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Abstract Cancer cells acquire the ability to reprogram their phenotype in response to targeted therapies, yet the transition from dormancy to proliferation in drug-resistant cancers remains poorly understood. In prostate cancer, we utilized high-plasticity mouse models and enzalutamide-resistant (ENZ-R) cellular models to elucidate NR2F1 as a key factor in lineage transition and ENZ resistance. Depletion of NR2F1 drives ENZ-R cells into a relative dormancy state, characterized by reduced proliferation and heightened drug resistance, while NR2F1 overexpression yields contrasting outcomes. Transcriptional sequencing analysis of NR2F1-silenced prostate cancer cells and tissues from the Cancer Genome Atlas-prostate cancer and SU2C cohorts indicated exosomes as the most enriched cell component, with pathways implicated in steroid hormone biosynthesis and drug metabolism. Moreover, NR2F1-AS1 forms a complex with SRSF1 to upregulate NR2F1 expression, facilitating its binding with ESR1 to sustain hormonal receptor expression and enhance proliferation in ENZ-R cells. Furthermore, HnRNPA2B1 interacts with NR2F1 and NR2F1-AS1, assisting their packaging into exosomes, wherein exosomal NR2F1 and NR2F1-AS1 promote the proliferation of dormant ENZ-R cells. Our works offer novel insights into the reawaking of dormant drug-resistant cancer cells governed by NR2F1 upregulation triggered by exosome-derived NR2F1-AS1 and NR2F1, suggesting therapeutic potential for phenotype reversal. Graphical Abstract

Abstract Understanding the genomic characteristics of livestock is crucial for improving breeding efficiency and conservation efforts. However, there is a relative lack of information on the genetic makeup of local goat breeds in Henan, China. In this study, we identified runs of homozygosity (ROH), genomic inbreeding coefficients (FROH), and selection signatures in four breeds including Funiu White (FNW), Huai (HG), Lushan Bullleg (LS), and Taihang black (THB). The genomic analysis utilized a dataset of 46,278 SNP markers and 102 animals. A total of 342, 567, 1285, and 180 ROH segments were detected in FNW, HG, LS, and THB, respectively, with an average of 15.55, 29.84, 32.95, and 8.18 segments per individual. The lengths of ROH segments varied from 69.36 Mb in THB to 417.06 Mb in LS, with the most common lengths being 2-4 Mb and 4-8 Mb. The highest number of longest ROH segments (> 16 Mb) were found in LS (328) and the highest average FROH value was observed in LS (0.173), followed by HG (0.128), while the lowest FROH values were in THB (0.029) and FNW (0.070). Furthermore, the analysis of ROH islands and Composite Likelihood Ratio (CLR) identified a total of 175 significant genes. Among these, 25 genes were found to overlap, detected by both methods. These genes were associated with a diverse range of traits including reproductive ability (GPRIN3), weight (CCSER1), immune response (HERC5 and TIGD2), embryo development (NAP1L5), environmental adaptation (KLHL3, TRHDE, and IFNGR1), and milk characteristics (FAM13A). Significant Gene Ontology (GO) terms related to embryo skeletal system morphogenesis, brain ventricle development, and growth were also identified. This study helps reveal the genetic architecture of Henan goat breeds and provides valuable insights for the effective conservation and breeding programs of local goat breeds in Henan.

BackgroundCockayne syndrome (CS) is a rare, multisystem, autosomal recessive disorder characterized by cachectic dwarfism, nervous system abnormalities, and premature aging. Mutations in the ERCC6 and ERCC8 genes are the predominant causes of Cockayne syndrome, with ERCC6 gene mutations present in approximately 75% of cases.MethodsTrio-based whole-exome sequencing (trio-WES) was employed to identify potential pathogenic variants associated with CS. Preimplantation genetic testing for monogenic disorders (PGT-M) was conducted to prevent the transmission of the pathogenic variant.ResultsTwo compound heterozygous mutations were identified in ERCC6—c.1297G>T (p. Glu433*) and c.1607T>G (p. Leu536Trp)—with c.1297G>T representing a novel mutation. Four blastocysts resulting from intracytoplasmic sperm injection were subjected to biopsy. Genetic analyses revealed that E1 harbored maternal mutations in diploid embryos, E2 and E3 carried both paternal and maternal mutations in non-diploid embryos, and E4 did not carry paternal or maternal mutations in diploid embryos. Following the transfer of the E4 embryos, a single successful pregnancy was achieved.ConclusionThe successful application of PGT-M in this family offers a potential approach for addressing other monogenic diseases. The findings of this study broaden the variant spectrum of ERCC6 and will contribute to the molecular diagnosis and genetic counseling of CS. This case highlights the feasibility and effectiveness of PGT-M in preventing CS and provides valuable insights for similarly affected families.

Amanita phalloides poisoning, renowned for its high mortality rates, is one of the most serious food safety issue in certain regions worldwide. Assessment of prognosis and development of more efficacious therapeutic strategies are critical importance for amanita phalloides poisoning patients. The aim of the study is to establish a nomogram to predict the clinical outcome of amanita phalloides poisoning patients based on the independent risk factor for prognosis. Herein, between January 2013 and September 2023, a cohort of 149 patients diagnosed with amanita phalloides poisoning was enrolled and randomly allocated into training and validation cohorts, comprising 102 and 47 patients, respectively. Multivariate logistic regression analysis was performed to identify the independent risk factors for morality of amanita phalloides poisoning patients in training cohort. Subsequently, a nomogram model was constructed to visually display the risk prediction model. The predictive accuracy of nomogram was verified by the validation cohort. The C index, the area under the receiver operating characteristic curve (AUC), and calibration plots were used to assessed the performance of nomogram. The clinical utility was evaluated by decision curve analysis (DCA). In the present study, the results showed that hepatic encephalopathy (HE), upper gastrointestinal bleeding (UGB), AST, and PT were the independent risk factors associated with the mortality of amantia phalloides poisoning patients. We constructed a new nomogram to evaluate the probability of death induced by amantia phalloides poisoning. The AUC for the prediction accuracy of the nomogram was 0.936 for the training cohort and 0.929 for the validation cohort. The calibration curves showed that the predicted probability matched the actual likelihood. The results of the DCA suggested that the nomogram has a good potential for clinical application. In summary, we developed a new nomogram to assess the probability of mortality for amanita phalloides poisoning patients. This nomogram might facilitate clinicians in making more efficacious treatment strategies for patients with amanita phalloides poisoning.

Concrete mixtures have an optimized mix design in view of attaining desired properties. However, after mixing, during further processing, it is typically not possible to further adjust the performance of the fresh and hardening concrete. A new and emerging approach is to actively control the concrete properties by means of responsive particles or polymers triggered by an externally applied signal. Active control of properties of concrete refers to the concept of on- demand changes of one or more properties of the concrete after mixing by triggering a response to one or more of the constituents using a specific trigger signal (e.g. thermal, chemical, electrical, magnetic...). The on-demand control of properties can focus on the processing stage (including e.g. pumping, casting, 3D printing), the curing and hardening stage (including e.g. control of capillary pressure, shrinkage, setting, and hardening) and even on the hardened stage during service life (e.g. active corrosion control, active crack healing...). Addressing specific obstacles in cementitious environments, ensuring responsive material stability, controlling signal applicability, cost, logistics, and on-site safety is crucial for successful implementation. A RILEM technical committee has been initiated in 2023, working on the concept of Active Control of Properties of Concrete (RILEM TC 317-ACP). The committee will focus on active control of properties of fresh and hardening concrete. This paper gives a short introduction to scope and activities of TC 317-ACP.

