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Abstract Background Lennert lymphoma (LL) is a variant of peripheral T-cell lymphoma, not otherwise specified (PTCL, NOS), also known as a lymphoepithelioid variant of PTCL. Because of the rarity and lack of clear-cut diagnostic criteria, LL is susceptible tomisdiagnosis. Although previously diagnosed with LL might be reclassified and evaluated with the advent of of molecular and/or genetic findings, cytomorphology and immunohistochemistry are still the key to give rise to correct diagnosis. Case presentation We report a case of a patient who was diagnosed as LL based on cytomorphology and immunohistochemistry. Routine stain (Hematoxlin and Eosin-H&E) revealed tumor cells were mainly small to medium-sized CD4(+) T cells, the CD8 +/TIA-1 + cytotoxic cells were less minority, no expressions of follicle helper T cell markers (CD10, BCL6, PD1, CXCL13, ICOS) or CD21(+) hyperplastic FDC network, or proliferation of high edndothelial venules were noted; however, numerous epithelioid histiocytes are noted in the background and scattered EBV(+) cells were also present. The patient was achieved complete remission after six courses of chemotherapy with cyclophosphamide, epirubicin, vincristine, etoposide, and prednisone regimen. She was followed for 5 years without recurrence or progression. Conclusions Classic LL is not difficult to diagnose by cytomorphology and immunohistochemistry, and the mutation profiles can be helpful to distinguish LL from other lymphomas.

Abstract Background Gender is a significant risk factor for late-onset Alzheimer’s disease (AD), often attributed to the decline of estrogen. The plant estrogen secoisolariciresinol diglucoside (SDG) has demonstrated anti-inflammatory and neuroprotective effects. However, the protective effects and mechanisms of SDG in female AD remain unclear. Methods Ten-month-old female APPswe/PSEN1dE9 (APP/PS1) transgenic mice were treated with SDG to assess its potential ameliorative effects on cognitive impairments in a female AD model through a series of behavioral and biochemical experiments. Serum levels of gut microbial metabolites enterodiol (END) and enterolactone (ENL) were quantified using HPLC-MS. Correlation analysis and broad-spectrum antibiotic cocktail (ABx) treatment were employed to demonstrate the involvement of END and ENL in SDG’s cognitive improvement effects in female APP/PS1 mice. Additionally, an acute neuroinflammation model was constructed in three-month-old C57BL/6J mice treated with lipopolysaccharide (LPS) and subjected to i.c.v. injection of G15, an inhibitor of G protein-coupled estrogen receptor (GPER), to investigate the mediating role of the estrogen receptor GPER in the cognitive benefits conferred by SDG. Results SDG administration resulted in significant improvements in spatial, recognition, and working memory in female APP/PS1 mice. Neuroprotective effects were observed, including enhanced expression of CREB/BDNF and PSD-95, reduced β-amyloid (Aβ) deposition, and decreased levels of TNF-α, IL-6, and IL-10. SDG also altered gut microbiota composition, increasing serum levels of END and ENL. Correlation analysis indicated significant associations between END, ENL, cognitive performance, hippocampal Aβ-related protein mRNA expression, and cortical neuroinflammatory cytokine levels. The removal of gut microbiota inhibited END and ENL production and eliminated the neuroprotective effects of SDG. Furthermore, GPER was found to mediate the inhibitory effects of SDG on neuroinflammatory responses. Conclusion These findings suggest that SDG promotes the production of gut microbial metabolites END and ENL, which inhibit cerebral β-amyloid deposition, activate GPER to enhance CREB/BDNF signaling pathways, and suppress neuroinflammatory responses. Consequently, SDG exerts neuroprotective effects and ameliorates cognitive impairments associated with AD in female mice.

Traditional high-temperature sterilization of chicken soup can easily lead to adverse effects on product quality and result in a short storage period, which fails to meet the demands for modern convenience and nutritional consumption. In this study, ultra high pressure combined with partial freezing multi-fence technology was applied to preserve chicken soup, aiming to extend its storage period, reduce nutritional loss, and enhance overall quality. The quality of chicken soup was compared and analyzed using pasteurization, high temperature and high pressure treatment, as well as ultra high pressure (400 MPa for 15 min) combined with partial freezing (−2.5 ℃) storage. Freshness indicators (total bacterial count, fat oxidation, protein oxidation), flavor-related parameters (soluble protein content, free amino acid content, inosine acid content, volatile substances), sensory evaluation scores were used to investigate the effects of these three sterilization methods combined with partial freezing technology on the storage stability and freshness of chicken soup. Furthermore, the impact of ultra high pressure combined with partial freezing technology on changes in the quality attributes of chicken soup during storage was explored. Results demonstrated that the group treated with ultra high pressure combined with partial freezing exhibited favorable microbial load values (with a total colony count only at 2.11 log CFU/mL) after being stored for 100 days. Malondialdehyde (MDA) values differed among the three groups subjected to different treatment methods: Higher MDA levels were observed in the high temperature and high pressure group compared to both pasteurization group and ultra high pressure group. Consistently lower MDA values were found in the ultra high pressure group throughout storage stages when compared against other two groups. The soluble protein content in the ultra high pressure group remained consistently higher at 5.22 mg/mL than that in other two groups. Additionally, the ultra high pressure group exhibited significantly higher levels of flavor substances (phenylalanine, proline, inosine, octanaldehyde, 2-heptanone, 2-amylfuran) compared to the other two groups. These findings demonstrate that the combination of ultra high pressure and partial freezing is more effective than traditional heat treatment in minimizing nutrient loss, preserving sensory quality of chicken soup, and extending shelf life.

Abstract Background The low live birth rate and difficult decision-making of the in vitro fertilization (IVF) treatment regimen bring great trouble to patients and clinicians. Based on the retrospective clinical data of patients undergoing the IVF cycle, this study aims to establish classification models for predicting live birth outcome (LBO) with machine learning methods. Methods The historical data of a total of 1405 patients undergoing IVF cycle were first collected and then analyzed by univariate and multivariate analysis. The statistically significant factors were identified and taken as input to build the artificial neural network (ANN) model and supporting vector machine (SVM) model for predicting the LBO. By comparing the model performance, the one with better results was selected as the final prediction model and applied in real clinical applications. Results Univariate and multivariate analysis shows that 7 factors were closely related to the LBO (with P

PurposeAlzheimer’s disease (AD) is a common neurodegenerative disease, which can lead to cognitive impairment and dementia. Since AD is tightly associated with aging and cellular senescence, objective of this study was to investigate the association between senescence-related genes and proteins (SRGs and SRPs) and the development of AD.DesignThe whole study was based on transcriptomic analysis of control and AD brain tissues and Mendelian randomization (MR) analysis.MethodsFor transcriptomic analysis, GSE5281 dataset from GEO database contains the transcriptomic data of human brain tissues (n = 161) from control group and AD patients. The expression of SRGs in control and AD brain tissues were compared by Student’s t test. For MR analysis, the instrumental single-nucleotide polymorphisms (SNPs) associated with 110 SRPs were filtered and selected from a large genome-wide association study (GWAS) for plasma proteome. The causality between plasma levels of SRPs and AD was explored using GWAS data of AD from Lambert et al. (17,008 cases and 37,154 controls) and further validated by using data from FinnGen consortium (6,489 patients and 170,489 controls). MR estimate was performed using the inverse-variance weighted (IVW) method and the heterogeneity and pleiotropy of results were tested.ResultsTranscriptomic analysis identified 36 up-regulated (including PLAUR) and 8 down-regulated SRGs in AD brain tissues. In addition, the MR results at both discovery and validation stages supported the causality between plasma levels of PLAUR (IVW-p = 3.04E-2, odds ratio [OR] = 1.15), CD55 (IVW-p = 1.56E-3, OR = 0.86), and SERPINE2 (IVW-p = 2.74E-2, OR = 0.91) and the risk of AD.ConclusionOur findings identified that PLAUR, as an SRG, may take part in the development of AD and found that high plasma levels of PLAUR was associated with increased risk of AD, indicating that this gene was a risk factor for this disease and providing the rationale of existing drugs or new preventative and therapeutic strategies.

