Fate mapping of Spp1 expression reveals age-dependent plasticity of disease-associated microglia-like cells after brain injury.

Microglial reactivity to injury and disease is emerging as a heterogeneous, dynamic, and crucial determinant in neurological disorders. However, the plasticity and fate of disease-associated microglia (DAM) remain largely unknown. We established a lineage tracing system, leveraging the expression dynamics of secreted phosphoprotein 1（Spp1） to label and track DAM-like microglia during brain injury and recovery. Fate mapping of Spp1+ microglia during stroke in juvenile mice revealed an irreversible state of DAM-like microglia that were ultimately eliminated from the injured brain. By contrast, DAM-like microglia in the neonatal stroke models exhibited high plasticity, regaining a homeostatic signature and integrating into the microglial network after recovery. Furthermore, neonatal injury had a lasting impact on microglia, rendering them intrinsically sensitized to subsequent immune challenges. Therefore, our findings highlight the plasticity and innate immune memory of neonatal microglia, shedding light on the fate of DAM-like microglia in various neuropathological conditions.

Computing whole embryo strain maps during gastrulation.

Gastrulation is a critical process during embryonic development that transforms a single-layered blastula into a multilayered embryo with distinct germ layers, which eventually give rise to all the tissues and organs of the organism. Studies across species have uncovered the mechanisms underlying the building blocks of gastrulation movements, such as localized in-plane and out-of-plane epithelial deformations. The next challenge is to understand dynamics on the scale of the embryo: this requires quantifying strain tensors, which rigorously describe the differences between the deformed configurations taken on by local clusters of cells at time instants of observation and their reference configuration at an initial time. We present a systematic strategy for computing such tensors from the local dynamics of cell clusters, which are chosen across the embryo from several regions whose morphogenetic fate is central to viable gastrulation. As an application of our approach, we demonstrate a strategy of identifying distinct Drosophila morphological domains using strain tensors.

Hoxc10-mediated 'positional memory' regulates cartilage formation subsequent to femoral heterotopic grafting.

The Hox gene plays a crucial role in the bone development, determining their structure and morphology. Limb bone grafts expressing Hox positive genes are commonly used for free transplantation to repair Hox negative mandibular critical bone defects. However, the specific role of original Hox genes in newly formed bone during the cross-layer bone grafting healing process remains unexplored. Our findings demonstrate that femurs ectopically grafted into the mandibular environment retained a significant ability to differentiate into cartilage and form cartilaginous callus, which may be a key factor contributing to differences in bone graft healing. Hoxc10, an embryonic layer-specific genes, regulates cartilage formation during bone healing. Mechanistically, we observed Hoxc10 retention in co-cultured femoral BMSCs. Knocking out Hoxc10 narrows the bone gap and reduces cartilage formation. In summary, we reveal Hoxc10's 'positional memory' after adult cross-layer bone graft, influencing the outcomes of autologous bone graft.

Beyond hype: unveiling the Real challenges in clinical translation of 3D printed bone scaffolds and the fresh prospects of bioprinted organoids.

Bone defects pose significant challenges in healthcare, with over 2 million bone repair surgeries performed globally each year. As a burgeoning force in the field of bone tissue engineering, 3D printing offers novel solutions to traditional bone transplantation procedures. However, current 3D-printed bone scaffolds still face three critical challenges in material selection, printing methods, cellular self-organization and co-culture, significantly impeding their clinical application. In this comprehensive review, we delve into the performance criteria that ideal bone scaffolds should possess, with a particular focus on the three core challenges faced by 3D printing technology during clinical translation. We summarize the latest advancements in non-traditional materials and advanced printing techniques, emphasizing the importance of integrating organ-like technologies with bioprinting. This combined approach enables more precise simulation of natural tissue structure and function. Our aim in writing this review is to propose effective strategies to address these challenges and promote the clinical translation of 3D-printed scaffolds for bone defect treatment.

Risk factors of different mortality periods in older patients with end-stage renal disease undergoing urgent-start peritoneal dialysis: a retrospective observational study.