Abstract Background To the best of our knowledge, no study has investigated the potential joint effect of large for gestational age (LGA) and assisted reproductive technology (ART) on the long-term health of children. Methods This was a prospective cohort study that recruited children whose parents had received ART treatment in the Center for Reproductive Medicine, Shandong Provincial Hospital, affiliated to Shandong University, between January 2006 and December 2017. Linear mixed model was used to compare the main outcomes. The mediation model was used to evaluate the intermediary effect of body mass index (BMI). Results 4138 (29.5%) children born LGA and 9910 (70.5%) children born appropriate for gestational age (AGA) were included in the present study. The offspring ranged from 0.4 to 9.9 years. LGAs conceived through ART were shown to have higher BMI, blood pressure, fasting blood glucose, fasting insulin, and homeostatic model assessment of insulin resistance values, even after controlling for all covariates. The odds of overweight and insulin resistance are also higher in LGA subjects. After adjusting for all covariates, LGAs conceived through ART had BMI and BMI z-scores that were 0.48 kg/m2 and 0.34 units greater than those of AGAs, respectively. The effect of LGA on BMI was identified as early as infancy and remained consistently significant throughout pre-puberty. Conclusions Compared to AGA, LGA children conceived from ART were associated with increased cardiovascular-metabolic events, which appeared as early as infancy and with no recovery by pre-puberty.

In this paper, we conducted a study of H-Toeplitz operators on the Dirichlet type space $ \mathfrak{D}_{t} $, which included several aspects. To begin, we established the matrix representation of the H-Toeplitz operator $ S_{\varphi} $ with respect to the orthonormal basis of $ \mathfrak{D}_t $. Subsequently, we characterized the compactness of $ S_{\varphi} $ in terms of the symbol $ \varphi $. Furthermore, we developed a new method to investigate the algebraic properties of H-Toeplitz operators, including self-adjointness, diagonality, co-isometry, partial isometry as well as commutativity.

Abstract The study aimed to determine the specific relative biological effectiveness (RBE) of various cells in the hippocampus following proton irradiation. Sixty Sprague–Dawley rats were randomly allocated to 5 groups receiving 20 or 30 Gy of proton or photon irradiation. Pathomorphological neuronal damage in the hippocampus was assessed using Hematoxylin–eosin (HE) staining. The expression level of NeuN, Nestin, Caspase-3, Olig2, CD68 and CD45 were determined by immunohistochemistry (IHC). The RBE range established by comparing the effects of proton and photon irradiation at equivalent biological outcomes. Proton20Gy induced more severe damage to neurons than photon20Gy, but showed no difference compared to photon30Gy. The RBE of neuron was determined to be 1.65. Similarly, both proton20Gy and proton30Gy resulted in more inhibition of oligodendrocytes and activation of microglia in the hippocampal regions than photon20Gy and photon30Gy. However, the expression of Olig2 was higher and CD68 was lower in the proton20Gy group than in the photon30Gy group. The RBE of oligodendrocyte and microglia was estimated to be between 1.1 to 1.65. For neural stem cells (NSCs) and immune cells, there were no significant difference in the expression of Nestin and CD45 between proton and photon irradiation (both 20 and 30 Gy). Therefore, the RBE for NSCs and immune cell was determined to be 1.1. These findings highlight the varying RBE values of different cells in the hippocampus in vivo. Moreover, the actual RBE of the hippocampus may be higher than 1.1, suggesting that using as RBE value of 1.1 in clinical practice may underestimate the toxicities induced by proton radiation.

Abstract Goats have achieved global prominence as essential livestock since their initial domestication, primarily owing to their remarkable adaptability to diverse environmental and production systems. Differential selection pressures influenced by climate have led to variations in their physical attributes, leaving genetic imprints within the genomes of goat breeds raised in diverse agroecological settings. In light of this, our study pursued a comprehensive analysis, merging environmental data with single nucleotide polymorphism (SNP) variations, to unearth indications of selection shaped by climate-mediated forces in goats. Through the examination of 43,300 SNPs from 51 indigenous goat breeds adapting to different climatic conditions using four analytical methods: latent factor mixed models (LFMM), F-statistics (Fst), Extended haplotype homozygosity across populations (XPEHH), and spatial analysis method (SAM), A total of 74 genes were revealed to display clear signs of selection, which are believed to be influenced by climatic conditions. Among these genes, 32 were consistently identified by at least two of the applied methods, and three genes (DENND1A, PLCB1, and ITPR2) were confirmed by all four approaches. Moreover, our investigation yielded 148 Gene Ontology (GO) terms based on these 74 genes, underlining pivotal biological pathways crucial for environmental adaptation. These pathways encompass functions like vascular smooth muscle contraction, cellular response to heat, GTPase regulator activity, rhythmic processes, and responses to temperature stimuli. Of significance, GO terms about endocrine regulation and energy metabolic responses, key for local adaptation were also uncovered, including biological processes, such as cell differentiation, regulation of peptide hormone secretion, and lipid metabolism. These findings contribute to our knowledge of the genetic structure of climate-triggered adaptation across the goat genome and have practical implications for marker-assisted breeding in goats.

Abstract Background Pulmonary primitive neuroectodermal tumor (PNET), a member of the Ewing sarcoma family of tumors, is a rare malignancy that is associated with a grim prognosis. To date, fewer than 30 cases of pulmonary PNET have been reported. In this case report, we present the clinical details of a 12-year-old girl with pulmonary PNET who underwent surgical treatment. We also conducted an analysis and summary of other relevant studies and the surgical outcomes. Case presentation In May 2018, a 12-year-old girl was admitted with symptoms of cough and blood-tinged phlegm. A computed tomography scan revealed a large mass, measuring 12.9 cm × 8.1 cm, in the right middle and lower lungs. A percutaneous lung biopsy confirmed poorly differentiated tumor cells with a nested growth pattern. Immunohistochemical staining demonstrated positive expression of CD99, CD56, Vimentin, and Synaptophysin. The patient was diagnosed with pulmonary PNET. Following three cycles of neoadjuvant chemotherapy, a substantial reduction in tumor volume was observed. Subsequently, the patient underwent a surgical procedure involving pneumonectomy and partial resection of the left atrium with the assistance of cardiopulmonary bypass. The patient was discharged 37 days after surgery. During a three-year follow-up period, she exhibited no signs of tumor recurrence and has successfully returned to school. Conclusions This case highlights the successful management of an advanced PNET with neoadjuvant chemotherapy, pneumonectomy, and partial resection of the left atrium employing cardiopulmonary bypass. The patient remained disease-free after three years. Our analysis of surgically treated cases indicates that neoadjuvant chemotherapy can contribute to improved prognoses for PNET patients. It is crucial to emphasize that complete surgical excision remains the cornerstone of treatment, underscoring the importance of surgeons considering radical surgical approaches whenever feasible for patients with pulmonary PNETs.

Tracheal defects, particularly those extending over long segments, present substantial challenges in reconstructive surgery due to complications in vascularization and integration with host tissues. Traditional methods, such as extended tracheostomies and alloplastic stents, often result in significant morbidity due to mucus plugging and mechanical erosion. Recent advances in vascularized composite allograft (VCA) transplantation have opened new avenues for effective tracheal reconstruction. This article reviews the evolution of tracheal reconstruction techniques, focusing on the shift from non-vascularized approaches to innovative revascularization methods that enhance graft integration and functionality. Key advancements include indirect revascularization techniques and the integration of regenerative medicine, which have shown promise in overcoming historical barriers to successful tracheal transplantation. Clinical case studies are presented to illustrate the complexities and outcomes of recent tracheal transplantation procedures, highlighting the potential for long-term success through the integration of advanced vascular engineering and immune modulation strategies. Furthermore, the role of chimerism in reducing graft rejection and the implications for future tracheal transplantation and tissue engineering efforts are discussed. This review underscores the transformative potential of VCA in tracheal reconstruction, paving the way for more reliable and effective treatments for extensive tracheal defects.

BackgroundEvidence from observational studies and clinical trials has associated gut microbiota with infectious diseases. However, the causal relationship between gut microbiota and infectious diseases remains unclear.MethodsWe identified gut microbiota based on phylum, class, order, family, and genus classifications, and obtained infectious disease datasets from the IEU OpenGWAS database. The two-sample Mendelian Randomization (MR) analysis was then performed to determine whether the gut microbiota were causally associated with different infectious diseases. In addition, we performed reverse MR analysis to test for causality.ResultsHerein, we characterized causal relationships between genetic predispositions in the gut microbiota and nine infectious diseases. Eight strong associations were found between genetic predisposition in the gut microbiota and infectious diseases. Specifically, the abundance of class Coriobacteriia, order Coriobacteriales, and family Coriobacteriaceae was found to be positively associated with the risk of lower respiratory tract infections (LRTIs). On the other hand, family Acidaminococcaceae, genus Clostridiumsensustricto1, and class Bacilli were positively associated with the risk of endocarditis, cellulitis, and osteomyelitis, respectively. We also discovered that the abundance of class Lentisphaeria and order Victivallales lowered the risk of sepsis.ConclusionThrough MR analysis, we found that gut microbiota were causally associated with infectious diseases. This finding offers new insights into the microbe-mediated infection mechanisms for further clinical research.