Soil water is the main water source for plants, which is replenished by rainfall in the water-limited agricultural systems. Quantifying temporal dynamics of water soil deficit and its replenishment by rainfall can evaluate whether soil water meet the water demand for plants. This would provide accurate guide for when and how the irrigation practices conducted. However, this topic has not been deeply elucidated. In this study, soil water content at varied soil depths and precipitation were continuously monitored during two growing seasons in an apple orchard in the Loess Plateau of China. Soil water storage, soil water deficit and replenishment were also quantified. The results showed that soil water content varied temporally due to the impacts of rainfalls. Soil water storage at 0 ~ 200 cm depth ranged from 272.5 mm to 355.6 mm and the degree of soil water deficit ranged from 0.34 to 0.53 correspondingly. Meanwhile, replenishment of soil water by rainfall was 13.00% in 2017 and 9.78% in 2018, respectively. The qualitative relationship between monthly rainfalls and replenishment indicated that soil water was replenished by rainwater only at soil layers shallower than 160 cm. From the temporal dynamics of soil water content and deficit conditions, soil water could meet the water demand at the fruit expanding stage of apple trees. Irrigation measures should be taken to reduce the soil drought stress at this stage. This study provided an effective hydrological basis to improve the irrigation management of orchards and the efficiency of water resource.

ObjectiveTo explore the insight, treatment attitude, and related influencing factors of hospitalized elderly patients suffering from major depression.MethodsA total of 141 hospitalized elderly patients with depression were selected as the research objects. Insight was evaluated by the total score of the Insight and Treatment Attitude questionnaire (ITAQ). The data collected included sociodemographic characteristics, psychiatric symptoms, delirium status, social functioning, social support, suicide risk, and cognitive function.ResultsThe sample included 74.5% of female patients, and the mean age was 67.53 (sd=7.19) years. The influencing factors of inpatients with depression included alcohol consumption, length of hospitalization, admission types, and the main caregivers (P

Abstract Accurate identification and localization of multiple abnormalities are crucial steps in the interpretation of chest X-rays (CXRs); however, the lack of a large CXR dataset with bounding boxes severely constrains accurate localization research based on deep learning. We created a large CXR dataset named CXR-AL14, containing 165,988 CXRs and 253,844 bounding boxes. On the basis of this dataset, a deep-learning-based framework was developed to identify and localize 14 common abnormalities and calculate the cardiothoracic ratio (CTR) simultaneously. The mean average precision values obtained by the model for 14 abnormalities reached 0.572-0.631 with an intersection-over-union threshold of 0.5, and the intraclass correlation coefficient of the CTR algorithm exceeded 0.95 on the held-out, multicentre and prospective test datasets. This framework shows an excellent performance, good generalization ability and strong clinical applicability, which is superior to senior radiologists and suitable for routine clinical settings.

Abstract Background R140Q mutation in isocitrate dehydrogenase 2 (IDH2) promotes leukemogenesis. Targeting IDH2/R140Q yields encouraging therapeutic effects in the clinical setting. However, therapeutic resistance occurs in 12% of IDH2/R140Q inhibitor treated patients. The IDH2/R140Q mutant converted TF-1 cells to proliferate in a cytokine-independent manner. This study investigated the signaling pathways involved in TF-1(R140Q) cell proliferation conversion as alternative therapeutic strategies to improve outcomes in patients with acute myeloid leukemia (AML) harboring IDH2/R140Q. Methods The effects of IDH2/R140Q mutation on TF-1 cell survival induced by GM-CSF withdrawal were evaluated using flow cytometry assay. The expression levels of apoptosis-related proteins, total or phosphorylated STAT3/5, ERK, and AKT in wild-type TF-1(WT) or TF-1(R140Q) cells under different conditions were evaluated using western blot analysis. Cell viability was tested using MTT assay. The mRNA expression levels of GM-CSF, IL-3, IL-6, G-CSF, leukemia inhibitory factor (LIF), oncostatin M (OSM), and IL-11 in TF-1(WT) and TF-1(R140Q) cells were quantified via RT-PCR. The secretion levels of GM-CSF, OSM, and LIF were determined using ELISA. Results Our results showed that STAT3 and STAT5 exhibited aberrant constitutive phosphorylation in TF-1(R140Q) cells compared with TF-1(WT) cells. Inhibition of STAT3/5 phosphorylation suppressed the cytokine-independent proliferation of TF-1(R140Q) cells. Moreover, the autocrine GM-CSF, LIF and OSM levels increased, which is consistent with constitutive STAT5/3 activation in TF-1(R140Q) cells, as compared with TF-1(WT) cells. Conclusions The autocrine cytokines, including GM-CSF, LIF, and OSM, contribute to constitutive STAT3/5 activation in TF-1(R140Q) cells, thereby modulating IDH2/R140Q-mediated malignant proliferation in TF-1 cells. Targeting STAT3/5 phosphorylation may be a novel strategy for the treatment of AML in patients harboring the IDH2/R140Q mutation. Video Abstract

Abstract Background Little was known about the relationship between perceived neighborhood environment and depression among residents living in mega-communities. Furthermore, the mediating effects of physical activity (PA) and anxiety in this relationship have not been investigated. Thus, this study aimed to comprehensively examine the association between perceived neighborhood environment and depression among residents living in mega-communities, and test whether PA and anxiety mediated the association. Methods A cross-sectional study on perceived neighborhood environment and depression was conducted among individuals who lived in mega-communities (n = 665) in Guiyang, China from July to August 2022. Perceived neighborhood environment was assessed from the following six aspects: traffic, building quality, accessibility, neighborhood, indoor, and pollution. Depression was measured by the Patients Health Questionnaire-9. Structural equation model was used to evaluate the association between perceived neighborhood environment and depression, and test the mediating effect of PA and anxiety in this association. Results We found that neighborhood (β = -0.144, p = 0.002) and PA (β = -0.074, p

Abstract Purpose Numerous clinical studies have explored sodium–glucose cotransporter 2 inhibitor (SGLT2i) in patients with chronic heart failure (CHF), with or without type 2 diabetes mellitus (T2DM), and SGLT2i were proved to significantly reduce CHF hospitalization, cardiovascular death, cardiovascular mortality, all-cause mortality and myocardial infarction in patients with or without T2DM. However, only a limited few have investigated the effects of SGLT-2i on HF disease-specific health status and cardiac function. This meta-analysis aims to assess the effects of SGLT2i on disease-specific health status and cardiac function in CHF patients. Methods A comprehensive search was conducted of trials by searching in PubMed, EMBASE, CENTRAL, Scopus, and Web of Science, and two Chinese databases (CNKI and Wanfang), Clinical Trials ( http://www.clinicaltrials.gov ) were also searched. Results A total of 18 randomized controlled trials (RCTs) involving 23,953 participants were included in the meta-analysis. The effects of SGLT2 inhibitors were compared with control or placebo groups in CHF with or without T2DM. The SGLT2 inhibitors group exhibited a significant reduction in pro b-type natriuretic peptide (NT-proBNP) levels by 136.03 pg/ml (95% confidence interval [CI]: −253.36, − 18.70; P = 0.02). Additionally, a greater proportion of patients in the SGLT2 inhibitors group showed a ≥ 20% decrease in NT-proBNP (RR = 1.45, 95% CI [0.92, 2.29], p = 0.072). However, no statistically significant difference was observed for the effects on B-type natriuretic peptide (BNP). The use of SGLT-2 inhibitors led to a noteworthy improvement in LVEF by 2.79% (95% CI [0.18, 5.39];P = 0.036). In terms of health status, as assessed by the Kansas City Cardiomyopathy Questionnaire (KCCQ) and 6-minute walk distance, SGLT2 inhibitors led to a significant improvement in KCCQ clinical summary (KCCQ-CS) score (WMD = 1.7, 95% CI [1.67, 1.73], P

