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IgG4-related disease (IgG4-RD) is a systemic autoimmune disease with unclear pathogenesis. We performed single-cell RNA-seq and surface proteome analyses on 61,379 PBMCs from 9 treatment-naive IgG4-RD patients and 7 age- and sex-matched healthy controls. Integrative analyses were performed for altered gene expression in IgG4-RD, and flow cytometry and immunofluorescence were used for validation. We observed expansion of plasmablasts with enhanced protein processing and activation, which correlated with the number of involved organs in IgG4-RD. Increased proportions of CD4+ cytotoxic T lymphocytes (CTLs), CD8+ CTLs-GNLY (granulysin), and γδT cells with enhanced chemotaxis and cytotoxicity but with suppressed inhibitory receptors characterize IgG4-RD. Prominent infiltration of lymphocytes with distinct compositions were found in different organs of IgG4-RD patients. Transcription factors (TFs), including PRDM1/XBP1 and RUNX3, were upregulated in IgG4-RD, promoting the differentiation of plasmablasts and CTLs, respectively. Monocytes in IgG4-RD have stronger expression of genes related to cell adhesion and chemotaxis, which may give rise to profibrotic macrophages in lesions. The gene activation pattern in peripheral immune cells indicated activation of multiple interaction pathways between cell types, in part through chemokines or growth factors and their receptors. Specific upregulation of TFs and expansion of plasmablasts and CTLs may be involved in the pathogenesis of IgG4-RD, and each of these populations are candidate targets for therapeutic interventions in this disease.

Introduction: Hereditary antithrombin-III deficiency can significantly increase the risk for thrombosis, which is common in limb deep vein and pulmonary cases. However, thrombotic microangiopathy (TMA) caused by hereditary antithrombin deficiency is rare.Case Presentation: We reported the case of a 32-year-old Chinese female patient with TMA with renal injury caused by decreased antithrombin-III activity due to a new mutation (chr1-173884049 c.50A>G) in SERPINC1, which encodes antithrombin-III. In this case, the patient had no history of relevant drug use, diabetes, or monoclonal plasma cells in the bone marrow puncture. Consequently, TMA of the kidney was considered secondary to hereditary antithrombin-III deficiency. Gene detection was the only clue that led us to suspect that TMA was caused by hereditary antithrombin deficiency.Conclusion: Our findings indicated that for patients with repeated findings of antithrombin-III activity less than 50%, the possibility of antithrombin-III deficiency and complete gene detection must be considered immediately after excluding the use of anticoagulants and lack of availability to facilitate early detection, diagnosis, and intervention.

BackgroundDoes short-interval second ejaculation improve sperm quality, embryo development and clinical outcomes for oligoasthenozoospermia males received intracytoplasmic sperm injection (ICSI) treatment?MethodsAll enrolled male patients underwent short-interval secondary ejaculation on the day of oocyte retrieval, and 786 sibling MII oocytes from 67 cycles were equally divided into two groups based on whether the injected spermatozoons originated from the first or second ejaculation. Semen parameters, embryo development efficiency, morphokinetic parameters and clinical outcomes were compared between the two groups to assess the efficiency and clinical value of short-interval second ejaculation in ICSI cycles.ResultsShort-interval second ejaculation significantly improved sperm motility, normal morphological rate, and sperm DNA integrity both before and after sperm swim-up. The high-quality blastocyst rate (24.79% versus 14.67%), available blastocyst rate (57.56% versus 48.44%), and oocyte utilization rate (52.93% versus 45.29%) were significantly higher in the second ejaculation group (P0.05). Time-lapse analysis showed that morphokinetic time points after the 7-cell stage were earlier in the second ejaculation group but without a significant difference (P>0.05), and abnormal embryo cleavage patterns between the two groups were not significantly different (P>0.05).ConclusionsShort-interval second ejaculation significantly improves sperm quality in oligoasthenozoospermic males, and is beneficial for blastocyst formation efficiency in ICSI cycles. This study suggested a non-invasive and simple but effective strategy for improving ICSI treatment outcomes.

Biological organisms are exposed to low-dose arsenic or N-nitro compounds (NOCs) alone or in combination worldwide, especially in areas with high cancer prevalence through drinking water or food exposure; however, information on their combined exposure effects is limited. Here, we conducted an in-depth study of the effects on the gut microbiota, metabolomics, and signaling pathways using rat models exposed to arsenic or N-methyl-N′-nitro-N-nitrosoguanidine (MNNG), one of the most active carcinogenic NOCs, separately or in combination with metabolomics and high-throughput sequencing. Compared to exposure alone, combined exposure to arsenic and MNNG exacerbated damage to gastric tissue morphology, interfered with intestinal microflora and substance metabolism, and exerted a stronger carcinogenic effect. This may be related to intestinal microbiota disorders, including Dyella, Oscillibacter, Myroides, and metabolic pathways such as glycine, serine, and threonine metabolism, arginine biosynthesis, central carbon metabolism in cancer, and purine and pyrimidine metabolism, thereby enhancing the cancer-causing effects of gonadotrophin-releasing hormone (GnRH), P53, and Wnt signaling pathways.

ObjectivesTo explore the value of radiomics based on Dual-energy CT (DECT) for discriminating preinvasive or MIA from IA appearing as GGNs before surgery.MethodsThe retrospective study included 92 patients with lung adenocarcinoma comprising 30 IA and 62 preinvasive-MIA, which were further divided into a training (n=64) and a test set (n=28). Clinical and radiographic features along with quantitative parameters were recorded. Radiomics features were derived from virtual monoenergetic images (VMI), including 50kev and 150kev images. Intraclass correlation coefficients (ICCs), Pearson’s correlation analysis and least absolute shrinkage and selection operator (LASSO) penalized logistic regression were conducted to eliminate unstable and redundant features. The performance of the models was evaluated by area under the curve (AUC) and the clinical utility was assessed using decision curve analysis (DCA).ResultsThe DECT-based radiomics model performed well with an AUC of 0.957 and 0.865 in the training and test set. The clinical-DECT model, comprising sex, age, tumor size, density, smoking, alcohol, effective atomic number, and normalized iodine concentration, had an AUC of 0.929 in the training and 0.719 in the test set. In addition, the radiomics model revealed a higher AUC value and a greater net benefit to patients than the clinical-DECT model.ConclusionDECT-based radiomics features were valuable in predicting the invasiveness of GGNs, yielding a better predictive performance than the clinical-DECT model.

Dianthus caryophyllus is an economic species often considered excellent cut flowers and is suitable for bouquets and gardens. Here, we assembled the haplotype-resolved genome of D. caryophyllus ‘Aili’ at the chromosome level for the first time. The total lengths of the two assembled haplotypes of carnation were 584.88 Mb for haplotype genome 1 (hap1) and 578.78 Mb for haplotype genome 2 (hap2), respectively. We predicted a total of 44,098 and 42,425 protein-coding genes, respectively. The remarkable structure variation was identified between two haplotypes. Moreover, we identified 403.80 Mb of transposable elements (TEs) in hap1, which accounted for 69.34% of the genome. In contrast, hap2 had 402.70 Mb of TEs, representing 69.61% of the genome. Long terminal repeats were the predominant transposable elements. Phylogenetic analysis showed that the species differentiation time between carnation and gypsophila was estimated to be ~54.43 MYA. The unique gene families of carnation genomes were identified in ‘Aili’ and previously published ‘Francesco’ and ‘Scarlet Queen’. The assembled and annotated haplotype-resolved D. caryophyllus genome not only promises to facilitate molecular biology studies but also contributes to genome-level evolutionary studies.

