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Teleost fishes, which are the largest and most diverse group of living vertebrates, have a rich history of ancient and recent polyploidy. Previous studies of allotetraploid common carp and goldfish (cyprinids) reported a dominant subgenome, which is more expressed and exhibits biased gene retention. However, the underlying mechanisms contributing to observed subgenome dominance remains poorly understood. Here we report high-quality genomes of twenty-one cyprinids to investigate the origin and subsequent subgenome evolution patterns following three independent allopolyploidy events. We identify the closest extant relatives of the diploid progenitor species, investigate genetic and epigenetic differences among subgenomes, and conclude that observed subgenome dominance patterns are likely due to a combination of maternal dominance and transposable element densities in each polyploid. These findings provide an important foundation to understanding subgenome dominance patterns observed in teleost fishes, and ultimately the role of polyploidy in contributing to evolutionary innovations.

Abstract Background Our previous study revealed that feeding the antimicrobial peptide (AMP) product Scy-hepc significantly enhances the growth of mariculture fish through the activation of the GH-Jak2-STAT5-IGF1 axis. However, the contribution of gut microbiota to this growth enhancement remains unclear. This study aimed to elucidate the potential mechanism involved in intestinal absorption and modulation of gut microbiota in Epinephelus akaara following Scy-hepc feeding. Results The results showed that a 35 day regimen of Scy-hpec markedly promoted the growth of E. akaara compared to groups supplemented with either florfenicol, B. subtilis, or a vector. The growth enhancement is likely attributed to alterations in microbiota colonization in the foregut and midgut, characterized by an increasing abundance of potential probiotics (Rhizobiaceae and Lysobacter) and a decreased abundance of opportunistic pathogens (Psychrobacter and Brevundimonas) as determined by 16S rRNA analysis. Additionally, similar to the effect of florfenicol feeding, Scy-hepc significantly improved host survival rate by over 20% in response to a lethal dose challenge with Edwardsiella tarda. Further investigations demonstrated that Scy-hepc is absorbed by the fish foregut (20–40 min) and midgut (20–30 min) as confirmed by Western blot, ELISA, and Immunofluorescence. The absorption of Scy-hepc affected the swimming, swarming and surfing motility of Vibrio harveyi and Bacillus thuringiensis isolated from E. akaara’s gut. Moreover, Scy-hepc induced the downregulation of 40 assembly genes and the upregulation expression of 5, with the most significant divergence in gene expression between opportunistic pathogens and probiotics concentrated in their motility genes (PomA/B, MotA/B). Conclusions In summary, this study shows that feeding AMP Scy-hepc can promote growth and bolster immunity in E. akaara. These beneficial effects are likely due to the absorption of Scy-hepc in the fish’s foregut and midgut, which modulates the colonization and motility of commensal bacteria, leading to favorable changes in the composition of the foregut and midgut microbiota. Therefore, a profound understanding of the mechanisms by which antimicrobial peptides affect host gut microbiota will contribute to a comprehensive assessment of their advantages and potential application prospects as substitutes for antibiotics in fish health and improving aquaculture practices.

The interpretability of machine learning reveals associations between input features and predicted physical properties in models, which are essential for discovering new materials. However, previous works were mainly devoted to algorithm improvement, while the essential multi-scale characteristics are not well addressed. This paper introduces distortion modes of oxygen octahedrons as cross-scale structural features to bridge chemical compositions and material properties. Combining model-agnostic interpretation methods, we are able to achieve interpretability even using simple machine learning schemes and develop a predictive model of effective mass for a widely used material type, namely perovskite oxides. With this framework, we reach the interpretability of the model, understanding the trend of the effective mass without any prior background information. Moreover, we obtained the knowledge only available to experts, i.e., the interpretation of effective mass from the s–p orbitals hybridization of B-site cations and O2− in ABO3 perovskite oxides.

Abstract Background The gut microbiota significantly influences the health and growth of red-spotted grouper (Epinephelus akaara), a well-known commercial marine fish from Fujian Province in southern China. However, variations in survival strategies and seasons can impact the stability of gut microbiota data, rendering it inaccurate in reflecting the state of gut microbiota. Which impedes the effective enhancement of aquaculture health through a nuanced understanding of gut microbiota. Inspired by this, we conducted a comprehensive analysis of the gut microbiota of wild and captive E. akaara in four seasons. Results Seventy-two E. akaara samples were collected from wild and captive populations in Dongshan city, during four different seasons. Four sections of the gut were collected to obtain comprehensive information on the gut microbial composition and sequenced using 16S rRNA next-generation Illumina MiSeq. We observed the highest gut microbial diversity in both captive and wild E. akaara during the winter season, and identified strong correlations with water temperature using Mantel analysis. Compared to wild E. akaara, we found a more complex microbial network in captive E. akaara, as evidenced by increased abundance of Bacillaceae, Moraxellaceae and Enterobacteriaceae. In contrast, Vibrionaceae, Clostridiaceae, Flavobacteriaceae and Rhodobacteraceae were found to be more active in wild E. akaara. However, some core microorganisms, such as Firmicutes and Photobacterium, showed similar distribution patterns in both wild and captive groups. Moreover, we found the common community composition and distribution characteristics of top 10 core microbes from foregut to hindgut in E. akaara. Conclusions Collectively, the study provides relatively more comprehensive description of the gut microbiota in E. akaara, taking into account survival strategies and temporal dimensions, which yields valuable insights into the gut microbiota of E. akaara and provides a valuable reference to its aquaculture.