Abstract Background Macrophages phenotypic deviation and immune imbalance play vital roles in pregnancy-associated diseases such as spontaneous miscarriage. Trophoblasts regulate phenotypic changes in macrophages, however, their underlying mechanism during pregnancy remains unclear. Therefore, this study aimed to elucidate the potential function of trophoblast-derived miRNAs (miR-410-5p) in macrophage polarization during pregnancy. Methods Patient decidual macrophage tissue samples in spontaneous abortion group and normal pregnancy group (those who had induced abortion for non-medical reasons) were collected at the Reproductive Medicine Center of Renmin Hospital of Wuhan University from April to December 2021. Furthermore, placental villi and decidua tissue samples were collected from patients who had experienced a spontaneous miscarriage and normal pregnant women for validation and subsequent experiments at the Shenzhen Zhongshan Obstetrics & Gynecology Hospital (formerly Shenzhen Zhongshan Urology Hospital), from March 2021 to September 2022. As an animal model, 36 female mice were randomly divided into six groups as follows: naive-control, lipopolysaccharide-model, agomir-negative control prevention, agomir-410-5p prevention, agomir-negative control treatment, and agomir-410-5p treatment groups. We analyzed the miR-410-5p expression in abortion tissue and plasma samples; and supplemented miR-410-5p to evaluate embryonic absorption in vivo. The main source of miR-410-5p at the maternal–fetal interface was analyzed, and the possible target gene, signal transducer and activator of transcription (STAT) 1, of miR-410-5p was predicted. The effect of miR-410-5p and STAT1 regulation on macrophage phenotype, oxidative metabolism, and mitochondrial membrane potential was analyzed in vitro. Results MiR-410-5p levels were lower in the spontaneous abortion group compared with the normal pregnancy group, and plasma miR-410-5p levels could predict pregnancy and spontaneous abortion. Prophylactic supplementation of miR-410-5p in pregnant mice reduced lipopolysaccharide-mediated embryonic absorption and downregulated the decidual macrophage pro-inflammatory phenotype. MiR-410-5p were mainly distributed in villi, and trophoblasts secreted exosomes-miR-410-5p at the maternal–fetal interface. After macrophages captured exosomes, the cells shifted to the tolerance phenotype. STAT1 was a potential target gene of miR-410-5p. MiR-410-5p bound to STAT1 mRNA, and inhibited the expression of STAT1 protein. STAT1 can drive macrophages to mature to a pro-inflammatory phenotype. MiR-410-5p competitive silencing of STAT1 can avoid macrophage immune disorders. Conclusion MiR-410-5p promotes M2 macrophage polarization by inhibiting STAT1, thus ensuring a healthy pregnancy. These findings are of great significance for diagnosing and preventing spontaneous miscarriage, providing a new perspective for further research in this field.

AbstractPinus bhutanica is a critically endangered conifer and occurs only in central Bhutan, northwestern Yunnan and southeastern Xizang in China. In this study, the complete chloroplast genome of Pinus bhutanica was first assembled based on next-generation sequencing. The genome sequence was 116,919 bp in length with an overall GC content of 38.75%. A total of 106 functional genes were detected in the genome, including 72 protein-coding genes (PCGs), 30 transfer RNA (tRNA) genes, and four ribosomal RNA (rRNA) genes. The phylogenetic tree reconstructed by 12 chloroplast genomes revealed that P. bhutanica is most closely related to Pinus wangii in subsection Strobus of Pinus.

From September 20 to 23, 2023, the 17th National Postgraduates Symposium on Environmental and Occupational Medicine was successfully held in Baotou, Inner Mongolia. This symposium was co-sponsored by the Editorial Board of Journal of Environmental and Occupational Medicine and School of Public Health, Baotou Medical College, Inner Mongolia University of Science and Technology. Themed "Research and practice: Healing the schism", the symposium aimed to activate academic thinking, expand research perspectives, encourage innovation awareness, enhance school-to-school exchanges, and cultivate young talents, especially to promote the close integration of academic research and public health practice. Participants from more than 30 universities and research institutions submitted a total of 82 articles. The symposium also gathered about 200 authors and postgraduates from all over the country to discuss the latest progress and future development in the field of environment and occupational medicine and strive to apply the research results to public health practice.

ObjectiveTo compare image quality and diagnostic performance using different b-values for the zooming technique with diffusion-weighted imaging (ZOOMit-DWI) in thyroid nodulesMaterials and methodsA total of 51 benign thyroid nodules and 50 thyroid papillary carcinomas were included. ZOOMit-DWI was performed with b-values of 0, 500, 1000, 1500 and 2000 s/mm2. The sharpness was evaluated as subjective index. The signal intensity ratio (SIR), signal-to-noise ratio (SNR) and apparent diffusion coefficient (ADC) were measured as objective indices. Pairwise comparisons were performed among the different b-value groups using the Friedman test. A receiver operating characteristic curve of the ADC value was used to evaluate diagnostic performance. The DeLong test was used to compare diagnostic effectiveness among the different b-value groupsResultsIn both the papillary carcinoma group (P = 0.670) and the benign nodule group (P = 0.185), the sharpness of nodules was similar between b-values of 1000 s/mm2and 1500 s/mm2. In the papillary carcinoma group, the SIRnodule was statistically higher in DWI images with a b-value of 1500 s/mm2than in DWI images with b-values of 500 s/mm2(P = 0.004), 1000 s/mm2(P = 0.002), and 2000 s/mm2(P = 0.003). When the b-values were 1500 s/mm2(P = 0.008) and 2000 s/mm2(P = 0.009), the SIRnodule significantly differed between the papillary carcinoma group and the benign nodule group. When b = 500 s/mm2, the ADC had an AUC of 0.888. When b = 1000 s/mm2, the ADC had an AUC of 0.881. When b = 1500 s/mm2, the ADC had an AUC of 0.896. When b = 2000 s/mm2, the ADC had an AUC of 0.871. The DeLong test showed comparable diagnostic effectiveness among the different b-value groups except for between b-values of 2000 s/mm2and 1500 s/mm2, with a b-value of 2000 s/mm2showing lower effectivenessConclusionThis study suggests that 1500 s/mm2may be a suitable b-value to differentiate benign and malignant thyroid nodules in ZOOMit-DWI images, which yielded better image quality

Background: Accumulating small unruptured intracranial aneurysms are detected due to the improved quality and higher frequency of cranial imaging, but treatment remains controversial. While surgery or endovascular treatment is effective for small aneurysms with a high risk of rupture, such interventions are unnecessary for aneurysms with a low risk of rupture. Consequently, it is imperative to accurately identify small aneurysms with a low risk of rupture. The purpose of this study was to develop a clinically practical model to predict small aneurysm ruptures based on a radiomics signature and clinical risk factors. Methods: A total of 293 patients having an aneurysm with a diameter of less than 5 mm, including 199 patients (67.9 %) with a ruptured aneurysm and 94 patients (32.1 %) without a ruptured aneurysm, were included in this study. Digital subtraction angiography or surgical treatment was required in all cases. Data on the clinical risk factors and the features on computed tomography angiography images associated with the aneurysm rupture status were collected simultaneously. We developed a clinical–radiomics model to predict aneurysm rupture status using multivariate logistic regression analysis. The combined clinical–radiomics model was constructed by nomogram analysis. The diagnostic performance, clinical utility, and model calibration were evaluated by operating characteristic curve analysis, decision curve analysis, and calibration analysis. Results: A combined clinical–radiomics model (Area Under Curve [AUC], 0.85; 95 % confidence interval [CI], 0.757–0.947) showed effective performance in the operating characteristic curve analysis. In the validation cohort, the performance of the combined model was better than that of the radiomics model (AUC, 0.75; 95 % CI, 0.645–0.865; Delong's test p-value = 0.01) and the clinical model (AUC, 0.74; 95 % CI, 0.625–0.851; Delong's test p-value

The extracellular matrix (ECM) is a complex three-dimensional structure composed of proteins, glycans, and proteoglycans, constituting a critical component of the tumor microenvironment. Complex interactions among immune cells, extracellular matrix, and tumor cells promote tumor development and metastasis, consequently influencing therapeutic efficacy. Hence, elucidating these interaction mechanisms is pivotal for precision cancer therapy. T lymphocytes are an important component of the immune system, exerting direct anti-tumor effects by attacking tumor cells or releasing lymphokines to enhance immune effects. The ECM significantly influences T cells function and infiltration within the tumor microenvironment, thereby impacting the behavior and biological characteristics of tumor cells. T cells are involved in regulating the synthesis, degradation, and remodeling of the extracellular matrix through the secretion of cytokines and enzymes. As a result, it affects the proliferation and invasive ability of tumor cells as well as the efficacy of immunotherapy. This review discusses the mechanisms underlying T lymphocyte-ECM interactions in the tumor immune microenvironment and their potential application in immunotherapy. It provides novel insights for the development of innovative tumor therapeutic strategies and drug.

Williams syndrome (WS) is characterized by a range of clinical features, including cardiovascular disease, distinctive facial traits, neurobehavioral disorders, and a condition known as transient infantile hypercalcemia. Among these, endocardial calcification represents a non-specific response to severe, etiologically diverse myocardial injuries. In this report, we document a unique case involving an infant with WS who exhibited rapidly progressive arterial stenosis and left ventricular endocardial calcification, associated with a novel heterozygous deletion. While arterial stenosis is the most frequently observed cardiovascular issue in WS, instances of endocardial calcification during infancy are exceedingly rare and have not previously been reported in the context of WS.