Abstract Restoration of extensive tracheal damage remains a significant challenge in respiratory medicine, particularly in instances stemming from conditions like infection, congenital anomalies, or stenosis. The trachea, an essential element of the lower respiratory tract, constitutes a fibrocartilaginous tube spanning approximately 10–12 cm in length. It is characterized by 18 ± 2 tracheal cartilages distributed anterolaterally with the dynamic trachealis muscle located posteriorly. While tracheotomy is a common approach for patients with short‐length defects, situations requiring replacement arise when the extent of lesion exceeds 1/2 of the length in adults (or 1/3 in children). Tissue engineering (TE) holds promise in developing biocompatible airway grafts for addressing challenges in tracheal regeneration. Despite the potential, the extensive clinical application of tissue‐engineered tracheal substitutes encounters obstacles, including insufficient revascularization, inadequate re‐epithelialization, suboptimal mechanical properties, and insufficient durability. These limitations have led to limited success in implementing tissue‐engineered tracheal implants in clinical settings. This review provides a comprehensive exploration of historical attempts and lessons learned in the field of tracheal TE, contextualizing the clinical prerequisites and vital criteria for effective tracheal grafts. The manufacturing approaches employed in TE, along with the clinical application of both tissue‐engineered and non‐tissue‐engineered approaches for tracheal reconstruction, are discussed in detail. By offering a holistic view on TE substitutes and their implications for the clinical management of long‐segment tracheal lesions, this review aims to contribute to the understanding and advancement of strategies in this critical area of respiratory medicine.

Abstract Background Polycystic ovarian syndrome (PCOS) is recognized as the most prevalent endocrine disorder among women of reproductive age. While the utilization of assisted reproductive technology (ART) has resulted in favorable outcomes for infertility treatment in PCOS patients, the inherent pathophysiological features of the condition give rise to complications and consequences during pregnancy and delivery for both the mother and offspring. This study was to assess the correlation between maternal PCOS and various pregnancy complications and neonatal outcomes undergone ART. Methods A systematic search was conducted on PubMed, EmBase, and the Cochrane Library to identify observational studies that investigated the association between PCOS and the risk of various pregnancy complications and neonatal outcomes, including gestational diabetes mellitus (GDM), hypertension in pregnancy (PIH), preeclampsia (PE), preterm birth, abortion, congenital malformations (CA), small for gestational age (SGA), large for gestational age (LGA), low birth weight (LBW), macrosomia, neonatal intensive care unit (NICU) admission and birth weight. Eligible studies were selected based on predetermined inclusion and exclusion criteria. The meta-analysis was conducted using Review Manager and Stata software, with odds ratios (ORs) or mean difference (MD), confidence intervals (CIs), and heterogeneity (I2) being calculated. The search was conducted up to March 2023. Results A total of 33 studies with a combined sample size of 92,810 participants were identified. The findings indicate that PCOS is significantly associated with an increased risk of GDM (OR 1.51, 95% CI:1.17–1.94), PIH (OR 1.72, 95% CI:1.25–2.39), PE (OR 2.12, 95% CI:1.49–3.02), preterm birth (OR 1.29, 95% CI:1.21–1.39), and LBW (OR 1.29, 95% CI:1.14–1.47). In subgroup analyses, the risks of GDM (OR 1.80, 95% CI:1.23–2.62) and abortion (OR 1.41, 95% CI:1.08–1.84) were elevated in fresh embryo transferred (ET) subgroup, whereas elevated risk of PE (OR 1.82, 95% CI:1.17–2.83) and preterm birth (OR 1.31, 95% CI:1.21–1.42) was identified in frozen ET subgroup. Whatever with or without hyperandrogenism, patients with PCOS had a higher risk in preterm birth (OR 1.69, 95% CI: 1.31–2.18; OR 1.24, 95% CI:1.02–1.50) and abortion (OR 1.38, 95% CI:1.12–1.71; OR 1.23, 95% CI:1.06–1.43). Conclusion Our findings suggest that individuals with PCOS undergone ART are at a notably elevated risk for experiencing pregnancy complications and unfavorable neonatal outcomes. Nevertheless, to establish a definitive association between PCOS and pregnancy-related outcomes, it is necessary to conduct extensive prospective, blinded cohort studies and effectively control for confounding variables.

Recently, pressure-sensing mats have been widely used to capture static and dynamic pressure over sleep for posture recognition. Both a full-size mat with a low-density sensing array for figuring out the structure of the whole body and a miniature scale mat with a high-density sensing array for identifying the local characteristics around the chest have been investigated. However, both of the mat systems may face the challenge in the trade-off between the computational complexity (involving the size, density, etc. of the mat) and the performance of sleep posture recognition, where high performance may requires overcomplex computation and result in time latency in real-time sleep posture monitoring. In this paper, a lightweight neural network named ConcatNet, is proposed to realize sleep postures (supine, left, right, and prone) recognition in real time while maintaining a favorable performance. In ConcatNet, the inception module is proposed to extract the image features under multiple receptive fields, while the multi-layer feature fusion module is utilized to fuse deep and shallow features to enhance the model performance. To further improve the efficiency of the model, the depthwise convolution is adopoted. ConcatNet models in 3 different scales (ConcatNet-S, ConcatNet-M, and ConcatNet-L) are built to explore the impact of the sensor density on sleep posture recognition performance. Experimental results exhibit that ConcatNet-M corresponding to medium sensor density ( ${16}\times {16}$ ) achieved the best comprehensive performance, with short-term data cross-validation accuracy at 95.56% and overnight data testing accuracy at 94.68%. The model size is 7.91KB, FLOPs is 56.47K, and the inference time is only 0.38ms, which shows an outstanding performance of real-time sleep posture recognition with minimum consumption, indicating the potential to be deployed in mobile devices.

Abstract The versatile manipulation of cross-scale droplets is essential in many fields. Magnetic excitation is widely used for droplet manipulation due to its distinguishing merits. However, facile magnetic actuation strategies are still lacked to realize versatile multiscale droplet manipulation. Here, a type of magnetically actuated Janus origami robot is readily fabricated for versatile cross-scale droplet manipulation including three-dimensional transport, merging, splitting, dispensing and release of daughter droplets, stirring and remote heating. The robot allows untethered droplet manipulation from ~3.2 nL to ~51.14 μL. It enables splitting of droplet, precise dispensing (minimum of ~3.2 nL) and release (minimum of ~30.2 nL) of daughter droplets. The combination of magnetically controlled rotation and photothermal properties further endows the robot with the ability to stir and heat droplets remotely. Finally, the application of the robot in polymerase chain reaction (PCR) is explored. The extraction and purification of nucleic acids can be successfully achieved.

Summary: Here, we present a protocol for inducing fibrosis in human kidney-2 (HK2) cells followed by quantitative real-time PCR analysis of fibrosis-related genes. We describe steps for growing and expanding cells, inducing HK2 fibrosis, and collecting cells for downstream applications. Given the limited cell quantity in culture flasks and the challenges of cell collection, we utilized 10-cm Petri dishes for cell harvesting, with each experimental group comprising five replicate samples.For complete details on the use and execution of this protocol, please refer to Zhang et al.1 : Publisher’s note: Undertaking any experimental protocol requires adherence to local institutional guidelines for laboratory safety and ethics.