Abstract Dielectric capacitors offer great potential for advanced electronics due to their high power densities, but their energy density still needs to be further improved. High-entropy strategy has emerged as an effective method for improving energy storage performance, however, discovering new high-entropy systems within a high-dimensional composition space is a daunting challenge for traditional trial-and-error experiments. Here, based on phase-field simulations and limited experimental data, we propose a generative learning approach to accelerate the discovery of high-entropy dielectrics in a practically infinite exploration space of over 1011 combinations. By encoding-decoding latent space regularities to facilitate data sampling and forward inference, we employ inverse design to screen out the most promising combinations via a ranking strategy. Through only 5 sets of targeted experiments, we successfully obtain a Bi(Mg0.5Ti0.5)O3-based high-entropy dielectric film with a significantly improved energy density of 156 J cm−3 at an electric field of 5104 kV cm−1, surpassing the pristine film by more than eight-fold. This work introduces an effective and innovative avenue for designing high-entropy dielectrics with drastically reduced experimental cycles, which could be also extended to expedite the design of other multicomponent material systems with desired properties.

Abstract Background Thesium chinense Turcz. (Named as Bai Rui Cao in Chinese) and its preparations (e.g., Bairui Granules) have been used to treat inflammatory diseases, such as acute mastitis, lobar pneumonia, tonsillitis, coronavirus disease 2019 (COVID-19), and upper respiratory tract infection. However, the material basis, pharmacological efficiency, and safety have not been illustrated. Methods Anti-inflammatory activity-guided isolation of constituents has been performed using multiple column chromatography, and their structures were elucidated by NMR spectroscopy and ECD calculations. The inhibitory effects on lung inflammation and safety of the crude ethanol extract (CE), Bairui Granules (BG), and the purified active constituents were evaluated using lipopolysaccharide (LPS)-stimulated acute lung inflammation (ALI) mice model or normal mice. Results Seven new compounds (1–7) and fifty-six known compounds (8–63) were isolated from T. chinense, and fifty-four were reported from this plant for the first time. The new flavonoid glycosides 1–2, new fatty acids 4–5, new alkaloid 7 as well as the known constituents including flavonoid aglycones 8–11, lignans 46–54, alkaloids 34 and 45, coumarins 57, phenylpropionic acids 27, and simple aromatic compounds 39, 44 and 58 exhibited anti-inflammatory activity. Network pharmacology analysis indicated that anti-inflammation of T. chinense was attributed to flavonoids and alkaloids by regulating inflammation-related proteins (e.g., TNF, NF-κB, TGF-β). Furthermore, constituents of T. chinense including kaempferol-3-O-glucorhamnoside (KN, also named as Bairuisu I, 19), astragalin (AG, Bairuisu II, 12), and kaempferol (KF, Bairuisu III, 8), as well as CE and BG could alleviate lung inflammation caused by LPS in mice by preventing neutrophils infiltration and the expression of the genes for pro-inflammatory cytokines NLRP3, caspase-1, IL-1β, and COX-2. After a 28-day subacute toxicity test, BG at doses of 4.875 g/kg and 9.750 g/kg (equivalent to onefold and twofold the clinically recommended dose) and CE at a dose of 11.138 g/kg (equivalent to fourfold the clinical dose of BG) were found to be safe and non-toxic. Conclusions The discovery of sixty-three constituents comprehensively illustrated the material basis of T. chinense. T. chinense and Bairui Granules could alleviate lung inflammation by regulating inflammation-related proteins and no toxicity was observed under the twofold of clinically used doses.