Abstract The maternal-fetal interface shares similarities with tumor tissues in terms of the immune microenvironment. Normal pregnancy is maintained due to the immunosuppressed state, but pyroptosis induced by MITA can trigger the body’s immune response and disrupt the immunosuppressed state of the maternal-fetal interface, leading to abortion. In this study, we explored the role of MITA and TRIM38 in regulating pyroptosis and maintaining the immune tolerance of the maternal-fetal interface during pregnancy. Our findings show that the interaction between MITA and TRIM38 plays a crucial role in maintaining the immunosuppressed state of the maternal-fetal interface. Specifically, we observed that TRIM38-mediated K48 ubiquitination of MITA was higher in M2 macrophages, leading to low expression levels of MITA and thus inhibiting pyroptosis. Conversely, in M1 macrophages, the ubiquitination of K48 was lower, resulting in higher expression levels of MITA and promoting pyroptosis. Our results also indicated that pyroptosis played an important role in hindering the transformation of M1 to M2 and maintaining the immunosuppressed state of the maternal-fetal interface. These discoveries help elucidate the mechanisms that support the preservation of the immune tolerance microenvironment at the maternal-fetal interface, playing a vital role in ensuring successful pregnancy.

Abstract Introduction This study aimed to compare the accuracy of seven implantable collamer lens (ICL) implantation vault prediction formulae. Methods We retrospectively analyzed 328 patients (328 eyes) who underwent ICL implantation and the prediction accuracy of seven formulae: NK, KS, WH, Luo, Zhu, Hun, and ZZ were compared. Moreover, the accuracy of the seven formulae for different ICL sizes was compared. The formulae were tested using mean absolute prediction error (MAE), median absolute prediction error (MedAE), prediction error (PE) percentages at ± 50 µm, ± 100 µm, ± 200 µm, and ± 300 µm, and Bland-Altman analysis. Results The PE of the seven formulae were statistically significant (P

Abstract Background Colletotrichum camelliae, one of the most important phytopathogenic fungi infecting tea plants (Camellia sinensis), causes brown blight disease resulting in significant economic losses in yield of some sensitive cultivated tea varieties. To better understand its phytopathogenic mechanism, the genetic information is worth being resolved. Results Here, a high-quality genomic sequence of C. camelliae (strain LT-3-1) was sequenced using PacBio RSII sequencing platform, one of the most advanced Three-generation sequencing platforms and assembled. The result showed that the fungal genomic sequence is 67.74 Mb in size (with the N50 contig 5.6 Mb in size) containing 14,849 putative genes, of which about 95.27% were annotated. The data revealed a large class of genomic clusters potentially related to fungal pathogenicity. Based on the Pathogen Host Interactions database, a total of 1698 genes (11.44% of the total ones) were annotated, containing 541 genes related to plant cell wall hydrolases which is remarkably higher than those of most species of Colletotrichum and others considered to be hemibiotrophic and necrotrophic fungi. It’s likely that the increase in cell wall-degrading enzymes reflects a crucial adaptive characteristic for infecting tea plants. Conclusion Considering that C. camelliae has a specific host range and unique morphological and biological traits that distinguish it from other species of the genus Colletotrichum, characterization of the fungal genome will improve our understanding of the fungus and its phytopathogenic mechanism as well.

Biomimetic structures often endow materials with excellent performance. In order to explore the impact of biomimetic structures on the performance of energetic materials, the sedum multiceps-like bionic structure dihydroxylammonium 5,5′-bistetrazole-1,1′-diolate (TKX-50) was constructed by self-assembly technology, and controllable particle size adjustment was achieved. Moreover, the effects of solvent ratio, solute content, stirring flow field, and temperature on the quality of sedum multiceps-like TKX-50 crystals were explored, and the formation mechanism of sedum multiceps-like TKX-50 crystals was analyzed. Then, the crystal morphology, crystal form and particle size distribution of sedum multiceps-like TKX-50 were characterized, furthermore, the thermal properties and mechanical sensitivity of sedum multiceps-like TKX-50 were emphatically studied. The results showed that the sedum multiceps-like biomimetic structure TKX-50 was assembled from needle shaped or sheet shaped small particle crystals, and the sedum multiceps-like structure did not change the explosive crystal form of TKX-50. What's more, the thermal decomposition activation energy of the prepared sedum multiceps-like TKX-50 crystal was at least 157.30 kJ⋅mol−1 and at most 185.27 kJ⋅mol−1, and the thermal energy was greatly affected by particle size. In addition, the minimum and maximum ultimate impact energy of the sedum multiceps-like TKX-50 crystals are 20 J and 55 J. The ultimate impact energy of the sedum multiceps-like TKX-50 crystal with different particle sizes is higher than that of the raw TKX-50 (15 J). As a consequence, the sedum multiceps-like bionic structure effectively improves the energy release of TKX-50, reduces the impact sensitivity, and improves the uniformity of particle size distribution.

The escalating resistance of agricultural pests to chemical insecticides necessitates the development of novel, efficient, and safe biological insecticides. Conus quercinus, a vermivorous cone snail, yields a crude venom rich in peptides for marine worm predation. This study screened six α-conotoxins with insecticidal potential from a previously constructed transcriptome database of C. quercinus, characterized by two disulfide bonds. These conotoxins were derived via solid-phase peptide synthesis (SPPS) and folded using two-step iodine oxidation for further insecticidal activity validation, such as CCK-8 assay and insect bioassay. The final results confirmed the insecticidal activities of the six α-conotoxins, with Qc1.15 and Qc1.18 exhibiting high insecticidal activity. In addition, structural analysis via homology modeling and functional insights from molecular docking offer a preliminary look into their potential insecticidal mechanisms. In summary, this study provides essential references and foundations for developing novel insecticides.

Summary: Background: Acute kidney injury (AKI) is a common and serious organ dysfunction in critically ill children. Early identification and prediction of AKI are of great significance. However, current AKI criteria are insufficiently sensitive and specific, and AKI heterogeneity limits the clinical value of AKI biomarkers. This study aimed to establish and validate an explainable prediction model based on the machine learning (ML) approach for AKI, and assess its prognostic implications in children admitted to the pediatric intensive care unit (PICU). Methods: This multicenter prospective study in China was conducted on critically ill children for the derivation and validation of the prediction model. The derivation cohort, consisting of 957 children admitted to four independent PICUs from September 2020 to January 2021, was separated for training and internal validation, and an external data set of 866 children admitted from February 2021 to February 2022 was employed for external validation. AKI was defined based on serum creatinine and urine output using the Kidney Disease: Improving Global Outcome (KDIGO) criteria. With 33 medical characteristics easily obtained or evaluated during the first 24 h after PICU admission, 11 ML algorithms were used to construct prediction models. Several evaluation indexes, including the area under the receiver-operating-characteristic curve (AUC), were used to compare the predictive performance. The SHapley Additive exPlanation method was used to rank the feature importance and explain the final model. A probability threshold for the final model was identified for AKI prediction and subgrouping. Clinical outcomes were evaluated in various subgroups determined by a combination of the final model and KDIGO criteria. Findings: The random forest (RF) model performed best in discriminative ability among the 11 ML models. After reducing features according to feature importance rank, an explainable final RF model was established with 8 features. The final model could accurately predict AKI in both internal (AUC = 0.929) and external (AUC = 0.910) validations, and has been translated into a convenient tool to facilitate its utility in clinical settings. Critically ill children with a probability exceeding or equal to the threshold in the final model had a higher risk of death and multiple organ dysfunctions, regardless of whether they met the KDIGO criteria for AKI. Interpretation: Our explainable ML model was not only successfully developed to accurately predict AKI but was also highly relevant to adverse outcomes in individual children at an early stage of PICU admission, and it mitigated the concern of the “black-box” issue with an undirect interpretation of the ML technique. Funding: The National Natural Science Foundation of China, Jiangsu Province Science and Technology Support Program, Key talent of women’s and children’s health of Jiangsu Province, and Postgraduate Research & Practice Innovation Program of Jiangsu Province.