BackgroundAutoimmune thyroid disease (AITD) ranks among the most prevalent thyroid diseases, with inflammatory cytokines playing a decisive role in its pathophysiological process. However, the causal relationship between the inflammatory cytokines and AITD remains elusive.MethodsA two-sample Mendelian randomization (MR) analysis was performed to elucidate the causal connection between AITD and 41 inflammatory cytokines. Genetic variations associated with inflammatory cytokines were sourced from the FinnGen biobank, whereas a comprehensive meta-analysis of genome-wide association studies (GWASs) yielded data on Graves’ disease (GD) and Hashimoto thyroiditis. Regarding the MR analysis, the inverse variance-weighted, MR-Egger, and weighted median methods were utilized. Additionally, sensitivity analysis was conducted using MR-Egger regression, MR-pleiotropy residual sum, and outliers.ResultsSeven causal associations were identified between inflammatory cytokines and AITD. High levels of tumor necrosis factor–β and low levels of stem cell growth factor–β were indicative of a higher risk of GD. In contrast, high levels of interleukin-12p70 (IL-12p70), IL-13, and interferon-γ and low levels of monocyte chemotactic protein–1 (MCP-1) and TNF-α suggested a higher risk of HD. Moreover, 14 causal associations were detected between AITD and inflammatory cytokines. GD increases the levels of macrophage inflammatory protein–1β, MCP-1, monokine induced by interferon-γ (MIG), interferon γ–induced protein 10 (IP-10), stromal cell–derived factor–1α, platelet-derived growth factor BB, β–nerve growth factor, IL-2ra, IL-4, and IL-17 in blood, whereas HD increases the levels of MIG, IL-2ra, IP-10, and IL-16 levels.ConclusionOur bidirectional MR analysis revealed a causal relationship between inflammatory cytokines and AITD. These findings offer valuable insights into the pathophysiological mechanisms underlying AITD.

Somatic cell reprogramming generates induced pluripotent stem cells (iPSCs), which serve as a crucial source of seed cells for personalized disease modeling and treatment in regenerative medicine. However, the process of reprogramming often causes substantial lineage manipulations, thereby increasing cellular heterogeneity. As a consequence, the process of harvesting monoclonal iPSCs is labor-intensive and leads to decreased reproducibility. Here, we report the first in-house developed robotic platform that uses a pin-tip-based micro-structure to manipulate radial shear flow for automated monoclonal iPSC colony selection (~1 s) in a non-invasive and label-free manner, which includes tasks for somatic cell reprogramming culturing, medium changes; time-lapse-based high-content imaging; and iPSCs monoclonal colony detection, selection, and expansion. Throughput-wise, this automated robotic system can perform approximately 24 somatic cell reprogramming tasks within 50 days in parallel via a scheduling program. Moreover, thanks to a dual flow-based iPSC selection process, the purity of iPSCs was enhanced, while simultaneously eliminating the need for single-cell subcloning. These iPSCs generated via the dual processing robotic approach demonstrated a purity 3.7 times greater than that of the conventional manual methods. In addition, the automatically produced human iPSCs exhibited typical pluripotent transcriptional profiles, differentiation potential, and karyotypes. In conclusion, this robotic method could offer a promising solution for the automated isolation or purification of lineage-specific cells derived from iPSCs, thereby accelerating the development of personalized medicines.

Summary: Chronic kidney disease (CKD) is a common disease that seriously endangers human health. However, the potential relationship between xanthine oxidoreductase (XOR) activity and CKD remains unclear. In this study, we used clinical data, CKD datasets from the Gene Expression Omnibus database, and untargeted metabolomics to explain the relationship between XOR activity and CKD. First, XOR activity showed high correlation with the biomarkers of CKD, such as serum creatinine, blood urea nitrogen, uric acid, and estimated glomerular filtration rate. Then, we used least absolute shrinkage and selection operator logical regression algorithm and random forest algorithm to screen CKD molecular markers from differentially expressed genes, and the results of qRT-PCR of XDH, KOX-1, and ROMO1 were in accordance with the results of bioinformatics analyses. In addition, untargeted metabolomics analysis revealed that the purine metabolism pathway was significantly enriched in CKD patients in the simulated models of kidney fibrosis.

Background: Observational studies suggest an association between gastrointestinal diseases and chronic obstructive pulmonary disease (COPD), but the causal relationship remains unclear.Methods: We conducted bidirectional Mendelian randomization (MR) analysis using summary data from genome-wide association study (GWAS) to explore the causal relationship between common gastrointestinal diseases and COPD. Gastrointestinal diseases included gastroesophageal reflux disease (GERD), peptic ulcer disease (PUD), irritable bowel syndrome (IBS), Crohn’s disease (CD), ulcerative colitis (UC), functional dyspepsia (FD), non-infectious gastroenteritis (NGE), and constipation (CP). Significant MR analysis results were replicated in the COPD validation cohort.Results: Bidirectional MR analysis supported a bidirectional causal relationship between GERD and COPD, and COPD was also found to increase the risk of IBS and CP. Our study also provided evidence for a bidirectional causal relationship between PUD and COPD, although the strength of evidence may be insufficient. Furthermore, we provided evidence that there is no causal association between CD, UC, FD, NGE, and COPD.Conclusion: This study offers some evidence to clarify the causal relationship between common gastrointestinal diseases and COPD. Further research is needed to understand the underlying mechanisms of these associations.

Summary: Here we examine whether our impressive ability to perceive upright faces arises from evolved orientation-specific mechanisms, our extensive experience with upright faces, or both factors. To do so, we tested Claudio, a man with a congenital joint disorder causing his head to be rotated back so that it is positioned between his shoulder blades. As a result, Claudio has seen more faces reversed in orientation to his own face than matched to it. Controls exhibited large inversion effects on all tasks, but Claudio performed similarly with upright and inverted faces in both detection and identity-matching tasks, indicating these abilities are the product of evolved mechanisms and experience. In contrast, he showed clear upright superiority when detecting “Thatcherized” faces (faces with vertically flipped features), suggesting experience plays a greater role in this judgment. Together, these findings indicate that both evolved orientation-specific mechanisms and experience contribute to our proficiency with upright faces.

Cardiac arrest (CA) is a severe worldwide health problem. Therapeutic hypothermia is widely used to reduce the cardiac injury and improve the neurological outcomes after CA. However, a few studies have reported the changes of serum metabolic characteristics after CA. The healthy male New Zealand Rabbits successfully resuscitated from 10-min asphyxia-induced CA were divided randomly into the normothermia (NT) group and mild therapeutic hypothermia (HT) group. The sham group underwent sham-operation. Survival was recorded and neurological deficit score (NDS) was assessed. The serum non-targeted metabolomics were detected using ultra-high-performance liquid chromatography-quadrupole time-of-flight tandem mass spectrometry (UPLC-Q-TOF-MS/MS) and gas chromatography tandem mass spectrometry (GC-MS/MS) at 15 min, 3 h, 6 h and 24 h after return of spontaneous circulation (ROSC). Our study showed that the heart rate (HR) significantly slowed down during 0.5–6 h post ROSC, consistent with the decreasing trend of body temperature in the HT group. Compared with the NT group, the levels of Lac and PCO2 at 24 h post ROSC were lower, while a significant increase in PO2 level at 24 h post ROSC was observed in the HT group. The survival rate of the HT group was significantly higher than that of the NT group, and NDS scores were remarkably increased at 24 h post ROSC in the NT group. Significant differences in metabolic profiles at 15 min, 3 h, 6 h and 24 h post ROSC were observed among the Sham, NT and HT groups. The differential metabolites detected by UPLC-Q-TOF-MS/MS and GC-MS/MS were screened for further study between every two groups (NT vs sham, HT vs sham and HT vs NT) at 15 min, 3 h, 6 h and 24 h post ROSC. Phenylalanine metabolism, alanine, aspartate and glutamate metabolism and tricarboxylic acid (TCA) cycle were enriched in NT vs sham, HT vs sham and HT vs NT respectively. Our study demonstrated that therapeutic hypothermia improves the survival and neurological outcomes in rabbit model of cardiac arrest, and firstly represents the dynamic metabolic changes in the hypothermia therapy for CA by comprehensive UPLC-Q-TOF-MS/MS- and GC-MS/MS-based metabolomics.