Summary: Background: The ability to accurately identify the absolute risk of neurosyphilis diagnosis for patients with syphilis would allow preventative and therapeutic interventions to be delivered to patients at high-risk, sparing patients at low-risk from unnecessary care. We aimed to develop, validate, and evaluate the clinical utility of simplified clinical diagnostic models for neurosyphilis diagnosis in HIV-negative patients with syphilis. Methods: We searched PubMed, China National Knowledge Infrastructure and UpToDate for publications about neurosyphilis diagnostic guidelines in English or Chinese from database inception until March 15, 2023. We developed and validated machine learning models with a uniform set of predictors based on six authoritative diagnostic guidelines across four continents to predict neurosyphilis using routinely collected data from real-world clinical practice in China and the United States (through the Dermatology Hospital of Southern Medical University in Guangzhou [659 recruited between August 2012 and March 2022, treated as Development cohort], the Beijing Youan Hospital of Capital Medical University in Beijng [480 recruited between December 2013 and April 2021, treated as External cohort 1], the Zhongshan Hospital of Xiamen University in Xiamen [493 recruited between November 2005 and November 2021, treated as External cohort 2] from China, and University of Washington School of Medicine in Seattle [16 recruited between September 2002 and April 2014, treated as External cohort 3] from United States). We included all these patients with syphilis into our analysis, and no patients were further excluded. We trained eXtreme gradient boosting (XGBoost) models to predict the diagnostic outcome of neurosyphilis according to each diagnostic guideline in two scenarios, respectively. Model performance was measured through both internal and external validation in terms of discrimination and calibration, and clinical utility was evaluated using decision curve analysis. Findings: The final simplified clinical diagnostic models included neurological symptoms, cerebrospinal fluid (CSF) protein, CSF white blood cell, and CSF venereal disease research laboratory test/rapid plasma reagin. The models showed good calibration with rescaled Brier score of 0.99 (95% CI 0.98–1.00) and excellent discrimination (the minimum value of area under the receiver operating characteristic curve, 0.84; 95% CI 0.81–0.88) when externally validated. Decision curve analysis demonstrated that the models were useful across a range of neurosyphilis probability thresholds between 0.33 and 0.66 compared to the alternatives of managing all patients with syphilis as if they do or do not have neurosyphilis. Interpretation: The simplified clinical diagnostic models comprised of readily available data show good performance, are generalisable across clinical settings, and have clinical utility over a broad range of probability thresholds. The models with a uniform set of predictors can simplify the sophisticated clinical diagnosis of neurosyphilis, and guide decisions on delivery of neurosyphilis health-care, ultimately, support accurate diagnosis and necessary treatment. Funding: The Natural Science Foundation of China General Program, Health Appropriate Technology Promotion Project of Guangdong Medical Research Foundation, Department of Science and technology of Guangdong Province Xinjiang Rural Science and Technology（Special Commissioner）Project, Southern Medical University Clinical Research Nursery Garden Project, Beijing Municipal Administration of Hospitals Incubating Program.

This paper proposes a hierarchical framework integrating deep reinforcement learning (DRL) and rule-based methods for multi-lane autonomous driving. We define an instantaneous desired speed (IDS) to mimic the common motivation for higher speed in different traffic situations as an intermediate action. High-level DRL is utilized to generate IDS directly, while the low-level rule-based policies including car following (CF) models and three-stage lane changing (LC) models are governed by the common goal of IDS. Not only the coupling between CF and LC behaviors is captured by the hierarchy, but also utilizing the benefits from both DRL and rule-based methods like more interpretability and learning ability. Owing to the decomposition and combination with rule-based models, traffic flow operations can be taken into account for individually controlled automated vehicles (AVs) with an extension of traffic flow adaptive (TFA) strategy through exposed critical parameters. A comprehensive evaluation for the proposed framework is conducted from both the individual and system perspective, comparing with a pure DRL model and widely used rule-based model IDM with MOBIL. The simulation results prove the effectiveness of the proposed framework.

Introduction: Triterpenoids and saponins have a broad range of pharmacological activities. Unlike most legumes which contain mainly oleanane-type scaffold, Astragalus membranaceus contains not only oleanane-type but also cycloartane-type saponins, for which the biosynthetic pathways are unknown. Objectives: This work aims to study the function and catalytic mechanism of oxidosqualene cyclases (OSCs), one of the most important enzymes in triterpenoid biosynthesis, in A. membranaceus. Methods: Two OSC genes, AmOSC2 and AmOSC3, were cloned from A. membranaceus. Their functions were studied by heterologous expression in tobacco and yeast, together with in vivo transient expression and virus-induced gene silencing. Site-directed mutagenesis and molecular docking were used to explain the catalytic mechanism for the conserved motif. Results: AmOSC2 is a β-amyrin synthase which showed higher expression levels in underground parts. It is associated with the production of β-amyrin and soyasaponins (oleanane-type) in vivo. AmOSC3 is a cycloartenol synthase expressed in both aerial and underground parts. It is related to the synthesis of astragalosides (cycloartane-type) in the roots, and to the synthesis of cycloartenol as a plant sterol precursor. From AmOSC2/3, conserved triad motifs VFM/VFN were discovered for β-amyrin/cycloartenol synthases, respectively. The motif is a critical determinant of yield as proved by 10 variants from different OSCs, where the variant containing the conserved motif increased the yield by up to 12.8-fold. Molecular docking and mutagenesis revealed that Val, Phe and Met residues acted together to stabilize the substrate, and the cation-π interactions from Phe played the major role. Conclusion: The study provides insights into the biogenic origin of oleanane-type and cycloartane-type triterpenoids in Astragalus membranaceus. The conserved motif offers new opportunities for OSC engineering.

Accurate data is the basis for all marine scientific research. Different from the traditional sampling monitoring process, it is fully automated for marine buoy monitoring from sample collection to data results, and the focus of data quality control is no longer focused on the "sample collection-analysis and testing" . In this study, the quality control system for marine buoy monitoring data through analysis of the buoy data in the past two years was designed, including six items: floating body stability, instrument equipment calibration, system operation and maintenance, data transmission and reception, contrast monitoring, abnormal data determination, and abnormal data determination and contrast monitoring were focused on. This research established a quality control method library, and proposed three levels of abnormal data determination rules for buoy data quality control: valid, credible, and relatively accurate, which was innovative. The first layer is the valid data set obtained after removing the obvious fault values, outliers, and other invalid data; the second layer is the credible data set obtained after screening by various quality control methods from the method library; the third layer is relatively accurate data set verified against field contrast monitoring results. Based on the marine buoy monitoring data in Zhejiang Province, the design ideas and methods of the quality control system for buoy monitoring data were proposed, which would help to improve the quality of the online monitoring data of buoys in the coastal waters of Zhejiang. This design would provide a reference for the national marine buoy monitoring data quality control.