ObjectiveThere has been a gradual increase in the prevalence of cesarean section deliveries and more healthcare professionals are considering the prophylactic use of corticosteroids before planned full-term cesarean sections. However, the association between dexamethasone administration before full-term cesarean delivery and short-term adverse neonatal outcomes is unclear. This study analyzed the disparities in short-term adverse neonatal effects in neonates born via full-term elective cesarean delivery with or without antenatal dexamethasone treatment.Study designThis single-center retrospective cohort study involved neonates aged 37–39 weeks. The primary neonatal outcomes included various short-term adverse events, including neonatal admission to the neonatal intensive care unit, neonatal access to the special care baby unit, transient neonatal respiratory distress, respiratory distress syndrome, and the requirement of intravenous antibiotics or ventilatory support. Multiple logistic regression analysis was used to assess the association between these outcomes and dexamethasone exposure while adjusting for covariates.ResultsOf the 543 neonates included in the study, 121 (22.2%) had been exposed to prenatal dexamethasone. When compared with the control group, the dexamethasone-exposed group exhibited significantly higher rates of transient neonatal respiratory distress, respiratory distress syndrome, administration of intravenous antibiotics, the need for ventilatory support, and longer duration of neonatal hospitalization (P

Background: Evaluation of biological changes at the molecular level has important clinical implications for improving the survival rate of esophageal squamous cell carcinoma (ESCC). Therefore, we plan to analyze and elucidate the expression of microRNA-133b (miR-133b), M2 pyruvate kinase (PKM2), and signal transducer and activator of transcription 3 (STAT3) in ESCC and their associated clinicopathological significance. Methods: The 72 patients with ESCC were selected as the experimental study group. Normal adjacent tissues (NAT) were matched as the control group. In this study, in situ hybridization was used to detect the expression of miR-133b in ESCC, and tissue expressions of PKM2 and STAT3 were detected by immunohistochemistry, and literature review was conducted. Results: Studies had shown that the positive expression of miR-133b in NAT was significantly higher than that in ESCC (χ 2 = 9.007, P = .003). PKM2 and STAT3 in ESCC had a significantly higher positive expression levels than those of NAT (χ 2 = 56.523, P = .000; χ 2 = 72.939, P = .000). From correlation analysis, there was a negative correlation between miR-133b and PKM2( r = −0.515, P

Key Clinical Message Balanced reciprocal chromosomal translocation carriers will have greater risk to experience recurrent miscarriages, embryonic death, and infertility. We show the pedigree carrying a paternal karyotype which was reported first. This research helps to better understand the clinical manifestations and prognosis of patients with this rare chromosomal abnormality.

ABSTRACT The unique, recently discovered fungus Didymella theifolia specifically infects local varieties of tea plant Camellia sinensis in China, and therefore, the characterization of its mycoviruses is important. Three double-stranded (ds) RNAs (1, 2, and 3, with 6,338, 5,910, and 727 bp in size, respectively) were identified in the avirulent D. theifolia strain CJP4-1, which exhibits normal growth and morphology. Characterization of these double-stranded RNAs (dsRNAs) revealed that the two largest elements are the genomic components of a novel botybirnavirus, tentatively named Didymella theifolia botybirnavirus 1 (DtBRV1). Conversely, dsRNA3 shares no detectable similarity with sequences deposited in public databases but has high similarity with the 5′-terminal regions of dsRNAs 1 and 2 and contains a duplicated region encoding a putative small peptide. All three dsRNAs are encapsidated in isometric virions ca. 40 nm in diameter, supporting the notion that dsRNA3 is a DtBRV1 satellite. SDS-polyacrylamide gel electrophoresis in combination with peptide mass fingerprint analysis revealed that the DtBRV1 capsid protein consists of polypeptides encoded by the 5′-terminal regions of both genomic components dsRNA1 and dsRNA2. Vertical transmission of DtBRV1 through conidia is efficient, while its horizontal transmission from CJP4-1 to other strains was not detected. DtBRV1, with or without dsRNA3, has no obvious effects on fungal growth and virulence, as illustrated following transfection of the virulent D. theifolia strain JYC1-6. In summary, DtBRV1 exhibits unique molecular traits and contributes to our understanding of mycovirus diversity. IMPORTANCE A novel botybirnavirus, infecting the tea plant pathogen Didymella theifolia and tentatively named Didymella theifolia botybirnavirus 1 (DtBRV1), together with an additional double-stranded RNA (dsRNA), was characterized. DtBRV1 comprises two dsRNAs (1 and 2) encapsidated in isometric virions, while dsRNA3 is a satellite. The satellite represents a unique specimen since it contains a duplicated region and has high similarity to the two botybirnavirus dsRNAs, supporting the notion that it most likely originated from a deficient genomic component. The biological characteristics of DtBRV1 were further determined. With their unique molecular traits, DtBRV1 and its related dsRNA expand our understanding of virus diversity, taxonomy, and evolution.

ABSTRACTThe two most common systemic amyloidosis types are immunoglobulin light chain (AL) and amyloid transthyretin (ATTR) amyloidosis, in which the precursor proteins responsible for amyloidosis are light chain and transthyretin, respectively. Identification of precursor proteins is paramount to determine the type of amyloidosis, given that both amyloidosis types lack specificity in clinical presentation. Congo red staining followed by immunohistochemistry or immunofluorescence using fibril protein-specific antibodies is crucial for the diagnosis of amyloidosis. Here we describe a patient who was initially diagnosed with AL amyloidosis due to strong positive kappa light chain staining results. However, the diagnosis was corrected to hereditary ATTR amyloidosis using mass spectrometry and gene sequencing, confirming the important role of mass spectrometry in identifying the amyloid precursor protein and ruling out false-positive result from immunohistochemistry.

Abstract Numerous studies have reported that circulating cytokines (CCs) are linked to age-related neurodegenerative diseases (ANDDs); however, there is a lack of systematic investigation for the causal association. A two-sample bidirectional Mendelian Randomisation (MR) method was utilized to evaluate the causal effect. We applied genetic variants correlated with concentrations of CCs from a genome-wide association study meta-analysis (n = 8293) as instrumental variables. Summary data of three major ANDDs [Alzheimer’s disease (AD), Parkinson’s disease (PD), and Amyotrophic lateral sclerosis (ALS)] were identified from the IEU OpenGWAS platform (n = 627, 266). Inverse-variance weighted method is the main approach to analyse causal effect, and MR results are verified by several sensitivity and pleiotropy analyses. In directional MR, it suggested that several CCs were nominally correlated with the risk of ANDDs, with a causal odds ratio (OR) of Interleukin (IL)-5 of 0.909 for AD; OR of IL-2 of 1.169 for PD; and OR of Beta nerve growth factor of 1.142 for ALS). In reverse MR, there were some suggestively causal effects of ANDDs on CCs (AD on increased Basic fibroblast growth factor and IL-12 and decreased Stem cell growth factor beta; PD on decreased Monokine induced by interferon-gamma; ALS on decreased Basic fibroblast growth factor and IL-17). The findings were stable across sensitivity and pleiotropy analyses. However, after Bonferroni correction, there is no statistically significant association between CCs and ANDDs. Through the genetic epidemiological approach, our study assessed the role and presented possible causal associations between CCs and ANDDs. Further studies are warranted to verify the causal associations.

Abstract Objective Heterozygous loss-of-function variants in the NPR2 gene cause short stature with nonspecific skeletal abnormalities and account for about 2 ~ 6% of idiopathic short stature. This study aimed to analyze and identify pathogenic variants in the NPR2 gene and explore the therapeutic response to recombinant growth hormone (rhGH). Methods NPR2 was sequenced in three Chinese Han patients with short stature via exome sequencing. In vitro functional experiments, homology modeling and molecular docking analysis of variants were performed to examine putative protein changes and the pathogenicity of the variants. Result Three patients received rhGH therapy for two years, and two NPR2 heterozygous variants were identified in three unrelated cases: c.1579 C > T,p.Leu527Phe in patient 1 and c.2842dupC,p.His948Profs*5 in patient 2. Subsequently, a small gene model was constructed, and transcriptional analysis of the synonymous variant (c.2643G > A) was performed in patient 3, which revealed the deletion of exon 17 and the premature formation of a stop codon (p.His840Gln*). Functional studies showed that both NPR2 variants, His948Profs*5 and His840Gln*, failed to produce cGMP in the homozygous state. Furthermore, the Leu527Phe variant of NPR2 was almost unresponsive to the stimulatory effect of ATP on CNP-dependent guanylyl cyclase activity. This loss of response to ATP has not been previously reported. The average age of patients at the start of treatment was 6.5 ± 1.8 years old, and their height increased by 1.59 ± 0.1 standard deviation score after 2 years of treatment. Conclusion In this report, two novel variants in NPR2 gene were described. Our findings broaden the genotypic spectrum of NPR2 variants in individuals with short stature and provid insights into the efficacy of rhGH in these patients.