BackgroundBreast cancer is a malignancy characterized by chromosomal instability (CIN). This study aimed to examine the potential diagnostic value of chromosomal instability, detected by low-pass whole-genome sequencing (LPWGS), in the preoperative evaluation of sentinel lymph node metastasis (SLNM) in breast cancer.MethodsA retrospective investigation of clinical records from 29 patients with breast cancer revealed two distinct groups based on sentinel lymph node biopsy (SLNB) results: the SLN metastasis group (24 cases) and the SLN non-metastasis group (five cases). CIN and CIN scores were evaluated using LPWGS. An analysis of univariate data and binary logistic regression was employed to identify factors influencing SLNM, and a curve with receiver operating characteristics (ROC) was constructed to assess the diagnostic utility of CIN in predicting SLNM.ResultsA significant association between the SLNM and CIN high groups was observed in breast cancer (P=0.011). The CIN score in the metastasis group (17,665.055 ± 8,630.691) was higher than that in the non-metastasis group (9,247.973 ± 3,692.873), demonstrating a significant difference (P=0.044). Univariate binary logistic regression analysis indicated that CIN was a significant predictor for SLNM (odds ratio: 4.036, 95% CI: 1.015–16.047, P=0.048). The AUC of CIN for preoperative diagnosis of SLNM was 0.808 (95%CI: 0.635–0.982, P=0.033), with a sensitivity value of 67.0% and specificity of 100.0% at a threshold of 13,563.ConclusionDetecting CIN through LPWGS demonstrates diagnostic potential in predicting SLNM in patients with breast cancer before surgery. This approach offers a novel method for assessing axillary lymph node status in clinical practice.

Abstract Despite significant progress in therapy, there remains a lack of substantial evidence regarding the molecular factors that lead to renal fibrosis. Neuraminidase 4 (NEU4), an enzyme that removes sialic acids from glycoconjugates, has an unclear role in chronic progressive fibrosis. Here, this study finds that NEU4 expression is markedly upregulated in mouse fibrotic kidneys induced by folic acid or unilateral ureter obstruction, and this elevation is observed in patients with renal fibrosis. NEU4 knockdown specifically in the kidney attenuates the epithelial‐to‐mesenchymal transition, reduces the production of pro‐fibrotic cytokines, and decreases cellular senescence in male mice. Conversely, NEU4 overexpression exacerbates the progression of renal fibrosis. Mechanistically, NEU4254‐388aa interacts with Yes‐associated protein (YAP) at WW2 domain (231‐263aa), promoting its nucleus translocation and activation of target genes, thereby contributing to renal fibrosis. 3,5,6,7,8,3ʹ,4ʹ‐Heptamethoxyflavone, a natural compound, is identified as a novel NEU4 inhibitor, effectively protecting mice from renal fibrosis in a NEU4‐dependent manner. Collectively, the findings suggest that NEU4 may represent a promising therapeutic target for kidney fibrosis.

We illustrated a rare case of malignant solitary fibrous tumor (MSFT) with epithelioid morphology in the occipital region of a 59-year-old female, in which a rare NAB2ex7-STAT6 exon15/16 double fusion subtype was detected by the Next-generation sequencing (NGS) and STAT6 immunohistochemistry (IHC) was diffusely and strongly positively expressed, without recurrence after 20 months of postoperative follow-up. The morphological and molecular genetic aspects and the differential diagnosis are described, and the relevant literature was assessed in order to broaden our understanding and diagnostic capability of this malignancy.

Abstract Background Small intestinal monomorphic–epitheliotropic intestinal T-cell lymphoma (MEITL) is a rare aggressive T-cell lymphoma originating in the gastrointestinal tract. This study aimed to investigate the clinicopathological features, immunophenotypes, and molecular genetic changes of MEITL. Methods The clinicopathological data for three patients with surgically resected MEITL of the small intestine were collected. Next, immunohistochemical labeling, Epstein–Barr virus (EBV) in situ hybridization, assessment of clonal rearrangement of T-cell receptor (TCR) genes, and next-generation sequencing (NGS) were performed. Results Of the three patients, two were male and one was female, with ages of 61, 67, and 73 years, respectively. Clinical manifestations were predominantly abdominal pain and distension. Histopathology revealed infiltrative growth of small-to-medium-sized lymphocytes with a consistent morphology between the intestinal walls, accompanied by an obvious pro-epithelial phenomenon. The expression of CD3, CD8, CD43, CD56, TIA-1, CD103, H3K36me3, and Bcl-2 was detected, and the Ki-67 proliferation index ranged from 50% to 80%. All three patients tested negative for EBER. However, monoclonal rearrangement of the TCR gene was detected in them. NGS testing showed a JAK3 mutation in all three cases. Further, STAT5B, SETD2, and TP53 mutations were each observed in two cases, and a BCOR mutation was found in one case. All patients were treated with chemotherapy after surgery. Two patients died 7 and 15 month post-operation, and one patient survived for 5 months of follow-up. Conclusions Our findings demonstrate that mutations in JAK3 and STAT5B of the JAK/STAT pathway and inactivation of the oncogene SETD2 markedly contribute to the lymphomagenesis of MEITL.

