Inhaled Macrophage Apoptotic Bodies-Engineered Microparticle Enabling Construction of Pro-Regenerative Microenvironment to Fight Hypoxic Lung Injury in Mice.

Oxygen therapy cannot rescue local lung hypoxia in patients with severe respiratory failure. Here, an inhalable platform is reported for overcoming the aberrant hypoxia-induced immune changes and alveolar damage using camouflaged poly(lactic-co-glycolic) acid (PLGA) microparticles with macrophage apoptotic body membrane (cMAB). cMABs are preloaded with mitochondria-targeting superoxide dismutase/catalase nanocomplexes (NCs) and modified with pathology-responsive macrophage growth factor colony-stimulating factor (CSF) chains, which form a core-shell platform called C-cMAB/NC with efficient deposition in deeper alveoli and high affinity to alveolar epithelial cells (AECs) after CSF chains are cleaved by matrix metalloproteinase 9. Therefore, NCs can be effectively transported into mitochondria to inhibit inflammasome-mediated AECs damage in mouse models of hypoxic acute lung injury. Additionally, the at-site CSF release is sufficient to rescue circulating monocytes and macrophages and alter their phenotypes, maximizing synergetic effects of NCs on creating a pro-regenerative microenvironment that enables resolution of lung injury and inflammation. This inhalable platform may have applications to numerous inflammatory lung diseases.

Analysis of Microbial Diversity and Community Structure of Rhizosphere Soil of Three Astragalus Species Grown in Special High-Cold Environment of Northwestern Yunnan, China.

Astragalus is a medicinal plant with obvious rhizosphere effects. At present, there are many Astragalus plants with high application value but low recognition and resource reserves in the northwestern area of Yunnan province, China. In this study, metagenomics was used to analyze the microbial diversity and community structure of rhizosphere soil of A. forrestii, A. acaulis, and A. ernestii plants grown in a special high-cold environment of northwestern Yunnan, China, at different altitudes ranging from 3225 to 4353 m. These microbes were taxonomically annotated to obtain 24 phyla and 501 genera for A. forrestii, 30 phyla and 504 genera for A. acaulis, as well as 39 phyla and 533 genera for A. ernestii. Overall, the dominant bacterial phyla included Proteobacteria, Actinobacteria, and Acidobacteria, while the dominant fungal ones were Ascomycota and Basidiomycota. At the genus level, Bradyrhizobium, Afipia, and Paraburkholderia were the most prevalent bacteria, and Hyaloscypha, Pseudogymnoascus, and Russula were the dominant fungal genera. Some of them are considered biocontrol microbes that could sustain the growth and health of host Astragalus plants. Redundancy analysis revealed that pH, TN, and SOM had a significant impact on the microbial community structures (p < 0.05). Finally, triterpene, flavonoid, polysaccharide, and amino acid metabolisms accounted for a high proportion of the enriched KEGG pathways, which possibly contributed to the synthesis of bioactive constituents in the Astragalus plants.

Efficacy of the newly designed "SkyWalker" robot compared to the MAKO robotic system in primary total knee arthroplasty: a one-year follow-up study.

PURPOSE: Robot-assisted surgical systems for performing total knee arthroplasty (TKA) have gained significant attention. This study was designed to compare the surgical outcomes in primary TKA surgery between the recently developed "SkyWalker" robot system and the more commonly used MAKO robot. METHODS: A total of 75 patients undergoing primary TKA surgery by the same surgical team were included in this study, with 30 patients in the "SkyWalker" group and 45 patients in the "MAKO" group. We documented the osteotomy plan for both robotic systems. The lower limb alignment angles were evaluated by postoperative radiographic assessment. The operation time, estimated blood loss, postoperative hospital stays, and changes in laboratory indexes were collected during hospitalization. In addition, a comparative evaluation of knee functional assessments and complications was conducted during six month and one year follow-ups. RESULTS: There were no significant differences between the two groups in terms of the accuracy of restoring lower limb alignment, estimated blood loss, or operation time. The knee function assessments at six months and one year postoperatively were similar in both groups. Except for day three after surgery, the level of interleukin-6 (IL-6) and the change in IL-6 (∆IL-6) from preoperative baseline were higher in the "SkyWalker" group than in the MAKO group (median: 20.53 vs. 14.17, P=0.050 and median: 17.30 vs. 10.09, P=0.042, respectively). Additionally, one patient from the MAKO group underwent revision surgery at nine months postoperatively due to ongoing periprosthetic discomfort. CONCLUSIONS: The newly developed "SkyWalker" robot showed comparable efficacy to the MAKO robot in terms of lower limb alignment accuracy and postoperative six month and one year follow-up of clinically assessed resumption of knee function.