Abstract Background To investigate the prevalence and prenatal diagnosis rate of chromosomal abnormalities (CA) in Zhejiang Province, China. Methods We estimated the annual changes in the detected prevalence of CA and prenatal diagnosis rate among 681,590 births in Zhejiang Province, China, between 2014 and 2020. Data were derived from the provincial birth defects surveillance system, which represents 30% of annual births in Zhejiang Province. The effect of maternal age was also evaluated. Results The detected prevalence of sex chromosomal abnormalities (1.70–7.30 per 10,000 births, P trend

Abstract Routing optimization is a well‐known and established topic with the fundamental goal of operating networks efficiently. Traditional optimization heuristics may suffer from performance penalty as it mismatches actual traffic, while artificial intelligence (AI) which has undergone a renaissance recently is gradually being applied to the network optimization and has shown excellent advantages. Especially deep reinforcement learning (DRL) is investigated as a key technology for routing optimization with the goal of enabling networks self‐driving. Therefore, we contributed in this paper a novel approach for practical intelligent routing method using DRL with GNN, which could be easily implemented as a northbound application on the SDN controller. Our method can not only output continuous control actions for routing optimization but also learn from some networks and generalize to other unseen ones. In order to emphasize the generalization and practicality of the intelligent routing method, we deploy it in a real SDN network for experimentation rather than simulation. The results show that the method can keep on optimizing the routing of traffic in other networks of different topologies after the training is stable. And compared with hop‐based OSPF, the optimal load‐balancing algorithm and the recent intelligent routing DROM, it reduces network delay by 16.1%, 19.6% and 14.3%, respectively, but at the expense of flow‐table space within the acceptable range.

Background:. Recombinant human thrombopoietin (rh-TPO) and eltrombopag are two distinct TPO receptor agonists (TPO-RAs) with different mechanisms. During the pandemic, when immunosuppressive medications are controversial, switching to another TPO-RA may be worth exploring in patients who do not benefit from their first TPO-RA. We investigated the outcomes of switching from rh-TPO to eltrombopag or vice versa in immune thrombocytopenia (ITP) patients. Methods:. This prospective, open-label, observational investigation included 96 adult ITP patients who needed to switch between rh-TPO and eltrombopag between January 2020 and January 2021 at Peking University People's Hospital in China. The study evaluated response rates and platelet counts at different time points after the switch, bleeding events, time to response, duration of response, and adverse events. Results:. At 6 weeks after switching, response was observed in 21/49 patients (43%) who switched for inefficacy and 34/47 patients (72%) who switched for non-efficacy-related issues. In the inefficacy group, 9/27 patients (33%) responded to eltrombopag, and 12/22 patients (55%) responded to rh-TPO. In the non-efficacy-related group, 21/26 (81%) and 13/21 (62%) patients in the eltrombopag and rh-TPO groups maintained their response rates at 6 weeks after switching, respectively. Response at 6 months was achieved in 24/49 patients (49%) switching for inefficacy and 37/47 patients (79%) switching for non-efficacy issues. In the inefficacy group, 13/27 patients (48%) responded to eltrombopag, and 11/22 patients (50%) responded to rh-TPO. In the non-efficacy-related group, 22/26 patients (85%) and 15/21 patients (71%) in the eltrombopag and rh-TPO groups maintained their response rates at 6 months after switching, respectively. Both eltrombopag and rh-TPO were well tolerated. Conclusions:. Our study confirmed the safety and effectiveness of switching between rh-TPO and eltrombopag for ITP patients who had no response to or experienced adverse events with their first TPO-RA. When the switch was motivated by other reasons, including patient preference and platelet count fluctuations, the probability of response was high. Registration:. ClinicalTrials.gov, NCT04214951.

Characterizing the soft protein corona on nanoparticles i.e. the outer layer of the corona, remains a longstanding challenge. Here, the authors develop an in situ method to monitor the dynamic processes of multilayered corona formation and evolution that offers a universal strategy to characterize the soft corona proteome.

Abstract Objectives To evaluate the value of monoenergetic images (MEI [+]) and iodine maps in dual-source dual-energy computed tomography (DECT) for assessing pancreatic ductal adenocarcinoma (PDAC), including the visually isoattenuating PDAC. Materials and methods This retrospective study included 75 PDAC patients, who underwent contrast-enhanced DECT examinations. Conventional polyenergetic image (PEI) and 40–80 keV MEI (+) (10-keV increments) were reconstructed. The tumor contrast, contrast-to-noise ratio (CNR) of the tumor and peripancreatic vessels, the signal-to-noise ratio (SNR) of the pancreas and tumor, and the tumor diameters were quantified. On iodine maps, the normalized iodine concentration (NIC) in the tumor and parenchyma was compared. For subjective analysis, two radiologists independently evaluated images on a 5-point scale. Results All the quantitative parameters were maximized at 40-keV MEI (+) and decreased gradually with increasing energy. The tumor contrast, SNR of pancreas and CNRs in 40–60 keV MEI (+) were significantly higher than those in PEI (p

Abstract Depression is a mental disease involving complex pathophysiological mechanisms, and there are many ways to establish depressive mouse models. The purpose of this study is to comprehensively compare the behavioral changes and its mechanism induced by two different models. This study established two depressive mouse models by maternal separation (MS) or lipopolysaccharide (LPS) administration, and added fluoxetine treatment group respectively for comparison. MS induced more apparent anxiety-like behavior while LPS induced more apparent depressive-like behavior. LPS increased peripheral inflammatory factors more apparent, which were mitigated by fluoxetine. MS inhibited the 5-HT system more obviously and was relieved by fluoxetine. LPS triggered stronger immune response in the hippocampus and prefrontal cortex (PFC). MS significantly reduced the expression of neurotrophic proteins and was alleviated by fluoxetine. Overall, LPS induced stronger system inflammation, while MS impaired the function of HPA axis and 5-HT system. Our results will contribute to a deeper understanding of the pathophysiology of different stress-induced depression and will also help researchers select appropriate models of depression for their own needs.

Abstract Turning behaviour is one of the most challenging driving manoeuvres that take place at intersections. Autonomous vehicles (AVs) are often overly conservative in these scenarios as they compromised to others’ behaviour to realize behavioural consistency. This paper proposes an intended cooperative motion planning (ICMP) that can actively predict the intentions of interacting participants. This helps achieve socially compliant cooperation and enables each vehicle to converge upon a set of consistent behaviours. The ICMP framework divides the integrated driving process into two related modules: prediction and planning. These modules are integrated using the mechanism of intended cooperation, which first introduces the criteria for a cooperative response and then maps them in the motion planning space. The prediction module applies a Gaussian mixture model to learn human drivers’ behaviour to determine conflict points, which helps to narrow down the solution spaces. In the planning module, paths are represented by quartic Bézier curves and speed is modelled as a polynomial function. Optimizations can then be used that maximize the efficiency and smoothness for path planning, and comfort and efficiency for speed planning. The test results show that ICMP‐based AVs had consistent interactions with other vehicles. Moreover, when compared with a potential field‐based method, the ICMP‐based method had better performance in terms of safety, comfort and efficiency, especially when interacting with multiple oncoming vehicles.

As a versatile type of enzyme, carboxylic acid reductases (CAR) can not only reduce various carboxylic acids to aldehydes in cooperation with cofactors ATP and NADPH but also catalyze the synthesis of amides and esters in the absence of NADPH. Here, we report an intramolecular cyclization catalyzed by CAR only with the use of ATP to transform amino acids into diverse lactams, including γ-/δ-/ε-lactams and chiral derivatives thereof. The observed wide substrate scope and selectivity enable potential applications to be implemented. Our results demonstrate that CAR-catalyzed lactamization is a promising approach for the synthesis of chiral lactam compounds under mild conditions, thereby enriching the toolbox for the biosynthesis of lactams as a viable alternative to purely chemical procedures.