BACKGROUND: The first six months of therapy represents a high-risk period for peritoneal dialysis (PD) failure. The risk of death in the first six months is higher for older patients treated with urgent-start PD (USPD). However, there are still gaps in research on mortality and risk factors for death in this particular group of patients. We aimed to investigate mortality rates and risk factors for death in older patients with end-stage renal disease (ESRD) receiving USPD within and after six months of therapy. METHODS: We retrospectively studied the clinical information of older adults aged ≥ 65 years with ESRD who received USPD between 2013 and 2019 in five Chinese hospitals. Patients were followed up to June 30, 2020. The mortality and risk factors for death in the first six months of USPD treatment and beyond were analyzed. RESULTS: Of the 379 elderly patients in the study, 130 died over the study period. During the follow-up period, the highest number (45, 34.6%) of deaths occurred within the first six months. Cardiovascular disease was the most common cause of death. The baseline New York Heart Association (NYHA) class III-IV cardiac function [hazard ratio (HR) = 2.457, 95% confidence interval (CI): 1.200-5.030, p = 0.014] and higher white blood cell (WBC) count (HR = 1.082, 95% CI: 1.021-1.147, p = 0.008) increased the mortality risk within six months of USPD. The baseline NYHA class III-IV cardiac function (HR = 1.945, 95% CI: 1.149-3.294, p = 0.013), lower WBC count (HR = 0.917, 95% CI: 0.845-0.996, p = 0.040), lower potassium levels (HR = 0.584, 95% CI: 0.429-0.796, p = 0.001), and higher calcium levels (HR = 2.160, 95% CI: 1.025-4.554, p = 0.043) increased the mortality risk after six months of USPD. CONCLUSION: Different risk factors correlated with mortality in older adults with ESRD within and after six months of undergoing USPD, including baseline NYHA class III-IV cardiac function, WBC count, potassium, and calcium levels.

Metagenomic profiling of cecal microbiota and antibiotic resistome in rodents.

The rodent gut microbiota is a known reservoir of antimicrobial resistance, yet the distribution of antibiotic resistance genes (ARGs) within rodent cecal microbial communities and the specific bacterial species harboring these ARGs remain largely underexplored. This study employed high-throughput sequencing of 122 samples from five distinct rodent species to comprehensively profile the diversity and distribution of ARGs and to identify the bacterial hosts of these genes. A gene catalog of the rodent cecal microbiome was constructed, comprising 22,757,369 non-redundant genes. Analysis of the microbial composition and diversity revealed that Bacillota and Bacteroidota were the dominant bacterial phyla across different rodent species, with significant variations in species composition among the rodents. In total, 3703 putative antimicrobial resistance protein-coding genes were identified, corresponding to 392 unique ARG types classified into 32 resistance classes. The most enriched ARGs in the rodent cecal microbiome were associated with multidrug resistance, followed by glycopeptide and elfamycin antibiotics. Procrustes analysis demonstrated a correlation between the structure of the microbial community and the resistome. Metagenomic assembly-based host tracking indicated that most ARG-carrying contigs originated from the bacterial family Oscillospiraceae. Additionally, 130 ARGs showed significant correlations with mobile genetic elements. These findings provide new insights into the cecal microbiota and the prevalence of ARGs across five rodent species. Future research on a wider range of wild rodent species carrying ARGs will further elucidate the mechanisms underlying the transmission of antimicrobial resistance.

Spatiotemporal Catalytic Nanozymes Microneedle Patches with Opposite Properties for Wound Management.