Transcriptomic landscape of endothelial cells: Key tumor microenvironment components indicating variable clinical outcomes in pancreatic ductal adenocarcinoma.

Endothelial cells (ECs) present in the tumor microenvironment (TME) exhibit significant diversity that may impact the efficacy of anti-tumor treatments. Thus, our study sought to elucidate the various clusters of ECs present in pancreatic ductal adenocarcinoma (PDAC) and explore their possible interactions and influence on clinical outcomes. We obtained single-cell transcriptome data from 24 PDAC tumors and 11 normal pancreases, minimizing any batch effects between samples. Next, we compared the relative abundance of various ECs clusters across distinct sample types. Pseudo-time analysis was employed to investigate the differentiation origin of ECs. A variety of bioinformatics methods were used to investigate potential communication between ECs and malignant cells, as well as assess metabolic changes, pathway alterations, and immune-related markers expression within distinct EC clusters. Lastly, we investigated the impact of particular ECs clusters on patient prognosis in bulk transcriptome data. Our study identified seven distinct clusters of ECs, denoted as CA4+ ECs, MMP2+ ECs, SPP1+ ECs, MT1F+ ECs, CCL5+ ECs, RGS5+ ECs, and TYROBP+ ECs. Pseudo-time analysis suggested that the loss of CA4+ ECs and MT1F+ ECs may promote malignant progression. Cell communication elucidated that MT1F+ ECs exhibited the strongest outgoing interaction strength, whereas RGS5+ ECs displayed the strongest incoming interaction strength. Furthermore, TYROBP+ ECs exhibited greater metabolic activity, and notably, CCL5+ ECs displayed increased expression of immune-related molecules. Lastly, across cohorts of bulk transcriptome levels, CA4+ ECs, MT1F+ ECs, and RGS5+ ECs consistently demonstrated prognostic indicative effects. PDAC patients exhibit the presence of seven distinct EC clusters, each demonstrating significant metabolic and immunological heterogeneity. Targeted therapeutic approaches directed toward CA4+ ECs and MT1F+ ECs may prove advantageous in addressing challenges associated with PDAC treatment. Additionally, variations in the relative abundance of CA4+ ECs, MT1F+ ECs, and RGS5+ ECs were indicated as predictive of patient prognosis.

Transcriptome data-based status of PI3K/AKT/mTOR pathway indicates heterogeneity and immune modulation in patients with pancreatic ductal adenocarcinoma.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal cancer with limited treatment options. The PI3K/AKT/mTOR pathway is commonly activated in PDAC and plays a critical role in its progression. METHODS AND RESULTS: In this study, the effect of taselisib (a selective PI3K inhibitor) on PDAC cell proliferation was investigated, and a significant decrease in viability was observed with increasing concentrations of taselisib. Differential analysis on samples from the Genotype-Tissue Expression and The Cancer Genome Atlas databases revealed 24 dysregulated PI3K/AKT/mTOR pathway-related genes (PRGs). Unsupervised clustering-based analysis of transcriptome cohorts revealed two clusters with high consistency between RNA-seq and microarray cohorts. Cluster B had higher enrichment of immune cells, particularly CD8+ T cells, and lower levels of immunosuppressive Treg cells. Moreover, we investigated the relationship between drug sensitivity and different clusters and found that cluster A had a better response to PI3K/AKT/mTOR pathway-related inhibitors and chemotherapy. Finally, cluster A exhibited significant activation of PI3K/AKT/mTOR and related oncogenic pathways, contributing to poor prognosis. The study also developed a risk score based on the expression profiles of PRGs and machine learning, which showed a significant increase in overall survival time among patients in the low-risk group. Importantly, the PI3K/AKT/mTOR pathway could be used to better predict individual risk scores, as evidenced by stratified survival analysis. CONCLUSIONS: These findings suggest that targeting the PI3K/AKT/mTOR pathway may have therapeutic potential in PDAC, and distinct pathway states, immune modulation and tumor microenvironments have prognostic value.

Rs1800629 polymorphism in TNF-alpha is associated with the susceptibility and initial short-term glucocorticoids efficacy in myasthenia gravis patients.