ObjectiveMalassezia furfur (M. furfur) is a lipophilic, conditionally pathogenic yeast that mainly causes skin infections, but the reports of related invasive infections are increasing. The aim of this study is to provide clinical data to assist physicians in the management of patients with invasive infections caused by M. furfur.MethodsA case of pulmonary infection caused by M. furfur in a hematopoietic stem cell transplant patient for aplastic anemia was reported. In addition, the literature on invasive infection by M. furfur published in PubMed and Web of Science in English until 31 July 2022 was reviewed.ResultsClinical data analysis of 86 patients (from 37 studies and our case) revealed that most of them were preterm (44.2%), followed by adults (31.4%). M. furfur fungemia occurred in 79.1% of the 86 patients, and 45 of them were clearly obtained from catheter blood. Other patients developed catheter-related infections, pneumonia, peripheral thromboembolism, endocarditis, meningitis, peritonitis and disseminated infections. Thirty-eight preterm infants had underlying diseases such as very low birth weight and/or multiple organ hypoplasia. The remaining patients had compromised immunity or severe gastrointestinal diseases. 97.7% of patients underwent invasive procedures and 80.2% received total parenteral nutrition (TPN). Fever, thrombocytopenia and leukocytosis accounted for 55.8%, 38.4% and 24.4% of patients with M. furfur invasive infections, respectively. 69.8% of the patients received antifungal therapy, mainly amphotericin B (AmB) or azoles. Of 84 patients with indwelling catheters, 58.3% underwent the removal of catheters. TPN were discontinued in 30 of 69 patients. The all-cause mortality of 86 patients was 27.9%.ConclusionsM. furfur can cause a variety of invasive infections. These patients mostly occur in premature infants, low immunity and severe gastrointestinal diseases. Indwelling catheters and TPN infusion are major risk factors. AmB, l-AmB and azoles are the most commonly used agents, and simultaneous removal of the catheter and termination of TPN infusion are important for the treatment of M. furfur invasive infections.

BackgroundGranulomatous lobular mastitis (GLM) is characterized by nonspecific chronic inflammation concentrated in breast lobules. Surgical resection is one of the most common treatment options for GLM. On the basis of our previous use of Breast Dermo-Glandular Flap (BDGF), we designed a new surgical approach for GLM, especially for cases where the focus is close to the nipple. Here we describe this new treatment approach.MethodsIn Peking Union Medical College Hospital (PUMCH) and Beijing Dangdai Hospital during January 2020—June 2021, we enrolled all 18 GLM patients who underwent surgery with the use of Dermis-Retained BDGF. All patients were women; most of the patients were 18–50 years old (88%); and the most common clinical manifestation of GLM was breast mass (60%). Then, we collected and analyzed data about the surgery and outcomes (drainage tubes moving time, relapse, patients’ shape satisfaction). We regarded GLM recurrence on the same side as relapse. If there was no complication and the patient's satisfaction was excellent or good, we rated the surgery as successful. We recorded the occurrence of all common postsurgical complications of the breast.ResultsThe debridement area was 3–5.5 (4.3 ± 0.7) cm; surgery time was 78–119 (95.6 ± 11.6) min; and mean debridement time (27.8 ± 8.9 min) was shorter than the time to obtain and transplant the flap (47.5 ± 12.9 min). Blood loss was less than 139 ml. As for bacterial culture, two patients had positive results, but they had no symptoms. No surgery-related complications happened. In terms of the outcomes, all of the drainage tubes were removed in less than 5 days, and only one patient experienced relapse after 1 year of surgery during the follow-up. The patients’ satisfaction with the breast shape was as follows: excellent (50%), good (22%), acceptable (22%), and poor (6%).ConclusionFor GLM patients refractory to conservative therapy or former unsatisfactory surgical management whose lesion is in the vicinity of the nipple and larger than 3 cm, Dermis-Retained BDGF is a suitable approach to fill the after-debridement defect below the nipple-areola and achieve a relatively satisfactory cosmetic outcome.

Biallelic variants in the USH2A gene cause Usher syndrome type 2 (USH2), in which patients’ symptoms are progressive night blindness, reduced visual field, decreased central vision and sensorineural hearing impairment. There is currently no effective drug for USH2. In this study, we isolated peripheral blood mononuclear cells from a patient with USH2. The pluripotency of induced cells was verified by the presence of cell surface markers, the expression of pluripotent genes, and the formation of teratomas. The generation of this induced pluripotent stem cell line provides an effective way to study USH2, such as disease modeling and drug screening.Usher syndrome type 2 (USH2) is a genetic disease mainly caused by biallelic variants in the USH2A gene. Patients usually present with progressive night blindness, reduced visual field, and then reduced central vision. Patients with USH2 also have sensorineural hearing impairment. There is currently no effective treatment for USH2, and the pathogenesis is still unclear. Therefore, it is of great significance to study the pathogenic mechanism of USH2A gene variants for the study of therapeutic targets. In this study, we obtained induced pluripotent stem cell (iPSC) line containing USH2A gene variants. We isolated mononuclear cells from the peripheral blood of patient and established iPSCs by reprogramming with nonintegrating vectors. We then confirmed the pluripotency of our generated iPSCs through the detection of multiple cell surface markers, the expression of pluripotency-related genes, and the ability to form teratomas with three germ layer structures in vivo. The generation of this cell line will facilitate research on USH2 disease and will play a role that cannot be underestimated in future organoid generation, drug screening, and research on drug targets as well as mechanisms.

Mutations in the HERC2 and OCA2 genes have the potential to affect pigment deposition and alter feather color in birds. Therefore, in this study, we evaluated HERC2-OCA2 gene locus polymorphisms in Korean and Beijing white quails using RNA-Seq and KASP technology. The expression levels of HERC2 and OCA2 mRNA in skin tissues were analyzed using RT-qPCR. Ten single nucleotide polymorphisms were identified by RNA-Seq, of which three (n.117627564T>A, n.117674275T>G, n.117686226A>C) exhibited significant association with feather color in quail. The expression of OCA2 mRNA was significantly lower in the skin of Beijing white quails than that in the skin of Korean quails. These results suggested that variants in HERC2-OCA2 intergenic region could influence the expression of OCA2, which may underlie diluted feather color in the Beijing white quail.

Haploidentical hematopoietic stem cell transplantation (haplo-HSCT), as one of the life-saving treatments for severe aplastic anemia (SAA), is widely used because of its great donor availability. Over decades, granulocyte colony-stimulating factor (G-CSF)/antithymocyte globulin (ATG)-based protocol (the so-called Beijing Protocol) has achieved favorable engraftment and survival outcomes. In this study, we modified the conventional Beijing Protocol: the full-dose Cyclophosphamide (Cy) (200 mg/kg in total) was divided into 42.75 mg/kg Cy on day -5 to day -2 and Low dose post-transplant Cy (PTCy) (14.5 mg/kg on days +3 and +4), hoping to reduce the incidence of severe acute graft-versus-host disease (aGVHD) and to guarantee successful and stable engraftment. Here we retrospectively reported and analyzed the data of first 17 patients with SAA who had received haplo-HSCT using this novel regimen between August 2020 and August 2022. The median follow-up was 522 days (range, 138-859 days). No patient developed primary graft failure. Four (23.5%) patients developed grade II bladder toxicity, two (11.8%) patients developed grade II cardiotoxicity. All patients achieved neutrophil and platelet engraftment at median times of 12 days (range, 11–20 days) and14 days (range, 8-36 days). During our follow-up, no patients developed grade III-IV aGVHD. The cumulative incidence of grade II and grade I aGVHD at 100 days was 23.5% (95% CI, 6.8%-49.9%) and 47.1% (95% CI, 23.0%-72.2%). Three patients (17.6%) developed chronic GVHD of skin, mouth, and eyes and all of which were mild. All patients are alive by the end of the follow-up, with a failure-free survival of 100%, which was defined as survival without treatment failures, such as death, graft failure, or relapse rate. The rate of cytomegalovirus (CMV) reactivation was 82.4% (95% CI, 64.3%-100%). The rate of Epstein-Barr virus (EBV) reactivation was 17.6% (95% CI, 3.8%-43.4%). No CMV disease and post-transplantation lymphoproliferative disorder (PTLD) occurred among these patients. In conclusion, the encouraging results of prolonged survival outcomes and reduced incidence of GVHD suggest promising effect of this novel regimen in haplo-HSCT for patients with SAA. Larger-sample prospective clinical trials are needed to confirm the effectiveness of this regimen.