Reactive oxygen species (ROS)-mediated biological catalysis involves serial programmed enzymatic reactions and plays an important part against infectious diseases; while the spatiotemporal control of catalytic treatment to break the limitations of the disease microenvironment is challenging. Here, a novel spatiotemporal catalytic microneedles patch (CMSP-MNs) integrated with dual-effective Cu2 MoS4 (CMS) and polydopamine (PDA) nanoparticles (NPs) for breaking microenvironment restrictions to treat wound infections is designed. Since CMS NPs are loaded in the needles, CMSP-MNs can catalytically generate diverse ROS to cause effective bacterial inactivation during bacterial infection process. Besides, PDA NPs are encapsulated in the backing layer, which facilitate ROS elimination and oxygen production for solving hypoxic problems in wound microenvironment and alleviating the expression of inflammatory factors during the inflammation process. Based on these features, it is demonstrated through cell and animal experiments that these nanozymes-integrated MNs patches can realize selective regulation of ROS level with bacterial inactivation and inflammatory treatment, resulting in minimized side effects of over-production ROS and effective anti-infected treatment. It is believed that the presented MNs can provide a new therapeutic strategy with spatiotemporal adjustable catalytic properties in biomedical areas.

Design, Screening, and Characterization of Engineered Phage Endolysins with Extracellular Antibacterial Activity against Gram-Negative Bacteria.

Phage-encoded endolysins are emerging antibacterial agents based on their ability to efficiently degrade peptidoglycan on Gram-positive bacteria, but the envelope characteristics of Gram-negative bacteria limit their application. Engineering modifications of endolysins can improve the optimization of their penetrative and antibacterial properties. This study constructed a screening platform to screen for engineered Artificial-Bp7e (Art-Bp7e) endolysins with extracellular antibacterial activity against Escherichia coli. An oligonucleotide of 20 repeated NNK codons was inserted upstream of the endolysin gene Bp7e to construct a chimeric endolysin library in the pColdTF vector. The chimeric Art-Bp7e proteins were expressed by transforming the plasmid library into E. coli BL21 and released by chloroform fumigation, and the protein activities were evaluated by the spotting method and the colony-counting method to screen for promising proteins. Sequence analysis showed that all screened proteins with extracellular activities had a chimeric peptide with a positive charge and an α-helical structure. Also, a representative protein, Art-Bp7e6, was further characterized. It exhibited broad antibacterial activity against E. coli (7/21), Salmonella enterica serovar Enteritidis (4/10), Pseudomonas aeruginosa (3/10), and even Staphylococcus aureus (1/10). In the transmembrane process, the chimeric peptide of Art-Bp7e6 depolarized the host cell envelope, increased the permeability of the cell, and facilitated the movement of Art-Bp7e6 across the envelope to hydrolyze the peptidoglycan. In conclusion, the screening platform successfully screened for chimeric endolysins with extracellular antibacterial activities against Gram-negative bacteria, which provides methodological support for the further screening of engineered endolysins with high extracellular activities against Gram-negative bacteria. Also, the established platform showed broad application prospects and can be used to screen various proteins. IMPORTANCE The presence of the envelope in Gram-negative bacteria limits the use of phage endolysins, and engineering endolysins is an efficient way to optimize their penetrative and antibacterial properties. We built a platform for endolysin engineering and screening. A random peptide was fused with the phage endolysin Bp7e to construct a chimeric endolysin library, and engineered Artificial-Bp7e (Art-Bp7e) endolysins with extracellular activity against Gram-negative bacteria were successfully screened from the library. The purposeful Art-Bp7e had a chimeric peptide with an abundant positive charge and an α-helical structure, which led Bp7e to acquire the ability for the extracellular lysis of Gram-negative bacteria and showed a broad lysis spectrum. The platform provides a huge library capacity without the limitations of reported proteins or peptides. It can be utilized for the further screening of optimal endolysins against Gram-negative bacteria as well as for the screening of additional proteins with specific modifications.

Amplicon-based metagenomic association analysis of gut microbiota in relation to egg-laying period and breeds of hens.