Assessment of physical performance is essential to predict the frailty level of older adults. The modified Physical Performance Test (mPPT) clinically assesses the performance of nine activities: standing balance, chair rising up & down, lifting a book, putting on and taking off a jacket, picking up a coin, turning 360°, walking, going upstairs, and going downstairs. The activity performing duration is the primary evaluation standard. In this study, wearable devices are leveraged to recognize and predict mPPT items’ duration automatically. This potentially allows frequent follow up of physical performance, and facilitates more appropriate interventions. Five devices, including accelerometers and gyroscopes, were attached to the waist, wrists and ankles of eight younger adults. The system was experimented within three aspects: machine learning models, sensor placement, and sampling frequencies, to which the non-causal six-stages temporal convolutional network using 6.25 Hz signals from the left wrist and right ankle obtained the optimal performance. The duration prediction error ranged from 0.63±0.29 s (turning 360°) to 8.21±16.41 s (walking). The results suggest the potential for the proposed system in the automatic recognition and segmentation of mPPT items. Future work includes improving the recognition performance of lifting a book and implementing the frailty score prediction.

Abstract During COVID‐19, awareness of proper hand washing has increased significantly. It is critical that people learn the correct hand washing techniques and adopt good hand washing habits. Hence, this study proposes using wearable devices to detect hand washing activity among other daily living activities (ADLs) and classify steps proposed by the World Health Organization (WHO). Two experiments were conducted with 16 participants, aged from 20 to 31. The first experiment was hand washing following WHO regulation (ten participants), and the second experiment was performing eight ADLs (eight participants). All participants wore two wearable devices equipped with accelerometers and gyroscopes; one on each wrist. Four machine learning classifiers were compared in classifying hand washing steps in the leave‐one‐subject‐out (LOSO) mode. The SVM model with Gaussian kernel achieved the best performance in classifying 11 washing hands steps, with an average F1‐score of 0.8501. When detected among the other ADLs, hand washing following WHO regulation obtained the F1‐score of 0.9871. The study demonstrates that wearable devices are feasible to detect hand washing activity and the hand washing techniques as well. The classification results of getting the soap and rubbing thumbs are low, which will be the main focus in the future study.

Exercise benefits the whole organism, yet, how tissues across the body orchestrally respond to exercise remains enigmatic. Here, in young and old mice, with or without exercise, and exposed to infectious injury, we characterized the phenotypic and molecular adaptations to a 12-month exercise across 14 tissues/organs at single-cell resolution. Overall, exercise protects tissues from infectious injury, although more effectively in young animals, and benefits aged individuals in terms of inflammaging suppression and tissue rejuvenation, with structural improvement in the central nervous system and systemic vasculature being the most prominent. In vascular endothelial cells, we found that readjusting the rhythmic machinery via the core circadian clock protein BMAL1 delayed senescence and facilitated recovery from infectious damage, recapitulating the beneficial effects of exercise. Our study underscores the effect of exercise in reconstituting the youthful circadian clock network and provides a foundation for further investigating the interplay between exercise, aging, and immune challenges across the whole organism.

In this paper, we design a hydrostatic electroactive soft actuator (HESA) inspired by octopus transverse musculature. We introduce the advantage of laser processing technology in HESA fabrication compared with existing similar actuators and discuss the effect of laser processing on the outer membrane of the actuator. In addition, a mathematical model is established for the single channel of the actuator, and the geometric parameters of the actuator are optimized by mathematical model simulation and experiments. We demonstrate the motion effect of the actuator. Our experiments show that the single piece of the actuator can achieve 32.2% strain in the axial direction and 7.8% strain in the radius direction. Furthermore, we stack three actuators together and describe their motion characteristics at different frequencies. The stacked actuators can realize axial elongation, radial shrinkage, and bend, which covers all the motion modes of the octopus biological transverse musculature. This study may lay a foundation for implementing the biomimetic soft actuator mimicking the octopus’s transverse musculature, which is one less discussed but crucial muscular composition in the octopus-inspired arm research.

Obesity is a metabolic disease associated with gut microbiota and low-grade chronic inflammation. Tremella fuciformis is a medicinal and edible fungus; polysaccharide (TP) is the main active component, which has a variety of biological activities, such as hypoglycemic and hypolipidemic. However, the anti-obesity effects and potential mechanisms of TP have never been reported. This study was conducted to elucidate the inhibitory effect of TP on high-fat diet (HFD)-induced obesity in mice. Mice were split into five groups: normal chow diet (NCD) group, NCD_TP_H group, HFD group, HFD_TP_L group and HFD_TP_H group. Our study showed that TP inhibited high-fat diet-induced weight gain and fat accumulation in mice and reduced blood glucose, hyperlipidemia and inflammation. TP also improved gut microbiota disorders by reducing the Firmicutes/Bacteroidetes ratio and modulating the relative abundance of specific gut microbiota. We also found that the anti-obesity and gut microbiota-modulating effects of TP could be transferred to HFD-fed mice via faecal microbiota transplantation (FMT), confirming that the gut microbiota was one of the targets of TP for obesity inhibition. Further studies showed that TP increased the production of short-chain fatty acids and the secretion of intestinal hormones. Our studies showed that TP inhibited obesity by modulating inflammation and the microbe-gut-brain axis, providing a rationale for developing TP to treat obesity and its complications.

BackgroundFor patients with locally advanced breast cancer (LABC), conventional TNM staging is not accurate in predicting survival outcomes. The aim of this study was to develop two accurate survival prediction models to guide clinical decision making.MethodsA retrospective analysis of 22,842 LABC patients was performed from 2010 to 2015 using the Surveillance, Epidemiology and End Results (SEER) database. An additional cohort of 200 patients from the Binzhou Medical University Hospital (BMUH) was analyzed. The least absolute shrinkage and selection operator (LASSO) regression was used to screen for variables. The identified variables were used to build a survival prediction model. The performance of the nomogram models was assessed based on the concordance index (C-index), calibration plot, receiver operating characteristic (ROC) curve, and decision curve analysis (DCA).ResultsThe LASSO analysis identified 9 variables in patients with LABC, including age, marital status, Grade, histological type, T-stage, N-stage, surgery, radiotherapy, and chemotherapy. In the training cohort, the C-index of the nomogram in predicting the overall survival (OS) was 0.767 [95% confidence intervals (95% CI): 0.751–0.775], cancer specific survival (CSS) was 0.765 (95% CI: 0.756–0.774). In the external validation cohort, the C-index of the nomogram in predicting the OS was 0.858 (95% CI: 0.812–0.904), the CSS was 0.866 (95% CI: 0.817–0.915). In the training cohort, the area under the receiver operator characteristics curve (AUC) values of the nomogram in prediction of the 1, 3, and 5-year OS were 0.836 (95% CI: 0.821–0.851), 0.769 (95% CI: 0.759–0.780), and 0.750 (95% CI: 0.738–0.762), respectively. The AUC values for prediction of the 1, 3, and 5-year CSS were 0.829 (95% CI: 0.811–0.847), 0.769 (95% CI: 0.757–0.780), and 0.745 (95% CI: 0.732–0.758), respectively. Results of the C-index, ROC curve, and DCA demonstrated that the nomogram was more accurate in predicting the OS and CSS of patients compared with conventional TNM staging.ConclusionTwo prediction models were developed and validated in this study which provided more accurate prediction of the OS and CSS in LABC patients than the TNM staging. The constructed models can be used for predicting survival outcomes and guide treatment plans for LABC patients.

Abstract A successful DNA‐encoded library (DEL) will consist of diverse skeletons and cover chemical space as comprehensive as possible to fully realize its potential in drug discovery and chemical biology. However, the lack of versatile on‐DNA arylation methods for phenols that are less nucleophilic and reactive poses a great hurdle for DEL to include diaryl ether, a privileged chemotype in pharmaceuticals and natural products. This work describes the use of “substrate activation” approach to address the arylation of DNA‐conjugated phenols. Diaryliodonium salt, a highly electrophilic and reactive arylation reagent, is employed as Ar+ sources to ensure highly selective on‐DNA arylation of phenols and oximes with both high yields and DNA fidelity. Notably, the new on‐DNA arylation reaction can be applied to the late‐stage modification of peptides containing tyrosine side‐chain and to synthesize DNA‐tagged analogues of existing drug molecules such as sorafenib, a known pan‐kinase inhibitor. The new on‐DNA diaryliodonium salts chemistry affords a greater flexibility in DEL design and synthesis.