LaCoO3 is well-known for its unique thermally induced transition of Co3+ (3d6) ions from a low spin (LS) state to a higher spin state of intermediate spin (IS) state or high spin (HS) state, due to a delicate balance between crystal-field splitting and Hund’s coupling. In this work, we try to stabilize all possible spin states in the same initial structural model and further investigate the spin-state effect on the redox performance of LaCoO3. We find that an initial model of pseudocubic with R3¯c tilting octahedra was effective in stabilizing all possible spin states. The oxygen vacancy formation values of LS > HS + LS > HS > IS indicate that the IS state is the most optimal spin state in oxygen vacancy formation, which results from a weakened Co-O bonding energy by eg orbital occupation. The oxygen migration barriers of LS > IS > HS + LS > HS show that oxygen migration is easier in the relatively loose structure and thus LS structure is the most unfavorable in oxygen migration. Combining the oxygen vacancy formation and migration results, we conclude that the higher spin states of IS and HS are more beneficial than LS in oxygen conduction. Our results confirm the influence of the spin-state effect on oxygen conduction and show that spin-state regulation is a good strategy for improving the redox performance of perovskites.

The perovskite crystal structure represents a semiconductor material poised for widespread application, underpinned by attributes encompassing heightened efficiency, cost-effectiveness and remarkable flexibility. Notably, strontium titanate (SrTiO3)-type perovskite, a prototypical ferroelectric dielectric material, has emerged as a pre-eminent matrix material for enhancing the energy storage capacity of perovskite. Typically, the strategy involves augmenting its dielectric constant through doping to enhance energy storage density. However, SrTiO3 doping data are plagued by significant dispersion, and the small sample size poses a formidable research hurdle, hindering the investigation of dielectric property and energy storage density enhancements. This study endeavours to address this challenge, our foundation lies in the compilation of 200 experimental records related to SrTiO3-type perovskite doping, constituting a small dataset. Subsequently, an interactive framework harnesses deep neural network models and a one-dimensional convolutional neural network model to predict and scrutinize the dataset. Distinctively, the mole percentage of doping elements exclusively serves as input features, yielding significantly enhanced accuracy in dielectric performance prediction. Lastly, rigorous comparisons with traditional machine learning models, specifically gradient boosting regression, validate the superiority and reliability of deep learning models. This research advances a novel, effective methodology and offers a valuable reference for designing and optimizing perovskite energy storage materials.

Cases of mixed neuroendocrine-non-neuroendocrine neoplasms (MiNENs) of the urinary system are rare, and reports of primary MiNENs in the ureter are lacking. Herein, we present the case of a 71-year-old man who presented with painless gross hematuria and weight loss. Contrast-enhanced abdominal computed tomography (CT) revealed a tumor, comprising small cell neuroendocrine carcinoma (SCNEC) and adenocarcinomatous components, attached to the ureter. The SCNEC components were strongly positive for synaptophysin, CD56 and INSM1 and adenocarcinomatous components were strongly positive for CDX2 and cytokeratin 20, respectively. Four weeks post-surgery, the patient received four cycles of cisplatin-based chemotherapy; the 7-month follow-up CT confirmed that he was healthy without disease recurrence. The occurrence of MiNEN in the ureter with SCNEC and adenocarcinomatous components is extremely rare, wherein histopathological and immunohistochemical features aid in the diagnosis MiNEN. With its aggressive nature, MiNEN can only be effectively treated by early diagnosis and radical surgery.

Abstract Neonatal mortality and morbidity are often caused by preterm birth and lower birth weight. Gestational diabetes mellitus (GDM) and gestational hypertension (GH) are the most prevalent maternal medical complications during pregnancy. However, evidence on effects of air pollution on adverse birth outcomes and pregnancy complications is mixed. Singleton live births conceived between January 1st, 2000, and December 31st, 2015, and reached at least 27 weeks of pregnancy in Kansas were included in the study. Trimester-specific and total pregnancy exposures to nitrogen dioxide (NO2), particulate matter with an aerodynamic diameter less than 2.5 μm (PM2.5), and ozone (O3) were estimated using spatiotemporal ensemble models and assigned to maternal residential census tracts. Logistic regression, discrete-time survival, and linear models were applied to assess the associations. After adjustment for demographics and socio-economic status (SES) factors, we found increases in the second and third trimesters and total pregnancy O3 exposures were significantly linked to preterm birth. Exposure to the second and third trimesters O3 was significantly associated with lower birth weight, and exposure to NO2 during the first trimester was linked to an increased risk of GDM. O3 exposures in the first trimester were connected to an elevated risk of GH. We didn’t observe consistent associations between adverse pregnancy and birth outcomes with PM2.5 exposure. Our findings indicate there is a positive link between increased O3 exposure during pregnancy and a higher risk of preterm birth, GH, and decreased birth weight. Our work supports limiting population exposure to air pollution, which may lower the likelihood of adverse birth and pregnancy outcomes.