BACKGROUND: The gut microbiota plays an essential role in maintaining gut homeostasis and improving performance, with the composition of microbial communities visibly differing across different laying stages in hens and significantly correlating with egg production. To gain further insights into the association between microbial community characteristics and laying periods in Hy-Line variety brown and Isa brown laying hens, we conducted a 16S rRNA amplicon sequencing survey. RESULTS: Our result revealed the diversity of bacteria in the early laying period was commonly higher than peak, and in Hy-Line variety brown laying hens were generally higher than Isa brown. Principal coordinate analysis (PCoA) and permutational multivariate analysis of variance (PERMANOVA) revealed that the structure and composition of the gut microbiota of laying hens exhibited significant differences among different groups. Phylum Firmicutes, Bacteroidota, Proteobacteria, and Fusobacteriota were found that dominant in the host's feces. Therein, the abundance of Fusobacteriota was higher in the peak period than in the early period, while the abundance of Cyanobacteria in the early period was higher in two breeds of hens. Furthermore, random forest based on machine learning showed that there were several distinctly abundant genera, which can be used as potential biomarkers to differentiate the different groups of laying periods and breeds. In addition, the prediction of biological function indicated the existing discrepancy in microbial function among the microbiota of four groups. CONCLUSIONS: Our findings offer new insights into the bacterial diversity and intestinal flora composition of different strains of laying hens during various laying periods, contributing significantly to the improvement of production performance and the prevention of chicken diseases.

Loss and recovery of myocardial mitochondria in mice under different tail suspension time: Apoptosis and mitochondrial fission, fusion and autophagy.

Long-term weightlessness in animals can cause changes in myocardial structure and function, in which mitochondria play an important role. Here, a tail suspension (TS) Kunming mouse (Mus musculus) model was used to simulate the effects of weightlessness on the heart. We investigated the effects of 2 and 4 weeks of TS (TS2 and TS4) on myocardial mitochondrial ultrastructure and oxidative respiratory function and on the molecular mechanisms of apoptosis and mitochondrial fission, autophagy and fusion-related signalling. Our study revealed significant changes in the ultrastructural features of cardiomyocytes in response to TS. The results showed: (1) mitochondrial swelling and disruption of cristae in TS2, but mitochondrial recovery and denser cristae in TS4; (2) an increase in the total number of mitochondria and number of sub-mitochondria in TS4; (3) no significant changes in the nuclear ultrastructure or DNA fragmentation among the two TS groups and the control group; (4) an increase in the bax/bcl-2 protein levels in the two TS groups, indicating increased activation of the bax-mediated apoptosis pathway; (5) no change in the phosphorylation ratio of dynamin-related protein 1 in the two TS groups; (6) an increase in the protein levels of optic atrophy 1 and mitofusin 2 in the two TS groups; and (7) in comparison to the TS2 group, an increase in the phosphorylation ratio of parkin and the ratio of LC3II to LC3I in TS4, suggesting an increase in autophagy. Taken together, these findings suggest that mitochondrial autophagy and fusion levels increased after 4 weeks of TS, leading to a restoration of the bax-mediated myocardial apoptosis pathway observed after 2 weeks of TS. NEW FINDINGS: What is the central question of this study? What are the effects of 2 and 4 weeks of tail suspension on myocardial mitochondrial ultrastructure and oxidative respiratory function and on the molecular mechanisms of apoptosis and mitochondrial fission, autophagy and fusion-related signalling? What is the main finding and its importance? Increased mitochondrial autophagy and fusion levels after 4 weeks of tail suspension help to reshape the morphology and increase the number of myocardial mitochondria.

Cardiac magnetic resonance radiomics for disease classification.