ObjectiveThis study aims to evaluate neonatal and children growth outcomes of cryotransfer of embryos developed from frozen gametes [double frozen transfer (DFT)].MethodsThis nested case-control study included 6,705 women who had a singleton live birth after embryo transfer at the Center for Reproductive Medicine, Shandong University, from 2008 to 2020. Of these, 745 women underwent frozen embryo transfer (FET) using embryos developed from frozen gametes (DFT). Propensity score methodology was used to balance the two groups by maternal age and body mass index (BMI) before evaluating outcomes. After age and BMI were matched using the propensity score methodology in a ratio of 1:4, the control groups enrolled 2,980 women who underwent fresh embryo transfer (ET) and 2,980 women underwent FET from fresh gametes. The children born were followed to at least 5 years of age, and some were followed up to 10 years. Neonatal outcomes and childhood growth measurements were compared among the three groups.ResultsThe average birth weight of the DFT group (3,462 g) was significantly higher than the FET group (3,458 g) and ET group (3,412 g). The rate of large for gestational age (LGA) babies in the DFT and FET group was higher than that for the ET group (30.9% vs. 24.8%; 29.4% vs. 24.8%, respectively). After adjusting for different confounder combinations in the three models, the birth weight and risk of LGA in the DFT and FET groups were still higher than in the ET group, and the values group of P for trend in the models were significant. In multiple linear regression analysis of the children’s development, the height Z-score of children born from the DFT and FET group was higher than that for children from the ET group (β = 0.21, 95% CI 0.07–0.35; b = 0.17, 95% CI 0.05–0.28, respectively). However, childhood growth measurements including body weight Z-score and BMI Z-score were not significantly different among the three groups. In addition, the proportion of male children born from DET was higher than that from ET.ConclusionsThere is an increased risk of LGA babies associated with pregnancies conceived from DFT. Children are inclined to be taller in the future in this group than after FET. The related etiology and pathophysiology mechanisms still need to be revealed. In the future, well-designed, observational studies with in-depth collection of patients’ characteristics may shed more light on this issue.

Summary: Background: Telemonitoring of circadian and sleep cycles could identify shift workers at increased risk of poor health, including cancer and cardiovascular diseases, thus supporting personalized prevention. Methods: The Circadiem cross-sectional study aimed at determining early warning signals of risk of health alteration in hospital nightshifters (NS) versus dayshifters (DS, alternating morning and afternoon shifts). Circadian rhythmicity in activity, sleep, and temperature was telemonitored on work and free days for one week. Participants wore a bluetooth low energy thoracic accelerometry and temperature sensor that was wirelessly connected to a GPRS gateway and a health data hub server. Hidden Markov modelling of activity quantified Rhythm Index, rest quality (probability, p1-1, of remaining at rest), and rest duration. Spectral analyses determined periods in body surface temperature and accelerometry. Parameters were compared and predictors of circadian and sleep disruption were identified by multivariate analyses using information criteria-based model selection. Clusters of individual shift work response profiles were recognized. Findings: Of 140 per-protocol participants (133 females), there were 63 NS and 77 DS. Both groups had similar median rest amount, yet NS had significantly worse median rest-activity Rhythm Index (0·38 [IQR, 0·29-0·47] vs. 0·69 [0·60-0·77], p

Assessing the performance of physical activities through the modified physical performance test (mPPT) is a known approach for predicting frailty levels in older adults. This study proposes a system comprising a continuous-wave (CW) radar for data acquisition and deep neural network (DNN) models (convolutional neural network (CNN) and convolutional recurrent neural network (CRNN)) as classifiers to automatically segment the mPPT items. These two DNN models were trained and evaluated in a leave-one-participant-out (LOPO) cross-validation procedure with a transfer learning method. To segment the mPPT items during recording by the radar, an additional flag activity was employed, which involves having the participants wave their hands at the start of each activity. Compared to the CNN, the CRNN achieved better classification performance, with the f1-score ranging from 0.3445 (lifting a book) to 0.9509 (standing balance). The recognition result was then used to segment the time-series data and predict each item’s duration. The average absolute duration prediction error ranged from 0.78 s (standing balance) to 2.78 s (climbing stairs). This result implies that the system has the potential to automatically segment mPPT items. Future works will be focused on accomplishing all the evaluation criteria automatically, for example, the steadiness and continuity of steps while turning 360°, and improving the low classification result of some mPPT items, such as lifting a book.

Phage therapy is recognized as a promising alternative to antibiotics in treating pulmonary bacterial infections, however, its use has not been reported for treating secondary bacterial infections during virus pandemics such as coronavirus disease 2019 (COVID-19). We enrolled 4 patients hospitalized with critical COVID-19 and pulmonary carbapenem-resistant Acinetobacter baumannii (CRAB) infections to compassionate phage therapy (at 2 successive doses of 109 plaque-forming unit phages). All patients in our COVID-19-specific intensive care unit (ICU) with CRAB positive in bronchoalveolar lavage fluid or sputum samples were eligible for study inclusion if antibiotic treatment failed to eradicate their CRAB infections. While phage susceptibility testing revealed an identical profile of CRAB strains from these patients, treatment with a pre-optimized 2-phage cocktail was associated with reduced CRAB burdens. Our results suggest the potential of phages on rapid responses to secondary CRAB outbreak in COVID-19 patients.

Abstract Background In the past decades, researchers have demonstrated the critical role of Toll-like receptors (TLRs) in the innate immune system. They recognize viral components and trigger immune signal cascades to subsequently promote the activation of the immune system. Main body Herpesviridae family members trigger TLRs to elicit cytokines in the process of infection to activate antiviral innate immune responses in host cells. This review aims to clarify the role of TLRs in the innate immunity defense against herpesviridae, and systematically describes the processes of TLR actions and herpesviridae recognition as well as the signal transduction pathways involved. Conclusions Future studies of the interactions between TLRs and herpesviridae infections, especially the subsequent signaling pathways, will not only contribute to the planning of effective antiviral therapies but also provide new molecular targets for the development of antiviral drugs.

Abstract Background A growing number of patients continue to receive total knee replacement (TKR) surgery. Nevertheless, such surgeries result in moderate to severe postoperative pain and difficulty in managing it. Musical interventions are regarded as a type of multimodal analgesia, achieving beneficial results in other clinical treatments. This study aims to evaluate the effect of musical interventions in improving short-term pain outcomes following TKR in order to determine a more reasonable and standard way of delivering musical intervention. Methods A systematic search was conducted to identify available and relevant randomized controlled trials (RCTs) regarding musical interventions compared against non-musical interventions in patients treated with TKR in Embase, MEDLINE, Cochrane Library, Web of Science, CNKI, and Wanfang Med Online up to 8 January 2020. The authors independently assessed study eligibility and risk of bias and collected the outcomes of interest to analyze. The statistical analysis was conducted using the Review Manager (RevMan) version 5.30 software. Results Eight RCTs comprised of 555 patients satisfied the inclusion criteria and were enrolled in the present study. The results showed no significant difference between the music and control groups in pain of the visual analog scale (VAS), during postoperative recovery room, back to the ward after surgery; anxiety degree of VAS; heart rate; respiratory rate; oxygen saturation; blood pressure, systolic blood pressure, and diastolic blood pressure. Nevertheless, significant differences were observed between the two groups in average increase in continuous passive motion (CPM) angles and LF/HF ratio (one kind index of heart rate variability). Conclusions Musical interventions fail to demonstrate an obvious effect in improving short-term pain outcomes following TKR. A reasonable standardization of musical interventions, including musical type, outcome measures used, outcomes measured, duration, timing and headphones or players, may improve pain outcomes with certain advantages and should be further explored after TKR.