Abstract Teleost fishes, which are the largest and most diverse group of living vertebrates, have a rich history of ancient and recent polyploidy. Previous studies of allotetraploid common carp and goldfish (cyprinids) reported a dominant subgenome, which is more expressed and exhibits biased gene retention. However, the underlying mechanisms contributing to observed ‘subgenome dominance’ remains poorly understood. Here we report high-quality genomes of twenty-one cyprinids to investigate the origin and subsequent subgenome evolution patterns following three independent allopolyploidy events. We identify the closest extant relatives of the diploid progenitor species, investigate genetic and epigenetic differences among subgenomes, and conclude that observed subgenome dominance patterns are likely due to a combination of maternal dominance and transposable element densities in each polyploid. These findings provide an important foundation to understanding subgenome dominance patterns observed in teleost fishes, and ultimately the role of polyploidy in contributing to evolutionary innovations.

Abstract We propose that the double barrier effect is expected to enhance the tunneling electroresistance (TER) in the ferroelectric tunnel junctions (FTJs). To demonstrate the feasibility of this mechanism, we design a model structure of Pt/BaTiO3/LaAlO3/Pt/BaTiO3/LaAlO3/Pt double barrier ferroelectric tunnel junction (DB-FTJ), which can be considered as two identical Pt/BaTiO3/LaAlO3/Pt single barrier ferroelectric tunnel junctions (SB-FTJs) connected in series. Based on density functional calculation, we obtain the giant TER ratio of 2.210 × 108% in the DB-FTJ, which is at least three orders of magnitude larger than that of the SB-FTJs of Pt/BaTiO3/LaAlO3/Pt, together with an ultra-low resistance area product (0.093 KΩμm2) in the high conductance state of the DB-FTJ. Moreover, it is possible to control the direction of polarization of the two single ferroelectric barriers separately and thus four resistance states can be achieved, making DB-FTJs promising as multi-state memory devices.

COPD poses a significant global public health challenge, primarily characterised by irreversible airflow restriction and persistent respiratory symptoms. The hallmark pathology of COPD includes sustained airway inflammation and the eventual destruction of lung tissue structure. While multiple risk factors are implicated in the disease's progression, the underlying mechanisms remain largely elusive. The perpetuation of inflammation is pivotal to the advancement of COPD, emphasising the importance of investigating these self-sustaining mechanisms for a deeper understanding of the pathogenesis. Autoimmune responses constitute a critical mechanism in maintaining inflammation, with burgeoning evidence pointing to their central role in COPD progression; yet, the intricacies of these mechanisms remain inadequately defined. This review elaborates on the evidence supporting the presence of autoimmune processes in COPD and examines the potential mechanisms through which autoimmune responses may drive the chronic inflammation characteristic of the disease. Moreover, we attempt to interpret the clinical manifestations of COPD through autoimmunity.

PurposeTo determine the 90 percent effective dose (ED90) of intrathecal sufentanil combined with ropivacaine 2.5 mg for labor analgesia and observe its safety for parturients and neonates.MethodsWe conducted a prospective, double-blind, biased coin up-and-down study. We injected a fixed 2.5 mg ropivacaine combined with a designated dose of sufentanil intrathecally to observe the labor analgesic effect. The initial dose of sufentanil was assigned 1.0 μg, and the remaining doses were assigned as per the biased coin up-and-down method. The criterion of successful response was defined as VAS ≤ 30 mm after intrathecal injection at 10 min. Safety was evaluated in terms of maternal and neonatal outcomes.ResultsThe ED90 dose of intrathecal sufentanil combined with ropivacaine 2.5 mg (0.1%, 2.5 mL) was 2.61 μg (95% CI, 2.44 to 2.70 μg) by isotonic regression. No respiratory depression, hypotension, or motor block was observed. Thirty-one (77.5%) parturients complained of pruritus, and 14 (35.0%) suffered nausea and vomiting. Three neonates reported a 1 min Apgar score of ≤7, and none reported a 5 min Apgar score of ≤7.ConclusionThe ED90 of intrathecal sufentanil combined with ropivacaine 2.5 mg for labor analgesia was 2.61 μg. The dose is safe for parturients and neonates.