OBJECTIVES: This study investigated the discriminability of quantitative radiomics features extracted from cardiac magnetic resonance (CMR) images for hypertrophic cardiomyopathy (HCM), dilated cardiomyopathy (DCM), and healthy (NOR) patients. METHODS: The data of two hundred and eighty-three patients with HCM (n = 48) or DCM (n = 52) and NOR (n = 123) were extracted from two publicly available datasets. Ten feature selection methods were first performed on twenty-one different sets of radiomics features extracted from the left ventricle, right ventricle, and myocardium segmented from CMR images in the end-diastolic frame, end-systolic frame, and a combination of both; then, nine classical machine learning methods were trained with the selected radiomics features to distinguish HCM, DCM, and NOR. Ninety classification models were constructed based on combinations of the ten feature selection methods and nine classifiers. The classification models were evaluated, and the optimal model was selected. The diagnostic performance of the selected model was also compared to that of state-of-the-art methods. RESULTS: The random forest minimum redundancy maximum relevance model with features based on LeastAxisLength, Maximum2DDiameterSlice, Median, MinorAxisLength, Sphericity, VoxelVolume, Kurtosis, Flatness, and Skewness was the highest performing model, achieving 91.2% classification accuracy. The cross-validated areas under the curve on the test dataset were 0.938, 0.966, and 0.936 for NOR, DCM, and HCM, respectively. Furthermore, compared with those of the state-of-the-art methods, the sensitivity and accuracy of this model were greatly improved. CONCLUSIONS: A predictive model was proposed based on CMR radiomics features for classifying HCM, DCM, and NOR patients. The model had good discriminability. KEY POINTS: • The first-order features and the features extracted from the LOG-filtered images have potential in distinguishing HCM patients from DCM patients. • The features extracted from the RV play little role in distinguishing DCM from HCM. • The VoxelVolume of the myocardium in the ED frame is important in the recognition of DCM.

Activation of the STING pathway induces peripheral sensitization via neuroinflammation in a rat model of bone cancer pain.

BACKGROUND: Neuroinflammation in the peripheral nervous system has been linked to cancer metastasis-induced bone pain. The stimulator of interferon genes (STING), an innate immune sensor for cytosolic DNA, plays an important role in inflammation and cancer metastasis and is reported to be a critical regulator of nociception. Here, we examined the role of STING in primary nociceptive neurons and chronic pain to determine if it could be a new target for treating bone cancer pain (BCP). METHODS: Walker 256 cancer cells were injected intratibially to induce bone cancer pain in rats. STING and its downstream inflammatory factors in dorsal root ganglia (DRG) were detected using western blotting and immunofluorescent staining. Transmission electron microscopy and the BCL2-associated X (Bax) expression were used to detect the mitochondrial stress in DRG neurons. C-176, a specific inhibitor of STING, was used to block STING activation and to test the pain behavior. RESULTS: Mechanical hyperalgesia and spontaneous pain were observed in BCP rats, accompanied by the upregulation of the STING expression in the ipsilateral L4-5 DRG neurons which showed significant mitochondrion stress. The STING/TANK-binding kinase 1 (TBK1)/nuclear factor-kappa B (NF-κB) pathway activation was observed in the DRGs of BCP rats as well as increased IL-1ß, IL-6, and TNF-α expression. C-176 alleviated bone cancer pain and reduced the STING and its downstream inflammatory pathway. CONCLUSION: We provide evidence that STING pathway activation leads to neuroinflammation and peripheral sensitization. Pharmacological blockade of STING may be a promising novel strategy for preventing BCP.

A new joint reconstruction technique in the treatment of giant cell tumors around the knee: Structural allograft and unicompartmental arthroplasty.

OBJECTIVE: The long-term prognosis of patients who underwent unicompartmental knee arthroplasty (UKA) with a structural allograft or hemiarticular allograft transplantation to treat giant cell tumors (GCTs) around the knee and the prosthesis survival rate were analyzed. METHODS: We retrospectively reviewed 73 patients who were diagnosed with GCTs around the knee and underwent surgery to restore joint function from 2000 to 2015. Patients were divided into two groups according to the surgical procedure used for functional knee reconstruction: hemiarticular allograft transplantation or structural allograft and UKA. The Knee Society Score (KSS) and Western Ontario and McMaster Universities Arthritis Index (WOMAC) were used to analyze postoperative knee function between the two groups. The Kellgren-Lawrence (K-L) classification system was used to evaluate the progression of osteoarthritis. The incidence of complications and the prosthesis survival rate were also investigated. RESULTS: Patients who underwent UKA to treat GCT demonstrated significantly improved knee function. The rate of an excellent or good KSS was significantly different between the two groups (p = 0.041 at the 1-year follow-up, p = 0.033 at the last follow-up). The proportion of severe cases according to WOMAC in the two groups was also different (p = 0.030 at the 1-year follow-up, p = 0.021 at the last follow-up). According to the K-L grade of unaffected compartments, UKA better prevented the progression of osteoarthritis (p = 0.034). CONCLUSIONS: Patients with GCTs around the knee could benefit from UKA. In addition to providing better knee function and range of motion, UKA could also slow the progression of osteoarthritis in the knee joint. This new surgical method could meet the needs of patients wishing to preserve joint integrity and favorable joint function.