Abstract Somatic cell reprogramming and oncogenic transformation share surprisingly similar features, yet transformed cells are resistant to reprogramming. Epigenetic barriers must block transformed cells from reprogramming, but the nature of those barriers is unclear. In this study, we generated a systematic panel of transformed mouse embryonic fibroblasts (MEFs) using oncogenic transgenes and discovered transformed cell lines compatible with reprogramming when transfected with Oct4/Sox2/Klf4/Myc. By comparing the reprogramming-capable and incapable transformed lines we identified multiple stages of failure in the reprogramming process. Some transformed lines failed at an early stage, whilst other lines seemed to progress through a conventional reprogramming process. Finally, we show that MEK inhibition overcomes one critical reprogramming barrier by indirectly suppressing a hyperacetylated active epigenetic state. This study reveals that diverse epigenetic barriers underly resistance to reprogramming of transformed cells.

Abstract Background The study was designed to evaluate the interobserver reliability and intraobserver repeatability of the 2021 Association Research Circulation Osseous (ARCO) classification and explore its guiding significance in the treatment of nontraumatic osteonecrosis of the femoral head (ONFH). Methods In this retrospective study, we randomly selected and investigated 50 sets of preoperative computed tomography or magnetic resonance imaging scans from 96 patients (139 hips) to validate the reliability and repeatability of the 2021 ARCO classification. Patients with a nano-hydroxyapatite/polyamide-66 support rod were included in the clinical efficacy study. The Harris hip score (HHS) was used to assess hip function. Femoral head collapse of > 2 mm was considered radiological failure. Total hip arthroplasty (THA) was performed for clinical failure, and follow-up was discontinued. Results The average kappa value of interobserver consistency was 0.652. The average rate of consistency was 90.25%, and the average kappa value of intraobserver consistency was 0.836. Eighty-two patients (122 hips) were enrolled and followed up for a mean of 43.57 ± 9.64 months. There was no significant difference in the HHS among the three groups before surgery, but the difference was statistically significant at the last follow-up. Among them, types 1 and 2 had significantly higher scores at the last follow-up than preoperatively (P 0.05).According to the imaging evaluation, the failure rate of type 1, 2, and 3 at the last follow-up was 0%, 19%, and 87%, respectively. Univariate analysis showed that the femoral head survival rate of radiography was significantly affected by the new classification system (P = 0.00). At the last follow-up, the incidence rate of THA in type 1, 2, and 3 was 5%, 7%, and 31%, respectively. Univariate analysis showed that the femoral head survival rate was significantly affected by the new classification system (P = 0.001). Conclusions The 2021 ARCO classification for early-stage ONFH shows substantial consistency and repeatability. We do not recommend femoral head-preserving surgery for patients with type 3 ONFH.

Southern Africa Territories 2 (SAT2) foot-and-mouth disease (FMD) has crossed long-standing regional boundaries in recent years and entered the Middle East. However, the existing vaccines offer poor cross-protection against the circulating strains in the field. Therefore, there is an urgent need for an alternative design approach for vaccines in anticipation of a pandemic of SAT2 Foot-and-mouth disease virus (FMDV). The porcine parvovirus (PPV) VP2 protein can embed exogenous epitopes into the four loops on its surface, assemble into virus-like particles (VLPs), and induce antibodies and cytokines to PPV and the exogenous epitope. In this study, chimeric porcine parvovirus VP2 VLPs (chimeric PPV-SAT2-VLPs) expressing the T-and/or B-cell epitopes of the structural protein VP1 of FMDV SAT2 were produced using the recombinant pFastBac™ Dual vector of baculoviruses in Sf9 and HF cells We used the Bac-to-Bac system to construct the recombinant baculoviruses. The VP2-VLP--SAT2 chimeras displayed chimeric T-cell epitope (amino acids 21–40 of VP1) and/or the B-cell epitope (amino acids 135–174) of SAT FMDV VP1 by substitution of the corresponding regions at the N terminus (amino acids 2–23) and/or loop 2 and/or loop 4 of the PPV VP2 protein, respectively. In mice, the chimeric PPV-SAT2-VLPs induced specific antibodies against PPV and the VP1 protein of SAT2 FMDV. The VP2-VLP-SAT2 chimeras induced specific antibodies to PPV and the VP1 protein specific epitopes of FMDV SAT2. In this study, as a proof-of-concept, successfully generated chimeric PPV-VP2 VLPs expressing epitopes of the structural protein VP1 of FMDV SAT2 that has a potential to prevent FMDV SAT2 and PPV infection in pigs.

Abstract Background Real-time quantitative PCR (RT-qPCR) is a crucial and widely used method for gene expression analysis. Selecting suitable reference genes is extremely important for the accuracy of RT-qPCR results. Commonly used reference genes are not always stable in various organisms or under different environmental conditions. With the increasing application of high-throughput sequencing, transcriptome analysis has become an effective method for identifying novel stable reference genes. Results In this study, we identified candidate reference genes based on transcriptome data covering embryos and larvae of early development, normal adult tissues, and the hindgut under sulfide stress using the coefficient of variation (CV) method in the echiuran Urechis unicinctus, resulting in 6834 (15.82%), 7110 (16.85%) and 13880 (35.87%) candidate reference genes, respectively. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses revealed that the candidate reference genes were significantly enriched in cellular metabolic process, protein metabolic process and ribosome in early development and normal adult tissues as well as in cellular localization and endocytosis in the hindgut under sulfide stress. Subsequently, ten genes including five new candidate reference genes and five commonly used reference genes, were validated by RT-qPCR. The expression stability of the ten genes was analyzed using four methods (geNorm, NormFinder, BestKeeper, and ∆Ct). The comprehensive results indicated that the new candidate reference genes were more stable than most commonly used reference genes. The commonly used ACTB was the most unstable gene. The candidate reference genes STX12, EHMT1, and LYAG were the most stable genes in early development, normal adult tissues, and hindgut under sulfide stress, respectively. The log2(TPM) of the transcriptome data was significantly negatively correlated with the Ct values of RT-qPCR (Ct = − 0.5405 log2(TPM) + 34.51), which made it possible to estimate the Ct value before RT-qPCR using transcriptome data. Conclusion Our study is the first to select reference genes for RT-qPCR from transcriptome data in Echiura and provides important information for future gene expression studies in U. unicinctus.

Abstract Background Cross‐lineage expression of the myeloid‐associated antigens CD13/CD33 is common in adult B‐lymphoblastic leukemia (B‐ALL) patients, yet its prognostic value is still controversial. Methods We conducted a retrospective study of 1005 de novo adult B‐ALL patients from January 2009 to December 2019 in our hospital. Logistic and Cox regression were used to analyze the prognostic value of CD13/CD33 expression in B‐ALL. A Cox regression model was established to predict overall survival (OS) for B‐ALL patients. Results Of the 1005 B‐ALL patients, 53.7% (n = 540) aberrantly expressed CD13/CD33 (CD13/CD33+). Patients in the CD13/CD33+ group showed a higher incidence of BCR::ABL1 rearrangement and minimal/measurable residual disease (MRD) positivity but similar complete remission rate, relapse‐free survival, mortality, and OS with CD13/CD33‐. CD13/CD33+ patients had a higher risk of MRD positivity than CD13/CD33‐ patients. Notably, CD13/CD33+ patients who underwent tyrosine kinase inhibitor (TKI) therapy had a better long‐term prognosis than those without TKI experience. Sex, group based on CD13/CD33 expression and TKI experience and white blood cell count were variables independently associated with OS. The Cox regression model integrating these three variables showed a moderate performance for OS prediction (C‐index: 0.724). Conclusions In real‐world practice, CD13/CD33 expression can predict the risk of MRD in patients without TKI experience, but has no adverse effect on the prognosis of adult B‐ALL patients. Incorporating CD13/CD33 into the standard antibody panels of B‐ALL diagnosis and MRD measurements can help predict relapse risk and decisions on therapy options.