The use of carbon fiber-reinforced resin matrix composites instead of metals to manufacture cryogenic propellant tanks for spacecrafts is a development trend in the world aerospace industry. Cryogenic mechanical properties of the composites should be investigated in detail due to that the ultra-low temperature environment may cause micro cracks in the composites, leading to propellant leakage. In the present study, cryogenic tensile properties of a carbon fiber reinforced silicon-containing epoxy resin aomposite are investigated using experimental and numerical simulation methods. A silicon-containing epoxy resin with excellent cryogenic mechanical properties is developed by introducing a synthesized organic silicon polymer epoxidized polysiloxane and Nano-SiO _2 into bisphenol F type epoxy resin. The tensile strength and modulus of the silicon-containing epoxy resin at −180 °C are 202.63 MPa and 7.81 GPa, which are 16.71% and 3.03% higher than those of bisphenol F type epoxy resin. The tensile strength of the silicon-containing epoxy resin at −180 °C is increased by 107.7% compared to that at room temperature, and the modulus at −180 °C is nearly twice that at room temperature. The carbon fiber reinforced silicon-containing epoxy resin composite is prepared by vacuum injection molding. The finite element model for the representative volume element of the composite unidirectional plate is established. The random sequence expansion method is used to randomly distribute the carbon fibers and simulate the thermal residual stress, the elastic performance, and the damage of the composite at cryogenic environments. Through comparison, it is found that the simulation results are in good agreement with the experimental results. The simulation reliability for cryogenic mechanical properties of carbon fiber reinforced resin matrix composites is verified. It is expected to provide a reference for the analysis and evaluation of cryogenic mechanical properties of composite tanks.

We applied excimer laser annealing (ELA) on indium-zinc oxide (IZO) and IZO/indium-gallium-zinc oxide (IGZO) heterojunction thin-film transistors (TFTs) to improve their electrical characteristics. The IZO and IZO/IGZO heterojunction thin films were prepared by the physical vapor deposition method without any other annealing process. The crystalline state and composition of the as-deposited film and the excimer-laser-annealed films were analyzed by X-ray diffraction and X-ray photoelectron spectroscopy. In order to further enhance the electrical performance of TFT, we constructed a dual-heterojunction TFT structure. The results showed that the field-effect mobility could be improved to 9.8 cm2/V·s. Surprisingly, the device also possessed good optical stability. The electron accumulation at the a-IZO/HfO, HfO/a-IGZO, and a-IGZO/gate insulator (GI) interfaces confirmed the a-IGZO-channel conduction. The dual-heterojunction TFT with IZO/HfO/a-IGZO-assisted ELA provides a guideline for overcoming the trade-off between high mobility (μ) and positive VTh control for stable enhancement mode operation with increased ID.

The impact of drought stress on plant growth in arid regions is a critical concern, necessitating the exploration of strategies to enhance plant drought resistance, particularly during the early stages of drought stress. This study focuses on the ectomycorrhizal fungus Cenococcum geophilum, renowned for its extensive genetic diversity and broad host compatibility, making it a crucial ally for host plants facing external stresses. We utilized Pinus massoniana seedlings inoculated with different ecotypic strains of C. geophilum under drought stress. The results showed that the inoculation of most strains of C. geophilum enhanced the drought resistance of P. massoniana seedlings under the early stages of drought stress, by influencing the water content, photosynthesis, accumulation of osmotic adjustment substances, and antioxidant enzyme activities in both shoots and roots of seedlings. Transcriptome analysis showed that mycorrhizal seedlings mainly regulated energy metabolism and reduction–oxidation reaction to resist early drought stress. Notably, the level of drought resistance observed in mycorrhizal seedlings was irrespective of the level of drought tolerance of C. geophilum strains. This study contributes essential data for understanding the drought response mechanisms of mycorrhizal P. massoniana seedlings inoculated by distinct C. geophilum ecotypes and guidance on selecting candidate species of ectomycorrhizal fungi for mycorrhizal afforestation in drought areas.

Clubroot disease, caused by Plasmodiophora brassicae, poses a significant global threat to cruciferous crops. The epidemic area of clubroot disease is expanding rapidly. In response to this pressing issue, there is a compelling need for the development of clubroot disease-resistant radish cultivars. China boasts an extensive array of radish varieties and germplasm resources. However, a comprehensive assessment of their resistance to clubroot has not yet been carried out, thereby impeding the effective utilization of germplasm and clubroot-resistant breeding. Therefore, it is urgent to systematically evaluate the clubroot resistance of the radish germplasm and identify resistant resources. In this study, clubroot resistance evaluations were conducted on 268 excellent radish varieties derived from 30 provinces in China, as well as seven accessions from Russia, North Korea, France, South Korea, and Germany. The resistance evaluation revealed a diverse range of resistance indices, with a mean disease index (DI) ranging from 0.6 to 58.5, showing significant disparities in clubroot resistance among these radish resources. A total of six accessions were characterized as highly resistant to clubroot, and a further 50 accessions were characterized as resistant. The disease-resistant radishes showed diversity in horticultural traits. Provinces in South China contributed significantly more resistance germplasm than those of North China. These materials are of great value for both genetic investigation and the crop breeding of clubroot resistance. Furthermore, we employed a previously established clubroot-resistance-linked SSR marker to analyze the clubroot-resistant resources. The accessions exhibited dissimilar genetic profiles from known clubroot-resistant germplasm, suggesting their potential status as novel sources of clubroot resistance. Conclusively, these newly identified accessions enriched the genetic diversity within the clubroot-resistant gene pool and may contribute to the future cloning of previously undiscovered clubroot-resistant genes.

During the production of nattokinase (NK) by Bacillus species, certain by-products such as poly-γ-glutamic acid (γ-PGA) are simultaneously synthesized. The impact of γ-PGA synthesis on NK production remains unclear. In this study, we knocked out the pgsC gene, a component of the γ-PGA synthetase cluster (pgsBCA), and constructed a novel recombinant strain, Bacillus licheniformis BL11. Next, we compared the fed-batch fermentation profiles of BL11 and its parental strain BL10, conducted transcriptional analysis, and measured intracellular ATP content. We also optimized glucose-feeding strategies under varying oxygen supply conditions. Our results indicated that the utilization rates of glucose and soybean meal were both improved in the pgsC-deficient strain BL11, and NK activity was enhanced. Furthermore, the transcriptional levels of genes involved in glycolysis and the TCA cycle were relatively upregulated in BL11. The maximal NK activity reached 2522.2 FU/mL at 54 h of fermentation using a constant glucose-feeding rate of 5.0 g/(L·h) under high oxygen supply conditions. The newly developed recombinant strain B. licheniformis BL11, along with the optimized feeding strategy, shows promise for large-scale NK production.