Effect of calcination temperatures on the performance of rectorite for cadmium immobilization in soil: Freeze-thaw, plant growth, and microbial diversity.

The immobilization of cadmium (Cd(II)) in soil using calcined rectorite (REC) was investigated in this research. The results of immobilization show that a small amount of REC calcined at 700 °C (REC-700 °C) could effectively immobilize 90% of Cd(II) in soil, while the immobilization efficiency of REC only reached 42%. Moreover, the immobilization efficiency of REC calcined at 300 °C and 500 °C (REC-300 °C and REC-500 °C) were lower than REC. To investigate the mechanism, the materials before and after immobilization were fully analyzed by Fourier transform infrared spectroscopy (FT-IR), powdery X-ray diffraction analysis (XRD), and scanning electron microscopy (SEM). The results indicate that the structure of REC has been changed after calcination at different temperatures and Cd(II) was successfully immobilized on materials. Losing free water, structural water and OH groups respectively, the layer spacing of REC-300 °C and REC-500 °C was shrunk. However, the crystal structure of REC was destroyed after calcination at 700 °C, resulting in the generation of new phases. According to the XRD result, more cadmium hydroxide (Cd(OH)2) were produced on REC-700 °C, indicating that more OH groups were formed during immobilization. Furthermore, Tessier test demonstrates that Cd(II) in soil changed from exchangeable state and water soluble state to carbonate bound state and iron manganese oxide bound state during immobilization. The result of microbial community indicates that REC-700 °C can restore the microbial composition of Cd(II)-contaminated soil. The effects of pH, freeze-thaw, REC dosage, and initial heavy metal concentration were also evaluated to provide a theoretical basis for the subsequent application of the material in the remediation of contaminated soil.

Utilizing nanozymes for combating COVID-19: advancements in diagnostics, treatments, and preventative measures.

The emergence of human severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) poses significant challenges to global public health. Despite the extensive efforts of researchers worldwide, there remains considerable opportunities for improvement in timely diagnosis, specific treatment, and effective vaccines for SARS-CoV-2. This is due, in part, to the large number of asymptomatic carriers, rapid virus mutations, inconsistent confinement policies, untimely diagnosis and limited clear treatment plans. The emerging of nanozymes offers a promising approach for combating SARS-CoV-2 due to their stable physicochemical properties and high surface areas, which enable easier and multiple nano-bio interactions in vivo. Nanozymes inspire the development of sensitive and economic nanosensors for rapid detection, facilitate the development of specific medicines with minimal side effects for targeted therapy, trigger defensive mechanisms in the form of vaccines, and eliminate SARS-CoV-2 in the environment for prevention. In this review, we briefly present the limitations of existing countermeasures against coronavirus disease 2019 (COVID-19). We then reviewed the applications of nanozyme-based platforms in the fields of diagnostics, therapeutics and the prevention in COVID-19. Finally, we propose opportunities and challenges for the further development of nanozyme-based platforms for COVID-19. We expect that our review will provide valuable insights into the new emerging and re-emerging infectious pandemic from the perspective of nanozymes.

Bioinspired programmable wettability arrays for droplets manipulation.