Abstract Background The concept of acute kidney injury (AKI) substages has been recommended to better phenotype AKI and identify high-risk patient groups and therefore improve the diagnostic accuracy of AKI. However, there remains a gap between the recommendation and the clinical application. The study aimed to explore the incidence of AKI substages based on a sensitive AKI biomarker of urinary cystatin C (uCysC), and to determine whether AKI substages were relevant with respect to outcome in critically ill children. Results The multicenter cohort study enrolled 793 children in pediatric intensive care unit (PICU) of four tertiary hospitals in China. Children were classified as non-AKI, sub-AKI and AKI substages A and B according to uCysC level at PICU admission. Sub-AKI was defined by admission uCysC level ≥ 1.26 mg/g uCr in children not meeting the KDIGO criteria of AKI. In children who fulfilled KDIGO criteria, those with uCysC

Abstract Atmospheric instability affects the formation of convective storms, but how it has changed during recent decades is unknown. Here we analyze the occurrence frequency of stable and unstable atmospheric conditions over land using homogenized radiosonde data from 1979 to 2020. We show that atmospheric stable (unstable) conditions have decreased (increased) significantly by ∼8%–32% (of time) from 1979 to 2020 over most land areas. In boreal summer, the mean positive buoyancy (i.e., convective available potential energy [CAPE]) also increases over East Asia while mean negative buoyancy (i.e., convective inhibition [CIN]) strengthens over Europe and North America from midnight‐dawn for unstable cases. The increased unstable cases and mean CAPE result from increased low‐level specific humidity and air temperature, which increase the buoyancy of a lifted parcel. The stronger CIN results from decreased near‐surface relatively humidity and decreased lapse rate in the lower troposphere. Our results suggest that the atmosphere has become increasingly unstable, which could lead to more convective storms.

In this paper, CrCoNi medium-entropy alloy coatings were prepared by laser cladding process, and ultrasonic impact treatment (UIT) with different impact amplitudes (0 μm, 10 μm, 15 μm, 20 μm) was performed on the coating surface to systematically study the microstructure and properties of the coatings. The results showed that the surface deformation of the coatings became more and more severe with the increase of ultrasonic impact amplitude. After the UIT treatment, the impact layer with obvious plastic deformation appeared on the top of the coating, and the depth of the impact layer gradually increased with the increase of the amplitude, and the influence range of the impact layer could be roughly judged according to the increase of the small-angle grain boundary on the top, which was about 200–400 μm at the amplitude of 20 μm. The grain size was 64.067 μm at an amplitude of 20 μm, which was about 34% of the original size. The microhardness of the coating was found to increase with the impact amplitude, and when the impact amplitude reached 20 μm, the microhardness of the coating reached 374.1 HV0.2, which was 122% higher than that of the unimpacted coating. Also, the wear resistance of the Cr–Co–Ni coating increased with the increase of impact amplitude, and the wear weight loss of the coating increased by 85.71% compared to the untreated specimen at an impact amplitude of 20 μm.

Abstract Background Hereditary tyrosinemia type 1 (HT1; OMIM# 276700) is a genetic metabolism disorder caused by disease-causing variants in the fumarylacetoacetate hydrolase (FAH) gene encoding the last enzyme of the tyrosine catabolic pathway. Herein, we describe the clinical features and genetic characteristics of HT1 in a five years and seven months old Chinese patient. Methods After clinical diagnosis of the proband with HT1, genetic testing was performed by Sanger sequencing of the FAH gene in all family members. Functional analysis of the disease-causing variant was performed by cDNA sequencing to understand the effect of the variant on FAH transcript. To further predict the variant effect, we used Human Splicing Finder (HSF) and PyMol in silico analysis. Results We identified a novel previously undescribed intronic variant in the FAH gene (c.914-1G>A). It was detected in a child who was homozygous for the variant and had the clinical presentation of HT1. cDNA sequencing showed that this splice-junction variant affected the transcription of FAH by formation of two different transcripts. Our observations and laboratory experiments were in line with in silico methods. Conclusions Our study provides new insight into the HT1 variant spectrum and a better understanding of this disease in the Chinese population. This will be useful for molecular diagnosis in our country in cases where premarital screening, prenatal diagnosis and preimplantation genetic diagnosis are planned.

Cone snails possess a diverse array of novel peptide toxins, which selectively target ion channels and receptors in the nervous and cardiovascular systems. These numerous novel peptide toxins are a valuable resource for future marine drug development. In this review, we compared and analyzed the sequence diversity, three-dimensional structural variations, and evolutionary aspects of venom insulin derived from different cone snail species. The comparative analysis reveals that there are significant variations in the sequences and three-dimensional structures of venom insulins from cone snails with different feeding habits. Notably, the venom insulin of some piscivorous cone snails exhibits a greater similarity to humans and zebrafish insulins. It is important to emphasize that these venom insulins play a crucial role in the predatory strategies of these cone snails. Furthermore, a phylogenetic tree was constructed to trace the lineage of venom insulin sequences, shedding light on the evolutionary interconnections among cone snails with diverse diets.

Efficient steel fiber—reinforced cementitious composites (SFRCC) should improve not only the ultimate tensile strength but also the residual tensile strength (post-cracking tensile strength) of the SFRCC matrix. The degradation of the post-cracking tensile strength of SFRCC depends on the pullout properties of the steel fibers from the cementitious matrix. When the straight steel fiber was pulled out from the matrix, the pullout resistance was affected by the actions of bonding and friction. After debonding, the load was transferred only by friction, and the pullout resistance decreased rapidly, resulting in a weak reinforcing effect. In addition, changing the fiber shape can effectively slow down the decreasing rate of the pullout resistance of the steel fibers, thus improving their reinforcing effects. In this study, the shape of the steel fibers was optimized to slow down the decrease in the pullout resistance of the steel fibers from the cementitious matrix, thus achieving better tensile properties of SFRCC. First, a calculation model for the steel fiber pullout resistance was established. On this basis, a method to optimize the shape of the steel fibers was proposed. Finally, the pulling out behavior of steel fibers with different end hook shapes was tested, and the influence of the steel fiber shape on the decreasing rate of the residual pullout resistance was analyzed. The results showed that the optimized hooked-end steel fibers had better pullout resistance than ordinary hooked end steel fibers of the same diameter, tensile strength, and matrix.

In order to investigate physiological and molecular mechanisms underlying the impacts of organic selenium and nanoselenium on the drought stress of pak choi (Brassica chinensis var. pekinensis. cv. ‘Suzhouqing’), we sprayed 20 mL of 0, 5, 10, 20 mg L−1 concentrations of organic selenium (DCK, DO5, DO10, DO20) and nanoselenium (DN5, DN10, DN20). We measured photosynthetic pigment, antioxidant and nutritional quality, performed transcriptome sequencing of leaves using RNA-seq technology, obtained 297,176,114 clean sequences, and identified differential expressed genes. Organic selenium and nanoselenium increased the photosynthetic capacity by upregulating light-trapping pigment proteins, regulated reactive oxygen species homeostasis by activating the antioxidant system through the upregulation of glutathione S-transferase, and maintained water homeostasis through glutathione oxidase activity, thus enhancing weight. They contributed to the elevated total selenium content by increasing expression levels of ABC transporter, adenylate kinase, and cysteine desulphurase. Additionally, hub genes related to these metabolic pathways were identified using a weighted gene coexpression network analysis. The consistent results with the upregulated genes identified in the Kyoto Encyclopedia of Genes and Genomes pathway confirmed the accuracy and reliability of the transcriptome sequencing data. This study provides scientific reference to further in-depth research on the molecular effect of selenium on crops under drought stress conditions.