Tumor necrosis factor-alpha (TNF-α) is a potent pro-inflammatory agent involved in various autoimmune and inflammatory diseases including myasthenia gravis (MG). In this study, we enrolled 409 adult MG patients and 487 healthy individuals to investigate the association between TNF-α polymorphism and MG. We found the rs1800629 A allele frequency was significantly higher in the MG group than in the control group. Subgroup analysis revealed that the A allele frequencies were significantly higher in the early-onset subgroup, non-thymoma subgroup, ocular-onset subgroup, and mild severity subgroup than in the control group. To minimize the interactions between clinical features, we used a comprehensive classification and found that the rs1800629 A allele frequency was significantly higher in the non-thymoma AChR-Ab negative subgroup than in the control group. In the analysis of initial short-term glucocorticoids (GC) efficacy in the treatment-naive patients, the rs1800629 A allele frequency was significantly higher in the unresponsive subgroup than in the responsive group and the control group. Logistic regression demonstrated the rs1800629 genotypes in the dominant model and disease duration prior to GC treatment independently contributed to initial short-term GC efficacy. In conclusion, our study revealed that in Chinese adult MG patients, rs1800629 polymorphism in TNF-α was associated with the susceptibility of MG and might indicate the initial short-term GC efficacy.

Combination of a bronchogenic cyst in the thoracic spinal canal with chronic myelocytic leukemia.

The presented case report describes an incredibly rare instance of an intramedullary bronchial cyst located in the thoracic spinal canal on the dorsal side of the spinal cord, which was observed in a patient with chronic myelogenous leukemia. A 29-year-old man presented with back pain for half a month, along with numbness and pain below the chest and ribs for 1 week. Hypersensitivity was present in the inferior plane of the long xiphoid process in the nervous system. Magnetic resonance imaging (MRI) showed intramedullary cystic lesions in the vertebral body plane of the third to the fourth thoracic vertebra. There was no recurrence during the 6-month postoperative follow-up period. The histopathological findings were consistent with bronchogenic cysts. Cystic lesions were eliminated through the posterior median approach. After the cyst ruptured during surgery, gel liquid was seen, and the majority of the cyst walls were removed. One week after the surgery, the hypersensitivity fully subsided. Six months following surgery, an updated MRI revealed no recurrence. Intramedullary bronchogenic cysts on the dorsal side of the thoracic spine are extremely uncommon. Diagnosis requires histopathological evidence, and it is challenging to diagnose before surgery. Prompt surgical resection is recommended in case of positive diagnosis.

Protocol for the single-crystal growth of chromium-based RECrO3 compounds.

Chromium-based perovskites have gained significant interest for their magnetic and ferroelectric properties. Rare-earth orthochromates are versatile multiferroic materials in catalysts, thermistors, and non-volatile memory. We present a protocol for RECrO3 crystal growth using a laser-diode floating-zone furnace. Steps include solid-phase calcination, sintering, and shaping. We provide detailed information on crystal growth parameters and Laue diffraction analysis. The successful growth of large orthochromate single crystals paves the way for exploring their intrinsic properties and potential applications. For complete details on the use and execution of this protocol, please refer to Zhu et al.1 and Zhu et al.2.

Nonlinear optical switch based on coherent perfect absorption.

Coherent perfect absorption (CPA) or reflection (CPR) are methods to realize the extreme manipulation on an optical field. We propose a scheme to operate a bistable switch with convertible CPA and/or CPR. Generally, CPA and CPR occur with different input-field phases. For example, CPA is realized when two input probe beams are in phase; instead, CPR is achieved when they are out of phase. In this scheme, a CPA state can be converted to a CPR state by an incoherent field although two input fields are in phase. When we use the incoherent field as a switching field, the CPA (CPR) state is treated as the closed (open) state. As a result, the switching efficiency can theoretically reach a maximum value, i.e., η = 1. In addition, the switch can be operated in the linear regime with a weak input field, and in the nonlinear or bistable regime with a strong input field. Moreover, the efficiency of the bistable switch is sensitively dependent on the input-field intensity. It provides a potential application of this work on sensitive optical detecting.

Flavobacterium lacisediminis sp. nov., a bacterium isolated from lake sediment.