The manipulation of liquid droplets demonstrates great importance in various areas from laboratory research to our daily life. Here, inspired by the unique microstructure of plant stomata, we present a surface with programmable wettability arrays for droplets manipulation. The substrate film of this surface is constructed by using a coaxial capillary microfluidics to emulsify and pack graphene oxide (GO) hybrid N-isopropylacrylamide (NIPAM) hydrogel solution into silica nanoparticles-dispersed ethoxylated trimethylolpropane triacrylate (ETPTA) phase. Because of the distribution of the silica nanoparticles on the ETPTA interface, the outer surface of the film could achieve favorable hydrophobic property under selective fluorosilane decoration. Owing to the outstanding photothermal energy transformation property of the GO, the encapsulated hydrophilic hydrogel arrays could shrink back into the holes to expose their hydrophobic surface with near-infrared (NIR) irradiation; this imparts the composite film with remotely switchable surface droplet adhesion status. Based on this phenomenon, we have demonstrated controllable droplet sliding on programmable wettability pathways, together with effective droplet transfer for printing with mask integration, which remains difficult to realize by existing techniques.

[Clinical Outcome and Risk Factors of Treatment Failure of Peritoneal Dialysis Associated Peritonitis Caused by Klebsiella Pneumoniae:A Multicenter Study].

Objective To investigate the treatment outcomes,prognosis,and risk factors of treatment failure of peritoneal dialysis associated peritonitis (PDAP) caused by Klebsiella pneumoniae,and thus provide clinical evidence for the prevention and treatment of this disease. Methods The clinical data of PDAP patients at four peritoneal dialysis centers from January 1,2014 to December 31,2019 were collected retrospectively.The treatment outcomes and prognosis were compared between the patients with PDAP caused by Klebsiella.pneumoniae and that caused by Escherichia coli.Kaplan-Meier method was employed to establish the survival curve of technical failure,and multivariate Logistic regression to analyze the risk factors of the treatment failure of PADP caused by Klebsiella pneumoniae. Results In the 4 peritoneal dialysis centers,1034 cases of PDAP occurred in 586 patients from 2014 to 2019,including 21 cases caused by Klebsiella pneumoniae and 98 cases caused by Escherichia coli.The incidence of Klebsiella pneumoniae caused PDAP was 0.0048 times per patient per year on average,ranging from 0.0024 to 0.0124 times per patient per year during 2014-2019.According to the Kaplan-Meier survival curve,the technical failure rate of Klebsiella pneumoniae caused PDAP was higher than that of Escherichia coli caused PDAP (P=0.022).The multivariate Logistic regression model showed that long-term dialysis was an independent risk factor for the treatment failure of Klebsiella pneumoniae caused PDAP (OR=1.082,95%CI=1.011-1.158,P=0.023).Klebsiella pneumoniae was highly sensitive to amikacin,meropenem,imipenem,piperacillin,and cefotetan,and it was highly resistant to ampicillin (81.82%),cefazolin (53.33%),tetracycline (50.00%),cefotaxime (43.75%),and chloramphenicol (42.86%). Conclusion The PDAP caused by Klebsiella pneumoniae had worse prognosis than that caused by Escherichia coli,and long-term dialysis was an independent risk factor for the treatment failure of Klebsiella pneumoniae caused PDAP.

Influence of Early-Onset Peritonitis on Mortality and Clinical Outcomes in ESRD Patients with Diabetes Mellitus on Peritoneal Dialysis: A Retrospective Multicenter Study.

INTRODUCTION: The impact of early-onset peritonitis (EOP) on patients with diabetes undergoing peritoneal dialysis (PD) has not been adequately addressed. We therefore sought to investigate the effects of EOP on the therapeutic response to management and long-term prognostic outcomes in patients with diabetes undergoing PD. METHODS: For this retrospective cohort study, we analyzed the data for patients with end-stage renal disease, who were also suffering from diabetes mellitus and had undergone PD between January 1, 2013, and December 31, 2018. EOP was defined as the first episode of peritoneal dialysis-related peritonitis (PDAP) occurring within 12 months of PD initiation. All patients were divided into an EOP group and a later-onset peritonitis (LOP) group. Clinical data, treatment results, and outcomes were compared between groups. RESULTS: Ultimately, 202 patients were enrolled for the analysis. Compared to the EOP group, the LOP group had more Streptococcus (p = 0.033) and Pseudomonas (p = 0.048). Patients with diabetes in the EOP group were less likely to have PDAP-related death (OR 0.13, CI: 0.02-0.82, p = 0.030). Patients with diabetes in the EOP group were more likely to have multiple episodes of PDAP and had higher rates of technical failure and poorer patient survival than those in the LOP group, as indicated by Kaplan-Meier analysis (p = 0.019, p = 0.004, and p < 0.001). In the multivariate Cox proportional hazards model, EOP was a significant predictor for multiple PDAP (HR 4.20, CI: 1.48-11.96, p = 0.007), technical failure (HR 6.37, CI: 2.21-18.38, p = 0.001), and poorer patient survival (HR 3.09, CI: 1.45-6.58, p = 0.003). CONCLUSIONS: The occurrence of EOP is significantly associated with lower rates of PDAP-related death and poorer clinical outcomes in patients with diabetes undergoing PD.