Cancer-associated fibroblasts (CAFs) play a substantial role in the tumor microenvironment, exhibiting a strong association with the advancement of various types of cancer, including breast, pancreatic, and prostate cancer. CAFs represent the most abundant mesenchymal cell population in breast cancer. Through diverse mechanisms, including the release of cytokines and exosomes, CAFs contribute to the progression of breast cancer by influencing tumor energy metabolism, promoting angiogenesis, impairing immune cell function, and remodeling the extracellular matrix. Moreover, CAFs considerably impact the response to treatment in breast cancer. Consequently, the development of interventions targeting CAFs has emerged as a promising therapeutic approach in the management of breast cancer. This article provides an analysis of the role of CAFs in breast cancer, specifically in relation to diagnosis, treatment, drug resistance, and prognosis. The paper succinctly outlines the diverse mechanisms through which CAFs contribute to the malignant behavior of breast cancer cells, including proliferation, invasion, metastasis, and drug resistance. Furthermore, the article emphasizes the potential of CAFs as valuable tools for early diagnosis, targeted therapy, treatment resistance, and prognosis assessment in breast cancer, thereby offering novel approaches for targeted therapy and overcoming treatment resistance in this disease.

ObjectiveCarcinosarcoma of the ovary is a rare pathological type of ovarian cancer that is highly aggressive and occurs most frequently in the female reproductive tract at the site of the uterus. Herein, we explore the clinicopathological features, diagnosis, differential diagnosis, and treatment options for carcinosarcoma of the ovary.MethodsWe analyzed the clinical data of a case of carcinosarcoma, observed its histological morphology and immunohistochemical characteristics, detected the homologous recombination repair deficiency gene mutation, and reviewed the relevant literature.ResultsA 76-year-old menopausal woman visited our hospital because of abdominal distension, difficulty in urination, and constipation. Ultrasonography demonstrated abnormalities in the uterus and pelvic cavity, suggesting that the patient should undergo surgery. Immunohistochemical findings of carcinosarcoma of the right ovary were as follows: CK fraction (+), vimentin fraction (+), CK5/6 foci (+), p16 (+), p53 in approximately 70% (+), WT-1 foci (+), ER foci (+), PR part (+), Her-2 (1+), CK7 fraction (+), CK20 foci (+), CD99 fraction (+), CD10 fraction (+), CD56 foci (+), c-kit foci (+), SMA part (+), desmin foci (+), PD-L1 (-), SALL4 (-), OCT3/4 (-), p63 (-), p40 (-), D2-40 (-), inhibin (-), PLAP (-), CD30 (-), and Ki67 hotspot in approximately 80% (+). The patient underwent tumor cytoreduction and adjuvant chemotherapy. Currently, she is being followed up for 16 months and has a good general condition.ConclusionThe diagnosis of carcinosarcoma relies on histopathological examination and differentiation of carcinosarcoma from immature teratoma. The current therapeutic regimen for carcinosarcoma is still based on tumor cytoreduction and platinum-containing chemotherapy; research on targeted therapy is still in progress.

Lead-free ceramics with excellent energy storage performance are important for high-power energy storage devices. In this study, 0.9BaTiO3-0.1Bi(Mg2/3Nb1/3)O3 (BT-BMN) ceramics with x wt% ZnO-Bi2O3-SiO2 (ZBS) (x = 2, 4, 6, 8, 10) glass additives were fabricated using the solid-state reaction method. X-ray diffraction (XRD) analysis revealed that the ZBS glass-added ceramics exhibited a perovskite structure, with the maximum relative density achieved at x = 6. The average grain size reduced obviously as the glass additive wt% increased. Also, the dielectric constant decreased and the breakdown strength increased with increases in the glass additives. The optimal energy storage density of 1.39 J/cm3 with an energy storage efficiency of 78.3% was obtained at x = 6 due to high maximum polarization and enhanced breakdown strength. The results demonstrate that this material is a potential candidate for high-pulse-power energy storage devices.

ObjectiveTo construct a decision-making process model on vaccination of coronavirus disease 2019 (COVID-19) vaccine and to explore reasons of unwilling to have the vaccination from public perspective for providing theoretical evidences to COVID-19 vaccination promotion. MethodsUsing a self-designed open-ended questionnaire on COVID-19 vaccine hesitancy, we conducted a survey among 347 students in a medical university during March 27 – 29, 2021 – one week after the students′ applying voluntarily for COVID-19 vaccination. Word frequency and text node analysis on collected information were carried out and word cloud maps were generated with NVivo 12 software. A theoretical framework for vaccination decision-making process model was constructed based on grounded theory. ResultsValid information were collected from all the participants. In the respondents′ responses in writing about reasons for having COVID-19 vaccination, the words with high frequency included COVID-19, prevention, vaccination, and free of charge; while, safety, vaccine, effectiveness and adverse reaction were among the high frequency words in the writings on COVID-19 vaccine hesitancy. In the respondents′ writing texts, 3 parent nodes and 9 child nodes were identified. According to theoretical models of bio-psycho-social medicine, protective behavior decision, and vaccine hesitation/vaccination willingness and considering the results of previous studies, the public motivation for COVID-19 vaccination could be summarized into three aspects with nine causal factors as following: objective biological determination (factors relevant to virology/pharmacology and physiology/pathology), subjective psychological determination (personal risk and benefit judgment, vaccine safety, vaccine efficacy, and perceived social responsibility), and social determination (service accessibility, information accessibility). The three determinant aspects with nine relevant factors ought to be concerned in the construction of theoretical framework of vaccination decision-making process model for the public. ConclusionA vaccination decision-making process model for the public was preliminarily constructed for the promotion of COVID-19 vaccination willingness and behavior in Chinese population.