A taxonomic identification using polyphasic approach was performed on strain TH16-21T, which was isolated from the interfacial sediment of Taihu Lake, PR China. Strain TH16-21T was Gram-stain-negative, aerobic, rod-shaped and catalase-positive. Phylogenetic analysis based on the 16S rRNA gene and genomic sequences indicated that strain TH16-21T was classified within the genus of Flavobacterium. The 16S rRNA gene sequence of strain TH16-21T showed the highest similarity to Flavobacterium cheniae NJ-26T (98.9 %). The average nucleotide identity and digital DNA-DNA hybridization values between strain TH16-21T and F. cheniae NJ-26T were 91.2 and 45.9 %, respectively. The respiratory quinone was menaquinone 6. The major cellular fatty acids (>10 %) comprised iso-C15 : 0, iso-C16 : 0, iso-C15 : 1 G and iso-C16 : 0 3-OH. The genomic DNA G+C content was 32.2 mol%. Phosphatidylethanolamine, six amino lipids and three phospholipids were the main polar lipids. Based on the phenotypic features and phylogenetic position, a novel species with the name Flavobacterium lacisediminis sp. nov. is proposed. The type strain is TH16-21T (=MCCC 1K04592T=KACC 22896T).

Excellent Energy Storage Performance in Epoxy Resin Dielectric Polymer Films by a Facile Hot-Pressing Method.

Epoxy resin (EP), as a kind of dielectric polymer, exhibits the advantages of low-curing shrinkage, high-insulating properties, and good thermal/chemical stability, which is widely used in electronic and electrical industry. However, the complicated preparation process of EP has limited their practical applications for energy storage. In this manuscript, bisphenol F epoxy resin (EPF) was successfully fabricated into polymer films with a thickness of 10~15 µm by a facile hot-pressing method. It was found that the curing degree of EPF was significantly affected by changing the ratio of EP monomer/curing agent, which led to the improvement in breakdown strength and energy storage performance. In particular, a high discharged energy density (Ud) of 6.5 J·cm-3 and efficiency (η) of 86% under an electric field of 600 MV·m-1 were obtained for the EPF film with an EP monomer/curing agent ratio of 1:1.5 by hot pressing at 130 °C, which indicates that the hot-pressing method could be facilely employed to produce high-quality EP films with excellent energy storage performance for pulse power capacitors.

Optimal validation of accuracy in antibody assays and reasonable definition of antibody positive/negative subgroups in neuroimmune diseases: a narrative review.

Background and Objective: In neuroimmune diseases, autoantibodies are not only used for diagnosis, but also as markers for assessing disease severity and treatment efficacy, and as variables in predicting the prognosis and in subgroup classification. Accuracy of an assay is a prerequisite for using antibodies in the diagnosis and management. The antibody positive subgroup is important in constellating phenotypes, while the antibody negative subgroup provides an opportunity for discovery of new antibodies. This review is to discuss the validation studies of diagnostic accuracy in antibody assays and reasonable definitions of antibody positive/negative subgroups in neuroimmune diseases. Methods: The literature discussing validation studies of diagnostic accuracy in antibody assays and reasonable definition of antibody positive/negative subgroups in autoimmune diseases was broadly searched and discussed. Key Content and Findings: The designs of a validation study, principles in defining the disease spectrum and biases, interpretation of the testing result and specific considerations for validation studies in neuroimmune diseases (such as phenotypes and inclusion criteria, control group selection, dynamic changes of antibody composition and sampling time, relationship between duration and severity of disease and antibody status, and pre-test factor), and improvement of antibody test techniques, as well as definitions and algorithms in defining antibody positive/negative subgroups in clinical practice and researches, are discussed. Conclusions: The successful implementation of validation studies of autoantibody assays in neuroimmune diseases depends on reasonable design, phenotypic profiles of included patients and potential inclusion bias, test result interpretation and the influence from inclusion criteria, control group selection, patient characteristics on specimen sampling and pre-test factors. Reasonable definitions on antibody positive/negative groups may be different in clinical practice and researches, and rigorous definitions are conducive to constellation of disease phenotype and the exploration of new antibodies within a disease entity.

A narrative review of identifying the culprit antibody in neuroimmune diseases: concept and clinical significance.