3cDe-Net: a cervical cancer cell detection network based on an improved backbone network and multiscale feature fusion.

BACKGROUND: Cervical cancer cell detection is an essential means of cervical cancer screening. However, for thin-prep cytology test (TCT)-based images, the detection accuracies of traditional computer-aided detection algorithms are typically low due to the overlapping of cells with blurred cytoplasmic boundaries. Some typical deep learning-based detection methods, e.g., ResNets and Inception-V3, are not always efficient for cervical images due to the differences between cervical cancer cell images and natural images. As a result, these traditional networks are difficult to directly apply to the clinical practice of cervical cancer screening. METHOD: We propose a cervical cancer cell detection network (3cDe-Net) based on an improved backbone network and multiscale feature fusion; the proposed network consists of the backbone network and a detection head. In the backbone network, a dilated convolution and a group convolution are introduced to improve the resolution and expression ability of the model. In the detection head, multiscale features are obtained based on a feature pyramid fusion network to ensure the accurate capture of small cells; then, based on the Faster region-based convolutional neural network (R-CNN), adaptive cervical cancer cell anchors are generated via unsupervised clustering. Furthermore, a new balanced L1-based loss function is defined, which reduces the unbalanced sample contribution loss. RESULT: Baselines including ResNet-50, ResNet-101, Inception-v3, ResNet-152 and the feature concatenation network are used on two different datasets (the Data-T and Herlev datasets), and the final quantitative results show the effectiveness of the proposed dilated convolution ResNet (DC-ResNet) backbone network. Furthermore, experiments conducted on both datasets show that the proposed 3cDe-Net, based on the optimal anchors, the defined new loss function, and DC-ResNet, outperforms existing methods and achieves a mean average precision (mAP) of 50.4%. By performing a horizontal comparison of the cells on an image, the category and location information of cancer cells can be obtained concurrently. CONCLUSION: The proposed 3cDe-Net can detect cancer cells and their locations on multicell pictures. The model directly processes and analyses samples at the picture level rather than at the cellular level, which is more efficient. In clinical settings, the mechanical workloads of doctors can be reduced, and their focus can be placed on higher-level review work.

Multibioinspired slippery surfaces with wettable bump arrays for droplets pumping.

Droplet manipulation is playing an important role in various fields, including scientific research, industrial production, and daily life. Here, inspired by the microstructures and functions of Namib desert beetles, Nepenthes pitcher plants, and emergent aquatic plants, we present a multibioinspired slippery surface for droplet manipulation by employing combined strategies of bottom-up colloidal self-assembly, top-down photolithography, and microstructured mold replication. The resultant multilayered hierarchical wettability surface consists of hollow hydrogel bump arrays and a lubricant-infused inverse opal film as the substrate. Based on capillary force, together with slippery properties of the substrate and wettability of the bump arrays, water droplets from all directions can be attracted to the bumps and be collected through hollow channels to a reservoir. Independent of extra energy input, droplet condensation, or coalescence, these surfaces have shown ideal droplet pumping and water collection efficiency. In particular, these slippery surfaces also exhibit remarkable features including versatility, generalization, and recyclability in practical use such as small droplet collection, which make them promising candidates for a wide range of applications.