AimsTo verify whether the oral insulin N11005 is administered as a prandial insulin by assessing the pharmacokinetics (PK), pharmacodynamics (PD), and safety profiles of N11005 with a short-acting biosynthetic human insulin (Novolin R) as reference.MethodsThis was a randomized, open-label, single-dose, crossover hyperinsulinemic-euglycemic clamp study in healthy Chinese male subjects. A total of 12 subjects were enrolled in the test (T) group (N11005, 300 IU, p.o.) and the reference (R) group (Novolin R, 0.1 IU/Kg, i.h.) with a washout period of 14 days. All subjects were administered on the same day of the clamp study. Glucose Infusion Rates (GIR), serum insulin, and C-peptide concentration were determined during every 8-hour clamp cycle. Trial registration: Clinicaltrials.gov identifier NCT04975022.ResultsAfter administration, the ratios of mean serum C-peptide concentration to baseline concentration in both T and R groups were lower than 50%, which confirmed the stability of the clamp platform. T group (N11005) showed a more rapid onset of action (tGIR10%max≈11 min) and a comparable duration of action to the R group, which was basically in line with the characteristics of prandial insulins. No adverse events (AEs) occurred throughout the study, which demonstrated that N11005 and Novolin R are safe and well-tolerated.ConclusionsThe PD profiles of the single-dose N11005 in the human body are similar to those of prandial insulins, with an excellent safety profile.Clinical trial registrationClinicaltrials.gov, identifier NCT04975022.

Abstract Regulated pyroptosis is critical for pathogen elimination by inducing infected cell rupture and pro‐inflammatory cytokines secretion, while overwhelmed pyroptosis contributes to organ dysfunction and pathological inflammatory response. Caffeic acid (CA) and ferulic acid (FA) are both well‐known antioxidant and anti‐inflammatory phenolic acids, which resemble in chemical structure. Here we found that CA, but not FA, protects macrophages from both Nigericin‐induced canonical and cytosolic lipopolysaccharide (LPS)‐induced non‐canonical pyroptosis and alleviates LPS‐induced mice sepsis. It significantly improved the survival of pyroptotic cells and LPS‐challenged mice and blocked proinflammatory cytokine secretion. The anti‐pyroptotic effect of CA is independent of its regulations in cellular lipid peroxidation, mitochondrial function, or pyroptosis‐associated gene transcription. Instead, CA arrests pyroptosis by directly associating with gasdermin D (GSDMD) and blocking its processing, resulting in reduced N‐GSDMD pore construction and less cellular content release. In LPS‐induced septic mice, CA inhibits GSDMD activation in peritoneal macrophages and reduces the serum levels of interleukin‐1β and tumor necrosis factor‐α as the known pyroptosis inhibitors, disulfiram and dimethyl fumarate. Collectively, these findings suggest that CA inhibits pyroptosis by targeting GSDMD and is a potential candidate for curbing the pyroptosis‐associated disease.

Recently, there has been growing interest in the role of circular RNAs (circRNAs) in the progression of human cancers. Cellular senescence, a known anti-tumour mechanism, has been observed in several types of cancer. However, the regulatory interplay of circRNAs with cellular senescence in pancreatic cancer (PC) is still unknown. Therefore, we identified circHIF-1α, hsa_circ_0007976, which was downregulated in senescent cells using circRNA microarray analysis. Meanwhile, significantly upregulated expression of circHIF-1α in pancreatic cancer tissue detected by reverse transcription-polymerase chain reaction (RT-qPCR) and in situ hybridization (ISH). High circHIF-1α expression levels were found to independently predict poor survival outcomes. Subsequent treatments with DOX and H2O2 resulted in significantly lower levels of circHIF-1α. CircHIF-1α knockdown induces cellular senescence and suppresses PC proliferation in vitro experiments. The ability of circHIF-1α knockdown to suppress the progression of PC cells was further confirmed in vivo experiments. Our results showed that circHIF-1α is mainly presented in the nucleus of PC cells, also in the cytoplasm. Mechanistically, circHIF-1α inhibited senescence and accelerated the progression of PC cells through miR-375 sponging, thereby promoting HIF-1α expression levels. Nuclear circHIF-1α interacted with human antigen R protein (HUR) to increase HIF-1α expression. Thus, our results demonstrated that circHIF-1α ameliorates senescence and exacerbates growth in PC cells by increasing HIF-1α through targeting miR-375 and HUR, suggesting that targeting circHIF-1α offers a potential therapeutic candidate for PC. [ABSTRACT FROM AUTHOR]