IntroductionSuccessful embryo implantation, is the initiating step of pregnancy, relies on not only the high quality of the embryo but also the synergistic development of a healthy endometrium. Characterization and identification of biomarkers for the receptive endometrium is an effective method for increasing the probability of successful embryo implantation.MethodsEndometrial tissues from 22 women with a history of recurrent implantation failure (RIF) and 19 fertile controls were collected using biopsy catheters on 7-9 days after the peak of luteinizing hormone. Differentially expressed proteins (DEPs) were identified in six patients with RIF and six fertile controls using isobaric tag for relative and absolute quantitation (iTRAQ)-based proteomics analysis.ResultsTwo hundred and sixty-three DEPs, including proteins with multiple bioactivities, such as protein translation, mitochondrial function, oxidoreductase activity, fatty acid and amino acid metabolism, were identified from iTRAQ. Four potential biomarkers for receptive endometrium named tubulin polymerization-promoting protein family member 3 TPPP3, S100 Calcium Binding Protein A13 (S100A13), 17b-hydroxysteroid dehydrogenase 2 (HSD17B2), and alpha-2-glycoprotein 1, zinc binding (AZGP1) were further verified using ProteinSimple Wes and immunohistochemical staining in all included samples (n=22 for RIF and n=19 for controls). Of the four proteins, the protein levels of TPPP3 and HSD17B2 were significantly downregulated in the endometrium of patients with RIF.DiscussionPoor endometrial receptivity is considered the main reason for the decrease in pregnancy success rates in patients suffering from RIF. iTRAQ techniques based on isotope markers can identify and quantify low abundance proteomics, and may be suitable for identifying differentially expressed proteins in RIF. This study provides novel evidence that TPPP3 and HSD17B2 may be effective targets for the diagnosis and treatment of non-receptive endometrium and RIF.

BackgroundAmnestic mild cognitive impairment (aMCI) is a pre-dementia condition associated with declined cognitive function dominated by memory impairment. The occurrence of aMCI is associated with the gut-brain axis. Previous studies have shown cognitive improvements in MCI after acupuncture treatment. This study evaluates whether acupuncture can produce a therapeutic effect in patients with aMCI by modulating the gut-brain axis.Methods and designThis is a prospective, parallel, multicenter randomized controlled trial. A total of 40 patients with aMCI will be randomly assigned to an acupuncture group (AG) or a waiting-list group (WG), participants in both groups will receive health education on improving cognitive function at each visit, and acupuncture will be conducted twice a week for 12 weeks in the AG. Another 20 matched healthy volunteers will be enrolled as normal control. The primary outcome will be the change in Alzheimer’s Disease Assessment Scale-cognitive scale score before and after treatment. Additionally, functional magnetic resonance imaging data, faeces, and blood will be collected from each participant to characterize the brain function, gut microbiota, and inflammatory cytokines, respectively. The differences between patients with aMCI and healthy participants, and the changes in the AG and WG groups before and after treatment will be observed. Ultimately, the correlation among brain function, gut microbiota, inflammatory cytokines, and clinical efficacy evaluation in patients with aMCI will be analyzed.DiscussionThis study will identify the efficacy and provide preliminary data on the possible mechanism of acupuncture in treating aMCI. Furthermore, it will also identify biomarkers of the gut microbiota, inflammatory cytokines, and brain function correlated with therapeutic effects. The results of this study will be published in peer-reviewed journals.Clinical trial registrationhttp://www.chictr.org.cn, identifier ChiCTR2200062084.

BackgroundThe COVID-19 pandemic hints at the importance of modernizing disease control system. To understand the scientific research strength of our country's disease control system in recent years is conducive to formulating more targeted policies or measures to promote the modernization of the disease control system.ObjectiveTo understand the scientific research strength and research hotspots of China's provincial-level centers for disease control and prevention (CDCs) from 2011 to 2020, and provide evidence for the development of scientific research work, discipline construction, and talent team construction in CDCs in the future.MethodsThe Science Citation Index Expanded (SCIE) and Social Science Citation Index (SSCI) of the Web of Science Core Collection were used to retrieve SCI-indexed English papers published by 31 provincial CDCs (excluding Taiwan Province, Hong Kong and Macau Special Administrative Regions) in our country from 2011 to 2020, and to screen literature with provincial CDCs as the first affiliation for bibliometric analysis and visual analysis. Bibliometric analysis included the SCI-indexed publications of different provincial CDCs (as co-affiliation and the first affiliation), the number of SCI-indexed papers published by provincial CDCs (as the first affiliation) and funding rates by years, the high-frequency authors of SCI-indexed papers published by provincial CDCs (as the first affiliation) and their distribution, and the characteristics of the journals. Visual analysis software Citespace 5.8.R1 was used to draw keyword co-occurrence maps, cluster information tables, and emergence maps to provide information on research hotspots and their evolution.ResultsFrom 2011 to 2020, the number of SCI-indexed papers from 31 provincial CDCs was 8420 (including co-affiliation), of which 2060 papers listed provincial CDCs as the first affiliation. The provincial CDCs of Zhejiang, Jiangsu, Shanghai, Beijing, Shandong, and Guangdong were the leading six institutes in terms of the total number of SCI-indexed papers contributed as co-affiliation or the first affiliation. There was a large gap in the total number of SCI-indexed papers among the provincial CDCs. The highest total number of SCI-indexed papers contributed by provincial CDCs as the first affiliation was Zhejiang CDC (448 papers), while the lowest number was Xinjiang CDC (only 1 paper). From 2011 to 2020, the total number of SCI-indexed papers contributed by the 31 provincial CDCs as the first affiliation showed an overall increasing trend. Except for 2011, which was 63.1%, the funding rates in other years exceeded 70%. In terms of high-frequency authors, 13 first authors published ≥10 SCI-indexed papers: Zhang Yingxiu from Shandong CDC had the highest number of SCI-indexed papers (47), followed by Hu Yu from Zhejiang CDC. Zhejiang, Jiangsu, Beijing, Guangdong, Shanghai, and Shandong still ranked the top six of ≥4 first authored-SCI papers. In terms of journal characteristics, the top 20 journals with the highest number of SCI papers published a total of 862 papers, accounting for 41.8% (862/2060), and PLOS ONE ranked the first (188 papers). The research hotspots were mainly concentrated in the fields of infection, child health, and epidemiology. The main keywords of the first three cluster categories were related to the research fields of adolescent overweight and obesity, HIV, and vaccine immunity. The results of keyword emergence showed that research hotspots shifted from overweight, obesity, and body mass index to antibodies, vaccines/vaccination, and cohorts.ConclusionThe past ten years have witnessed increasing numbers of SCI-indexed papers published by provincial CDCs in our country and a stubbornly high funding rate. However, the gap among the provincial CDCs is still large seeing that economically developed eastern provincial CDCs published more SCI-indexed papers. Research hotspots have gradually shifted from overweight, obesity, and body mass index to antibodies, vaccines/vaccination, and cohorts.

Abstract Background Pulmonary infection is a frequent complication among stroke patients and adversely affects clinical outcomes, increases the length of hospitalization stay and costs, and aggravates the financial burden of the national medical health system. Early identification and management of high-risk patients are necessary and imperative to reduce the incidence of stroke-associated pneumonia (SAP). Aim The evidence-based practice project evaluated the effectiveness of a standard care bundle intervention in preventing the occurrence of SAP. Methods The project was conducted in a neurology department of a teaching hospital. Given the variation in assessment and management standards, evidence-based practice (EBP) methodology was used to establish a process for quality improvement. A thorough literature search was conducted to identify evidence-based interventions to manage and prevent SAP. Thorough critiques of the literature and synthesis of the evidence were completed. A systematic management flow and care bundle interventions were established. The care bundle included interventions, such as the utilization of tools for SAP risk screening; dysphagia screening and rehabilitation; feeding modification, oral care, airway management, position management, and the nursing techniques of traditional Chinese medicine. Results A significant improvement was observed in preventing SAP in patients in the postimplementation group compared with those in the preimplementation group (14.0% vs. 37.2%, p = 0.025). In addition, significantly lower duration of hospitalization, lower rate of aspiration, and improvements in albumin and oral hygiene were found after the implementation of the care bundle. Conclusions Evidence-based care bundles successfully empower nurses to reduce the incidence of SAP. The management flow of SAP prevention could be promoted to other units of the neurology department in the future. The results of the project reflect positively on the capacity to implement EBP in an acute care setting for stroke. The EBP methodology can be utilized to solve other clinical problems.

In recent years, photocured ceramics has become one of the rapidly developing additive manufacturing technologies. Bioceramics have a promising future in tissue engineering due to their good cellular compatibility, however, a single bioceramic material is difficult to take into account both mechanical properties and biocompatibility, so the application and promotion are greatly limited. In this paper, the modification and design methods of bioceramic materials suitable for photocuring were reviewed. The comprehensive effects of material modification, surface modification, structural design and microstructural regulation on the biological properties such as bone conduction, bone induction, antibacterial, angiogenesis promotion and other biological properties as well as and basic mechanical properties of were discussed. It was pointed out that the function of photocurable bioceramics can be fully realized and its further application can be promoted through the combination of modification and regulation methods, and the realization and interaction mechanism of multifunction should be explored.