The emergence of vancomycin-resistant Enterococcus (VRE) and vancomycin resistance genes (VRGs) complicates the application of vancomycin, which is a last-line agent for human infectious diseases, and pharmaceutical wastewater treatment plants (PWWTPs) are widely thought to be important sources of corresponding antibiotic resistance genes (ARGs). In this study, two VRGs (vanA and vanB) were evaluated in two PWWTPs using quantitative polymerase chain reaction (qPCR) analysis to characterize the occurrence and fate of VRGs. The VRG concentration tended to decrease throughout all processing stages, while anaerobic treatment promoted the propagation of antibiotic-resistant bacteria and led to an increase in VRG abundance. Finally, the absolute concentrations of vanA and vanB exceeded 104 copies/mL in the effluents, and a significant amount of VRGs was transferred to sludge at 1.68 × 1017 copies/d. Redundancy analysis demonstrated that the relative abundance of ARGs was significantly correlated with the concentrations of vancomycin and COD. Furthermore, the relative abundance of vanA was increased in wastewater with multiple antibiotics, while the relative abundance of vanB only increased in the presence of vancomycin. This observation implied different intrinsic resistance mechanisms for different VRG subtypes. Overall, in this report, we describe the first comprehensive study on the fate and behavior of VRGs with different physicochemical or biochemical treatments and different antibiotic selection pressures in PWWTPs; this report provides important references for the environmental spread of VRGs.

With the increasing stringency of the Energy Efficiency Design Index (EEDI) requirements, improving the efficiency of the propeller has emerged as a significant challenge in the development of eco-friendly ships. Cavitation inevitably occurs, and it reduces the hydrodynamic performance of the propeller and erodes the blade surface, leading to increased fuel consumption. Therefore, reducing cavitation is crucial for ships to meet the EEDI requirement. This paper investigates the fatigue life and hydrodynamic performance of the propeller under different cavitation numbers and speeds. The relationship between propeller fatigue life and propulsion efficiency under cavitation conditions is explored. In simulation, the Schnerr–Sauer theoretical model is employed as the cavitation model. The nominal stress method (S-N method) is used to calculate the blade fatigue strength. The KP957 propeller is taken as the research object. The hydrodynamic performance of the propellor under different cavitation numbers is studied by means of the finite volume method. The surface pressure and wall shear stress of the blade within the cycle are calculated, and they are conveniently loaded in the dynamic process to calculate the stress and strain of the propeller using the finite element method. Subsequently, the fatigue life of the propeller is determined based on the S-N curve of the blade material. The validity of the study is established by comparing the cavitation results with the experimental results from the Korean Ocean Engineering Research Institute (KORDI) for the KS1295 ship at a speed of 15.7 knots, where the cavitation number in the wake field is 2.5553, and a good consistency is obtained. The findings emphasize the significant impact of cavitation on blade service life and vibration.

We propose a method to enhance the accuracy of arrival time picking of noisy microseismic recordings. A series of intrinsic mode functions (IMFs) of the microseismic signal are initially decomposed by employing the ensemble empirical mode decomposition. Subsequently, the sample entropy values of the obtained IMFs are calculated and applied to set an appropriate threshold for selecting IMFs. These are then reconstructed to distinguish between noise and useful signals. Ultimately, the Akaike information criterion picker is used to determine the arrival time of the denoised signal. Test results using synthetic noisy microseismic recordings demonstrate that the proposed approach can significantly reduce picking errors, with errors within the range of 1–3 sample intervals. The proposed method can also give a more stable picking result when applied to different microseismic recordings with different signal-to-noise ratios. Further application in real microseismic recordings confirms that the developed method can estimate an accurate arrival time of noisy microseismic recordings.

With the rapid increase of urban rail transit networks, the environmental problems induced by vibrations from subway traffic become more and more prominent. Most subway tunnels are constructed by the shield machine, which are assembled by tunnel linings connected by joints. This study investigates the effect of the tunnel longitudinal joints on the train-induced vibrations from a subway shield-driven tunnel in a homogeneous half-space. The shield-driven tunnel is considered as an elastic lining ring connected by longitudinal joints, while the ground is simplified as a homogeneous elastic half-space. The general solution for the tunnel and the ground are derived by using the thin-shell theory and the elastic continuum theory, respectively. By satisfying the boundary conditions on the tunnel-ground interface, the tunnel is coupled to the ground in a half-space domain. The responses during the running of a metro train are calculated by coupling the tunnel-ground model with the vehicle-track model. The longitudinal joint has a significant impact on ground vibrations, which increases the running RMS values of the vertical velocity by 20% ∼ 70% and of the horizontal verticity by 10% ∼ 20%. As the stiffness of the longitudinal joint decreases, the ground vibrations increase.

In this paper, we define and study quasi-monoidal comonads on a monoidal category. It generalize the (Hom type) coquasi-bialgebras to a non-braided setting. We investigate their corepresentations and their coquasitriangular structures. We also discuss their gauge equivalence relations.

Abstract. Hematopoietic stem cell transplantation (HSCT) is a highly effective and unique medical procedure for the treatment of most hematological malignancies. The first allogeneic transplantation was performed by E. Donnall Thomas in 1957. Since then, the field has evolved and expanded worldwide. The first successful allogenic HSCT (allo-HSCT) in China was conducted in 1981. Although the development of allo-HSCT in China lagged, China has since made considerable contributions to the process of HSCT worldwide, with more than 10,000 HSCTs performed annually. In particular, haploid HSCT (haplo-HSCT) technology represented in the Beijing Protocol has demonstrated similar efficacy to human leukocyte antigen-matched HSCT and has gradually become the pre-dominant choice for allo-HSCT in China. Currently, the number of haplo-HSCT procedures exceeds 5000 per year, and the Beijing Protocol has been greatly improved by implementing updated individualized strategies for controlling complications, relapse, and infection management. In addition, innovative haplo-HSCT technologies developed by different medical transplantation centers, such as Soochow, Zhejiang, Fujian, Chongqing, and Anhui, have emerged, providing inspiration for the refinement of global practice. This review will focus on the current activity in this field and highlight important trends that are vital in China's allo-HSCT process, examining the current viewpoint and future directions.

Background: Breast cancer is the most common malignancy in women. Clinical models such as Oncotype DX recurrence score (RS) and Clinical Treatment Score post–5 years (CTS5) model for survival prediction are crucial for clinical practice. However, it remains unclear whether CTS5 or RS would be a more powerful clinical model for recurrence risk evaluation. Therefore, we conducted the present study to compare the performance of CTS5 risk model and RS on different recurrence evaluation. And we further integrated the two models into a novel nomogram to improve the power for prognosis prediction. Methods: Female patients with invasive hormone receptor positive breast cancer in the Surveillance, Epidemiology, and End Results Program (SEER) database with RS data available were included. The clinicopathological data were directly extracted from SEER database. Participants were divided into three subsets according to recurrence timing (60 months) for model evaluation. Survival receiver operating characteristic curve and C-index were calculated to evaluate discrimination. Calibration curve were used to visual inspection for calibration. Model comparison was assessed by net reclassification index (NRI) method. Nomogram prognostic model was developed with the combination of CTS5 score and RS and also included other critical clinicopathological parameters. Results: In total, 64044 breast cancer patients were enrolled for analysis. The number of patients with survival 60 months (late recurrence subset) were 64044, 36878 and 15926, respectively. For model discrimination, CTS5 model was superior to RS for overall survival (OS) prediction (likelihood ratio test P