Abstract Background Porous-coated metaphyseal sleeves are designed to fill bone loss and facilitate osseo-integration when bone loss occurs during revision total knee arthroplasty (TKA). The purpose of this paper was to evaluate the clinical and radiographic outcomes of porous-coated metaphyseal sleeves for severe bone loss in revision TKA. Methods Form December 2014 to March 2018, we retrospectively analyzed 36 patients receiving revision TKAs. They had Anderson Orthopaedic Research Institute (AORI) Type II and III tibial bone loss and were treated with metaphyseal sleeve. The patients were followed up for a mean time of 28.5 months. The Knee Society Score (KSS), the Hospital for Special Surgery (HSS) Knee Score, Visual Analog Scale (VAS) score and the range of motion (ROM), radiographic findings of sleeve osteo-integration were also recorded. The paired t test was used to compare the KSS, the HSS knee score and VAS score before and after the revision TKAs. A value of P

Esophageal squamous cell carcinoma (ESCC) is the primary subtype of esophageal cancer (EC) characterized by a high incidence rate and extremely poor prognosis worldwide. Previous studies suggested that the specific cell death signal was linked to different immune subtypes in multiple cancers, while a comprehensive investigation on ESCC is to be performed yet. In the current study, we dissected different cell death signals in ESCC tumors and then integrated that functional information to stratify ESCC patients into different immunogenic cell death (ICD) subtypes. By systematically analyzing the transcriptomes of 857 patients and proteomic profile of 124 patients, we found that the signals of necroptosis, pyroptosis, and ferroptosis are positively associated with activated immunity in ESCC. We identified two ICD pattern terms, namely, ICD-high and ICD-low subtypes that positively correlated to both progression-free survival and overall survival. In addition, cell fraction deconvolution analysis revealed that more infiltrated leukocytes were enriched in ICD-high types, especially antigen-presenting cells, such as dendritic cells and macrophages. With the XGBoost algorithm, we further developed a 14-gene signature which can simplify the subtyping for allocating new samples, by which we validated the prognosis value of the signature and proved that the ICD score scheme could serve as a promising biomarker for stratifying patients with immunotherapy in several immune checkpoint blockade treatment cohorts. Collectively, we successfully constructed the ICD scheme, which enables predicting of the prognosis or immunotherapy efficacy in ESCC patients and uncovered the critical interplay between cell death signals and immune status in ESCC.

Despite much attention on the history of goat evolution, information on origin, demographic history, and expansion route remains controversial. To address these questions, we collected 4,189 published goat DNA sequences including 1,228 sequences from 57 breeds in China and 2,961 sequences including 193 goat breeds from 71 other countries and carried out an integrated analysis. We found goat breeds from South China had the highest genetic diversity of lineage B, and subclades B2 only were found in Southwest China, suggesting that lineage B (particularly, subclade B2) probably originated from Southwest China and its surrounding areas. In addition, in this study, we found that lineage A from South China also presented higher genetic diversity and earlier expansion time (10, 606 years ago), even earlier than breeds from the Middle East. Hence, we speculated that South China and surrounding areas were the origin of lineage B and also the transportation hub for lineage A spreading to North China and Southwest Asia. Furthermore, according to the analysis of correlation between genetic differentiation value λ1 and λ2 and geographical distance, we further confirmed two phases of migration in goat breeds of North China. These results will contribute to a better understanding of the origin and migration history of domestic goat.

Abstract The formation of a stable gas cavity on the surfaces of solid bodies is essential for many practical applications, such as drag reduction and energy savings, owing to the transformation of the originally sticky solid–liquid interface into a free‐slip liquid–vapor interface by the creation of either liquid repellency or a Leidenfrost state on the surfaces. Here, it is shown that the simple infusion of a textured sphere with a smooth, slippery liquid layer can more easily create and sustain a stable gas cavity in a liquid at lower impact velocities compared to a dry solid sphere with the same contact angle. With a key parameter of curvature ratio, the early lamella dynamics during water entry of spheres and drops impact on planes are first unified. With the perspective of wetting transition, the unforeseen phenomenon of prone to cavity formation are successfully explained, which is the preferential lamella detachment from a slippery surface due to the higher viscosity of the lubricant relative to air. It is envisioned that the findings will provide an important and fundamental contribution to the quest for energy‐efficient transport.

The digestive tract microorganisms play a very important role in the host's nutrient intake, environmental suitability, and affect the host's physiological mechanism. Previous studies showed that in different seasons, mammalian gut microbes would be different. However, most of them are concentrated in wild animals. It remains unclear how seasonal change affects the gut microbes of Chinese merino fine-wool Sheep. Therefore, in this experiment, we continuously collected blood and feces samples of 50 Chinese merino fine-wool sheep in different seasons, measured the physiological indicators of blood, and passed 16S rRNA amplicon sequencing, determined the microbial community structure of fecal microorganisms and predicted flora function by PICRUSt. The results of blood physiological indicators showed that WBC, Neu and Bas in spring were significantly higher than those of other seasons. Fecal microbial sequencing revealed seasonal changes in gut microbial diversity and richness. Among them, Chinese merino fine-wool sheep had the highest gut microbes in summer. Firmicutes and Bacteroidetes were the dominant phyla, and they were unaffected by seasonal fluctuations. LEfSE analysis was used to analyze representative microorganisms in different seasons. The Lachnospiraceae and its genera (Lachnospiraceae_NK4A136_group, Lachnospiraceae_AC2044_group, g_unclassified_f_ Lachnospiraceae) were representative microorganisms in the three seasons of spring, summer and winter with harsh environmental conditions; while in autumn with better environmental conditions, the Ruminococcaceae and its genus (Ruminococcaceae_UCG-009 and Ruminococcaceae_UCG-005) were the representative microorganism. In autumn, the ABC transporter and the pyruvate metabolic pathway were significantly higher than other seasons. Correlation analysis results showed that Lachnospiraceae participated in the ABC transporters metabolic pathway, which caused changes in the blood physiological indicators. Overall, our results showed that, in response to seasonal changes, Chinese merino fine-wool sheep under house-feeding have adjusted their own gut microbial community structure, causing changes in the metabolism, and thus changing the physiological conditions of the blood. In the cold season, producers should focus on regulating the nutritional level of feed, enhancing the level of butyric acid in young animals to increase the ABC transporter, resist the external harsh environment, and improve the survival rate.

ObjectiveThe purpose of this study was to clarify the influence of the vanishing twin (VT) on the perinatal outcomes in the surviving singleton and further identify the susceptible window.Study designRetrospective cohort study.MethodsA total of 636 survivors of a vanished co-twin and 11,148 singleton controls were enrolled. The exposed group was further divided into early VT (EVT, VT ≤13 weeks, N = 593) and late VT subgroups (LVT, VT >13 weeks, N = 43) according to the gestational age of the twin vanishing. All participants were conceived through in vitro fertilization (IVF). Perinatal outcomes including gestational age, birthweight, and the incidence of preterm birth (PTB), low birthweight (LBW), small for gestational age (SGA), neonatal intensive care unit (NICU) admission, umbilical cord abnormality, jaundice of the newborn, and oligohydramnios were compared among the groups.ResultsIn our birth cohort, about 5.4% of all singleton deliveries originated from vanishing twin pregnancies. Compared with the singletons, both early and late VT pregnancy had a significantly lower birth weight (3337.57±532.24 g and 2916.05±526.07 g vs. 3446.15±526.07 g; p < 0.001 and p < 0.001), more frequent neonatal jaundice (47.0% and 60.5% vs. 40.6%; p = 0.002 and p = 0.008), and decreased incidence of umbilical cord abnormality (15.5% and 7.0% vs. 19.9%; p = 0.009 and p = 0.034). Newborns in the early VT group were more likely to manifest as SGA (5.4% vs. 3.6%, p = 0.002) and suffered oligohydramnios (5.4% vs. 3.4%; p = 0.008) than the primary singletons. In addition, the gestational age of late VT survivors was shorter than that of the controls (37.25 ± 3.25 vs. 39.04 ± 1.63, p = 0.001) and had a significantly higher risk of PTB (30.2% vs. 6.6%; p < 0.001) and NICU admission (27.9% vs. 9.4%, p < 0.001). All differences except for SGA maintain significance after adjusting for maternal age, BMI, and parity.ConclusionsSingletons with a vanished co-twin had worse perinatal outcomes compared with the original singletons, with LVT burden even much on the survival one. Therefore, close monitoring during the perinatal period was suggested in this type of neonates. Moreover, elective single embryo transfer should also be fully considered which could tackle the problem at its root.