Background and Objective: Neuroimmune disease is a group of autoimmune diseases that are directed against antigens of the nervous system. Autoantibody testing is of great significance in early diagnosis, clinical severity assessment, prognosis, and efficacy evaluation. With the discovery of new antibodies and the development of antibody detection techniques, multiple antibodies have been found to coexist in patients with neuroimmune diseases. In this narrative review, we aim to define the culprit antibody and discuss the correlation between culprit antibodies and the clinical phenotype of neuroimmune diseases. Methods: We searched Medline, Embase, Web of Science, and CNKI from inception to February 2021 to acquire references on the relationship between neuroimmune diseases and antibodies. Eligible articles were reviewed regarding the relationship between antibodies and phenotypes. Key Content and Findings: By reviewing relevant references and discussion, we propose the concept of "culprit antibody", namely, the pathogenic antibody which has a corresponding causal relationship with one or more phenotypes during the course of a patient's neuroimmune disease. The proposal, significance, and relevant clinical research of culprit antibodies related to neuroimmune diseases are elaborated as the proposal of concept and determination points of casual relationship, association with clinical phenotypes and core phenotypes, the role in antibody overlapping syndrome in the same patient, and different stages. Conclusions: In the era of precision medicine, proposing the concept of culprit antibodies and clarifying relevant evidence chains are helpful for precise and effective immune intervention.

A multicenter clinical study on parent-implemented early intervention for children with global developmental delay.

Objective: Early identification and intervention for children with global developmental delay (GDD) can significantly improve their prognosis and reduce the possibility of developing intellectual disability in the future. This study aimed to explore the clinical effectiveness of a parent-implemented early intervention program (PIEIP) for GDD, providing a research basis for the extended application of this intervention strategy in the future. Methods: During the period between September 2019 and August 2020, children aged 3 to 6 months diagnosed with GDD were selected from each research center as the experimental group and the control group. For the experimental group, the PIEIP intervention was conducted for the parent-child pair. Mid-term and end-stage assessments were performed, respectively, at 12 and 24 months of age, and parenting stress surveys were completed. Results: The average age of the enrolled children was 4.56 ± 1.08 months for the experimental group (n = 153) and 4.50 ± 1.04 months for the control group (n = 153). The comparative analysis of the variation in the progress between the two groups by independent t-test showed that, after the experimental intervention, the developmental quotient (DQ) of locomotor, personal-social, and language, as well as the general quotient (GQ) of the Griffiths Mental Development Scale-Chinese (GDS-C), the children in the experimental group demonstrated higher progress than those in the control group (P < 0.05). Furthermore, there was a significant decrease in the mean standard score of dysfunctional interaction, difficult children and the total level of parental stress in the term test for the experimental groups (P < 0.001 for all). Conclusions: PIEIP intervention can significantly improve the developmental outcome and prognosis of children with GDD, especially in the areas of locomotor, personal-social, and language.

Clinical Reasoning: A 49-Year-Old Woman With Isolated Sinus Intracranial Dural Arteriovenous Fistula With Perimedullary Drainage.

While demyelination is the most common etiology of longitudinally extensive myelopathy, other causes are important to recognize. In this study, we present the case of a longitudinal cervical lesion with a very rare cause. We discuss the approach to the differential diagnosis and workup for longitudinal myelopathy. This clinical reasoning case also illustrates the anatomical relationship between symptomatic spinal cord lesions and nonsymptomatic intracranial etiologies.

Associations of preterm and early-term birth with suspected developmental coordination disorder: a national retrospective cohort study in children aged 3-10 years.

BACKGROUND: This study analyzed the motor development and suspected developmental coordination disorder of very and moderately preterm (< 34+0 gestational age), late preterm (34+0-36+6 gestational week), and early-term (37+0-38+6 gestational week) children compared to their full-term peers with a national population-based sample in China. METHODS: A total of 1673 children (799 girls, 874 boys) aged 3-10 years old were individually assessed with the Movement Assessment Battery for Children-second edition (MABC-2). The association between gestational age and motor performance of children was analyzed using a multilevel regression model. RESULTS: The global motor performance [ß = - 5.111, 95% confidence interval (CI) = - 9.200 to - 1.022; P = 0.015] and balance (ß = - 5.182, 95% CI = - 5.055 to - 1.158; P = 0.003) for very and moderately preterm children aged 3-6 years old were significantly lower than their full-term peers when adjusting for confounders. Late preterm and early-term children showed no difference. Moreover, very and moderately preterm children aged 3-6 years had a higher risk of suspected developmental coordination disorder (DCD) (≤ 5 percentile of MABC-2 score) when adjusting for potential confounders [odds ratio (OR) = 2.931, 95% CI = 1.067-8.054; P = 0.038]. Late preterm and early-term children showed no difference in motor performance from their full-term peers (each P > 0.05). CONCLUSIONS: Our findings have important implications for understanding motor impairment in children born at different gestational ages. Very and moderately preterm preschoolers have an increased risk of DCD, and long-term follow-up should be provided for early detection and intervention.