Abstract Background Diffusion-weighted imaging (DWI) is an essential technique for optic nerve diseases. However, the image quality of optic nerve DWI is decreased by the distortions and artifacts associated with conventional techniques. In order to establish this method as a critical tool in optic nerve diseases, reproducibility and feasibility of new technical and conventional approaches of DWI need to be systematically investigated. Methods DWIs were acquired using ss-EPI, readout-segmented EPI (rs-EPI) DWI, and reduced field-of-view (rFOV) DWI. 26 volunteers (mean age 31.2 years) underwent repeated MRI examinations in order to assess scan–rescan reproducibility and accuracy. The apparent diffusion coefficient (ADC) values (three ROIs were measured on each side) were determined to evaluate the reproducibility of each sequence and the differences between the three techniques. To quantify the geometric distortion artifacts, the length of optic nerve and the maximum angle of optic nerve were defined and compared to T2-weighted imaging. In addition, two readers evaluated four different aspects of image quality on 5-point Likert scales. Results rs-EPI DWI (ICCs: 0.916, 0.797 and 0.781) and rFOV DWI (ICCs: 0.850, 0.595 and 0.750) showed higher reproducibility (ICCs: ROI1, ROI2 and ROI3) of mean ADC value in all three ROIs than ss-EPI DWI (ICCs: 0.810, 0.442 and 0.379). The quantitative analysis of geometric distortion yielded a higher agreement of both rs-EPI DWI and rFOV DWI with T2-weighted imaging than ss-EPI. rs-EPI DWI (2.38 ± 0.90) and rFOV DWI (2.46 ± 0.58) were superior to ss-EPI DWI (1.58 ± 0.64) with respect to overall image quality and other aspects of image quality, each with P

Abstract Background Bracing is the most common conservative treatment for preventing the progression of adolescent idiopathic scoliosis (AIS) in patients with a curve of 25°–40°. X-ray examinations are traditionally performed in the standing position. However, school-age teenagers may take more time to sit. Thus far, little is known about three-dimensional (3D) correction in the sitting position. Hence, this study aimed to determine the effects of standing and sitting positions on 3D parameters during brace correction. Methods We evaluated a single-center cohort of patients receiving conservative treatment for thoracic curvature (32 patients with AIS with a Lenke I curve). The 3D parameters of their standing and sitting positions were analyzed using the EOS imaging system during their first visit and after bracing. Results At the patients’ first visit, sagittal plane parameters such as thoracic kyphosis (TK), lumbar lordosis (LL), and sacral slope decreased when transitioning from the standing position to the sitting position (standing 29° ± 6°, 42° ± 8°, and 42° ± 8° vs. sitting 22° ± 5°, 27° ± 6°, and 24° ± 4°; p

BackgroundPatients with gout carry an excess risk for cardiovascular disease (CVD), but the contribution of subclinical atherosclerosis to the CVD risk has never been reported. In this study, we aimed to explore the predictive factors for incident major adverse cardiovascular events (MACE) in gout patients without a previous history of CVD or cerebral vascular disease.MethodsA single-center, long-term follow-up cohort analysis was performed to assess subclinical atherosclerosis at baseline since 2008. Patients with a previous history of CVD or cerebrovascular disease were excluded. The outcome of the study was the first MACE. The presence of subclinical atherosclerosis was assessed by carotid plaque (CP), and carotid intima-media thickness (CMIT) was determined by ultrasound. An ultrasound scan of bilateral feet and ankles was performed at baseline. The association between tophi, carotid atherosclerosis, and the risk of developing incident MACE was evaluated using Cox proportional hazards models with adjustment for the CVD risk scores.ResultsA total of 240 consecutive patients with primary gout were recruited. Their mean age was 44.0 years, with male predominance (238, 99.2%). During a median follow-up of 10.3 years, incident MACE was ascertained in 28 (11.7%) patients. In a Cox hazards model, controlling for the CV risk scores, the presence of at least two tophi (HR, 2.12–5.25, p < 0.05) and carotid plaque (HR, 3.72–4.01, p < 0.05) were identified as independent predictors of incident MACE in gout patients.ConclusionsThe presence of at least two tophi and carotid plaque on an ultrasound could independently predict MACE in addition to conventional cardiovascular risk factors in gout patients.

Recent studies have shown that microtransplant (MST) could improve outcome of patients with elderly acute myeloid leukemia (EAML). To further standardize the MST therapy and improve outcomes in EAML patients, based on analysis of the literature on MST, especially MST with EAML from January 1st, 2011 to November 30th, 2022, the International Microtransplant Interest Group provides recommendations and considerations for MST in the treatment of EAML. Four major issues related to MST for treating EAML were addressed: therapeutic principle of MST (1), candidates for MST (2), induction chemotherapy regimens (3), and post-remission therapy based on MST (4). Others included donor screening, infusion of donor cells, laboratory examinations, and complications of treatment.

Perfluorooctane sulfonate (PFOS) is a synthetic chemical and an environmental pollutant widely recognized for its industrial use, given its thermal and chemical stability. Growing evidence suggests that PFOS exposure is linked with epigenomic alteration and disease progression. Whether PFOS toxicity could lead to a phenotypical epigenetic state is of interest in toxicology research. Given the limited studies on kidney cancer and disease, the molecular mechanisms underlying the epigenetic modulated state upon PFOS exposure remains unclear. This study explores epigenetic indicators associated with PFOS exposure in A498 kidney cancer cells. We demonstrate a data-driven approach to identify critical features by classifying the epigenetic states upon PFOS exposure. By combining single-cell super-resolution imaging and machine learning analysis, we show that the repressive epigenetic markers are distinctively different upon PFOS exposure. Further we note that, PFOS exposure altered the spatial distribution of H3K9me3 and H3K27me3 with nanoscale imaging. Quantification of gene expression related to tumorigenesis indicates altered expression levels upon PFOS exposure. Our results suggest that the epigenetic changes partake in establishing PFOS-induced toxicity development. Furthermore, the distribution of H3K9me3/H3K27me3 alteration could act as one of the drivers for PFOS-induced phenotype development in disease progression.

X-ray source based on the Thomson scattering of laser interacting with energetic electron beams features high photon energy, small spot size, and good collimation. However, the photon number is insufficient for practical application because of the small cross section of the Thomson scattering. To solve this problem, here, we replace a traditional Gaussian laser pulse with a flying focus laser pulse to extend interaction length and restrain nonlinear effects. Simulation results show that the scattered photon number can be increased by about 25 and 2 times for high and low energy lasers, respectively. In particular, a 1010 photon number can be generated with a 10 J flying focus laser pulse, and the energy spread can also be greatly reduced for high energy laser, from a broad spectrum to a monoenergetic peak. Combining these two advantages, the peak spectrum brightness of x ray is 3 × 108 photons/keV at 240 keV, which is about three orders of magnitude more than the traditional case.