Abstract With the advent of the Internet of Things era, the connection between electronic devices and humans is getting closer and closer. New‐concept electronic devices including e‐skins, nanogenerators, brain–machine interfaces, and implantable medical devices, can work on or inside human bodies, calling for wearing comfort, super flexibility, biodegradability, and stability under complex deformations. However, conventional electronics based on metal and plastic substrates cannot effectively meet these new application requirements. Therefore, a series of advanced electronic devices based on flexible porous substrates (e.g., paper, fabric, electrospun nanofibers, wood, and elastic polymer sponge) is being developed to address these challenges by virtue of their superior biocompatibility, breathability, deformability, and robustness. The porous structure of these substrates can not only improve device performance but also enable new functions, but due to their wide variety, choosing the right porous substrate is crucial for preparing high‐performance electronics for specific applications. Herein, the properties of different flexible porous substrates are summarized and their basic principles of design, manufacture, and use are highlighted. Subsequently, various functionalization methods of these porous substrates are briefly introduced and compared. Then, the latest advances in flexible porous substrate‐based electronics are demonstrated. Finally, the remaining challenges and future directions are discussed.

Purpose The direct anterior approach (DAA) for total hip arthroplasty (THA) can be performed with patients in either in the lateral decubitus or supine position. Prompted by the lack of studies addressing differences between the two positions, this investigation aimed to examine clinical and radiographic outcomes and compare the lateral decubitus versus the supine position for THA using the DAA. Methods Between January 1 and October 1, 2020, 90 patients who underwent primary unilateral THA using the DAA were recruited, with 54 (60%) undergoing THA in the supine position (SP group) and 36 (40%) in the lateral decubitus position (LP group). Technical information, clinical and radiographic outcomes, and patient-reported outcomes, including the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and Short-Form-12 (SF-12) were evaluated. All data were subjected to several statistical tests. Results There were no preoperative differences in baseline characteristics between the LP and SP groups, which were also similar in terms of operative duration, length of hospital stay, and blood loss. Radiographic assessment confirmed satisfactory positioning of the prosthesis in both groups. There were no significant differences in terms of CK-MB and hemoglobin levels, Harris Hip Score, WOMAC, UCLA, visual analog scale score, and SF-12. The incidence of complications in the LP group was lower than in the SP group. Conclusion Total hip arthroplasty performed via DAA in the LP and SP groups yielded excellent clinical outcomes, although the incidence of complications in the former was lower than in the latter.

Conductive hydrogel is a vital candidate for the fabrication of flexible and wearable electric sensors due to its good designability and biocompatibility. These well-designed conductive hydrogel–based flexible strain sensors show great potential in human motion monitoring, artificial skin, brain computer interface (BCI), and so on. However, easy drying and freezing of conductive hydrogels with high water content greatly limited their further application. Herein, we proposed a natural polymer-based conductive hydrogel with excellent mechanical property, low water loss, and freeze-tolerance. The main hydrogel network was formed by the Schiff base reaction between the hydrazide-grafted hyaluronic acid and the oxidized chitosan, and the added KCl worked as the conductive filler. The reversible crosslinking in the prepared hydrogel resulted in its resilience and self-healing feature. At the same time, the synthetic effect of KCl and glycerol endowed our hydrogel with outstanding anti-freezing property, while glycerol also endowed this hydrogel with anti-drying property. When this hydrogel was assembled as a flexible strain sensor, it showed good sensitivity (GF = 2.64), durability, and stability even under cold condition (−37°C).

Modeling thrombus growth in pathological flows allows evaluation of risk under patient-specific pharmacological, hematological, and hemodynamical conditions. We have developed a 3D multiscale framework for the prediction of thrombus growth under flow on a spatially resolved surface presenting collagen and tissue factor (TF). The multiscale framework is composed of four coupled modules: a Neural Network (NN) that accounts for platelet signaling, a Lattice Kinetic Monte Carlo (LKMC) simulation for tracking platelet positions, a Finite Volume Method (FVM) simulator for solving convection-diffusion-reaction equations describing agonist release and transport, and a Lattice Boltzmann (LB) flow solver for computing the blood flow field over the growing thrombus. A reduced model of the coagulation cascade was embedded into the framework to account for TF-driven thrombin production. The 3D model was first tested against in vitro microfluidics experiments of whole blood perfusion with various antiplatelet agents targeting COX-1, P2Y1, or the IP receptor. The model was able to accurately capture the evolution and morphology of the growing thrombus. Certain problems of 2D models for thrombus growth (artifactual dendritic growth) were naturally avoided with realistic trajectories of platelets in 3D flow. The generalizability of the 3D multiscale solver enabled simulations of important clinical situations, such as cylindrical blood vessels and acute flow narrowing (stenosis). Enhanced platelet-platelet bonding at pathologically high shear rates (e.g., von Willebrand factor unfolding) was required for accurately describing thrombus growth in stenotic flows. Overall, the approach allows consideration of patient-specific platelet signaling and vascular geometry for the prediction of thrombotic episodes.

BackgroundPrimary breast signet ring cell carcinoma (SRCC) is a rare type of breast cancer with typical morphological characteristics, high aggressiveness, and poor prognosis. SRCC is different from mucinous breast adenocarcinoma (MBC). However, only a few studies have explored the clinicopathological features and prognosis of SRCC and MBC.MethodsData retrieved from the Surveillance, Epidemiology, and End-Results (SEER) database (2004–2015) were used to explore the prognostic effect of clinicopathological features and treatment modalities on survival outcomes of SRCC and MBC patients. Kaplan–Meier plot analysis, multivariate Cox proportional risk model, propensity score matching (PSM), and subgroup analysis were performed.ResultsA total of 167 patients with SRCC and 11,648 patients with MBC were included in the study. SRCC patients exhibited higher histological grade (p < 0.001), larger tumor volume (p < 0.001), higher rate of lymph node metastasis (p < 0.001), and higher frequency of distal metastasis (p < 0.001) compared with MBC patients. Cox proportional hazards regression analysis showed that SRCC patients had lower overall survival (OS) and breast cancer-specific survival (BCSS) compared with MBC patients. Subgroup survival analysis showed that the SRCC patients had lower OS and BCSS in subgroups including younger than 60 years old, white race, married, without chemotherapy, and received radiotherapy compared with the MBC patients in these subgroups. In addition, the SRCC patients had lower BCSS in subgroups including other races (including Asian or Pacific Islander and American Indian/Alaska Native), without surgery, and lymph node metastasis.ConclusionThe findings showed that primary breast SRCC patients have unique clinical characteristics and worse prognosis compared with MBC patients. Notably, different treatment methods resulted in different prognosis for SRCC and MBC types; therefore, SRCC patients should be distinguished from MBC patients to improve efficacy of treatment.

BackgroundInvasive micropapillary breast carcinoma (IMPC) is a relatively rare pathological type of invasive breast cancer. Little is currently known on the efficacy and safety of breast-conserving treatment (BCT, lumpectomy plus postsurgical radiation) compared with mastectomy in women diagnosed with early-stage IMPC. Accordingly, we sought to investigate the long-term prognostic differences between BCT and mastectomy in patients with T1-3N0-3M0 invasive micropapillary breast carcinoma using data from the Surveillance, Epidemiology, and End Results (SEER) database.Materials and MethodsWe retrospectively analyzed 1,203 female patients diagnosed with early-stage IMPC between 2004 and 2015 from the SEER database. The impact of different surgical approaches on patient prognosis was assessed by the Kaplan-Meier method and Cox proportional risk models.ResultsA total of 609 and 594 patients underwent mastectomy and BCT, respectively. Compared with patients who underwent a mastectomy, patients in the BCT group were older and had lower tumor diameters, lower rates of lymph nodes metastasis, and higher rates of ER receptor positivity and PR receptor positivity (p 0.05).ConclusionIn women with early-stage IMPC, BCT was at least equivalent to mastectomy in terms of survival outcomes. When both procedures are feasible, BCT should be recommended as the standard surgical treatment, especially for patients with T2 disease.