BACKGROUND: Residential greenness is linked to birth outcomes. However, the role of greenspace morphology remains poorly understood. Additionally, evidence is lacking regarding whether these relationships vary by subpopulation. OBJECTIVE: We examined the association between preterm birth and residential greenspace morphology, including percentage, shape, connectedness, aggregation, closeness, and fragmentation. METHODS: We analyzed 2,063,444 singleton live births between 2001 to 2016 in Georgia, USA. Thirty-meter resolution landcover data from National Land Cover Databased (2001–2016) were obtained to calculate greenspace morphology metrics for 1,953 census tracts in Georgia. A twostage logistic regression examined associations between each greenspace morphology metric and preterm birth at individual level. Stratified analysis was conducted by maternal race, ethnicity, education, urbanicity, poverty rate, and greenspace percentage. RESULTS: Higher greenspace percentage, aggregation, closeness, shape complexity, connectedness, and lower fragmentation were linked to a lower risk of preterm birth. After adjusting for poverty rate, associations with morphology attenuated, except for fragmentation [odds ratio (OR) = 1.014; 95% confidence interval (CI): 1.0001, 1.026] across the entire population. Strongest associations were found among black mothers and in highpoverty areas. Specifically, the odds of preterm birth in the highest quartile of greenspace percentage were 0.962 (95% CI: 0.933, 0.991) times the odds in the lowest quartile. Additionally, a lower risk of preterm birth was associated with higher greenspace aggregation (OR = 0.969; 95% CI: 0.947, 0.992), and a higher risk of preterm birth was associated with higher fragmentation (OR = 1.028; 95% CI: 1.009, 1.047), both in the black mothers group. In tracts with a high poverty rate, a lower risk of preterm birth associate with higher greenspace percentage (OR = 0.953; 95% CI: 0.910, 0.999), aggregation (OR = 0.976; 95% CI: 0.955, 0.997), and lower fragmentation (OR = 0.976; 95% CI: 0.958, 0.994). The association with greenspace morphology was most pronounced in census tracts with a medium level of greenspace percentage. DISCUSSION: Our study complements other studies by showing the importance and protective effects of greenspace morphology. The observed effects are particularly prominent in census tracts characterized by a moderate level of greenspace percentage, high poverty rates, and among black women. Our findings suggest the need for tailored greenspace planning strategies based on varying levels of greenness in different areas. For locations with low greenness, increasing the greenspace percentage may be prioritized. In areas with a medium level of greenness, strategic enhancement of greenspace morphology is recommended. For areas with high greenness, the focus should be on improving spatial closeness of greenspace. [ABSTRACT FROM AUTHOR]

Piezoelectric ceramics with excellent piezoelectric properties and a high Curie temperature are important for numerous electromechanical devices in a broad range of temperature environments. In this work, the relaxor ferroelectric Pb(Yb1/2Nb1/2)O3 end member was selected to be introduced into a BiScO3-PbTiO3 high-temperature piezoelectric ceramic to reduce the dielectric loss and improve the piezoelectric properties while slightly reducing the Curie temperature. The phase structure and dielectric, ferroelectric and piezoelectric properties of 0.025Pb(Yb1/2Nb1/2)O3-(0.975−x)BiScO3-xPbTiO3 (0.60 ≤ x ≤ 0.63) ceramics were systematically analyzed, and the best electrical properties were observed in the morphotropic phase boundary region x = 0.61 with d33 = 370 pC/N, kp = 44%, Pr = 33.9 μC/cm2. Importantly, no significant depolarization was observed in the x = 0.61 ceramic from room temperature to 290 °C, demonstrating its good thermal stability and potential applications in a wide range of temperature environments.

Class II ceramics are a material with high permittivity but low reliability of their capacitance and bias voltage due to high the temperature sensitivity of their dielectric permittivity. In this work, a BST-based (Ba0.9−xSrxCa0.1)TiO3·0.03(Bi2O3·3TiO2) (x = 0.2, 0.25, 0.3, 0.35, 0.4) composition with Y5U characteristics was investigated through compositional control to develop high-permittivity and voltage-stable ceramic compositions. Sr doping can increase the breakdown strength (Eb) but decreases the Curie temperature (Tc). The composition at x = 0.3 can obtain optimal comprehensive electrical properties, with high permittivity of 4206, low dielectric loss of ~0.009, and moderate breakdown strength (Eb) of 77.6 kV/cm, which meets Y5U specifications. Typically, a low bias-voltage dependence of capacitance is confirmed with a variation rate of 7.64% under 20 kV/cm. This strategy provides a promising candidate for high-permittivity Class II ceramic dielectrics that can be used in this field.