Dynamic extracellular matrix (ECM) mechanics plays a crucial role in tissue development and disease progression through regulation of stem cell behavior, differentiation, and fate determination. Periodontitis is a typical case characterized by decreased ECM stiffness within diseased periodontal tissues as well as with irreversible loss of osteogenesis capacity of periodontal tissue-derived human periodontal tissue-derived MSCs (hMSCs) even returning back to a physiological mechanical microenvironment. We hypothesized that the hMSCs extendedly residing in the soft ECM of diseased periodontal tissues may memorize the mechanical information and have further effect on ultimate cell fate besides the current mechanical microenvironment. Using a soft priming and subsequent stiff culture system based on collagen-modified polydimethylsiloxane substrates, we were able to discover that extended preconditioning on soft matrices (e.g., 7 days of exposure) led to approximately one-third decrease in cell spreading, two-third decrease in osteogenic markers (e.g., RUNX2 and OPN) of hMSCs, and one-thirteenth decrease in the production of mineralized nodules. The significant loss of osteogenic ability may attribute to the long-term residing of hMSCs in diseased periodontal tissue featured with reduced stiffness. This is associated with the regulation of transcriptional activity through alterations of subcellular localization of yes-associated protein and nuclear feature-mediated chromatin organization. Collectively, we reconstructed phenomena of irreversible loss of hMSC osteogenesis capacity in diseased periodontal tissues in our system and revealed the critical effect of preconditioning duration on soft matrices as well as the potential mechanisms in determining ultimate hMSC fate.

Objectives Small cell lung cancer (SCLC) is a lethal human malignancy, and previous studies support the contribution of microRNA to cancer progression. The prognostic value of miR-219-5p in patients with SCLC remains unclear. This study aimed to evaluate the predictive value of miR-219-5p with respect to mortality in patients with SCLC and to incorporate miR-219-5p level into a prediction model and nomogram for mortality.Design Retrospective observational cohort study.Setting and participants Our main cohort included data from 133 patients with SCLC between 1 March 2010 and 1 June 2015 from the Suzhou Xiangcheng People’s Hospital. Data from 86 patients with non-SCLC at Sichuan Cancer Hospital and the First Affiliated Hospital of Soochow University were used for external validation.Outcome measures Tissue samples were taken during admission and stored, and miR-219-5p levels were measured at a later date. A Cox proportional hazard model was used for survival analyses and for analysing risk factors to create a nomogram for mortality prediction. The accuracy of the model was evaluated by C-index and calibration curve.Results Mortality in patients with a high level of miR-219-5p (≥1.50) (n=67) was 74.6%, while mortality in the low-level group (n=66) was 100.0%. Based on univariate analysis, we included significant factors (p47.9 (HR=0.45, 95% CI 0.24–0.83, p=0.01) remained statistically significant factors for improved overall survival. The nomogram had good accuracy in estimating the risk, with a bootstrap-corrected C-index of 0.691. External validation indicated an area under the curve of 0.749 (0.709–0.788).Conclusions The miR-219-5p level was associated with a reduced risk of mortality in patients with SCLC. A nomogram incorporating MiR-219-5p level and clinical factors demonstrated good accuracy in estimating the risk of overall mortality. Prospective validation of the prognostic nomogram is needed.

BackgroundAMKL without DS is a rare but aggressive hematological malignant disease in children, and it is associated with inferior outcomes. Several researchers have regarded pediatric AMKL without DS as high-risk or at least intermediate-risk AML and proposed that upfront allogenic hematopoietic stem cell transplantation (HSCT) in first complete remission might improve long-term survival.Patients and methodWe conducted a retrospective study with twenty-five pediatric (< 14 years old) AMKL patients without DS who underwent haploidentical HSCT in the Peking University Institute of Hematology, Peking University People’s Hospital from July 2016 to July 2021. The diagnostic criteria of AMKL without DS were adapted from the FAB and WHO: ≥ 20% blasts in the bone marrow, and those blasts expressed at least one or more of the platelet glycoproteins: CD41, CD61, or CD42. AMKL with DS and therapy related AML was excluded. Children without a suitable closely HLA-matched related or unrelated donor (donors with more than nine out of 10 matching HLA-A, HLA-B, HLA-C, HLA-DR, and HLA-DQ loci), were eligible to receive haploidentical HSCT. Definition was adapted from international cooperation group. All statistical tests were conducted with SPSS v.24 and R v.3.6.3.ResultsThe 2-year OS was 54.5 ± 10.3%, and the EFS was 50.9 ± 10.2% in pediatric AMKL without DS undergoing haplo-HSCT. Statistically significantly better EFS was observed in patients with trisomy 19 than in patients without trisomy 19 (80 ± 12.6% and 33.3 ± 12.2%, respectively, P = 0.045), and OS was better in patients with trisomy 19 but with no statistical significance (P = 0.114). MRD negative pre-HSCT patients showed a better OS and EFS than those who were positive (P < 0.001 and P = 0.003, respectively). Eleven patients relapsed post HSCT. The median time to relapse post HSCT was 2.1 months (range: 1.0–14.4 months). The 2-year cumulative incidence of relapse (CIR) was 46.1 ± 11.6%. One patient developed bronchiolitis obliterans and respiratory failure and died at d + 98 post HSCT.ConclusionAMKL without DS is a rare but aggressive hematological malignant disease in children, and it is associated with inferior outcomes. Trisomy 19 and MRD negative pre-HSCT might contribute to a better EFS and OS. Our TRM was low, haplo-HSCT might be an option for high-risk AMKL without DS.

IntroductionAlthough geriatric assessment (GA) has been used for a long time in the field of geriatrics and internal medicine, there are few studies on its application in the field of breast surgery. Therefore, the utility of specific GA domains for the assessment of older patients with breast cancer remains unclear. The aim of the present study was to evaluate the association between specific GA domains and the survival rate of older patients with breast cancer.MethodsWe used the database of Peking Union Medical College Hospital to identify older patients who were newly diagnosed with breast cancer between 2012 and 2018 and retrospectively analysed the data of 541 patients aged ≥65 years. Patients with metastatic cancer and those with missing vital status data were excluded. The primary outcomes were overall survival (OS) and breast cancer-specific survival. The GA domains used in this study included functional status, comorbidities, and psychological state. Multivariate regression analysis was used to estimate hazard ratios for these three domains.ResultsAfter a median follow-up of 72 months, we observed a significant relationship between functional impairment and mortality (adjusted HR: 3.06, 95% confidence interval [CI]: 1.83-5.10, P

ObjectiveTo investigate the diagnostic value of quantitative parameters of spectral computed tomography (CT) in ischaemic stroke areas.MethodsThe medical records of 57 patients with acute ischaemic stroke (AIS) who underwent plain computed tomography (CT) head scans, CT angiography (CTA), and CT perfusion (CTP) were retrospectively reviewed. The ischaemic areas (including the core infarct area and penumbra) and non-ischaemic areas in each patient were quantitatively analyzed using F-STROKE software. Two independent readers measured the corresponding values of the spectroscopic quantitative parameters (effective atomic number [Zeff value], iodine density value, and iodine–no-water value) in the ischaemic area and contralateral normal area alone. The differences in spectroscopic quantitative parameters between the two groups were compared, and their diagnostic efficacy was obtained.ResultsThe Zeff, iodine–no-water value, and iodine density value of the ischaemic area all showed significant lower than those of non-ischaemic tissue (P < 0.001). For differentiating the ischaemic area from non-ischaemic tissue, the area under the curve (AUC) of the Zeff value reached 0.869 (cut-off value: 7.385; sensitivity: 93.0%; specificity: 70.2%), the AUC of the iodine density value reached 0.932 (cut-off value: 0.235; sensitivity: 91.2%; specificity: 82.5%), and the AUC of the iodine–no-water value reached 0.922 (cut-off value: 0.205; sensitivity: 96.5%; specificity: 78.9%).ConclusionThe study showed the spectral CT would be a potential novel rapid method for identifying AIS. The spectral CT quantitative parameters (Zeff, iodine density values, and iodine–no-water values) can effectively differentiate the ischaemic area from non-ischaemic tissue in stroke patients.