene on moderate temperature-pyrolyzed biochars produced at 400 and 500 °C were biodegraded, less than that on high temperature-pyrolyzed biochars produced at ≥600 °C (48.8-60.8%) and low temperature-pyrolyzed biochars produced at ≤300 °C (63.4-92.5%). Phenanthrene adsorbed largely on the low temperature-pyrolyzed biochars by partition mechanism and thus is easily desorbed to water for a dominated intracellular biodegradation. On the high temperature-pyrolyzed biochars, phenanthrene is adsorbed largely by pore-filling mechanism and thus less desorbed to water for intracellular biodegradation. However, high temperature-pyrolyzed biochars can promote microbes to produce siderophore, H2O2 and thus release extracellular •OH for a dominated degradation of adsorbed phenanthrene by Fenton-like reaction. With the increase of biochar pyrolysis temperature, desorption and consequently the intracellular biodegradation of adsorbed phenanthrene on biochars decreased, while the secretion of siderophore and H2O2 by microbes on biochars increased to produce more extracellular •OH for degradation by Fenton-like reaction. The results could provide deep insights into the role of biochar pyrolysis temperature on biodegradation of biochar-adsorbed organic compounds, and optimize the selection of biochar with higher adsorption performance and easier regeneration for soil remediation.

Targeted Delivery of Arctigenin Using Sialic Acid Conjugate-Modified Liposomes for the Treatment of Breast Cancer.

Arctigenin (ATG) is a broad-spectrum antitumor drug with an excellent inhibitory effect on malignant tumors such as breast cancer, glioblastoma, liver cancer, and colon cancer. However, the clinical application of ATG is limited by its poor water solubility and quick hydrolysis in the liver, intestine, and plasma, which might hinder its application. Sialic acid (SA) recognizes selectin receptors overexpressed on the surface of tumor-associated macrophages. In this study, SA was conjugated with octadecylamine (ODA) to prepare SA-ODA, which was employed to prepare SA functionalized nanoliposomes (SA-Lip) to achieve breast cancer targeting. The formulations were finely optimized using the Box-Behnken design to achieve higher ATG loading. The size, ζ potential, entrapment efficiency, drug loading, and release behavior of ATG@SA-Lip were fully investigated in comparison with conventional ATG@Lip. The ATG@SA-Lip displayed more potent cytotoxicity and higher cellular internalization compared to ATG@Sol and ATG@Lip in both MCF7 and 4T1 cells. Notably, ATG@SA-Lip showed the lowest impact on the immune system. Our study demonstrates that SA-Lip has strong potential as a delivery system for the targeted delivery of ATG.

scSID: A lightweight algorithm for identifying rare cell types by capturing differential expression from single-cell sequencing data.

Single-cell RNA sequencing (scRNA-seq) is currently an important technology for identifying cell types and studying diseases at the genetic level. Identifying rare cell types is biologically important as one of the downstream data analyses of single-cell RNA sequencing. Although rare cell identification methods have been developed, most of these suffer from insufficient mining of intercellular similarities, low scalability, and being time-consuming. In this paper, we propose a single-cell similarity division algorithm (scSID) for identifying rare cells. It takes cell-to-cell similarity into consideration by analyzing both inter-cluster and intra-cluster similarities, and discovers rare cell types based on the similarity differences. We show that scSID outperforms other existing methods by benchmarking it on different experimental datasets. Application of scSID to multiple datasets, including 68K PBMC and intestine, highlights its exceptional scalability and remarkable ability to identify rare cell populations.

Characterisation of a Novel Hybrid IncFIIpHN7A8:IncR:IncN Plasmid Co-Harboring blaNDM-5 and blaKPC-2 from a Clinical ST11 Carbapenem-Resistant Klebsiella pneumoniae Strain.

Purpose: We aimed to characterize a novel blaNDM-5 and blaKPC-2 co-carrying hybrid plasmid from a clinical carbapenem-resistant Klebsiella pneumoniae (CRKP) strain. Methods: Antimicrobial susceptibility was determined by the broth microdilution method. Plasmid size and localization were estimated using S1 nuclease pulsed-field gel electrophoresis (S1-PFGE) and Southern blotting. Plasmid transfer ability was evaluated by conjugation experiments. Whole genome sequencing (WGS) was performed using Illumina NovaSeq6000 and Oxford Nanopore MinION platforms. Genomic characteristics were analyzed using bioinformatics methods. Results: Strain ZY27320 was a multidrug-resistant (MDR) clinical ST11 K. pneumoniae strain that confers high-level resistance to carbapenems (meropenem, MIC 128 mg/L; imipenem, MIC 64 mg/L) and ceftazidime/avibactam (MIC >128/4 mg/L). Both S1-PFGE-Southern blotting and whole genome sequencing revealed that the carbapenemase genes blaKPC-2 and blaNDM-5 were carried by the same IncFIIpHN7A8:IncR:IncN hybrid plasmid (pKPC2_NDM5). Conjugation experiments indicated that pKPC2_NDM5 was a non-conjugative plasmid. Conclusion: This is the first report of a hybrid plasmid carrying both carbapenemase genes blaNDM-5 and blaKPC-2 in a clinical K. pneumoniae ST11 isolate that confers resistance to both ceftazidime/avibactam and carbapenems, thereby presenting a serious threat to treatment in clinical practice.